Cosmetics eliciting mental responses related to the sensation of well-being
By employing fMRI to measure cosmetic-evoked brain activity, the method addresses the lack of understanding in topical cosmetics' mental response elicitation, enabling the development of products that induce well-being-related responses through precise brain network activation.
Patent Information
- Application Number
- PCT/US2025/011902
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2024-01-19
- Filing Date
- 2025-01-16
- Publication Date
- 2025-07-24
AI Technical Summary
The ability of topical cosmetics to elicit well-being-related mental responses is not well-characterized, and existing methods rely on declarative data susceptible to external and internal biases, lacking direct measurement of brain activity associated with emotional and sensory processing.
A method using functional magnetic resonance imaging (fMRI) to directly measure cosmetic-evoked brain activity, identifying activation of interoceptive, emotion and memory, reward, and cognitive processing brain networks in response to topical cosmetic textures, allowing for the development of cosmetics that induce well-being-related mental responses.
Enables precise identification and formulation of cosmetics that activate specific brain networks associated with well-being, improving product development and consumer experience by directly measuring brain activity without declarative data biases.
Smart Images

Figure US2025011902_24072025_PF_FP_ABST
Abstract
Description
COSMETICS ELICITING MENTAL RESPONSES RELATED TO THE SENSATION OF WELL-BEINGCROSS-REFERENCE TO RELATED APPLICATION
[0001] This application claims priority from U.S. provisional application No. 63 / 622,780, filed January 19, 2024, the contents of which are hereby incorporated by reference in their entirety.FIELD OF THE INVENTION
[0002] Provided herein are methods for identifying topical cosmetics that elicit well-being- related mental responses, e.g., brain activity. Also provided are topical cosmetics, including ingredients, compositions, and consumer products, that elicit a well-being-related mental response in a subject.BACKGROUND OF THE INVENTION
[0003] In the field of cosmetics, tactile experience of cosmetic texture is known to play a pivotal role in consumer satisfaction and product success. Interestingly, in addition to its role in detecting and discriminating tactile stimuli, the sensation of touch can give rise to emotional experiences. Thus, the tactile experience of topical cosmetics may involve a combination of sensory and emotional mental processing. The ability of different topical cosmetic textures to elicit specific mental responses, however, is not well-characterized.
[0004] Well-being has emerged as a desirable state for individuals. The state of well-being has been described multidimensionally, encompassing mental aspects that result in a sense of positivity and contentment. As such, multiple factors likely drive a sense of well-being in a subject, including various emotional responses. The ability of different textures, such as those of topical cosmetics, to elicit mental responses that contribute to a sense of well-being is not well-understood.
[0005] Thus, there exists a need for identifying topical cosmetics capable of eliciting well-being- related mental responses. The methods and compositions provided herein address these and other needs in the art.SUMMARY OF THE INVENTION
[0006] In an aspect is provided a method for identifying a topical cosmetic that elicits a wellbeing-related mental response in a subject, including determining from a cosmetic -evoked brainactivity representing a response to touching a target tissue including a test topical cosmetic, whether at least one of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain network is activated. In some embodiments, the cosmetic-evoked brain activity is determined by a method including: a. identifying a control brain activity in a subject under a control condition; b. identifying a test brain activity in the subject in response to touching the target tissue including the test topical cosmetic; and c. determining the cosmetic-evoked brain activity by comparing the control brain activity and the test brain activity; where the identifying includes functional magnetic resonance imaging. In some embodiments, the control condition is one or more of a resting state, touching the target tissue not including a topical cosmetic, or touching the target tissue including a control topical cosmetic. In some embodiments, at least 2, 3, or more of the interoceptive brain network, the emotion and memory brain network, the reward brain network, or the cognitive processing brain network are activated. In some embodiments, the determining whether the interoceptive brain network is activated includes determining whether one or more of, independently, an insula, a secondary somatosensory cortex, a primary somatosensory cortex, an orbitofrontal cortex, an anterior cingulate cortex, a hippocampus, or an amygdala is activated. In some embodiments, the determining whether the emotion and memory brain network is activated includes determining whether one or more of, independently, a hippocampus, an amygdala, a temporal pole, a nucleus accumbens, a zona incerta, an orbitofrontal cortex, a cerebellum, an anterior cingulate cortex, or an insula is activated. In some embodiments, the determining whether the reward brain network is activated includes determining whether one or more of, independently, a putamcn, a nucleus accumbens, a cerebellum, an anterior cingulate cortex, a hippocampus, an amygdala, an insula, or an orbitofrontal cortex is activated. In some embodiments, the determining whether the cognitive processing brain network is activated includes determining whether one or more of, independently, an inferior frontal gyrus, an anterior cingulate cortex, or a dorsolateral prefrontal cortex is activated. In some embodiments, the insula is an anterior insula, a posterior insula, a right dorsal posterior insula, or any combination thereof. In some embodiments, the cosmetic-evoked brain activity and the target tissue are from the same subject. In some embodiments, the cosmetic-evoked brain activity and the target tissue are from different subjects. In some embodiments, the test topical cosmetic is a cosmetic ingredient, a cosmetic composition, or a consumer product. In some embodiments, the control topical cosmetic is a cosmetic ingredient, a cosmetic composition, or aconsumer product. In some embodiments, the target tissue is tissue of hands, arms, face, lips, legs, torso, or scalp.
[0007] In an aspect is provides a topical cosmetic that elicits a well-being-related mental response in a subject determined according to a method described herein, wherein the topical cosmetic is a cosmetic ingredient, a cosmetic composition, or a consumer product.
[0008] In an aspect is a method for producing a topical cosmetic that elicits a well-being-related mental response in a subject, including: (i) identifying, according to a method described herein, a cosmetic ingredient or cosmetic composition that elicits a well-being-related mental response; and (ii) formulating the cosmetic ingredient or cosmetic composition that elicits the well-being-related mental response into a topical cosmetic composition or consumer product.
[0009] In an aspect is provided a consumer product including a topical cosmetic that elicits a well-being-related mental response determined according to a method described herein, where the consumer product is a personal care product or a cosmetic product.
[0010] In an aspect is provided use of a topical cosmetic described herein or a consumer product described herein to elicit a well-being-related mental response in a subject upon application to a target tissue.
[0011] 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.BRIEF DESCRIPTION OF THE DRAWINGS
[0012] FIGS. 1A and IB show the overall experimental block design and a detailed description of an exemplary single block, respectively. In FIG. IB, “Apply” refers to time that the cream is applied to the subject (13 seconds in duration), “Area” followed by a number refers to the time when the subject massages the specific predefined tissue area (12 seconds in duration), and “Rest” refers to a period of no stimulation (12 seconds in duration). “Min” refers to minutes.DETAILED DESCRIPTION OF THE INVENTION
[0013] In the cosmetics industry, understanding the emotional experience of consumers during product usage is paramount. This knowledge not only aids in product development and improvement, but also fosters the brand-consumer connection. The tactile experience of cosmetic textures is known to contribute significantly to product acceptance and market success. While thesense of touch is traditionally appreciated for its role in detecting and discriminating stimuli, tactile experiences also give rise to emotional responses. Thus, the use of topical cosmetics may elicit a combination of sensory and emotional mental processing in response to cosmetic texture. Understanding the mental responses elicited by different textures is crucial for formulating products that deliver desirable consumer experiences.
[0014] Well-being is a complex, multifaceted state that is highly desirable for individuals. Definitions of well-being typically include the sensation of happiness, prosperity, health, contentment, the ability to cope with the normal stresses of daily life, high satisfaction with life, a sense of meaning and purpose, and the ability to contribute to community. World Health Organization, 2001; Huppert, 2009; Gabriel et al., 2021. Studies designed to elucidate the neural basis of well-being have identified a variety of cortical and subcortical brain regions that participate in shared and overlapping brain networks, including networks involved in emotion and memory processing, reward processing, higher-order cognitive processing, and interoceptive processing. Dolcos, 2018. Thus, from a neuroscientific perspective, a sensation of well-being likely includes various brain regions and brain networks that drive positive and reduce negative emotions. Activation of brain regions and networks believed to elicit sensations of well-being in a subject are referred to herein interchangeably as well-being-related responses and well-being- related mental responses. Although factors such as environment and genetics can impact an individual’s sense of well-being, activities such as mindfulness training and physical exercise have also been shown to enhance well-being. Dolcos, 2018.
[0015] Evidence suggests that cosmetic usage may also deliver an increased sense of well-being and self-esteem. For example, women have reported an increase in positive emotions and a decrease in negative emotions following professional hairdressing. Picot- Lemas son et al., 2001. However, most studies investigating cosmetic effects on emotional response have used declarative measures, collecting verbal and written opinions to indirectly understand the mental effects of the cosmetic. Unfortunately, declarative data, including self-reporting, 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. Gabriel et al., (2021) attempted to provide a more direct analysis of the emotional impact of cosmetic application by recording brain activity using electroencephalography (EEG). Although EEG has high temporal resolution, it suffers from limited spatial resolution, providing signals that reflect broad superficial regions of the brain. Asdescribed above, brain networks involved in well-being include superficial (e.g., cortical) and deep (e.g., subcortical) brain regions and networks. Therefore, the impact of cosmetics on brain structures believed to participate in the sensation of well-being is unknown, let alone an understanding of the ability of cosmetic textures to elicit well-being-related mental responses. Thus, there is a need for methods identifying topical cosmetics capable of eliciting well-being related responses, and topical cosmetics designed according to the results of such methods.
[0016] The methods provided herein include imaging brain activity in superficial and deep brain regions elicited in response to the tactile experience of a topical cosmetic on a target tissue (a cosmetic-evoked brain activity). This enables an assessment of the brain regions and brain networks that are activated in response to the texture of a topical cosmetic when present on a target tissue, thus allowing a determination of whether the topical cosmetic elicits a well-being-related mental response. In some embodiments, the brain activity evoked may be in response to one or more changes to the target tissue including, but not limited to, mechanical, chemical, and / or topographical changes, the presence of a film, or evaporation resulting from the application and optionally the penetration of the topical cosmetic on the target tissue. Thus, in some embodiments, the brain activity evoked may be in response to one or more changes in the target tissue resulting from the interaction of the topical cosmetic with the target tissue.
[0017] The methods described herein are advantageous because they directly measure the mental response to the texture of the topical cosmetic, e.g., during usage. Further, the methods do not require declarative data from the test subject undergoing brain imaging, which circumvents potential difficulties associated with declarative analyses as described above. However, the use of declarative measures in the methods provided herein is not excluded.
[0018] The methods described herein elucidate topical cosmetics, e.g., cosmetic ingredients, cosmetic compositions, and consumer products, that induce a well-being-related mental response. These findings can be used to produce cosmetic ingredients, cosmetic compositions, and consumer products that induce a well-being-related mental response. The methods provided herein enable the production of topical cosmetics, e.g., cosmetic ingredients, cosmetic compositions, and consumer products, that can induce activity in brain networks and brain regions associated with well-being with a precision previously unrealized. Thus, in an aspect is provided methods for identifying a topical cosmetic that elicits a well-being-related mental response in a subject,including determining from a cosmetic -evoked brain activity representing a response to touching a target tissue including a test topical cosmetic, whether at least one of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain network is activated. In some embodiments, the well-being-related mental response is evidenced by the activation of brain regions associated with the sensation of well-being. In some embodiments, the brain region is one or more of an insula, a secondary somatosensory cortex, a primary somatosensory cortex, a hippocampus, an amygdala, a temporal pole, a nucleus accumbens, a zona incerta, a putamen, an inferior frontal gyrus, an anterior cingulate cortex, a dorsolateral prefrontal cortex, or an orbitofrontal cortex. In some embodiments, the brain regions participate in one or more brain networks related to a sensation of well-being. In some embodiments, the well-being-related mental response is determined by the activation of brain networks associated with the sensation of well-being. In some embodiments, the brain networks related to a sensation of well-being include at least one of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain network.
[0019] The results generated according to the methods, e.g., brain regions, brain networks activated by the topical cosmetic (test topical cosmetic), may be collected in a database. In some embodiments, the database is searchable, e.g., by querying. In some embodiments, the database may include a user interface to facilitate searching (querying) and data extraction. In some embodiments, the database may be queried to identify topical cosmetics useful for formulating a cosmetic composition, e.g., an existing or new composition, that induces a well-being-related mental response in a subject.
[0020] Also provided herein are topical cosmetics, such as cosmetic ingredients, cosmetic compositions, and consumer products (e.g., cosmetic consumer produces), that elicit a well-being- related mental response in a subject.
[0021] The methods and compositions described herein are advantageous in that they can be used to determine useful and reliable information from brain imaging data, which can improve the production speed, efficiency, and reliability of topical cosmetics produced for purposes of inducing a well-being-related mental response.
[0022] 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.
[0023] 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.
[0024] 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.Definitions
[0025] 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.
[0026] 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.
[0027] 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.”
[0028] The terms “comprise,” “comprising,” “comprises,” “comprised of’ and grammatical variants thereof as used herein are synonymous with “include,” “including,” “includes,” “contain,” “containing,” “contains,” and grammatical variants thereof, and are inclusive or open-ended anddo not exclude additional, non-recited members, elements or method steps. The terms “comprise,” “comprising,” “comprises,” “comprised of,” “include,” “including,” “includes,” “contain,” “containing,” “contains,” and grammatical variants thereof also include the term "consisting of.”
[0029] “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.
[0030] As used herein, the term “subject” may refer to the user (e.g., person) who has a tactile experience of the topical cosmetic present on a target tissue. The term “subject” refers to a human. In some embodiments, the subject is a human. In some cases, the subject has the tactile experience while touching tissue of her own body that includes the topical cosmetic. In some cases, the subject has the tactile experience while touching tissue on a different person, where that other person’s tissue includes the topical cosmetic.
[0031] Induce, evoke, elicit, drive, and grammatical variants thereof may be alternatively used to indicate a cause-and-effect relationship. For example, a topical cosmetic may elicit, induce, evoke, or drive brain activity underlying a well-being-related mental response in a subject upon tactile experience of the topical cosmetic, e.g., on a target tissue.
[0032] The term “increased” as used herein can 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.
[0033] The term “decreased” as used herein can 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.
[0034] " Brain activity" refers to the physiological and biochemical activity within the human brain, or a region of the brain, associated with mental activity. Such activity may be evidence by, but not limited to, increases in blood flow to active brain regions, changes in oxygen level in theblood, increases in metabolic activity (e.g., glucose consumption), changes in electrical potential of neurons, and the release of neurotransmitters. Brain activity can be measured non-invasively by, for example, measuring changes in electrical fields, 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.
[0035] 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.
[0036] As used herein, the terms “frontal,” “anterior,” “posterior,” “superior,” and “inferior” have their customary meanings in anatomy. See, for example, Stedman's Medical Dictionary. Specific locations within the brain, or volumes within the brain, can also be described by reference to three-dimensional coordinate systems. One such system is that described by Talairach and Tournox (Stereotaxic Coplanar Atlas of the Human Brain, published by Thieme in 1988, ISBN 9783137117018) and is based upon a single brain considered by the authors to be typical. The brain images or maps of individual subjects can be compared to such template brains by visual comparison, or computer software programs can be used which map the individual brains onto a template brain. For example, the Statistical Parametric Mapping (SPM) software, described below, automatically performs spatial registration and normalization of individual brains onto the MNI (Montreal Neurological Institute) template. Software is also available which determines the correspondence amongst MNI coordinates and Talairach coordinates (e.g., MRIcro, available at da.se.edu / psyc / faculty / rorden / mricro.html; see also Rorden and Brett (2000), Behavioural Neurology, 12:191-200).
[0037] 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 fMRI instrument.
[0038] 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 upperand 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.
[0039] 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 IDENTIFYING TOPICAL COSMETICS THAT ELICIT WELL- BEING-RELATED MENTAL RESPONSES
[0040] The methods provided herein are useful for identifying topical cosmetics that elicit a wellbeing-related mental response in a subject upon tactile experience of the topical cosmetic present on a tissue. Therefore, in an aspect is provided a method for identifying a topical cosmetic that elicits a well-being-related mental response in a subject, including determining from a cosmetic- evoked brain activity representing a response to touching a target tissue including a test topical cosmetic, whether at least one of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain network is activated. In another aspect is provided a method for identifying a topical cosmetic that elicits a well-being-related mental response in a subject, including determining from a cosmetic-evoked brain activity representing a response to touching a target tissue including a test topical cosmetic, whether one or more of an insula, a secondary somatosensory cortex, a primary somatosensory cortex, ahippocampus, an amygdala, a temporal pole, a nucleus accumbens, a zona incerta, a putamen, an inferior frontal gyrus, an anterior cingulate cortex, a dorsolateral prefrontal cortex, orbitofrontal cortex, or a cerebellum is activated.A. Cosmetic-Evoked Brain Activity
[0041] Cosmetic-evoked brain activity as described herein represents a response to touching a target tissue including a test topical cosmetic. In some embodiments, the test topical cosmetic is the topical cosmetic for which it is to be determined if it elicits a well-being-related mental response in a subject. In some embodiments, the cosmetic-evoked brain activity is the brain activity used to determine whether brain networks or brain regions associated with a sensation of well-being are activated in a subject. See, e.g., Section LB. To identify the brain activity evoked by the test topical cosmetic, brain activity unrelated to the tactile experience of the test topical cosmetic may be identified and accounted for. Thus, in some embodiments, a method of determining a cosmetic-evoked brain activity in a subject is provided.
[0042] In some embodiments, the method for determining a cosmetic -evoked brain activity in the subject includes identifying a control brain activity in the subject. In some embodiments, the control brain activity is brain activity recorded during a subject’s state of rest. Resting state brain activity may be used to identify the natural ongoing brain activity that exists in a subject. In some embodiments, the resting state is a control condition, and the resting state brain activity is a control brain activity.
[0043] In some embodiments, the control brain activity is brain activity identified in response to touching a target tissue under a control condition. In some embodiments, the control condition is an absence of any topical cosmetic on the target tissue. For example, the control condition may include touching target tissue that is clean. Clean tissue may, for example, be free from any cosmetics, soaps, or other topical applications that might change the tactile experience of the tissue.
[0044] In some embodiments, the control condition is the presence of a control topical cosmetic. For example, the control condition may include touching target tissue on which has been applied a control topical cosmetic that elicits a known mental response, e.g., a well-being-related mental response. In some embodiments, the control topical cosmetic is a topical cosmetic that is different from a topical cosmetic to be tested (e.g., test topical cosmetic). In some embodiments, the control brain activity in response to the control topical cosmetic is unknown. In some embodiments, thecontrol topical cosmetic may be a commercially available topical cosmetic. In some embodiments, the control topical cosmetic is used as a baseline to compare against the test topical cosmetic. For example, the control topical cosmetic may be used as a baseline to determine whether a test topical cosmetic elicits an increased or decreased well-being-related mental response compared to a wellbeing-related mental response elicited by the control topical cosmetic.
[0045] In some embodiments, the method includes one or more control conditions. In some embodiments, the control brain activity may be identified during a subject’s period of rest. No touching of target tissue occurs during the rest period. In some embodiments, the control brain activity may be identified under a control condition where the target tissue does not include a topical cosmetic, e.g., the target tissue is clean, when touched. In some embodiments, the control brain activity may be identified under a control condition where a control topical cosmetic is present on the target tissue when touched. In some embodiments, the control brain activity may be identified under a control condition where the target tissue does not include a topical cosmetic when touched, e.g., the target tissue is clean, and identified under conditions where a control topical cosmetic is present on the target tissue when touched. In some embodiments, the control brain activity may be identified under a control condition where the target tissue does not include a topical cosmetic when touched, e.g., the target tissue is clean, identified under conditions where a control topical cosmetic is present on the target tissue when touched, and identified during a subject’s resting state (no touching of target tissue). In some cases, if necessary for clarity, when a control brain activity is identified under control conditions including a control topical cosmetic, the control brain activity may be referred to as control topical brain activity. In some embodiments, the control brain activity is the resulting activity after comparison of a control condition brain activity (e.g., in response to touching clean target tissue or target tissue including a control topical cosmetic) with a resting state brain activity.
[0046] To determine the cosmetic-evoked brain activity, brain activity in response to the topical cosmetic to be tested is also identified (e.g., test topical cosmetic). In some embodiments, a test brain activity in the subject in response to touching the target tissue including the test topical cosmetic is identified. As stated above, the test topical cosmetic is the topical cosmetic for which it is to be determined if it elicits a well-being -related emotional response in a subject. In some embodiments, the test brain activity is the resulting activity after comparison of the test brain activity with resting state brain activity.
[0047] In some embodiments, the resting state brain activity is compared with the control brain activity (e.g., control brain activity, control topical brain activity) and / or the test brain activity. In some embodiments, such a comparison accounts for (e.g., removes) the natural ongoing activity of the subject’s brain in the identified control and / or test brain activity. In some embodiments, the control brain activity, the control topical brain activity, and the test brain activity referred to herein are the brain activity for each condition after comparing with the resting state brain activity.
[0048] In some embodiments, the method includes determining the cosmetic-evoked brain activity by comparing the control brain activity and the test brain activity. For example, the control brain activity and test brain activity may be contrasted. In some cases, the control brain activity may be subtracted from the test brain activity. In some embodiments, a statistical method may be used to compare the control brain activity and test brain activity to determine which brain activity is specific to the test topical cosmetic. Any method of comparison is contemplated as suitable for the methods described herein so long as the method of comparison determines brain activity that is specifically elicited by the test topical cosmetic (cosmetic-evoked brain activity). Thus, the cosmetic-evoked brain activity represents brain activity elicited in response to touching target tissue including the test topical cosmetic. In some embodiments, the control brain activity and the test brain activity may be the brain activity resulting after comparing, e.g., contrasting, with a resting state brain activity.
[0049] In some embodiments, the test brain activity is compared to control brain activity under control conditions in the absence of a topical cosmetic to determine the cosmetic-evoked brain activity. In some embodiments, the test brain activity is compared to control brain activity under control conditions in the presence of a control topical cosmetic to determine the cosmetic-evoked brain activity. In some embodiments, the test brain activity and the control brain activity are the brain activity resulting after contrasting with a resting state brain activity.
[0050] In some embodiments, the control brain activity identified under control conditions in the absence of a topical cosmetic is compared to control brain activity identified under control conditions in the presence of a control topical cosmetic to determine a control cosmetic-evoked brain activity. A control cosmetic-evoked brain activity is similar to a cosmetic-evoked brain activity in that the control cosmetic-evoked brain activity is specifically elicited by the tactile experience of the target tissue including the control topical cosmetic. For example, as withcomparing control brain activity under control conditions in the absence of a topical cosmetic with test brain activity, the basic touch sensation may be accounted for (e.g., removed) in the control cosmetic-evoked brain activity. In some embodiments, the control cosmetic-evoked brain activity is compared with the test brain activity that has been compared to the control brain activity under control conditions in the absence of a topical cosmetic to determine the cosmetic-evoked brain activity. This may be referred to as a complex comparison. Complex comparisons include comparing comparisons, such as contrasting contrasts. For example, a complex comparison may include comparing (e.g., contrasting) a comparison (e.g., contrast) between a control brain activity (in the absence of a topical cosmetic) and a control topical brain activity with a comparison (e.g., contrast) between the control brain activity (in the absence of a topical cosmetic) and the test brain activity. Another example would be comparing (e.g., contrasting) a comparison (e.g., contrast) between a resting state brain activity and a control brain activity with a comparison (e.g., contrast) between the resting state brain activity and the test brain activity.
[0051] In some embodiments, the type of comparison may remove different types of brain activity unrelated to the brain activity response specifically evoked by the test topical cosmetic. In some embodiments, the comparisons may be used to determine the cosmetic-evoked brain activity and whether and the extent to which the cosmetic-evoked brain activity activates brain regions and / or networks related to a sense of well-being. For example, comparing the control cosmetic- evoked brain activity to the comparison of the control brain activity (in the absence of a topical cosmetic) and the test brain activity may indicate whether the test topical cosmetic provides an increased or decreased well-being-related mental response. See, e.g., Section I-B.
[0052] It is contemplated that any brain activity described herein, e.g., test brain activity, control brain activity, topical control brain activity, resting brain activity, etc., may be identified using any brain imaging method (see, e.g., Section 1-C). In some embodiments, the brain imaging method includes the ability to image both superficial and deep brain regions. In some embodiments, identifying includes analyzing the brain imaging data.B. Well-Being-Related Mental Responses
[0053] The methods provided herein allow for determining whether a topical cosmetic (e.g., test topical cosmetic) elicits a well-being-related mental response from cosmetic-evoked brain activity. As described supra, studies have suggested various brain regions and brain networks involved inthe sensation of well-being. Therefore, the methods provided herein determine whether one or more of the brain regions or brain networks are activated by the topical cosmetic (e.g., test topical cosmetic).
[0054] In some embodiments, a well-being-related mental response includes the activation of at least one of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain.
[0055] Interoception refers to the internal sensing of the body. The interoceptive brain network includes both the autonomic and central nervous system, and a dynamic interaction between the two to detect and regulate the body. The interoceptive pathway at the level of the central nervous system includes the hippocampus, amygdala, insula, primary and secondary somatosensory cortices, anterior cingulate cortex, orbitofrontal cortex, medial prefrontal cortex, parabrachial nucleus, thalamus, hypothalamus, nucleus tractus solitarius, periaqueductal grey, locus coeruleus, and ventromedial medulla. Bernston and Khalsa, 2021. In some embodiments, the well-being- related mental response includes the activation of the interoceptive brain network. In some embodiments, activation of the interoceptive brain network includes activation of one or more of a hippocampus, an amygdala, an insula, a primary somatosensory cortex, a secondary somatosensory cortex, an anterior cingulate cortex, an orbitofrontal cortex, a medial prefrontal cortex, a parabrachial nucleus, a thalamus, a hypothalamus, a nucleus tractus solitarius, a periaqueductal gray, a locus coeruleus, or a ventromedial medulla. In some embodiments, activation of the interoceptive brain network includes activation of one or more of an insula, a secondary somatosensory cortex, a primary somatosensory cortex, an amygdala, a hippocampus, an anterior cingulate cortex, or an orbitofrontal cortex. In some embodiments, activation of the interoceptive brain network includes activation of one or more of an insula, a secondary somatosensory cortex, a primary somatosensory cortex, an orbitofrontal cortex, an anterior cingulate cortex, a hippocampus, or amygdala. In some embodiments, activation of the insula includes activation in an anterior insula, a posterior insula, a right dorsal lateral insula, or any combination thereof.
[0056] The emotion and memory brain network as described herein includes the amygdala and hippocampus, brain regions know to be involved in emotion and memory, and those regions that project to or from these regions, including the nucleus accumbens, zona incerta, temporal pole,orbitofrontal cortex, anterior cingulate cortex, insula, temporal cortex, posterior cingulate cortex, cerebellum, and prefrontal cortex. In some embodiments, the well-being-related mental response includes the activation of the emotion and memory brain network. In some embodiments, activation of the emotion and memory brain network includes activation of one or more of a hippocampus, an amygdala, a zona incerta, a nucleus accumbens, a temporal pole, an orbitofrontal cortex, an anterior cingulate cortex, an insula, a temporal cortex, a posterior cingulate cortex, or a prefrontal cortex. In some embodiments, activation of the emotion and memory brain network includes activation of one or more of a hippocampus, an amygdala, a temporal pole, a nucleus accumbens, a zona incerta, an orbitofrontal cortex, a cerebellum, or an anterior cingulate cortex. In some embodiments, activation of the emotion and memory brain network includes activation of a hippocampus and / or an amygdala. In some embodiments, activation of the insula includes activation in an anterior insula, a posterior insula, a right dorsal lateral insula, or any combination thereof.
[0057] The reward brain network as described herein refers to brain structures involved in reward-related cognition, including positive-valenced emotions and motivational behavior. The reward brain network includes the nucleus accumbens, putamen, orbitofrontal cortex, caudate nucleus, olfactory tubercle, ventral tegmental area, substantia nigra, prefrontal cortex, anterior cingulate cortex, insula, hippocampus, cerebellum, hypothalamus, subthalamic nucleus, globus pallidus, ventral pallidum, parabrachial nucleus, and amygdala. In some embodiments, the wellbeing-related mental response includes the activation of the reward brain network. In some embodiments, activation of the reward brain network includes activation of one or more of a nucleus accumbens, a putamen, a caudate nucleus, an olfactory tubercle, a ventral tegmental area, a substantia nigra, a prefrontal cortex, an orbitofrontal cortex, an anterior cingulate cortex, an insula, a hippocampus, a hypothalamus, a subthalamic nucleus, a globus pallidus, a ventral pallidum, a parabrachial nucleus, or an amygdala. In some embodiments, the well-being-related mental response includes the activation of the reward brain network. In some embodiments, activation of the reward brain network includes activation of one or more of a putamen, a nucleus accumbens, a cerebellum, an anterior cingulate cortex, a hippocampus, an amygdala, or an orbitofrontal cortex. In some embodiments, activation of the insula includes activation in an anterior insula, a posterior insula, a right dorsal lateral insula, or any combination thereof.
[0058] The cognitive processing brain network described herein refers generally to brain regions involved in cognitive processing including decision making, working memory, impulse control, and language comprehension and production. In some embodiments, the well-being-related mental response includes the activation of the cognitive processing brain network. In some embodiments, activation of the reward brain network includes activation of one or more of an inferior frontal gyrus, an anterior cingulate cortex, or a dorsolateral prefrontal cortex.
[0059] In some embodiments, the well-being-related mental response includes the activation of two or more of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain network. In some embodiments, the well-being- related mental response includes the activation of three or more of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain network. In some embodiments, the well-being-related mental response includes the activation of an interoceptive brain network, an emotion and memory brain network, a reward brain network, and a cognitive processing brain network.
[0060] It will be appreciated that the brain networks described herein in some cases include overlapping or shared brain regions. Since the brain is composed of a finite number of anatomical regions, such overlap is not unexpected considering the breadth of brain function. In some embodiments, the well-being-related mental response may be determined based on the brain regions activated by the test topical cosmetic. Thus, in an aspect is provided a method for identifying a topical cosmetic that elicits a well-being-related mental response in a subject, including determining from a cosmetic-evoked brain activity representing a response to touching a target tissue including a test topical cosmetic, whether one or more brain regions related to a sensation of well-being are activated. In some embodiments, the brain regions related to a sensation of well-being include one or more of a hippocampus, an amygdala, an insula, a primary somatosensory cortex, a secondary somatosensory cortex, an anterior cingulate cortex, an orbitofrontal cortex, a medial prefrontal cortex, a cerebellum, a parabrachial nucleus, a thalamus, a hypothalamus, a nucleus tractus solitarius, a periaqueductal gray, a locus coeruleus, a ventromedial medulla, a zona incerta, a nucleus accumbens, a temporal pole, a temporal cortex, a posterior cingulate cortex, a prefrontal cortex, a putamen, a caudate nucleus, an olfactory tubercle, a ventral tegmental area, a substantia nigra, a hippocampus, a subthalamic nucleus, a globus pallidus, a ventral pallidum, an amygdala, an inferior frontal gyrus, or a dorsolateral prefrontalcortex. In some embodiments, the brain regions related to a sensation of well-being include one or more of an insula, a secondary somatosensory cortex, a primary somatosensory cortex, a hippocampus, an amygdala, a temporal pole, a nucleus accumbens, a zona incerta, a putamen, an inferior frontal gyrus, an anterior cingulate cortex, a dorsolateral prefrontal cortex, or an orbitofrontal cortex, or a cerebellum is activated. In some embodiments, the brain regions related to a sensation of well-being include one or more of an insula, a secondary somatosensory cortex, or a primary somatosensory cortex. In some embodiments, the brain regions related to a sensation of well-being include one or more of a hippocampus, an amygdala, a temporal pole, a nucleus accumbens, or a zona incerta. In some embodiments, the brain regions related to a sensation of well-being include one or more of a nucleus accumbens, a putamen, or an orbitofrontal cortex. In some embodiments, the brain regions related to a sensation of well-being include one or more an inferior frontal gyrus, an anterior cingulate cortex, or a dorsolateral prefrontal cortex. In some embodiments, the brain regions related to a sensation of well-being include a hippocampus and / or an amygdala. In some embodiments, the brain regions related to a sensation of well-being include an anterior insula, a posterior insula, a right dorsal lateral insula, or any combination thereof. In some embodiments, the brain regions related to a sensation of well-being include an anterior cingulate cortex. No distinction is made between the left and right hemisphere unless made explicit by the terminology or context.
[0061] In some embodiments, the strength of the well-being-related mental response may be determined. In some embodiments, the strength of the well-being-related mental response is determined by the number of brain networks activated. For example, in some embodiments, a test topical cosmetic may activate one, two, three, or four brain networks, and the strength of the well- being-related mental response is related to the total number of activated brain networks, e.g., where four activated brain networks is a well-being-related mental response that is stronger than a topical cosmetic that activates one, two, or three brain networks. As such, in some embodiments, the number of brain networks activated is indicative of the strength of the well-being-related mental response. In some embodiments, the strength of the well-being-related mental response in a brain network is determined by the by the number of brain regions within the brain network that are activated. Thus, in some embodiments, the strength of activation of a brain network may be determined. In embodiments, the strength of activation of a brain network is determined by the total number of brain regions activated in the brain network. In embodiments, the strength ofactivation of a brain network is determined by the degree of activation of one or more brain regions activated in the brain network. See, e.g., Section I-C. In some embodiments, the degree of activation in one or more brain networks may be used to determine the strength of the well-being- related mental response. In some embodiments, the strength of the well-being-related mental response is determined by the total number of brain regions activated. In some embodiments, the strength of the well-being-related mental response is determined by the degree of activation in one or more brain regions (see, e.g., Section I-C). In some embodiments, the strength of the well-being- related mental response of a test topical cosmetic may be determined by comparing the brain networks and / or brain regions activated against the brain networks and / or brain regions activated by a control topical cosmetic. In some cases, the control topical cosmetic is a topical cosmetic having a known well-being-related mental response, e.g., determined according to the methods described herein. The brain networks and brain regions described here refer to any of the brain networks and brain regions described herein.C. Brain Imaging Methods and Analyses
[0062] The methods described herein include the use of brain imaging data collected from subjects experiencing tactile sensations of target tissue including topical cosmetics and / or under control conditions. Thus, in some embodiments, the methods described herein include the use of brain imaging methods. Methods for identifying brain activity elicited in a subject in response to tactile experiences described herein, e.g., see, Section I-A, include any method useful for identifying brain activity and changes thereof. 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), positron emission tomography (PET), functional near-infrared spectroscopy (fNIRS), single-photon emission computed tomography (SPECT), and functional ultrasound imaging (fUS). 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. It is contemplated that the brain imaging method used herein be suitable for use with human subjects. In some embodiments, the brain imaging method is fMRI. In some embodiments, the subject is suitable for fMRI, as is known in the art.
[0063] For purposes of identifying brain activity in response to tactile stimuli, in some embodiments, the subject has a normal sense of touch. Demographic information, e.g., age, gender, sex, ethnicity, nationality, etc., and psychological data may also be collected and / or associated with brain imaging data. Psychological data may be collected using questionnaires. All data is subject to and in compliance with privacy and data protection practices as required.
[0064] In some embodiments, brain activity (e.g., cosmetic-evoked brain activity, control topical brain activity, test brain activity) is identified during the application of the control topical cosmetic and / or the test topical cosmetic to a target tissue. For example, the brain activity is identified in a subject when the control topical cosmetic and / or the test topical cosmetic is applied to the target tissue. In some embodiments, brain activity (e.g., cosmetic-evoked brain activity, control topical brain activity, test brain activity) is identified after application of the control topical cosmetic and / or the test topical cosmetic to a target tissue. For example, the brain activity is identified in a subject at a time after the control topical cosmetic and / or the test topical cosmetic has been applied to the target tissue. Therefore, in some embodiments, the brain activity is identified in a subject touching a target tissue on which a control topical cosmetic or test topical cosmetic has been previously applied. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 45, 60 or more minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20 or more minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15 or more minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is 1, 2, 3, 4, 5 or more minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is about 1 to 15 minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue andidentifying brain activity in response to touching the target tissue is about 1 to 10 minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is about 1 to 5 minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is about 1 to 2 minutes. In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue is about 1 minute.
[0065] In some cases, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue allows the topical cosmetic to interact with (e.g., penetrate) the target tissue. Thus, in some cases, the microstructure of the target tissue is changed by the interaction of the topical cosmetic, e.g., control topical cosmetic, test topical cosmetic. In some embodiments, the cosmetic -evoked brain activity is brain activity evoked in response to a change in the target tissue resulting from the application of the topical cosmetic to the target tissue. In some embodiments, the change in the target tissue is a change in the microstructure of the target tissue. In some embodiments, the delay between application of the control topical cosmetic or test topical cosmetic to the target tissue and identifying brain activity in response to touching the target tissue allows the topical cosmetic to form a film on the target tissue, e.g., after water evaporation. In some embodiments, the cosmetic- evoked brain activity is brain activity evoked in response to a film present on the target tissue resulting from the application of the topical cosmetic to the target tissue. It is contemplated that the cosmetic-evoked brain activity may be a response to one or more changes to the target tissue, including mechanical, chemical, and topographical changes, the presence of a film, evaporation, that result from the application and / or the interaction (e.g., penetration) of the topical cosmetic with the target tissue.
[0066] In some embodiments, the target tissue is any tissue of the human body. In some embodiments, the target tissue is the tissue of the hands, arms, face, lips, legs, torso, or scalp. In some embodiments, the target tissue is skin. In some embodiments, skin is any part of the skin of the human body, including the skin of the face, including the lips and eyelids, undereye skin, the neck, the scalp, and the skin of the hands, arms, legs, or torso. In some embodiments, the target tissue is the skin at the level of the face, including the eye contour and the contour of the lips, andat the level of the neck. In some embodiments, the target tissue described herein is the skin of the hands. In some embodiments, the target tissue described herein is the skin of the arms. In some embodiments, the target tissue described herein is the skin of the legs. In some embodiments, the target tissue described herein is the skin of the torso.
[0067] In some embodiments, the cosmetic-evoked brain activity and the target tissue are from the same subject. For example, the subject in which brain activity is identified touches the target tissue of itself. In some embodiments, the cosmetic-evoked brain activity and the target tissue are from different subjects. For example, in some embodiments, the subject in which brain activity is identified touches a target tissue of another subject. Touching may be active or passive. For example, in some embodiments, the subject may actively massage, stroke, press, or otherwise actively interact with the target tissue. In some embodiments, the target tissue may be contacted (e.g., massaged, brushed, pressed, stroked, or otherwise placed on) with the subject such that the subject from which the brain activity is identified passively, e.g., lacking intentional motor activity, experiences the target tissue.
[0068] The identified activity in a brain region may be an increase in activity, which may be referred to as activation of the brain region, a suppression (e.g., decrease) in activity, which may be referred to as deactivation of the brain region, or no change in activity. 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 identified may have a different degree or directionality of activity compared to one or more of the other brain regions in which activity is also identified.
[0069] In some embodiments, activation of a brain region is determined by whether a number of adjacent voxels is activated beyond a statistically defined threshold value. In some embodiments, the number of adjacent voxels is equal to or greater than a statistically defined minimal number of voxels to constitute a scientifically relevant brain region of interest. In some embodiments, deactivation of a brain region is determined by whether a number of adjacent voxels is suppressed beyond a statistically defined threshold value. In some embodiments, the number of adjacent voxels is equal to or greater than a statistically defined minimal number of voxels to constitute a scientifically relevant brain region of interest. In some embodiments, the size of the brain region may contribute to determining the statistically defined minimal number of voxels.
[0070] Methods for analyzing changes in brain activity are well known in the art, and computer software packages for data analysis are commercially or freely available. By way of example, SPECT, PET or MRI data may be analyzed by Dot or EMMA (Extensible MATLAB® Medical image Analysis) packages freely available from the MNI, the Statistical Parametric Mapping (SPM) software package, freely available from the Functional Imaging Laboratory of the Wellcome Department of Imaging Neuroscience at the University College of London, UK (fil.ion.ucl.ac.uk / spm / ), BrainVoyager (Brain Innovation, Maastricht, Netherlands), FSL (FMRIB Software Library, Oxford University, FMRIB, Oxford Center for Functional MRI of the Brain), among other programs. The EMMA and SPM software are based upon the MATLAB® programming language (MathWorks, Inc., Natick, Mass.), with additional routines in the C programming language. NiPreps offers fMRIprep, a licensable application for the preprocessing of fMRI data.
[0071] SPM analysis, for example, employes a parametric statistical model at each voxel, using a general linear model (GLM) to describe the data in terms of experimental and confounding effects and residual variability. Hypotheses expressed in terms of the model parameters are assessed at each voxel with univariate statistics. Temporal convolution of the GLM for fMRI enables the application of results from serially correlated regression, permitting the construction of statistic images from the variability fMRI time series. To avoid issues that arise with multiple comparisons, in some embodiments, voxel-based thresholding or cluster-extent based thresholding may be used. In some embodiments, voxel-based thresholding includes the family-wise error rate (FWER) or false-discovery rate (FDR). In some embodiments, FWER may be used in combination with random field theory for voxel-based thresholding. In some embodiments, the continuous random fields theory is used to address multiple comparisons. The theory of continuous random fields assumes the statistic image to be a good lattice representation of an underlying continuous stationary random field. Results for the Euler characteristic lead to corrected p-values for each voxel hypothesis. In addition, the theory permits the computation of corrected p-values for clusters of k voxels exceeding a given threshold, and for entire sets of supra-threshold clusters, leading to more powerful statistical tests at the expense of some localizing power (see Friston et ai., Magnetic Resonance in Medicine 35346-3551996 and citations thereof, which is incorporated herein by reference).
[0072] In some embodiments, the statistical approach used to evaluate the general set of fMRI data is a time-series variant of the Analysis of Variance (ANOVA) form of a GLM. The statistical analysis tests each voxel of the brain, for each subject, against the null hypothesis (that over the duration of the testing the rise and fall of the BOLD signal coming from that voxel does not correlate with the onsets and offsets of the cycles of tactile stimulation). A weighted model is created that begins with a simple square wave type model of the on-off timing events for a single task variable of interest.
[0073] The ANOVA model allows regressors to be used to model nuisance variables. In some embodiments, the global signal strength of the whole brain is used as such a regressor. The global signal strength of the brain will account for fluctuations in the brain caused by respiratory cycles, cardiac flow cycles, blinking etc. These signal variations occur across the whole brain and may often be a greater magnitude than the localized changes in the BOLD signal resulting from the stimulus related brain activity. These signal variations occurring across the brain can be subtracted from the measured fMRI signals to show the signals resulting from the tactile stimuli and control conditions.
[0074] The resulting product of the ANOVA computation on a single-person's fMRI data is a 3- dimensional matrix of t-values which can be represented as a 3-dimensional map. This t-value map can then be converted into a probability map (a map of corresponding p-values) and the results can be displayed graphically at whatever threshold is desired (e.g., p < 0.01). The results may be overlain on a higher-resolution MRI image, in order to facilitate identification of finer-grained neuroanatomical structures.
[0075] In some embodiments, data from more than one subject may be combined. For example, each subject's brain may first be normalized into a common 3-dimensional stereotactic space before each individual's t-map is computed. Then the value of the sum of the contrast weights for each voxel from each subject computed during the ANOVA (basically, the numerator of the t- statistic) is entered as a single data point in a second-level t-statistic computation. In this second- level computation, the mean value for each voxel across subjects is modeled as the effect term and the variance between subjects as the error term. An important consequence of this approach is that it is very unlikely that a voxel will show significant activation on the group-level map, unless virtually all of the subjects show activation at that voxel. Also, brain areas are only considered tobe activated if a number of adjoining voxels (from the contrast) show a statistical significance above the designated probability standard. As indicated supra, in some embodiments, the number of adjacent voxels is equal to or greater than a statistically defined minimal number of voxels to constitute a scientifically relevant region of interest. In some embodiments, the size of the brain region may contribute to determining the statistically defined minimal number of voxels.
[0076] For purposes of statistical analysis and graphical display, the raw data on brain activity is usually grouped into voxels corresponding to fixed volumes of the subject brain. The voxel size may vary depending upon the resolution capability of the brain activity measuring device or the desired degree of precision in identifying brain regions. In some cases, smaller voxels have worse signal to noise ratios and greater susceptibility to artifacts due to partial volume effects. Functional voxels are cubes, or cuboids measuring, for example, 0.5 mm to 7 mm per side (e.g., of 2x2x2 mm3). The data can then be displayed graphically by color-coding the voxels according to some statistical value and showing cross-sections in which levels of activity or changes in levels of activity are mapped in two-dimensions. By generating a series of such co-planar cross-sections, the entire brain volume can be mapped. When conducting statistical analyses on brain images, an appropriate probability value for assessing statistical significance may be selected. The chosen value may vary depending upon the purpose of the statistical analysis and the level of certainty required. In some embodiments, the level of statistical significance is p < 0.05. In some embodiments, the level of statistical significance is p < 0.01. In some embodiments, the level of statistical significance is p < 0.001. In some embodiments, the p value may be corrected for multiple comparisons. Non-limiting methods of data analysis and statistical methods suitable for fMRI data are described in Soares et al., “A Hitchhiker’ s Guide to Functional Resonance Imaging,” (2016) Frontiers in Neuroscience, pp. 1-35, which is incorporated herein by reference.
[0077] In some embodiments, brain activity, including cosmetic-evoked brain activity, control brain activity, test brain activity, is identified in a single subject. In some embodiments, the brain activity, including cosmetic-evoked brain activity, control brain activity, and test brain activity, identified in a single subject is an average or other statistical representation of the brain activity, including cosmetic-evoked brain activity, control brain activity, test brain activity, identified in a single subject in response to two or more exposures to the same topical cosmetic. For example, in some cases, comparison of brain activity includes comparing brain activity, including cosmetic- evoked brain activity, control brain activity, test brain activity, that are an average or otherstatistical representation of the brain activity. In some embodiments, the brain activity, including cosmetic-evoked brain activity, control brain activity, and test brain activity, identified in a single subject is an average or other statistical representation of the brain activity, including cosmetic- evoked brain activity, control brain activity, test brain activity, identified in a plurality of subjects. In some embodiments, the brain activity, including cosmetic-evoked brain activity, control brain activity, and test brain activity, is an average or other statistical representation of the brain activity, including cosmetic-evoked brain activity, control brain activity, test brain activity, identified in a plurality of subjects.
[0078] In some embodiments, the brain activity, including cosmetic-evoked brain activity, control brain activity, and test brain activity, identified in a single subject is an average or other statistical representation of the brain activity, including cosmetic-evoked brain activity, control brain activity, test brain activity, identified in a plurality of subjects. In some embodiments, brain activity, including cosmetic-evoked brain activity, control brain activity, test brain activity, is identified by consolidating the evoked brain activity identified across a plurality of subjects. In some embodiments, brain activity, including cosmetic-evoked brain activity, control brain activity, test brain activity, identified in a single subject that is consolidated is an average or other statistical representation of the brain activity, including cosmetic-evoked brain activity, control brain activity, test brain activity, identified in the single subject in response to two or more exposures to the same topical cosmetic. Alternatively, each brain activity identified, without undergoing averaging or other statistical analysis, from a single subject may be included in the consolidation.
[0079] In some embodiments, for example when using fMRI, the brain activity, including cosmetic-evoked brain activity, control brain activity, and test brain activity, contains a probability for each brain region imaged, which representing the probability of the brain region responding (e.g., activating or deactivating) to the stimulus. In some embodiments, the probability for each brain region is determined by consolidating the brain activity patterns (e.g., cosmetic-evoked brain activity, control brain activity, test brain activity) across a plurality of subjects.
[0080] Methods of analyzing brain imaging data collected from a single or a plurality of subjects depend on the method of brain imaging used. General concepts of analysis include data processing, such as pre- and post-processing to extract stimulus (e.g., topical cosmetic) evoked brain activity from artifacts such as movement artifacts, electrical noise, etc. Data may also undergo spatialsmoothing and / or temporal filtering as required for appropriate analyses. In some embodiments, data may be processed for purposes of identifying and / or aligning brain regions across multiple subjects. For example, when using fMRI, in some embodiments, brain images may be aligned to a reference brain scan and / or normalized to a standard brain. Brain normalization to a reference may be used to compensate for individual anatomical difference for example when determining brain activity across a plurality of subjects. Brain normalization methods and coordinate systems are known in the art and include, but are not limited, transformation to Talairach space or MNI space. In some embodiments, brain normalization may be used for consolidating the evoked brain activity patterns identified across a plurality of subjects.
[0081] In some embodiments, when using fMRI, the brain activity (e.g., cosmetic-evoked brain activity, control brain activity, test brain activity) is identified using a fixed effects analysis. A fixed effects analysis may be suitable for identifying brain activity (e.g., cosmetic-evoked brain activity, 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 using fMRI, the brain activity (e.g., cosmetic -evoked brain activity, control brain activity, test brain activity) is identified using a random effects analysis. A random effects analysis may be suitable when identifying brain activity (e.g., cosmetic-evoked brain activity, 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 using fMRI, the brain activity (e.g., cosmetic-evoked brain activity, control brain activity, test brain activity) is identified using a mixed-effects analysis. A mixed-effects analysis may also be suitable when identifying brain activity (e.g., cosmetic -evoked brain activity, 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. Non-limiting examples of such platforms include 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).1. Topical cosmetic stimuli
[0082] As described above, the brain activity of interest in the methods described herein is the activity that is elicited by a topical cosmetic. For simplicity, the term topical cosmetic used in this section refers to any topical cosmetic described herein, e.g., test topical cosmetic, control topical cosmetic. In some embodiments, the topical cosmetic (test topical cosmetic, control topical cosmetic) is a cosmetic ingredient, a cosmetic composition, or a consumer product. In some embodiments, the test topical cosmetic and the control topical cosmetic are the same type of topical cosmetic, e.g., a cosmetic ingredient, a cosmetic composition, or a consumer product. In some embodiments, the test topical cosmetic and the control topical cosmetic are different types of topical cosmetics.
[0083] In some embodiments, the topical cosmetic (test topical cosmetic, control topical cosmetic) is a cosmetic ingredient. In some embodiments, the cosmetic ingredient is an active cosmetic ingredient. An active cosmetic ingredient refers to a compound capable of exerting at least one cosmetic effect on a tissue, such as skin, hair, and / or nails. A cosmetic effect means any non-therapeutic effect aimed at modifying and / or improving the visual appearance and / or mechanical properties of a tissue (e.g., skin, hair, and / or nails), such as protecting them from external aggressions (sun, wind, humidity, dryness, chemicals), preventing and / or correcting phenomena related to aging, or preventing or treating the effects caused by stress, fatigue, and / or inflammation. In some embodiments, the active cosmetic ingredient is an agent having any non- therapeutic effect that modifies and / or improves the visual appearance and / or mechanical properties of a tissue (e.g., skin, hair, and / or nails). In some embodiments, the cosmetic ingredient is an anti- wrinkle agent, an anti-aging agent, an antioxidant agent, an anti-inflammatory agent, an anti-stress agent, a moisturizing agent, a soothing agent, an anti-redness agent, a decongestant agent, an exfoliant or exfoliating agent, a matting agent, a refatting agent, a seboregulating agent, a lightening active ingredient, an anti-stain active ingredient, an anti-dark undereye circle or anti- undereye bag agent, an anti-fatigue agent, an anti-pollution active ingredient, a tensor agent, a filter or sunscreen, or any combination thereof.
[0084] In some embodiments, the cosmetic ingredient is a non-active cosmetic ingredient. For example, a non-active cosmetic ingredient may be useful in the preparation of a cosmetic composition or consumer product, but which itself does not exert a non-therapeutic effect. In someembodiments, the cosmetic ingredient is a functional ingredient. Functional ingredients may, for example, modify and / or improve the visual appearance and / or mechanical properties of a tissue (e.g., skin, hair, and / or nails) although not being classified as an active cosmetic. In some embodiments, the cosmetic ingredient is an excipient. In some embodiments, the cosmetic ingredient is a gelling agent, an emulsifier, a surfactant, a powder, a solubilizer, a preservative, an oil, or a wax. In some embodiments, the cosmetic ingredient is glyceryl stearate, PEG (e.g., PEG- 100 strearate), isononyl isononanoate, mineral oil, dimethicone, phenoxyethanol, methylparaben, ethylparaben, butylparaben, propylparaben, water, or sodium hydroxide. In some embodiments, the cosmetic ingredient is sodium phytate, alcohol, xanthan gum, C12-C16 alcohols, hydrogenated lecithin, palmitic acid, isoamyl laurate, shorea stenoptera seed butter, diisopropyl adipate, shea butter cetyl esters, behenyl alcohol, butyrospermum parkii (shea) butter unsaponifiables, soybean glycerides, macadamia ternifolia seed oil, dimethicone, fragrance, helianthus annuus (sunflower) seed oil, tocopherol, phenoxyethanol, or caprylyl glycol.
[0085] In some embodiments, the topical cosmetic is a cosmetic composition. For example, a cosmetic composition may be a composition containing an active cosmetic ingredient, a non-active cosmetic ingredient, a functional ingredient, and / or an excipient. In some embodiments, the cosmetic composition is a composition containing an active cosmetic ingredient. In some embodiments, the cosmetic composition is a composition containing a non-active cosmetic ingredient. In some embodiments, the cosmetic composition is a composition containing a functional ingredient. In some embodiments, the cosmetic composition is a composition containing an excipient. In some embodiments, the cosmetic composition is a composition containing an active cosmetic ingredient and / or a non-active cosmetic ingredient. In some embodiments, the cosmetic composition is a composition containing an active cosmetic ingredient and / or a functional ingredient. In some embodiments, the cosmetic composition is a composition containing an active cosmetic ingredient and / or an excipient. In some embodiments, the cosmetic composition is a composition containing a functional ingredient and / or an excipient. In some embodiments, the cosmetic composition is a composition that is formulated into a consumer product. In some embodiments, the cosmetic composition is a cream, a lotion, a gel, a foam, a paste, a salve, a balm, a powder, a varnish, an emulsion, or an ointment.
[0086] In some embodiments, the topical cosmetic is a consumer product. Consumer products described herein may contain active, non-active, functional, or excipient cosmetic ingredients. Insome embodiments, the consumer product is a facial or body powder, a foundation, a make-up product, an oil (e.g., body oil, facial oil), a mousse, a cream, a wax, a balm (e.g., lip balm), a mask, a lotion (e.g., a body lotion, facial lotion), a spray, a personal care product, a nail care product, a baby care product, a non-aerosol body spray, a body milk, a body cream, a sunscreen lotion, a sunscreen spray, a sun block, a roll-on product, an aerosol product, a natural spray product, a hair care product, a cleansing product; and the like.
[0087] Methods for applying (to a target tissue) the topical cosmetic may depend on the type of 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 topical cosmetic is applied by a trained experimenter. In some embodiments, the topical cosmetic is applied by the subject. In some embodiments, the topical cosmetic is applied by a different subject. It is appreciated that appropriate methods of application for the topical cosmetics used will be compatible with the requirements needed to perform brain imaging.D. Databases
[0088] Topical cosmetics and their ability to elicit a well-being-related mental response, as determined according to the methods described herein, may be stored in a database. In some embodiments, additional information, such as demographic and / or psychological data of the test subject(s), may be associated with the topical cosmetic tested. In some embodiments, the demographic data may include one or more of country, age, gender, or ethnicity information. In some embodiments, the database may include information about the topical cosmetic, e.g., ingredients, chemical structure, concentration(s) of cosmetic ingredient(s), regulatory information, etc.
[0089] 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 topical cosmetic, demographic group (e.g., country, age, gender, ethnicity), etc. In some embodiments, the database may be queried to provide topical cosmetics that elicit a well-being- related mental response, and optional the strength of the response in relation to other topical cosmetics.
[0090] In some embodiments, the database may be used for producing topical cosmetics that elicit a well-being-related response in a subject. In some embodiments, the database may be used to modify an existing topical cosmetic such that it elicits or increases a well-being-related response in a subject. In some embodiments, the database information may be used for training machine learning (ML) models and / or artificial intelligence (Al). In some embodiments, the ML and / or Al is trained to determine whether a topical cosmetic will evoke a well-being-related mental response.II. METHODS OF PRODUCING A TOPICAL COSMETIC THAT ELICITES A WELLBEING-RELATED MENTAL RESPONSE
[0091] The methods for identifying topical cosmetics that elicit well-being-related mental responses described herein offer the unique ability to swiftly and strategically produce topical cosmetics (e.g., cosmetic ingredients, cosmetic compositions, and / or consumer products) having the ability to elicit a well-being-related mental response in a subject. Thus, in an aspect is provided methods for producing a topical cosmetic that elicits a well-being-related mental response in a subject, including identifying, according to the methods described herein, a cosmetic ingredient or cosmetic composition that elicits a well-being-related mental response; and formulating the cosmetic ingredient or cosmetic composition that elicits the well-being-related mental response into a topical cosmetic composition or consumer product.
[0092] In some embodiments, the topical cosmetic (cosmetic composition or consumer product) is a new topical cosmetic. For example, an objective may be to produce a topical cosmetic that elicits a well-being-related mental response in a subject upon exposure. In this case, it would be possible to query a database as described herein to identify cosmetic ingredients and / or cosmetic composition with which to formulate the topical cosmetic. Furthermore, it may be possible to refine the query to identify topical cosmetics that will elicit well-being-related mental responses for use in a global population or a specific demographic group.
[0093] In some embodiments, the topical cosmetic (cosmetic composition or consumer product) is an existing topical cosmetic in which the cosmetic ingredients are known. In this case, the topical cosmetic may be modified to elicit a well-being-related mental response and / or increase the well- being-related mental response. In this case, it would be possible to query a database described herein to identify cosmetic ingredients and / or cosmetic compositions that would be compatible with the existing topical cosmetic (cosmetic composition or consumer product) and would inducea well-being -related mental response in a subject. In some embodiments, the query may further include a restriction to identify topical cosmetics that elicit well-being-related mental responses for use in a global population or specific demographic group.III. CONSUMER PRODUCTS THAT ELICIT WELL-BENG-RELATED MENTAL RESPONSES
[0094] Also provided herein are topical cosmetic ingredients, cosmetic compositions, and consumer products that elicit a well-being-related mental response in a subject as determined according to the methods described herein. Topical cosmetics, e.g., cosmetic compositions and consumer products, produced according to the methods described herein are also provided. The topical cosmetic ingredients and cosmetic compositions determined according to the methods herein to induce a well-being-related mental response and topical cosmetics, e.g., cosmetic compositions, produce according to the methods provided herein are widely applicable to any cosmetic product.
[0095] Also provided are consumer products containing a topical cosmetic, such as a cosmetic ingredient or cosmetic composition determined according to the methods herein to elicit a well- being-related mental response, or a topical cosmetic, such as a cosmetic composition determined according to the methods herein to elicit a well-being-related mental response, produced according to the methods provided herein. In some embodiments, the consumer product is a personal care product or a cosmetic product. Consumer products may include, for example, 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 handkerchief, cosmetic preparations, dental and oral hygiene products such as toothpastes, tooth gels.
[0096] In an aspect is provided use of a topical cosmetic, e.g., cosmetic ingredient, cosmetic composition, or consumer product described herein to induce a mental state in a consumer. In an aspect is provided use of a topical cosmetic, e.g., cosmetic ingredient, cosmetic composition, or consumer product described herein, to elicit a well-being-related mental response in a subject upon application to a target tissue.EXEMPLARY EMBODIMENTS
[0097] Among the provided embodiments are:1. A method for identifying a topical cosmetic that elicits a well-being-related mental response in a subject, comprising determining from a cosmetic-evoked brain activity representing a response to touching a target tissue comprising a test topical cosmetic, whether at least one of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain network is activated.2. The method of embodiment 1, wherein the cosmetic-evoked brain activity is determined by a method comprising: a.identifying a control brain activity in a subject under a control condition; b. identifying a test brain activity in the subject in response to touching the target tissue comprising the test topical cosmetic; and c. determining the cosmetic-evoked brain activity by comparing the control brain activity and the test brain activity; wherein the identifying comprises functional magnetic resonance imaging.3. The method of embodiment 2, wherein the control condition is one or more of a resting state, touching the target tissue not comprising a topical cosmetic, or touching the target tissue comprising a control topical cosmetic.4. The method of any one of embodiments 1-3, wherein at least 2, 3, or more of the interoceptive brain network, the emotion and memory brain network, the reward brain network, or the cognitive processing brain network are activated.5. The method of any one of embodiments 1-4, wherein the determining whether the interoceptive brain network is activated comprises determining whether one or more of, independently, an insula, a secondary somatosensory cortex, a primary somatosensory cortex, an orbitofrontal cortex, an anterior cingulate cortex, a hippocampus, or an amygdala is activated.6. The method of any one of embodiments 1-5, wherein the determining whether the emotion and memory brain network is activated comprises determining whether one or more of, independently, a hippocampus, an amygdala, a temporal pole, a nucleus accumbens, a zona incerta, an orbitofrontal cortex, a cerebellum, an anterior cingulate cortex, or an insula is activated.7. The method of any one of embodiments 1-6, wherein the determining whether the reward brain network is activated comprises determining whether one or more of, independently, a putamen, anucleus accumbens, a cerebellum, an anterior cingulate cortex, a hippocampus, an amygdala, an insula, or an orbitofrontal cortex is activated.8. The method of any one of embodiments 1-7, wherein the determining whether the cognitive processing brain network is activated comprises determining whether one or more of, independently, an inferior frontal gyrus, an anterior cingulate cortex, or a dorsolateral prefrontal cortex is activated.9. The method of any one of embodiments 5-8, wherein the insula is an anterior insula, a posterior insula, a right dorsal posterior insula, or any combination thereof.10. The method of any one of embodiments 1-9, wherein the cosmetic-evoked brain activity and the target tissue are from the same subject.11. The method of any one of embodiments 1-9, wherein the cosmetic-evoked brain activity and the target tissue are from different subjects.12. The method of any one of embodiments 1-11, wherein the test topical cosmetic is a cosmetic ingredient, a cosmetic composition, or a consumer product.13. The method of any one of embodiments 3-12, wherein the control topical cosmetic is a cosmetic ingredient, a cosmetic composition, or a consumer product.14. The method of any one of embodiments 1-13, wherein the target tissue is tissue of hands, arms, face, lips, legs, torso, or scalp.15. A topical cosmetic that elicits a well-being-related mental response in a subject determined according to a method of any one of embodiments 1-14, wherein the topical cosmetic is a cosmetic ingredient, a cosmetic composition, or a consumer product.16. A method for producing a topical cosmetic that elicits a well-being-related mental response in a subject, comprising: (i) identifying, according to the method of any one of embodiments 1-14, a cosmetic ingredient or cosmetic composition that elicits a well-being-related mental response; and (ii) formulating the cosmetic ingredient or cosmetic composition that elicits the well-being- related mental response into a topical cosmetic composition or consumer product.17. A consumer product comprising a topical cosmetic that elicits a well-being-related mental response determined according to any one of embodiments 1-14, wherein the consumer product is a personal care product or a cosmetic product.18. Use of a topical cosmetic according to embodiment 15 or a consumer product according to embodiment 17 to elicit a well-being-related mental response in a subject upon application to a target tissue.IV. EXAMPLESThe following examples are included for illustrative purposes only and are not intended to limit the scope of the invention.Example 1: Assessment of Brain Activity in Response to Topical Cosmetics
[0098] The effects of two topical creams on emotions and well-being were assessed using functional magnetic resonance imaging (fMRI).
[0099] Subjects: 20 healthy female participants, right-handed, 18-45 years old, were recruited according to inclusion and exclusion criteria for fMRI studies. Prior to the onset of the study, each subject completed a medical screening form and an informed consent form. Subjects were informed about the experimental procedure and trained on it prior to the experiment.
[0100] Experimental Design: Experiments proceeded according to a block design. FIGS. 1 A and IB show the overall experimental block design and a detail description of a single block, respectively.
[0101] Three different conditions were tested: (1) Skin massage without a topical cosmetic (Control); (2) Skin massage after application of a control topical cosmetic (Control Cream); and (3) Skin massage after application of test topical cosmetic (Test Cream). Table El below shows the ingredients for the topical cosmetic creams used. The 3 experimental conditions were performed in a pseudo-randomized order, always starting with the cream free massage, followed by massage with Test Cream or Control Cream in a randomized order.
[0102] At the beginning of each block, the experimenter cleaned the subject’s hands and wrists with a perfume free make-up remover wipe, rinsed them with a wet cotton pad, and dried them with a tissue (duration approximately 1 minute). This was followed by a 2-minute rest period.Next, the experimenter delivered 80 pL of cream to a predefined area. The volunteers (subjects) massaged this area for approximately 12 seconds (6 rounds, approximately 2 seconds / round) to make the cream penetrate the skin. This scenario was repeated two more times on two other predefined areas. The predefined areas included the back of the left hand, the top surface of the left wrist, and the bottom surface of the left wrist. After approximately 1 minute, the subject was asked to massage the three different areas of her left hand and wrist using her right hand for approximately 12 seconds each (6 rounds, approximately 2 seconds / round), to feel the sensory effect left by the cream.
[0103] Data Acquisition and Pre-processing: Functional MR1 (fMRI) measures brain activity by detecting changes in the Blood Oxygenation Level Dependent (BOLD) signal. By comparing the BOLD signal during periods of rest and activation, regional changes in brain activity can be measured as a result of exposure to a stimulus.
[0104] Functional magnetic resonance imaging was performed with a GE 3 Tesla SIGNA™ Premier MRI Scanner with a 48-Channel Head Coil. First, T2*-weighted echo-planar images was acquired with the following parameters: 2-mm slice thickness, TR = 1500 ms, TE = 30 ms, flip angle = 90 deg, FOV = 220 mm, voxel size 2x2x2 mm3, ascending interleaved acquisition. Then, Tl-weighted structural images were acquired with a resolution of Ixlxl mm3. Brain imaging data was collected throughout the experiment such that brain activity for each condition and step of the experiment was acquired, including during periods of rest.
[0105] Brain imaging data was preprocessed using fMRIprep (nipreps.org), a neuroimaging preprocessing tools application for task-based and resting state fMRI. Slice timing correction, motion correction and a high pass filter was applied to the functional images. Data was then coregistered to the structural images and normalized to the T1 standard template in the Montreal Neurological Institute and Hospital (MNI) space.
[0106] Data Analysis; To assess the sensory effect of stimulations on the sensation of well-being, simple contrasts analysis was carried out to measure differences in brain activation during the massage of skin after application and penetration of creams (or no cream, Control) compared to resting state records. Then, data obtained from the three blocks were contrasted (complex contrasts) to assess the added effects of the topical cosmetics to the massage alone. Brain region activity from the contrasts satisfying a false-discovery rate of q(FDR) < 0.05 and uncorrected p < 0.01 are reported.
[0107] Results: Simple contrasts performed between the rest state and a stimulation condition (Test Cream, Control Cream, Control) revealed that all stimulation conditions elicited consistent and robust activity in somatosensory-related areas. However, the Test Cream showed stronger activation of the right primary somatosensory cortex (SI), right dorsal posterior insula, secondary somatosensory cortex (SII), putamen, nucleus accumbens, hippocampus, and temporal pole compared to the Control and Control Cream.
[0108] Complex contrasts were determined using the simple contrasts described above. Comparison of the Test Cream simple contrast to the Control simple contrast showed the BOLD signal in response to the Test Cream was greater in the somatosensory cortices (SI and SII), dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, upper and lower brain stem nuclei, anterior insula, posterior insula, zona incerta, hippocampus, amygdala, nucleus accumbens, and putamen, compared to the BOLD signal in response to the Control condition.
[0109] Comparing the Test Cream simple contrast to the Control Cream simple contrast showed larger BOLD responses in the somatosensory cortices (SI and SII), anterior cingulate cortex, nucleus accumbens, putamen, cerebellum, and the inferior frontal gyrus compared to the Control Cream BOLD responses.
[0110] These data suggest that the Test Cream selectively elicited, compared to the control conditions, stronger brain activity in brain regions involved in sensation including somatosensorycortices and interoceptive brain networks, brain regions involved in emotion and memory processing, brain regions involved in reward processing, and brain regions involved in cognitive processing. These results suggest that the Test Cream elicits activity in the interoceptive, emotion and memory, reward, and cognitive processing networks of the brain. Furthermore, these brain regions and networks are believed to participate in or form the brain networks involved in the experience of well-being. Therefore, the results viewed collectively suggest the Test Cream elicits well-being-related mental responses in addition to eliciting the activity in brain regions and brain networks known to be involved in interoception, emotion, memory, reward, and cognition.
[0111] 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
CLAIMSWhat is claimed is:
1. A method for identifying a topical cosmetic that elicits a well-being-related mental response in a subject, comprising determining from a cosmetic-evoked brain activity representing a response to touching a target tissue comprising a test topical cosmetic, whether at least one of an interoceptive brain network, an emotion and memory brain network, a reward brain network, or a cognitive processing brain network is activated.
2. The method of claim 1, wherein the cosmetic-evoked brain activity is determined by a method comprising: a. identifying a control brain activity in a subject under a control condition; b. identifying a test brain activity in the subject in response to touching the target tissue comprising the test topical cosmetic; and c. determining the cosmetic-evoked brain activity by comparing the control brain activity and the test brain activity; wherein the identifying comprises functional magnetic resonance imaging.
3. The method of claim 2, wherein the control condition is one or more of a resting state, touching the target tissue not comprising a topical cosmetic, or touching the target tissue comprising a control topical cosmetic.
4. The method of any one of claims 1-3, wherein at least 2, 3, or more of the interoceptive brain network, the emotion and memory brain network, the reward brain network, or the cognitive processing brain network arc activated.
5. The method of any one of claims 1-4, wherein the determining whether the interoceptive brain network is activated comprises determining whether one or more of, independently, an insula, a secondary somatosensory cortex, a primary somatosensory cortex, an orbitofrontal cortex, an anterior cingulate cortex, a hippocampus, or an amygdala is activated.
6. The method of any one of claims 1-5, wherein the determining whether the emotion and memory brain network is activated comprises determining whether one or more of, independently, a hippocampus, an amygdala, a temporal pole, a nucleus accumbens, a zona incerta, an orbitofrontal cortex, a cerebellum, an anterior cingulate cortex, or an insula is activated.
7. The method of any one of claims 1-6, wherein the determining whether the reward brain network is activated comprises determining whether one or more of, independently, a putamen, a nucleus accumbens, a cerebellum, an anterior cingulate cortex, a hippocampus, an amygdala, an insula, or an orbitofrontal cortex is activated.
8. The method of any one of claims 1-7, wherein the determining whether the cognitive processing brain network is activated comprises determining whether one or more of, independently, an inferior frontal gyrus, an anterior cingulate cortex, or a dorsolateral prefrontal cortex is activated.
9. The method of any one of claims 5-8, wherein the insula is an anterior insula, a posterior insula, a right dorsal posterior insula, or any combination thereof.
10. The method of any one of claims 1-9, wherein the cosmetic-evoked brain activity and the target tissue arc from the same subject.
11. The method of any one of claims 1-9, wherein the cosmetic-evoked brain activity and the target tissue are from different subjects.
12. The method of any one of claims 1-11, wherein the test topical cosmetic is a cosmetic ingredient, a cosmetic composition, or a consumer product.
13. The method of any one of claims 3-12, wherein the control topical cosmetic is a cosmetic ingredient, a cosmetic composition, or a consumer product.
14. The method of any one of claims 1-13, wherein the target tissue is tissue of hands, arms, face, lips, legs, torso, or scalp.
15. A topical cosmetic that elicits a well-being -related mental response in a subject determined according to a method of any one of claims 1-14, wherein the topical cosmetic is a cosmetic ingredient, a cosmetic composition, or a consumer product.
16. A method for producing a topical cosmetic that elicits a well-being-related mental response in a subject, comprising:(i) identifying, according to the method of any one of claims 1-14, a cosmetic ingredient or cosmetic composition that elicits a well-being-related mental response; and(ii) formulating the cosmetic ingredient or cosmetic composition that elicits the wellbeing-related mental response into a topical cosmetic composition or consumer product.
17. A consumer product comprising a topical cosmetic that elicits a well-being-related mental response determined according to any one of claims 1-14, wherein the consumer product is a personal care product or a cosmetic product.
18. Use of a topical cosmetic according to claim 15 or a consumer product according to claim 17 to elicit a well-being-related mental response in a subject upon application to a target tissue.
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