Enhancing cognition and memory through stimulation with various odorants

Abstract

This document relates to the enhancement of cognition and memory through stimulation by a plurality of odorants, disclosing a system for improving the remote transfer effect of cognition in a human, a device for use in the system, and a method of delivering an aroma. The system for improving the remote transfer effect of cognition in a human comprises: a module for establishing a daily treatment schedule comprising a plurality of time intervals separated by intervals; a module for inputting the daily treatment schedule into an aroma delivery device such that the device delivers one of a plurality of aromas during each time interval and ceases delivery of the aroma at the end of the time interval; wherein the aromas delivered during successive time intervals are sufficiently different from one another so as to be distinguished by the human; wherein the daily treatment schedule is repeated each day for a predetermined treatment duration.

Description

[0001] This application is a divisional of the Chinese national phase of the PCT application No. PCT / US2019 / 027298, international filing date 12 April 2019, entitled “Enhancing cognition and memory through multiple odorant stimulation” which entered the Chinese national phase on 30 October 2020 and has application number 201980029503.2. BACKGROUND

[0002] Environmental enrichment has been shown to have a positive impact on cognitive function, such as reducing cognitive decline in various animal models. Enriching the environment can be accomplished in a variety of ways, including but not limited to introducing various objects, sounds, smells, colors, animals, etc. Thousands of research papers have been published drawing this conclusion, and cognitive benefits have been shown to reduce or overcome human neurological conditions in animal models, such as Alzheimer’s disease, memory loss, vascular dementia, neuronal death in aging, traumatic brain injury, head injury, Parkinson’s disease, seizures, stroke, multiple sclerosis, anxiety, autism, ADHD, Huntington’s disease, Down Syndrome, stress, depression, cerebral palsy, chemo brain, schizophrenia, Fetal Alcohol Syndrome, lead exposure, addiction, and cancer, among others. Significant behavioral changes have been observed in children with autism after just six months of environmental enrichment exercise.

[0003] Of the various stimuli used in environmental enrichment, cognition has been found to be closely related to olfaction. Olfaction is the only sense with a large direct pathway to cognitive and emotional areas of the brain. Olfactory loss precedes memory loss caused by aging and various forms of dementia. Olfactory loss triggers a massive loss of neurons in the brain. After age 50, olfactory ability has been found to accurately predict all-cause mortality in the next five years.

[0004] Biologically, olfactory stimulation activates the entorhinal cortex. The entorhinal cortex decreases with age and other factors such as Alzheimer’s disease and other forms of dementia. As the entorhinal cortex decreases, it releases the dentate gyrus and CA3 (a subregion of the hippocampus) from inhibition, thereby interfering with memory. Therefore, restoring olfaction should increase neurogenesis and / or neural complexity in the entorhinal cortex, thereby normalizing dentate gyrus / CA3 activity and restoring memory.

[0005] Interventions based on environmental enrichment can be costly or difficult to maintain, as in the case of exercise. Currently, there is a lack of environmental enrichment modalities that effectively improve cognitive function and memory while being low cost and easy to use or maintain. More specifically, there is a lack of environmental enrichment modalities that take advantage of the close association of olfaction with cognitive and emotional areas of the brain. SUMMARY

[0006] Provided herein are methods, kits, and devices for improving cognitive function and memory and preventing loss of these functions. In some embodiments, the environment of an aging brain is improved by reversing and / or preventing the decline of the sensory system in older adults and in people with or at risk of developing neurodegenerative conditions and / or decreased cognitive ability. In some embodiments, cognitive outcomes in children and / or young adults are improved. In other embodiments, the methods can be used to reduce colic in infants, normalize brain development in preterm infants, lower cognitive age in adults, and reduce or prevent migraines and headaches. The methods, kits, and devices described herein can have a large impact on cognition with minimal effort and cost. They can be used widely and effectively in older adults, children, and other populations in need of improved cognitive ability.

[0007] Generally, the present invention relates to methods and devices for improving cognitive function in the brain by stimulating olfaction. In most embodiments, the stimulation is achieved by subjecting the treatment recipient to unique scents on a rotating schedule of time intervals. It has been found that a single, specific scent, while potentially pleasant, does not have a significant cognitive benefit. However, when the treatment recipient is subjected to a daily rotation of different scents, the olfactory stimulation triggers accelerated production of new neurons (neurogenesis), as has been shown in mice, and / or increased neural complexity, resulting in substantial improvements in general cognition and memory (far transfer effects) compared to practice effects on the same task (near transfer effects).

[0008] Far transfer is the improvement in memory that is independent of practice on a specific task, and thus improves people's general memory. Near transfer refers to the ability to get better at a specific task through practice on that task, but does not result in improvements in other cognitive abilities. There are many computer games and other activities that are advertised to improve brain activity. These activities are all examples of "near transfer."

[0009] One aspect of the invention maximizes far transfer effects by providing an olfactory stimulation schedule that includes a variety of scents, some of which are novel to the recipient.

[0010] Another aspect of the invention maximizes far transfer effects by providing an olfactory stimulation schedule that rotates the scents presented to the recipient.

[0011] Another aspect of the application provides an olfactory stimulation schedule that provides a pleasant smell to the recipient.

[0012] Yet another aspect of the application provides an olfactory stimulation schedule that is delivered consistently over a period of months.

[0013] Therapeutic programs, particularly those that are self-administered or administered at home by a family member over a long period of time, require dedication and discipline. It is understood that the efficacy of a therapeutic program improves if the therapy is administered consistently. Therefore, one aspect of the application attempts to maximize the consistency of administration possible by making the program as pleasant as possible to administer, easy to administer, and as unobtrusive as possible to the recipient's lifestyle. This is achieved through "ease of use factors".

[0014] One aspect of the application provides a pleasant aroma as an ease of use factor.

[0015] Another aspect of the application is a device that produces a rotating aroma as an ease of use factor.

[0016] Another aspect of the application is a device that rotates an aroma on a schedule as an ease of use factor.

[0017] Another aspect of the application is an automatic presentation of an aroma schedule while the recipient is sleeping as an ease of use factor.

[0018] It has been determined that when a recipient is sleeping, the smell does not wake the person. Therefore, the recipient will not be awakened when subjected to an unpleasant smell. Therefore, an unpleasant smell is generally more novel to the recipient than a pleasant smell. With this in mind, one aspect of the application provides a potentially unpleasant smell while the recipient is sleeping.

[0019] Another aspect of the application provides a schedule that includes a potentially pleasant smell and a potentially less pleasant smell, where the less pleasant smell occurs during a time interval when the recipient will not be awake. For example, a pleasant smell will be scheduled at a time when the recipient is likely to be going to sleep and in the morning when the recipient is likely to be awake. A less traditional or potentially unpleasant smell will be scheduled in the middle of the night when the recipient is less likely to be awake.

[0020] Another aspect of the application provides an identification system whereby the recipient can mark an aroma as unpleasant, or rate the aroma on a scale, and therefore the aroma delivery system schedules the aroma with the lowest rating during the hours when the recipient is most likely to be asleep.

[0021] Yet another aspect of the present invention is to track the aromas that the recipient has been exposed to throughout the treatment program to ensure that novelty is maintained. Through experimentation, it has been determined that a number of aromas provide maximum efficacy. In one embodiment, at least seven embodiments are used.

[0022] In another embodiment, at least four aromas are used. However, the device that provides these aromas is capable of simultaneously "playing" or emitting one or more of the aromas. Thus, two or more base aromas can be mixed together to create a new aroma.

[0023] In another embodiment, a device is provided that can simultaneously play multiple base aromas (also referred to as mixing the aromas) as well as varying the intensity of each base aroma. Thus, using only four base aromas, an almost infinite number of aromas can be created.

[0024] As known to those skilled in the art, a sleep cycle is composed of individual stages that repeat every 90 to 110 minutes. One model divides the sleep cycle into five stages: the first stage is light sleep, characterized by a reduction in muscle, brain, and eye activity; the second stage involves a slowing of heart rate and breathing patterns, as well as a slight decrease in body temperature. The third stage is the onset of deep sleep and involves very slow delta waves produced by the brain; the fourth stage is very deep sleep with rhythmic breathing, limited muscle activity, and continued delta wave production; and the fifth stage is called the REM (rapid eye movement) stage. This is the dream stage, characterized by elevated blood pressure, heart rate, respiratory rate, and rapid eye movements. The therapeutic efficacy of the olfactory stimulation therapy of the present invention can vary depending on the sleep stage in which the recipient is in. For example, it can be determined that the treatment delivered in the third and fourth stages is not effective, while the treatment delivered during REM is the most effective of all stages.

[0025] With this in mind, one aspect of the present invention includes a sleep stage tracking system, such as a heart rate monitor, a respiration monitor, a blood pressure monitor, a brain wave sensor, or any combination thereof. The sleep stage tracking system is used in conjunction with the aroma delivery schedule to ensure that the intermittent time intervals (periods between aroma delivery intervals) occur during sleep stages that are less effective, and the aroma intervals occur during sleep stages that have maximum effectiveness.

[0026] Described herein is a method of improving at least one of cognitive function and memory by treating a subject in need thereof according to an olfactory stimulation regimen. In one embodiment, the method comprises: a) releasing one or more scents to the subject in an initial step on a first day; and b) releasing one or more scents to the subject in a subsequent step on a subsequent day, the one or more scents in the subsequent step being different from the one or more scents in the initial step, thereby improving at least one of cognitive function and memory in the subject. In some embodiments, the method is provided in conjunction with other forms of environmental, sensory, or tactile stimulation. In other embodiments, the olfactory stimulation is provided without tactile stimulation or without other forms of environmental or sensory stimulation.

[0027] In one embodiment, the subject treated with the method experiences statistically improved cognitive function as measured by a Stroop test, a Rey Auditory Verbal Learning Test (RAVLT), a Wechsler Adult Intelligence Scale (WAIS) test, or a combination thereof, as compared to an untreated subject. In one embodiment, the method improves or reduces age-related memory loss in the subject. In one embodiment, the memory of the subject is improved. In one embodiment, the method improves cognition, memory, intelligence quotient (IQ), or a combination thereof.

[0028] In one embodiment, the method prevents, reverses, halts, or slows progression of a neurodegenerative disease or condition. In one embodiment, the neurodegenerative disease or condition is Alzheimer’s disease, Parkinson’s disease, motor neuron disease, Huntington’s disease, or dementia.

[0029] In one embodiment, the method improves memory, intelligence, sleep, brain normalization, gait, balance, Alzheimer’s disease, Parkinson’s disease, motor neuron disease, Huntington’s disease, other forms of dementia, agitation, post-traumatic stress disorder (PTSD), panic attacks, stress, generalized anxiety disorder (GAD), obsessive compulsive disorder (OCD), social anxiety disorder (SAD), phobias, depression, major depressive disorder (MDD), premenstrual syndrome (PMS), hypertension, angina, migraine, sleep disorders, or a combination thereof.

[0030] In one embodiment, the method improves stroke rehabilitation, seizure, prenatal alcohol syndrome, lead exposure, multiple sclerosis, addiction, schizophrenia, Down's syndrome, mu-opioid receptor loss, fragile X syndrome, Rett Syndrome, Potocki-Lupski Syndrome, repetitive behavior, Lewy body dementia, frontotemporal dementia, or progression or outcome of Creutzfeldt-Jakob disease.

[0031] In one embodiment, the method reduces dementia or destructive behaviors associated with dementia, increases self-esteem, reduces stress, lowers blood pressure, increases relaxation, prevents oxidative damage, improves postural stability, improves gait, increases deep sleep, improves mood, reduces anxiety, improves vigor, improves quality of life, improves cognition, or improves depression or depressive symptoms.

[0032] In one embodiment, the method improves cognitive processing speed, attentional capacity, executive function, or a combination thereof. In one embodiment, the method improves sequential processing, mental control, attention, concentration, memory span, short-term auditory memory, verbal learning and memory, sequential processing, mechanical learning and memory, encoding, auditory processing, working memory, information conversion, visual-spatial imagery, or a combination thereof. In one embodiment, the method improves cognition, memory, intelligence quotient (IQ), or a combination thereof.

[0033] In one embodiment, the subject is an elderly person. In one embodiment, the subject experiences age-related cognitive function deficits, including but not limited to memory deficits. In one embodiment, the subject is at least about 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or about 100 years old. In one embodiment, the subject is an elderly person 55 years of age or older. In another embodiment, the subject is a young person 18-55 years of age.

[0034] In one embodiment, the subject is a child. In some embodiments, the child is a child who exhibits normal cognitive abilities (regardless of performance or results in cognitive assessments), such as a child who does not meet the diagnostic criteria for autism. In some embodiments, the child is a typical child who does not exhibit or experience any particular challenges to his or her environment or cognitive abilities. In some embodiments, the child has one or more developmental disorders. Representative examples of developmental disorders include, but are not limited to, autism, ADHD, and developmental delay. In one embodiment, the child is autistic. In other embodiments, the child has one or more developmental disorders other than autism.

[0035] In some embodiments, the olfactory stimulation regimen is performed over a period of 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In some embodiments, the olfactory stimulation regimen is performed over a period of 2 days or more. In some embodiments, the olfactory stimulation regimen is performed over a period of at least 1, 2, 3, or 4 weeks. In some embodiments, the olfactory stimulation regimen is performed over a period of at least 1, 2, 3, 4, 5, or 6 months. In some embodiments, the olfactory stimulation regimen is performed over a period of at least 7, 8, 9, 10, 11, or 12 months. In some embodiments, the olfactory stimulation regimen is performed over a period of about 3 months. In some embodiments, the olfactory stimulation regimen is performed over a period of about 6 months.

[0036] In some embodiments, the aromas used in the olfactory stimulation regimen are from one or more aroma categories selected from the group consisting of floral, woody, and spicy. In some embodiments, the aromas used are from two or three of these categories. Optionally, in some embodiments, additional aroma categories can be used, such as oriental and / or fresh.

[0037] In some embodiments, the aromas used in the olfactory stimulation regimen are from one or more aroma categories selected from the group consisting of fruity, floral, woody, resinous, and spicy. In some embodiments, the aromas used are from two, three, four, or all five of these categories.

[0038] In some embodiments, the aromas used in the olfactory stimulation regimen are selected from the group consisting of lavender, citrus, jasmine, clove, mint, cinnamon, mint, clove, lemon grass, coffee, anise, basil, thyme, chamomile, rosemary, cucumber, coconut, fresh cotton, violet, vanilla, forest pine, pomegranate, pear, orange, apple, rosehip, saffron, sage, eucalyptus, frankincense, nutmeg, and sandalwood. In some embodiments, the aromas used are from any combination of two or more of these group members.

[0039] In some embodiments, the steps of the olfactory stimulation protocol are performed at night. In some embodiments, the steps of the olfactory stimulation protocol are performed during the day. In some embodiments, the steps of the olfactory stimulation protocol are performed both during the day and at night.

[0040] In some embodiments, the olfactory stimulation protocol is performed as a series of stimulation cycles, each cycle containing at least two olfactory stimulation steps. In some embodiments, the olfactory stimulation protocol includes at least one stimulation cycle containing at least 3, 4, 5, 6, 7, 8, 9, or 10 steps. In some embodiments, the olfactory stimulation protocol includes repeating at least one stimulation cycle within a specified time period. In some embodiments, the olfactory stimulation protocol includes a stimulation cycle with 6 steps. In some embodiments, the olfactory stimulation protocol includes a stimulation cycle with 7 steps.

[0041] In some embodiments, at least one step of the olfactory stimulation protocol includes: a) continuously releasing at least one aroma for a first duration; and b) ceasing the release of said at least one aroma for a second duration. In one embodiment, the first duration is about 5 minutes. In one embodiment, the second duration is about 1 minute.

[0042] In one embodiment, the at least one step further includes repeating a) and b). In one embodiment, a) and b) are repeated until the subject has been exposed to at least one aroma for a specified exposure period. In one embodiment, the specified exposure period is about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In one embodiment, the specified exposure period is as long as about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes.

[0043] In some implementations, each step of the olfactory stimulation protocol includes: a) continuously releasing at least one aroma during a first duration; and b) ceasing the release of the at least one aroma during a second duration.

[0044] In some embodiments, an atomizer or diffuser is used to apply each step of the olfactory stimulation program. In some embodiments, each step of the olfactory stimulation program is applied by ventilation, heating, humidification, or vaporization, atomization, or aerosolization of one or more fragrances, or a combination thereof. In some embodiments, at least one candle, tea lamp diffuser, atomizing diffuser, room sprayer, evaporative diffuser, evaporative fan diffuser, vaporizing diffuser, wearable evaporative diffuser, ultrasonic diffuser, thermal evaporative diffuser, evaporative pad diffuser, cream, wick, open odorant container, or any combination thereof is used to apply each step of the olfactory stimulation program.

[0045] In some embodiments, at least one step of the olfactory stimulation protocol exposes the subject to an aroma. In some embodiments, each step of the olfactory stimulation protocol exposes the subject to an aroma. In some embodiments, at least one step of the olfactory stimulation protocol exposes the subject to multiple aromas. In some embodiments, each step of the olfactory stimulation protocol exposes the subject to multiple aromas.

[0046] In some embodiments, each step of the olfactory stimulation protocol exposes the subject to one or more aromas for at least about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In some embodiments, each step of the olfactory stimulation protocol exposes the subject to one or more aromas for up to about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In some embodiments, each step of the olfactory stimulation protocol includes exposing the subject to one or more aromas for about 30 minutes.

[0047] In some embodiments, the olfactory stimulation program includes performing at least two, three, four, or five steps daily. In some embodiments, the olfactory stimulation program includes performing two steps daily. In one embodiment, the two steps utilize one or more of the same aromas.

[0048] In some embodiments, the olfactory stimulation protocol includes releasing one or more aromas once daily. In some embodiments, the olfactory stimulation protocol includes a series of steps exposing the subject to different aromas. In some embodiments, the olfactory stimulation protocol includes a series of steps exposing the subject to the same aroma.

[0049] In some embodiments, the method includes an olfactory stimulation step of periodically applying an olfactory stimulation protocol. In some embodiments, the olfactory stimulation protocol includes releasing one or more aromas at least once a day. In some embodiments, the olfactory stimulation protocol includes releasing one or more aromas at least twice a day. In some embodiments, the olfactory stimulation protocol includes releasing one or more aromas daily.

[0050] The present invention also provides a method for improving cognitive function and / or memory in a subject requiring olfactory stimulation. In one embodiment, the method includes: a) an earlier step of exposing the subject to one or more aromas; and b) a subsequent step of exposing the subject to one or more aromas that are different from the one or more aromas in the earlier step, thereby improving the subject's cognitive function. Additionally, a method for improving the cognitive abilities of a subject requiring olfactory stimulation is provided. In one embodiment, the method includes exposing the subject to a variety of aromas during a treatment period, said treatment period comprising a series of exposures, at least two of which are groups of one or more different aromas.

[0051] A method for improving cognitive abilities through olfactory stimulation using a series of odorant exposure steps is also provided. In one embodiment, the method includes an earlier odorant exposure step, which includes exposing a subject to one or more odorants in a first group; and a subsequent odorant exposure step, which includes exposing the subject to one or more odorants in a second group, wherein the first and second groups do not have the same odorants. A method for improving cognitive function and / or memory through olfactory stimulation steps is also provided. In one embodiment, the method includes exposing a subject to one or more aromas in a first group; and exposing the subject to one or more aromas in a second group, wherein the first and second groups do not have the same aromas.

[0052] A method is also provided for improving cognitive function and / or memory by exposing a subject to a variety of aromas over a period of time. In one embodiment, the method includes exposing the subject to one or more aromas in a first group; and exposing the subject to one or more aromas in a second group, wherein the first group and the second group have different aromas.

[0053] A method for improving cognitive function and / or memory by treating a subject in need according to an olfactory stimulation protocol is also provided. In one embodiment, the method includes a series of steps, each step of which releases one or more aromas to the subject, with no two consecutive steps releasing the same aroma.

[0054] A method for improving cognitive function and / or memory by treating a subject in need according to an olfactory stimulation protocol is also provided. In one embodiment, the method includes alternating olfactory stimulation steps, each step releasing one or more aromas to the subject, with no two consecutive steps releasing the same aroma.

[0055] A method is also provided for improving cognitive function and / or memory by treating a subject in need according to an olfactory stimulation protocol. In one embodiment, the method includes performing an olfactory stimulation step daily, each step including releasing one or more aromas to the subject at least once, with no two consecutive olfactory stimulation steps releasing the same aroma. In one embodiment, at least one step includes releasing one or more aromas to the subject at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 times. In one embodiment, each step includes releasing one or more aromas to the subject at least 2, 3, 4, 5, 6, 7, 8, 9, or 10 times.

[0056] A method is also provided for improving cognitive function and / or memory by treating a subject in need according to an olfactory stimulation protocol. In one embodiment, the method includes: a) performing an olfactory stimulation cycle comprising a series of olfactory stimulation steps, performing only one olfactory stimulation step per day, and each step including releasing one or more aromas to the subject at least once; and b) repeating the olfactory stimulation cycle in a). In one embodiment, the olfactory stimulation cycle in a) is further included for repeating for a specified duration.

[0057] An olfactory stimulation toolkit is also provided. In one embodiment, the toolkit includes: a) an aroma releasing device suitable for releasing multiple aromas; and b) a schedule for releasing multiple aromas. In one embodiment, the schedule includes: (i) releasing one or more aromas from the aroma releasing device in an initial step on a first day; and (ii) releasing one or more aromas from the aroma releasing device in subsequent steps on a subsequent day, wherein the one or more aromas in the subsequent steps are different from the one or more aromas in the initial steps. In one embodiment, the schedule is provided in the specification.

[0058] In some embodiments, the multiple aromas are selected from one or more aroma categories chosen from the group consisting of floral, oriental, woody, aromatic, and fresh. In one embodiment, the multiple aromas are selected from one or more aroma categories chosen from the group consisting of floral, woody, and aromatic. In some embodiments, the multiple aromas are selected from one or more aroma categories chosen from the group consisting of fruity, floral, woody, resinous, and aromatic. In some embodiments, the multiple aromas are selected from the group consisting of lavender, citrus, jasmine, clove, mint, cinnamon, mint, clove, lemongrass, coffee, anise, basil, thyme, chamomile, rosemary, cucumber, coconut, fresh cotton, violet, vanilla, forest pine, pomegranate, pear, orange, apple, rosehip, saffron, sage, eucalyptus, frankincense, nutmeg, and sandalwood.

[0059] In some embodiments, the schedule includes steps performed at night. In some embodiments, the schedule includes steps performed during the day. In some embodiments, the schedule includes steps performed over periods of 2, 3, 4, 5, 6, 7, 8, 9, or 10 days. In some embodiments, the schedule includes steps performed over periods of 2 or more days. In some embodiments, the schedule includes steps performed over periods of at least 1, 2, 3, or 4 weeks. In some embodiments, the schedule includes steps performed over periods of at least 1, 2, 3, 4, 5, or 6 months. In some embodiments, the schedule includes steps performed over periods of approximately 3 months. In some embodiments, the schedule includes steps performed over periods of approximately 6 months. In some embodiments, the schedule includes steps performed as a series of stimulation cycles, each stimulation cycle containing at least two olfactory stimulation steps. In some embodiments, the schedule includes at least one stimulation cycle containing at least 3, 4, 5, 6, 7, 8, 9, or 10 steps. In some embodiments, the schedule includes repeating at least one stimulation cycle within a specified period. In some embodiments, the schedule includes a stimulation cycle of 6 steps. In some implementations, the timetable includes a 7-step stimulation cycle.

[0060] In some embodiments, at least one step of the timetable includes: a) continuously releasing at least one aroma during a first duration; and b) ceasing the release of at least one aroma during a second duration. In one embodiment, the first duration is about 5 minutes. In one embodiment, the second duration is about 1 minute. In one embodiment, the at least one step further includes repeating a) and b). In one embodiment, a) and b) are repeated within a specified release period. In one embodiment, the specified release period is about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In one embodiment, the specified exposure period is as long as about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes.

[0061] In some embodiments, each step of the timetable includes: a) continuously releasing at least one aroma during a first duration; and b) ceasing the release of at least one aroma during a second duration.

[0062] In some implementations, the aroma-releasing device includes an atomizer or a diffuser.

[0063] In some embodiments, the aroma releasing device is adapted to release a variety of aromas by means of ventilation, heating, humidification, vaporization, atomization, or gas atomization, or a combination thereof. In some embodiments, the aroma releasing device comprises at least one candle, tea lamp diffuser, atomizing diffuser, room sprayer, evaporative diffuser, evaporative fan diffuser, vaporizing diffuser, wearable evaporative diffuser, ultrasonic diffuser, thermal evaporative diffuser, evaporative pad diffuser, cream, wick, open-cell fragrance container, or any combination thereof.

[0064] In some embodiments, at least one step of the timetable releases an aroma. In some embodiments, each step of the timetable releases an aroma. In some embodiments, at least one step of the timetable releases multiple aromas. In some embodiments, each step of the timetable releases multiple aromas. In some embodiments, each step of the timetable releases one or more aromas for at least about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In some embodiments, each step of the timetable releases one or more aromas for up to about 5 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, about 30 minutes, about 35 minutes, about 40 minutes, about 45 minutes, about 50 minutes, about 55 minutes, or about 60 minutes. In some embodiments, each step of the timetable releases one or more aromas for about 30 minutes. In some embodiments, the timetable includes releasing one or more aromas at least 2, 3, 4, or 5 times per day. In some implementations, the schedule includes releasing one or more fragrances twice a day.

[0065] In one embodiment, the same one or more aromas are released on a given day. In some embodiments, the schedule includes releasing one or more aromas once a day. In some embodiments, the schedule includes consecutive steps of releasing different aromas. In some embodiments, the schedule includes consecutive steps of releasing the same aroma. In some embodiments, the schedule includes periodic application of olfactory stimulation steps. In some embodiments, the schedule includes releasing one or more aromas at least once a day. In some embodiments, the schedule includes releasing one or more aromas at least twice a day. In some embodiments, the schedule includes releasing one or more aromas daily. Attached Figure Description

[0066] These and other aspects, features, and advantages of the present invention will become apparent and elucidated from the following description of embodiments of the invention, with reference to the accompanying drawings, in which:

[0067] Figure 1 is a graph showing the decline in cognitive function over time;

[0068] Figure 2 This is a timeline showing the implementation schemes of the method of the present invention;

[0069] Figure 3 This is a timeline illustrating an embodiment of the daily schedule of the method of the present invention;

[0070] Figure 4It is a diagram showing the human sleep cycle;

[0071] Figure 5 is a diagram of the scent wheel;

[0072] Figure 6 is a diagram illustrating an embodiment of the aroma alternation of the present invention;

[0073] Figure 7 is a diagram showing Henning's Prism;

[0074] Figure 8 This is a diagram of the fragrance wheel formed from one side of the Henning prism;

[0075] Figure 9 This is a perspective view of an embodiment of the device of the present invention;

[0076] Figure 10 yes Figure 9 A cross-sectional view of an embodiment of the device;

[0077] Figure 11 This is a perspective view of an embodiment of the box of the present invention;

[0078] Figure 12 yes Figure 11 A cross-sectional view of the box;

[0079] Figure 13 This is a front view of an embodiment of the fragrance cushion packaging of the present invention;

[0080] Figure 14 This is a perspective view of an embodiment of the gel sheet of the present invention; and,

[0081] Figure 15 This is a side view of an embodiment of the CPAP mask of the present invention;

[0082] Figure 16 This is a graph illustrating the changes in the Stroop fraction using the present invention;

[0083] Figure 17 This is a graph showing the changes in Ray's auditory-verbal learning test scores using the present invention;

[0084] Figure 18 This is a graph showing the variation of scores in the Wechsler Adult Intelligence Scale-III alphanumeric sorting using the present invention; and,

[0085] Figure 19 This is a graph showing the variation of the digital inverted score in the Wechsler Adult Intelligence Scale-III using the present invention. Detailed Implementation

[0086] Specific embodiments of the invention will now be described with reference to the accompanying drawings. However, the invention may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art. The terminology used in the detailed description of the embodiments shown in the drawings is not intended to limit the invention. In the drawings, the same numerals refer to the same elements.

[0087] Definitions

[0088] Unless otherwise specified, all scientific and technical terms used in this application have the meanings commonly used in the art. As used in this application, the following words or phrases have specific meanings.

[0089] As used in this article, “releasing” a fragrance to a subject, or “exposing” a subject to a fragrance, means presenting the fragrance to the subject’s environment in a way that is sufficient to stimulate the subject’s olfactory system.

[0090] As used herein, “reduction” or “increase” means a decrease or increase in a detectable or noticeable amount, respectively. In some embodiments, one of the assessment tools described herein is used to measure this decrease or increase. In some embodiments, decrease or increase indicates a “significant difference”.

[0091] As used in this article, “improvement” means a state that results in improvement, such as alleviating the symptoms of a bad condition or enhancing a desired state, such as memory.

[0092] As used herein, "significant difference" or "significant disparity" means a difference that is detectable in a manner that is reasonably reliable to a person skilled in the art, such as a statistically significant difference, or, in this case, a sufficiently large difference that can be detected with a reasonable level of reliability. In one instance, a 10% increase or decrease relative to a reference value is a significant difference. In other instances, an increase or decrease of 20%, 30%, 40%, or 50% relative to a reference value is considered a significant difference. In yet another instance, a doubling of the reference value is considered significant. The reference value can be, for example, an untreated subject, or the baseline (pre-treatment) value of the same subject.

[0093] As used herein, ranges and quantities can be expressed as “about” a specific value or range. “About” also includes precise quantities. Therefore, “about 5 minutes” means “about 5 minutes” and also “5 minutes”. Typically, the term “about” includes quantities ranging from less than 10% to more than 10% of a specific value or range. For example, “about 10 minutes” means “from 9 minutes to 11 minutes”.

[0094] As used herein, unless otherwise expressly stated, “an” or “a” means at least one.

[0095] Environmental enrichment

[0096] In animal models of more than a dozen human neurological disorders, environmental enrichment has been shown to alleviate human-like symptoms, including age-related cognitive decline (Patel et al., 2012; Segovia et al., 2006; Valero et al., 2007) and cognitive decline in Alzheimer's disease (Arendash et al., 2004; Arranz et al., 2011; Basak et al., 2008; Berardi et al., 2007; Costa et al., 2007; Jankowsky et al., 2015; Lazarov et al., 2005; Polito et al., 2014). In humans, environmental enrichment, including exercise, computer gaming, social activities, and nutrition, has been shown to reduce the risk of cognitive decline in aging and disease (Herzog et al., 2008; Kirk-Sanchez and McGough, 2014; Klimova, 2016; Williams and Kemper, 2010). However, it is difficult to prove that cognitive decline is reversible, and when such improvements are present, the effects are often minimal (Herzog et al., 2008; Rodakowski et al., 2015). Furthermore, it has been shown to be difficult to get people to adhere to interventions such as regular physical exercise routines (Williams et al., 2007).

[0097] The olfactory system undergoes significant degeneration in older adults, with 18% experiencing olfactory dysfunction and 46% of those over 80 years of age having very limited olfactory capacity (Doty et al., 1984; Hoffman et al., 1998; Liu et al., 2016; Murphy et al., 2002; Pinto et al., 2015; Toussaint et al., 2015). This decline begins concurrently with the cognitive decline observed in older adults (Park et al., 2003; Salthouse, 2009). The decline in cognitive function with age is illustrated in Figure 1, which shows the initial decline around age 60, continuing with increasing individual age. Inductive reasoning, spatial orientation, perceptual speed, numerical ability, verbal ability, and verbal memory are all affected. Unlike other sensory systems, the olfactory system projects directly to cognitive areas, and the loss or damage of the olfactory system results in a significant loss of volume in these cognitive areas in humans of any age (Bitter et al., 2010a; 2010b; 2011; Yao et al., 2014). Normal human aging is accompanied by a decline in olfactory capacity (Dong et al., 2017; Hoffman et al., 2016; Seubert et al., 2017) and a decline in olfactory projection sites (which include cognitive areas of the brain) (Kollndorfer et al., 2015; Segura et al., 2013). Furthermore, olfactory function decline predicts an increased risk of mild cognitive impairment (MCI) and that individuals with MCI will continue to develop Alzheimer's disease (Adams et al., 2017; Devanand et al., 2000; Lafaille-Magnan et al., 2017; Peter et al., 2003; Roberts et al., 2016; Schubert et al., 2008; 2017; Swan and Carmelli, 2002). Notably, olfactory function also predicts all-cause mortality in older adults (Gopinath et al., 2011; Pinto et al., 2014).

[0098] Loss of olfaction occurs before or simultaneously with the onset of various cognitive disorders, such as Alzheimer's disease, Parkinson's disease, Lewy body dementia, frontotemporal dementia, Creutzfeldt-Jakob disease, mild cognitive impairment, and schizophrenia (Conti et al., 2013; Devanand et al., 2000; Devanand et al., 2010; Doty et al., 1988; Li et al., 2010; Luzzi et al., 2007; Meusel et al., 2010; Nguyen et al., 2010; Parrao et al., 2012; Ponson et al., 2004; Ross et al., 2006; Tabaton et al., 2004; Wattendorf et al., 2009). Given the wide variety of etiologies of these cognitive disorders, this increases the likelihood that loss of olfactory stimulation leads to cognitive decline in each of these disorders.

[0099] In humans experiencing loss of smell due to various issues such as post-infectious olfactory dysfunction, head trauma, Parkinson's disease, and aging, increased olfactory experience has been shown to improve olfactory recognition, olfactory discrimination, and to a lesser extent, the olfactory threshold (Damm et al., 2014; Geiβler et al., 2014; Haehner et al., 2013; Hummel et al., 2009; Konstantinidis et al., 2013; Patel et al., 2017). These results were obtained through exposure to four odorants derived from each of four odor groups: resinous (eucalyptus), floral (rose), fruity (lemon), and aromatic (clove). Further improvements in olfactory capacity were observed with increasing exposure duration, concentration, and number of odorants (Altundag et al., 2015; Damm et al., 2014; Konstantinidis et al., 2016). In addition to improved sensory abilities, older adults exposed to increased olfactory stimulation have also shown improvements in cognitive function (such as enhanced verbal fluency), reduced depressive symptoms, and improved well-being (Wegener et al., 2018). Olfactory stimulation also reduced falls in older adults (Sakamoto et al., 2012).

[0100] Individuals with autism exhibit olfactory dysfunction, displaying abnormal sniff responses to both dissimilar odors (Rozenkrantz et al., 2015) and social odors (Endevelt-Shapira et al., 2018). They also exhibit abnormal olfactory responses (Boudjarane et al., 2017; Tonacci et al., 2017). When diverse autistic rodent models are placed in enriched environments, their human-like symptoms of the disorder are alleviated (Kerr et al., 2010; Kondo et al., 2008; Lacaria et al., 2012; Lonetti et al., 2010; Nag et al., 2009; Restio et al., 2005; Reynolds et al., 2013; Schneider & Przewlocki, 2005; Schneider et al., 2006).

[0101] Environmental enrichment, including olfactory stimulation combined with tactile stimulation, has been successfully used to treat children with classic autism (Woo and Leon, 2013; Woo et al., 2015). In two randomized clinical trials, parents delivered novel multisensory stimuli, characterized by olfactory stimulation, for 15–30 minutes each morning and evening for six months. As measured by the Subjective Autism Scale for Children, 42% of enriched children showed significant improvement in symptoms, compared to 7% in standard care controls who showed such improvement. Enriched children showed an IQ improvement of more than 8 points compared to controls who showed an improvement of approximately one point. The Short Sensory Profile showed an improvement of 11 points in enriched children, compared to approximately one point in controls. As measured by the objective Reynell Developmental Language Scale, receptive language improvement was more than 200% in enriched children with autism, compared to less than 20% in controls. Ultimately, after 6 months, using the objective Autism Diagnostic Observation Schedule, 21% of children with autism were considered to have lost their diagnosis, while the control group did not reach this level of improvement.

[0102] A review of results from over 1,000 children across the entire autism spectrum who received this treatment at home (Aronoff et al., 2016) showed that these children outperformed children in university clinical trials, with an effect size of 1.85. Not only were core autism symptoms improved, but comorbid symptoms present in almost every child with the condition also improved. These comorbid symptoms included sensory processing, self-awareness, communication, mood, sleep, eating, motor skills, learning, memory, anxiety, and attention span. The treatment had a similar effect across the entire autism spectrum, with equal improvement in both girls and boys, and was effective across all tested ages (2–18 years). Dosage / response results were also observed for parental compliance and symptom improvement in their children.

[0103] Time table

[0104] Now refer to the attached diagram, and first refer to... Figure 2 and Figure 3 The diagram illustrates a general description of method 10 of the present invention. Method 10 generally involves subjecting a treatment recipient to a daily schedule 20 consisting of aroma time intervals 30 separated by discontinuities 40. Depending on the treatment recipient and desired results, the daily schedule may be applied for several days, weeks, months, or years. Because treatment method 10 has no negative side effects or disadvantages other than the potential expenditure of fragrance, benefits can be found in continuing the schedule 20 indefinitely.

[0105] Figure 3 A non-limiting example of a daily schedule 20 initiated at bedtime B is provided. Bedtime is chosen because it allows for easy delivery of treatment to people who are not moving, and for effective delivery of aroma to people in relatively small, enclosed rooms, such as bedrooms. However, it should be noted that the effectiveness of treatment may not be reduced if it is delivered during the day, such as to people sitting in front of a computer, driving a vehicle, or otherwise stationary relative to the delivery device; or if the delivery device moves with the recipient throughout their daily activities, such as in the case of wearable devices.

[0106] exist Figure 3 In this implementation, the recipient activates an aroma delivery device (detailed below) that includes a timer configured to deliver various scents at predetermined time intervals. In this example, the time interval 30 is approximately 30 minutes long and is separated by pauses 40 lasting 5 minutes. However, it should be understood that these intervals and pauses are merely non-limiting examples and can vary based on recipient preferences, subjective outcomes, physician recommendations based on empirical evidence, sleep duration, etc. Starting with a 30-minute time interval with 5-minute pauses yielded good results.

[0107] The daily schedule 20 begins each day with a start event. For recipients with regular daily routines, the start event can be a set time of day, rather than starting at bedtime. For example, in this implementation, the first time interval 30 of the daily schedule 20 could begin at midnight and last until 12:30 AM. Thus, the first interruption 40 spans from 12:30 AM to 12:35 AM, and the second time interval 30 begins at 12:35 AM and lasts until 1:05 AM. These time intervals 30 and interruptions repeat this pattern until a predetermined number N of time intervals 30 and interruptions 40 occur. Like the duration of the time intervals 30, the number N can vary based on the recipient's typically achieved sleep duration and subjective or objective outcomes. Typically, N should be at least 3 for optimal results.

[0108] In another implementation, the initiation event may be related to the recipient's sleep cycle. Figure 4 This is a diagram of the 50-stage sleep cycle in humans. The 50-stage sleep cycle consists of stages that repeat every 90 to 110 minutes. One model divides the sleep cycle into five stages: Stage 1 is light sleep, characterized by reduced activity of muscles, brain, and eyes; Stage 2 involves a slowing of heart rate and breathing patterns, as well as a slight decrease in body temperature; Stage 3 is the beginning of deep sleep and involves very slow delta waves produced by the brain; Stage 4 is very deep sleep, characterized by rhythmic breathing, limited muscle activity, and continuous delta wave production; and Stage 5 is called the REM (Rapid Eye Movement) stage. This is the dreaming stage, characterized by increased blood pressure, heart rate, respiratory rate, and rapid eye movements.

[0109] See again Figure 4 It shows that the sleep cycle begins in stage one and progresses rapidly to stage four within the first hour of falling asleep. About an hour later, when a person enters REM sleep (which typically lasts only about 5 minutes), heart rate, blood pressure, and respiratory rate increase rapidly. After REM sleep, the cycle repeats to some extent.

[0110] It is worth noting that throughout the night, the degree to which sleepers enter deep sleep decreases. For example, as Figure 4 As shown in the diagram, stage four was barely reached during the second cycle. The second cycle also ended with a 10-minute REM sleep phase instead of 5 minutes. The third cycle entered only stage two sleep, followed by a 15-minute REM sleep phase. The fourth cycle also entered only stage two sleep, followed by a 30-60 minute REM sleep phase.

[0111] There is still much to learn about the human sleep cycle. Scientists often believe that experiences and lessons are transformed into long-term memories during sleep, and that REM sleep plays a crucial role in acquiring learning material—both declarative and procedural memory (two forms of recent transfer). Researchers have recently begun to hypothesize that deep restorative sleep (also known as "slow-wave sleep (SWS)") plays a significant role in declarative memory by processing and consolidating newly acquired information.

[0112] With this in mind, one aspect of the invention includes a sleep stage tracking system, such as a heart rate monitor, a respiration monitor, a blood pressure monitor, an electroencephalogram (EEG) sensor, or any combination thereof. The sleep stage tracking system is used in conjunction with an aroma delivery schedule to ensure that intermittent time intervals (slots between aroma delivery intervals) occur during sleep stages with poor efficacy and that aroma delivery intervals occur during sleep stages with maximum efficacy. The therapeutic efficacy of the olfactory stimulation therapy of the present invention may vary depending on the recipient's sleep stage. For example, it may be determined that treatment delivered during stages three and four is ineffective, while treatment delivered during REM sleep is most effective across all stages.

[0113] Assuming that delivering the aroma at a point in the sleep cycle that is not optimal for distant migration might not reduce effectiveness, the benefit of tracking the sleep cycle might simply be avoiding interruptions during the peak of the distant migration effect. For example, if REM sleep is determined to be the optimal phase of the sleep cycle for the distant migration effect, then avoiding interruptions during the REM phase, especially the first two or three REM phases that last only 5–15 minutes, could be beneficial.

[0114] Similarly, if it is determined that stage four is the most beneficial time to apply olfactory stimulation, it is important to ensure that a 30-minute interval is scheduled between the first two sleep cycles, as the first two cycles are usually the only cycles that lead into stage four.

[0115] One embodiment of the method of the present invention provides time intervals 30 consistent with the sleep cycle by using monitoring. Because sleep cycles are consistent with changes in biological factors such as blood pressure, heart rate, respiratory rate, brain wave activity, and eye movements, those skilled in the art will recognize that many techniques exist for monitoring individual sleep stages. Therefore, the duration of the time intervals 30 and the duration of the interruptions 40 can be selected to synchronize with the sleep cycle. In this embodiment, depending on the recipient's sleep duration, there may be as few as three time intervals or as many as six or seven time intervals.

[0116] One implementation of this synchronization method involves recording the recipient's sleep patterns over several days to establish a typical pattern. Delivery devices are then scheduled to operate on a near-synchronized timetable. Under this method, the recipient does not need to use monitoring devices unless recalibration is required.

[0117] Another implementation of this synchronization method involves continuously monitoring one or more of the aforementioned biological factors. For example, heart rate monitors come in many common forms, including but not limited to optical wearable devices, chest straps, airbed pulse detectors, etc. Continuous monitoring of biological factors is performed, and sleep cycles are determined based on the data collected. The device then activates and deactivates various aromas according to a schedule created based on the data. Therefore, the schedule may vary slightly from evening to night. This method may be best suited for recipients whose daily lives have changed.

[0118] Alternation

[0119] One aspect of the invention is that the aroma delivered to the recipient is novel. This does not mean that the recipient is completely unfamiliar with the aroma throughout his or her life, but simply that the aroma changes at each time interval and is not reintroduced within a predetermined number of time intervals. In one embodiment, at least seven different aromas are used, and no aroma is repeated until the other six aromas have been used. In other embodiments, a large number of aromas are used, making it unlikely that an aroma will be used twice throughout the treatment.

[0120] As a general guideline, it is believed that the newer the aroma, the greater its impact. Additionally, it is believed that within a specific daily schedule, consecutive aromas should be as different as possible. To achieve this, one implementation provides an alternation that avoids placing two aromatic scents from the same aroma group adjacent to each other.

[0121] Scents are sometimes categorized into scent groups, often referred to as scent wheels or scent charts. Many different scent charts exist. One widely used chart, used only as an example in this article, was developed by perfume taxonomist Michael Edwards in 1992 and has been revised several times since. The 2010 version of Michael Edwards' scent wheel is shown below. Figure 4 The references provided, and published in Michael Edwards & Co.'s Fragrances of the World in 2011, are incorporated herein by reference.

[0122] As shown in Figure 5, there are four main fragrance families: floral, oriental, woody, and fresh. These are divided into subgroups and arranged to show their relationships to each other. For example, the floral family is divided into floral, soft floral, and oriental floral. The oriental family is divided into soft oriental, oriental, and oriental woody. The oriental floral subgroup from the oriental floral family is arranged next to the soft oriental subgroup from the oriental family because these two are most similar, even though they belong to different families.

[0123] The aroma wheel in Figure 5 is useful because further aroma differences are easily visualized through their corresponding proximity on the wheel. For example, the aromas of the mossy-woody subgroup are found to contrast with those of the floral subgroup. Thus, it is easy to assess how the brain will process amber as very different from the aroma of fresh-cut flowers.

[0124] When creating the rotation, the aroma wheel in Figure 5 can be used to establish guidelines for aroma varieties. For example, a spacing of 1-5 subgroups between consecutive aromas can maximize the effectiveness of the olfactory stimulation schedule 20. Similarly, it can be determined that at least one aroma from each of the four families should be represented in a single daily schedule 20.

[0125] Figure 6 provides an exemplary cycle 60, in which at least one subgroup separates consecutive time intervals 30, and all four families are represented on the seven time intervals 30 of the time schedule 20.

[0126] Figure 7 provides another example of a fragrance diagram developed by the German psychologist Hans Henning in 1916. Henning H (1916) Der Geruch. Leipzig, Germany. The diagram in Figure 7 is called the Henning Prism and is a three-dimensional prism consisting of three rectangular faces, each of which can be used as a fragrance wheel. The corners of the prism include fragrance families: aromatic (floral or floral), ethereal (fruity), rotten, resinous, burnt, and spicy. Each face shares two families with its adjacent faces. Thus, one face of the prism includes the following families: floral, fruity, spicy, and resinous. Another face includes the following families: floral, spicy, burnt, and rotten. The third face includes the following families: burnt, rotten, fruity, and resinous. Because the rotten and burnt families are generally not preferred, it is assumed that... Figure 8 The face shown is preferred. Figure 8 This approach was adopted, and a wheel was formed that included subgroups between families.

[0127] Intensity

[0128] The intensity or strength of the aromatic scent produced during treatment must be strong enough to affect the recipient, but not so strong as to leave a lingering odor on furniture or other objects in the room where the treatment is administered. Ideally, the aroma delivered during each time interval 30 will dissipate during the interval 40 between the time intervals. Interestingly, since the recipient is not affected by the aroma while sleeping, there is no need to worry about the aroma being too strong to disrupt sleep patterns. However, as discussed above, loss of smell occurs with age and should be aggravated with treatment. Therefore, one embodiment of the invention is to adjust the intensity level to a level that is easily detectable by the recipient without being excessively strong before the treatment procedure.

[0129] Another embodiment of the invention includes an apparatus that allows fragrances to be mixed by simultaneously “playing” two or more boxes. The apparatus also allows the intensity of each fragrance box to be adjusted by increasing or decreasing the airflow through the boxes. In this way, the “recipe” can be changed not only by adjusting the box being played, but also by adjusting the intensity of each box being played. For example, if the “recipe” involves a mixture of cherry and vanilla, the cherry box can be played at 50% intensity, while the vanilla box can be played at 10% intensity. For example, if vanilla is played at 50% and cherry at 10%, this produces different aromas.

[0130] Device

[0131] Various devices are envisioned for use in practicing method 10 of the present invention. These devices can generally be divided into two categories – forced ventilation devices and evaporation devices. Forced ventilation devices typically include one or more aroma cartridges coupled to a machine that pumps air through the cartridges via one or more fans, bellows, turbines, etc., preferably at a selectable rate so that the intensity can be varied. Some embodiments include multiple cartridges on a selectable turntable that plays one cartridge at a time. Other devices include multiple cartridge coupling assemblies or “play heads” to allow cartridges to be played simultaneously.

[0132] The evaporation device involves aroma boxes, pads, or gels contained within a dispensing device, or may be layered such that, once opened, the exposed layer with the first aroma begins to evaporate, thereby releasing the first aroma. The aroma layers may be separated by odorless layers to provide an interruption 40 between aroma time intervals 30. The dispensing device may have a mechanized lid for selectively covering and uncovering the aroma boxes, or may have a heater associated with each aroma box that raises the temperature of the gel to a level that causes evaporation.

[0133] Now for reference Figure 9The image illustrates a first embodiment of the device 100 of the present invention. Device 100 is a forced-ventilation device housing four boxes 102, 104, 106, and 108. Each box may be a disposable device that allows airflow to diffuse fragrance. Alternatively, for ecological and cost considerations, the boxes may be refillable and reusable. Further details regarding the individual boxes are provided below.

[0134] refer to Figure 9 and Figure 10 An embodiment of device 100 includes a housing 110 having cavities 112, 114, 116, and 118, the cavities being sized and shaped to accommodate boxes 102, 104, 106, and 108, respectively. Each cavity 112, 114, 116, and 118 may be equipped with retractable lids 122, 124, 126, and 128, respectively, to preserve unused boxes and prevent the fragrance from escaping.

[0135] It is conceivable that each box and its corresponding compartment have a unique shape corresponding to a fragrance family. In this way, the recipient is required to place the box belonging to each fragrance family into device 100. In examples of device 100, the chosen shapes for boxes 102, 104, 106, and 108 are circular, square, triangular, and elliptical. Alternatively, each box can be coded, and each compartment can be equipped with a code reader, allowing device 100 to know which fragrance is inserted into each compartment.

[0136] The casing has a vent 110 formed in one wall through which the fragrance from the box is released. A side wall was chosen because most users will place the device 100 on a bedside table. The vent 110 can then be positioned so that it faces the recipient.

[0137] Internally, the device includes one or more fans 130 located below the cavity. The fans 130 are powered by motors 132 and are connected to the motors via shafts 134. A control panel 140 drives the logic for activating and deactivating each motor, as well as the logic functions discussed in detail below. In an embodiment with one fan, the airflow through the individual boxes is controlled by covers 122, 124, 126, and 128.

[0138] The device 100 is shown drawing air downwards through the box and into the central outer shell cavity 120. The air is forced out through vents 110, which are the only outlets for the unused cavities, given that the lids are closed and fans operate on each cavity with its lid open. This design allows the central outer shell cavity 120 to be used as a mixing chamber when more than one fragrance box is in use simultaneously. To protect electronic components, such as the motor 132 and control board 140, a barrier 121 is provided to isolate these components from the central outer shell cavity 120.

[0139] Those skilled in the art will recognize that the device 100 can be designed to reverse the airflow without departing from the spirit of the invention. Reversing the airflow can be achieved simply by reversing the direction of the fan 130. This design may be advantageous because the risk of residue accumulating in the cavity 120 is lower.

[0140] The control board 140 is electrically connected to the fan motor 132 and includes wireless connectivity technology, such as the ability to connect to electronic devices (such as smartphones or readers). The application downloadable to the device includes control logic that allows users to customize treatment schedules. Alternatively, physicians can create schedules 20 that can be downloaded by the user.

[0141] The application provides various controls and options that can be incorporated into a daily schedule, including aroma rotation, intensity, timing, reminders, aroma shuffle, etc. The application preferably tracks aroma rotation to assess which aromas may have been repeatedly played during the treatment procedure. These aromas can be marked by the application as losing novelty and thus removed from the rotation or mixed with other aromas the next time they are used.

[0142] The application can wirelessly connect to the various biometric sensors listed above, enabling the schedule to be dynamically timed. For example, a heart rate monitor can be worn when the user goes to bed. As discussed above, the activation of the heart rate monitor is sensed by the application, and the application begins to monitor the user's sleep stages to determine the timing of the daily schedule 20.

[0143] Alternatively, if a biometric sensor is not used, the handheld electronic device itself can be used by the control panel to indicate the start of the daily schedule 20. For example, device 100 may include a USB charging port 111 connected to the control panel. Users can use this USB port to charge their mobile phones at night. Inserting a mobile phone into device 100 can be used as an indication that the daily schedule 20 should begin. Ease of use is maximized when daily distractions are minimized, as most people are accustomed to charging their smartphones at night.

[0144] The control panel 140 is also used to track the use of the boxes. Depending on the box's structure, the application can be used to provide the user with instructions on when a specific box needs to be replaced.

[0145] Figure 11An embodiment of the box 102 of the present invention is shown. This embodiment is a disposable embodiment and includes a housing 150 having a top 152 and a bottom 154. The top 152 and bottom 154 are ventilated to allow air to pass through. The box 102 will be accompanied by a removable film (not shown) covering the top 152 and bottom 154 until the box is ready to be used, thereby preserving the odorant contained therein.

[0146] Figure 12 A cross-sectional view of the box 102 is shown, which allows the view of the absorbent odorant pad 156. The pad 156 may be formed as a wad, such as a cotton ball or polyester fiber filler, and should be loosely packed to allow air to flow through it. Alternatively, the pad 156 may be slightly smaller than the interior of the box, allowing air to circulate around the pad 156. In this embodiment, a denser wadding material may be used, which may retain more odorant than embodiments requiring airflow through the pad 156.

[0147] exist Figure 12 In one embodiment of the box 150, the top 152 is removable and replaceable. This embodiment reduces plastic waste and cost. The odorant pad 156 can be offered or sold individually or in a package containing multiple packages, instead of replacing the entire box. Figure 10 The packaging 160 of pad 156 is shown, which is arranged such that each row 162 represents a different fragrance family, and each column 164 thus represents a different day of the week.

[0148] As described above, one aspect of the invention provides an evaporation device relating to an aroma box, pad, or gel contained within a dispensing device, or which may be layered such that, once opened, the exposed layer having a first aroma begins to evaporate, thereby releasing the first aroma. The aroma layer may be separated by an odorless layer to provide an interruption 40 between aroma time intervals 30.

[0149] Figure 14 An embodiment 180 of an evaporation apparatus is shown. This apparatus comprises a gel sheet consisting of a plurality of odorant layers 182 separated by an odorless layer 184. In this example, there are six odorant layers 182 separated by five odorless layers. The odorant layers are designed to evaporate at a desired rate, such that each odorant layer represents a time interval 30. The odorless layers are designed to evaporate at a desired rate, such that each odorless layer represents an interval 40. During manufacturing, the desired timing of each layer can be controlled by the layer thickness. The odorless layer 184 is then thinner than the odorant layers 182. The gel sheet 180 is disposed on a substrate 186 such that only the top layer evaporates.

[0150] The gel sheet 180 provides the basis for the various delivery mechanisms covered by this invention. Additionally, it is conceivable that the gel sheet 180 could be shaped such that it can be removed from the substrate 186 and applied directly to the recipient's upper lip or chin like a pat. In this embodiment, it may be desirable to include an odorless layer 184 as a top layer, allowing the user a few minutes to fall asleep before experiencing the scented agent.

[0151] Figure 15 A slightly modified CPAP mask 200 is shown to accommodate a gel sheet 180. The mask 200 has a nozzle 206 connected to a gas delivery tube (not shown) of a typical CPAP machine. The nozzle 206 includes a compartment 202 with a cover 204 that can be opened to allow the gel sheet 180 to be placed therein. The sheet 180 is positioned such that a substrate 186 is on top. During use, gas flowing from the CPAP machine through the nozzle 206 passes beneath the bottom exposed layer of the sheet 180 and is inhaled by the user. In the morning, the empty substrate 186 is discarded.

[0152] Other devices utilizing the gel sheet 180 are envisioned, including but not limited to insertable air purifiers, non-CPAP masks, pendants and other wearable devices, nasal plugs, heat-activated devices, diffusers, etc.

[0153] Example

[0154] The following embodiments are provided to illustrate the present invention and to assist those skilled in the art in preparing and using it. These embodiments are not intended to limit the scope of the invention in any way.

[0155] Example 1 : Environmental enrichment of a classroom in a city

[0156] This example demonstrates that using multiple olfactory stimuli in school-aged children enhances brain responses. Children in urban schools were exposed to olfactory stimulation for 30 minutes daily in classrooms using essential oil scents, rotating through five different scents each day (n=25 children), for three months. A control group of 23 children received no such stimulation. Stroop test scores were monitored during this period. This test assesses cognitive processing speed, attention, and executive function. Furthermore, the Stroop test showed strong correlations with IQ, general behavior, and school performance (Imbrosciano and Berlach, 2005).

[0157] like Figure 16As shown, in this test, the improvement observed in children with enhanced olfactory abilities was more than 10 times greater than that observed in the control group. All classes were taught by the same teachers, so this phenomenon is unlikely to be due to differences in the teachers' teaching abilities. Although many attempts have been made to improve cognitive outcomes in elementary school children, such attempts have generally been unsuccessful in improving their cognitive abilities.

[0158] Example 2: Environmental enrichment of the elderly

[0159] This example demonstrates the positive effects of olfactory stimulation on the cognitive abilities of older adults. Older adults were tested using standard, validated cognitive assessments and then retested after receiving daily olfactory stimulation. The stimulated older adults showed improvements of 181%, 268%, and 1,258% compared to the control group.

[0160] A set of pleasant aromas were provided to older adults, who were asked to expose themselves to the aromas for 30 minutes each morning and 30 minutes each evening for six months using a provided nebulizer. Forty older adults (60-75 years old) either provided themselves with the patterned olfactory stimulation at home or were assigned to a group that did not experience the increased olfactory stimulation. Three cognitive tests were administered at the start of the trial and then repeated after six months.

[0161] In a test demonstrating verbal learning and memory (Ray's auditory-verbal learning), older adults with enhanced olfactory function performed 181% better than the control group. Figure 17 In tests of sequential processing, mental control, attention, concentration, memory span, and short-term auditory memory (WAIS III alphanumeric sorting), the enriched group had a 268% advantage over the control group. Figure 18 Finally, in tests of rote learning and memory, attention, encoding and auditory processing, working memory, information transfer, mental control, and visuospatial imaging (WAIS III digit reversal), the enriched group performed 1,258% better than the control group. Figure 19 ).

[0162] These cognitive benefits are about one to two orders of magnitude better than computer games, direct brain stimulation, exercise, or social interaction (Clememson and Stark, 2015; Ezzyat et al., 2018; Hertzog et al., 2009; Kirk-Sanchez and McGough, 2014; Kucewisc et al., 2018).

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[0250] Although the invention has been described with reference to specific embodiments and applications, those skilled in the art can produce other embodiments and modifications based on this teaching without departing from the spirit or scope of the claimed invention. Therefore, it should be understood that the accompanying drawings and descriptions are provided by way of example to facilitate understanding of the invention and should not be construed as limiting the scope of the invention.

Claims

1. A system for improving the long-transfer effect of human cognition, comprising: A module for creating a daily treatment schedule that includes multiple time intervals separated by interruptions; A module for inputting the daily treatment schedule into the aroma delivery device, such that the device delivers one of a variety of aromas during each time interval and stops delivering the aroma at the end of the time interval; The aromas delivered during consecutive time intervals are sufficiently distinct from each other to be distinguishable by the human being. During the daily treatment schedule, it is ensured that no aroma is repeated; The daily treatment schedule is repeated daily for a predetermined treatment duration, and two or more of the various aromas are used in the repeated days. The various aromas mentioned therein are selected from one or more aroma categories chosen from the group consisting of fruity, floral, oriental, woody, and fresh aromas.

2. The system of claim 1, wherein the plurality of aromas are derived from the resinous aroma category.

3. The system of claim 1, wherein the plurality of aromas are derived from the aromatic aroma category.

4. The system of claim 1, wherein establishing the daily treatment schedule comprising the plurality of time intervals separated by discontinuities includes: Arrange multiple 30-minute time intervals separated by 5-minute intervals.

5. The system of claim 1, wherein establishing the daily treatment schedule comprising the plurality of time intervals separated by discontinuities includes: Arrange at least three time intervals separated by discontinuities.

6. The system of claim 1, wherein inputting the daily treatment schedule into the aroma delivery device comprises: The device is wirelessly connected to a handheld electronic device, which has an application that allows the schedule to be uploaded to the aroma delivery device.

7. The system of claim 1, wherein inputting the daily treatment schedule into the aroma delivery device includes setting a start time.

8. The system of claim 1, wherein establishing a daily treatment schedule includes making the initiation of the schedule based on activities indicating that the user will go to bed.

9. The system of claim 8, wherein the activity includes inserting a handheld device into the aroma delivery device.

10. The system of claim 8, wherein the activity includes a biometric sensor wirelessly connected to a handheld device to provide data indicating that the user has begun a sleep cycle.

11. An apparatus for use in the system of claim 1, comprising: A housing that defines a cavity, the cavity being sized to receive a removable fragrance box; Ventilation opening; A fan, which is adjacent to the cavity and is capable of moving air through the cavity; An electric motor, which is associated with the fan; A control board that controls the motor according to a daily schedule comprising multiple time intervals separated by discontinuities, and initiates the daily schedule when an event begins; During the time interval, the fan is activated, causing air to be pushed through the vent and the cavity, thereby releasing the scent when the fragrance box is placed into the cavity.

12. The apparatus of claim 11, further comprising a control panel that controls the exposure of the aroma box to air from the fan.

13. The apparatus of claim 11, wherein the start event includes a time of day.

14. The apparatus of claim 11, wherein the start event includes data received from a biometric sensor indicating that the user has begun a sleep cycle.

15. The apparatus of claim 11, further comprising a personal electronic device wirelessly connected to the control panel, wherein the personal electronic device provides the daily schedule.

16. The apparatus of claim 15, wherein the start event is determined by the personal electronic device.

17. A system for delivering aromas that improves the long-distance transfer effect of human cognition, comprising: A module for creating timetables with multiple time intervals; A module that delivers aroma during each time interval; After the first time interval, each aroma is different from the aroma of the previous time interval; During the aforementioned time schedule, it is ensured that no aroma is repeated; The schedule is repeated daily for a predetermined duration, wherein two or more of the various fragrances are used on the repeated days.

18. The system of claim 17, wherein the duration of the time interval is up to 30 minutes.

19. The system of claim 17, wherein the timetable has three final time intervals.

20. The system of claim 17, further comprising activating the schedule when the user is asleep.

21. The system of claim 17, further comprising initiating the timetable using a wirelessly connected handheld device.

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