Methods for predicting mental states elicited by olfactory and gustatory stimuli
Patent Information
- Application Number
- PCT/US2026/019933
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2025-03-21
- Filing Date
- 2026-03-19
- Publication Date
- 2026-09-24
AI Technical Summary
Existing methods struggle to accurately predict and induce specific mental states in subjects using olfactory and gustatory stimuli due to limitations in determining brain activity patterns and the sensitivity of current techniques, which may not account for the complex interplay of brain regions and the potential for multiple mental states to be induced by a single stimulus.
A method involving brain imaging and artificial intelligence to create mental state-specific brain activity maps, allowing for the identification and comparison of brain regions activated by stimuli, and the use of predictive models to determine the mental states elicited, including the strength of induction.
Enables precise determination of mental states induced by olfactory and gustatory stimuli, enabling the formulation of compositions that reliably elicit desired emotional and cognitive states with improved accuracy and reliability.
Abstract
Description
IFF101181-WO-PCTMETHODS FOR PREDICTING MENTAL STATES ELICITED BY OLFACTORY AND GUSTATORY STIMULI CROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims the benefit of U.S. Provisional Application No. 63 / 775.542, filed March 21, 2025, which is incorporated by reference in its entirety.FIELD OF THE INVENTION
[0002] Provided herein are methods for predicting a mental state elicited by an olfactory stimulus or gustatory stimulus. Also provided are compositions, e.g., accords and fully formulated fragrances and flavors, formulated to elicit a desired mental state in a subject, and consumer products containing such compositions.BACKGROUND OF THE INVENTION
[0003] The ability of odors and flavors to impact a subject, such as a human subject, psychologically (e.g., psychophysiologically) is widely recognized, and there exists broad interest in using fragrances and flavors for purposes of inducing emotional and / or cognitive states. However, formulating compositions capable of eliciting desired mental states in a subject has remained challenging due, at least in part, to difficulties in determining which mental states are elicited by a fragrance or flavor.
[0004] Thus, there exists a need for methods of predicting mental states elicited by olfactory stimuli and gustatory stimuli, and fragrances and flavors formulated to elicit mental states. The methods and compositions provided herein address these and other needs in the art.SUMMARY OF THE INVENTION
[0005] In an aspect is provided a method for producing a mental state-specific brain activity map, including: (a) identifying in one or more subjects a control brain activity, wherein the control brain activity represents brain activity evoked by exposure to a control stimulus, wherein the control stimulus is an olfactory stimulus or a gustatory stimulus that elicits a known mental state in a subject; and (b) determining, based on the control brain activity, one or more brain regions activated by the control stimulus to produce a mental state-specific brain activity map. In some embodiments, the known mental state elicited by the control stimulus is determined based onIFF101181-WO-PCTscientific literature, expert analysis, psychological testing, psychophysiological testing, behavioral testing, or any combination thereof. In some embodiments, the control stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor. In some embodiments, the control brain activity includes control brain activity from two or more or a plurality of subjects. In some embodiments, the determining of step (b) includes inputting the control brain activity into a fingerprinting algorithm. In some embodiments, the fingerprinting algorithm is a Partial Least Squares (PLS) model, a penalized regression model, a Classification and Regression Tree (CART) model, a Bayesian network model, or any combination thereof. In some embodiments, the CART model is an Extreme Gradient Boosting (XGBoost) model, a Random Forest model, a Chi-Square Automatic Interaction Detection (CHAID) model, or any combination thereof. In some embodiments, the penalized regression model is an adaptive Least Absolute Shrinkage and Selection Operator (LASSO) model, an adaptive Ridge regression model, an adaptive Elastic Net model, or any combination thereof. In some embodiments, the PLS model is a Partial Least Squares Discriminant Analysis (PLS-DA) and / or a Partial Least Squares Regression (PLS-R) analysis. In some embodiments, the control brain activity is identified using brain imaging. In some embodiments, the brain imaging is functional magnetic resonance imaging (fMRI). In some embodiments, the control brain activity includes a statistical value for each of the one or more brain regions, wherein the statistical value represents a probability that the brain region is activated by exposure to the control stimulus. In some embodiments, the statistical value for each of the one or more brain regions is a t-statistic and / or a beta value. In some embodiments, the t-statistics and / or beta values are normalized, baseline corrected, or scaled. In some embodiments, a brain region is a voxel, a region of interest (ROI), a macro-area, a lobe, or any combination thereof. In some embodiments, the statistical value for the ROI, the macro-area, or the lobe is, independently, a combination of the t-statistic and / or a combination of the beta values of all voxels contained in the ROI, the macro-area, or the lobe. In some embodiments, the method further includes producing a global network when more than one mental state-specific brain activity map is produced, and wherein the global network includes brain regions found in at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, 95%, 99%, or more of all mental state-specific brain activity maps produced.
[0006] In an aspect is provided a method for predicting a mental state elicited by an olfactory stimulus or a gustatory stimulus, including: (a) identifying in one or more subjects a test brainIFF101181-WO-PCTactivity, wherein the test brain activity represents brain activity evoked by exposure to a test stimulus, wherein the test stimulus is an olfactory stimulus or a gustatory stimulus that elicits an unknown mental state in a subject; (b) determining, based on the test brain activity, one or more brain regions activated by the test stimulus to produce a test mental state brain activity map; and (c) comparing the test mental state brain activity map to one or more mental state-specific brain activity maps produced according to the methods described herein that represents a known mental state, thereby determining whether the test stimulus elicits the mental state. In some embodiments, the method further includes comparing the test mental state brain activity map to a global network. In some embodiments, the test stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor. In some embodiments, the test brain activity includes test brain activity from two or more or a plurality of subjects. In some embodiments, the comparing of step (c) includes a qualitative comparison and / or predictive modeling. In some embodiments, the qualitative comparison includes calculating a percent similarity between the test mental state brain activity map and the mental state-specific brain activity map. In some embodiments, the qualitative comparison includes calculating a percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network. In some embodiments, the predictive modeling includes: (a) training a predictive model on the one or more mental state-specific brain activity maps produced according to the methods described herein; and (b) inputting the test mental state brain activity map into the trained predictive model to predict a mental state elicited by the test stimulus. In some embodiments, the predictive modeling includes: (a) training a predictive model on the one or more mental state- specific brain activity maps and a global network produced according to the methods described herein; and (b) inputting the test mental state brain activity map into the trained predictive model to predict a mental state elicited by the test stimulus. In some embodiments, the predictive model is a heuristic optimization algorithm. In some embodiments, the heuristic optimization algorithm is a differential evolution algorithm, a particle swarm optimization algorithm, and / or a genetic algorithm. In some embodiments, the comparing of step (c) further determines a strength by which the test stimulus elicits the mental state. In some embodiments, the test brain activity is identified using brain imaging. In some embodiments, the brain imaging is fMRI. In some embodiments, the test brain activity includes a statistical value for each of the one or more brain regions, wherein the statistical value represents a probability that the brain region isIFF101181-WO-PCTactivated by exposure to the test stimulus. In some embodiments, the statistical value for each of the one or more brain regions is a t-statistic and / or a beta value. In some embodiments, the t-statistics and / or beta values are normalized, baseline corrected, or scaled. In some embodiments, a brain region is a voxel, an ROI, a macro-area, a lobe, or any combination thereof. In some embodiments, the statistical value of the ROI, the macro-area, or the lobe is, independently, a combination of the t-statistic and / or a combination of a beta value of all voxels contained in the ROI, the macro-area, or the lobe.
[0007] In an aspect is provided a fragrance or flavor that elicits a mental state in a subject, identified according to the methods provided herein. In some embodiments, the fragrance or the flavor is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.
[0008] In an aspect is provided a method for producing a fragrance composition or a flavor composition that elicits a mental state in a subject, including: a) identifying a fragrance or a flavor that elicits a target mental state in a subject according to the methods provided herein; and b) incorporating the fragrance or the flavor that elicits the target mental state in a fragrance composition or a flavor composition. In some embodiments, the fragrance composition or the flavor composition is a new fragrance composition or a new flavor composition, and the new fragrance composition or the new flavor composition is being produced to elicit the target mental state in a subject. In some embodiments, the fragrance composition or the flavor composition is an existing fragrance composition or an existing flavor composition, and the existing fragrance composition or the existing flavor composition is being modified to elicit the target mental state in a subject. In some embodiments, the fragrance or the flavor is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor. In some embodiments, the fragrance is incorporated in a fragrance composition. In some embodiments, the fragrance composition is an accord or a full fragrance. In some embodiments, the flavor is incorporated in a flavor composition. In some embodiments, the flavor composition is a flavor accord or full flavor.
[0009] In an aspect is provided a consumer product including a fragrance or flavor that elicits a mental state or a fragrance composition or flavor composition produced according to the methods provided herein. In some embodiments, the consumer product is a household product, a fabric care product, an air care product, a personal care product, a cosmetic product, a fine fragrance, aIFF101181-WO-PCTbeverage product, a baked good, a confectionery good, a culinary product, a dairy product, a snack product, an oral care product, a health care product, or a nutritional product.
[0010] In an aspect is provided a use of a fragrance or flavor that elicits a mental state, a fragrance composition or flavor composition produced according to the methods provided herein, or a consumer product that elicits a target mental state in a subject. In an aspect is provided a method of eliciting a target mental state in a subject, including delivering a fragrance or flavor that elicits a mental state, a fragrance composition or flavor composition produced according to the methods provided herein, or a consumer product that elicits a mental state, to a subject.
[0011] In an aspect is provided a method for identifying an olfactory stimulus or a gustatory stimulus that elicits a mental state in a subject, including: (a) comparing a test mental state brain activity map, determined in response to a test stimulus, with one or more mental state-specific brain activity maps, wherein the one or more mental state- specific brain activity maps include an adventure brain activity map, an attention brain activity map, a craving brain activity map, a drive brain activity map, an energy brain activity map, a focus brain activity map, a happiness brain activity map, a learning brain activity map, a memory brain activity map, a mindfulness brain activity map, a relaxation brain activity map, a reward brain activity map, a seduction brain activity map, or a self-esteem brain activity map; and (b) identifying the test stimulus as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map is at least 20%, 30%, 40%, 50%, 60%. 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more.
[0012] In an aspect is provided a method for identifying an olfactory stimulus or gustatory stimulus that elicits a mental state in a subject, including: (a) comparing a test mental state brain activity map, determined in response to a test stimulus, with a global network and one or more mental state- specific brain activity maps, wherein the one or more mental state- specific brain activity maps include an adventure brain activity map, an attention brain activity map, a craving brain activity map, a drive brain activity map, an energy brain activity map, a focus brain activity map, a happiness brain activity map, a learning brain activity map, a memory brain activity map, a mindfulness brain activity map, a relaxation brain activity map, a reward brain activity map, aIFF101181-WO-PCTseduction brain activity map, or a self-esteem brain activity map; and (b) identifying the test stimulus as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more.
[0013] In an aspect is provided an olfactory stimulus or a gustatory stimulus that elicits an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject, determined according to the methods described herein, wherein the olfactory stimulus is a fragrance ingredient, a fragrance accord, a full fragrance and the gustatory stimulus is a flavor ingredient, a flavor accord, or a full flavor.
[0014] In an aspect is provided a method for producing a a fragrance composition or flavor composition that elicits a mental state in a subject, including: a) identifying an olfactory stimulus or a gustatory stimulus that elicits one or more mental states selected from an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, and a positive self-esteem mental state in a subject according to the methods described herein; and b) incorporating the olfactory stimulus or the gustatory stimulus that elicits the mental state into a fragrance composition or a flavor composition.
[0015] In an aspect is provided a consumer product comprising an olfactory stimulus or a gustatory stimulus that elicits an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject.
[0016] In an aspect is provided a method of eliciting a mental state in a subject, including delivering an olfactory stimulus or a gustatory stimulus that elicits a mental state in a subject to a subject, wherein the mental state is one or more of adventurous, attentive, craving, driven, energetic, focused, happy, learning, memory, mindfulness, relaxed, reward, seductive, or positive self-esteem. In an aspect is provided use of an olfactory stimulus or a gustatory stimulus that elicits a mental state in a subject to elicit a mental state in a subject, wherein the mental state is one orIFF101181-WO-PCTmore of adventurous, attentive, craving, driven, energetic, focused, happy, learning, memory, mindfulness, relaxed, reward, seductive, or positive self-esteem.
[0017] Each of the aspects and embodiments described herein are capable of being used together, unless excluded either explicitly or clearly from the context of the embodiment or aspect.DETAILED DESCRIPTION OF THE INVENTION
[0018] The mammalian olfactory pathway is an evolutionarily old pathway that differs from canonical thalamocortical sensory pathways in that it forms direct, and in some cases reciprocal, connections with brain structures involved in emotion and memory. For example, olfactory sensory neurons present in the nose convey sensory information to the olfactory bulb, located in the forebrain, where they form synapses with projection neurons that directly or indirectly target limbic system structures such as the hippocampus and amygdala, which are involved in memory and emotion. Thus, the sense of smell is uniquely positioned neuroanatomically to directly influence a subject’s mental state.
[0019] The sense of smell can be engaged in distinct ways. For example, orthonasal olfaction, which occurs when a subject inhales or sniffs, allows the subject to smell odors from outside of the body by pulling odor molecules into the nostrils where they bind to olfactory receptors in the nose and thereby engage the olfactory pathway. The olfactory pathway may also be engaged by retronasal olfaction, which occurs during exhalation and allows the subject to smell odors originating from inside the mouth, for example during eating and drinking. During exhalation, odor molecules present in the mouth are pushed through the nasopharynx into the nasal cavity, where they bind to olfactory receptors. Retronasal olfaction gives rise to the perception of flavor, e.g., in food and beverages, and is commonly associated with the sense of taste. The sense of smell is therefore key to both the appreciation of fragrances and flavors.
[0020] Despite longstanding interest in using olfactory stimuli and gustatory stimuli to elicit specific mental states (e.g., emotional and / or cognitive states) in subjects, production of compositions and consumer products that reliably induce a mental state in a subject is not a straightforward task. Strategies to determine mental states induced by fragrances and flavors, e.g., fragrance ingredients, fragrance accords, full fragrances, flavor ingredients, flavor accords, and full flavors, have typically included explicit (conscious) analyses, e.g., declarative measures such as subject self-reporting; implicit (unconscious) analyses, such as brain imaging, e.g.,IFF101181-WO-PCTelectroencephalography (EEG) and functional magnetic resonance imaging (fMRI), psychophysiological and behavioral measures, such as heart rate, blood pressure, skin temperature, skin conductance, muscle tension, facial emotions, eye tracking, implicit association, and projective tests; and combinations thereof. Declarative measures allow a test subject to explicitly describe their mental state in response to a stimulus, while brain imaging techniques measure implicit responses to stimuli by detecting brain activity. US 10,042,023, for example, describes the use of fMRI to determine whether a fragrance activates the dopaminergic pathway, which is associated with the sensation of reward, among other behavioral processes. Published International application W02018 / 115107 describes a method of combining declarative measures and brain imaging techniques to compare odorants with similar hedonicity but which evoke different feelings. These strategies, however, provide only a limited determination of mental states evoked by a fragrance, e.g., an odor.
[0021] The brain is composed of a finite number of anatomical regions; however, the brain is capable of producing mental states that may exceed the total number of its constituting regions. This suggests that a brain region may participate in more than one mental, e.g., emotional or cognitive, state. To illustrate, the dopaminergic pathway is known to be involved not only in reward processing but also in behaviors such as movement, cognition, motivation, and neuroendocrine function. Thus, without assessing activity in additional brain areas, it may be difficult to determine exactly which mental state is induced by an olfactory stimulus or a gustatory stimulus. Furthermore, the level and directionality of activation in a brain region, when considered amongst the activity of all brain regions, may be important for determining differences between mental states.
[0022] Issues may also arise when attempting to match a brain activity pattern to a declarative measure. For example, self-reporting data can be susceptible to external factors, such as social pressure or desirability, or internal factors such as the inability to recall or articulate an experience. Thus, even if a global pattern of brain activity is assessed, it is possible to inadvertently match the activity to an incorrect mental state if rigorous procedures and analyses are not used.
[0023] Furthermore, it is possible that an olfactory stimulus or a gustatory stimulus can induce more than one mental state. The current techniques for determining a mental state induced by an olfactory stimulus or gustatory stimulus using brain imaging and declarative data may not beIFF101181-WO-PCTsensitive enough to determine differences in related (e.g., correlated) mental states or in determining whether an olfactory stimulus or gustatory stimulus induces one or more mental states, and. optionally, a strength by which the olfactory stimulus or gustatory stimulus induces the mental state.
[0024] Thus, there remains a need for improved methods of determining mental states induced by olfactory stimuli or gustatory stimuli, and compositions designed according to the results of such methods. The methods and compositions provided herein address such needs, among others, and offer unexpected advantages over alternative methods.
[0025] The methods provided herein include imaging brain activity evoked in response to an olfactory stimulus or gustatory stimulus that elicits a known mental state and analyzing the evoked brain activity, e.g., using artificial intelligence, to produce a mental state- specific brain activity map, where the mental state- specific brain activity map represents a brain region activation pattern that underlies the mental state. The method further includes determining a mental state induced by an olfactory stimulus or gustatory stimulus where the mental state elicited is unknown by comparing a test mental state brain activity map, where the test mental state brain activity map includes one or more brain regions activated in response to the olfactory stimulus or gustatory stimulus, to a mental state- specific brain activity map to determine whether the olfactory stimulus or gustatory stimulus elicits the mental state. In some embodiments, the method includes a determination of the extent (e.g., strength) to which the mental state is elicited by the olfactory stimulus or gustatory stimulus. The methods provided herein thus allow a determination of one or more mental states induced by an olfactory stimulus or gustatory stimulus and, optionally, provide a measure of the strength with which the olfactory stimulus or gustatory stimulus elicits the mental state.
[0026] The methods described herein are advantageous because they account for the ability of a brain region to participate in more than one mental state and for the ability of an olfactory stimulus or gustatory stimulus to induce more than one mental state. The methods are further advantageous in their ability to determine the strength with which the olfactory stimulus or gustatory stimulus elicits each mental state. In addition, the methods include the use of artificial intelligence for extracting mental state- specific brain activity maps and test mental state brain activity maps and for performing comparisons, for example between mental state-specific brain activity maps andIFF101181-WO-PCTtest mental state brain activity maps. The use of artificial intelligence in multiple steps of the method is advantageous in allowing an unbiased analysis of brain activity.
[0027] The methods described herein elucidate olfactory stimuli, e.g., fragrance ingredients, fragrance accords, and full fragrances, and gustatory stimuli, e.g., flavor ingredients, flavor accords, and full flavors, that induce one or more mental states and the strength with which the state is induced. These findings can be used to produce compositions (flavors, fragrances) that induce one or more mental states in a subject, optionally at different intensities (e.g., strength with which the mental state is induced).
[0028] The methods provided herein enable the production of compositions that induce mental states with a precision previously unrealized. Thus, in an aspect is provided methods for preparing a fragrance or flavor composition that induces a mental state in a subject from exposure to the fragrance or flavor composition. In some embodiments, the fragrance or flavor composition is a newly designed fragrance or flavor. In some embodiments, the fragrance or flavor composition is an existing composition to which a fragrance or flavor ingredient or combination of ingredients known to induce a desired mental state are added. In this way. the result of the methods for determining mental states induced by fragrances and flavors can be used to develop new fragrance and flavor compositions or modify existing fragrance and flavor compositions to elicit one or more desired mental states. In some embodiments, the result of the methods for determining mental states induced by fragrances and flavors can be used to develop new fragrance and flavor compositions or modify existing fragrance and flavor compositions to elicit or enhance the strength of the one or more desired mental states. In some embodiments, the methods provided herein allow for the creation of ingredients (fragrance ingredients, flavor ingredients) that evoke a mental state.
[0029] The methods described herein may be computer-implemented unless context specifies otherwise (such as e.g. where measurement steps and / or wet steps are involved). Thus, the methods described herein are typically performed using a computer system or computer device. Any reference to an action such as “obtaining,” “processing,” “determining,” may therefore refer to a processor performing the action, or a processor executing instructions that cause the processor to perform the action.
[0030] The results generated according to the methods provided herein may be collected in a database. In some embodiments, the database is searchable, e.g., by querying. In someIFF101181-WO-PCTembodiments, the database may include a user interface to facilitate searching (querying) and data extraction. In some embodiments, the database may be queried to identify fragrances and flavors useful for formulating a composition, optionally an existing or new composition, that induces one or more desired mental states in a subject. A desired mental state may also be referred to herein alternatively as a target mental state. In some embodiments, the database may be used to predict a consumer’s mental state in response to a fragrance or flavor composition, e.g., an existing composition or new composition, without the need to perform experimentation. For example, the mental state may be predicted based on the ingredients or combinations of ingredients, e.g., accords, in the fragrance or flavor composition in view of the known mental states induced by the ingredients and / or combinations of ingredients, optionally with a strength based on the known strength of the mental states induced by the ingredients and / or combinations of ingredients.
[0031] Also provided herein are ingredients and compositions, such as accords and full fragrances or flavors, that elicit a mental state in a subject. Fully formulated flavors and fragrances, flavor and fragrance accords, and consumer products containing ingredients and / or compositions that elicit a mental state in a subject are also provided.
[0032] Additionally, as described in Section V, mental state- specific brain activity maps were identified for sensations related to adventurousness, attention, craving, drive, energy, focus, happiness, learning, memory, mindfulness, relaxation, reward, seduction, and positive self-esteem according to the methods described herein. With these mental state-specific brain activity maps, brain activity evoked by test stimuli (e.g., olfactory stimuli or gustatory stimuli) could be compared against the mental state-specific brain activity map to identify which mental states were evoked by the test stimulus. Thus, provided herein are methods for determining whether an olfactory stimulus or a gustatory stimulus, elicits one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a rewarded, a seductive, or a positive self-esteem mental state in a subject. These terms are used to describe the mental state for purposes of simplicity, and more comprehensive descriptions of these mental states is provided below. The methods provided herein include imaging brain activity evoked in response to an olfactory stimulus or gustatory stimulus to determine a test mental state brain activity map, and determining, from the test mental state brain activity map, whether one or more mental state-specific brain activity maps are activated. In some embodiments, determining activation of a mental state-specific brain activity map includes determining how many brainIFF101181-WO-PCTregions of the mental state-specific brain activity map show an increase in activity in the test mental state brain activity map. In some embodiments, the method further includes determining activation of a global network, which may be accomplished by determining how many brain regions of the global network show an increase in activity in the test mental state brain activity map. In some embodiments, determining activation of a mental state-specific brain activity map includes determining how many brain regions of the mental state- specific brain activity map show an increase or decrease in activity in the test mental state brain activity map. In some embodiments, the method further includes determining activation of a global network, which may be accomplished by determining how many brain regions of the global network show an increase or decrease in activity in the test mental state brain activity map.
[0033] The methods and compositions described herein are advantageous in that they provide useful and reliable information from brain imaging data, which can improve the production speed, efficiency, and reliability of fragrance and flavor compositions produced for purposes of inducing a desired mental state. The methods described herein allow for the creation of fragrance and flavor formulation guidelines for producing a composition that induces a desired mental state in a subject.
[0034] This disclosure is not limited by the exemplary methods and materials disclosed herein, and any methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of this disclosure.
[0035] The headings provided herein are not limitations of the various aspects or embodiments of this disclosure which can be had by reference to the specification as a whole. The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described. Any terms defined are more fully defined by reference to the specification as a whole.
[0036] All publications, including patent documents, scientific articles and databases, referred to in this application are incorporated by reference in their entirety for all purposes to the same extent as if each individual publication were individually incorporated by reference. Nothing herein is to be construed as an admission that such publications constitute prior art. If a definition set forth herein is contrary to or otherwise inconsistent with a definition set forth in the patents, applications, published applications and other publications that are herein incorporated by reference, the definition set forth herein prevails over the definition that is incorporated herein by reference.IFF101181-WO-PCTDefinitions
[0037] Definitions of terms may appear throughout the specification. It is to be understood that this disclosure is not limited to particular embodiments described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.
[0038] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs.
[0039] It must be noted that as used herein and in the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. For example, “a” or “an” include “at least one” and “one or more.”
[0040] The terms “comprising,” “comprises,” “comprise,” and “comprised of’ as used herein are synonymous with “including,” “includes,” “include,” “containing,” “contains,” “contain,” “having,” “have.” “has.” and grammatical variants thereof, and are inclusive or open-ended and do not exclude additional, non-recited members, elements, or method steps. The terms “comprising,” “comprises,” “comprise.” “comprised of.” “including,” “includes,” “include” “containing,” “contains,” “contain,” ‘having,” “have,” “has,” and grammatical variants thereof also include the term “consisting of.” It is understood that wherever aspects are described herein with the language “comprising,” otherwise analogous aspects described in terms of “consisting of and / or “consisting essentially of’ are also provided.
[0041] The term “consisting of’ means “including and limited to.”
[0042] The term “consisting essentially of’ means the specified material of a composition, or the specified steps of a methods, and those additional materials or steps that do not materially affect the basic characteristics of the material or method.
[0043] It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only,” and the like in connection with the recitation of claim elements or use of a “negative” limitation.IFF101181-WO-PCT
[0044] “Optional” or “optionally” means that the subsequently described event or circumstance may or may not occur, and that the description includes instances where said event or circumstance occurs and instances where it does not.
[0045] Fragrance, and grammatical variants thereof, may be used for simplicity herein to refer to fragrance ingredients, and combinations of fragrance ingredients, such as accords and full fragrances. In some embodiments, the fragrance is a fragrance ingredient. In some embodiments, the fragrance is a fragrance accord. In some embodiments, the fragrance is a full fragrance, e.g., a perfume. In some embodiments, the fragrance is a fragrance composition.
[0046] A fragrance ingredient, as is known by a person of skill in the art, may itself include many individual chemical compounds and may possess a pleasant smell. A fragrance ingredient may be any natural oil or extract, or chemical compound used in a fragrance composition. Natural oils and extracts are described in The Essential Oils by E. Guenther published by Van Nostrand and may include extracts and distillates from any part of suitable plants: roots, rhizomes, bulbs, corms, stem, bark, heartwood, leaves, flowers, seeds, and fruit. Examples of such extracts and distillates include, but are not limited to. citrus fruit oils such as orange or lemon oil, tree oils such as pine oil or cedarwood oil, herb oils such as peppermint oil, thyme oil, rosemary oil, clove oil, or flower extracts such as rose oil, or geranium oil. A wide variety of synthetic fragrance ingredients are also known for use in perfume creation, including, but not limited to. materials possessing a variety of chemical functional groups, such as acetals, alkenes, alcohols, aldehydes, amides, amines, esters, ethers, imines, nitriles, ketals, ketones, oximes, thiols, thioketones, etc. A fragrance accord typically has less than 25 individual materials and has a singular or simple scent direction, e.g., floral accord, woody accord. A fully formulated fragrance can be made from combining accords, or one or more accords and individual ingredients, or multiple individual ingredients, and has a more complex scent description, e.g., fruity-floral-woody. Fragrances may also contain additives (e.g. solvents or solubilizers such as surfactants) that are compatible with the products into which they are incorporated.
[0047] The terms “fragrance composition,” “fragrance formulation,” “perfume composition,” and variants, including grammatical variants, thereof mean the same and refer to a composition that is a mixture of fragrance ingredients and / or fragrance accords including, for example, but not limited to. alcohols, aldehydes, ketones, esters, ethers, lactones, nitriles, natural extracts (e.g.. essentialIFF101181-WO-PCToils, absolutes, CO2 extracts, enfleurages, isolates either pure or purified using physical processes), synthetic oils, mercaptans, accords and / or ingredients as describe supra, etc., which are admixed so that the combined odors of the components produce a fragrance.
[0048] Flavor, and grammatical variants thereof, may be used for simplicity herein to refer to flavor ingredients, and combinations of flavor ingredients, such as flavor accords and full flavors. A flavor is taken in the mouth, and may be perceived by the sense of smell, e.g., by retronasal olfaction. A flavor may have a singular or simple flavor direction, e.g., apple flavor, meat flavor, or a more complex flavor direction e.g. apple pie, BBQ flavor. A flavor may be added to food or beverages to impart, modify, or enhance the flavor of the food or beverage. Flavors may include, but are not limited to, flavor ingredients (which include natural flavoring substances and extracts as well as synthetic flavor substances), natural flavor complexes, thermal process flavors or smoke flavors, and combinations thereof, and may further contain non-flavor ingredients. A flavor accord may consist of a few to more than 40 ingredients, e.g., as listed above. Flavors may be incorporated into flavoring preparations, food products, oral care products, health care products, nutritional products, or beverages. Flavors may also contain additives (e.g. solvents or solubilizers such as surfactants) that are compatible with the products into which they are incorporated. In some embodiments, the flavor is a flavor ingredient. In some embodiments, the flavor is a flavor accord. In some embodiments, the flavor is a full flavor. In some embodiments, the flavor is a flavor composition
[0049] The terms “flavor composition,” “flavor formulation,” “taste composition,” and variants, including grammatical variants, thereof mean the same and refer to a composition that is a mixture of flavor ingredients and / or flavor accords. Non-limiting examples of flavor ingredients and accords include, but are not limited to, flavor ingredients and flavor accords described supra, which are admixed so that the combined properties, including odors, of the components produce a flavor.
[0050] Fragrance and flavor ingredients are described more fully in S. Arctander, Perfume, Flavors, and Chemicals. Vols. I and II, Montclair, N.J., the Merck Index, 8th Edition, Merck & CO., Inc. Rahway, N.J., Allured's Flavor and Fragrance Materials 2013 Published by Allured Publishing Corp ASIN: B01FKWD33S, and Surburg and Panten Eds, Common Fragrance andIFF101181-WO-PCTFlavor Materials: Preparation, Properties & Uses, 6thEdition, Published by Wiley-VCH (2016) ISBN- 10:3527331603, each of which is incorporated herein by reference in their entirety.
[0051] As used herein, the term “subject” refers to the user of a fragrance or flavor. The subject may also be the intended recipient of a fragrance or flavor, for example when it is used or administered by another. The term “subject” refers to a human or non-human subject. Non-limiting examples of non-human subjects include non-human primates, dogs, cats, mice, rats, guinea pigs, rabbits, pigs, fowl, horses, cows, goats, sheep, cetaceans, etc. In some embodiments, the subject is a human.
[0052] Induce, evoke, elicit, drive, impart, provoke, promote, enhance, and grammatical variants thereof may be alternatively used to indicate a cause-and-effect relationship. For example, an olfactory stimulus or gustatory stimulus may induce, elicit, evoke, impart, provoke, drive, promote, or enhance brain activity underlying a mental state in a subject upon exposure to the olfactory stimulus or the gustatory stimulus, thereby causing the subject to perceive (e.g., experience) the mental state. Thus, in some embodiments, the olfactory stimulus or gustatory stimulus elicits the mental state in the subject.
[0053] The term “increased” as used herein may refer to a quantity or activity that is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 50%, 100%, or 200% more than the quantity or activity for which the increased quantity or activity is being compared. The terms “increased,” “elevated,” “enhanced,” “greater than,” “improved,” “more” and the like are used interchangeably herein.
[0054] The term “decreased” as used herein may refer to a quantity or activity that is at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 11%, 12%. 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 50%, 100%, or 200% less than the quantity or activity for which the decreased quantity or activity is being compared. The terms “decreased,” “lowered,” “reduced,” “less,” “less than,” and the like are used interchangeably herein.
[0055] “Brain activity” refers to the physiological and biochemical activity within the brain, e.g., a human brain, or a region of the brain, associated with mental activity. Such activity may be evidenced by, but not limited to, increases or decreases in blood flow to brain regions, changes in oxygen level in the blood, increases or decreases in metabolic activity (e.g., glucose consumption), changes in electrical potential of neurons, and the release of neurotransmitters or neuromodulators.IFF101181-WO-PCTBrain activity can be measured non-invasively by, for example, measuring changes in electrical fields and / or magnetic fields emanating from the cranium or by the blood oxygen level dependent (BOLD) method, which is a recognized technique for measuring brain activity which correlates with the increased energy consumption by the brain and the contrast between oxyhemoglobin and de-oxyhemoglobin. Exemplary brain imaging methods are further described in Section I-D.
[0056] The term “brain region” as used herein refers to a volume of tissue within the human brain, which can be of any shape, and which can be characterized anatomically, spatially, and / or functionally. Brain regions are further described in Section LD.
[0057] The term “voxel,” as used herein, refers to a multidimensional data point corresponding to a specific volume in space, and particularly refers to such a data point obtained from a brain imaging procedure and corresponding to a specific volume within the brain. Voxel size is dependent on the experimental procedure and equipment, notably the resolution of the magnetic resonance imaging (MRI) instrument.
[0058] The terms “computer system” or “computer device” includes the hardware, software and data storage devices for embodying a system or carrying out a computer implemented method. For example, a computer system may comprise one or more processing units such as a central processing unit (CPU) and / or a graphical processing unit (GPU), input means, output means and data storage, which may be embodied as one or more connected computing devices. In some embodiments, the computer system has a display or includes a computing device that has a display to provide a visual output display. The data storage may comprise RAM, disk drives or other computer readable media. The computer system may include a plurality of computing devices connected by a network and able to communicate with each other over that network. For example, a computer system may be implemented as a cloud computer. The term “computer readable media” includes, without limitation, any non-transitory medium or media which can be read and accessed directly by a computer or computer system. The media can include, but are not limited to, magnetic storage media such as floppy discs, hard disc storage media and magnetic tape; optical storage media such as optical discs or CD-ROMs; electrical storage media such as memory, including RAM, ROM and flash memory; and hybrids and combinations of the above such as magnetic / optical storage media. In some embodiments, the methods provided herein are computer-implemented methods. In some embodiments, the methods provided herein are performed using aIFF101181-WO-PCTcomputer system. In some embodiments, a non-transitory computer-readable medium stores instructions that, when executed by a processor, cause the processor to execute the methods.
[0059] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within this disclosure. The upper and lower limits of these smaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within this disclosure, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in this disclosure.
[0060] Values and ranges may be presented herein with numerical values being preceded by the term “about.” The term “about” is used herein to provide literal support for the exact number that it precedes, as well as a number that is near to or approximately the number that the term precedes. In determining whether a number is near to or approximately a specifically recited number, the near or approximating unrecited number can be a number which, in the context in which it is presented, provides the substantial equivalent of the specifically recited number. For example, in connection with a numerical value, the term “about” refers to a range of -10% to +10% of the numerical value, unless the term is otherwise specifically defined in context. All values and ranges may implicitly include the term “about” unless the context dictates otherwise.I. METHODS FOR PREDICTING MENTAL STATES ELICITED BY AN OLFACTORY STIMULUS OR A GUSTATORY STIMULUS
[0061] Provided herein are methods for predicting a mental state elicited in a subject upon exposure to an olfactory stimulus or a gustatory stimulus, where the mental state elicited by the olfactory stimulus or the gustatory stimulus is not previously known. An olfactory stimulus or gustatory stimulus where the mental state elicited is unknown may be referred to herein alternatively as a test stimulus.
[0062] In some embodiments, the methods for predicting a mental state elicited by a test stimulus include the use of one or more mental state- specific brain activity maps, which are furtherIFF101181-WO-PCTdescribed in Section I-A below. A mental state- specific brain activity map represents a brain activity evoked by an olfactory stimulus or gustatory stimulus that is known to elicit a specific mental state in a subject. An olfactory stimulus or gustatory stimulus where the mental state elicited is known may be referred to herein alternatively as a control stimulus. Brain activity evoked by a control stimulus may be referred to herein as a control brain activity.
[0063] For purposes of predicting a mental state elicited by a test stimulus, in some embodiments, the one or more mental state-specific brain activity maps are compared with a test mental state brain activity map, which is determined from brain activity evoked by a test stimulus. See, e.g., Section I-B. Brain activity evoked by a test stimulus, e.g., an olfactory stimulus or gustatory stimulus for which determination of a mental state elicited is desired, may be referred to herein as a test brain activity. In some embodiments, the comparison between the mental state-specific brain activity map and the test mental state brain activity map determines whether one or more mental states are elicited by the test stimulus. In some embodiments, the comparison between the mental state- specific brain activity map and the test mental state brain activity map provides a measure indicating how strongly the test stimulus elicits a mental state.
[0064] The following sections describe, inter alia, methods for producing a mental state-specific brain activity map and a test mental state brain activity map, methods for comparing such maps to predict the mental states elicited in subjects by test stimuli, and methods of imaging and analyzing brain activity and storing data.A. Mental State- Specific Brain Activity Maps
[0065] The determination of brain activity that underlies a mental state according to the methods provided herein facilitates the prediction of whether an olfactory stimulus or gustatory stimulus elicits a mental state in a subject. Thus, in an aspect is provided a method for producing a mental state- specific brain activity map. In some embodiments, the method includes identifying in one or more subjects a control brain activity, where the control brain activity represents brain activity evoked by exposure to a control stimulus. In some embodiments, the method further includes determining, based on the control brain activity, one or more brain regions activated by the control stimulus to produce a mental state-specific brain activity map. In some embodiments, the mental state- specific brain activity map represents the brain activity underlying the evoked known mental state. In some embodiments, the mental state-specific brain activity maps may be used to determineIFF101181-WO-PCTthe mental states induced by stimuli, e.g., olfactory stimuli or gustatory stimuli, for which the mental state it induces is unknown.
[0066] Mental state-specific brain activity maps may be created for any mental state of interest according to the methods provided herein and used according to the methods provided herein. In some embodiments, a mental state is any emotional or cognitive state. In some embodiments, a mental state is any emotional or cognitive state indicative of or underlying a physical state. For example, physical states for which a mental state may exist or may be detected include, but are not limited to, satiety, sleep (e.g., sleep stages), wakefulness, or fatigue. In some embodiments, the mental state is an emotional or cognitive state that is known to include activity in one or more, optionally two or more, brain regions. For example, a mental state may be a mental state studied using psychological and / or neuroscientific methods. Non-limiting examples of mental states include, but are not limited to, energy, relaxation, happiness, mindfulness, memory, learning, seduction, self-esteem, motivation, focus, attention, craving, reward, adventure, satiety, sleep, wakefulness, and fatigue. In some embodiments, the mental state is one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state. See, e.g., Section II, below.
[0067] In some embodiments, the known mental state elicited by a control stimulus is determined based on scientific literature, expert analysis, psychological testing, psychophysiological testing, behavioral testing, or any combination thereof. In some embodiments, the known mental state elicited by the control stimulus is known from empirical data. In some embodiments, the known mental state elicited by the control stimulus is known from implicit testing and / or explicit testing.
[0068] In some embodiments, the known mental state elicited by the control stimulus is known from a psychological test. In some embodiments, the psychological test is an explicit test. In some embodiments, the psychological test is a declarative test. In some embodiments, the psychological test is not performed on the same subject that undergoes brain imaging to determine brain activity evoked by the control stimulus. In some embodiments, the psychological test is performed on the same subject that undergoes brain imaging to determine brain activity evoked by the control stimulus, hi cases where psychological testing, including, but not limited to, declarative testing is used, the experimental design controls for potential issues with psychological test reporting.IFF101181-WO-PCT
[0069] In some embodiments, the known mental state elicited by the control stimulus is known from scientific literature. Non-limiting examples of scientific literature include scientific research publications, scientific textbooks, meta-analyses of scientific research publications, and / or publicly available scientific databases.
[0070] In some embodiments, the known mental state elicited by the control stimulus is known from aromatherapy. For example, the control stimulus may be an olfactory stimulus that has been studied according to aromatherapy methods. In some embodiments, the known mental state elicited by the control stimulus is known from aromachology. For example, the control stimulus may be an olfactory stimulus that has been studied according to aromachology methods. Aromatherapy and aromachology methods are generally known in the art.
[0071] In some embodiments, the known mental state elicited by the control stimulus is known from psychophysiological data. Psychophysiological data, for example, may include, but is not limited to, one or more of a heart rate (e.g., HRV), a blood pressure, a skin temperature, a skin conductance, a muscle tension, or a brain activity (e.g., neural activity, brain oscillatory activity).
[0072] In some embodiments, the known mental state elicited by the control stimulus is known from behavioral data. Behavioral data, for example, may include, but is not limited to, one or more of facial emotion, eye tracking, implicit tests (e.g., implicit association testing), or projection tests.
[0073] In some embodiments, the known mental state elicited by the control stimulus is known from expert analysis. For example, it may be the case that experts such as perfumers or flavorists provide the identity of the mental state elicited by the control stimulus. An expert may be able to provide such information based on her understanding and training in her field.
[0074] In some embodiments, the known mental state elicited by the control stimulus is predicted to elicit the known mental state with a level of strength. In some embodiments, the strength is determined based on a consistency across the scientific literature, the expert analysis, the psychological testing, the psychophysiological testing, the behavioral testing, or any combination thereof, in identifying the control stimulus as eliciting the known mental state. By way of example, if every method used to identify the known mental state elicited by the control stimulus reports the same mental state, the control stimulus is considered to strongly elicit the mental state. However, if the methods used to identify the known mental state do not consistently indicate the same mental state as elicited by the control stimulus, the strength by which the control stimulus elicits the knownIFF101181-WO-PCTmental state will be less than a control stimulus that strongly elicits a mental state. In some embodiments, the strength is represented by a numerical value. In some embodiments, the numerical value is part of a range of numerical values. Any suitable range of numerical values is contemplated for use as long as it is appropriate to the objective, e.g., a scale to determine a level of strength. In some embodiments, the strength is represented by a value in a range from 0 to 1. hi some embodiments, the strength is represented by a value in a range from 0% to 100%.
[0075] In some embodiments, the strength may be used to produce the mental state-specific brain activity map. For example, when more than one control stimulus is used for a single mental state, the strength may be used as a weight to determine how much the brain activity evoked by the control stimulus will contribute to the mental state- specific brain activity map for the specific known mental state. Alternatively, if brain activity evoked by control stimuli for a specific known mental state are not combined to produce the mental state-specific brain activity map, the strength may be used as a measure of how strongly the control stimulus elicits a known mental state. Thus, in some cases, comparing a mental state-specific brain activity map from a control stimulus with a predicted strength with a test mental state brain activity map provides a strength by which the test stimulus elicits a mental state. Additional methods of determining a strength by which the test stimulus elicits a mental state are described in Section I-C.
[0076] In some embodiments, a graded strength prediction (e.g., a numerical value of a range) is not provided for a known mental state elicited by the control stimulus. For example, in some embodiments, if at least one of the scientific literature, the expert analysis, the psychological testing, the psychophysiological testing, or the behavioral testing used in identifying the control stimulus as eliciting the known mental state states that the mental state is elicited, the olfactory stimulus or gustatory stimulus is considered to elicit the known mental state. In some embodiments, if at least one of the scientific literature, the expert analysis, the psychological testing, the psychophysiological testing, or the behavioral testing used in identifying the control stimulus as eliciting the known mental state states that the mental state is elicited, the olfactory stimulus or gustatory stimulus is denoted with a value of 1 or 100%, indicating that it elicits the mental state. In some embodiments, if none of the scientific literature, the expert analysis, the psychological testing, the psychophysiological testing, or the behavioral testing used in identifying the control stimulus as eliciting the known mental state states that the mental state is elicited, the olfactory stimulus or gustatory stimulus is denoted with a value of 0 or 0%, indicating that it doesIFF101181-WO-PCTnot elicit the mental state. In some cases, denoting a value of 0 or 0% for an olfactory stimulus or gustatory stimulus indicates that the stimulus does not elicit the mental state. For example, in some cases. 0 or 0% may be used when the evidence, e.g.. scientific literature, expert analysis, psychological testing, psychophysiological testing, or behavioral testing, specifically states that the mental state is not elicited. However, it will also be appreciated that in some instances, there may be insufficient evidence to determine whether a stimulus elicits a mental state. In such cases, denoting a value of 0 or 0% for an olfactory stimulus or gustatory stimulus may indicate that there is insufficient evidence to confirm that the stimulus elicits the mental state (e.g., at that time). In some embodiments, when it is uncertain based on the evidence, e.g., scientific literature, expert analysis, psychological testing, psychophysiological testing, or behavioral testing, that an olfactory stimulus or gustatory stimulus elicits a mental state, a low value, e.g., about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 15%, or 20%, may be denoted for the stimulus. In some embodiments, a strength by which a test stimulus elicits a mental state may be determined using mental statespecific brain activity maps lacking a predicted strength, for example, as described in Section I-C below.
[0077] In some embodiments, if there is a contradiction in one or more of the scientific literature, the expert analysis, the psychological testing, the psychophysiological testing, or the behavioral testing used in identifying the control stimulus as eliciting the known mental state, the stimulus is not used as a control stimulus. For example, in cases where the results conflict within or between testing methods such that a piece of evidence suggests that the mental state is elicited and another piece of evidence suggests that the mental state is not elicited, the stimulus is not used as a control stimulus to create, either alone or in combination, a mental state-specific brain activity map. hi some embodiments, when there is no evidence indicating that a stimulus does or does not elicit a mental state, the stimulus is not used as a control stimulus to create, either alone or in combination, a mental state- specific brain activity map.
[0078] In some embodiments, the control stimulus is an olfactory stimulus. In some embodiments, the control stimulus is a gustatory stimulus. In some embodiments, the control stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor. In some embodiments, the control stimulus is a fragrance ingredient. In some embodiments, the control stimulus is a fragrance accord. In some embodiments, the control stimulus is a full fragrance. In some embodiments, the control stimulus is a flavor ingredient. InIFF101181-WO-PCTsome embodiments, the control stimulus is a flavor accord. In some embodiments, the control stimulus is a full flavor. In some embodiments, the control stimulus elicits a known mental state. In some embodiments, the control stimulus elicits a known mental state with a predicted strength.
[0079] In some cases, the control brain activity identified in response to a control stimulus is determined by imaging brain activity in more than one subject in response to the same control stimulus. In cases where the brain activity of more than one subject in response to the same control stimulus is performed, the brain activity in each subject may be combined to produce the control brain activity. Section I-D describes various methods by which brain activity, including control brain activity and test brain activity, may be identified and processed for use according to the methods provided herein.
[0080] In some embodiments, the control brain activity is a combination of control brain activity evoked by control stimuli eliciting the same known mental state. In some embodiments, for example when a predicted strength is determined for each control stimulus, the control brain activity is a weighted combination of control brain activity evoked by control stimuli eliciting the same known mental state.
[0081] In some embodiments, the control brain activity is analyzed to determine one or more brain regions activated by the control stimulus to produce a mental state-specific brain activity map. Activation, as further described in, e.g., Section I-D below, may include increases in brain activity and / or decreases in brain activity in one or more brain regions. In some embodiments, when two or more brain regions are imaged, the activity may represent a mixture of brain regions with an increase in activity, a decrease in activity, or no changes in activity. In some embodiments, the mental state-specific brain activity map includes brain regions with increased activity. In some embodiments, the mental state-specific brain activity map includes brain regions with decreased activity. In some embodiments, the mental state- specific brain activity map includes brain regions with increased activity and brain regions with decreased activity. In some embodiments, the mental state- specific brain activity map includes brain regions with no change in activity.
[0082] The determination of the one or more brain regions activated by a control stimulus to produce the mental state- specific brain activity map may include the use of artificial intelligence, machine learning, statistics, and / or data science. For example, such algorithms may be used to identify unique features from complex data structures and / or reduce data dimensionality. Such anIFF101181-WO-PCTapproach may reduce the complexity of the dataset by identifying a unique pattern or features that can be used to describe the data. This approach also offers a computationally efficient means of representing complex or high dimensional datasets, which may allow for further analysis. Therefore, in some embodiments, determining a mental state-specific brain activity map includes inputting control brain activity into an artificial intelligence algorithm. In some embodiments, the algorithm is a dimensionality reduction algorithm. In some embodiments, the algorithm is a fingerprinting algorithm. In some embodiments, the fingerprinting algorithm is a Partial Least Squares (PLS) model, a Classification and Regression Tree (CART) model, a Bayesian network model, or any combination thereof. In some embodiments, the fingerprinting algorithm is a Partial Least Squares (PLS) model, a penalized regression model, a Classification and Regression Tree (CART) model, a Bayesian network model, or any combination thereof. In some embodiments, the output of the algorithm is the mental state- specific brain activity map. In some embodiments, the output of the algorithm is further processed to produce the mental state- specific brain activity map.
[0083] In some embodiments, the fingerprinting algorithm is a PLS model. In some embodiments, the PLS model performance is assessed with a Goodness of Fit index (GoF) and / or a Predictive Relevance (Q2index). In some embodiments, the GoF is at least 0.2, 0.25, 0.3, 0.35, 0.4. In some embodiments, the GoF is at least 0.3. In some embodiments, the GoF is at least 0.35. In some embodiments, the GoF is at least 0.36. In some embodiments, the GoF is greater than 0.36. In some embodiments, the GoF is greater than 0.4. In some embodiments, the Q2index is greater than 0. In some embodiments, the stability of the PLS model is assessed. For example, in some cases, for the PLS model, the number of factors (e.g., brain regions) is chosen to explain about 60-80% of the variance.
[0084] In some embodiments, the PLS model is a Partial Least Squares Discriminant Analysis (PLS-DA) and / or a Partial Least Squares Regression (PLS-R) analysis. In some embodiments, the PLS model is a PLS-DA. In some embodiments, the PLS model is a PLS-R analysis. In some embodiments, the PLS standardized beta coefficients may be further used to determine the mental state-specific brain activity map. For example, the PLS standardized beta coefficients, which indicate how strongly a variable, e.g., brain region, contributes to a latent variable, e.g., the mental state, may be used to determine the mental state-specific brain activity map. For example, in some cases, brain regions with a PLS standardized beta coefficient above a certain threshold may beIFF101181-WO-PCTused to limit the number of brain regions representing the mental state- specific brain activity map. In some embodiments, for example when PLS-R is used, the variable importance in projection (VIP) may be further used to determine the mental state- specific brain activity map. For example, the VIP, which indicates how strongly a variable, e.g., brain region, contributes to a latent variable, e.g., the mental state, may be used to determine the mental state-specific brain activity map. In some embodiments, for example when PLS-DA is used, the variable importance in discrimination (VID) may be further used to determine the mental state- specific brain activity map. For example, the VID, which indicates how strongly a variable, e.g., brain region, contributes to a latent variable, e.g., the mental state, may be used to determine the mental state-specific brain activity map. In some embodiments, the output of multiple algorithms may be assessed to determine a mental statespecific brain activity map. For example, PLS standardized beta coefficients, VIP, and / or VID may be used in combination to determine a mental state-specific brain activity map. Such analyses are a non-limiting example of how algorithm output may be further processed to produce the mental state- specific brain activity map.
[0085] In some embodiments, the fingerprinting algorithm is a penalized regression model. In some embodiments, the penalized regression model is an adaptive Least Absolute Shrinkage and Selection Operator (LASSO) model and / or an adaptive Ridge regression model and / or adaptive Elastic Net model or any combination thereof. In some embodiments, the penalized regression model performance is assessed by a Mean Squared Error, a misclassification rate, and / or an area under a receiver operating characteristic curve (AUC-ROC). For example, a low Mean Squared Error and / or misclassification rate indicates acceptable performance, where 0 is the theoretical optimal performance. Thus, in some embodiments, penalized regression model performance is assessed based on the closeness of the Mean Squared Error and / or misclassification rate to 0.
[0086] In some embodiments, the fingerprinting algorithm is a CART model. In some embodiments, the CART model performance is assessed by a Gini Index and / or Mean Squared Error. For example, a low Gini Index and / or Mean Squared Error indicates acceptable performance, where 0 is the theoretical optimal performance. Thus, in some embodiments, CART model performance is assessed based on the closeness of the Gini Index and / or Mean Squared Error to 0. In some embodiments, the CART model is an Extreme Gradient Boosting (XGBoost) model, a Random Forest model, a Chi-Square Automatic Interaction Detection (CHAID) model, or any combination thereof.IFF101181-WO-PCT
[0087] In some embodiments, the CART model is an XGBoost model. XGBoost, a gradient boosting framework, is known for its efficiency and performance in handling large datasets and complex interactions. In some embodiments, the CART model is a Random Forest model. Random Forest, an aggregation method, combines multiple decision trees to improve predictive accuracy and control overfitting. In some embodiments, the CART model is a CHAID model. CHAID, a decision tree technique, is used for detecting interactions between variables and segmenting data into homogenous groups.
[0088] In some embodiments, the fingerprinting algorithm is a Bayesian network model. A Bayesian network is a type of probabilistic graphical model that represents a set of variables and their conditional dependencies through a directed acyclic graph. In some embodiments, the Bayesian network model performance is assessed by a Bayesian Information Criterion (BIC). For example, lower BIC values indicate acceptable model performance, and BIC values may be negative (e.g., -100)
[0089] In some embodiments, the CART model output may be further analyzed. For example, in some embodiments, the output of the CART model may be analyzed to determine a contributory value of a variable to the output.
[0090] In some embodiments, the relationship between an activated brain region determined according to the algorithm and a mental state may be characterized. For example, further analysis may determine whether the determined brain region positively or negatively influenced the mental states. This further analysis may also be used to determine, limit, or refine the brain regions representing the mental state-specific brain activity map. It is contemplated that any method of identifying a directionality of a relationship between a variable and a predicted outcome may be used according to the methods provided herein for producing a mental state-specific brain activity map. Thus, in some embodiments, the further analysis includes the use of an additional algorithm. Non-limiting examples of such algorithms include, but are not limited to, Shapley Additive Explanations (SHAP), Partial Dependence Plots (PDP), Individual Conditional Expectation (ICE) plots, and Accumulated Local Effects (ALE) plots. In some embodiments, the algorithm is SHAP. In some embodiments, a SHAP value, which indicates the contributory value of a variable, may be used to select brain regions constituting the mental state- specific brain activity map. For example, as with VIP and VID describe supra, SHAP values above a certain threshold may beIFF101181-WO-PCTused to limit the number of brain regions representing the mental state- specific brain activity map. In some embodiments, the algorithm is PDF. For example, as with PLS standardized beta coefficients describe supra, PDP output above a certain threshold may be used to limit the number of brain regions representing the mental state- specific brain activity map. In some embodiments, the output of multiple algorithms may be assessed to determine a mental state- specific brain activity map. For example, PDP output and / or SHAP values may be used in combination to determine a mental state- specific brain activity map. Such analyses are a non-limiting example of how algorithm output may be further processed to produce the mental state- specific brain activity map.
[0091] Methods for producing a mental state- specific brain activity map may include one or more algorithms, including additional algorithms, described herein to identify from a large and complex brain imaging dataset one or more brain regions underlying a known mental state elicited by a control stimulus. In some cases, combining algorithms may enhance the uniqueness and discriminability of the mental state- specific brain activity map.
[0092] In some embodiments, the mental state-specific brain activity map includes brain regions identified by one or more algorithms as described herein. In some embodiments, the mental statespecific brain activity map includes brain regions identified by one or more algorithms as described herein and a value, e.g., PLS standardized beta coefficient, VID value, VIP value, SHAP value, and / or a value determined by analysis of the brain imaging data, for example, a t-statistic and / or a beta value. In some embodiments, the mental state-specific brain activity map includes brain regions identified by one or more algorithms as described herein and a PLS standardized beta coefficient. In some embodiments, the mental state- specific brain activity map includes brain regions identified by one or more algorithms as described herein and a VIP value. In some embodiments, the mental state- specific brain activity map includes brain regions identified by one or more algorithms as described herein and a VID value. In some embodiments, the mental statespecific brain activity map includes brain regions identified by one or more algorithms as described herein and a SHAP value. In some embodiments, the mental state- specific brain activity map includes brain regions identified by one or more algorithms as described herein and a t-statistic. In some embodiments, the mental state-specific brain activity map includes brain regions identified by one or more algorithms as described herein and a beta value. In some embodiments, the mental state-specific brain activity map includes brain regions identified by one or more algorithms asIFF101181-WO-PCTdescribed herein and one or more of a PLS standardized beta coefficient, VIP value, VID value, SHAP value, a t-statistic, or a beta value. In some embodiments, the mental state-specific brain activity map includes brain regions identified by one or more algorithms as described herein and a t-statistic and / or a beta value. In some embodiments, the t-statistic and / or the beta value, independently, may be normalized, baseline corrected, or scaled. Methods of normalization, correction, and scaling t-statistics and / or beta values are generally known in the art. In some embodiments, the mental state-specific brain activity map includes brain regions identified by a t-statistic and / or a beta value that satisfies a predetermined threshold. In some embodiments, the mental state-specific brain activity map includes brain regions identified by a t-statistic and a beta value that satisfies a predetermined threshold. In some embodiments, the mental state-specific brain activity map includes brain regions identified by a t-statistic that satisfies a predetermined threshold. In some embodiments, the mental state-specific brain activity map includes brain regions identified by a beta value that satisfies a predetermined threshold. In some embodiments, the predetermined threshold is defined by a confidence interval. For example, for a brain region to be considered part of the mental state- specific brain activity map, the t-statistic and / or beta value for the brain region satisfies a confidence level of at least 75%, 80%, 85%, 90%, 95%, or more. In some embodiments, the confidence level is at least 80%. In some embodiments, the confidence level is at least 85%. In some embodiments, the confidence level is at least 90%. In some embodiments, the confidence level is at least 95%. In some embodiments, the confidence level is at least 96%. In some embodiments, the confidence level is at least 97%. In some embodiments, the confidence level is at least 98%. In some embodiments, the confidence level is at least 99%. In some embodiments, the predetermined threshold is determined by determining a confidence interval for a t-statistic and / or a beta value derived from the analysis of the brain activity of one or more or a plurality of subjects. In some embodiments, the brain activity from the one or more or plurality of subjects is a test brain activity and / or a control brain activity. In some embodiments, brain regions identified for inclusion in a mental state-specific brain activity map are used to calculate the predetermined threshold. In some embodiments, only brain regions identified for inclusion in a mental state-specific brain activity map are used to calculate the predetermined threshold. Examples of imaging data specific values are described in detail in Section I-D below. Suitable thresholds for values described herein will depend on a variety of factors, including butIFF101181-WO-PCTnot limited to data quality and algorithmic selection, which will be appreciated by a person of skill in the art.
[0093] In some embodiments, the mental state-specific brain activity map includes brain regions identified by a t- statistic and / or a beta value that satisfies a predetermined threshold and a VIP value that satisfies a predetermined threshold. In some embodiments, the VIP value predetermined threshold is at least 0.7, 0.8, 0.9. or 1. In some embodiments, the VIP value predetermined threshold is at least 0.8, 0.9, or 1. In some embodiments, the VIP value predetermined threshold is at least 1. In some embodiments, when PLS-R is used, components where R2X (i.e., brain regions) achieves approximately 60%, 70%. 80%, 85%, 90%, 95%, 99% or more of explained variance are included in the mental state-specific brain activity map. In some embodiments, when PLS-R is used, components where R2X (i.e., brain regions) achieves approximately 60%, 70%, 80%, 85%, 90%, 95%, 99% or more of explained variance, the t-statistic and / or beta value satisfy a predetermined threshold, and the VIP value satisfies a predetermined threshold are included in the mental state-specific brain activity map.
[0094] In some embodiments, the mental state- specific brain activity map includes brain regions identified by a t-statistic and / or a beta value that satisfies a predetermined threshold and a VID value that satisfies a predetermined threshold. In some embodiments, the VID value predetermined threshold is at least 0.7, 0.8, 0.9, or 1. In some embodiments, the VID value predetermined threshold is at least 0.8, 0.9, or 1. In some embodiments, the VID value predetermined threshold is at least 1. In some embodiments, when PLS-DA is used, components where R2X (i.e., brain regions) achieves approximately 60%, 70%, 80%, 85%, 90%, 95%. 99% or more of explained variance are included in the mental state- specific brain activity map. In some embodiments, when PLS-DA is used, components where R2X (i.e., brain regions) achieves approximately 60%, 70%, 80%, 85%, 90%, 95%, 99% or more of explained variance, the t-statistic and / or beta value satisfy a predetermined threshold, and the VID value satisfies a predetermined threshold are included in the mental state- specific brain activity map.
[0095] In some embodiments, for example when more than one mental state- specific brain activity map is determined according to the methods described herein, a cross-comparison may be performed to further determine brain regions that are unique to a mental state and / or are common across mental states. For example, if a brain region is found in 30%, 40%, 50%, 60%, 70%. 80%,IFF101181-WO-PCT90%, or more of all mental state-specific brain activity maps, the brain region may not be considered unique to one mental state. In some embodiments, a brain region found to be in 30%, 40%, 50%. 60%, 70%, 80%, 90%, or more of all mental state-specific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in at least 50% of all mental state- specific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in at least 60% of all mental state- specific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in at least 70% of all mental state- specific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in at least 80% of all mental statespecific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in at least 85% of all mental state- specific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in at least 90% of all mental state-specific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in at least 95% of all mental state- specific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in at least 99% of all mental state-specific brain activity maps is classified as part of a global network. In some embodiments, a brain region found to be in all mental state- specific brain activity maps (e.g., 100% of all mental state-specific brain activity maps) is classified as part of a global network. In some embodiments, the global network includes brain regions that may represent broadly responsive processes (e.g., brain activity) that could be involved in many types of mental states. In some embodiments, the global network may represent a common pathway or general arousal mechanism from odor stimuli (e.g.. olfactory or gustatory stimuli). By contrast, brain regions identified in 60%, 50%, 40%, 30%, 20%, 10%, or fewer mental state-specific brain activity maps may be considered unique to a mental state. In some embodiments, brain regions identified in less than 60% of all mental state-specific brain activity maps may be considered unique to a mental state. In some embodiments, brain regions identified in less than 50% of all mental state-specific brain activity maps may be considered unique to a mental state. In some embodiments, brain regions identified in less than 40% of all mental state-specific brain activity maps may be considered unique to a mental state. In some embodiments, brain regions identified in less than 30% of all mental state- specific brain activity maps may be considered unique to a mental state. In some embodiments, brain regions identified in less than 20% of all mental state-specific brainIFF101181-WO-PCTactivity maps may be considered unique to a mental state. In some embodiments, brain regions identified in less than 15% of all mental state- specific brain activity maps may be considered unique to a mental state. In some embodiments, brain regions identified in less than 10% of all mental state- specific brain activity maps may be considered unique to a mental state. In some embodiments, brain regions identified in less than 5% of all mental state- specific brain activity maps may be considered unique to a mental state. In some embodiments, brain regions identified in only one of all the mental state-specific brain activity maps may be considered unique to a mental state. In some embodiments, the mental state-specific brain activity map does not include the brain regions of the global network.
[0096] In some cases, the use of a global network in addition to the mental state- specific brain activity map may allow for the identification of a global network reflecting general effects of odors (e.g., overall stimulation), whereas brain regions unique to a mental state- specific brain activity map may represent a unique neural or physiological signature of a particular mental state (e.g., a region linked specifically to relaxation, energy, etc.). Thus, in some embodiments, production of a mental state- specific brain activity according to the methods described herein may further include producing a global network. In some embodiments, a global network is produced when at least two or more mental state- specific brain activity maps are produced. In some embodiments, a global network is not produced.
[0097] As detailed below, the mental state- specific brain activity maps produced according to the provided methods may be used to predict mental states evoked by an olfactory stimulus or a gustatory stimulus where the mental state induced is unknown (e.g.. a test stimulus). Such predictions may proceed by comparing a mental state-specific brain activity map to a test mental state brain activity map. In some embodiments, the mental state-specific brain activity maps and the global network produced according to the provided methods may be used to predict mental states evoked by an olfactory stimulus or a gustatory stimulus where the mental state induced is unknown (e.g., a test stimulus). Such predictions may proceed by comparing a mental statespecific brain activity map and a global network to a test mental state brain activity map. Methods for comparison are further described, for example, in Section I-C and Section V.B. Test Mental State Brain Activity MapsIFF101181-WO-PCT
[0098] A test mental state brain activity map represents brain activity evoked in response to a test stimulus. It is the test mental state brain activity map that may be compared with the mental statespecific brain activity map, described above, to allow the prediction of one or more mental states elicited by the test stimulus. In some embodiments, the test mental state brain activity map may further be compared with a global network, as described above. Thus, in an aspect is provided a method for producing a test mental state brain activity map, including identifying in one or more subjects a test brain activity, where the test brain activity represents brain activity evoked by exposure to a test stimulus and determining, based on the test brain activity, one or more brain regions activated by the test stimulus to produce a test mental state brain activity map.
[0099] In some embodiments, the test stimulus is an olfactory stimulus. In some embodiments, the test stimulus is a gustatory stimulus. In some embodiments, the test stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor. In some embodiments, the test stimulus is a fragrance ingredient. In some embodiments, the test stimulus is a fragrance accord. In some embodiments, the test stimulus is a full fragrance. In some embodiments, the test stimulus is a flavor ingredient. In some embodiments, the test stimulus is a flavor accord. In some embodiments, the test stimulus is a full flavor. Unlike a control stimulus, however, in some embodiments, a mental state elicited by the test stimulus is unknown. In some embodiments, the strength by which the test stimulus elicits a mental state is unknown. In some embodiments, the test stimulus elicits one or more mental states. In some embodiments, the test stimulus elicits one or more mental states, each of which is elicited with a strength. In some embodiments, the methods for comparing the test mental state brain activity map with one or more mental state-specific brain activity maps produces a predicted strength. In some embodiments, the methods for comparing the test mental state brain activity map with one or more mental statespecific brain activity maps and a global network produces a predicted strength.
[0100] In some cases, the test brain activity identified in response to a test stimulus is determined by imaging brain activity in more than one subject in response to the same test stimulus. In cases where the brain activity of more than one subject in response to the same test stimulus is performed, the brain activity in each subject may be combined to produce the test brain activity. Section I-D describes various methods by which brain activity, including control brain activity and test brain activity, may be identified and processed for use according to the methods provided herein.IFF101181-WO-PCT
[0101] In some embodiments, the test brain activity is analyzed to determine one or more brain regions activated by the test stimulus to produce a test mental state brain activity map. Activation, as further described in Section I-D below, may include increases in brain activity and / or decreases in brain activity in one or more brain regions. In some embodiments, when two or more brain regions are imaged, the activity may represent a mixture of brain regions with an increase in activity, a decrease in activity, or no change in activity. In some embodiments, the test mental state brain activity map includes brain regions with increased activity. In some embodiments, the test mental state brain activity map includes brain regions with decreased activity. In some embodiments, the test mental state brain activity map includes brain regions with increased activity and brain regions with decreased activity. In some embodiments, the test mental state brain activity map includes brain regions with no change in activity. In some embodiments, the test mental state brain activity map includes a t-statistic and / or a beta value for all brain regions. In some embodiments, the t-statistics and / or the beta values may be normalized, baseline corrected, or scaled. Examples of imaging data specific values are described in detail in Section I-D below.
[0102] As with the determination of the mental state- specific brain activity map, in some embodiments, the determination of the one or more brain regions activated by a test stimulus to produce the test mental state brain activity map may include the use of artificial intelligence, machine learning, statistics, and / or data science. Artificial intelligence algorithms contemplated for producing a test mental state brain activity may be the same as those described in Section I-A for producing the mental state- specific brain activity map. Therefore, in some embodiments, determining a test mental state brain activity map includes inputting test brain activity into an artificial intelligence algorithm. In some embodiments, the algorithm is a dimensionality reduction algorithm. In some embodiments, the algorithm is a fingerprinting algorithm. In some embodiments, the fingerprinting algorithm is a Partial Least Squares (PLS) model, a Classification and Regression Tree (CART) model, a Bayesian network model, or any combination thereof. In some embodiments, the fingerprinting algorithm is a Partial Least Squares (PLS) model, a penalized regression model, a Classification and Regression Tree (CART) model, a Bayesian network model, or any combination thereof. In some embodiments, the output of the algorithm is the test mental state brain activity map. In some embodiments, the output of the algorithm is further processed to produce the test mental state brain activity map. The methods and further analysesIFF101181-WO-PCTapplicable for producing a test mental state brain activity map may be the same as those described in Section I-A for producing a mental state- specific brain activity map.
[0103] Methods for producing a test mental state brain activity map may include one or more of the algorithms described herein, including, e.g., in Section I-A, to identify from a large and complex brain imaging dataset one or more brain regions underlying an unknown mental state elicited by a test stimulus, hi some cases, combining algorithms may enhance the uniqueness and discriminability of the test mental state brain activity.
[0104] In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and a value, e.g., PLS standardized beta coefficient, VIP value, VID value, SHAP value, and / or a value determined by analysis of the brain imaging data, for example, a t-statistic or beta value. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and a PLS standardized beta coefficient. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and a VIP value. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and a VID value. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and a SHAP value. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and a t-statistic. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and a beta value. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and one or more of a PLS standardized beta coefficient, a VIP value, a VID value, a SHAP value, a t-statistic, or a beta value. In some embodiments, the test mental state brain activity map includes brain regions identified by one or more algorithms as described herein and a t-statistic and / or a beta value. In some embodiments, the test mental state brain activity map includes brain regions identified by a t-statistic and / or a beta value that satisfies a predetermined threshold. In some embodiments, the test mental state brain activity map includes brain regions identified by a t-statistic and a beta value that satisfies a predetermined threshold. In some embodiments, the test mental state brain activityIFF101181-WO-PCTmap includes brain regions identified by a t-statistic that satisfies a predetermined threshold. In some embodiments, the test mental state brain activity map includes brain regions identified by a beta value that satisfies a predetermined threshold. In some embodiments, the predetermined threshold is defined by a confidence interval. For example, for a brain region to be considered part of the test mental state brain activity map, the t-statistic and / or beta value for the brain region satisfies a confidence level of at least 75%, 80%, 85%, 90%, 95%, or more. In some embodiments, the confidence level is at least 80%. In some embodiments, the confidence level is at least 85%. In some embodiments, the confidence level is at least 90%. In some embodiments, the confidence level is at least 95%. In some embodiments, the confidence level is at least 96%. In some embodiments, the confidence level is at least 97%. In some embodiments, the confidence level is at least 98%. In some embodiments, the confidence level is at least 99%. In some embodiments, the predetermined threshold is determined by determining a confidence interval for a t-statistic and / or a beta value derived from the analysis of the brain activity of one or more or a plurality of subjects. In some embodiments, the brain activity from the one or more or plurality of subjects is a test brain activity and / or a control brain activity. In some embodiments, brain regions included in a mental state-specific brain activity map are used to calculate the predetermined threshold. In some embodiments, only brain regions included in a mental state-specific brain activity map are used to calculate the predetermined threshold. Examples of imaging data specific values are described in detail in Section I-D below.
[0105] In some embodiments, for example when PLS-R is used to determine the test mental state brain activity map, the methods and predetermined thresholds are as described in Section LA for creation of the mental state-specific brain activity map. In some embodiments, for example when PLS-DA is used to determine the test mental state brain activity map, the methods and predetermined thresholds are as described in Section I-A for creation of the mental state- specific brain activity map.
[0106] In some embodiments, the algorithmic methods used to produce the mental state- specific brain activity map are the same algorithmic methods used to produce the test mental state brain activity map. In some embodiments, the algorithmic methods used to produce the mental statespecific brain activity map are different from the algorithmic methods used to produce the test mental state brain activity map.IFF101181-WO-PCT
[0107] In some embodiments, an algorithmic method is not used to produce the test mental state brain activity map. For example, in some embodiments, the test mental state brain activity map includes activated brain regions based on classical methods of determining whether there is change in activity in a brain region in response to a stimulus. In some embodiments, the test mental state brain activity map includes brain regions identified by a t-statistic and / or a beta value that satisfies a predetermined threshold. In some embodiments, the test mental state brain activity map includes brain regions identified by a t-statistic and a beta value that satisfies a predetermined threshold. In some embodiments, the test mental state brain activity map includes brain regions identified by a t-statistic that satisfies a predetermined threshold. In some embodiments, the test mental state brain activity map includes brain regions identified by a beta value that satisfies a predetermined threshold. In some embodiments, the predetermined threshold is defined by a confidence interval. For example, for a brain region to be considered part of the test mental state brain activity map, the t-statistic and / or beta value for the brain region satisfies a confidence level of at least 75%, 80%, 85%. 90%, 95%, or more. In some embodiments, the confidence level is at least 80%. In some embodiments, the confidence level is at least 85%. In some embodiments, the confidence level is at least 90%. In some embodiments, the confidence level is at least 95%. In some embodiments, the confidence level is at least 96%. In some embodiments, the confidence level is at least 97%. In some embodiments, the confidence level is at least 98%. In some embodiments, the confidence level is at least 99%. In some embodiments, the predetermined threshold is determined by determining a confidence interval for a t-statistic and / or a beta value derived from the analysis of the brain activity of one or more or a plurality of subjects. In some embodiments, the brain activity from the one or more or plurality of subjects is a test brain activity and / or a control brain activity. In some embodiments, brain regions included in a mental state- specific brain activity map are used to calculate the predetermined threshold. In some embodiments, only brain regions included in a mental state- specific brain activity map are used to calculate the predetermined threshold. Examples of imaging data specific values are described in detail in Section I-D below. In some embodiments, when two or more brain regions are imaged, the activity may represent a mixture of brain regions with an increase in activity, a decrease in activity, or no change in activity. In some embodiments, the test mental state brain activity map includes brain regions with increased activity. In some embodiments, the test mental state brain activity map includes brain regions with decreased activity. In some embodiments, the test mental state brainIFF101181-WO-PCTactivity map includes brain regions with increased activity and brain regions with decreased activity. In some embodiments, the test mental state brain activity map includes brain regions with no change in activity.C. Predicting Mental States Elicited by Olfactory Stimuli and Gustatory Stimuli
[0108] Mental state-specific brain activity maps and test mental state brain activity maps produced according to the methods provided herein may be compared to predict a mental state elicited by a test stimulus, e.g., an olfactory stimulus or a gustatory stimulus. Thus, in an aspect is provided a method for predicting a mental state elicited by an olfactory stimulus or gustatory stimulus, including comparing a test mental state brain activity map to one or more mental state-specific brain activity maps to predict whether the olfactory stimulus or gustatory stimulus (e.g., test stimulus) elicits one or more mental states. In another aspect, the method for predicting a mental state elicited by an olfactory stimulus or gustatory stimulus, includes comparing a test mental state brain activity map to one or more mental state- specific brain activity maps and a global network to predict whether the olfactory stimulus or gustatory stimulus (e.g., test stimulus) elicits one or more mental states. In some embodiments, the predicting is the identification or determination of a mental state elicited by an olfactory or gustatory stimulus.
[0109] As described previously, the test stimuli and control stimuli may be olfactory stimuli or gustatory stimuli. An olfactory stimulus, e.g., a test stimulus or a control stimulus, may be a fragrance ingredient, a fragrance accord, or a full fragrance. A gustatory stimulus, e.g., a test stimulus or control stimulus, may be a flavor ingredient, a flavor accord, or a full flavor. In some embodiments, the test stimulus and the control stimulus are the same type of olfactory stimulus or gustatory stimulus. For example, if the control stimulus used to produce the mental state- specific brain activity map was a fragrance ingredient, the test stimulus used to produce the test mental state brain activity map is a fragrance ingredient. In some embodiments, the test stimulus and the control stimulus are different types of olfactory stimuli or gustatory stimuli. For example, if the control stimulus used to produce the mental state- specific brain activity map was a fragrance ingredient, the test stimulus used to produce the test mental state brain activity map was a fragrance accord or a full fragrance, but not a fragrance ingredient. Any combination of same and different test stimuli and control stimuli is contemplated for use according to the methods herein.IFF101181-WO-PCT
[0110] In some embodiments, the comparing the test mental state brain activity map to one or more mental state-specific brain activity maps includes a qualitative comparison. In some embodiments, the qualitative comparison includes determining a percent similarity between the test mental state brain activity map and the mental state- specific brain activity map. For example, in some embodiments, the percent similarity is determined by quantifying the overlap in active brain regions in the test mental state brain activity map and the mental state- specific brain activity map. As a further example, the number and identity of active brain regions of a test mental state brain activity map may be compared with the active brain regions of the mental state- specific brain activity map, and the percentage of overlap between the two maps, e.g., the number of brain regions of the mental state- specific brain activity map determined to be active in the test mental state brain activity map, may be determined. In some embodiments, the number of active brain regions in the test mental state brain activity map that correspond to the brain regions of the mental state- specific brain activity map may be determined (e.g., counted) and the percentage of brain regions in the mental state-specific map that are active in the test mental state brain activity map is the percent similarity. In some embodiments, the test mental state brain activity map includes more active brain regions than the brain regions of the mental state-specific brain activity map. For example, the mental state- specific brain activity map may be a result of analysis, e.g., as described herein, to extract the fundamental brain regions underlying the mental state driven by the stimulus. As such, in some cases, the number of brain regions in the mental state-specific brain activity map may be fewer than the brain regions of the test mental state brain activity, which may have more active brain regions but include the brain activity in the fundamental brain regions underlying the mental state represented by the mental state- specific brain activity map. In some embodiments, the additional active brain regions in the test mental state brain activity map are not counted in the qualitative determination. Thus, in some embodiments, the objective is to determine whether a mental state-specific brain activity map is represented in the test mental state brain activity map, e.g., by counting the number of active brain regions in the test mental state brain activity map that correspond to the mental state-specific brain activity map and quantifying the results as, e.g., a percentage (e.g., a percent similarity).
[0111] In some embodiments, a minimum threshold of percent similarity may be defined to determine whether a mental state is elicited by the test stimulus. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brainIFF101181-WO-PCTregions of the mental state- specific brain activity map and the test mental state brain activity map is at least 20%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%. 96%, 97%, 98%, 99%, or 100%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 20%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 25%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 30%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 35%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 40%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 45%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 50%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 55%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 60%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 65%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 70%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percentIFF101181-WO-PCTsimilarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 75%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 80%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 85%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 90%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 95%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 96%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 97%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 98%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is at least 99%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the test mental state brain activity map is 100%.
[0112] In some embodiments, a test mental state brain activity map may be compared to a mental state- specific brain activity map and a global network. In some embodiments, the comparing the test mental state brain activity map to one or more mental state-specific brain activity maps and a global network includes a qualitative comparison. In some embodiments, the qualitative comparison includes determining a percent similarity between the test mental state brain activity map and the mental state- specific brain activity map and the global network. For example, in some embodiments, the percent similarity is determined by quantifying the overlap in active brainIFF101181-WO-PCTregions in the test mental state brain activity map and the mental state- specific brain activity map and the global network. As a further example, the number and identity of active brain regions of a test mental state brain activity map may be compared with the brain regions of the mental statespecific brain activity map and the brain regions of the global network, and the percentage of overlap between the maps, e.g., the number of brain regions of the mental state-specific brain activity map and global network determined to be active in the test mental state brain activity map, may be determined.
[0113] In some embodiments, the number of active brain regions in the test mental state brain activity map that correspond to the brain regions of the mental state- specific brain activity map and the global network may be determined (e.g., counted) and the percentage of brain regions in the mental state- specific map and global network that are active in the test mental state brain activity map is the percent similarity. In some embodiments, the test mental state brain activity map includes more active brain regions than the brain regions of the mental state- specific brain activity map and the global network. For example, the mental state- specific brain activity map and global network may be a result of analysis, e.g., as described herein, to extract the fundamental brain regions underlying the mental state driven by the stimulus and the global network. As such, in some cases, the number of brain regions in the mental state-specific brain activity map and the global network may be fewer than the brain regions of the test mental state brain activity, which may have more active brain regions but include the brain activity in the fundamental brain regions underlying the mental state represented by the mental state-specific brain activity map and the global network. In some embodiments, the more (e.g., additional) active brain regions in the test mental state brain activity map are not counted in the qualitative determination. Thus, in some embodiments, the objective is to determine whether a mental state- specific brain activity map and the global network are represented in the test mental state brain activity map, e.g., by counting the number of active brain regions in the test mental state brain activity map that correspond to the mental state- specific brain activity map and the global network and quantifying the results as, e.g., a percentage (e.g., a percent similarity).
[0114] In some embodiments, when both a mental state- specific brain activity map and a global network are used, a minimum threshold of percent similarity to the mental state-specific brain activity map and the global network (e.g., brain regions of the mental state- specific brain activity map and the global network in total), may be defined to determine whether a mental state is elicitedIFF101181-WO-PCTby the test stimulus. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 20%, 30%, 40%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 20%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 25%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 30%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 35%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the global network in total and the test mental state brain activity map is at least 40%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 45%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 50%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 55%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 60%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mentalIFF101181-WO-PCTstate-specific brain activity map and the global network in total and the test mental state brain activity map is at least 65%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 70%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 75%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 80%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 85%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the global network in total and the test mental state brain activity map is at least 90%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 95%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 96%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 97%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brain activity map and the global network in total and the test mental state brain activity map is at least 98%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state-specific brain activity map and the global network in total and the test mental state brain activity map is at least 99%. In some embodiments, for a test stimulus to be considered as eliciting a mental state, the percent similarity between the brain regions of the mental state- specific brainIFF101181-WO-PCTactivity map and the global network in total and the test mental state brain activity map is 100%. In some embodiments, the percent similarity to the mental state-specific brain activity map and the global network (e.g.. brain regions of the mental state- specific brain activity map and the global network in total) is not achieved if the percent similarity includes only brain regions from the global network. For example, to predict that a mental state is elicited when using both a mental state-specific brain activity map and a global network, brain regions of the mental state- specific brain activity map are included in the determining the percent similarity. If the percent similarity is achieved only by virtue of the global network brain regions being active, it may not be concluded that the mental state is elicited by the test stimulus. In some embodiments, a brain region of the global network is not excluded from a mental state-specific brain activity map. Thus, in some cases, a brain region of the global network may also be a brain region of the mental state- specific brain activity map. In such cases, the brain region is counted only once when determining the percent similarity.
[0115] In some embodiments, the percent similarity may be used to determine the strength by which the test stimulus elicits the mental state. For example, if a test mental state brain activity map has 100% similarity to a mental state-specific brain activity map, it may be concluded that the olfactory stimulus or gustatory stimulus (test stimulus) strongly elicits the mental state represented by the mental state-specific brain activity map. If, however, the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map is less than 100%. it may be concluded that the olfactory stimulus or gustatory stimulus (test stimulus) elicits the mental state less strongly or even weakly, depending on the percent similarity. For example, in some embodiments, a percent similarity below 20% may indicate that the test stimulus weakly elicits the mental state. When a global network is included in the comparison, the strength determination may proceed similarly. For example, if a test mental state brain activity map has 100% similarity to a mental state-specific brain activity map and global network, it may be concluded that the olfactory stimulus or gustatory stimulus (test stimulus) strongly elicits the mental state represented by the mental state- specific brain activity map. If, however, the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map and the global network is less than 100%, it may be concluded that the olfactory stimulus or gustatory stimulus (test stimulus) elicits the mental state less strongly or even weakly, depending on the percent similarity. For example, in some embodiments, a percent similarityIFF101181-WO-PCTbelow 20% may indicate that the test stimulus weakly elicits the mental state. In some embodiments, when a global network is used for comparison, if the percent similarity threshold is achieved only by overlap with the global network, it may be concluded that test stimulus does not elicit the mental state.
[0116] When considering the percent similarity, it may be further appreciated that brain regions may be defined according to a Brainnetome Atlas (see, e.g., Section I-D and Table 1). As described below, the Brainnetome Atlas divides the brain into regions at multiple scales (i.e., 246 ROIs, 48 macro-areas, and 14 lobes). In some cases, this represents a significant reduction in the number of elements for evaluation compared to classic fMRI data analysis, which is typically conducted at the voxel space, where 100,000 voxels are normally analyzed. Therefore, despite considering the whole brain in both cases, compared to the voxel space, the possible elements for analysis according to the methods herein may be reduced by 99.7% (e.g., 100,000 voxels vs. 246 ROIs). However, when assigning specific mental states to stimuli (e.g., gustatory or olfactory stimuli), each mental state- specific brain activity map is not defined at the whole brain level, therefore, after a reduction in the number of elements to use for the analysis (voxels vs ROIs), the anatomical areas are further reduced to focus on highly specific portions of the brain. For example, when a mental state- specific brain activity map includes between 50 and 80 ROIs, it means that between 70% and 80% of the total areas of the brain are not included in the analysis. Similarly, when a mental state-specific brain activity map includes between 10 and 16 macro-areas, between 70% and 80% of the total areas of the brain are not included in the analysis. This is a significant shift from classic, standardized fMRI data analysis procedures where a full brain approach is often selected. While the full brain approach has its advantages in many situations, it is also more prone to false positive results. A strict focus is likely necessary to correctly translate the brain activity generated by a stimulus into a mental state elicited in a subject. Therefore, when describing the minimum percent similarity thresholds required by a stimulus to elicit a mental state, a 20% activation of a network (e.g., mental state-specific brain activity map, global network), for example, means checking if 20% of only a portion of 20% of the brain is showing significant activation, rather than the full brain; moreover, the 20% threshold is set on a significantly reduced number of elements (ROIs, macro-areas) rather than a large amount of voxels, where finding significant activation could be easier.IFF101181-WO-PCT
[0117] It should also be appreciated that in addition to quantifying the overlap of brain regions between the test mental state brain activity map and the mental state- specific brain activity map, the level of activation may be considered. For example, the qualitative comparison may consider both the number of overlapping brain regions and the level to which the brain regions were activated to determine a percent similarity. By way of example, if there is 100% overlap in the brain regions of the test mental state brain activity map and the mental state-specific brain activity map, and the level of activation in each of the brain regions is the same, the percent similarity would be 100%. Thus, in some embodiments, the level of activation may contribute to the calculation of the percent similarity. It will be appreciated that the value denoting the level of activation will depend on the type of brain imaging used and / or how the brain imaging data is analyzed. In some embodiments, for example when the brain imaging method is fMRI, the value is a t- statistic and / or beta value. It will be further appreciated that the percent similarity calculated to account for the overlap in brain regions and the activation level of the brain regions provides a measure of how strongly the mental state is elicited by the test stimulus, for example with 100% being strongly activated, as described above. In cases where a global network is used for determining the percent similarity, the same concepts in this paragraph apply.
[0118] In some embodiments, in addition to quantifying the overlap of brain regions between the test mental state brain activity map and the mental state-specific brain activity map, additional outputs of the algorithm used to determine the test mental state brain activity map and the mental state- specific brain activity map may be considered. For example, the qualitative comparison may consider both the number of overlapping brain regions and the importance of the brain region in explaining the mental state. In some embodiments, the importance of the brain region in explaining the mental state (e.g., explanatory value) is an output of the algorithm used. In some embodiments, the algorithm provides a numerical value to indicate the importance of the brain region in explaining the mental state. Such numerical value may be referred to alternatively as an explanatory value herein. In some embodiments, the numerical value is a SHAP value, for example when a SHAP model is used. In some embodiments, the numerical value is a PLS standardized beta coefficient, for example when a PLS model is used. In some embodiments, the numerical value is a VIP value, for example when a PLS-R analysis is used. In some embodiments, the numerical value is a VID value, for example when PLS-DA is used. Other algorithms, e.g., Random Forest, can provide explanatory values or can be further analyzed to determineIFF101181-WO-PCTexplanatory values. By way of example, if there is 100% overlap in the brain regions of the test mental state brain activity map and the mental state-specific brain activity map, and the numerical value (e.g., explanatory value) in each of the brain regions is the same, the percent similarity would be 100%. Thus, in some embodiments, the explanatory value may contribute to the calculation of the percent similarity. It will be appreciated that the explanatory value will depend on the type of algorithm used to determine the test mental state brain activity map and the mental state- specific brain activity map. It will be further appreciated that the percent similarity calculated to account for the overlap in brain regions and the explanatory value of the brain regions provides a measure of how strongly the mental state is elicited by the test stimulus, for example with 100% being strongly activated, as described above. In cases where a global network is used for determining the percent similarity, the same concepts in this paragraph apply.
[0119] In some embodiments, the algorithm or combination of algorithms for determining a mental state- specific brain activity map is the same as the algorithm or combination of algorithms for determining a test mental state brain activity map. In some embodiments, using the same algorithm or combination of algorithms allows the percent similarity to be calculated, including when explanatory values are considered. In some embodiments, the algorithm or combination of algorithms for determining a mental state- specific brain activity map is different from the algorithm or combination of algorithms for determining a test mental state brain activity map. In some embodiments, when the algorithm or combination of algorithms are different, additional steps may be taken to allow for a percent similarity to be calculated.
[0120] The comparing of the test mental state brain activity map to one or more mental statespecific brain activity maps may be accomplished using artificial intelligence, machine learning, statistics, and / or data science. In some embodiments, the comparing the test mental state brain activity map to one or more mental state-specific brain activity maps is performed using an artificial intelligence algorithm. In some embodiments, the algorithm is a predictive model. For example, a predictive model may be trained on the one or more mental state- specific brain activity maps such that inputting a test mental state brain activity map into the trained model allows the model to predict the mental state elicited by the test stimulus. In some embodiments, the predictive model provides as output a classification label (e.g., a mental state) and / or scores, such as one or more probabilities of an observation (test mental state brain activity map) belonging to one or more mental states.IFF101181-WO-PCT
[0121] The comparing of the test mental state brain activity map to one or more mental statespecific brain activity maps and a global network may be accomplished using artificial intelligence, machine learning, statistics, and / or data science. In some embodiments, the comparing the test mental state brain activity map to one or more mental state- specific brain activity maps and a global network is performed using an artificial intelligence algorithm. In some embodiments, the algorithm is a predictive model. For example, a predictive model may be trained on the one or more mental state-specific brain activity maps and global networks such that inputting a test mental state brain activity map into the trained model allows the model to predict the mental state elicited by the test stimulus. In some embodiments, the predictive model provides as output a classification label (e.g., a mental state) and / or scores, such as one or more probabilities of an observation (test mental state brain activity map) belonging to one or more mental states.
[0122] In some embodiments, the predictive algorithm is a heuristic optimization algorithm. Any suitable optimization algorithm capable of solving an optimization problem may be used to perform the comparison. Non-limiting examples of optimization algorithms suitable for comparing include, but are not limited to, differential evolution, particle swarm optimization, Fast Iterative Shrinkage-Thresholding Algorithm (FISTA), and genetic algorithms. In some embodiments, the optimization algorithm is differential evolution. In some embodiments, the optimization algorithm is particle swarm optimization. In some embodiments, the optimization algorithm is FISTA. In some embodiments, the optimization algorithm is a genetic algorithm. In some embodiments, the genetic algorithm is a Fast Elitist Non-dominated Sorting Genetic Algorithm. In some embodiments, the predictive algorithm provides a strength measure. For example, the robustness, which is measured using the overall variance, optionally expressed as a standard deviation, and the convergence stability may be measured to determine the strength by which the test stimulus elicits the mental state. In some cases, when the robustness is less than 1 standard deviation and the convergence stability possesses 90-95% similarity, the test stimulus may be considered to strongly elicit the mental state. It will be appreciated that robustness measures and convergence stability measures may be considered together to determine a strength by which the mental state is elicited, where the strength is determined on a sliding scale in view of the measures.
[0123] In some embodiments, a combination of prediction methods, e.g., combinations of percent similarity measures, combinations of predictive algorithms, or combinations of percent similarityIFF101181-WO-PCTmeasures and predictive algorithms may be used to determine whether a mental state is elicited by a test stimulus.
[0124] In some embodiments, the methods of comparing test mental state brain activity maps and mental state- specific brain activity maps allow the prediction of one or more mental states elicited by a test stimulus. In some embodiments, the methods of comparing test mental state- specific brain activity maps with the mental state- specific brain activity map and the global network allow the prediction of one or more mental states elicited by a test stimulus. In some embodiments, the methods allow prediction of one or more mental states elicited by the test stimulus and a measure of the strength by which the test stimulus elicits the mental state.D. Brain Imaging Methods, Stimuli, and Analyses
[0125] The methods described herein include the use of brain imaging data collected from subjects exposed to an olfactory stimulus, e.g., a fragrance ingredient, a fragrance accord, a full fragrance, or gustatory stimulus, e.g., a flavor ingredient, a flavor accord, or a full flavor. Thus, in some embodiments, the methods described herein include the use of brain imaging methods. Methods for detecting brain activity evoked in a subject by exposure to an olfactory stimulus or a gustatory stimulus, e.g., control stimuli and test stimuli, include any method useful for detecting activity and changes thereof in one or more brain regions. Non-limiting examples of brain imaging methods suitable for use according to the methods herein include functional magnetic resonance imaging (fMRI), arterial spin labeling (ASL) MR perfusion (e.g., pulsed ASL (PASL)), continuous ASL (CASL), pseudocontinous ASL (PCASL), velocity-selective ASL (VS-ASL), electroencephalography (EEG), magnetoencephalography (MEG), positron emission tomography (PET), functional near-infrared spectroscopy (fNIRS), single-photon emission computed tomography (SPECT), and functional ultrasound imaging (fUS). In some embodiments, one or more methods of the brain imaging may be used. For example, in some cases, two or more brain imaging methods may be used, e.g., EEG and fMRI, EEG and fNIRS, etc. In some embodiments, the brain imaging methods for use herein detect activity in brain regions of and below the cortex. In some embodiments, the brain imaging methods for use herein detect activity in superficial and deep brain regions. In some embodiments, the brain imaging methods for use herein detect activity in superficial brain regions. It is contemplated that the brain imaging method used herein beIFF101181-WO-PCTsuitable for use with human subjects. In some embodiments, the subject is suitable for the specific type of brain imaging used, as is known in the art.
[0126] For purposes of detecting brain activity in response to olfactory stimuli, in some embodiments, the subject is normosmic. In addition to self-reporting, various tests are commercially available (e.g., Sniffin Stick Test (Burghardt®, Wedel, Germany)) to assess whether a subject’s sense of smell is normal (normosmic). For purposes of detecting brain activity in response to gustatory stimuli, in some embodiments, the subject is normogeusic. In addition to self-reporting, various tests are available (e.g., chemical testing (e.g., three drop test, taste tablets, taste strips, filter paper discs), electrical testing (e.g., electrogustometry, gustatory evoked potentials)) to assess whether a subject’s sense of taste is normal (normogeusic). Demographic information, e.g., age, gender, sex, ethnicity, nationality, etc., sensory data, and / or psychological data may also be collected and / or associated with brain imaging data. Non-limiting examples for use in collecting psychological and sensory data include, but are not limited to, Edinburgh Handedness Inventory, PANAS (positive / negative affective states), STAI (anxiety), FPQ (Food preference questionnaire), SAM ratings for valence, arousal and dominance (pleasantness, intensity, and how overwhelming the feeling is), Likert scales (to rate different parameters as liking or spiciness or other sensory aspects), intensity scales, hedonic evaluation (how nice / engaging / positive a stimulus is), ranking of attributes, dominant attributes (write down descriptors of a fragrance / flavor), CATA selection of attributes (from a list of attributes, which ones belong to the sample you’re smelling / tasting?). All data is subject to and in compliance with privacy and data protection practices as required.
[0127] In some embodiments, the brain imaging method for use herein detects activity throughout the entire brain. Following collection of brain activity across the brain, analyses may focus on specific brain regions imaged across the brain to determine activation of the brain region. In some embodiments, the brain imaging method for use herein detects activity in predetermined brain regions. For example, in some cases, brain regions may be selected before experimentation for imaging. A selection of specific brain regions for imaging prior to experimentation may be determined from a study of scientific literature and / or empirical evidence. Such a selection may be specific to a mental state.IFF101181-WO-PCT
[0128] A brain region may be an anatomically defined brain structure, a subregion of an anatomically defined brain structure, a functionally defined brain structure, or a subregion of a functionally defined brain structure. In some embodiments, the brain regions include an anatomically defined brain structure, a subregion of an anatomically defined brain structure, a functionally defined brain structure, a subregion of a functionally defined brain structure, or a combination thereof. In some embodiments, the brain regions include an anatomically defined brain structure, a subregion of an anatomically defined brain structure, or a combination thereof. In some embodiments, the brain regions include a functionally defined brain structure, a subregion of a functionally defined brain structure, or a combination thereof. In some embodiments, the brain regions do not include three or more of a ventral tegmental area (VTA), a prefrontal cortex (PFC), a striatum, and a hippocampal-amygdala complex.
[0129] In some embodiments, the brain imaging data may be projected onto a brain atlas. In this way, brain imaging data may be mapped to locations in the brain allowing the identification of activity in mapped brain regions. Thus, in some embodiments, a brain atlas is used to determine activated brain regions. In some embodiments, the brain atlas used for projecting brain imaging data is the Brainnetome Atlas (atlas.brainnetome.org; Brainnetome Center, Institute of Automation, Chinese Academy of Sciences). In this atlas, the brain is split into 246 regions of interest (ROIs), which in turn can be grouped in 48 macro-areas (24 for the left hemisphere and 24 for the right hemisphere) and 14 lobe areas (7 for the left hemisphere and 7 for the right hemisphere). A numerical value ranging between 1 and 246 may be used as a more compact label to identify each ROI. A numerical value ranging between 1 and 48 may be used as a more compact label to identify each macro-area. A numerical value ranging between 1 and 14 may be used as a more compact label to identify each lobe. Table 1 provides a description of ROIs, macro-areas, and lobes identified according to the Brainnetome Atlas. In Table 1, the progressive numerical label for each ROI is assigned by row, considering first the structure on the left hemisphere and then the structure on the right hemisphere. For example, the medial area 8 is the first row of the table, therefore the left a8m ROI can be identified as ROI number 1 and the right medial area 8 can be identified as ROI number 2. The dorsolateral area 8 is the second row of the table, therefore the left a8dl ROI can be identified as ROI number 3 and the right dorsolateral area 8 can be identified as ROI number 4. The ROIs in the remaining part of Table 1 can be progressively identified with a numerical label following this criterion. For the macro-areas and the lobes, theIFF101181-WO-PCTnumerical value present in brackets in Table 1 can be used as a more compact label to identify each macro-area and each lobe. For example, the left superior frontal gyrus can be identified as macro-area number 1, and the right superior frontal gyrus can be identified as macro-area number 2. For example, the left frontal lobe can be identified as lobe number 1, and the right frontal lobe can be identified as lobe number 2.
[0130] Table 1: Exemplary lobes, macro-areas, ROIs, and anatomical and modified Cyto-architectonic descriptions. The reference number corresponding to the lobe, macro-area, or ROI is shown in parentheses. The number to the left of the dash represents the lobe, macro-area, or ROI in the left hemisphere while the number to the right of the dash represents the corresponding lobe, macro-area, or ROI in the right hemisphere.Anatomical and modified Lobe Macro Left and Right Hemisphere ROIs Cyto-architectonic descriptions SFG_L(R)_7_1 (1-2) A8m, medial area 8 SFG_L(R)_7_2 (3-4) A8dl, dorsolateral area 8 SFG, Superior SFG_L(R)_7_3 (5-6) A91, lateral area 9 Frontal Gyrus SFG_L(R)_7_4 (7-8) A6dl, dorsolateral area 6 (1-2) SFG_L(R)_7_5 (9-10) A6m, medial area 6 SFG_L(R)_7_6 (11-12) A9m, medial area 9 SFG_L(R)_7_7 (13-14) AlOm, medial area 10 MFG_L(R)_7_1 (15-16) A9 / 46d, dorsal area 9 / 46 MFG_L(R)_7_2 (17-18) IF J, inferior frontal junction MFG, Middle MFG_L(R)_7_3 (19-20) A46, area 46Frontal Gyrus MFG_L(R)_7_4 (21-22) A9 / 46v, ventral area 9 / 46 (3-4) MFG_L(R)_7_5 (23-24) A8vl, ventrolateral area 8 FrontalMFG_L(R)_7_6 (25-26) A6vl, ventrolateral area 6 Lobe (1-2)MFG_L(R)_7_7 (27-28) A101, lateral arealO IFG_L(R)_6_1 (29-30) A44d, dorsal area 44 IFG_L(R)_6_2 (31-32) IFS, inf erior frontal sulcus IFG, Inferior IFG_L(R)_6_3 (33-34) A45c, caudal area 45 Frontal Gyrus(5-6) IFG_L(R)_6_4 (35-36) A45r, rostral area 45IFG_L(R)_6_5 (37-38) A44op, opercular area 44 IFG_L(R)_6_6 (39-40) A44v, ventral area 44 OrG_L(R)_6_l (41-42) A14m, medial area 14 OrG_L(R)_6_2 (43-44) A12 / 47o, orbital area 12 / 47 OrG, OrbitalOrG_L(R)_6_3 (45-46) Alli, lateral area 11 Gyrus (7-8)OrG_L(R)_6_4 (47-48) Alim, medial area 11OrG_L(R)_6_5 (49-50) A13, area 13IFF101181-WO-PCTOrG_L(R)_6_6 (51-52) A12 / 471, lateral area 12 / 47A4hf, area 4(head and face PrG_L(R)_6_l (53-54)region)A6cdl, caudal dorsolateral PrG_L(R)_6_2 (55-56)area 6A4ul, area 4( upper limb PrG, Precentral PrG_L(R)_6_3 (57-58)region)Gyrus (9-10)PrG_L(R)_6_4 (59-60) A4t, area 4(trunk region) A4tl, area 4( tongue and PrG_L(R)_6_5 (61-62)larynx region)A6cvl, caudal ventrolateral PrG_L(R)_6_6 (63-64)area 6A1 / 2 / 3U, areal / 2 / 3 (lower PCL_L(R)_2_1 (65-66)PCL, Paracentral limb region) Lobule (11-12) A4U, area 4, (lower limb PCL_L(R)_2_2 (67-68)region) STG_L(R)_6_1 (69-70) A38m, medial area 38 STG_L(R)_6_2 (71-72) A41 / 42, area 41 / 42 STG, SuperiorSTG_L(R)_6_3 (73-74) TE1.0 and TE1.2 Temporal Gyrus(13-14) STG_L(R)_6_4 (75-76) A22c, caudal area 22STG_L(R)_6_5 (77-78) A381, lateral area 38 STG_L(R)_6_6 (79-80) A22r, rostral area 22 MTG_L(R)_4_1 (81-82) A21c, caudal area 21 MTG, Middle MTG_L(R)_4_2 (83-84) A21r, rostral area 21 Temporal Gyrus MTG_L(R)_4_3 (85-86) A37dl, dorsolateral area37 (15-16) aSTS, anterior superior MTG_L(R)_4_4 (87-88)temporal sulcus A20iv, intermediate ventral ITG_L(R)_7_1 (89-90)area 20Temporal A37elv, extremeLobe (3-4) ITG_L(R)_7_2 (91-92)lateroventral area37 ITG_L(R)_7_3 (93-94) A20r, rostral area 20 ITG, InferiorA20il, intermediate lateral Temporal Gyrus ITG_L(R)_7_4 (95-96)area 20(17-18)ITG_L(R)_7_5 (97-98) A37vl, ventrolateral area 37A20cl, caudolateral of area ITG_L(R)_7_6 (99-100)20A20cv, caudoventral of area ITG_L(R)_7_7 (101-102)20FuG_L(R)_3_l (103-104) A20rv, rostroventral area 20 FuG, FusiformFuG_L(R)_3_2 (105-106) A37mv, medioventral area37 Gyrus (19-20)FuG_L(R)_3_3 (107-108) A37lv, lateroventral area37 PhG_L(R)_6_l (109-110) A35 / 36r, rostral area 35 / 36PhG_L(R)_6_2 (111-112) A35 / 36c, caudal area 35 / 36IFF101181-WO-PCTTL, area TL (lateral PPHC, PhG_L(R)_6_3 (113-114) posterior parahippocampal gyrus)PhG, A28 / 34, area 28 / 34 (EC, Parahippocampal PhG_L(R)_6_4 (115-116)entorhinal cortex) Gyrus (21-22) TI, area TI( temporal PhG_L(R)_6_5 (117-118)agranular insular cortex) PhG_L(R)_6_6 (119-120) TH, area TH (medial PPHC) pSTS, posterior rpSTS, rostroposterior pSTS_L(R)_2_l (121-122)Superior superior temporal sulcus Temporal Sulcus cpSTS, caudoposterior (23-24) pSTS_L(R)_2_2 (123-124)superior temporal sulcus SPL_L(R)_5_1 (125-126) A7r, rostral area 7 SPL_L(R)_5_2 (127-128) A7c, caudal area 7 SPL, SuperiorParietal Lobule SPL_L(R)_5_3 (129-130) A51, lateral area 5(25-26) SPL_L(R)_5_4 (131-132) A7pc, postcentral area 7 A7ip, intraparietal area SPL_L(R)_5_5 (133-134)7(hIP3) IPL_L(R)_6_1 (135-136) A39c, caudal area 39(PGp)A39rd, rostrodorsal area IPL_L(R)_6_2 (137-138)39(Hip3)A40rd, rostrodorsal area IPL, Inferior IPL_L(R)_6_3 (139-140)40(PFt)Parietal Lobule(27-28) IPL_L(R)_6_4 (141-142) A40c, caudal area 40(PFm)A39rv, rostroventral area IPL_L(R)_6_5 (143-144)Parietal 39(PGa)Lobe (5-6) A40rv, rostroventral area IPL_L(R)_6_6 (145-146)40(PFop) PCun_L(R)_4_l (147-148) A7m, medial area 7(PEp) PCun_L(R)_4_2 (149-150) A5m, medial area 5(PEm) Pcun, Precuneus(29-30) dmPOS, dorsomedial PCun_L(R)_4_3 (151-152)parietooccipital sulcus( PEr) PCun_L(R)_4_4 (153-154) A31, area 31 (Lcl)Al / 2 / 3ulhf, area l / 2 / 3( upper PoG_L(R)_4_l (155-156)limb, head and face region) Al / 2 / 3tonIa, area PoG, Postcentral PoG_L(R)_4_2 (157-158) l / 2 / 3(tongue and larynx Gyrus (31-32) region)PoG_L(R)_4_3 (159-160) A2, area 2Al / 2 / 3tru, areal / 2 / 3(trunk PoG_L(R)_4_4 (161-162)region)INS_L(R)_6_1 (163-164) G, hypergranular insula INS_L(R)_6_2 (165-166) via, ventral agranular insula Insular INS, Insular INS_L(R)_6_3 (167-168) dla, dorsal agranular insula Lobe (7-8) Gyrus (33-34) vld / vlg, ventral dysgranular INS_L(R)_6_4 (169-170)and granular insulaINS_L(R)_6_5 (171-172) dig, dorsal granular insulaIFF101181-WO-PCTdid, dorsal dysgranular INS_L(R)_6_6 (173-174)insulaCG_L(R)_7_1 (175-176) A23d, dorsal area 23 CG_L(R)_7_2 (177-178) A24rv, rostroventral area 24 Limbic CG_L(R)_7_3 (179-180) A32p, pregenual area 32 CG, CingulateLobe (9- CG_L(R)_7_4 (181-182) A23v, ventral area 23Gyrus (35-36)10) CG_L(R)_7_5 (183-184) A24cd, caudodorsal area 24CG_L(R)_7_6 (185-186) A23c, caudal area 23 CG_L(R)_7_7 (187-188) A32sg, subgenual area 32 MVOcC _L(R)_5_1 (189-190) cLinG, caudal lingual gyrus MVOcC, MVOcC _L(R)_5_2 (191-192) rCunG, rostral cuneus gyrus Medio Ventral MVOcC _L(R)_5_3 (193-194) cCunG, caudal cuneus gyrus Occipital Cortex MVOcC _L(R)_5_4 (195-196) rLinG, rostral lingual gyrus (37-38) vmPOS, ventromedial MVOcC _L(R)_5_5 (197-198)parietooccipital sulcus Occipital mOccG, middle occipital LOcC_L(R)_4_l (199-200)Lobe (11- gyrus12) LOcC _L(R)_4_2 (201-202) V5 / MT+, area V5 / MT+ LOcC, lateral LOcC _L(R)_4_3 (203-204) OPC, occipital polar cortex Occipital Cortex LOcC_L(R)_4_4 (205-206) iOccG, inferior occipital (39-40) gyrusmsOccG, medial superior LOcC _L(R)_2_1 (207-208)occipital gyrus IsOccG, lateral superior LOcC _L(R)_2_2 (209-210)occipital gyrus Amyg, Amyg_L(R)_2_l (211-212) mAmyg, medial amygdala Amygdala (41- 42) Amyg_L(R)_2_2 (213-214) lAmyg, lateral amygdala Hipp, Hipp_L(R)_2_l (215-216) rHipp, rostral hippocampus Hippocampus(43-44) Hipp_L(R)_2_2 (217-218) cHipp, caudal hippocampus BG_L(R)_6_1 (219-220) vCa, ventral caudate BG_L(R)_6_2 (221-22) GP, globus pallidus BG_L(R)_6_3 (223-224) NAC, nucleus accumbens Subcortical BG, BasalGanglia (45-46) BG_L(R)_6_4 (225-226) vmPu, ventromedial Nuclei (13- putamen14)BG_L(R)_6_5 (227-228) dCa, dorsal caudate BG_L(R)_6_6 (229-230) dlPu, dorsolateral putamen mPFtha, medial pre-frontal Tha_L(R)_8_l (231-232)thalamusmPMtha, pre-motor Tha, Thalamus Tha_L(R)_8_2 (233-234)thalamus(47-48)Tha_L(R)_8_3 (235-236) Stha, sensory thalamus rTtha, rostral temporal Tha_L(R)_8_4 (237-238)thalamusIFF101181-WO-PCTPPtha, posterior parietal Tha_L(R)_8_5 (239-240) thalamus Tha_L(R)_8_6 (241-242) Otha, occipital thalamus cTtha, caudal temporal Tha_L(R)_8_7 (243-244) thalamus IPFtha, lateral pre-frontal Tha_L(R)_8_8 (245-246)thalamus
[0131] The Brainnetome Atlas may be updated from time to time to include additional ROIs, macro-areas, and / or lobes. ROIs, macro-areas, and lobes are used herein with reference to the Brainetomme Atlas. Thus, in some embodiments, a brain region is an ROI, a macro-area, or a lobe as defined according to the Brainnetome Atlas. In some embodiments, when one or more brain regions are assessed according to the methods provided herein, the one or more brain regions are ROIs, macro-areas, lobes, or any combination thereof, defined according to the Brainnetome Atlas. For example, when determining a mental state- specific brain activity map and / or a test mental state brain activity map according to the methods provided herein, the one or more brain regions may be ROIs, macro-areas, lobes, or any combination thereof, defined according to the Brainnetome Atlas. In some embodiments, any combination of ROIs, macro-areas, and lobes may be used for producing the mental state-specific brain activity map and / or the test mental state brain activity map. For example, ROIs and macro-areas: ROIs and lobes; macro-areas and lobes; or ROIs, macro-areas, and lobes, are used for producing the mental state- specific brain activity map and / or the test mental state brain activity map. In some embodiments, ROIs may be used for producing the mental state- specific brain activity map and / or the test mental state brain activity map. In some embodiments, macro-areas may be used for producing the mental state- specific brain activity map and / or the test mental state brain activity map. In some embodiments, lobes may be used for producing the mental state-specific brain activity map and / or the test mental state brain activity map.
[0132] Because a global network may be determined by comparing mental state-specific brain activity maps, the global network may include the brain regions, e.g., ROIs. macro-areas, and / or lobes, as described for the mental state- specific brain activity maps. In some embodiments, the global network includes ROIs, macro-areas, lobes, or any combination thereof. In some embodiments, the global network includes ROIs. In some embodiments, the global network includes macro-areas. In some embodiments, the global network includes lobes.IFF101181-WO-PCT
[0133] In some embodiments, the brain imaging method for use herein detects activity in 2, 3, 4, 5, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90, 100, 150, 200, 250, 300, 350, 400, 450, 500, or more brain regions. In some embodiments, the activity is identified in 5 or more brain regions. In some embodiments, the activity is identified in 10 or more brain regions. In some embodiments, the activity is identified in 20 or more brain regions. In some embodiments, the activity is identified in 40 or more brain regions. In some embodiments, the activity is identified in 60 or more brain regions. In some embodiments, the activity is identified in 80 or more brain regions. In some embodiments, the activity is identified in 100 or more brain regions. In some embodiments, the activity is identified in between about 5 and 100 brain regions. In some embodiments, the activity is identified in between about 5 and 200 brain regions. In some embodiments, the activity is identified in between about 5 and 250 brain regions.
[0134] The identified activity in a brain region may be an increase in activity of the brain region, a decrease (e.g., suppression) in activity of the brain region, or no change in activity of the brain region. Thus, there may be a directionality, or lack thereof, to the activity identified in the brain region. It should be appreciated that each brain region in which activity is detected may have a different directionality of activity compared to one or more of the other brain regions in which activity is also detected. In some embodiments, the directionality of activity in the one or more brain regions is used (e.g., included) for determining the mental state-specific brain activity map and test mental state brain activity map in accordance with methods for determining the maps provided herein. See, e.g., Section I-A and I-B. In some embodiments, brain regions with an increase in activity are used (e.g., included) for determining the mental state- specific brain activity map and test mental state brain activity map in accordance with methods for determining the maps provided herein. In some embodiments, brain regions with an increase in activity and brain regions with a decrease in activity are used (e.g., included) for determining the mental state- specific brain activity map and test mental state brain activity map in accordance with methods for determining the maps provided herein. Methods for identifying activity in brain regions may be specific to the type of brain imaging method used, and relevant methods will be understood by a person of skill in the art.IFF101181-WO-PCT1. fMRI Methods and Analyses
[0135] In some embodiments, the brain imaging method for use according to the methods described herein is fMRI. Methods for analyzing changes in brain activity when using fMRI methods are well known in the art, and computer software packages for data analysis are commercially or freely available. Non-limiting examples of such analysis software packages and platforms include, but are not limited to, BrainVoyager (Brain Innovation, Maastricht, Netherlands), fMRIprep (NiPreps), FSL (FMRIB Software Library, Oxford University, FMRIB, Oxford Center for Functional MRI of the Brain), Matlab® (MathWorks®, Inc. Natick, MA), and Python (Python Software Foundation, Wilmington, DE).
[0136] Standard pre-processing of fMRI data may include, but is not limited to, intensity normalization, slice timing correction, motion correction, detrending and temporal filtering, spatial normalization by aligning the fMRI data to a standardized brain coordinate system, and spatial smoothing to reduce the noise and improve signal-to-noise ratio by averaging the signal across neighboring voxels. Spatial normalization may be accomplished in MNI or Talairach space. For example, MNI (Montreal Neurological Institute) template is a standardized brain template that represents an average brain based on the anatomical features of many individuals. As described above, spatial normalization provides a consistent coordinate system that allows researchers to compare and combine data across studies and is often included in neuroimaging tools and analysis software packages.
[0137] Further processing of pre-processed data may include identification of brain regions that are active in response to a specific stimuli or condition, e.g., control stimuli and test stimuli. Statistical analysis allows detection of voxels or regions where the neural activation differs significantly between two conditions. In some embodiments, the difference in activation is determined between a resting condition and a stimulus condition (test stimulus, control stimulus) condition. In some embodiments, the resting condition is a resting state in the presence of a standard stimulus, e.g., air, a reference stimulus, or a vehicle such as a solvent in which a test or control stimulus is dissolved. See Section LD-2. The brain activity evoked by a standard stimulus during resting state may be referred to herein as a baseline brain activity. In some embodiments, the baseline brain activity may be compared against brain activity during the presence of a stimulusIFF101181-WO-PCT(e.g., control stimulus, test stimulus) to determine the brain activity evoked by the stimulus (e.g., control brain activity, test brain activity).
[0138] In some embodiments, a subject may be asked to complete a task while experiencing a stimulus (e.g., control stimulus or test stimulus). In some embodiments, the task is passive and does not require any response from the subject. In some embodiments, the task is active and the subject may be required to act in response to the task. In some embodiments, the subject acts by providing a verbal response. In some embodiments, the subject acts by providing a written response, e.g., handwritten (e.g., on paper or a touchscreen) or typed (e.g., using a keyboard). In some embodiments, the subject acts by providing a response by selection, e.g., by manually pressing a button or performing a keystroke to select a desired response. In some embodiments, the response is recorded manually by the experimenter. In some embodiments, the response is recorded automatically. In some embodiments, the responses from the subjects are stored, optionally, in a database. In some embodiments, the responses from the subject are correlated with the brain activity elicited by the stimulus to induce a specific mental state. In some embodiments, the task is presented on an fMRI-compatible screen. In some embodiments, the task is presented on a standard PC screen. In some embodiments, the task is presented on a touchscreen, e.g., a mobile device, tablet. In some embodiments, the task is printed on paper. In some embodiments, the task may be performed in the presence of the control stimulus and the test stimulus such that comparing the control brain activity against the test brain activity allows a determination of the effect of the test stimulus on the task. In some embodiments, a baseline brain activity (e.g., determined under resting state conditions, optionally in the presence of a standard stimulus) may be compared against the control brain activity and / or the test brain activity before comparing the control brain activity and test brain activity.
[0139] The two most commonly used methods for processing fMRI data are the General Linear Model (GLM) and t-tests. GLM involves modeling the fMRI time series as a linear combination of regressors that represent the experimental conditions or tasks. The GLM estimates the contribution of each regressor to the observed fMRI signal and tests for significant differences in activation between conditions. Thus, GLM may be used to compare an ideal response (model) against a real response (obtained from the data) by the means of a statistical test. An exemplary statistical test used to compare the means of two groups or conditions is a t-test. In fMRI analysis, t-tests can be applied voxel-wise to assess the differences in activation between two experimentalIFF101181-WO-PCTconditions. The t- statistic is calculated for each voxel, indicating the degree of activation difference between conditions, and statistical thresholds are applied to determine significant activations. It will be appreciated that con'ections for multiple comparisons may be used, e.g., Bonferroni correction. The resulting statistical maps indicating activated brain region may be represented as a statistical parametric map or a z-score map. These maps can be visualized and interpreted to identify regions that show significant activation related to the specific experimental conditions or tasks.
[0140] Another measure used in fMRI is the beta value. Beta values represent the measure of magnetic susceptibility, or the consumption of oxygen by neurons. It is a percentage score where 0% represents the baseline condition, but it is an open scale, meaning that consumption of oxygen in a task condition can be above 100% of the oxygen consumption during the baseline, or even below it.
[0141] In some embodiments, when two or more or a plurality of subjects are imaged according to the methods provided herein, the data from each subject is averaged. In some embodiments, the average data is analyzed to identify brain activity (e.g., control brain activity, test brain activity). In some embodiments, when two or more or a plurality of subjects are imaged according to the methods provided herein a fixed effects analysis model may be used. A fixed effects analysis may be suitable for identifying brain activity (e.g., control brain activity, test brain activity) from a plurality of subjects, e.g., when consolidating the brain activity identified across a plurality of subjects. In some embodiments, when two or more or a plurality of subjects are imaged according to the methods provided herein a random effects analysis model may be used. A random effects analysis may be suitable when identifying brain activity (e.g., control brain activity, test brain activity) from a plurality of subjects, e.g., when consolidating the brain activity identified across a plurality of subjects. In some embodiments, when two or more or a plurality of subjects are imaged according to the methods provided herein a mixed effects analysis model may be used. A mixed-effects analysis may also be suitable when identifying brain activity (e.g., control brain activity, test brain activity) from a plurality of subjects, e.g., when consolidating the brain activity patterns identified across a plurality of subjects. As described above, various platforms for performing data analysis, including those described herein, are commercially or freely available.IFF101181-WO-PCT
[0142] In some embodiments, t-statistics and / or beta values are used according to the methods described herein for producing a mental state- specific brain activity map and / or a test mental state brain activity map. In some embodiments, statistical parametric map and / or z-score map are used according to the methods described herein for producing a mental state- specific brain activity map and / or test mental state brain activity map. The statistical parametric map and / or z-score map may be used as the t-statistic and / or beta value described for use. Other or additional methods of normalizing, baseline correcting, and / or scaling t-statistics and / or beta values may be used as appropriate and may be used according to the methods described herein for producing a mental state- specific brain activity map and / or test mental state brain activity map.
[0143] In some embodiments, the entire brain is imaged using fMRI. In some embodiments, processed data, including voxels with corresponding t-statistics and / or beta values are projected onto the Brainnetome Atlas described above. To reiterate, in this atlas, the brain is split into 246 ROIs, which in turn can be grouped in 48 macro-areas (24 per hemisphere) and 14 lobe areas (7 per hemisphere). In some embodiments, a brain region described herein is a voxel projected onto the Brainnetome Atlas. In some embodiments, a brain region is an ROI, a macro-area, or a lobe as defined according to the Brainnetome Atlas onto which voxels of processed data are mapped. In some embodiments, the t-statistic and / or beta value of the voxels projected onto an ROI, macroarea, or lobe are combined to produce a t-statistic and / or beta value representative of the ROI, macro-area, or lobe, respectively. Because, according to the Brainnetomme Atlas, ROIs may be combined to form a macro-area, in some embodiments, the representative t-statistic and / or beta value of ROIs forming a macro-area may be combined to produce the representative t-statistic and / or beta value of a macro-area. Because, according to the Brainnetomme Atlas, macro-areas may be combined to form a lobe, in some embodiments, the representative t-statistic and / or beta value of macro-areas forming a lobe may be combined to produce the representative t-statistic and / or beta value of a lobe. In some embodiments, the method of combining the t-statistics and / or combining the beta values is by averaging. In some embodiments, the method of combining the t-statistics and / or combining the beta values is by selecting the minimum or maximum value among the ROIs composing the macro-area, or the minimum or maximum of the macro-areas composing the lobe. In some embodiments, the method of combining the t-statistics and / or combining the beta values is by using the median. In some embodiments, the method of combining the t-statistic and / or combining the beta value is by averaging and determining a standard deviation (e.g., one to threeIFF101181-WO-PCTstandard deviations). In some embodiments, the method of combining the t-statistic and / or combining the beta value is by using the mode. In some embodiments, the method of combining the t-statistic and / or combining the beta value is by using a weighted average including or excluding non-significant values. For example, if 4 of 10 ROIs in a macro-area have significant beta values, the average beta value may be determined over the 4 ROIs or the 10 ROIs. In some embodiments, the method of combining the t-statistic and / or combining the beta value when determining for a lobe may use any method of combination described herein starting from either macro-areas composing the lobe or the ROIs composing the lobe. Alternatively, the method of combining the t-statistic and / or combining the beta value when determining for a lobe may use any method of combination described herein starting from the voxels composing each ROI, macroarea, or lobe.
[0144] In some embodiments, the mental state-specific brain activity maps and / or the test mental state brain activity maps are produced by determining one or more brain regions, such as voxels, ROIs, macro-areas, lobes, or any combination thereof, activated by the stimulus (e.g., control stimulus, test stimulus). In some embodiments, the brain regions are voxels. In some embodiments, the brain regions are ROIs. In some embodiments, the brain regions are macro-areas. In some embodiments, the brain regions are lobes. In some embodiments, the one or more brain regions are one type of or any combination of voxels, ROIs, macro-areas, or lobes. For example, when the one or more brain regions are of one type, the one or more brain regions are all voxels, ROIs, macro-areas, or lobes. For example, when the one or more brain regions are a combination, the one or more brain regions may include two or more of voxels, ROIs, macro-areas, or lobes. In some embodiments, the type of brain regions for the mental state- specific brain activity map and the test brain activity map are the same. For example, in some embodiments, the mental statespecific brain activity map includes ROIs and is compared to a test mental state brain activity map including ROIs.2. Olfactory Stimuli and Gustatory Stimuli
[0145] As described above, the brain activity of interest in the methods described herein is the activity that is evoked by exposure to olfactory stimuli and gustatory stimuli. In some embodiments, a standard olfactory stimulus may be used to determine a baseline brain activity. In some embodiments, the standard olfactory stimulus is air. In some embodiments, the standardIFF101181-WO-PCTolfactory stimulus is a vehicle, e.g., solvent, in which the olfactory stimuli are dissolved. In some embodiments, the standard olfactory stimulus is an olfactory stimulus that is used consistently throughout the experimental design as a reference (reference olfactory stimulus). In some embodiments, the baseline brain activity assists in identifying the olfactory stimulus evoked brain activity.
[0146] In some embodiments, a standard gustatory stimulus may be used to determine a baseline brain activity. In some embodiments, the standard gustatory stimulus is plain water. In some embodiments, the standard gustatory stimulus is a flavorless sugar-acid base. In some embodiments, the standard gustatory stimulus is a flavored base. In some embodiments, the standard gustatory stimulus is a flavorless matrix. In some embodiments, the standard gustatory stimulus is a standard flavor. In some embodiments, the standard gustatory stimulus is a gustatory stimulus that is used consistently throughout the experimental design as a reference (reference gustatory stimulus). In some embodiments, the standard gustatory stimulus is an existing consumer product. In some embodiments, the standard gustatory stimulus is unflavored. In some embodiments, the standard gustatory stimulus is a flavored base to which a test stimulus may be added.
[0147] A baseline brain activity may be analyzed according to any of the methods described herein so long as the analysis is sound and consistent with the analytical objectives, which will be understood according to experimental design and method of imaging used.
[0148] Methods for delivering the olfactory stimulus may depend on the type of stimulus and the brain imaging used. Any method that is compatible with the brain imaging method is contemplated for use according to the methods herein. In some embodiments, the olfactory stimulus is delivered by an olfactometer. In some embodiments, the olfactometer is suitable for fMRI experiments. In some embodiments, the olfactory stimulus is delivered using a pellet positioned under the subject’ s nose. In some embodiments, the subject is exposed to a plurality of olfactory stimuli. In some embodiments, the olfactory stimuli are delivered at iso-intensity.
[0149] Methods for delivering the gustatory stimulus may depend on the type of stimulus and the brain imaging used. Any method that is compatible with the brain imaging method is contemplated for use according to the methods herein. In some embodiments, the gustatory stimulus is delivered by a gustometer. In some embodiments, the gustometer is suitable for fMRI experiments. In someIFF101181-WO-PCTembodiments, the gustatory stimulus is delivered manually by the subject being imaged. For example, the subject may drink from a cup. In some embodiments, the subject is exposed to a plurality of gustatory stimuli. In some embodiments, the gustatory stimuli are delivered at isointensity.E. Databases
[0150] Olfactory stimuli and gustatory stimuli (test stimuli, control stimuli) and their corresponding mental state, and optionally strength ratings, as determined according to the methods described herein, may be stored in a database. In some embodiments, the database is configured to store a plurality of olfactory stimuli and / or gustatory stimuli, mental states, and, optionally, associated strength rating, using a suitable data storage format and schema. In some embodiments, additional information, such as demographic, psychological, and / or sensory test data, may be associated with the olfactory stimulus or gustatory stimulus, mental state, and, optionally, strength ratings. In some embodiments, the demographic data may include one or more of country, age, gender, ethnicity, or nationality information. In some embodiments, psychological and / or sensory test data are collected using, for example, but not limited to, Edinburgh Handedness Inventory, PANAS (positive / negative affective states), STAI (anxiety), FPQ (Food preference questionnaire), SAM ratings for valence, arousal and dominance (pleasantness, intensity, and how overwhelming the feeling is), Likert scales (to rate different parameters as liking or spiciness or other sensory aspects), intensity scales, hedonic evaluation (how nice / engaging / positive a stimulus is), ranking of attributes, dominant attributes (write down descriptors of a fragrance / flavor), CATA selection of attributes (from a list of attributes, which ones belong to the sample you’re smelling / tasting?). In some embodiments, a pleasantness rating for the olfactory stimulus or the gustatory stimulus is included in the database. In some embodiments, the database may include information about the olfactory stimulus or gustatory stimulus, e.g., ingredients, chemical structure, concentration(s) of ingredient(s), regulatory information, etc.
[0151] The databases may be manipulatable and / or searchable. For example, the database may include a query module that allows the storage, identification, modification, updating, accessing, etc. of data stored therein. In some embodiments, a user interface may be used to query the database. For example, the database may be queried to extract all information relating to a particular mental state, demographic group (e.g., country, age, gender, ethnicity, nationality),IFF101181-WO-PCTolfactory stimulus or gustatory stimulus, and / or strength rating, and optionally pleasantness. In some embodiments, the database may be queried to provide olfactory stimuli or gustatory stimuli that induce a particular mental state, optionally with a specific strength.
[0152] In some embodiments, the database may be used for producing new fragrances and flavors that induce a desired mental state, optionally with a desired strength. In some embodiments, the database may be used for producing new ingredients (fragrance ingredients, flavor ingredients) that induce a desired mental state, optionally with a desired strength. In some embodiments, the database may be used to modify an existing fragrance or flavor such that it elicits a new mental state or enhances (strengthens) an existing mental state. In some embodiments, the database may be used to determine which mental states, and optionally their strength, are elicited by an existing fragrance or flavor.II. METHODS FOR IDENTIFYING OLFACTORY AND GUSTATORY STIMULI THAT ELICIT A MENTAL STATE
[0153] As described in Section V, mental state- specific brain activity maps were identified for each of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, and a positive self-esteem mental state according to the methods described herein. The mental state-specific brain activity maps corresponding to these states are referred to herein as an adventure brain activity map, an attention brain activity map, a craving brain activity map, a drive brain activity map, an energy brain activity map, a focus brain activity map, a happiness brain activity map, a learning brain activity map. a memory brain activity map, a mindfulness brain activity map. a relaxation brain activity map, a reward brain activity map, a seduction brain activity map, or a self-esteem brain activity map, respectively. Furthermore, in some embodiments, because two or more mental statespecific brain activity maps were produced, a global network could be determined according to the methods described herein, e.g., Section LA. In some embodiments, the global network was identified for ROIs and macro-areas according to Section I-D. It will be appreciated that the mental state- specific brain activity maps and test mental state brain activity maps may be produced according to the methods described herein.
[0154] Methods for identifying whether a test stimulus elicits one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, aIFF101181-WO-PCTmindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state may be accomplished according to any means described herein. For example, see Section I-C. In some embodiments, the methods further include determining a strength by which the test stimulus elicits the mental state, e.g., as described in Section I-C.
[0155] In an aspect is provided a method for identifying an olfactory stimulus or gustatory stimulus that elicits a mental state in a subject, including: (a) comparing a test mental state brain activity map, determined in response to a test stimulus, with one or more mental state- specific brain activity maps, where the one or more mental state- specific brain activity maps include an adventure brain activity map, an attention brain activity map, a craving brain activity map, a drive brain activity map, an energy brain activity map, a focus brain activity map, a happiness brain activity map, a learning brain activity map, a memory brain activity map, a mindfulness brain activity map, a relaxation brain activity map. a reward brain activity map, a seduction brain activity map, or a self-esteem brain activity map; and (b) identifying the test stimulus as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map is at least 20%, 30%, 40%, 50%, 60%. 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more. In some embodiments, the one or more mental state- specific brain activity maps each include one or more brain regions, wherein the one or more brain regions correspond to ROIs, macro-areas, or lobes as defined by the Brainnetome Atlas. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental statespecific brain activity map is at least 40%, 50%, 60%, 70%, 80%, 85%. 90%, 95%, 96%, 97%, 98%, 99% or more. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental statespecific brain activity map is at least 40%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused,IFF101181-WO-PCTa happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map is at least 50%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map is at least 60%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map is at least 70%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map is at least 80%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map is at least 85%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map is at least 90%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map is at least 95%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteemIFF101181-WO-PCTmental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map is 100%.
[0156] In another aspect is provided a method for identifying an olfactory stimulus or gustatory stimulus that elicits a mental state in a subject, including: (a) comparing a test mental state brain activity map, determined in response to a test stimulus, with a global network and one or more mental state-specific brain activity maps, where the one or more mental state- specific brain activity maps include an adventure brain activity map, an attention brain activity map, a craving brain activity map, a drive brain activity map, an energy brain activity map, a focus brain activity map, a happiness brain activity map, a learning brain activity map, a memory brain activity map, a mindfulness brain activity map, a relaxation brain activity map, a reward brain activity map, a seduction brain activity map, or a self-esteem brain activity map; and (b) identifying the test stimulus as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or more. In some embodiments, the global network and the one or more mental state- specific brain activity maps each include one or more brain regions, where the one or more brain regions correspond to ROIs or macro-areas as defined by the Brainnetome Atlas. In some embodiments, the global network and the one or more mental state-specific brain activity maps each include one or more brain regions, where the one or more brain regions correspond to ROIs or macro-areas as defined by the Brainnetome Atlas, and the percent similarity is determined by comparing the brain regions of the test mental state brain activity with the brain regions of the global network and the brain regions of the mental state-specific brain activity map in total, and the at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more percent similarity is not exclusive to the one or more brain regions of the global network. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 40%. 50%, 60%, 70%, 80%. 85%, 90%, 95%, 96%, 97%. 98%, 99% or more.IFF101181-WO-PCTIn some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 40%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 50%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map and the global network is at least 60%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 70%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 75%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 80%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the testIFF101181-WO-PCTmental state brain activity map and the mental state-specific brain activity map and the global network is at least 85%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map and the global network is at least 90%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 95%. In some embodiments, the test stimulus is identified as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is 100%. In some embodiments, the percent similarity is not satisfied to determine that the test stimulus elicits a mental state if the percent similarity is only achieved by an overlap with the brain regions of the global network.
[0157] In some embodiments, the global network includes brain regions corresponding to ROIs 16, 17, 24, 29, 31, 33, 34, 35, 36, 37, 38. 39. 40. 45. 46. 49. 51, 52, 61, 63, 86, 100, 135, 136, 138, 151, 167, 169, 188, 194, 199, 204, 212, 223, 225, 234, and 243. In some embodiments, the global network includes brain regions corresponding to macro-areas 5, 7, 29, 41, and 42. In some embodiments, if the mental state-specific brain activity map includes ROIs, the global network for comparison includes ROIs. In some embodiments, if the mental state- specific brain activity map includes macro-areas, the global network for comparison includes macro-areas. In some embodiments, the global network includes the same type of brain regions (e.g„ ROIs, macro-areas, or lobes) as the mental state-specific brain activity map. In some embodiments, the test mental state brain activity map includes the same type of brain regions (e.g„ ROIs, macro-areas, or lobes) as the mental state- specific brain activity map. In some embodiments, the test mental state brain activity map includes the same type of brain regions (e.g., ROIs, macro-areas, or lobes) as the mental state- specific brain activity map and the global network.IFF101181-WO-PCT
[0158] In some embodiments, the mental state- specific brain activity map corresponds to a sensation of adventure. The sensation of adventure includes feelings of thrill, a rush, adrenaline, courage, assertiveness, daring, fearlessness, boldness, and / or spontaneity. In some embodiments, the mental state- specific brain activity map corresponding to a sensation of adventure is referred to as an adventure brain activity map. In some embodiments, the adventure brain activity map includes brain regions corresponding to ROIs 2, 6, 26, 32, 42, 45, 46, 49, 50, 58, 63, 65, 75, 84, 85, 86, 87, 92, 95, 98, 99, 105, 111, 120, 121, 123, 126, 128, 130, 131, 136, 139, 140, 146, 150, 151, 160, 162, 163, 171. 177, 178, 186, 187, 188, 194, 197, 202, 213, 218, 231, 232, 234, 238, and 243. In some embodiments, the adventure brain activity map includes brain regions corresponding to macro-areas 7, 8, 10, 11, 20, 23, 28, 29, 30, 32, and 45. In some embodiments, the adventure brain activity map includes brain regions corresponding to lobes 1, 3, 4, 9, 10, 11, and 12.
[0159] In some embodiments, the mental state-specific brain activity map corresponds to a sensation of attention. The sensation of attention includes feelings of alertness, salience, surprise, perception (e.g., acute awareness of one’s environment), imminence of an impending event, spatial and / or visual attention or awareness, and / or sensory awareness. In some embodiments, the mental state- specific brain activity map corresponding to a sensation of attention is referred to as an attention brain activity map. In some embodiments, the attention brain activity map includes brain regions corresponding to ROIs 7, 11, 13, 14, 15, 16, 27, 29, 31, 32, 33, 34, 37, 38, 39, 40, 51, 52, 53, 57, 58, 61, 62, 63, 65, 83, 84, 89, 90, 94, 95, 103, 105, 114, 115, 124, 127, 135, 136, 143, 147, 150, 151. 153, 164, 167, 168, 169, 173. 178, 179, 180, 183, 185, 188. 196. 197, 199, 200, 201, 204, 205, 208, 211, 212, 215, 219, 224, 225, and 229. In some embodiments, the attention brain activity map includes brain regions corresponding to macro-areas 6, 17, 21, 29, 33, 34, 35, 36, 39, 41, 42, 45. 46, and 48. In some embodiments, the attention brain activity map includes brain regions corresponding to lobes 7, 9, 10, 11, 12, 13, and 14.
[0160] In some embodiments, the mental state-specific brain activity map corresponds to a sensation of craving. The sensation of craving includes feelings of yearning, urge, longing, emotional or physical hunger, passionate wish or aspiration, hankering, and / or appetite. In some embodiments, the mental state- specific brain activity map corresponding to a sensation of craving is referred to as a craving brain activity map. In some embodiments, the craving brain activity map includes brain regions corresponding to ROIs 14, 15, 16, 17, 19, 21, 23, 29, 31, 33, 35, 37, 38, 39, 41, 45, 46, 49, 50, 51, 63, 65, 70, 83, 94, 97, 99, 100, 106, 117, 118, 119, 120, 123, 127, 132, 135,IFF101181-WO-PCT136, 138, 144, 147, 149, 151, 167, 168, 169, 172, 174, 179, 180, 182, 187, 188, 189, 190, 191, 193, 194, 195, 200, 202, 204, 207, 209, 210, 223, and 234. In some embodiments, the craving brain activity map includes brain regions corresponding to macro-areas 5, 7, 8. 17. 18. 20. 23, 24, 29, 30, 34, 37, 39, and 45. In some embodiments, the craving brain activity map includes brain regions corresponding to lobes 3, 4, 5, 7, 8, 11, and 12.
[0161] In some embodiments, the mental state- specific brain activity map corresponds to a sensation of drive. The sensation of drive includes feelings of motivation, engagement, yearning, ambitiousness, determination, initiative, zeal, passion, vigor, persistence, aspiration, grit, and / or momentum. In some embodiments, the mental state-specific brain activity map corresponding to a sensation of drive is referred to as a drive brain activity map. In some embodiments, the drive brain activity map includes brain regions corresponding to ROIs 6, 13, 14, 19, 20, 24, 27, 28, 29, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40. 41. 42. 45. 46. 51. 52. 61, 62, 63, 64, 65, 76, 80, 82, 95, 111, 115, 116, 125, 133, 135, 143, 145, 167, 168, 171, 177, 178, 187, 188, 196, 197, 199, 201, 207, 212, 217, 220, and 224. In some embodiments, the drive brain activity map includes brain regions corresponding to macro-areas 4, 5, 6, 7, 11, 14, 16, 24, 33, 35, 36, 37, 39, 41, 42, and 43. In some embodiments, the drive brain activity map includes brain regions corresponding to lobes 7, 8, 10, 11, 12, 13, and 14.
[0162] In some embodiments, the mental state-specific brain activity map corresponds to a sensation of energy. The sensation of energy includes feelings of an urge for motor activation and voluntary movement, vibrancy, vitality, stimulation, exuberance, and / or upliftment. In some embodiments, the mental state-specific brain activity map corresponding to a sensation of energy is referred to as an energy brain activity map. In some embodiments, the energy brain activity map includes brain regions corresponding to ROIs 17, 24, 29, 31, 33, 35, 37, 39, 46, 49, 50, 51, 69, 70, 71, 75, 96, 98, 100, 116, 117, 123, 125, 129, 130, 131, 133, 139, 143, 144, 146, 151, 165, 167, 168, 170, 172, 177, 194, 196, 199, 202, 210, 211, 212, 213, 214, 220, 221, 222, 223, 224, 225, 226, 228, 230, 231, 232, 233, 234, 238, 239, 242, and 243. In some embodiments, the energy brain activity map includes brain regions corresponding to macro-areas 5, 7, 11, 23, 25, 28, 41, 42, 45, and 46. In some embodiments, the energy brain activity map includes brain regions corresponding to lobes 5, 7, 10, 11, 12. 13. and 14.IFF101181-WO-PCT
[0163] In some embodiments, the mental state- specific brain activity map corresponds to a sensation of focus. The sensation of focus includes feelings of perceptual depth and sustained attention, selective concentration, immersion, clarity of perception, intentionality, resistance to external interference, cognitive absorption, mental alignment, and / or vigilant observation. In some embodiments, the mental state-specific brain activity map corresponding to a sensation of focus is referred to as a focus brain activity map. In some embodiments, the focus brain activity map includes brain regions corresponding to ROIs 16, 17, 18, 24, 25, 26, 29, 31, 33, 36, 37, 44, 51, 52, 56, 63, 66, 75, 86, 88. 98. 100, 102, 105, 123, 125, 126, 127, 128, 129, 130, 131, 132, 135, 136, 137, 138, 139, 140, 143, 144, 147, 148, 149, 150, 167, 168, 169, 170, 171, 173, 175, 176, 180, 183, 189, 192, 194, 195, 199, 201, 202, 204, 205, 207, 208, 209, 215, 221, 234, 241, 242, and 243. In some embodiments, the focus brain activity map includes brain regions corresponding to macroareas 5, 7, 12, 22, 28, 29, 30, 32, 33, 35, 38, 39, and 41. In some embodiments, the focus brain activity map includes brain regions corresponding to lobes 5, 6, 7, 9, 10, 11, and 12.
[0164] In some embodiments, the mental state- specific brain activity map corresponds to a sensation of happiness. The sensation of happiness includes feelings of positivity, well-being awareness, self-referential processing, life satisfaction, pleasure, joy, contentment, optimism, hope, ecstasy, euphoria, playful, fun, and / or amused. In some embodiments, the mental statespecific brain activity map corresponding to a sensation of happiness is referred to as a happiness brain activity map. In some embodiments, the happiness brain activity map includes brain regions corresponding to ROIs 13, 15, 16, 17, 18, 20, 22, 23, 24, 28, 29, 30, 31. 32. 33. 34. 35. 36, 37, 38, 39, 40, 41, 42, 44, 46, 49, 51, 52, 54, 61, 63, 74, 82, 86, 105, 113, 116, 118, 132, 133, 135, 136, 138, 139, 142, 144, 147, 151, 155, 163, 164, 165, 167, 168, 169, 172, 173, 174, 179, 186, 187, 188, 194. 199, 200, 206, 208. 211, 216, 219, 223. 225, 228, 229, and 234. In some embodiments, the happiness brain activity map includes brain regions corresponding to macro-areas 3, 4, 6, 8, 11, 12, 14, 16, 29, 34, 41, 42, 44, 45, and 46. In some embodiments, the happiness brain activity map includes brain regions corresponding to lobes 2, 3, 4, 5, 7, 8, and 12.
[0165] In some embodiments, the mental state-specific brain activity map corresponds to a sensation of learning. The sensation of learning includes feelings leading to notion acquisition, assimilation, apperception, skill development, knowledge construction, comprehension, cognitive growth, conceptualization, and / or neuroplastic adaptation. In some embodiments, the mental statespecific brain activity map corresponding to a sensation of learning is referred to as a learningIFF101181-WO-PCTbrain activity map. In some embodiments, the learning brain activity map includes brain regions corresponding to ROIs 9, 17, 22, 24, 31, 33, 34, 35, 36, 37, 38, 39, 40, 44, 47, 51, 52, 54, 60. 61, 62, 63, 64, 72. 73. 77, 81, 84, 87, 89, 95. 98. 100. Ill, 112, 119, 120, 137. 138, 141, 146, 155, 156, 157, 158, 160, 163, 164, 167, 169, 171, 172, 173, 174, 175, 176, 190, 191, 193, 194, 195, 200, 204, 206, 207, 208, 214, 216, 218, 229, 232, 233, and 245. In some embodiments, the learning brain activity map includes brain regions corresponding to macro-areas 5, 7, 9, 13, 15, 31, 32, 33, 34, 38, 40, 41, 42, and 44. In some embodiments, the learning brain activity map includes brain regions corresponding to lobes 1, 2, 7, 8, 10, 11, and 12.
[0166] In some embodiments, the mental state- specific brain activity map corresponds to a sensation of memory. The sensation of memory includes feelings of encoding, consolidating, retaining and recalling information, feelings of information recognition, representation, activation and retrieval, unforgettability, nostalgia, and / or recollection. In some embodiments, the mental state- specific brain activity map corresponding to a sensation of memory is referred to as a memory brain activity map. In some embodiments, the memory brain activity map includes brain regions corresponding to ROIs 9, 13, 17, 31, 33, 35, 36, 37, 39, 43, 45, 46, 49, 51, 61, 62, 63, 64, 70, 86, 99, 100, 111, 114, 122, 124, 129, 130, 131, 136, 139, 140, 145, 146, 154, 155, 157, 159, 160, 162, 163, 170, 174, 190, 204. 209, 211, 212, 219, 223, 225, 231, 234, 235, 237, 239, 242, 243, and 245. In some embodiments, the memory brain activity map includes brain regions corresponding to macro-areas 9, 10, 11, 17, 20, 26, 28, 31, 32, 38, 44, and 47. In some embodiments, the memory brain activity map includes brain regions corresponding to lobes 4, 5, 6, 7, 10, 11, 12.
[0167] In some embodiments, the mental state-specific brain activity map corresponds to a sensation of mindfulness. The sensation of mindfulness includes feelings of a present-focused state as opposed to self-focused thinking, bodily awareness, emotional distancing and / or regulation, self -regulation, calm awareness, and / or resilience. In some embodiments, the mental state-specific brain activity map corresponding to a sensation of mindfulness is referred to as a mindfulness brain activity map. In some embodiments, the mindfulness brain activity map includes brain regions corresponding to ROIs 1, 4, 17, 20, 22, 24, 28, 31, 33, 35, 36, 37, 39, 43, 45, 49, 50, 51, 69, 70, 75, 77, 86, 88, 94, 96, 99, 106, 109, 110, 117, 121, 123, 128, 129, 130, 136, 137, 139, 140, 142, 148, 149. 150, 154, 157, 167, 169, 177. 186, 194, 200, 209, 211, 212. 213. 214, 215, 216, 223, 225, 226, 230, 236, and 245. In some embodiments, the mindfulness brain activity map includes brain regions corresponding to macro-areas 7, 23, 26, 27, 28, 29, 30, 33, 41, 42, 43, and 47. InIFF101181-WO-PCTsome embodiments, the mindfulness brain activity map includes brain regions corresponding to lobes 1, 2, 5, 6, 7, 11, and 12.
[0168] In some embodiments, the mental state- specific brain activity map corresponds to a sensation of relaxation. The sensation of relaxation includes feelings of calmness, low arousal, reduced sensory awareness, internal focus, smoothness, quietness, regulation of voluntary movement, sleepiness, ease, gentleness, comfort, peace, reassurance, security, balance, emotional harmonization, and / or cocooning. In some embodiments, the mental state-specific brain activity map corresponding to a sensation of relaxation is referred to as a relaxation brain activity map. In some embodiments, the relaxation brain activity map includes brain regions corresponding to ROIs 1, 4, 5, 7, 8, 16, 18, 20, 29, 31, 34, 37, 38, 39, 40, 41, 45, 51, 52, 56, 57, 59, 61, 63, 64, 65, 67, 73, 74, 82, 86, 88, 96, 101, 106, 114, 118, 122, 138, 144, 145, 146, 148, 161, 167, 169, 171, 173, 180, 183, 185. 187, 188, 192, 194. 195, 196, 198, 199, 203. 204, 206, 209, 214. 223. 225, and 244. In some embodiments, the relaxation brain activity map includes brain regions corresponding to macro-areas 1, 5, 7, 11, 16, 18, 20, 24, 25, 29, 30, 33, 42, and 45. In some embodiments, the relaxation brain activity map includes brain regions corresponding to lobes 4, 7, 9, 11, 12, 13, and 14.
[0169] In some embodiments, the mental state-specific brain activity map corresponds to a sensation of reward. The sensation of reward includes feelings of gratification, satisfaction, pleasure, incentive, benefit, accomplishment, and / or recognition. In some embodiments, the mental state-specific brain activity map corresponding to a sensation of reward is referred to as a reward brain activity map. In some embodiments, the reward brain activity map includes brain regions corresponding to ROIs 3, 5, 13, 15, 16, 17, 24, 29, 31, 34, 35, 36, 38, 39, 40, 41, 44, 45, 47, 48, 50, 51, 52, 63, 64, 70, 77, 81, 83, 89, 98, 99, 100, 121, 127, 128, 138, 140, 145, 146, 147, 148, 149, 151, 160, 165, 176, 177, 178, 182, 189, 190, 191, 192, 193, 194, 199, 204, 205, 206, 207, 209, 212, 223, 231, 232, 233, 237, 238, 240, 242, 243, 244, and 246. In some embodiments, the reward brain activity map includes brain regions corresponding to macro-areas 3, 5, 6, 7, 8, 10, 15, 19, 22, 23, 29, 37, 38, 39, and 40. In some embodiments, the reward brain activity map includes brain regions corresponding to lobes 1, 3, 5, 7, 9, 11, and 12.
[0170] In some embodiments, the mental state-specific brain activity map corresponds to a sensation of seduction. The sensation of seduction includes feelings of sexual arousal, desire,IFF101181-WO-PCTsensual stimulation, attraction, sexual reward, enticement, sexual attraction, romanticism, allure, charm, sparks, sexy, sensuous, provocation, charisma, attraction, mystery, intimacy, admiration, and / or deep connection. In some embodiments, the mental state-specific brain activity map corresponding to a sensation of seduction is referred to as a seduction brain activity map. In some embodiments, the seduction brain activity map includes brain regions corresponding to ROIs 4, 5, 14, 24, 27, 30, 33, 34, 37, 40, 41, 42, 46, 48, 50, 51, 61, 63, 64, 76, 81, 82, 85, 86, 88, 91, 93, 98, 100, 102, 103, 105, 115, 121, 135, 138, 140, 148, 151, 153, 154, 167, 169, 170, 171, 173, 176, 179, 180, 181, 182, 184, 187, 188, 189. 190, 191, 193, 194, 197, 199. 200, 203, 204, 207, 208, 212, 219, 223, 225, 231, 232, 237, 238, 239, 240, 242, 243, and 244. In some embodiments, the seduction brain activity map includes brain regions corresponding to macro-areas 8, 15, 17, 18, 19, 21, 23, 37, 38, 39, 40, and 48. In some embodiments, the seduction brain activity map includes brain regions corresponding to lobes 1, 2, 4, 7, 11, 12, and 14.
[0171] In some embodiments, the mental state-specific brain activity map corresponds to a sensation of self-esteem (e.g., positive self-esteem). The sensation of self-esteem includes feelings of self-worth, self-respect, self-confidence, self-appreciation, self-love, self-assurance, sense of identity, personal value, self-integrity, and / or self-acceptance. In some embodiments, the mental state- specific brain activity map corresponding to a sensation of self-esteem is referred to as a self-esteem brain activity map. In some embodiments, the self-esteem brain activity map includes brain regions corresponding to ROIs 13, 14, 16, 20, 21, 22, 23, 28, 33, 34, 36, 40, 44, 49, 51, 53, 61, 62, 63, 81, 83, 86, 95, 105, 135. 137, 138, 141, 145. 178, 181, 182, 189. 190, 193, 194, 196, 197, 199, 204, 205, 206, 210, 212, 213, 214, 215, 216, 217, 218, 221, 230, 231, 232, 234, 237, 238, 239, 242, 243, 244, and 246. In some embodiments, the self-esteem brain activity map includes brain regions corresponding to macro-areas 3, 6. 8, 18, 19, 22, 31, 37, 38, 43, 44, 46, 47, and 48. In some embodiments, the self-esteem brain activity map includes brain regions corresponding to lobes 2, 9, 10, 11, 12, 13, and 14.
[0172] In some embodiments, the test stimulus is identified to elicit 0, 1, 2, 3, 4, or more mental states selected from adventurous, attentive, craving, driven, energetic, focused, happy, learning, memory, mindfulness, relaxed, reward, seductive, or positive self-esteem, according to the activated mental state-specific brain activity map. In some embodiments, a strength by which the test stimulus elicits the mental state is determined.IFF101181-WO-PCTIII. METHODS FOR PRODUCING A FRAGRANCE OR FEAVOR COMPOSITION THAT ELICITS A MENTAE STATE
[0173] The methods for determining a mental state induced by an olfactory stimulus or gustatory stimulus described herein offer the unique ability to swiftly and strategically produce fragrance and flavor compositions having the ability to elicit a mental state, optionally with a specific strength, in a subject. The mental states and, optionally, corresponding strength ratings for olfactory stimuli or gustatory stimuli may serve as a guide for fragrance and flavor composition development. Thus, also provided herein are methods for producing fragrance and flavor compositions that induce one or more mental states in a subject, optionally with a specific strength.
[0174] In an aspect is provided methods for producing a fragrance or flavor composition that elicits a mental state in a subject. In an aspect is provided methods for producing fragrance and flavor compositions that elicit one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject, optionally with a specific strength. In some embodiments, the fragrance composition is a fragrance accord. In some embodiments, the fragrance composition is a full fragrance. In some embodiments, the flavor composition is a flavor accord. In some embodiments, the flavor composition is a full flavor.
[0175] In some embodiments, the methods include identifying, according to the methods of determining a mental state induced by an olfactory stimulus, a fragrance ingredient and / or fragrance accord that induces a mental state. In some embodiments, the fragrance ingredient and / or accord that induces a mental state may be identified from a database as described herein. In some embodiments, the methods include formulating the fragrance ingredient and / or accord into an accord or full fragrance. In some embodiments, the strength of the mental state associated with the fragrance ingredient and / or fragrance accord may be used to produce an accord or full fragrance that induces a mental state with a desired intensity.
[0176] In some embodiments, the fragrance composition is a new fragrance composition. In some embodiments, the mental state and. optionally strength, are used to develop a new fragrance composition. For example, an objective may be to produce a fragrance composition that elicits a mental state in a subject upon exposure. In this case, it would be possible to query a database as described herein to identify fragrance ingredients and accords with which to formulate theIFF101181-WO-PCTfragrance composition. Furthermore, it may be possible to refine the query to identify fragrance ingredients and / or accords for a specific mental state, and optionally strength, for use in a global population or specific demographic group.
[0177] In some embodiments, the fragrance composition is an existing fragrance composition in which the fragrance ingredients are known. In this case, the fragrance composition may be modified to induce a desired mental state and / or enhance the ability of the fragrance composition to induce a desired mental state. In this case, it would be possible to query a database described herein to identify fragrance ingredients that would be compatible with the existing fragrance and would induce or enhance a desired mental state response in a subject. In some embodiments, the query may further include a restriction to identify fragrance ingredients and / or accords that induce a desired mental state, optionally with a specific strength, for use in a global population or specific demographic group.
[0178] In some embodiments, the methods include identifying, according to the method of determining a mental state induced by a gustatory stimulus, a flavor ingredient and / or flavor accord that induces a mental state. In some embodiments, the flavor ingredient and / or accord that induces a mental state may be identified from a database as described herein. In some embodiments, the methods include formulating the flavor ingredient and / or accord into an accord or full flavor. In some embodiments, the strength of the mental state associated with the flavor ingredient and / or flavor accord may be used to produce an accord or full flavor that induces a mental state with a desired intensity.
[0179] In some embodiments, the flavor composition is a new flavor composition. In some embodiments, the mental state and, optionally strength, are used to develop a new flavor composition. For example, an objective may be to produce a flavor composition that elicits a mental state in a subject upon exposure. In this case, it would be possible to query a database as described herein to identify flavor ingredients and accords with which to formulate the flavor composition. Furthermore, it may be possible to refine the query to identify flavor ingredients and / or accords for a specific mental state, and optionally strength, for use in a global population or specific demographic group.
[0180] In some embodiments, the flavor composition is an existing flavor composition in which the flavor ingredients are known. In this case, the flavor composition may be modified to induce aIFF101181-WO-PCTdesired mental state and / or enhance the ability of the flavor composition to induce a desired mental state, hi this case, it would be possible to query a database described herein to identify flavor ingredients that would be compatible with the existing flavor and would induce or enhance a desired mental state response in a subject. In some embodiments, the query may further include a restriction to identify flavor ingredients and / or accords that induce a desired mental state, optionally with a specific strength, for use in a global population or specific demographic group.
[0181] It should be appreciated that the methods described herein for creating a new or modifying an existing fragrance or flavor composition to induce a mental state may also be used to create new or modified fragrances or flavors that suppress, or do not elicit, a mental state. Furthermore, it will be appreciated that the methods described herein allow, for example when used in combination with, e.g., chemical structure information, for the creation of new ingredients (fragrance ingredients, flavor ingredients) that elicit a desired mental state, optionally with a desired strength.
[0182] In an aspect is provided use of a fragrance or flavor that elicits a mental state, a fragrance composition or flavor composition produced according to the methods provided herein, or a consumer product, to elicit a target mental state in a subject
[0183] In an aspect is provided a method of eliciting a target mental state in a subject, including delivering a fragrance or flavor that elicits a mental state, a fragrance composition or flavor composition produced according to the methods provided herein, or a consumer product as described herein to a subject. In some embodiments, the delivering occurs by the subject using the fragrance or flavor that elicits a mental state, the fragrance composition or flavor composition produced according to the methods provided herein, or the consumer product as described herein. For example, in some cases, the subject may use, such as, but not limited to, apply, spray, wash, eat, drink, taste, or otherwise engage as applicable with the fragrance or flavor that elicits a mental state, the fragrance composition or flavor composition produced according to the methods provided herein, or the consumer product, which will elicit the mental state in the subject. Thus, in some embodiments, the delivering occurs by a purposeful or active use of the fragrance or flavor that elicits a mental state, the fragrance composition or flavor composition produced according to the methods provided herein, or the consumer product as described herein. In some embodiments, the delivering occurs by a subject encountering the fragrance or flavor that elicits a mental state,IFF101181-WO-PCTthe fragrance composition or flavor composition produced according to the methods provided herein, or the consumer product as described herein without using the fragrance or flavor that elicits a mental state, the fragrance composition or flavor composition produced according to the methods provided herein, or the consumer product as described herein. For example, a subject who comes into contact with another person who has used, e.g., applied, washed, sprayed, eaten, drank, tasted, or otherwise engaged as applicable, the fragrance or flavor that elicits a mental state, the fragrance composition or flavor composition produced according to the methods provided herein, or the consumer product as described herein, and the encounter elicits the mental state in the subject. As another example, a subject who comes into contact with an object or area where a fragrance or flavor that elicits a mental state, a fragrance composition or flavor composition produced according to the methods provided herein, or a consumer product as described herein was used, e.g., applied, washed, sprayed, eaten, drank, tasted, or otherwise engaged as applicable, and the encounter elicits the mental state in the subject. Thus, in some embodiments, the delivering occurs by a passive interaction with the fragrance or flavor that elicits a mental state, the fragrance composition or flavor composition produced according to the methods provided herein, or the consumer product as described herein.IV. MENTAL STATE-ELICITING FRAGRANCES, FLAVORS, AND CONSUMER PRODUCTS
[0184] Also provided herein are fragrance ingredients, fragrance accords, full fragrances, flavor ingredients, flavor accords, and full flavors that elicit a mental state determined according to the methods described herein. Fragrance and flavor compositions produced according to the methods described herein are also provided.
[0185] The fragrance ingredients, fragrance accords, and full fragrances determined according to the methods herein to elicit a mental state and fragrance compositions produce according to the methods provided herein are widely applicable to any perfumery product, including perfumes and colognes, the perfuming of personal care products such as soaps, shower gels, and hair care products, fabric care products, air fresheners, and cosmetic preparations. In some embodiments, fragrance ingredients, fragrance accords, and full fragrances determined according to the methods herein to elicit a mental state and fragrance compositions produce according to the methods provided herein are used to perfume cleaning agents, such as, but not limited to, detergents,IFF101181-WO-PCTdishwashing materials, scrubbing compositions, window cleaners and the like. In these preparations, fragrance ingredients, fragrance accords, full fragrances, and fragrance compositions can be used alone or in combination with other perfuming compositions, solvents, adjuvants, and the like. The nature and variety of the other ingredients that can also be employed are known to those with skill in the art. Many types of additional fragrances can be employed so long as the fragrance is complementary (i.e., compatible) with the other components being employed.
[0186] The fragrance ingredients, fragrance accords, full fragrances, and fragrance compositions provided herein may be well- suited for use in a variety of consumer products and can be used as a neat fragrance formulation (e.g., in a fine fragrance) or may be encapsulated and / or delivered using a suitable carrier material. Some well-known materials include, for example, polymers, oligomers, other non-polymers such as surfactants, emulsifiers, lipids including fats, waxes and phospholipids, organic oils, mineral oils, petrolatum, natural oils, perfume fixatives, fibers, starches, sugars and solid surface materials such as zeolite and silica.
[0187] Also provided are consumer products containing a fragrance ingredient, fragrance accord, or full fragrance determined according to the methods herein to elicit a mental state or a fragrance composition produced according to the methods provided herein. In some embodiments, the consumer product is a household product, a fabric care product, a personal care product, or a cosmetic product. Consumer products may include, for example, perfumes, colognes, bar soaps, liquid soaps, shower gels, foam baths, cosmetics, skin care products such as creams, lotions and shaving products, hair care products for shampooing, rinsing, conditioning, bleaching, coloring, dyeing and styling, deodorants and antiperspirants, feminine care products such as tampons and feminine napkins, baby care products such as diapers, bibs and wipes, family care products such as bath tissues, facial tissues, paper handkerchiefs or paper towels, fabric products such as fabric softeners and fresheners, air care products such as air fresheners and fragrance delivery systems, cosmetic preparations, cleaning agents and disinfectants such as detergents, dishwashing materials, scrubbing compositions, glass and metal cleaners such as window cleaners, countertop cleaners, floor and carpet cleaners, toilet cleaners and bleach additives, washing agents such as allpurpose, heavy duty, and hand washing or fine fabric washing agents including laundry detergents and rinse additives.IFF101181-WO-PCT
[0188] In an aspect is provided use of a fragrance ingredient, fragrance accord, full fragrance, fragrance composition described herein, or consumer product containing a fragrance ingredient, fragrance accord, full fragrance, or fragrance composition described herein to elicit a mental state in a consumer.
[0189] In an aspect is provided use of a fragrance ingredient, fragrance accord, full fragrance, or fragrance composition described herein, or consumer product containing a fragrance ingredient, fragrance accord, full fragrance, or fragrance composition described herein to elicit one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state, optionally with a specific strength, in a consumer.
[0190] The flavor ingredients, flavor accords, and full flavors determined according to the methods herein to elicit a mental state and flavor compositions produced according to the methods provided herein are widely applicable to any food product, including, but not limited to, beverages, baked goods, bars, confectionery goods, culinary products, dairy products, and snack products, as well as oral care products, health care products, and nutritional products. In these preparations, flavor compositions can be used alone or in combination with other flavor compositions, solvents, adjuvants, and the like. The nature and variety of the other ingredients that can also be employed are known to those with skill in the art. Many types of additional flavors can be employed so long as the flavor is complementary (i.e., compatible) with the other components being employed.
[0191] Also provided are consumer products containing a flavor ingredient, flavor accord, or full flavor determined according to the methods herein to elicit a mental state or a flavor composition produce according to the methods provided herein. In some embodiments, the consumer product is a food product. In some embodiments the food product is a beverage, a baked good, a bar, a confectionery good, a culinary product, a dairy product, or a snack product. In some embodiments, the consumer product is an oral care product. In some embodiments, the oral care product is a dental and oral hygiene product such as toothpastes, tooth gels, dental flosses, denture cleansers, denture adhesives, dentifrices, tooth whitening, chewable gum, and mouthwashes. In some embodiments, the consumer product is a health care product. Non-limiting examples of health care products include syrups, gummies, tablets, capsules, chewable or drinkable medications, drinks, and powders. In some embodiments, the consumer product is a nutritional product. Non-limitingIFF101181-WO-PCTexamples of nutritional products include tablets, capsules, drinks, powders, and other non-limiting forms of nutritional supplements.
[0192] In an aspect is provided use of a flavor ingredient, flavor accord, full flavor, or flavor composition described herein, or consumer product containing a flavor ingredient, flavor accord, full flavor, or flavor composition described herein to elicit a mental state in a consumer.
[0193] In an aspect is provided use of a flavor ingredient, flavor accord, full flavor, or flavor composition described herein, or consumer product containing a flavor ingredient, flavor accord, full flavor, or flavor composition described herein to elicit one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state, optionally with a specific strength, in a consumer.EXEMPLARY EMBODIMENTS
[0194] Among the provided embodiments are:1. A method for producing a mental state-specific brain activity map, comprising: (a) identifying in one or more subjects a control brain activity, wherein the control brain activity represents brain activity evoked by exposure to a control stimulus, wherein the control stimulus is an olfactory stimulus or a gustatory stimulus that elicits a known mental state in a subject; and (b) determining, based on the control brain activity, one or more brain regions activated by the control stimulus to produce a mental state-specific brain activity map.2. The method of embodiment 1, wherein the known mental state elicited by the control stimulus is determined based on scientific literature, expert analysis, psychological testing, psychophysiological testing, behavioral testing, or any combination thereof.3. The method of embodiment 1 or embodiment 2, wherein the control stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.4. The method of any one of embodiments 1-3. wherein the control brain activity comprises control brain activity from two or more or a plurality of subjects.5. The method of any one of embodiments 1-4, wherein the determining of step (b) comprises inputting the control brain activity into a fingerprinting algorithm.IFF101181-WO-PCT6. The method of embodiment 5, wherein the fingerprinting algorithm is a Partial Least Squares (PLS) model, a Classification and Regression Tree (CART) model, a Bayesian network model, or any combination thereof.7. The method of embodiment 6, wherein the CART model is an Extreme Gradient Boosting (XGBoost) model, a Random Forest model, a Chi-Square Automatic Interaction Detection (CHAID) model, or any combination thereof.8. The method of embodiment 6 or embodiment 7. wherein the PLS model is a Partial Least Squares Discriminant Analysis (PLS-DA) and / or a Partial Least Squares Regression (PLS-R) analysis.9. The method of any one of embodiments 1-8, wherein the control brain activity is identified using brain imaging.10. The method of embodiment 9. wherein the brain imaging is functional magnetic resonance imaging (fMRI).11. The method of any one of embodiments 1-10, wherein the control brain activity comprises a statistical value for each of the one or more brain regions, wherein the statistical value represents a probability that the brain region is activated by exposure to the control stimulus.12. The method of embodiment 11, wherein the statistical value for each of the one or more brain regions is a t-statistic and / or a beta value.13. The method of any one of embodiments 1-12, wherein a brain region is a voxel, a region of interest (ROI), a macro-area, a lobe, or any combination thereof.14. The method of embodiment 13, wherein the statistical value for the ROI, the macro-area, or the lobe is, independently, a combination of the t-statistic and / or a combination of the beta values of all voxels contained in the ROI, the macro-area, or the lobe.15. A method for predicting a mental state elicited by an olfactory stimulus or a gustatory stimulus, comprising: (a) identifying in one or more subjects a test brain activity, wherein the test brain activity represents brain activity evoked by exposure to a test stimulus, wherein the test stimulus is an olfactory stimulus or a gustatory stimulus that elicits an unknown mental state in a subject; (b) determining, based on the test brain activity, one or more brain regions activated by the test stimulus to produce a test mental state brain activity map; and (c) comparing the test mental stateIFF101181-WO-PCTbrain activity map to one or more mental state- specific brain activity maps produced according to the method of any one of embodiments 1-14 that represent a known mental state, thereby determining whether the test stimulus elicits the mental state.16. The method of embodiment 15. wherein the test stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.17. The method of embodiment 15 or embodiment 16, wherein the test brain activity comprises test brain activity from two or more or a plurality of subjects.18. The method of any one of embodiments 15-17, wherein the comparing of step (c) comprises a qualitative comparison and / or predictive modeling.19. The method of embodiment 18, wherein the qualitative comparison comprises calculating a percent similarity between the test mental state brain activity map and the mental state-specific brain activity map.20. The method of embodiment 18 or embodiment 19, wherein the predictive modeling comprises: (a) training a predictive model on the one or more mental state-specific brain activity maps produced according to the method of any one of embodiments 1-14; and (b) inputting the test mental state brain activity map into the trained predictive model to predict a mental state elicited by the test stimulus.21. The method of embodiment 20, wherein the predictive model is a heuristic optimization algorithm, optionally a differential evolution algorithm, a particle swarm optimization algorithm, and / or a genetic algorithm.22. The method of any one of embodiments 15-21, wherein the comparing of step (c) further determines a strength by which the test stimulus elicits the mental state.23. The method of any one of embodiments 15-22, wherein the test brain activity is identified using brain imaging.24. The method of embodiment 23, wherein the brain imaging is fMRI.25. The method of any one of embodiments 15-24, wherein the test brain activity comprises a statistical value for each of the one or more brain regions, wherein the statistical value represents a probability that the brain region is activated by exposure to the test stimulus.IFF101181-WO-PCT26. The method of embodiment 25, wherein the statistical value for each of the one or more brain regions is a t-statistic and / or a beta value.27. The method of any one of embodiments 15-26, wherein a brain region is a voxel, an ROI, a macro-area, a lobe, or any combination thereof.28. The method of embodiment 27, wherein the statistical value of the ROI, the macro-area, or the lobe is, independently, a combination of the t-statistic and / or a combination of a beta value of all voxels contained in the ROI, the macro-area, or the lobe.29. A fragrance or flavor that elicits a mental state in a subject, identified according to the method of any one of embodiments 1-28.30. The fragrance or flavor of embodiment 29, wherein the fragrance or the flavor is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.31. A method for producing a fragrance composition or a flavor composition that elicits a mental state in a subject, comprising: a) identifying a fragrance or a flavor that elicits a target mental state in a subject according to the method of any one of embodiments 15-28; and b) incorporating the fragrance or the flavor that elicits the target mental state in a fragrance composition or a flavor composition.32. The method of embodiment 31, wherein the fragrance composition or the flavor composition is a new fragrance composition or a new flavor composition, and the new fragrance composition or the new flavor composition is being produced to elicit the target mental state in a subject. 33. The method of embodiment 31, wherein the fragrance composition or the flavor composition is an existing fragrance composition or an existing flavor composition, and the existing fragrance composition or the existing flavor composition is being modified to elicit the target mental state in a subject.34. The method of any one of embodiments 31-33, wherein the fragrance or the flavor is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.35. The method of any one of embodiments 31-34, wherein the fragrance is incorporated in a fragrance composition.IFF101181-WO-PCT36. The method of any one of embodiments 31-35, wherein the fragrance composition is a fragrance accord or a full fragrance.37. The method of any one of embodiments 31-34, wherein the flavor is incorporated in a flavor composition.38. The method of any one of embodiments 31-34 or 37, wherein the flavor composition is a flavor accord or full flavor.39. A consumer product comprising a fragrance or flavor according to embodiment 29 or embodiment 30 or a fragrance composition or flavor composition produced according to the method of any one of embodiments 31-38.40. The consumer product of embodiment 39, wherein the consumer product is a household product, a fabric care product, a personal care product, a cosmetic product, a fine fragrance, a beverage product, a baked good, a confectionery good, a culinary product, a dairy product, a snack product, an oral care product, a health care product, or a nutritional product.41. Use of a fragrance or flavor according to embodiment 29 or embodiment 30, a fragrance composition or flavor composition produced according to the method of any one of embodiments 31-38, or a consumer product according to embodiment 39 or embodiment 40 to elicit a target mental state in a subject.42. A method of eliciting a target mental state in a subject, comprising delivering a fragrance or flavor according to embodiment 29 or embodiment 30, a fragrance composition or flavor composition produced according to the method of any one of embodiments 31-38, or a consumer product according to embodiment 39 or embodiment 40 to a subject.V. EXAMPLES
[0195] The following examples are included for illustrative purposes only and are not intended to limit the scope of the invention.Example 1: fMRI Olfactory Stimulus Experimental Protocol
[0196] Participants: Tests were performed with participants in different locations throughout the world. Protocols were approved by the applicable regulatory authorities for research on human beings.IFF101181-WO-PCT
[0197] Participants were adults (over 18 years old), neurologically sound and had a normal sense of smell as declared by themselves or as assessed by the Sniffin Stick Test. Participants did not have contraindications for fMRI experimentation (standard criteria, e.g.. non-claustrophobic and righthanded).
[0198] Fragrances: Two to twelve fragrances, each composed of 5 to 20 ingredients, were prepared at iso-intensity diluted in a non-odorant solvent. Dilutions were done in accordance with regulatory procedures (e.g., IFRA norms) to achieve iso-intensity. In some experiments, single ingredients and full fragrances were used. See, e.g., Examples 3-5.
[0199] Experimental Design: Participants were fitted with a dark eye mask and placed within an fMRI scanner. Scent was delivered manually to subjects’ nose according to a standardized proprietary procedure. No task was asked of the subjects other than to smell.
[0200] Odorants were delivered in a random order and repeated at least 3 times. Sniffing time was limited to four seconds followed by a 16 second rest period. The inter stimulus interval was + / -30 seconds.
[0201] A T1 -weighted anatomical scan (1 x 1 x 8.8 mm3) was acquired for co-registration of the functional images and the participant’s brain anatomy. The participant's brain image was normalized to fit a common space that allowed comparison between several participants (MNI space).
[0202] Data Acquisition and Analysis: Images were acquired on a 3T MRI multiband scanner (Koninklijke Philips N.V., Amsterdam Netherlands) equipped with a 48-channel head coil allowing for measurement of functional brain images (T2* TR 2250 sequence with 3 x 3 x 3 mm3resolution). Brain activation following each exposure was analyzed using BrainVoyager and proprietary software.
[0203] Random group analyses (RFX) were performed from the functional run (BOLD). A two-step procedure was used. Pre- and post-processing of the data was carried out with BrainVoyager (versions 21.2 or higher). The images were realigned to a reference scan (correction for head movement), normalized in MNI space (to compensate for individual anatomical differences), and temporal filtered and spatially smoothed (max 5 mm).IFF101181-WO-PCT
[0204] For post-processing of the data, evoked brain activity was exported with an alpha risk <0.001 (GLM with RFX model and Bonferroni correction t > 3.88 to avoid test repetition statistical error), functional coverage must have been > 99% of the cortex. Outliers > 4 standard deviations were eliminated and interpolated (voxel resolution Ixlxl mm or better).Example 2: fMRI Gustatory Stimulus Experimental Protocol
[0205] Methods for fMRI imaging of responses to gustatory stimuli are the same as described in Example 1. However, gustatory stimuli will be delivered using an fMRI-compatible gustometer.Example 3: Mental States Elicited by Fragrances
[0206] This Example describes an exemplary method for predicting mental states elicited by fragrances.
[0207] Methods: fMRI imaging of brain activity evoked in response to an olfactory stimulus, as well as pre- and post-processing of brain imaging data, was accomplished according to the methods described in Example 1.
[0208] The olfactory stimuli included two fully formulated fragrances, E2 and H3, containing 40 and 61 fragrance ingredients, respectively, which elicited unknown mental states. The olfactory stimuli were delivered to subjects and brain activity evoked in response to each olfactory stimulus was identified according to the described methods (See, e.g., Example 1). Beta values were determined for each voxel, and the beta values for voxels present in a region of interest (ROI), as described in Table 1 above, were averaged to generate a mean and standard deviation for each ROI. The mean, standard deviation, sample size, and alpha risk (20%) were used to calculate the confidence intervals of the beta values for each ROI. The confidence intervals were added to the mean values to produce a threshold beta value. Therefore, any value of beta above the threshold value would indicate a significantly active ROI (increased or decreased activity) in response to the olfactory stimulus. The analysis thus produced a test mental state brain activity map for each fragrance.
[0209] To predict the mental states elicited by the olfactory stimulus, the test mental state brain activity maps for each fragrance were compared to mental state- specific brain activity maps.
[0210] Mental state- specific brain activity maps were produced by identifying, using the fMRI and processing methods described in Example 1, brain activity in response to olfactory stimuliIFF101181-WO-PCTknown from scientific literature and expert analysis to elicit different mental states (control stimuli). For the brain activity evoked by each control stimulus, beta values were determined for each voxel, and the beta values for voxels present in a region of interest (ROI), as described in Table 1, were averaged to generate a mean and standard deviation for each ROI. This information, in combination with the sample size, allowed the determination of a 20% alpha risk (80% confidence interval). The mean beta values for each ROI were analyzed using a Partial Least Squares Discriminant Analysis (PLS-DA) to determine active ROIs underlying the mental state elicited by the control olfactory stimulus, thus producing the mental state-specific brain activity map. This method was used to produce mental state-specific brain activity maps for the mental states of positive self-esteem and energy, among others.
[0211] The active ROIs from the test mental state brain activity maps were compared with the active ROIs of each mental state- specific brain activity map to determine the amount of overlap in active ROIs. The overlap was determined by counting the number of active ROIs in the test mental state brain activity map that corresponded to the active ROIs of the mental state-specific brain activity map. The amount of overlap was presented as a percentage (e.g., a percent similarity).
[0212] The same analysis was also conducted at the level of macro-areas and lobes, as described in Table 1.
[0213] Results: Fragrance E2 was found to more strongly elicit the mental state of positive self-esteem compared to H3, with E2 evoking a 46% overlap in active ROIs and H3 evoking a 38% overlap. However, H3 more strongly elicited an energized mental state, having an overlap in active ROIs compared to the ROIs of the mental state-specific brain activity map of 49%, compared to E2’s 43%.
[0214] These results were also seen at the level of macro-areas and lobes, although the percentage of overlap increased as the size of the brain region increased. For example, at the macro-area and lobe level, E2 was found to more strongly elicit the self-esteem mental state, having 56% and 57% overlap with the mental state-specific brain activity map, respectively, compared to H3, which had 48% and 42% overlap, respectively. H3 more strongly elicited the energized mental state compared to E2 at the macro-area but not the lobe level (60% overlap for H3 compared to 56% overlap for E2 using macro-areas and 57% overlap for E2 and H3 using lobes).IFF101181-WO-PCT
[0215] These data suggest that the exemplary methods allow for the prediction of mental states elicited by fragrances, including the extent to which the mental state is elicited by the fragrance, which may allow a mental state profile of a fragrance to be appreciated.Example 4: Methods for Producing a Mental State-Specific Brain Activity Map
[0216] This Example describes exemplary methods for producing mental state- specific brain activity maps. The methods described were used to produce the mental state-specific brain activity maps for each of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, and a positive self-esteem mental state.
[0217] fMRI imaging of brain activity evoked in response to an olfactory stimulus, as well as pre-and post-processing of brain imaging data, was accomplished according to the methods described in Example 1. Olfactory stimuli included a plurality of fragrances, each composed of 1 fragrance ingredient, prepared at iso-intensity diluted in a non-odorant solvent. Dilutions were done in accordance with regulatory procedures (e.g., IFRA norms) to achieve iso-intensity.
[0218] Each olfactory stimulus was given a strength level denoted as a value from 0 to 1, with 1 indicating the fragrance ingredient strongly elicited a mental state and 0 indicating uncertainty or evidence suggesting that the ingredient did not elicit a mental state, for each mental state of interest (see above). The strength level value was determined based on scientific literature and expert analysis as to whether the fragrance elicited the mental state.
[0219] Average t-statistics and beta values were determined from population imaging data for each olfactory stimulus by averaging the t-statistic and beta values, independently, for the voxels in the ROI, macro-area, or lobe according to the Brainnetomme Atlas (see, e.g., Table 1 above). Partial Least Squares Regression (PLS-R) analysis was performed using, independently, the average data at the level of ROIs, macro-areas, and lobes. The mental states were considered the response variable (Y) and the ROIs, macro-areas, or lobes, depending on the level of analysis, were the predictor variables (X). Model quality was assessed per mental state to determine the number of components to be used where R2X achieves approximately 80% of explained variance for ROIs, macro-areas, and lobes. For the selected components, each brain region at each level (ROI, macroarea, or lobe) included an associated variable importance in projection (VIP) score. Brain regions (ROIs, macro-areas, or lobes) with a VIP score above 1 in all selected components for both t-IFF101181-WO-PCTstatistic and beta values were included as part of a particular mental state- specific brain activity map. A VIP score above 1 represents a 95% confidence level (alpha = 0.05) that a specific brain region contributes to the mental state-specific brain activity map.
[0220] A threshold was established to determine whether a brain region (ROI, macro-area, or lobe) was active by calculating a confidence interval that took into account the entirety of the dataset for olfactory stimuli. A specific threshold was calculated for beta values and t-statistics separately. Only the brain regions identified as belonging to a mental state-specific brain activity map contributed to the threshold calculation.
[0221] Using the strategy outlined above, mental state-specific brain activity maps were produced for each of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, and a positive self-esteem mental state. The ROIs, macro-areas, and lobes for each brain activity map are described above. See. e.g„ Section II.
[0222] The mental state-specific brain activity maps are used to describe which brain regions (ROIs, macro-areas or lobes) are more active (or more relevant) during specific emotional and cognitive processes. However, it is well known that the human brain does not work through compartmentalized blocks, despite the specialization of some areas (the best-known example of specialization is probably the so-called “brain homunculus”). For this reason, some areas of the brain are expected to contribute to more than a single process, while others can be more specific to single mental states. To account for this physiological behavior, in some cases, at the ROI and macro-area levels, a so-called “global network,” including those ROIs or those macro-areas appearing to contribute to at least 7 of the mental state-specific brain activity maps (that is, at least 50% of the 14 mental state- specific brain activity maps that are described above in Section II) was determined. This global network overlaps, to different degrees, with the 14 mental state-specific brain activity maps: the lowest overlap is 0% (meaning that no global network brain regions contribute to the mental state- specific brain activity map for a certain mental state), while the highest overlap was 32%, meaning that, in the “worst case scenario,” a mental state-specific brain activity map is constituted by 68% of unique (non-global) brain regions. Because of this difference in overlap between the global network and the mental state- specific brain activity maps, along with the fact that this overlap does not necessarily involve the same region in two different mental state-IFF101181-WO-PCTspecific brain activity maps, the specific brain regions of the global network may be included within the mental state-specific brain map for each mental state. However, when a global network and mental state-specific brain activity map are used for determining a percent similarity with a test mental state brain activity map, a brain region that is present in both the global network and the mental state-specific brain activity map is counted only once for the calculation.
[0223] To test if a gustatory or olfactory stimulus elicits one of the mental states, test brain activity is processed as described above to identify beta values and t-statistics for ROIs, macro-areas and lobes, e.g., to produce a test mental state brain activity map. The test mental state brain activity map is compared against the mental state- specific brain activity maps to determine a percent similarity. This is done by counting the number of ROIs, macro-areas, or lobes in the test brain activity map that correspond to the ROIs, macro-areas, or lobes (as applicable, e.g., ROI to ROI comparison) of the mental state-specific brain activity map that have a value that meets or exceeds the threshold for activation as determined above. If at least 30%, 40%, 50%, 60%, 70%, 80%, 90%, or more of the brain regions in the test mental state brain activity that correspond to the brain regions of the mental state-specific activity map meet or exceed the activation threshold, either in the t-statistic or beta value, the stimulus may be considered to elicit the mental state.Example 5: Mental States Elicited by Fragrance Ingredients and Compositions
[0224] This Example describes how the methods described herein for predicting mental states evoked by olfactory and gustatory stimuli can be used to identify mental states selectively evoked by such stimuli.
[0225] Methods: fMRI imaging of brain activity evoked in response to an olfactory stimulus, as well as pre- and post-processing of brain imaging data, was accomplished according to the methods described in Example 1. Two fragrance ingredients, Al and Bl, and a fragrance composition containing fragrance ingredient Bl at 0.59% wt% of the fragrance composition, all of which elicited unknown mental states (test stimuli), were prepared at iso-intensity diluted in a nonodorant solvent. Dilutions were done in accordance with regulatory procedures (e.g., IFRA norms) to achieve iso-intensity.
[0226] Analysis: Test mental state brain activity maps were produced as described in Example 4 and compared against the mental state- specific brain activity maps produced for each of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, aIFF101181-WO-PCTmemory, a mindfulness, a relaxed, a reward, a seductive, and a positive self-esteem mental state. The production of the mental state- specific brain activity map and the comparison to determine the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map were conducted as described in Example 4. See also Section II for the mental state- specific brain activity maps. ROIs were used for the analysis, meaning that the ROIs of the test mental state brain activity map and ROIs of the mental state-specific brain activity maps were compared. A percent similarity of at least 40% was required for the stimulus to be considered as eliciting a mental state.
[0227] Results: Analysis of ingredient Al resulted in a percent similarity of 41% (beta value) and 53% (t- statistic) to the Reward mental state- specific brain activity map (reward brain activity map) and only 36% (beta value and t-statistic) to the Learning mental state- specific brain activity map (learning brain activity map). These results suggest that the Al fragrance ingredient enhanced feelings of reward but not feelings of learning. This effect was replicated three times with percent similarities of 41%, 45%, and 46% (beta value) and 53%, 42%, and 51% (t-statistic) for the reward brain activity map and percent similarities of 36%, 36%, and 37% (beta value) and 36%, 23%, and 30% (t-statistic) for the learning brain activity map.
[0228] The analysis of ingredient B 1 resulted in a percent similarity to the Attention mental statespecific brain activity map (attention brain activity map) of 47% (beta value) and 49% (t-statistic). The analysis further showed that B 1 had a percent similarity to the Memory mental state-specific brain activity map (memory brain activity map) of 39% (beta value) and 34% (t-statistic). These results suggest that the B 1 fragrance ingredient enhanced attention but not memory.
[0229] To determine whether a fragrance ingredient identified to elicit a mental state would elicit the same mental state when the ingredient was included in a composition, a fragrance composition including Bl (0.59 wt%) was prepared and analyzed to determine whether the fragrance composition elicited an Attention mental state.
[0230] The fragrance composition including Bl showed a percent similarity of 51% (beta value) and 46% (t-statistic) to the attention brain activity map. In addition, the fragrance composition including B 1 showed a percent similarity of 39% (beta value) and 34% (t-statistic) to the memory brain activity map. Both results were similar to what was observed at the ingredient level for B 1.IFF101181-WO-PCT
[0231] These results demonstrate the discriminability and reliability of the methods for predicting and identifying mental states elicited by fragrance and flavors as described herein. These results further suggest an ability to use ingredients that elicit a mental state in a composition to elicit the mental state of the ingredient.
[0232] The present invention is not intended to be limited in scope to the particular disclosed embodiments, which are provided, for example, to illustrate various aspects of the invention. Various modifications to the compositions and methods described will become apparent from the description and teachings herein. Such variations may be practiced without departing from the true scope and spirit of the disclosure and are intended to fall within the scope of the present disclosure. Although the invention may be described in connection with specific preferred embodiments, it should be understood that the invention as claimed should not be unduly limited to such specific embodiments. Indeed, various modifications of the described modes for carrying out the invention which are obvious to those skilled in the art are intended to be within the scope of the following claims.
Claims
IFF101181-WO-PCTCLAIMSWhat is claimed is:
1. A method for producing a mental state-specific brain activity map, comprising: (a) identifying in one or more subjects a control brain activity, wherein the control brain activity represents brain activity evoked by exposure to a control stimulus, wherein the control stimulus is an olfactory stimulus or a gustatory stimulus that elicits a known mental state in a subject; and(b) determining, based on the control brain activity, one or more brain regions activated by the control stimulus to produce a mental state-specific brain activity map.
2. The method of claim 1, wherein the control stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.
3. The method of claim 1 or claim 2, wherein the control brain activity comprises control brain activity from two or more or a plurality of subjects.
4. The method of any one of claims 1-3, wherein the determining of step (b) comprises inputting the control brain activity into a fingerprinting algorithm.
5. The method of claim 4, wherein the fingerprinting algorithm is a Partial Least Squares (PLS) model, a penalized regression model, a Classification and Regression Tree (CART) model, a Bayesian network model, or any combination thereof.
6. The method of claim 5, wherein the CART model is an Extreme Gradient Boosting (XGBoost) model, a Random Forest model, a Chi-Square Automatic Interaction Detection (CHAID) model, or any combination thereof.
7. The method of claim 5 or claim 6, wherein the penalized regression model is an adaptive Least Absolute Shrinkage and Selection Operator (LASSO) model, an adaptive Ridge regression model, an adaptive Elastic Net model, or any combination thereof.IFF101181-WO-PCT8. The method of any one of claims 5-7, wherein the PLS model is a Partial Least Squares Discriminant Analysis (PLS-DA) and / or a Partial Least Squares Regression (PLS-R) analysis.
9. The method of any one of claims 1-8, wherein the control brain activity is identified using brain imaging, optionally wherein the brain imaging is functional magnetic resonance imaging (fMRI).
10. The method of any one of claims 1-9, wherein the control brain activity comprises a statistical value for each of the one or more brain regions, wherein the statistical value represents a probability that the brain region is activated by exposure to the control stimulus.
11. The method of claim 10, wherein the statistical value for each of the one or more brain regions is a t-statistic and / or a beta value, optionally wherein the t-statistics and / or beta values are normalized, baseline corrected, or scaled.
12. The method of any one of claims 1-11, wherein a brain region is a voxel, a region of interest (RO I), a macro-area, a lobe, or any combination thereof.
13. The method of claim 12, wherein the statistical value for the ROI, the macro-area, or the lobe is, independently, a combination of the t-statistic and / or a combination of the beta values of all voxels contained in the ROI, the macro-area, or the lobe.
14. The method of any one of claims 1-13, further comprising producing a global network when more than one mental state-specific brain activity map is produced, and wherein the global network comprises brain regions found in at least 30%, 40%. 50%, 60%, 70%, 80%. 90%, 95%, 99%, or more of all mental state-specific brain activity maps produced.
15. A method for predicting a mental state elicited by an olfactory stimulus or a gustatory stimulus, comprising:IFF101181-WO-PCT(a) identifying in one or more subjects a test brain activity, wherein the test brain activity represents brain activity evoked by exposure to a test stimulus, wherein the test stimulus is an olfactory stimulus or a gustatory stimulus that elicits an unknown mental state in a subject;(b) determining, based on the test brain activity, one or more brain regions activated by the test stimulus to produce a test mental state brain activity map; and(c) comparing the test mental state brain activity map to one or more mental state-specific brain activity maps produced according to the method of any one of claims 1-14 that represent a known mental state, thereby determining whether the test stimulus elicits the mental state.
16. The method of claim 15, further comprising comparing the test mental state brain activity map to a global network.
17. The method of claim 15 or claim 16, wherein the test stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.
18. The method of any one of claims 15-17, wherein the test brain activity comprises test brain activity from two or more or a plurality of subjects.
19. The method of any one of claims 15-18, wherein the comparing of step (c) comprises a qualitative comparison and / or predictive modeling.
20. The method of claim 19, wherein the qualitative comparison comprises calculating a percent similarity between the test mental state brain activity map and the mental state- specific brain activity map.
21. The method of claim 19 or claim 20, wherein the qualitative comparison comprises calculating a percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network.
22. The method of any one of claims 19-21, wherein the predictive modeling comprises:IFF101181-WO-PCT(a) training a predictive model on the one or more mental state-specific brain activity maps produced according to the method of any one of claims 1-14; and(b) inputting the test mental state brain activity map into the trained predictive model to predict a mental state elicited by the test stimulus.
23. The method of any one of claims 19-22, wherein the predictive modeling comprises:(a) training a predictive model on the one or more mental state-specific brain activity maps and a global network produced according to the method of any one of claims 1-14; and(b) inputting the test mental state brain activity map into the trained predictive model to predict a mental state elicited by the test stimulus.
24. The method of any one of claims 19-23, wherein the predictive modeling comprises a heuristic optimization algorithm, optionally a differential evolution algorithm, a particle swarm optimization algorithm, and / or a genetic algorithm.
25. The method of any one of claims 15-24, wherein the comparing of step (c) further determines a strength by which the test stimulus elicits the mental state.
26. The method of any one of claims 15-25, wherein the test brain activity is identified using brain imaging, optionally wherein the brain imaging is functional magnetic resonance imaging (fMRI).
27. The method of any one of claims 15-26, wherein the test brain activity comprises a statistical value for each of the one or more brain regions, wherein the statistical value represents a probability that the brain region is activated by exposure to the test stimulus.
28. The method of claim 27, wherein the statistical value for each of the one or more brain regions is a t-statistic and / or a beta value, optionally wherein the t-statistic and / or beta values are normalized, baseline corrected, or scaled.IFF101181-WO-PCT29. The method of any one of claims 15-28, wherein a brain region is a voxel, an ROI, a macro-area, a lobe, or any combination thereof.
30. The method of claim 29, wherein the statistical value of the ROI, the macro-area, or the lobe is, independently, a combination of the t-statistic and / or a combination of a beta value of all voxels contained in the ROI, the macro-area, or the lobe.
31. A fragrance or flavor that elicits a mental state in a subject, identified according to the method of any one of claims 15-30.
32. The fragrance or flavor of claim 31, wherein the fragrance or the flavor is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.
33. A method for producing a fragrance composition or a flavor composition that elicits a mental state in a subject, comprising:a) identifying a fragrance or a flavor that elicits a target mental state in a subject according to the method of any one of claims 15-30; andb) incorporating the fragrance or the flavor that elicits the target mental state in a fragrance composition or a flavor composition.
34. The method of claim 33. wherein the fragrance or the flavor is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.
35. A consumer product comprising a fragrance or flavor according to claim 31 or claim 32 or a fragrance composition or flavor composition produced according to the method of claim 33 or claim 34.
36. The consumer product of claim 35, wherein the consumer product is a household product, a fabric care product, an air care product, a personal care product, a cosmetic product, aIFF101181-WO-PCTfine fragrance, a beverage product, a baked good, a confectionery good, a culinary product, a dairy product, a snack product, an oral care product, a health care product, or a nutritional product.
37. A method of eliciting a target mental state in a subject, comprising delivering a fragrance or flavor according to claim 31 or claim 32, a fragrance composition or flavor composition produced according to the method of claim 33 or claim 34, or a consumer product according to claim 35 or claim 36 to a subject.
38. A method for identifying an olfactory stimulus or a gustatory stimulus that elicits a mental state in a subject, comprising:(a) comparing a test mental state brain activity map, determined in response to a test stimulus, with one or more mental state-specific brain activity maps, wherein the one or more mental state- specific brain activity maps include an adventure brain activity map, an attention brain activity map. a craving brain activity map, a drive brain activity map, an energy brain activity map, a focus brain activity map, a happiness brain activity map, a learning brain activity map, a memory brain activity map, a mindfulness brain activity map, a relaxation brain activity map, a reward brain activity map, a seduction brain activity map, or a self-esteem brain activity map; and (b) identifying the test stimulus as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject when the percent similarity between the test mental state brain activity map and the mental state- specific brain activity map is at least 20%, 30%. 40%. 50%, 60%, 70%, 80%. 85%. 90%, 95%, 96%, 97%. 98%. 99%, or more.
39. A method for identifying an olfactory stimulus or gustatory stimulus that elicits a mental state in a subject, comprising:(a) comparing a test mental state brain activity map, determined in response to a test stimulus, with a global network and one or more mental state-specific brain activity maps, wherein the one or more mental state- specific brain activity maps include an adventure brain activity map, an attention brain activity map, a craving brain activity map, a drive brain activity map, an energy brain activity map, a focus brain activity map, a happiness brain activity map, a learning brain activity map, a memory brain activity map, a mindfulness brain activity map, a relaxation brainIFF101181-WO-PCTactivity map, a reward brain activity map, a seduction brain activity map, or a self-esteem brain activity map; and(b) identifying the test stimulus as eliciting one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject when the percent similarity between the test mental state brain activity map and the mental state-specific brain activity map and the global network is at least 20%, 30%, 40%, 50%, 60%, 70%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or more.
40. The method of claim 38 or claim 39, wherein the test mental state brain activity map is determined by a method comprising:a) identifying a baseline brain activity in a subject;b) identifying a test brain activity in the subject in response to the test stimulus; and c) determining the test mental state brain activity map by comparing the baseline brain activity and the test brain activity;wherein the identifying comprises brain imaging.
41. The method of claim 40, wherein the baseline brain activity is activity in response to a resting state and / or a standard stimulus.
42. The method of any one of claims 39-41, wherein the global network comprises brain regions corresponding to:a) ROIs 16, 17, 24, 29, 31, 33, 34, 35, 36, 37, 38, 39, 40, 45, 46, 49, 51, 52, 61, 63, 86, 100, 135, 136, 138, 151, 167, 169, 188, 194, 199, 204, 212, 223, 225, 234, and 243; and / orb) macro-areas 5, 7, 29, 41, and 42.
43. The method of any one of claims 38-42, wherein the adventure brain activity map comprises brain regions corresponding to:a) ROIs 2, 6. 26, 32, 42, 45, 46, 49, 50.
58. 63, 65, 75, 84, 85, 86, 87, 92.
95. 98, 99, 105, 111, 120, 121, 123, 126, 128, 130, 131, 136, 139, 140, 146, 150, 151, 160, 162,IFF101181-WO-PCT163, 171, 177, 178, 186, 187, 188, 194, 197, 202, 213, 218, 231, 232, 234, 238, and 243; and / orb) macro-areas 7, 8.
10.
11. 20, 23, 28, 29, 30, 32, and 45; and / orc) lobes 1, 3, 4, 9, 10, 11, and 12.
44. The method of any one of claims 38-43, wherein the attention brain activity map comprises brain regions corresponding to:a) ROIs 7, 11, 13, 14, 15.
16. 27, 29, 31, 32, 33, 34, 37, 38, 39, 40, 51.
52. 53, 57, 58, 61, 62, 63, 65, 83, 84, 89, 90, 94, 95, 103, 105, 114, 115, 124, 127, 135, 136, 143, 147, 150, 151, 153, 164, 167, 168, 169, 173, 178, 179, 180, 183, 185, 188, 196, 197, 199, 200, 201, 204. 205, 208, 211, 212. 215, 219, 224, 225. and 229; and / orb) macro-areas 6, 17, 21, 29, 33, 34, 35, 36, 39, 41, 42, 45, 46, and 48; and / or c) lobes 7, 9, 10, 11. 12, 13, and 14.
45. The method of any one of claims 38-44, wherein the craving brain activity map comprises brain regions corresponding to:a) ROIs 14, 15, 16, 17, 19, 21, 23, 29, 31, 33, 35, 37, 38, 39, 41, 45, 46, 49, 50, 51, 63, 65, 70, 83, 94, 97, 99, 100, 106, 117, 118, 119, 120, 123, 127, 132, 135, 136, 138, 144, 147, 149. 151, 167, 168, 169, 172, 174, 179, 180, 182, 187, 188, 189, 190, 191, 193, 194, 195, 200, 202, 204, 207, 209, 210, 223, and 234; and / orb) macro-areas 5, 7, 8, 17, 18, 20, 23, 24, 29, 30, 34, 37, 39, and 45; and / or c) lobes 3, 4, 5, 7, 8, 11, and 12.
46. The method of any one of claims 38-45, wherein the drive brain activity map comprises brain regions corresponding to:a) ROIs 6, 13, 14, 19, 20, 24, 27, 28, 29, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 45, 46, 51, 52. 61, 62, 63, 64, 65, 76, 80. 82, 95, 111, 115, 116, 125, 133, 135, 143, 145, 167, 168, 171, 177, 178, 187, 188, 196, 197, 199, 201, 207, 212, 217, 220, and 224; and / orb) macro-areas 4, 5, 6, 7, 11, 14, 16, 24, 33.
35.
36.
37. 39, 41, 42, and 43; and / or c) lobes 7, 8, 10, 11, 12, 13, and 14.IFF101181-WO-PCT47. The method of any one of claims 38-46, wherein the energy brain activity map comprises brain regions corresponding to:a) ROIs 17, 24, 29, 31, 33, 35, 37, 39, 46, 49, 50, 51, 69, 70, 71, 75, 96, 98, 100, 116, 117, 123, 125, 129, 130, 131, 133, 139, 143, 144, 146, 151, 165, 167, 168, 170, 172, 177, 194, 196, 199, 202, 210, 211, 212, 213, 214, 220, 221, 222, 223, 224, 225, 226, 228, 230, 231, 232, 233, 234, 238, 239, 242, and 243; and / orb) macro-areas 5, 7, 11, 23. 25, 28, 41, 42, 45, and 46; and / orc) lobes 5, 7, 10, 11, 12, 13, and 14.
48. The method of any one of claims 38-47, wherein the focus brain activity map comprises brain regions corresponding to:a) ROIs 16, 17, 18, 24, 25, 26, 29, 31, 33, 36, 37, 44, 51, 52, 56, 63, 66, 75. 86, 88, 98, 100, 102, 105.
123. 125, 126, 127, 128.
129. 130, 131, 132, 135.
136. 137, 138, 139, 140, 143, 144, 147, 148, 149, 150, 167, 168, 169, 170, 171, 173, 175, 176, 180, 183, 189, 192, 194, 195, 199, 201, 202, 204, 205, 207, 208, 209, 215, 221, 234, 241, 242. and 243; and / orb) macro-areas 5, 7, 12, 22, 28, 29, 30, 32, 33, 35, 38, 39, and 41; and / or c) lobes 5, 6. 7, 9, 10, 11, and 12.
49. The method of any one of claims 38-48, wherein the happiness brain activity map comprises brain regions corresponding to:a) ROIs 13, 15, 16, 17, 18, 20, 22, 23, 24, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 44, 46, 49, 51, 52, 54, 61, 63, 74, 82. 86, 105, 113, 116, 118, 132, 133, 135, 136, 138, 139, 142, 144, 147, 151, 155, 163, 164, 165, 167, 168, 169, 172, 173, 174, 179, 186, 187, 188, 194, 199, 200, 206, 208, 211, 216, 219, 223, 225, 228, 229, and 234; and / or b) macro-areas 3, 4, 6, 8, 11, 12, 14, 16, 29, 34, 41, 42. 44, 45, and 46; and / or c) lobes 2, 3, 4, 5, 7, 8, and 12.
50. The method of any one of claims 38-49, wherein the learning brain activity map comprises brain regions corresponding to:IFF101181-WO-PCTa) ROIs 9, 17, 22, 24, 31, 33, 34, 35, 36, 37, 38, 39, 40, 44, 47, 51, 52, 54, 60, 61, 62, 63, 64, 72, 73, 77, 81, 84, 87, 89, 95, 98, 100, 111, 112, 119, 120, 137, 138, 141, 146, 155, 156. 157, 158, 160, 163.
164. 167, 169, 171, 172. 173, 174, 175, 176. 190, 191, 193, 194, 195, 200, 204, 206, 207, 208, 214, 216, 218, 229, 232, 233, and 245; and / orb) macro-areas 5, 7, 9, 13, 15, 31, 32, 33, 34, 38, 40, 41, 42, and 44; and / or c) lobes 1, 2, 7, 8, 10, 11, and 12.
51. The method of any one of claims 38-50, wherein the memory brain activity map comprises brain regions corresponding to:a) ROIs 9, 13, 17, 31, 33, 35, 36, 37, 39, 43, 45, 46, 49, 51, 61, 62, 63, 64, 70, 86, 99, 100, 111, 114. 122, 124, 129, 130, 131. 136, 139, 140, 145, 146. 154, 155, 157, 159, 160, 162, 163, 170, 174, 190, 204, 209, 211, 212, 219, 223, 225, 231, 234, 235, 237, 239, 242, 243, and 245; and / orb) macro-areas 9, 10, 11, 17, 20, 26.
28.
31. 32, 38. 44, and 47; and / or c) lobes 4, 5, 6, 7, 10, 11, 12.
52. The method of any one of claims 38-51, wherein mindfulness brain activity map comprises brain regions corresponding to:a) ROIs 1, 4, 17, 20, 22, 24, 28, 31, 33.
35. 36, 37, 39, 43, 45, 49, 50, 51.
69. 70, 75, 77, 86, 88, 94, 96, 99, 106, 109, 110, 117, 121, 123, 128, 129, 130, 136, 137, 139, 140, 142, 148, 149, 150, 154, 157, 167, 169, 177, 186, 194, 200, 209, 211, 212, 213, 214, 215, 216, 223. 225, 226, 230, 236. and 245; and / orb) macro-areas 7, 23, 26, 27, 28, 29, 30, 33, 41, 42, 43, and 47; and / or c) lobes 1, 2, 5, 6, 7, 11, and 12.
53. The method of any one of claims 38-52, wherein the relaxation brain activity map comprises brain regions corresponding to:a) ROIs 1, 4, 5, 7, 8, 16, 18, 20, 29, 31, 34, 37, 38, 39, 40, 41, 45, 51, 52, 56, 57, 59, 61, 63, 64, 65, 67, 73, 74, 82, 86, 88, 96, 101, 106, 114, 118, 122, 138, 144, 145, 146, 148, 161. 167, 169, 171, 173. 180, 183, 185, 187. 188, 192, 194, 195, 196. 198, 199, 203, 204, 206, 209, 214, 223, 225, and 244; and / orIFF101181-WO-PCTb) macro-areas 1, 5, 7, 11, 16, 18, 20, 24, 25, 29, 30, 33, 42, and 45; and / or c) lobes 4, 7, 9, 11, 12, 13, and 14.
54. The method of any one of claims 38-53, wherein the reward brain activity map comprises brain regions corresponding to:a) ROls 3, 5, 13, 15, 16, 17, 24, 29, 31, 34, 35, 36, 38, 39, 40, 41, 44, 45, 47, 48, 50, 51, 52, 63, 64, 70, 77, 81, 83, 89, 98, 99, 100, 121, 127, 128, 138, 140, 145, 146, 147, 148, 149. 151, 160, 165, 176. 177, 178, 182, 189, 190, 191, 192, 193. 194, 199, 204, 205, 206, 207, 209, 212, 223, 231, 232, 233, 237, 238, 240, 242, 243, 244, and 246; and / or b) macro-areas 3, 5, 6, 7, 8, 10, 15, 19, 22, 23, 29, 37, 38, 39, and 40; and / or c) lobes 1, 3. 5, 7, 9. 11, and 12.
55. The method of any one of claims 38-54, wherein the seduction brain activity map comprises brain regions corresponding to:a) ROIs 4, 5, 14, 24, 27, 30, 33, 34, 37, 40, 41, 42, 46, 48, 50, 51, 61, 63, 64, 76, 81, 82, 85, 86, 88, 91, 93, 98, 100, 102, 103, 105. 115, 121, 135, 138, 140, 148, 151, 153, 154, 167, 169, 170, 171, 173, 176, 179, 180, 181, 182, 184, 187, 188, 189, 190, 191, 193, 194, 197, 199, 200, 203, 204, 207, 208, 212, 219, 223, 225, 231, 232, 237, 238, 239, 240, 242, 243. and 244; and / orb) macro-areas 8, 15, 17, 18, 19, 21, 23, 37, 38, 39, 40, and 48; and / or c) lobes 1, 2, 4, 7, 11, 12, and 14.
56. The method of any one of claims 38-55, wherein the self-esteem brain activity map comprises brain regions corresponding to:a) ROIs 13, 14, 16, 20, 21, 22, 23, 28, 33, 34, 36, 40, 44, 49, 51, 53, 61, 62, 63, 81, 83, 86, 95, 105, 135, 137, 138, 141, 145, 178, 181, 182, 189, 190, 193, 194, 196, 197, 199, 204, 205, 206, 210, 212, 213. 214, 215, 216, 217. 218, 221, 230, 231. 232, 234, 237, 238, 239, 242, 243, 244, and 246; and / orb) macro-areas 3, 6, 8, 18, 19, 22, 31, 37, 38, 43, 44, 46, 47, and 48; and / or c) lobes 2, 9.
10.
11. 12, 13, and 14.IFF101181-WO-PCT57. The method of any one of claims 38-56, wherein the test stimulus is identified as eliciting 0, 1, 2, 3, 4, or more mental states.
58. The methods of any one of claims 38-57, further comprising determining a strength by which the test stimulus elicits one or more of an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state.
59. The method of any one of claims 38-58, wherein the test stimulus is a fragrance ingredient, a fragrance accord, a full fragrance, a flavor ingredient, a flavor accord, or a full flavor.
60. The method of any one of claims 41-59, wherein the standard stimulus is a standard olfactory stimulus or a standard gustatory stimulus.
61. The method of any one of claims 40-60, wherein the brain imaging method is functional magnetic resonance imaging (fMRI).
62. An olfactory stimulus or a gustatory stimulus that elicits an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject, determined according to the method of any one of claims 38-61, wherein the olfactory stimulus is a fragrance ingredient, a fragrance accord, a full fragrance and the gustatory stimulus is a flavor ingredient, a flavor accord, or a full flavor.
63. A method for producing a fragrance composition or flavor composition that elicits a mental state in a subject, comprising:a) identifying an olfactory stimulus or a gustatory stimulus that elicits one or more mental states selected from an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, and a positive self-esteem mental state in a subject according to the methods of any one of claims 38-61; and b) incorporating the olfactory stimulus or the gustatory stimulus that elicits the mental stateIFF101181-WO-PCTinto a fragrance composition or a flavor composition.
64. The method of claim 63, wherein the fragrance composition or flavor composition is a new fragrance or a new flavor composition, and the new fragrance composition or the new flavor composition is being prepared to elicit the one or more mental states in a subject.
65. The method of claim 63, wherein the fragrance composition or the flavor composition is an existing fragrance composition or an existing flavor composition, and the existing fragrance composition or the existing flavor composition is being modified to elicit the one or more mental states in a subject.
66. The method of any one of claims 63-65, wherein the olfactory stimulus is a fragrance ingredient and / or a fragrance accord, and the fragrance ingredient and / or the fragrance accord is incorporated into a fragrance composition.
67. The method of any one of claims 63-66, wherein the fragrance composition is an accord or a full fragrance.
68. The method of any one of claims 63-65. wherein the gustatory stimulus is a flavor ingredient and / or a flavor accord, and the flavor ingredient and / or the flavor accord is incorporated into a flavor composition.
69. The method of any one of claims 63-65 or 68, wherein the flavor composition is a flavor accord or a full flavor.
70. A consumer product comprising an olfactory stimulus or a gustatory stimulus that elicits an adventurous, an attentive, a craving, a driven, an energetic, a focused, a happy, a learning, a memory, a mindfulness, a relaxed, a reward, a seductive, or a positive self-esteem mental state in a subject according to claim 62, or a fragrance composition or a flavor composition produced according to the methods of any one of claims 63-69.IFF101181-WO-PCT71. The consumer product of claim 70, wherein the consumer product is a household product, a fabric care product, an air care product, a personal care product, a cosmetic product, a fine fragrance, a beverage product, a food product, an oral care product, a health care product, or a nutritional product.
72. Use of an olfactory stimulus or a gustatory stimulus that elicits a mental state in a subject according to claim 62, a fragrance composition or a flavor composition produced according to the method of any one of claims 63-69. or a consumer product according to claim 70 or claim 71 to elicit a mental state in a subject, wherein the mental state is one or more of adventurous, attentive, craving, driven, energetic, focused, happy, learning, memory, mindfulness, relaxed, reward, seductive, or positive self-esteem.
73. A method of eliciting a mental state in a subject, comprising delivering an olfactory stimulus or a gustatory stimulus that elicits a mental state in a subject according to claim 62, a fragrance composition or a flavor composition produced according to the method of any one of claims 63-69, or a consumer product according to claim 70 or claim 71 to a subject, wherein the mental state is one or more of adventurous, attentive, craving, driven, energetic, focused, happy, learning, memory, mindfulness, relaxed, reward, seductive, or positive self-esteem.