System of olfactory treatment based on sleep stage

Abstract

There is provided a system of providing therapeutic stimulation to a patient during sleep, the system comprising: a stimulator, configured to release one or more scents; a patient monitor, comprising at least one sensor configured to measure at least one physiological parameter or environmental parameter of the patient; and a controller, configured to: identify a sleep state of the patient, and responsive to, at least, the identified sleep state, provide a stimulus to the patient, the stimulus being based on, at least, an ordering of one or more scents, and a respective intensity and respective release pattern of each of one or more scents.

Description

[0001] SYSTEM OF OLFACTORY TREATMENT BASED ON SLEEP STAGE

[0002] FIELD AND BACKGROUND OF THE INVENTION

[0003] The present invention, in some embodiments thereof, relates to the field of olfactory treatment and / or evaluation and more particularly, but not exclusively, to a system and a method for providing olfactory treatment during sleep.

[0004] Background art includes a scientific publication “Sleep stage detection using only heart rate.” By Mitsukura, Yasue, et al. disclosing that “A new easy model for monitoring the sleep stages is built on only heart rate calculated by the electrocardiogram. This enabled us to easily assess the sleep quality based on five stages. This experiment included a total of 50 subjects. The overall accuracy in determining the five sleep stages was 66.0 percent. Four stages for sleep are identified accurately compared with other conventional methods. Despite there are no five sleep stage separation method using only heart rate, our method achieved the five separation for sleep with a relatively good accuracy. This study represents a great contribution to the field of sleep science. Because sleep stages can be recognized by the heart rate alone, sleep can be noninvasively assessed with any heart rate meter. This method will make it easier to determine sleep stages and diagnose sleep disorders”, (abstract).

[0005] Background art includes a scientific publication “Sleep classification from wrist-worn accelerometer data using random forests.” By Sundararajan, Kalaivani, et al. disclosing that “Accurate and low-cost sleep measurement tools are needed in both clinical and epidemiological research. To this end, wearable accelerometers are widely used as they are both low in price and provide reasonably accurate estimates of movement. Techniques to classify sleep from the high-resolution accelerometer data primarily rely on heuristic algorithms. In this paper, we explore the potential of detecting sleep using Random forests. Models were trained using data from three different studies where 134 adult participants (70 with sleep disorder and 64 good healthy sleepers) wore an accelerometer on their wrist during a one-night polysomnography recording in the clinic. The Random forests were able to distinguish sleepwake states with an Fl score of 73.93% on a previously unseen test set of 24 participants... These Random forest models have been made open-source to aid further research. In line with literature, sleep stage classification turned out to be difficult using only accelerometer data”, (abstract). Background art includes scientific publication “Information processing during sleep: the effect of olfactory stimuli on dream content and dream emotions.” By Schredl, Michael, et al. disclosing that “Research has shown that external stimuli presented during sleep can affect dream content, thus reflecting information processing of the sleeping brain. Olfactory stimuli should have a stronger effect on dream emotions because their processing is linked directly to the limbic system. Because selective olfactory stimulation does not increase arousal activity, intense olfactory stimulation is therefore a prime paradigmty for studying information processing during sleep. Fifteen healthy, normosmic volunteers were studied by intranasal chemosensory stimulation during rapid eye movement sleep based on air-dilution olfactometry. For olfactory stimulation, hydrogen sulphide (smell of rotten eggs) and phenyl ethyl alcohol (smell of roses) was used and compared with a control condition without stimulation. The olfactory stimuli affected significantly the emotional content of dreams: the positively toned stimulus yielded more positively toned dreams, whereas the negative stimulus was followed by more negatively toned dreams. Direct incorporations, i.e. the dreamer is smelling something, were not found. The findings indicate that information processing of olfactory stimuli is present in sleep and that the emotional tone of dreams can be influenced significantly depending upon the hedonic characteristic of the stimulus used. It would be interesting to conduct learning experiments (associating specific odours with declarative material) to study whether this declarative material is incorporated into subsequent dreams if the corresponding odour cue is presented during sleep. It would also be interesting to study the effect of positively toned olfactory stimuli on nightmares.”, (abstract).

[0006] Background art includes scientific publication “Automation of classification of sleep stages and estimation of sleep efficiency using actigraphy.” By Kim, Hyejin, Dongsin Kim, and Junhyoung Oh. et al. disclosing that “Our model demonstrated that automated sleep classification results could perfectly match the PSG results. Since models with acceleration features showed modest performance in differentiating some sleep stages, further research on acceleration features must be done. In addition, the sleep efficiency model demonstrated modest results. However, an investigation into the effects of HRV-derived and acceleration features is required”, (abstract).

[0007] Background art includes scientific publication “Stimulus-specific enhancement of fear extinction during slow-wave sleep.” By Hauner, Katherina K. et al. disclosing that “Sleep can strengthen memory for emotional information, but whether emotional memories can be specifically targeted and modified during sleep is unknown. In human subjects who underwent olfactory contextual fear conditioning, re-exposure to the odorant context in slow-wave sleep promoted stimulus-specific fear extinction, with parallel reductions of hippocampal activity and reorganization of amygdala ensemble patterns. Thus, fear extinction may be selectively enhanced during sleep, even without re-exposure to the feared stimulus itself.”, (abstract).

[0008] Background art includes scientific publication “Stimulus-specific enhancement of fear extinction during slow-wave sleep.” By Hauner, Katherina K., et al. disclosing that “Sleep can strengthen memory for emotional information, but whether emotional memories can be specifically targeted and modified during sleep is unknown. In human subjects who underwent olfactory contextual fear conditioning, re-exposure to the odorant context in slow-wave sleep promoted stimulus-specific fear extinction, with parallel reductions of hippocampal activity and reorganization of amygdala ensemble patterns. Thus, fear extinction may be selectively enhanced during sleep, even without re-exposure to the feared stimulus itself.”, (abstract).

[0009] Background art includes scientific publication “Effect of conditioned stimulus exposure during slow wave sleep on fear memory extinction in humans.” By He, Jia, et al. disclosing that “Repeated exposure to a neutral conditioned stimulus (CS) in the absence of a noxious unconditioned stimulus (US) elicits fear memory extinction. The aim of the current study was to investigate the effects of mild tone exposure (CS) during slow wave sleep (SWS) on fear memory extinction in humans... Conditioned stimulus re-exposure during slow wave sleep promoted fear memory extinction without altering sleep profiles. t”. (abstract).

[0010] Background art includes scientific publication “Olfactory identification deficits and increased mortality in the community.” By Devanand, Davangere P., et alet al. disclosing that “To examine the association between odor identification deficits and future mortality in a multiethnic community cohort of older adults. . ..Impaired odor identification, particularly in the anosmic range, is associated with increased mortality in older adults even after controlling for dementia and medical comorbidity.”, (abstract).

[0011] Background art includes scientific publication “Olfactory stimulation for people with dementia: A rapid review.” By D’Andrea, Federica, et al. et al. disclosing that “There is a growing interest in using olfactory (smell) stimulation in dementia care. This study aims to extend current knowledge by synthesising the evidence on the efficacy of interventions using olfactory stimulation for people with dementia and to assess the effects of different types of odours and administration methods using a mixed methods approach. The rapid review was conducted based on searches in six electronic databases. A narrative approach was applied to assess 20 studies included in the review. Fourteen studies used a quasi-experimental design, five studies used an experimental design and one was a case study. High heterogeneity was found on odours and methods of application used, with the majority of studies administering lavender oil using a diffuser. Mixed results were reported on the benefits of olfactory stimulation on responsive behaviours and cognitive function. Although the evidence available is limited, encouraging results were found regarding olfactory stimulation and increased sleep duration, food intake and improved balance. It was not possible to draw any overall conclusion in relation to the effect of olfactory stimulation. However, this review shows promising results that support further investigation of olfactory stimulation as a nonpharmacological intervention for people with dementia. The review is limited due to the low to moderate quality of studies included. Furthermore, the broad range of approaches was employed, and comparison between the studies was difficult. Further high-quality mixed method studies using robust and detailed protocols are needed to clarify the effects of olfactory stimuli and any other factors that may influence the responses of people with dementia.”, (abstract).

[0012] Background art includes scientific publication “Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults.” By Woo, Cynthia C., et al. disclosing that “Minimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health.”, (abstract).

[0013] Background art includes scientific publication “The effect of lavender aromatherapy on autonomic nervous system in midlife women with insomnia.” By Chien, Li-Wei, Su Li Cheng, and Chi Feng Liu. disclosing that “The objective of this study is to determine the effects of 12 weeks of lavender aromatherapy on self-reported sleep and heart rate variability (HRV) in the midlife women with insomnia. Sixty-seven women aged 45-55 years, with a CPSQI (Chinese version of Pittsburgh Sleep Quality Index) greater than 5, were recruited from communities in Taiwan. The experimental group () received lavender inhalation, 20 min each time, twice per week, for 12 weeks, with a total of 24 times. The control group (n=34) received health education program for sleep hygiene with no intervention. The study of HRV was analyzed by time- and frequency-domain methods. Significant decrease in mean heart rate (HR) and increases in SDNN (standard deviation of the normal-to-normal (NN) intervals), RMSDD (square root of the mean squared differences of successive NN intervals), and HF (high frequency) of spectral powers analysis after lavender inhalation were observed in the 4th and 12th weeks of aromatherapy. The total CPSQI score of study subjects was significantly decreased in the experimental group (p<0.001), while no significant difference was observed across the same time period (p=0.776) in the control group. Resting HR and HRV measurements at baseline 1 month and 3 months after allocation showed no significant difference between the experimental and control groups. The study demonstrated that lavender inhalation may have a persistent short-term effect on HRV with an increase in parasympathetic modulation. Women receiving aromatherapy experienced a significant improvement in sleep quality after intervention. However, lavender aromatherapy does not appear to confer benefit on HRV in the long-term followup.”, (abstract).

[0014] Background art includes scientific publication “Odors enhance slow-wave activity in non-rapid eye movement sleep.” By Perl, Ofer, et al., disclosing that “Most forms of suprathreshold sensory stimulation perturb sleep. In contrast presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. ...Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5-4 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement (NREM) sleep. Theincrease was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow frequency oscillations.”, (abstract).

[0015] Background art includes scientific publication “Reciprocal relationships between sleep and smell.” By Gaeta, Giuliano, and Donald A. Wilson., disclosing that “Despite major anatomical differences with other mammalian sensory systems, olfaction shares with those systems a modulation by sleep / wake states. Sleep modulates odor sensitivity and serves as an important regulator of both perceptual and associative odor memory. In addition, however, olfaction also has an important modulatory impact on sleep. Odors can affect the latency to sleep onset, as well as the quality and duration of sleep. Olfactory modulation of sleep may be mediated by direct synaptic interaction between the olfactory system and sleep control nuclei, and / or indirectly through odor modulation of arousal and respiration. This reciprocal interaction between sleep and olfaction presents novel opportunities for sleep related modulation of memory and perception, as well as development of non-pharmacological olfactory treatments of simple sleep disorders.”, (abstract).

[0016] Background art includes scientific publication “Lavender and the nervous system.” By K oulivand, Peir Hossein, Maryam Khaleghi Ghadiri, and Ali Gorji. disclosing that “Lavender is traditionally alleged to have a variety of therapeutic and curative properties, ranging from inducing relaxation to treating parasitic infections, burns, insect bites, and spasm. There is growing evidence suggesting that lavender oil may be an effective medicament in treatment of several neurological disorders. Several animal and human investigations suggest anxiolytic, mood stabilizer, sedative, analgesic, and anticonvulsive and neuroprotective properties for lavender. These studies raised the possibility of revival of lavender therapeutic efficacy in neurological disorders. In this paper, a survey on current experimental and clinical state of knowledge about the effect of lavender on the nervous system is given.”, (abstract).

[0017] Background art includes scientific publication “An olfactory stimulus modifies nighttime sleep in young men and women.” By Goel, Namni, Hyungsoo Kim, and Raymund P. Lao. disclosing that “Aromatherapy is an anecdotal method for modifying sleep and mood. However, whether olfactory exposure to essential oils affects night-time objective sleep remains untested. Previous studies also demonstrate superior olfactory abilities in women. Therefore, this study investigated the effects of an olfactory stimulus on subsequent sleep and assessed gender differences in such effects. Thirty-one young healthy sleepers (16 men and 15 women, aged 18 to 30 yr, mean+SD, 20.5+2.4 yr) completed 3 consecutive overnight sessions in a sleep laboratory: one adaptation, one stimulus, and one control night (the latter 2 nights in counterbalanced order). Subjects received an intermittent presentation (first 2 min of each 10 min interval) of an olfactory (lavender oil) or a control (distilled water) stimulus between 23:10 and 23:40 h. Standard polysomnographic sleep and self-rated sleepiness and mood data were collected. Lavender increased the percentage of deep or slow-wave sleep (SWS) in men and women. All subjects reported higher vigor the morning after lavender exposure, corroborating the restorative SWS increase. Lavender also increased stage 2 (light) sleep, and decreased rapideye movement (REM) sleep and the amount of time to reach wake after first falling asleep (wake after sleep onset latency) in women, with opposite effects in men. Thus, lavender serves as a mild sedative and has practical applications as a novel, nonphotic method for promoting deep sleep in young men and women and for producing gender-dependent sleep effects.”, (abstract).

[0018] Background art includes scientific publication “Sleepless in the hospital: A systematic review of non-pharmacological sleep interventions” By Miller, Megan A., et al. disclosing that “Overall, the review was unable to recommend any specific intervention due to the current state of the literature. The majority of included research was limited in quality due to lack of controls, lack of blinding, and reliance on self-reported outcomes. However, the literature suggests melatonin and CBT-I likely have the most promise to improve sleep in inpatient medical settings. Additionally, environmental modifications, including designated quiet time and ear plugs / eye masks, could be easily adopted in the care environment and may support sleep improvement. More rigorous research in nonpharmacological sleep interventions for hospitalized individuals is required to inform clinical recommendations”, (abstract).

[0019] Background art includes scientific publication “Effect of Rosa damascene aromatherapy on sleep quality in cardiac patients: a randomized controlled trial..” By Hajibagheri, Ali, Atye Babaii, and Mohsen Adib-Hajbaghery.disclosing that “Rosa damascene aromatherapy can significantly improve the sleep quality of patients hospitalized in CCUs”. (abstract).

[0020] Background art includes scientific publication “Odors enhance slow-wave activity in non-rapid eye movement sleep.” By Perl, Ofer, et al. disclosing that “Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9-15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5^1 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations.”, (abstract).

[0021] Background art includes scientific publication “Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.” By Vance, David E., et al. disclosing that “Olfactory training (OT), or smell training, consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning / memory. OT is also associated with increases in the volume / size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.”, (abstract).

[0022] Background art includes scientific publication “Olfactory bulb habituation to odor stimuli.” By Chaudhury, Dipesh, et al. disclosing that “Habituation is a simple form of memory, yet its neurobiological mechanisms are only beginning to be understood in mammals. In the olfactory system, the neural correlates of habituation at a fast experimental timescale involving very short intertrial intervals (tens of seconds) have been shown to depend on synaptic adaptation in olfactory cortex. In contrast, behavioral habituation to odorants on a longer timescale with intertrial intervals of several minutes depends on processes in the olfactory bulb, as demonstrated by pharmacological studies. We here show that behavioral habituation to odorants on this longer timescale has a neuronal activity correlate in the olfactory bulb. Spiking responses of mitral cells in the rat olfactory bulb adapt to, and recover from, repeated odorant stimulation with 5 -min intertrial intervals with a time course similar to that of behavioral habituation. Moreover, both the behavioral and neuronal effects of odor habituation require functioning N-methyl-d-aspartic acid receptors in the olfactory bulb. (PsycINFO Database Record (c) 2016 APA, all rights reserved)”, (abstract).

[0023] Background art includes scientific publication “Influence of fragrances on human psychophysiological activity: With special reference to human electroencephalographic response.” By Sowndhararajan, Kandhasamy, and Songmun Kim. disclosing that “The influence of fragrances such as perfumes and room fresheners on the psychophysiological activities of humans has been known for a long time, and its significance is gradually increasing in the medicinal and cosmetic industries. A fragrance consists of volatile chemicals with a molecular weight of less than 300 Da that humans perceive through the olfactory system. In humans, about 300 active olfactory receptor genes are devoted to detecting thousands of different fragrance molecules through a large family of olfactory receptors of a diverse protein sequence. The sense of smell plays an important role in the physiological effects of mood, stress, and working capacity. Electrophysiological studies have revealed that various fragrances affected spontaneous brain activities and cognitive functions, which are measured by an electroencephalograph (EEG). The EEG is a good temporal measure of responses in the central nervous system and it provides information about the physiological state of the brain both in health and disease. The EEG power spectrum is classified into different frequency bands such as delta (0.5-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), beta (13-30 Hz) and gamma (30-50 Hz), and each band is correlated with different features of brain states. A quantitative EEG uses computer software to provide the topographic mapping of the brain activity in frontal, temporal, parietal and occipital brain regions. It is well known that decreases of alpha and beta activities and increases of delta and theta activities are associated with brain pathology and general cognitive decline. In the last few decades, many scientific studies were conducted to investigate the effect of inhalation of aroma on human brain functions. The studies have suggested a significant role for olfactory stimulation in the alteration of cognition, mood, and social behavior. This review aims to evaluate the available literature regarding the influence of fragrances on the psychophysiological activities of humans with special reference to EEG changes.”, (abstract).

[0024] Background art includes scientific publication “Overnight olfactory enrichment using an odorant diffuser improves memory and modifies the uncinate fasciculus in older adults.” By Woo, Cynthia C., et al. disclosing that “Minimal olfactory enrichment administered at night produces improvements in both cognitive and neural functioning. Thus, olfactory enrichment may provide an effective and low-effort pathway to improved brain health”, (abstract).

[0025] Background art includes scientific publication “Information processing during sleep: the effect of olfactory stimuli on dream content and dream emotions.” By Schredl, Michael, et al. disclosing that “Research has shown that external stimuli presented during sleep can affect dream content, thus reflecting information processing of the sleeping brain. Olfactory stimuli should have a stronger effect on dream emotions because their processing is linked directly to the limbic system. Because selective olfactory stimulation does not increase arousal activity, intense olfactory stimulation is therefore a prime paradigm for studying information processing during sleep. Fifteen healthy, normosmic volunteers were studied by intranasal chemosensory stimulation during rapid eye movement sleep based on air-dilution olfactometry. For olfactory stimulation, hydrogen sulphide (smell of rotten eggs) and phenyl ethyl alcohol (smell of roses) was used and compared with a control condition without stimulation. The olfactory stimuli affected significantly the emotional content of dreams: the positively toned stimulus yielded more positively toned dreams, whereas the negative stimulus was followed by more negatively toned dreams. Direct incorporations, i.e. the dreamer is smelling something, were not found. The findings indicate that information processing of olfactory stimuli is present in sleep and that the emotional tone of dreams can be influenced significantly depending upon the hedonic characteristic of the stimulus used. It would be interesting to conduct learning experiments (associating specific odours with declarative material) to study whether this declarative material is incorporated into subsequent dreams if the corresponding odour cue is presented during sleep. It would also be interesting to study the effect of positively toned olfactory stimuli on nightmares.”, (abstract).

[0026] Background art includes scientific publication “Development and study of ezzence: a modular scent wearable to improve wellbeing in home sleep environments.” By Amores, Judith, Mae Dotan, and Pattie Maes disclosing that “Ezzence is the first smartphone-controlled olfactometer designed for both day and night conditions. We discuss the design and technical implementation of Ezzence and report on a study to evaluate the feasibility of using the device in home-based sleep environments. The study results (N = 40) show that participants were satisfied with the device and found it easy to use. Furthermore, participants reported a significant improvement in sleep quality when using the device with scent in comparison to the control condition (p = 0.003), as well as better mood the following morning (p = 0.038) and shorter timis e to sleep onset (p = 0.008). The device is integrated with a wearable EEG and real-time sleep staging algorithm to release scent during specific sleep stages (Nl, N2, N3, and REM), which is important for certain use cases (e.g., to study the effect of scent on REM dreams, or to improve memory consolidation with a re-exposure of scent during N2 and N3). Ezzence can be used for several applications, including those that require scent triggered day and night. They include targeted memory reactivation, longitudinal health treatments, therapy, and mental or physical exercises. Finally, this article proposes an interaction framework to understand relationships between scents and environments based on proxemic dimensions and passive or active interactions during sleep.”, (abstract). Background art includes scientific publication “Odors enhance slow-wave activity in non-rapid eye movement sleep.” By Perl, Ofer, et al. disclosing that “Most forms of suprathreshold sensory stimulation perturb sleep. In contrast, presentation of pure olfactory or mild trigeminal odorants does not lead to behavioral or physiological arousal. In fact, some odors promote objective and subjective measures of sleep quality in humans and rodents. The brain mechanisms underlying these sleep-protective properties of olfaction remain unclear. Slow oscillations in the electroencephalogram (EEG) are a marker of deep sleep, and K complexes (KCs) are an EEG marker of cortical response to sensory interference. We therefore hypothesized that odorants presented during sleep will increase power in slow EEG oscillations. Moreover, given that odorants do not drive sleep interruption, we hypothesized that unlike other sensory stimuli odorants would not drive KCs. To test these hypotheses we used polysomnography to measure sleep in 34 healthy subjects (19 women, 15 men; mean age 26.5 ± 2.5 yr) who were repeatedly presented with odor stimuli via a computer-controlled air-dilution olfactometer over the course of a single night. Each participant was exposed to one of four odorants, lavender oil (n = 13), vetiver oil (n = 5), vanillin (n = 12), or ammonium sulfide (n = 4), for durations of 5, 10, and 20 s every 9-15 min. Consistent with our hypotheses, we found that odor presentation during sleep enhanced the power of delta (0.5^1 Hz) and slow spindle (9-12 Hz) frequencies during non-rapid eye movement sleep. The increase was proportionate to odor duration. In addition, odor presentation did not modulate the occurrence of KCs. These findings imply a sleep-promoting olfactory mechanism that may deepen sleep through driving increased slow-frequency oscillations.”, (abstract).

[0027] Background art includes scientific publication “Olfactory aversive conditioning during sleep reduces cigarette-smoking behavior.” By Arzi, Anat, et al. disclosing that “Recent findings suggest that novel associations can be learned during sleep. However, whether associative learning during sleep can alter later waking behavior and whether such behavioral changes last for minutes, hours, or days remain unknown. We tested the hypothesis that olfactory aversive conditioning during sleep will alter cigarette-smoking behavior during ensuing wakefulness. A total of 66 human subjects wishing to quit smoking participated in the study (23 females; mean age, 28.7 ± 5.2 years). Subjects completed a daily smoking diary detailing the number of cigarettes smoked during 7 d before and following a 1 d or night protocol of conditioning between cigarette odor and profoundly unpleasant odors. We observed significant reductions in the number of cigarettes smoked following olfactory aversive conditioning during stage 2 and rapid eye movement (REM) sleep but not following aversive conditioning during wakefulness (p < 0.05). Moreover, the reduction in smoking following aversive conditioning during stage 2 (34.4 ± 30.1 %) was greater and longer lasting compared with the reduction following aversive conditioning during REM (11.9 ± 19.2%, p < 0.05). Finally, the reduction in smoking following aversive conditioning during sleep was significantly greater than in two separate control sleep experiments that tested aversive odors alone and the effects of cigarette odors and aversive odors without pairing. To conclude, a single night of olfactory aversive conditioning during sleep significantly reduced cigarette-smoking behavior in a sleep stage-dependent manner, and this effect persisted for several days.”, (abstract).

[0028] Background art includes scientific publication “Local targeted memory reactivation in human sleep.” By Bar, Ella, et al. disclosing that “Memory consolidation can be promoted via targeted memory reactivation (TMR) that re-presents training cues or context during sleep. Whether TMR acts locally or globally on cortical sleep oscillations remains unknown. Here, we exploit the unique functional neuroanatomy of olfaction with its ipsilateral stimulus processing to perform local TMR in one brain hemisphere. Participants learned associations between words and locations in left or right visual fields with contextual odor throughout. We found lateralized event-related potentials during task training that indicate unihemispheric memory processes. During post-learning naps, odors were presented to one nostril in non-rapid eye movement (NREM) sleep. Memory for specific words processed in the cued hemisphere (ipsilateral to stimulated nostril) was improved after local TMR during sleep. Unilateral odor cues locally modulated slow-wave (SW) power such that regional SW power increase was lower in the cued hemisphere relative to the uncued hemisphere and negatively correlated with select memories for cued words. Moreover, local TMR improved phase-amplitude coupling (PAC) between slow oscillations and sleep spindles specifically in the cued hemisphere. The effects on memory performance and cortical sleep oscillations were not observed when unilateral olfactory stimulation during sleep followed learning without contextual odor. Thus, TMR in human sleep transcends global action by selectively promoting specific memories associated with local sleep oscillations.”, (abstract).

[0029] Background art includes scientific publication “Humans can learn new information during sleep.” By Arzi, Anat, et al., disclosing that “During sleep, humans can strengthen previously acquired memories, but whether they can acquire entirely new information remains unknown. The nonverbal nature of the olfactory sniff response, in which pleasant odors drive stronger sniffs and unpleasant odors drive weaker sniffs, allowed us to test learning in humans during sleep. Using partial-reinforcement trace conditioning, we paired pleasant and unpleasant odors with different tones during sleep and then measured the sniff response to tones alone during the same nights' sleep and during ensuing wake. We found that sleeping subjects learned novel associations between tones and odors such that they then sniffed in response to tones alone. Moreover, these newly learned tone-induced sniffs differed according to the odor pleasantness that was previously associated with the tone during sleep. This acquired behavior persisted throughout the night and into ensuing wake, without later awareness of the learning process. Thus, humans learned new information during sleep.”, (abstract).

[0030] Background art includes scientific publication “Psychometric properties of the disturbing dream and nightmare severity index-Korean version.” By Lee, Ruda, Barry Krakow, and Sooyeon Suh. disclosing that “The DDNSI is a reliable measure of nightmare severity that can be used in various settings.” (abstract).

[0031] Background art includes scientific publication “The Nightmare Disorder Index: development and initial validation in a sample of nurses.” Dietch, Jessica R., et al. disclosing that “NDI is an efficient and valid self-report assessment of nightmare disorder. Nurses have high rates of nightmares and nightmare disorder which are associated with poorer psychosocial functioning. We recommend increased nightmare screening particularly for high-risk populations such as healthcare workers.” (abstract).

[0032] Background art includes scientific publication “Nightmare distress questionnaire: associated factors.” Schredl, Michael, et al. disclosing that “A large variety of factors are associated with nightmare distress, a finding that is of clinical importance. The construct harm avoidance, however, was not helpful in explaining interindividual differences in nightmare distress. Furthermore, the relationship between nightmare distress and other factors, eg, education or agreeableness, is not yet understood.” (abstract)

[0033] U.S patent application No. 20200222658 disclosing “Disclosed herein are methods, kits, and devices for improving cognitive function and memory through olfactory stimulation. In some embodiments, olfactory stimulation is performed by releasing one or more scents according to an olfactory stimulation regimen or schedule. The methods, kits and devices described herein can provide a large impact on cognition with minimal effort and cost. They can be used widely and effectively among older adults, children, and other populations in need of improved cognitive performance.” (abstract) US patent application No. 20170304582 disclosing “The present invention relates to systems for brain stimulation during sleep and methods for increasing vividness of a subject's dreams or for directing the subject matter of a subject's dreams. The system comprises a brain stimulation module and at least one of a brain energy source and / or a hypnotic source. The methods involve administering to a subject a brain energy molecule and / or a hypnotic and providing to the subject during restorative sleep a sensory stimulation.”, (abstract)

[0034] International patent application No. 1020120092249 disclosing “A sleep inducing apparatus and a controlling method thereof are provided to stimulate at least one sense of a user based on the current state of the user for inducing the sound sleep or changing the sleeping condition. CONSTITUTION: A sleep inducing apparatus includes a sleeping condition sensor(210), an outputting unit(220), a memory unit(230), a communication unit(240), and a controller(250). The sleeping condition sensor detects the sleeping condition of a user using a camera, a microphone, and a pressure sensor. The outputting unit controls the sleeping condition of the user using a vibration output unit, a sound output unit, a scent output unit, and a light output unit. The memory unit is for saving software for operating a driver for driving the controller and other parts of the apparatus. The controller controls the outputting unit”, (abstract)

[0035] US patent application No. disclosing “A method and apparatus for affecting the dreams of the subject or individual is presented. The apparatus first predicts or detects the desired sleep state and presents a scent to the subject. The apparatus then awakens the subject after a given period of time using external stimulus. The desired sleep state may be the REM sleep state, and the period of time may be one minute. Upon awakening, the subject will recall dreams that have been affected by the emitted scent. If the scent is pleasant, then the subject will recall having pleasant dreams.” (abstract)

[0036] International patent application No. 2020081172 disclosing “A Pavlovian conditioned reflex sleep induction kit includes at least one physiological sensor, wherein the at least one physiological sensor is configured to detect at least a physiological parameter of a user and transmit a detection signal to an automatically activated scent diffuser, wherein the automatically activated scent diffuser is configured to receive an electronic activation signal and to diffuse a scent as a function of the electronic activation signal, a control circuit configured to receive the detection signal from the at least one physiological sensor, to ascertain that the user is entering a hypnagogic state, and to transmit the electronic activation signal to the automatically activated scent diffuser, thereby conditioning the user to respond to subsequent sensing of the same scent. For later use, a user-activated scent diffuser is provided, that diffuses the same scent upon activation by a user, to trigger the conditioned reflex to fall asleep.” (abstract)

[0037] SUMMARY OF THE INVENTION

[0038] Following is a non-exclusive list including some examples of embodiments of the invention. The invention also includes embodiments which include fewer than all the features in an example and embodiments using features from multipel examples, also if not expressly listed below.

[0039] Example 1. A method for lowering a patient’s heart rate using olfactory stimulation during sleep, comprising: selecting a patient suffering from elevated heart rate, during sleep; monitoring one or more of the patient’s physiological parameters; identifying in said monitored parameters an indicator for providing olfactory stimulus; and providing an olfactory stimulus in response to said identifying.

[0040] Example 2. The method of example 1, comprising selecting an olfactory stimulus, wherein said selecting comprises selecting at least one scent.

[0041] Example 3. The method of example 2, wherein said selecting an olfactory stimulus comprises selecting a set of scents, wherein each scent is from a different scent family or has a different effect on the patient, and wherein said providing comprises providing the set of scents to the patient.

[0042] Example 4. The method of any of examples 2 to 3, wherein the selecting comprises selecting a release pattern, comprises determining one or more of: order of scents; intensity of scents; and / or continuous or intermittent release, wherein intermittent release comprises determining a release pulse length and intervals between pulses.

[0043] Example 5. The method of example 1 , wherein the monitoring comprises monitoring the heart rate of the patient and wherein said identifying comprises identifying a heart rate abnormality. Example 6. The method of example 5, wherein said identifying a heart rate abnormality comprises detecting elevated heart rate and wherein said providing comprises providing the olfactory stimulus until regular heart rate is detected.

[0044] Example 7. The method of any of examples 1 to 6, wherein the selecting comprises selecting at least one scent having a relaxing effect on the patient.

[0045] Example 8. The method of any of examples 1 to 7, wherein the monitoring comprises monitoring the patient's sleep, and wherein the identifying comprises identifying a sleep stage.

[0046] Example 9. The method of any of examples 1 to 8, wherein the monitoring comprises measuring one or more of the patient’s physiological parameters and wherein the identifying comprises identifying a sleep stage based on said physiological parameters, substantially in real-time, during sleep.

[0047] Example 10. The method of example 9, wherein the patient’s physiological parameters comprise one or more of, heart rate, heart rate variability, accelerometer data, respiratory rate, body temperature, blood oxygen level, and gyroscope data.

[0048] Example 11. The method of example 8 , wherein said sleep stage is a REM sleep stage, and wherein the selecting comprises selecting at least one scent having a positive effect on the patient.

[0049] Example 12. The method of any of examples 8 or 11, wherein said sleep stage is a deep sleep stage, and wherein the selecting comprises selecting at least one scent having a relaxing effect on the patient.

[0050] Example 13. The method of any of examples 8 to 7, wherein said sleep stage is a light sleep stage, and wherein the selecting comprises selecting at least one scent having a relaxing effect on the patient.

[0051] Example 14. The method of any of examples 8 to 13, wherein the providing comprises providing the olfactory stimulus from said identifying until the end of the sleep stage.

[0052] Example 15. The method of any of examples 8 to 14, wherein the providing comprises providing the olfactory stimulus at each sleep stage.

[0053] Example 16. A method for treating a patient suffering from a mental condition using olfactory stimulation, comprising: influencing dreams content for reducing nightmares; deepening the patient's sleep; and lowering heart rate.

[0054] Example 17. The method of example 16, wherein the influencing comprises: a) monitoring at least one physiological parameter of the patient during sleep; b) identifying a REM sleep stage; c) selecting at least one scent having a positive effect on the patient; and d) providing the at least one scent to the patient, during at least a portion of the REM sleep stage.

[0055] Example 18. The method of any of examples 16 or 17, wherein the deepening comprises: a) monitoring at least one physiological parameter of the patient during sleep; b) identifying a deep sleep stage; c) selecting at least one scent having a relaxing effect on the patient; and d) providing the at least one scent to the patient, during at least a portion of the deep sleep stage.

[0056] Example 19. The method of example 18, wherein the method comprises identifying a light sleep stage, selecting at least one scent having a sleeping effect on the patient, and providing the at least one scent to the patient until a deep sleep stage is detected.

[0057] Example 20. The method of any of examples 16 to 19, wherein the heart rate lowering comprises: a) monitoring at least one physiological parameter of the patient during sleep; b) identifying a sleep stage and / or physiological indication; c) selecting at least one scent perceived by the patient as a relaxing or positive scent; and d) providing the at least one scent to the patient, during at least a portion of the REM sleep stage.

[0058] Example 21. The method of example 20, wherein the identifying comprises identifying a REM sleep stage.

[0059] Example 22. The method of any of examples 20 or 21, wherein the monitoring comprises monitoring the patient's heart rate, wherein the identifying comprises identifying a heart rate abnormality, wherein the selecting compat least one scent having a relaxing effect on the patient, and providing the at least one scent until heart rate regulation is detected. Example 23. The method of any of examples 16 to 20, comprises selecting a patient suffering from PTSD.

[0060] Example 24. The method of any of examples 16 to 21, comprises selecting a patient suffering from nightmares on a weekly basis.

[0061] Example 25. The method of any of examples 16 to 24, comprises selecting a patient suffering from sleep disorders resulting from mental health conditions.

[0062] Example 26. The method of any of examples 16 to 25, comprises selecting a patient suffering from chronic sleep disorders

[0063] Example 27. A method for deepening the patient's sleep, comprising: a) monitoring at least one physiological parameter of the patient during sleep; b) identifying a deep sleep stage; c) selecting at least one scent having a relaxing effect on the patient; and d) providing the at least one scent to the patient, during at least a portion of the deep sleep stage.

[0064] Example 28. A method for treating cognitive loss using olfactory stimulation during sleep, comprising: monitoring the patient during sleep; identifying a REM sleep stage or a deep sleep stage; selecting at least one scent intended for and stimulating the hippocampus; and providing the at least one scent to the patient.

[0065] Example 29. The method of example 28, comprises identifying a light sleep stage, selecting at least one scent having a relaxing effect on the patient, and providing the at least one scent to the patient.

[0066] Example 30. The method of any of examples 28 or 29, wherein the at least one scent is a plurality of scents, and wherein the providing comprises providing the plurality of scents in turns.

[0067] Example 31. The method of any of examples 28 or 30, wherein the providing comprises mixing two or more scents by providing thereof simultaneously.

[0068] Example 32. The method of any of examples 28 or 31, wherein the selecting comprises selecting a set of scents, each from a different scent family, or each has a different effect on the patient. Example 33. A method for detecting diminished olfaction of a patient, during sleep, comprising: determining the patient's physiological reaction when sensing an olfactory stimulation; exposing the patient to olfactory stimuli during sleep; monitoring the patient's physiological reaction to said stimuli; identifying whether the patient senses the olfactory stimuli, based on said determining, where a lack of change in the detected patient's physiological reaction indicates an olfaction decrease.

[0069] Example 34. The method of example 33, comprises detecting an early stage of cognitive loss by detecting diminished olfaction.

[0070] Example 35. The method of any of examples 33 or 34, comprises informing the patient on the detected diminished olfaction and recommending attending a medical professional.

[0071] Example 36. The method of example 35, wherein the informing comprises notifying a caregiver.

[0072] Example 37. The method of any of examples 33 to 36, wherein the exposing comprises exposing the patient to a series of scents of varied intensity for evaluating olfactory sensitivity.

[0073] Example 38. A method for personalizing an olfactory treatment, administered during sleep learning the patient; providing an olfactory treatment based on said learning; monitoring the patient’s physiological parameters; identifying the patient’s reaction to said olfactory stimulus, based on said learning; adjusting the olfactory treatment based on said patient’s reaction.

[0074] Example 39. The method of example 38, wherein the learning comprises learning to identify sleep stages during the patient's sleep based on patient-specific sleep pattern.

[0075] Example 40. The method of any of examples 38 or 39, wherein the learning comprises learning the patient's reaction to a plurality of olfactory stimuli.

[0076] Example 41. The method of any of examples 38 to 40, wherein the providing comprises selecting an olfactory stimulus based on said learning and monitoring a change in one or more of the patient’s physiological parameters. Example 42. The method of any of examples 38 to 41 , wherein the method comprises collecting historical data and learning therefrom regarding the patient’s reaction to olfactory stimuli.

[0077] Example 43. The method of any of examples 38 to 42, wherein the adjusting comprises modifying the olfactory stimulus for enhancing a desired patient’s reaction.

[0078] Example 44. A system for providing olfactory to a patient during sleep, comprising: a stimulator, configured to release a plurality of scents ; a patient monitor comprises at least one sensor for measuring at least one of the patient's physiological parameters or environmental parameters; and a controller, configured to receive data from the patient monitor, and control the stimulator operation accordingly.

[0079] Example 45. The system of example 44, wherein the stimulator comprises a scent diffuser, and wherein the scent diffuser comprises more than one cartridge, wherein each cartridge is configured for containing a different scent substance.

[0080] Example 46. The system of claim 45, wherein each cartridge comprises an aerosolizer for atomization or nebulization of a liquid scent substance, within a volume thereof.

[0081] Example 47. The system of any of examples 45 to 46, wherein the stimulator comprises a mixing tank, located at an outlet of each cartridge, for allowing scent emerging from the cartridges to blend.

[0082] Example 48. The system of any of examples 44 or 47, wherein the at least one sensor is one or more of a heart rate meter, an accelerometer, a gyroscope sensor, a respiratory monitor, an infrared sensor, a body temperature sensor, a room temperature sensor, a light sensor, a noise sensor, a camera, a microphone or a clock.

[0083] Example 49. The system of any of examples 44 or 48, wherein the controller comprises an Al component, configured to identify a patient sleep stage based on data from at least one sensor.

[0084] Example 50. The system of example 49, wherein the Al component is configured to learn the patient’s individual sleep patterns.

[0085] Example 51. The system of any of claima 49 or 50, wherein the Al component is configured to learn the patient’s reaction to different scents.

[0086] Example 52. The system of any of examples 45 to 51 , wherein the scent diffuser is configured to be located near the patient while sleeping, no more than 100 cm from the patient’s bed. Example 53. The system of any of examples 45 to 52, wherein the scent diffuser comprises a motor, controlled by the controller, and configured to direct an outlet of the cartridge toward the patient.

[0087] Example 54. The system of any of examples 45 to 53, wherein the scent diffuser comprises a plurality of fans, each fan directing a scent released from a cartridge of the plurality of cartridges.

[0088] Example 55. The system of any of examples 45 to 54, wherein the scent diffuser comprises an air purifier.

[0089] Example 56. The system of calim 55, wherein the air purifier, comprise one or more of a fan, a filter, or a suction device.

[0090] Example 57. The system of any of examples 55 to 56, wherein the air purifier, comprise an atomizer or nebulizer for releasing or at least one atomized smell adsorption material.

[0091] Example 58. The system of any of examples 45 to 49, comprises an external sensor for detecting if the patient is in bed.

[0092] Example 59. The system of example 58, where the external sensor comprises one or more os a sound sensor, a temperature sensor, a camera, an infra-red sensor, or a radar.

[0093] According to some embodiments of the presently described subject matter, there is provided a system of providing therapeutic stimulation to a patient during sleep, the system comprising: a) a stimulator, configured to release one or more scents; b) a patient monitor, comprising at least one sensor configured to measure at least one physiological parameter or environmental parameter of the patient; and c) a controller, configured to:

[0094] (i) identify a sleep state of the patient, and

[0095] (ii) responsive to, at least, the identified sleep state, provide a stimulus to the patient, the stimulus being based on, at least, an ordering of one or more scents, and a respective intensity and respective release pattern of each of one or more scents.

[0096] In addition to the above features, the system according to this aspect of the presently disclosed subject matter can comprise one or more of features (i) to (xxiv) listed below, in any desired combination or permutation which is technically possible:

[0097] (i) the controller is configured to identify the sleep state of the patient based on, at least, physiological parameters and / or environmental parameters of the patient.

[0098] (ii) the physiological parameters comprise: heart rate, respiration rate, accelerometer motion measurement, and / or beat-to-beat-interval (BBI). (iii) the environmental parameters comprise: light level, time-of-day, distance of a patient device, and / or noise level.

[0099] (iv) the controller is further configured to identify the sleep state of the patient based on, at least, a machine learning model that was trained utilizing a plurality of training samples, wherein each training sample of the plurality comprises: a. data indicative of a heart rate, respiration rate, accelerometer motion measurement, noise level, time-of-day, distance of patient-held device, and / or beat-to-beat-interval (BBI) of a human subject; and b. a ground truth sleep state of the human subject.

[0100] (v) the ground truth sleep state is derivative of, at least, polysomnography performed on the human subject.

[0101] (vi) the controller is configured to identify the sleep state of the patient based on, at least, previous tracking of sleep states of the patient.

[0102] (vii) the controller is configured to identify the sleep state of the patient based on, at least, given typical sleep state transitions of human subjects.

[0103] (viii) the controller is configured to identify one or more sleep states selected from: wakefulness, pending sleep onset, abnormal / elevated heart rate, shortened BBI, rapid-eye movement (REM) sleep, and / or deep sleep.

[0104] (ix) the controller is further configured to: responsive to the identified sleep state being pending sleep onset state: providing the stimulus to the patient, the stimulus comprising a first release of a scent, the release of the stimulus being within five minutes of the identification of pending sleep onset state, thereby providing a calming effect to enable the patient’s sleeping.

[0105] (x) the controller is further configured to: a) responsive to the identified sleep state being deep sleep: provide two or more releases of the stimulus, at a first release interval, and b) responsive to subsequently identifying a sleep stage of the patient as being REM sleep: provide two or more releases of the stimulus, at a second release interval that is at least 50% longer than the first release interval, thereby enabling the patient to remain in sleep.

[0106] (xi) the stimulus comprises scents of three different families, the families being selected from a list consisting of: floral, fruity non-citrus, citrus, woody, minty, sweet, and spicy, thereby stimulating a plurality of parts of the patent’s brain, and improving cognition in the patient.

[0107] (xii) the controller is further configured to: responsive to the identified sleep state being REM sleep: provide the stimulus; thereby improving patient mental state and / or reducing patient nightmares.

[0108] (xiii) the controller is further configured to: provide the stimulus in two or more releases, at release intervals of between 5 and 15 minutes.

[0109] (xiv) the stimulus is non-trigeminal.

[0110] (xv) the controller is further configured to: responsive to identifying a period of elevated heart rate of the patient: providing the stimulus to the patient until the patient’s heart rate is identified as non-elevated.

[0111] (xvi) the controller is further configured to: provide the stimulus in two or more releases, at release intervals of between 5 and 15 minutes.

[0112] (xvii) the stimulus comprises one or more of scents based on: linalool, nerolidol, bornyl acetate, bisabolol, myrcene, terpinen-4-ol, linalyl acetate, perillyl alcohol, camphor, beta caryophyllene, and / or alpha-pinene, thereby creating a relaxing effect in the patient.

[0113] (xviii) the controller is further configured to: responsive to identifying a period of shortened BBI of the patient: providing the stimulus to the patient until the patient’s BBI is identified as non-shortened.

[0114] (xix) the controller is further configured to: provide the stimulus in two or more releases, at release intervals of between 5 and 15 minutes.

[0115] (xx) the stimulus comprises one or more of scents based on: linalool, nerolidol, bornyl acetate, bisabolol, myrcene, terpinen-4-ol, linalyl acetate, perillyl alcohol, camphor, beta caryophyllene, and alpha-pinene, thereby creating a relaxing effect in the patient.

[0116] (xxi) the controller is further configured to: responsive to the identified sleep state being deep sleep: provide two or more releases of the stimulus, at intervals of between 5 and 15 minutes; thereby lengthening and / or deepening the patient’s deep sleep. (xxii) the stimulus comprises one or more of scents based on: linalool, nerolidol, bornyl acetate, bisabolol, myrcene, terpinen-4-ol, linalyl acetate, perillyl alcohol, camphor, beta caryophyllene, and alpha-pinene, thereby creating a relaxing effect in the patient.

[0117] (xxiii) the one or more scents are selected based on a personalization model.

[0118] (xxiv) the one or more scents are selected based on a habituation avoidance model.

[0119] According to another aspect of the presently disclosed subject matter there is provided a computer-implemented method of providing therapeutic stimulation to a patient during sleep, the method comprising: a) identifying a sleep state of the patient, and b) responsive to, at least, the identified sleep state, controlling a stimulator to provide a stimulus to the patient, the stimulus comprising one or more scents, and being based on, at least, an ordering of one or more scents, and a respective intensity and respective release pattern of each of one or more scents.

[0120] This aspect of the disclosed subject matter can further optionally comprise one or more of features (i) to (xxiv) listed above with respect to the system, mutatis mutandis, in any desired combination or permutation which is technically possible.

[0121] According to another aspect of the presently disclosed subject matter there is provided a computer program product comprising a computer readable non-transitory storage medium containing program instructions, which program instructions when read by a processor, cause the processing circuitry to perform a method of providing therapeutic stimulation to a patient during sleep, the method comprising: a) identifying a sleep state of the patient, and b) responsive to, at least, the identified sleep state, controlling a stimulator to provide a stimulus to the patient, the stimulus comprising one or more scents, and being based on, at least, an ordering of one or more scents, and a respective intensity and respective release pattern of each of one or more scents.

[0122] This aspect of the disclosed subject matter can further optionally comprise one or more of features (i) to (xxiv) listed above with respect to the system, mutatis mutandis, in any desired combination or permutation which is technically possible.

[0123] Unless otherwise defined, all technical and / or scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present disclosure pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of embodiments of the present disclosure, exemplary methods and / or materials are described below. In case of conflict, the patent specification, including definitions, controls. In addition, the materials, methods, and examples are illustrative only and are not intended to be necessarily limiting.

[0124] As will be appreciated by one skilled in the art, aspects of the present disclosure may be embodied as a system, method, or computer program product. Accordingly, aspects of the present disclosure may take the form of an entirely hardware embodiment, an entirely software embodiment (including firmware, resident software, microcode, etc.) or an embodiment combining software and hardware aspects that may all generally be referred to herein as a “circuit,” “module” or “system” (e.g., a method may be implemented using “computer circuitry”). Furthermore, some embodiments of the present disclosure may take the form of a computer program product embodied in one or more computer readable medium(s) having computer readable program code embodied thereon. Implementation of the method and / or system of some embodiments of the present disclosure can involve performing and / or completing selected tasks manually, automatically, or a combination thereof. Moreover, according to actual instrumentation and equipment of some embodiments of the method and / or system of the present disclosure, several selected tasks could be implemented by hardware, by software or by firmware and / or by a combination thereof, e.g., using an operating system.

[0125] For example, hardware for performing selected tasks according to some embodiments of the present disclosure could be implemented as a chip or a circuit. As software, selected tasks according to some embodiments of the present disclosure could be implemented as a plurality of software instructions being executed by a computer using any suitable operating system. In some embodiments of the present disclosure, one or more tasks performed in method and / or by system are performed by a data processor (also referred to herein as a “digital processor”, in reference to data processors which operate using groups of digital bits), such as a computing platform for executing a plurality of instructions. Instruction executing elements of the processor may comprise, for example, one or more microprocessor chips, ASICs, and / or FPGAs. Optionally, the data processor includes a volatile memory for storing instructions and / or data and / or a non-volatile storage, for example, a magnetic hard-disk and / or removable media, for storing instructions and / or data. Optionally, a network connection is provided as well. A display and / or a user input device such as a keyboard or mouse are optionally provided as well. Any of these implementations are referred to herein more generally as instances of computer circuitry.

[0126] Any combination of one or more computer readable medium(s) may be utilized for some embodiments of the present disclosure. The computer readable medium may be a computer readable signal medium or a computer readable storage medium. A computer readable storage medium may be, for example, but not limited to, an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, apparatus, or device, or any suitable combination of the foregoing. More specific examples (a non-exhaustive list) of the computer readable storage medium would include the following: an electrical connection having one or more wires, a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), an optical fiber, a portable compact disc read-only memory (CD-ROM), an optical storage device, a magnetic storage device, or any suitable combination of the foregoing. In the context of this document, a computer readable storage medium may be any tangible medium that can contain or store a program for use by or in connection with an instruction execution system, apparatus, or device. A computer readable storage medium may also contain or store information for use by such a program, for example, data structured in the way it is recorded by the computer readable storage medium so that a computer program can access it as, for example, one or more tables, lists, arrays, data trees, and / or another data structure. Herein a computer readable storage medium which records data in a form retrievable as groups of digital bits is also referred to as a digital memory. It should be understood that a computer readable storage medium, in some embodiments, is optionally also used as a computer writable storage medium, in the case of a computer readable storage medium which is not read-only in nature, and / or in a read-only state.

[0127] Herein, a data processor is said to be “configured” to perform data processing actions insofar as it is coupled to a computer readable medium to receive instructions and / or data therefrom, process them, and / or store processing results in the same or another computer readable medium. The processing performed (optionally on the data) is specified by the instructions, with the effect that the processor operates according to the instructions. The act of processing may be referred to additionally or alternatively by one or more other terms; for example: comparing, estimating, determining, calculating, identifying, associating, storing, analyzing, selecting, and / or transforming. For example, in some embodiments, a digital processor receives instructions and data from a digital memory, processes the data according to the instructions, and / or stores processing results in the digital memory. In some embodiments, “providing” processing results comprises one or more of transmitting, storing and / or presenting processing results. Presenting optionally comprises showing on a display, indicating by sound, printing on a printout, or otherwise giving results in a form accessible to human sensory capabilities.

[0128] A computer readable signal medium may include a propagated data signal with computer readable program code embodied therein, for example, in baseband or as part of a carrier wave. Such a propagated signal may take any of a variety of forms, including, but not limited to, electro-magnetic, optical, or any suitable combination thereof. A computer readable signal medium may be any computer readable medium that is not a computer readable storage medium and that can communicate, propagate, or transport a program for use by or in connection with an instruction execution system, apparatus, or device.

[0129] Program code embodied on a computer readable medium and / or data used thereby may be transmitted using any appropriate medium, including but not limited to wireless, wireline, optical fiber cable, RF, etc., or any suitable combination of the foregoing.

[0130] Computer program code for carrying out operations for some embodiments of the present disclosure may be written in any combination of one or more programming languages, including an object-oriented programming language such as Java, Smalltalk, C++ or the like and conventional procedural programming languages, such as the “C” programming language or similar programming languages. Additionally or alternatively, sequences of logical operations (optionally logical operations corresponding to computer instructions) may be embedded in the design of an ASIC and / or in the configuration of an FPGA device. The program code may execute entirely on the user’s computer, partly on the user’s computer (e.g., as a stand-alone software package), partly on the user’s computer and partly on a remote computer or entirely on the remote computer or server. In the latter scenario, the remote computer may be connected to the user’s computer through any type of network, including a local area network (LAN) or a wide area network (WAN), or the connection may be made to an external computer (for example, through the Internet using an Internet Service Provider).

[0131] Some embodiments of the present disclosure may be described below with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems) and computer program products according to embodiments of the present disclosure. It will be understood that each block of the flowchart illustrations and / or block diagrams, and combinations of blocks in the flowchart illustrations and / or block diagrams, can be implemented by computer program instructions. These computer program instructions may be provided to a processor of a general purpose computer, special purpose computer, or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other programmable data processing apparatus, create means for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0132] These computer program instructions may also be stored in a computer readable medium that can direct a computer, other programmable data processing apparatus, or other devices to function in a particular manner, such that the instructions stored in the computer readable medium produce an article of manufacture including instructions which implement the function / act specified in the flowchart and / or block diagram block or blocks.

[0133] The computer program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other devices to cause a series of operational steps to be performed on the computer, other programmable apparatus or other devices to produce a computer implemented process such that the instructions which execute on the computer or other programmable apparatus provide processes for implementing the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0134] Some of the methods described herein are generally designed only for use by a computer; and may not be feasible or practical for performing purely manually, by a human expert. A human expert who wanted to manually perform similar tasks, such inspecting objects, might be expected to use completely different methods, e.g., making use of expert knowledge and / or the pattern recognition capabilities of the human brain, which would be vastly more efficient than manually going through the steps of the methods described herein.

[0135] BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0136] Some embodiments of the present disclosure are herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example, and for purposes of illustrative discussion of embodiments of the present disclosure. In this regard, the description taken with the drawings makes apparent to those skilled in the art how embodiments of the present disclosure may be practiced.

[0137] In the drawings:

[0138] FIG. 1A schematically illustrates a simplified block diagram of a system 100 for providing olfactory stimulation to a patient, in accordance with exemplary embodiments of the invention;

[0139] FIG. IB schematically illustrates a simplified block diagram illustration of a system 100 for providing olfactory stimulation during sleep, in accordance with some exemplary embodiments of the invention;

[0140] FIG. 2 is a simplified flowchart of a method for providing olfactory stimulation to a patient, in accordance with some exemplary embodiments of the invention;

[0141] FIG. 3 is a simplified flowchart of a method to provide a patient-specific olfactory stimulation to a patient, in accordance with some exemplary embodiments of the invention.;

[0142] FIGs. 4A-B are a more detailed flowchart of a method for providing olfactory stimulation to a patient, in accordance with some exemplary embodiments of the invention;

[0143] FIG. 5 is a simplified flowchart of a method for deepening and improving sleep by olfactory stimulation, in accordance with some exemplary embodiments of the invention;

[0144] FIG. 6 is a simplified flowchart of a method for treating mental health conditions by olfactory stimulation during sleep, in accordance with some exemplary embodiments of the invention;

[0145] FIG. 7 is a simplified flowchart of a method for identifying dementia by olfactory stimulation, in accordance with some exemplary embodiments of the invention;

[0146] FIGs. 8A-B are a more detailed flowchart of a method for identifying dementia by olfactory stimulation, in accordance with some exemplary embodiments of the invention; FIGs. 9A-C schematically illustrate side views of a scent diffuser, in accordance with some exemplary embodiments of the invention;

[0147] FIG. 9D schematically illustrates an exploded view of a scent diffuser, in accordance with some exemplary embodiments of the invention;

[0148] FIG. 9E schematically illustrates an aerosolizer of a scent diffuser, in accordance with some exemplary embodiments of the invention;

[0149] FIG. 9F schematically illustrates a perspective view of a scent diffuser for releasing a plurality of scents, in accordance with some exemplary embodiments of the invention;

[0150] FIGs. 10A-B schematically illustrate perspective side views of a positioned scent diffuser, in accordance with some exemplary embodiments of the invention;

[0151] FIG. IOC schematically illustrates a side view of a positioned scent diffuser with an adaptor for installing thereof, in accordance with some exemplary embodiments of the invention;

[0152] FIG. 11A schematically illustrates a controller of a system for providing olfactory stimulation during sleep, in accordance with some exemplary embodiments of the invention;

[0153] FIG. 11B schematically illustrates a software of a controller, in accordance with some exemplary embodiments of the invention;

[0154] FIG. 12 schematically illustrates an exemplary flow diagram of an olfactory treatment using a system for providing olfactory stimulation, in accordance with some exemplary embodiments of the invention;

[0155] FIG. 13 is a simplified flowchart of a method for training a system for providing olfactory stimulation to a patient during sleep, in accordance with some exemplary embodiments of the invention;

[0156] FIGs. 14A-B are a flowchart of a method for training a system to classify sleep satges, in accordance with some exemplary embodiments of the invention;

[0157] FIGs. 15A-B are a flowchart of a method for training a system to select an olfactory stimulation, in accordance with some exemplary embodiments of the invention;

[0158] FIG. 16 is a flowchart of a method for personalizing an olfactory treatment, in accordance with some exemplary embodiments of the invention;

[0159] FIG. 17 is a flowchart of a method for improving olfactory exposure effectiveness, in accordance with some exemplary embodiments of the invention.

[0160] FIGs. 18A-C are bar charts showing an example of patients' feedback on olfactory treatment during sleep, applied in accordance with some embodiments of the invention; FIG. 19A is a table with average results of heart rate, during the entire night's sleep or during REM sleep, of nights free from olfactory stimulation versus nights when the patient was exposed to olfactory treatment, in accordance with some exemplary embodiments of the;

[0161] FIG. 19B is a table with average results of heart rate change resulting from exposure to olfactory treatment, during the entire night's sleep or during REM sleep, in accordance with some exemplary embodiments of the invention; and

[0162] FIGs. 19C-D are graphs showing an example of changes in the heart rate of one patient during sleep, as a result of exposing thereof to olfactory stimulation, in accordance with some exemplary embodiments of the invention.

[0163] FIG. 20 schematically illustrates a potential effect of olfactory stimulation on a patient’s brain, in accordance with some exemplary embodiments of the invention.

[0164] FIGs. 21A-C are graphs showing an example of changes in the heart rate, oxygen, and stress of one patient during sleep, as a result of exposing thereof to olfactory stimulation, in accordance with some exemplary embodiments of the invention.

[0165] FIGs. 22A-C are graphs showing an example of changes in the average heart rate, average beat-to-beat interval, and stress of one patient during sleep, as a result of exposing thereof to olfactory stimulation based on different scents, in accordance with some exemplary embodiments of the invention.

[0166] DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

[0167] The present invention, in some embodiments thereof, relates to the field of olfactory treatment and more particularly, but not exclusively, to a system and a method for providing olfactory stimulation during sleep

[0168] Overview

[0169] An aspect of some embodiments of the invention relates to a method for lowering the heart rate of a patient by exposing the patient to olfactory stimulation, optionally, during sleep. Olfactory stimulation has a direct connection to the brain and can potentially influence the autonomic nerve system. In some embodiments, an olfactory stimulation perceived by the patient as relaxing can activate the parasympathetic nervous system (PSNS), which slows the heart rate and / or breathing rate, lowers blood pressure, and / or promotes digestion. In some embodiments, an olfactory stimulus is provided to the patient based on an indication (e.g., physiological indication). In some embodiments, the indication is a specific sleep stage. In some embodiments, the stimulus is provided during a sleep stage where the influence of the stimulation is maximal and / or relatively enhanced, having the potential advantage of increasing the treatment effectiveness. Alternatively or additionally, the stimulus is provided in a controlled manner, during a sleep stage characterized by elevation of heart rate potentially leading to reducing and / or avoiding stimulation in other sleep stages. This controlled stimulation administration hasthe potential advantage of reducing and / or avoiding adaptation of the olfactory system (e.g., sense of smell) of the patient.

[0170] In some embodiments, said sleep stage, where olfactory stimulation is applied, is a REM (Rapid Eye Movement) sleep stage. REM sleep is often associated with vivid dreams, and the brain activity during REM sleep is similar to that during wakefulness. This increased and / or intense brain activity may necessitate a higher demand for oxygen and nutrients, which is facilitated by an increased heart rate to ensure sufficient blood flow to the brain. In some embodiments, exposing the patient to an olfactory stimulus, having a calming and / or relaxing influence thereof potentially reduces the patient’s heart rate, optionally while provided, alternatively or additionally, after the patient is no longer exposed to the stimulation. For example, in some embodiments, exposing a patient to a calming and / or relaxing fragrance during a REM sleep stage, potentially reduces the patient's heartbeat during the rest of the night sleep, optionally, including during following REM stages, while the stimulation is no longer provided.

[0171] In some embodiments, the olfactory stimulation is provided at times when the efficiency thereof is enhanced, having the potential advantage of reducing and / or avoiding olfactory habituation, in addition to lowering fragrance substances amounts and / or costs. For example, the stimulation is provided during a REM stage, where there is a relatively high probability that the patient will experience nightmares and / or an increase in physiological parameters such as heart rate, blood pressure, and / or respiratory rate resulting from said nightmares. In another example, the heart rate during REM is close to the patient’s resting heart rate, such that it is desirable to provide olfactory stimulation to lower the heart rate during sleep for a patient suffering from a relatively high resting heart rate.

[0172] In some embodiments, alternatively or additionally to indication-based stimulation, olfactory stimulation can be provided through the course of sleep and / or a portion thereof, optionally, regardless of the sleep stage. In some embodiments, the indication for exposing the patient is a deviation of heart rate and / or heart rate variability from a regular rate. An increase in heart rate during sleep can caused by various reasons, such as the patient experiencing a dream, particularly a nightmare, stress and / or anxiety during sleep, sleep disorders, such as sleep apnea (e.g., obstructive sleep apnea) which can cause significant fluctuations in heart rate, certain medications with stimulating effects, chronic health conditions such as heart disease, and / or high blood pressure can lead to an elevated heart rate during sleep. Heart rate increase can be a sudden increase and / or a general increase (for example, caused by changes in blood pressure). In some embodiments, the deviation from a regular heart rate is evaluated considering a current sleep stage, for example, the heart rate during REM is compared to a typical heart rate during REM, which is usually higher than during other sleep stages and / or heart rate during deep sleep is compared to a typical heart rate during deep sleep, which is usually lower than in other sleep stages.

[0173] In some embodiments, a deviation of heart rate and / or heart rate variability from a regular rate is detected during a REM stage, when the patient is already exposed to an olfactory stimulus, the olfactory stimulation can be enhanced, for example, by increasing the intensity and / or by changing the fragrances.

[0174] In some embodiments, the method comprises detecting an elevated heart rate and providing a fragrance that potentially activates the parasympathetic nervous system, such as a fragrance having a calming and / or relaxing effect on the patient which leads to an heart rate decrease.

[0175] Alternatively or additionally, the method comprises detecting a slower-than-normal heart rate and providing a fragrance that potentially activates the sympathetic nervous system, such as a fragrance having an exciting effect on the patient.

[0176] In some embodiments, the olfactory treatment has a long-term effect, for example, an influence on the autonomic nerve system that can extend during daytime and / or over several days. For example, improving dream content and / or emotions during sleep can potentially break a cycle of poor sleep and sleep avoidance which might result in chronic fatigue (e.g., a patient experiences interrupted sleep as a result of nightmares, and despite feeling fatigued throughout the day, avoids sleeping at night to prevent experiencing nightmare). Breaking this cycle potentially has a long-term effect of reducing chronic fatigue.

[0177] An aspect of some embodiments of the invention relates to a method for treating post- traumatic stress disorder (PTSD) by exposing the patient to olfactory stimulation during sleep. 31

[0178] In some embodiments, the method can be utilized for treating other mental health conditions such as generalized anxiety disorder and / or depression.

[0179] During night and / or other sleep times patients who suffer from PTSD are typically alert, frequently wake up, can't get back to sleep, and / or might have difficulty entering into a deep sleep state. Individuals with PTSD commonly experience nightmares usually related to the traumatic events they have experienced. Experiencing this nightmare can disrupt sleep, adding to sleep disturbances and difficulties with falling asleep or staying asleep, which are common for individuals with PTSD. In addition, the nightmares can be vivid causing distress, and / or evoke intense emotional reactions, such as fear, anxiety, or helplessness. Furthermore, these feelings may contribute to distress during waking time and / or avoidance of sleep.

[0180] Providing the patient with olfactory treatment before and / or during sleep can potentially ease one or more of the aforementioned symptoms, having the potential advantage of improving the patient's sleep which leads to improvement in quality of life and overall wellbeing. An additional potential advantage of the olfactory treatment is reducing the need and / or dependency of the patient on consuming medications to be able to sleep and / or reduce the overall medication consumption for dealing with the disorder.

[0181] In some embodiments, the treatment can be employed by the patient, optionally, at home, optionally by using a home-use system. Home usage potentially reduces environmental changes and discomfort due to treatment and has the potential advantage of reducing and / or minimizing sleep interference. Alternatively or additionally, the method can be employed in treatment facilities and / or sleep laboratories, optionally by a caregiver.

[0182] In some embodiments, alternatively or additionally to relieving the disorder's symptoms, olfactory treatment can potentially have long-term effects. Without being bound to theory, an olfactory stimulation according to some embodiments of the invention can potentially train the brain to increase calm and regulate how stress responds. In addition, olfactory stimulation can affect the brain (e.g., due to the intricate neural pathways involved in olfaction). Research has shown that PTSD is a brain-based disorder, and olfactory treatment can also influence those areas of the brain implicated in PTSD.

[0183] In some embodiments, the treatment comprises exposing the patient to olfactory stimuli that potentially influence dream content, having the potential advantage of reducing and / or avoiding nightmares. For example, lowering the intensity and / or severity of nightmares, reducing nightmares length and / or nightmares frequency.

[0184] In some embodiments, the treatment comprises exposing the patient to fragrance(s) optionally, perceived thereby as pleasant and / or positive, which can affect the dream content to be more pleasant and / or positive to the patient. In some embodiments, the exposure is performed during at least a portion of one or more REM sleep stages. The REM phase is associated with vivid dreaming, such that providing olfactory stimulation during thereof has the potential advantage of enhancing treatment effectiveness. In addition, providing olfactory stimulation upon detecting a REM sleep stage potentially reduces the stimulation duration having the potential advantage of reducing adaptation of the olfactory system. In some embodiments, the emotional content of dreams is independent of other conditions of the patient, such as apnea and perceived risk of awakening.

[0185] It is noted, that olfactory stimulation is provided selectively during REM sleep. In one example, when influencing the content of dreams and / or the emotional state of the patient during dreams to potentially reduce nightmares, a stimulus having a positive effect on the patient is provided during REM. In a second example, when improving memory (e.g., treating dementia), a scent that stimulates the brain (e.g., enhancing synaptic strengthening) is provided during REM (REM sleep is associated with procedural memory consolidation and / or emotional memory consolidation). When lowering heart rate, a relaxing and / or claiming stimulation is provided during REM sleep.

[0186] In some embodiments, the method comprises detecting a sleep stage, such as REM sleep stage, while it occurs, optionally at the initial thereof. For example, in some embodiments, a sleep stage is detected about 1-2 minutes then its beginning. For example, about 0.5-2 minutes, or 1-5 minutes, or 2-10 minutes, or about 1.1 minutes, or about 5 minutes, or lower or higher, or intermediate numbers of minutes.

[0187] In some embodiments, the method comprises indicating that the patient is experiencing a nightmare and exposing the patient to a pleasant fragrance for potentially influencing the dream content such as ceasing the nightmare, and / or reducing the severity thereof. Alternatively or additionally, a relaxing fragrance is provided, for calming fear and / or anxiety caused by the nightmare.

[0188] In some embodiments, the method comprises exposing the patient to fragrance perceived thereby as claiming during a deep sleep stage, for potentially alleviating stress, anxiety, and / or fear. The deep sleep stage is associated with memory consolidation including the processing of emotional memories, the consolidation of emotional experiences, and the regulation of emotional reactivity.

[0189] In some embodiments, olfactory stimulation is provided for deepening and / or improving the patient’s sleep. In some embodiments, the method comprises exposing the patient to relaxing fragrance(s) during a deep sleep stage for potentially prolonging the stage duration, having the potential advantage of enhancing the depth, duration, and / or quality of the total sleep.

[0190] In some embodiments, the method comprises exposing the patient to calming fragrance(s) for promoting relaxation and reducing stress and anxiety during light sleep stages. This exposure potentially promotes entry into deep sleep, and / or increases the proportion of deep sleep relative to total sleep.

[0191] In some embodiments, the method comprises exposing the patient to fragrance(s) having a calming, relaxing and / or anesthetizing (e.g., sleeping) effect on the patient, during a pre-sleep awakening period. PTSD patients often experience hyperarousal, making it difficult to relax and / or feel safe enough to initiate sleep. Exposing the patient to fragrance(s) having a calming and / or relaxing effect thereof has the potential advantage of promoting sleep initiation.

[0192] In some embodiments, if undesired wakening accrues during the course of sleep, the fragrance(s) are provided to potentially assist the patient in regaining sleep. In some embodiments, the stimulation is provided to the patient before being wholly aroused, having the potential advantage of easing sleep recovery and / or preventing the awakening. In some embodiments, the patient is monitored to detect signs of wakening, and once detected, the stimulation is provided.

[0193] In some embodiments, the method comprises exposing the patient to olfactory stimulation to reduce heart rate during sleep. Heart rate during sleep in individuals with PTSD can be negatively influenced by a combination of factors, including for example hyperarousal symptoms, nightmares, sleep disturbances, and / or medication effects.

[0194] Nightmares and / or intrusive memories for example related to a traumatic event can trigger physiological arousal responses during sleep, including increases in heart rate and / or blood pressure. The emotional effect of nightmares may lead to elevated heart rate during a REM (rapid eye movement) sleep stage when dreams are most vivid. In some embodiments, the method comprises exposing the patient to a fragrance(s) perceived by the patient as relaxing and / or positive, during a REM sleep stage, to potentially reduce the patient's heart rate. Alternatively or additionally, the stimulation is provided upon heart rate elevation detection, optionally, until achieving regulation of the heart rate. In some embodiments, the patient's heart rate is monitored during an REM sleep stage, while the patient is exposed to olfactory stimulation. An increase in the heart rate, exceeding the relatively high heart rate typical of REM, can indicate that the patient is experiencing a nightmare. In some embodiments, one such increase is detected, the olfactory stimulation is modified to potentially reduce the relatively high heart rate. For example, the fragrance intensity is amplified, the fragrance(s) is replaced and / or combined with other fragrance(s),

[0195] In some embodiments, the method comprises exposing the patient to olfactory stimulation during at least a portion of the patient’s sleep, optionally, during the entire course of sleep, regardless of the sleep stage. In some embodiments, PTSD is associated with various sleep disturbances, including insomnia, fragmented sleep, and alterations in sleep architecture. Disrupted sleep patterns may contribute to fluctuations in heart rate during different stages of sleep, such as prolonged periods of elevated heart rate or frequent awakenings.

[0196] An aspect of some embodiments of the invention relates to diagnosing cognitive loss, while the patient is asleep, by detecting anosmia (partial and / or complete loss of the sense of smell). Without being bound to theory, it was found that diminishing sense of smell can be an early symptom of neurodegenerative diseases for example, dementia Alzheimer's, and / or Parkinson's disease, such that changes in smell perception may precede a cognitive decline. Anosmia detection potentially allows early detection of neurodegenerative diseases, having the potential advantage of slowing down the progression thereof, increasing the effectiveness of symptom management, and / or delaying the onset of severe cognitive decline.

[0197] In some embodiments, the method comprises learning the patient's physiological reaction when exposed and senses (e.g., smells) one or more fragrances, optionally while the patient is awake, and then monitoring the patient during sleep for detecting a lack of said reaction which indicates anosmia.

[0198] In some embodiments, the learning step comprises monitoring one or more of the patient's physiological parameters such as heart rate, heart rate variability, breathing rate, and / or patient’s movements during a controlled exposure of the awake patient to olfactory stimulation. The patient indicates the ability thereof to smell the provided fragrance(s), and data regarding changes in the patient’s physiological parameters while sensing the fragrance(s) is collected. In some embodiments, this data is used to train a system to detect the patient’s physiological response to using the sense of smell thereof. In some embodiments, this data is used as a baseline for detecting a decline in the patient’s sense of smell. In some embodiments, this data is used for an initial evaluation of the patient's smelling abilities. For example, if the patient indicates on lack of ability to sense intense fragrances, it may indicate anosmia. In some embodiments, this evaluation comprises a preliminary stage of monitoring the patient’s sense of smell for obtaining a baseline about the olfactory abilities thereof. For example, impaired sense of smell due to disease and / or prolonged exposure to chemical substances, or inability to smell certain fragrances, for example, due to genetics. In some embodiments, the learning step is passive on the part of the patient. The patient is exposed to olfactory stimulation, while the physiological parameter(s) thereof are monitored, optionally, during sleep. In some embodiments, the monitoring is performed by a system that can deduce when the patient can smell an introduced fragrance, for example, while recognizing a typical physiological reaction (e.g., change in physiological parameters) to a fragrance, optionally a specific fragrance. For example, increased heart rate, blood pressure, and / or respiratory rate as a result of exposure to fragrance(s) having a relaxing, calming and / or positive effect on the patient.

[0199] In some embodiments, the method comprises monitoring the state of the patient's sense of smell periodically, optionally, during sleep, optionally, at night, and / or every number of nights. One or more of the patient’s physiological parameters are measured while the patient is exposed to different olfactory stimuli, such as different fragrances and / or different release intensities. The patient's reaction to the fragrances is evaluated to detect that the patient can smell the introduced fragrance and / or to evaluate the sense of smell sensitivity. For example, in some embodiments, the evaluation comprises exposing the patient to scents and / or intensities that the patient can small, based on preliminary tests thereon, a lack of physical reaction to this exposure can indicate a decrease and / or loss of smell. In another example, the patient is exposed to fragrances of different intensities, and / or to fragrances of a different stimulation level, optionally, in ascending order. The intensity to which the patient will react indicates the sensitivity of the sense of smell thereof. In addition, a comparison with previous results can indicate if there is a decrease in the olfactory sensation.

[0200] Monitoring at night while the patient is asleep has the potential advantage of reducing patient distractions. Performing the measurements, as the patient is passive (e.g., asleep and / or lying in bed), has the potential advantage of simplifying the process for the patient, and potentially enhancing patient compliance with treatment. Optionally said measurements are by an automatic system that controls the fragrance release and / or patient’s monitoring, If a diminishment in the patient's sense of smell is detected, a notice is given. In some embodiments, the patient is informed and / or recommended to reach medical guidance. Alternatively or additionally, a caregiver is informed, for example in cases where the patient's cognitive state is poor.

[0201] An aspect of some embodiments of the invention relates to treating dementia and / or other neurodegenerative diseases by exposing the patient to olfactory stimulation (olfactory enrichment) during sleep. Herein treatment can refer to symptom improvement, memory improvement, stopping and / or delaying the disease, and / or causing changes in the areas of the brain damaged by the disease.

[0202] In some embodiments, the method of treating can be utilized for memory improvement, for example for older adults.

[0203] In some embodiments, treating comprises exposing the patient to olfactory stimulation for stimulating the brain. In some embodiments, treating comprises stimulating the brain during memory storage processes for potentially increasing treatment effectiveness

[0204] Without being bound to theory, critical memory storage processes (memory consolidation ) may occur during sleep. The deep sleep stage is associated with declarative memory consolidation and semantic memory consolidation. The REM sleep stage is associated with procedural memory consolidation and / or emotional memory consolidation.

[0205] In some embodiments, the method comprises identifying a deep sleep stage and / or a REM sleep stage and providing olfactory stimulation. In some embodiments, the method comprises promoting deep sleep, optionally by exposing the patient to olfactory stimulation having a relaxing and / or anesthetizing effect thereof during a light sleep stage and / or during falling asleep.

[0206] In some embodiments, the method comprises exposing the patient to a plurality of fragrances for potentially enhancing brain stimulation. In some embodiments, the plurality of fragrance comprises about 4 fragrances, for example, 1- 4 fragrances, or 2-7 fragrances, or 4- 15 fragrances, or 4 fragrances, or 3 fragrances, or 6 fragrances, or lower or higher or intermediate numbers of fragrances. In some embodiments, each or some of the fragrances have a different effect on the patient, alternatively or additionally, each or some of the fragrances are from another fragrance family. In addition, the plurality of fragrances has the potential advantage of reducing and / or avoiding adaptation of the brain to the stimulation and / or adaption of the olfactory system to a fragrance. For example, replacing a fragrance with another fragrance, optionally, from a different fragrance family, having the same and / or substantially the same influence on the patient. In another example, a fragrance is replaced with a fragrance that has a different influence on the patient.

[0207] In some embodiments, one or more fragrances are altered between nights during the treatment, alternatively or additionally, one or more fragrances are altered during the night, optionally during a sleep stage.

[0208] In some embodiments, the fragrances are introduced to the patient in turns, optionally with long enough intervals therebetween for potentially reducing and / or avoiding fragrance blending and / or olfactory habituation. Alternatively or additionally, the fragrances are introduced in turns with some overlap in time between fragrances.

[0209] In some embodiments, one or more fragrances are introduced simultaneously for fragrance mixing. A mixture of scents potentially has a different influence on the patient compared to the separate fragrance components. In some embodiments, the fragrance mixing is performed in a controlled manner, where the percentage, intensity, and / or type of each fragrance is determined to obtain a desired effect of the mixed fragrant. Mixing the plurality of fragrances potentially increases the number and / or variety of olfactory stimulations without increasing the number of based fragrances, having the potential advantage of simplifying the equipment and / or costs.

[0210] In some embodiments, olfactory enrichment is utilized for training the olfactory center to potentially improve the patient’s smelling abilities and / or maintain the sensitivity thereof, olfactory training may potentially lead to improving and / or maintaining the cognitive processing abilities related to the sense of smell. Without being bound to theory, in some cases, a deterioration of olfactory ability occurs before a deterioration of cognitive abilities. For example, COVID-19 can result in olfactory loss and long-term cognitive loss. The olfactory training (e.g., olfactory improvement) can potentially reduce, delay, and / or prevent cognitive decline. Alternatively or additionally, this training can be beneficial for individuals with olfactory impairments seeking to regain their sense of smell, and / or individuals with other reasons, such as professionals in fields like wine tasting, and / or perfumery.

[0211] In some embodiments, the training comprises exposure to a plurality of fragrances, optionally regular exposure, and optionally during sleep. Exposure during sleep has the potential advantage of simplifying the process for the patient and / or improving the patient’s compliance, which potentially promotes regular exposure. In some embodiments, the plurality of fragrances comprises different fragrances such as herbs, flowers, essential oils, or aromatic compounds. A fragrance mixing (e.g., mixing of one or more base fragrances) potentially increases the number of fragrances that can be provided to the patient, having the potential advantage of improving the olfactory treatment.

[0212] An aspect of some embodiments of the invention relates to a method for personalizing an olfactory treatment, optionally provided during sleep. In some embodiments, the method comprises personalizing one or more olfactory treatments such as treatment for lowering heart rate, treatment for deepening sleep, treatment for distress disorders, procedure detecting anosmia, and / or treatment for neurodegenerative diseases. Although there are some fragrances known to have a relaxing and / or positive influence on patients, based on statistical data, the fragrance perception of an individual is often subjective and dependent, for example, on past experiences, cultural influences, exposure and familiarity, and / or individual differences in sensory perception.

[0213] In some embodiments, the method comprises evaluating the patient's response to different fragrances and selecting the fragrance(s) having a desired effect thereon, optionally, during a pre-treatment period (e.g., a learning period). In some embodiments, the patient is exposed to different fragrances and provides feedback regarding their influence thereon. Alternatively or additionally, the patient’s physiological reaction to the exposure is evaluated, optionally during sleep, alternatively or additionally, while the patient is awake.

[0214] In some embodiments, the patient’s brain activity as a response to olfactory stimulation is evaluated, for example by EEG (Electroencephalogram) and or PSG (Polysomnography).

[0215] In some embodiments, the patient’s physiological parameters as a response to olfactory stimulation are evaluated. Monitoring physiological parameters does not require a sleep laboratory, and can be performed at home, optionally, by the patient. For example, tracking the patient’s heart rate and / or heart rate variability, breathing rate, body temperature, and / or movements during sleep

[0216] In some embodiments, this evaluation is performed during the treatment learning stage, alternatively or additionally this evaluation is an ongoing process that accompanies the treatment. The ongoing process allows the adjustment of the patient-specific fragrance selection, for example, according to a patient's time-varying preferences or responses to treatment. In some embodiments, the ongoing process comprises reporting to a carrier and / or a treatment center regarding changes in the patient’s response to treatment and / or regarding treatment modification(s).

[0217] In some embodiments, the personalization method comprises exposing the patient to olfactory stimulation based on a patient-specific indication(s). In some embodiments, olfactory stimulation is provided based on the detection of a specific sleep stage, and the method comprises learning the patient sleep pattern and / or learning the patient physical characteristics during sleep, for potentially improving the detection of sleep stages.

[0218] In some embodiments, the personalization method comprises exposing the patient to olfactory stimulation based on an irregularity of physiological parameters and / or irregularity of the patient’s behavior during sleep, and the method comprises learning the patient's characterizing physiological parameters and / or behavior during sleep and / or different sleep stages, for potentially improve detection of a deviation from regularity. In some embodiments, the personalization method comprises collecting historical data and / or receiving data regarding the patient's medical history. The data can be used for defining patient-specific indicators for providing treatment and / or defining the stimulation selection.

[0219] In some embodiments, the personalization method comprises exposing the patient to a plurality of default fragrances, optionally selected based on statistical data and the patient is requested to select one or more fragrances based on the personal preferences thereof. In some embodiments, the default fragrances are known in the literature, alternatively or additionally, selected based on the influence thereof on a control group and / or other patients.

[0220] In some embodiments, the personalization method comprises receiving suggestions from the patient regarding fragrance which has a desired effect thereon. For example, fragrance(s) refers to positive experiences and / or memories, and / or reminding a loved one, such as the aroma of a childhood meal and / or the fragrance of a loved one's perfume. This suggestion can promote the use of unconventional fragrances during treatment, having the potential advantage of improving treatment effectiveness.

[0221] In some embodiments, the personalization method comprises subjecting the patient to positive conditioning which includes exposing the patient to one or more fragrance(s) during a calming and / or positive experience(s), potentially leading the patient to associate the one or more fragrance(s) with the filing thereof during the experience(s). Then, the one or more fragrance(s) are introduced to the patient during olfactory treatment. In some embodiments, a fragrance is selected based on the nature of the feeling and / or experience of the conditioning. For example, a fragrance introduced to the patient during a calming experience may potentially have a calming effect thereon, and potentially be selected when a calming influence is required.

[0222] An aspect of some embodiments of the invention relates to the personalization of an olfactory treatment. The personalization is performed using a system and / or an Al component thereof. The system can apply personalization to each method described above and / or in this document. In some embodiments, the personalization is applied to tailor the treatment to the patient, having the potential advantage of improving treatment effectviness.

[0223] In some embodiments, the personalization comprises the identification of sleep stages according to the patient's physiological parameters. In some embodiments, the identification requires an analysis of a plurality of measurements and / or a combination thereof, optionally, using the system and / or the Al component, which performs machine learning. For example, identifying a REM sleep stage requires an analysis of heart rate, breathing rate, movements during sleep, and / or part of the night. In some embodiments, the Al component is trained based on pairs of physiological parameters and sleep stage, where the sleep stage was detected by a sleep tracker and / or brain waves (e.g., via electroencephalography (EEG)). In some embodiments, the Al is trained using patient-specific data, alternatively or additionally, the system is trained using data from a plurality of patients and then personalized using patientspecific data.

[0224] In some embodiments, personalization includes the identification of individual sleep patterns. For example, the proportion of deep sleep tends to be higher during the initial part of the night, whereas REM sleep predominates during the latter part. These proportions vary from patient to patient, and the personalization comprises learning thereof. In another example, the personalization includes learning typical sleep stages lengths, which vary from patient to patient.

[0225] In some embodiments, personalization includes the identification state of the patient which requires attention. For example, learning the patient's resting heart rate and / or heart rate during different sleep stages, for detecting a deviation from a regular heart rate. Another example is learning the patient's reaction to nightmares, for detecting nightmares while occurring.

[0226] In some embodiments, personalization comprises evaluating the effect of fragrances on a patient and selecting the stimulation when needed. The effect of a fragrance on a patient varies from patient to patient and depends on several factors, such as genetics, previous exposure, culture, and more. In some embodiments, the patient is exposed to many fragrances and / or release patterns thereof, and the physiological parameters thereof are analyzed to identify whether the fragrances have an effect and, if so, whether the effect is positive. Alternatively or additionally, The patient is exposed while awake and provides feedback on the effect of the fragrances thereof. In some embodiments, the system is trained based on Pairs of physiology parameters and the effect that caused them, and / or fragrances and the effect thereof on the patient. In some embodiments, this evaluation is performed during a pre-treatment procedure, alternatively or additionally, during treatment.

[0227] An aspect of some embodiments of the invention relates to a fragrance diffuser for personal use, optionally, sleep-orientated for providing olfactory treatment to a patient during sleep.

[0228] In some embodiments, the fragrance diffuser is configured to be placed near the patient, and release fragrance(s) locally, optionally, toward the patient. This local release has the potential advantage of reducing and / or avoiding an excessive release of fragrance(s) into a room and / or saturation of the room with scent(s). Reducing and / or avoiding fragrance(s) saturation potentially allows the clearance of odors between discharge episodes, and / or replacing a fragrance while potentially reducing and / or avoiding unwanted fragrance blending. An additional potential advantage of reducing and / or avoiding fragrance(s) saturation is reducing and / or avoiding habituation of the patient's sense of smell.

[0229] In addition, this local release potentially reduces exposure of another individual who shares a room and / or bed with the patient during sleep. This reduced exposure has the potential advantage of reducing unwanted effects and / or sleep disturbances to said individual.

[0230] In some embodiments, the scent diffuser releases fragrance(s) in intensity such that fragrance(s) reaches the patient in a desired sensing intensity, considering the location of the patient relative to the scent diffuser (e.g., distance and / or orientation).

[0231] In some embodiments, the scent diffuser can adjust the fragrance(s) release according to the distance and / or orientation thereof relative to the patient, and / or patient’s bed. In some embodiments, the patient inputs information said distance and / or orientation, and the scent diffuser adjusts the release intensity accordingly. Alternatively or additionally, the scent diffuser adjusts the release intensity automatically, by being operated by a controller. In some embodiments, the controller receives signals from a camera, detects the location of the scent diffuser and the patient and / or the patient’s bed, and calculates the relative distance therebetween.

[0232] In some embodiments, the fragrance diffuser comprises a motor, allowing moving a portion thereof for adjusting the direction of scent(s) release. For example, rotating the body thereof and / or rotating an outlet opening for modifying the orientation thereof.

[0233] In some embodiments, the fragrance diffuser comprises a movable arm for adjusting the distance thereof from the patient. In some embodiments, the arm is electric and can be remotely controlled by a remote control, a smartwatch and / or a smartphone. In some embodiments, the arm is controlled by a controller which automatically moves thereof to be at a desired location relative to the patient (desired distance and / or orientation).

[0234] In some embodiments, the fragrance diffuser is configured to release more than one fragrance according to a treatment plan, according to the requirements of an olfactory treatment plan. In some embodiments, the fragrance diffuser comprises more than one container (e.g., cartridge) containing a fluid fragrance (e.g., a liquid fragrance substance) and an aerosolizer, such as a piezoelectric disc, optionally, for each container. In some embodiments, the aerosolizer is located within the volume of the container, potentially reducing and / or avoiding noise, such as the noise created by the atomization and / or nebulization of a liquid at an outlet of a container. In some embodiments, the atomized and / or nebulized fragrance is convected out from the container and toward the patient using a fan. In some embodiments, the fragrance diffuser comprises a plurality of fans, optionally a fan for each container. A plurality of fans allows the use of relatively small fans while obtaining a desired fragrance convection, relatively small fans are potentially less noisy during operation, having the potential advantage of reducing disturbances to patient’s sleep.

[0235] In some embodiments, the fragrance diffuser comprises an air purifier for clearing the room of fragrances, if needed, having the potential advantage of reducing and / or avoiding adaptation of the sense of smell. The air purifier can be for example at least one fan, filter, and / or odor-absorbing material(s). In some embodiments, the air purifier is used to establish a desired release pattern. For example, the air purifier is used to clean the air between pulses of fragrance release, to obtain an intermittent and / or pulsed release.

[0236] In some embodiments, the fragrance diffuser is used to execute any of the methods described above and / or in this document.

[0237] Before explaining at least one embodiment of the present disclosure in detail, it is to be understood that the present disclosure is not necessarily limited in its application to the details of construction and the arrangement of the components and / or methods set forth in the following description and / or illustrated in the drawings and / or given in the Examples, drawings. Features described in the current disclosure, including features of the invention, are capable of other embodiments or of being practiced or carried out in various ways.

[0238] Referring now to the drawings, Fig. 1A showing a simplified block diagram of a system 100 for providing olfactory stimulation to a patient, in accordance with some exemplary embodiments of the invention. Herein, a patient is referring to a subject diagnosed with a disease, disorder, and / or medical condition that can potentially be treated by olfactory stimulation, and / or any individual that may benefit from olfactory treatment. In some embodiments, the methods and systems are used for people who do not have a medical diagnosis and / or as a preventive.

[0239] System 100 comprises a stimulator 102, that provides an olfactory stimulus to a patient, controlled by a controller 104 to provide the olfactory stimulus to the patient. In some embodiments of the invention, controller 104 uses an input from an optional monitor 106 to determine control of said stimulus. Monitor 106 is used to monitor one or more of the patient's physiology parameters, and / or the patient’s environment, In some embodiments of the invention, monitor 106 comprises at least one physiological sensor 108 for sensing one or more physiological parameters of the patient, for example, heart rate, heart rate variability (HRV), body temperature and / or a camera (e.g, to identify patient movement and / or eye state and / or movement. Optionally or alternatively, monitor 106 includes an environmental sensor, such as a sound sensor, temperature sensor, camera infra-red sensor, a radar, and / or a light sensor.

[0240] In some embodiments, said stimulus is selected to affect one or more of the patient's autonomic nervous system, the patient’s sleep state, the patient’s brain activity, and / or the patient’s thoughts and / or feelings. In some embodiments, the stimulus effect is short-term. For example, providing stimulation to potentially relieve and / or cease a nightmare the patient is experiencing at a moment. Alternatively or additionally, the stimulus effect is short-term. For example, providing stimulation to improve a patient’s memory.

[0241] For example, the stimulus may be selected to have a calming effect on the patient's autonomic nervous system, having the potential advantage of improving the patient’s overall well-being and / or having a positive health outcome. In one example, controller 104 controls the delivery (e.g., timing, amount, content) to have a desired effect. Optionally or alternatively, the scents are pre-selected, for example by the patient and / or a caregiver to have a desired effect and / or by the controller. In some embodiments, the scents and / or the delivery are adjusted by the controller, during treatment, for example, if habituation is detected (e.g., a decline in the patient’s response to olfactory stimulation) the controller may replace scents and / or alter the delivery (for example, extend the intervals between releases, and / or sets a release pause

[0242] In some embodiments, monitor 106 is mounted near and / or on the patient such that at least one sensor 106 can measure the patient’s physiological parameters, such as the patient’s vital signs. In some embodiments, monitor 106 can be implanted in the patient, alternatively or additionally, monitor 106 can be Distant but patient-oriented.

[0243] In some embodiments, controller 104 is configured to process the data received from sensor 106 and to identify a patient state, such as a physiological and / or a mental state during sleep. Herein, a physiological state can refer to a state of sleep and / or state defined by one or more of the patient's physical parameters, such as high heart rate, high breathing rate, and / or excessive movements during sleep. A mental state can maybe defined by a change of one or more physiological parameters identified by system 100 as a mental (and / or emotional) state. For example, increased sweating optionally together with an increase in heart rate may indicate nightmares, fear, anxiety, and / or stress. In some embodiments, controller 104 is configured to determine if to provide the patient a stimulus, based on said identified state of the patient. In some embodiments, controller 104 is configured to determine stimulus parameters such as the type, intensity duration and / or pattern of administration.

[0244] In some embodiments, controller 104 comprises and / or has access to a memory (such as memory 1108 shown in Fig. 11 A). In some embodiments, the memory comprises short-term and / or long-term treatment protocols).

[0245] Referring now to Fig. IB showing a simplified block diagram illustration of a system 100 for providing olfactory stimulation during sleep, in accordance with some exemplary embodiments of the invention.

[0246] In some embodiments, system 100 is configured to provide olfactory stimulus to a patient, during the course of the patient’s sleep. Stimulating the olfactory system of the patient during sleep and / or during a desired sleep stage has the potential advantage of improving treatment effectiveness. In some embodiments, system 100 is activated and / or controlled automatically during sleep, by controller 104, having the potential advantage of increasing the patient’s compliance with treatment.

[0247] In some embodiments, stimulator 102 comprises an odorant delivery device 202.

[0248] In some embodiments, odorant delivery device 202 is configured to be placed in the room near the sleeping patient, such as on a nightstand, and / or hanging by the bed. In some embodiments, system 100 comprises an arm for holding odorant delivery device 202, optionally, an adjustable arm that allows modifying the location of odorant delivery device 202.

[0249] In some embodiments, the position of delivery device 202 can be set and / or adjusted to aim the patient, e.g., release the at least one scent in the patient’s direction and / or in proximity to the patient. The localized release potentially reduces scent(s) saturation in the room, having the potential advantage of reducing the patient’s olfactory habituation in addition to reducing and / or minimizing a disturbance to another individual sleeping in the same room with the patient. In addition, reducing and / or avoiding scent(s) saturation allows for replacement between scent(s) while reducing and / or avoiding undesired scent(s) blending and / or allowing for scent(s) evacuation optionally, when needed. An additional potential advantage of the localized release is reducing the amount of scent substance(s) required to achieve a desired stimulation level (e.f., scent intensity). In some embodiments, the positioning and / or repositioning of odorant delivery device 202 is achieved by said adjustable arm. Alternatively or additionally, odorant delivery device 202 comprises a motor for at least a portion thereof. For example, a motor for rotating the body of odorant delivery device 202, and or a motor for adjusting the orientation of the outlet thereof.

[0250] In some embodiments, odorant delivery device 202 comprises and / or is connected to an air purifier 210, configured to clean the air from scents. In some embodiments, air purifier 210 comprises one or more of a fan, a filter, and / or suction device for evacuating air which comprises scents. Alternatively or additionally, air purifier 210 comprises an atomizer and / or nebulizer for releasing vaporable and / or atomized smell adsorption material(s).

[0251] In some embodiments, air purifier 210 is controlled by control 104, which operates thereof for example, in the intervals between scent pulses, before replacing scents, when the room is saturated with a certain scent, and / or when olfactory habituation of the patient is detected.

[0252] In some embodiments, monitor 106 comprises a camera, and controller 104 comprises an image processor configured to assess the distance of the patient from odorant delivery device 202. In some embodiments, the adjustable arm can be automatically controlled by controller 104, such that controller 104 moves the arm to position odorant delivery device 202 in a desired distance and / or orientation from the patient and / or the patient’s nose. Alternatively, or additionally, odorant delivery device 202 comprises a movable component, such as a rotatable body that can rotate around the longitudinal axis of the device. Alternatively or additionally, odorant delivery device 202 comprises a rotatable aperture from which the scents are released.

[0253] Alternatively or additionally to odorant delivery device 202 that is configured to be placed in the room near the sleeping patient, odorant delivery device 202 can be wearable and / or positioned within the bed, such as in the pillow and / or sheets.

[0254] In some embodiments, odorant delivery device 202 comprises at least one atomizer and / or nebulizer, which disperses a liquid scent substance as described in this document. Alternatively or additionally, odorant delivery device 202 comprises an ultrasonic scent diffuser, heat scent diffuser, and / or vent clip.

[0255] In some embodiments, system 100 comprises a monitor 206 which optionally comprises a wearable device, having the potential advantage of allowing monitoring of a sleeping patient without being disconnected by patient movement during sleep and / or potentially less interfering with the patient’s sleep. For example, in some embodiments, monitor 200 is configured to be worn on the patient’s wrist, having the potential advantage of reducing discomfort during sleep and / or sleep disruption. Alternatively or additionally to a wearable device, monitor 206 may comprise a device configured to be located in the room and / or on the bed. For example, a device mounted on the mattress and / or sheets.

[0256] Monitor 106 comprises at least one sensor for tracking the patient's sleep (e.g., a sleep tracker). In some embodiments, the at least one sensor 108 is configured to track at least one of the patient’s physiological parameters which indicates the stages of a sleep cycle and / or a mental and / or physiological stage of the patient during sleep.

[0257] In some embodiments, monitor 106 is a dedicated device provided with system 100. Alternatively or additionally, monitor 106 can be an off-the-shelf product such as a smartwatch or activity band (such as, the Apple Watch, Samsung Galaxy Watch, Fitbit, Oura, Gramin and / or Huawei), that comprises at least one sensor 108, and can transmit data to controller 104. In some embodiments, monitor 106 is a shelf product and / or an off-the-shelf product on which an application of system 100 can be installed, potentially for real-time and / or substantially realtime sleep stages identification and / or for communicating with controller 104.

[0258] In some embodiments, controller 104 is comprised in monitor 206, alternatively or additionally, controller 104 is comprised in odorant delivery device 202. In some embodiments, controller 204 is separated from monitor 206 and / or odorant delivery device 202, and optionally, has a wireless connection thereto.

[0259] In some embodiments, at least one sensor 108 is configured to measure physiological data. In some embodiments, monitor 206 comprises a heart rate meter for measuring the patient's heart rate and / or heart rate variability (HRV), an accelerometer and / or gyroscope to detect movement, such as patterns of movement associated with different sleep stages, an infrared sensor for detecting blood oxygen level, temperature sensor a respiratory rate sensor, and / or a blood pressure sensor.

[0260] In some embodiments, monitor 206 further comprises at least one sensor for monitoring the patient’s environment. For example, room temperature sensor, humidity sensor, light sensor, noise sensor, and / or clock indicating the time of day.

[0261] In some embodiments, at least one sensor is an external device located external to monitor 106, optionally, incorporated in stimulator 102, alternatively or additionally, positioned in the room and / or next to the patient bed and transmits to monitor 106 and / or controller 104.

[0262] In some embodiments, as previously noted, monitor 206 comprises a camera (and / or a radar and / or an infra red sensor), which can detect the presence of the patient in bed, the patient’s movements while sleeping, and / or a state of the patient’s eyes (open, closed, and / or moving). Alternatively or additionally, another sensor can be mounted in bed, for example, a pressure sensor, for detecting if the patient is lying thereon.

[0263] Alternatively or additionally, the controller uses the camera’s images to monitor the environment. For example, evaluatinglighting levels in the room. In some embodiments, the camera (and / or a radar and / or an infare red sensor) feeds controller 104 which uses the data therefrom (e.g., camera images) to evaluate the distance and / or orientation of the patient in relation to odorant delivery device 202.

[0264] In some embodiments, upon detecting that the patient enters the bed, controller 104 automatically turns-on odorant delivery device 202 and / or activates it from standby mode . Alternatively or additionally, controller 104 turns on and / or activates odor release when the patient’s physiological parameters indicate that the patient has fallen asleep.

[0265] In some embodiments, monitor 206 comprises a microphone and / or a sound sensor for detecting if the patient is sleep-talking, which can indicate that the patient is dreaming and / or experiencing nightmares, alternatively or additionally the microphone can detect noise levels in the room. In some embodiments, the microphone and / or a sound sensor can detect the patient’s breathing rate, and breathing abnormalities, such as elevated breathing rate, sleep apnea, and / or snoring.

[0266] In some embodiments, system 100 comprises a log, recording and / or storing treatment historical data, and / or sensors raw data such as audio from a microphone and / or images / video from a camera.

[0267] Referring to Fig. 2, showing a simplified flowchart of a method for providing olfactory stimulation to a patient, in accordance with some exemplary embodiments of the invention.

[0268] The method of Fig. 2 includes:

[0269] Selecting a patient (202);

[0270] Monitoring at least one of the patient’s physiological parameters (204);

[0271] Identifying an indication for providing a stimulation (206);

[0272] Selecting at least one stimulation and / or stimulation properties (208); and

[0273] Providing the stimulation to the patient (208).

[0274] Referring to Fig. 3, showing a simplified flowchart of a method to provide a patientspecific olfactory stimulation to a patient, in accordance with some exemplary embodiments of the invention.

[0275] The method of Fig. 3 includes: Selecting a patient (302);

[0276] Learning the patient (304);

[0277] Monitoring at least one of the patient’s physiological parameters (306);

[0278] Identifying an indication for providing a stimulation (308);

[0279] Selecting a patient-customized stimulation (310);

[0280] Providing the selected stimulation to the patient (312);

[0281] Monitoring the patient's reaction to the stimulation (314); and

[0282] Adjusting the system, if needed (316).

[0283] Referring to Figs. 4A-B, showing a more detailed flowchart of a method for providing olfactory stimulation to a patient, in accordance with some exemplary embodiments of the invention. The method of Figs. 4-B is a detailed embodiment of the method of Fig. 2 with features of Fig. 3 described as being optional. In some embodiments, olfactory stimulation is provided to treat mental and / or cognitive conditions. Herein treating can refer to relieving, improving, and / or preventing symptoms, delaying or ceasing disease progression.

[0284] At 402, a patient is selected, optionally a patient diagnosed with mental and / or cognitive conditions is selected. Alternatively or additionally, a patient experiencing and / or suffering from one or more of the symptoms of mental and / or cognitive conditions, such as nightmares, fear, anxiety, stress, sleep disorders, and / or high blood pressure. In some embodiments, the patient is experiencing the symptoms during sleep. In some embodiments, the patient is diagnosed with or is at risk of cognitive disease, or an individual interested in promoting cognitive improvement, preventing and / or delaying cognitive decline, such as memory loss.

[0285] In some embodiments, the patient is selected by a caregiver, such as an attending physician, alternatively or additionally, the treatment can be initiated by the patient, such that the patient can be any individual who can benefit from the treatment.

[0286] At 404, in some embodiments, patient-specific learning is performed, for example, as described in this document.

[0287] In some embodiments, the learning comprises learning the effect of different scents and / or different scent administration patterns on the patient.

[0288] In some embodiments, the learning comprises learning the patient's physiological characteristics during sleep and / or during the different stages of sleep.

[0289] In some embodiments, the learning comprises measuring the patient's resting heart rate (RHR), the number of heartbeats per minute while the body is at rest, measured when a person is awake and calm and has not been engaging in any physical activity for a while. For example, in some embodiments, the patient wears a monitor (e.g., patient monitor 106) during a period before sleep, for example, during 2-4 hours before sleep.

[0290] In some embodiments, the patient’s RHR is used as a reference for detecting changes in the patient’s sleep.

[0291] In some embodiments, the patient’s RHR is used as a reference for detecting sleep entrance. The patient's heart rate usually decreases during sleep compared to the patient’s RHR. In some embodiments, the patient RHR is used as a reference for detecting sleep entrance.

[0292] In some embodiments, the patient’s RHR is used as a reference for evaluating the quality of sleep, heart rate during REM sleep generally remains relatively close to the resting heart rate (RHR). A high heart rate during REM sleep, compared to RHR indicates that the patient is experiencing anxiety and / or nightmares.At 406, the patient is monitored, optionally, during sleep. In some embodiments, the monitoring comprises measuring at least one of the patient’s physiological parameters. In some embodiments, the at least one of the patient’s physiological parameters can indicate a patient’s being asleep and / or a patient’s sleep stage. In some embodiments, the at least one of the patient’s physiological parameters can indicate a physiological abnormality and / or mental state, such as distress and / or fear.

[0293] In some embodiments, monitoring the patient comprises measuring one or more of: heart rate (BPM), heart rate variability (HRV), accelerometer data (X, Y, Z), gyroscope Data (angular velocity of one, two, or three axes), sleep / wake data, blood oxygen level, respiratory rate, and / or skin temperature. In some embodiments, monitoring the patient comprises monitoring environmental factors, such as room temperature and humidity, time of day, ambient light and darkness, and / or noise level.

[0294] In some embodiments, the monitoring comprises measuring the patient’s physical parameters and / or environment repeatedly, at a frequency that allows to obtain substantial realtime monitoring.

[0295] For example, the patient is measured about every minute. For example, about 0.5-2 minutes, or 1-10 minutes, or 0.8-20 minutes, or about 1.1 minutes, or about 5 minutes, or lower or higher, or intermediate numbers of minutes.

[0296] At 408, the measured data is processed, optionally, by a controller. In some embodiments, the measured data is processed based on a statistical database. Alternatively, or additionally, the measured data is processed based on patient-based collected data.

[0297] At 410, in some embodiments, a patient’s sleep stage is identified. In some embodiments, the sleep stage is identified based on the combination of one or more of the monitored parameters described in Act 406. In some embodiments, the sleep stage is identified within about a minute from the initial thereof. For example, about 0.5-2 minutes, or 1-5 minutes, or 0.8-1.5 minutes, or about 1.1 minutes or lower or higher, or intermediate numbers of minutes.

[0298] In some embodiments, a sleep stage is identified based on heart rate meter measurements. Without being bound to theory, the heart rate and heart rate variability differ in each sleep stage. Differences in heart rate variability are generally compared using the low-to- high frequency (LF:HF) ratio. In some embodiments, the LF:HF ratio is used for discriminating between REM (random eye movement sleep and non-REM (NREM) sleep, as the LF:HF ratio is generally higher during REM sleep than during other sleep stages.

[0299] In some embodiments, the LF:HF ratio is used for identifying the three sleep stages: light sleep, REM (random eye movement sleep), and deep sleep. In other embodiments the LF:HF ratio is further used for identifying arousal state.

[0300] Alternatively or additionally, accelerometer data and / or Gyroscope Data (angular velocity can be used to distinguish between sleep and arousal stages, and / or between (REM) and non-REM stages, during sleep. For example, during REM sleep there are minimal body movements (to protect from injury or sleep disruption as a result of acting out vivid dreams), such that a REM stage can be identified by the relatively reduced body movements.

[0301] In some embodiments, a sleep stage is identified based on a correlation between sleep stages and physiological parameters and / or change(s) in physiological parameters, where the sleep stage classification is based on brain activity measurements, such as EEG (electroencephalogram) and / or PSG (polysomnography). In some embodiments, a system (e.g., system 100) and / or an Al component thereof, is trained based on labeled EEG and / or PSG measurements, linking the different sleep stages with characteristic physiological parameters and / or change(s) thereof, enabling the detection of sleep stages based for example on changes in the heart rate values and / or accelerometer parameters.

[0302] At 412, in some embodiments, alternatively or additionally to identifying a sleep stage, a state of the patient, such as a physiological abnormality and / or a mental state can be detected and / or classified. For example, mental distress and / or anxiety during sleep can be identified by detecting an increased heart rate, increased blood pressure, increased respiratory rate, and / or changes in body temperature.

[0303] In some embodiments, sleep stage detection and / or physiological abnormality and / or a mental state is based on threshold values, for example, fixed and / or personalized. For example,

[0304] An increase in the rate is determined according to the average resting heart rate for an adult population or is based on a patient's specific resting heart rate. In another example, An increase in the rate is determined by a fixed percentage, about 5-10% of the heart rate at rest, or the percentage is patient-specific.At 414, an olfactory stimulation is selected optionally based on the identified sleep stage and / or state of the patient. In some embodiments, at least one scent is selected based on a desired effect on the patient. For example, a scent having a positive effect, a scent having a calming and / or relaxing effect, and / or a scent that stimulates (substantially stimulates) the brain

[0305] In some embodiments, the at least one scent is selected based on statistical information, for example, desired results according to literature and / or effect on a control group (e.g., a trial group and / or a population of other patients).

[0306] For example, for stress reduction, anxiety relief, and / or enhanced sleep depth, the following scents and / or similar scents can be used: Lavender, Chamomile, Roses, Nocturnal, Jasmine, PEA, Bergamot, Sandalwood, Ylang-Ylang, Valerian, and Vanilla. In some embodiments, one or more of these scents are utilized to address PTSD, lower heart rate, and / or improve overall sleep quality.

[0307] In some embodiments, the at least one scent is selected based on patient-specific information. In some embodiments, the at least one scent is selected based on a patient's preferences, for example, described by the patient during daytime. In some embodiments, the at least one scent is selected based on the patient's reaction thereto, optionally as detected by the system (e.g. system 100).

[0308] In some embodiments, the at least one scent is a scent(s) for which the patient has undergone positive conditioning, having the potential advantage of enhancing the desired influence of the at least one scent on the patient. In some embodiments, the positive conditioning comprises exposing the patient during daytime to at least one scent while experiencing positive events such as a trip, interaction with animals, romantic experiences and / or relaxing experiences such as meditation. In some embodiments, the patient is prompted, optionally by the system to activate the release of the at least one scent during positive experiences. In some embodiments, the patient is instructed to initiate positive experiences and / or to release a scent during a positive experience. In some embodiments, the patient's physiological parameters are monitored to confirm that it is indeed a positive experience for the patient. For example, an increase in heart rate and / or sweating during a relaxing experience, such as meditation, may indicate that the patient is not relaxed and may experience fear, stress, and / or anxiety.

[0309] In some embodiments, the patient is provided with a mobile form of the scent, such as a scent tablet, a perfume bottle, and / or a small and portable scent diffuser. Alternatively or additionally, if the positive experience occurs at the patient's home, the patient is asked to activate the odorant delivery device (e.g., odorant delivery device 202) of the system (e.g., system 100).

[0310] In some embodiments, alternatively or additionally to selecting an olfactory stimulation based on a sleep stage, at least one scent can be selected according to a patient’s state such as physiological abnormality and / or mental state. In some embodiments, the monitored physiological parameters of the patient can indicate emotional distress, resulting for example from experiencing a nightmare. For example, elevated heart rate, elevated respiratory rate, increased body temperature and / or amount of sweat, increased movements, and / or any combination thereof, may indicate such distress.

[0311] In some embodiments, this indication prompts the administration of at least one scent which is perceived by the patient as a positive scent for potentially modifying the dream content to be more pleasant for the patient. This administration has the potential advantage of reducing the severity and / or duration of the nightmare.

[0312] Alternatively or additionally, the indication prompts the administration of at least one scent having a relaxing effect on the patient for potentially alleviating stress, anxiety, and / or fear that might be caused by the nightmare.

[0313] In some embodiments, the at least one scent is selected to have no and / or a relatively reduced awakening effect, having the potential advantage of reducing unwanted awakening or disturbance of the patient's sleep.

[0314] In some embodiments, more than one scent is selected, having the potential advantage of reducing habituation of the olfactory stimulation and / or habituation of the brain stimulation.

[0315] For example, for cognitive treatment, scents from various groups are provided to offer diverse brain stimulation, such as more than one of Orange, Lemon, Rosemary, Sage, Cinnamon, Strawberry, alongside previously mentioned scents and / or others.

[0316] In some embodiments, the more than one scent is selected, optionally for providing during a sleep stage, alternatively or additionally for providing during the course of sleep. In some embodiments, at least three scents are selected. In some embodiments, the scents are selected as a set of scents, optionally including at least three scents. In some embodiments, the set comprises 4 scents, such that at least three scents are provided during a sleep stage and an additional scent, optionally, a scent perceived by the patient as natural scent, for potentially resetting the sense of smell and / or cleaning the room from the released scents. Alternatively or additionally, cleaning the room is performed by releasing vaporable / atomized smell adsorption material (e.g., odor adsorber), such as water, baking soda, vinegar, or any combination thereof and / or other safe scent-eliminating liquids. In some embodiments, cleaning the room can be performed by air suction, a filter and / or a fan optionally together an odor adsorber release.

[0317] In some embodiments, this cleaning can be activated automatically, optionally by a controller (controller 104). In some embodiments, an odorant delivery device (e.g., an odorant delivery device 102) comprises a filter mode and / or scent-eliminating liquids. In some embodiments, resetting the sense of smell and / or cleaning the room from the released scents is performed upon detection of olfactory habituation. Alternatively or additionally, this process may be performed periodically to potentially prevent such habituation.

[0318] In some embodiments, the set, optionally of four scents, comprises at least one of the following scent types families:

[0319] Fresh scents family, optionally comprises the subcategories: Citrus, Green, Aquatic, and some aspects of Aromatic. These scents are characterized by their crisp, clean, and uplifting qualities. They often include notes from fresh-cut grass, sea breezes, citrus fruits like lemon and bergamot, and aromatic herbs such as lavender and rosemary;

[0320] Floral scents family, optionally comprises the subcategories: Single Floral (Soliflores), Floral Bouquet, and some soft Orientals when they are heavily influenced by floral notes. This family encompasses a wide range of scents that mimic the aroma of flowers, for example, from the delicate scent of a single rose to complex bouquets combining multiple floral notes.

[0321] Without being bound to theory, Floral scents are often associated with femininity and romance;

[0322] Oriental scents family optionally comprises the subcategories: Oriental (Amber), Spicy, Gourmand, and Powdery. These scents are characterized by perceiving as warm, rich, inviting, and often have a bit of sweetness or spice. They include notes like vanilla, cinnamon, chocolate, and amber. This family comprises scents that evoke warmth and comfort, often with a sensual or exotic twist; and

[0323] Woody scents family optionally comprises the subcategories: woody, mossy woods, dry woods, and leather, these scents are characterized by their deep, earthy base notes that can range from the dry aroma of cedarwood to the damp, verdant scent of moss. This family also includes leathery and smoky notes, evoking images of forests, leather, and a hint of the outdoors.

[0324] In some embodiments, the set comprises a sent from each scent family, such that each scent has a different effect on the patient. In other embodiments, the set comprises sent having a similar effect in the patient, for different scent families, allowing to replace therebetween when olfactory habituation is detected. In some embodiments, the selection of the olfactory stimulation comprises selecting to provide the scents of the set in turn, optionally with time intervals therebetween. Alternatively or additionally, two or more scents can be provided simultaneously, introduced to the patient as a combination and / or integration of scents.

[0325] In some embodiments, two or more of the scents from the set are mixed, each mixture potentially has a different effect on the patient. In some embodiments, the effect of a mixture is pre-tested, optionally, on the patient, alternatively or additionally, on a control group (population of other patients). In some embodiments, a process of trial and error is performed, a mixture is provided and the reaction thereof on the patient is evaluated, during treatment.

[0326] In some embodiments, the mixing comprises pre-setting the percentages of each scent in the mixture, since mixtures with different percentages have different effects on the patient. The mixing potentially increases the number of active scents that can be provided to the patient without requiring increasing the number of base scents, having the potential advantage of simplifying the equipment and / or reducing costs.

[0327] In some embodiments, the scent mixing is performed in a controlled manner, potentially avoiding percentages and / or scent combinations with a reduced effect and / or undesired effect on the patient (such as a negative effect, for example, if the mixture scents perceived by the patient as unpleasant and evokes negative emotions during sleep).

[0328] In some embodiments, the effect of different scent combinations on a patient is evaluated in an early stage of learning the patient (for example, in Act 404), for example, exposing the patient to scent mixtures while awake and receiving feedback regarding the effect thereon. Alternatively or additionally, the patient’s physiological reaction (e.g., changes in the patient’s physiological parameter(s)) can be evaluated, while the patient is asleep and / or awake, optionally at a pre-treatment period and / or during treatment.

[0329] In some embodiments, the mixing comprises combining scents from the same category, for example, calming scents, and or scents from the same scent family, for example, lavender and chamomile, both from the fresh scents family. Alternatively or additionally, the mixing comprises combining scents from the different categories, for example, a calming scent with a scent for stimulating brain activity, and or scents from the different scent families.

[0330] In some embodiments, the combination comprises for example Lavender (fresh scents family) and Vanilla (Oriental scents Family), Jasmine (Floral scents family) and Sandalwood (Woody scents family), Camomile (Fresh scents family) and Patchouli (Woody scents family), and / or Rose (Floral scents family) and Amber (Oriental scents family). This combination has the potential advantage of reducing and / or avoiding habituation. For example, if a Lavender scent is provided to the patient, optionally first or the set, and habituation is dictated (e.g., based on the patient’s monitored parameters), a vanilla scent can be added to potentially reduce and / or avoid habituation. In addition, the combination of scent potentially results in different effects on the patient, compared to scent administration in turn.

[0331] In some embodiments, the selection comprises selecting a percentage of each combined scent to potentially control the effect of the combined scents. For example, 50% lavender and 50% vanilla. In another example, 40% camomile, 40% rose, and 20% patchouli.

[0332] In some embodiments, the selection is based on guidelines and / or stimulation tables for each disease. In some embodiments, the stimulation tables are personalized. In some embodiments, the selection is based on personalized historical data and / or on analyses thereof indicating which stimulation affects the patient and / or in what manner. Alternatively or additionally, the historical data obtained from a plurality of patients sharing the same conditions. In some embodiments, the selection is performed based on Idata stored in a memory (e.g., memory 1108).

[0333] At 416, a delivery pattern is selected. In some embodiments, the at least one scent is delivered intermittently. The intermittent delivery has an additional potential advantage of reducing habituation of the brain to the olfactory stimulus and / or maintaining the brain's responsiveness to the stimulation. For example, in the case of an intermittent release pattern, the at least one scent can be provided for 30-60 seconds once every 5 minutes.

[0334] In some embodiments, the selected pattern releases scents intermittently such that the intervals between release pulses are long enough to potentially reduce and or avoid mixing between two or more types of scents. Long enough intervals potentially allow the room return the room to a baseline scent atmosphere and have the potential advantage of reducing and / or avoiding olfactory habituation.

[0335] In some embodiments, release pulses are generated using a relatively small amount of scent substance(s), having an effect on the patient for a limited time before dispersing in the room. In some embodiments, the amount of scent substance(s) for a single pulse is determined by a wanted time of effect, such the larger the amount, the longer the time of effect.

[0336] Alternatively or additionally, the system prompted the patient to activate the release of the at least one scent during positive experiences. In some embodiments, the pattern selection considers the diffusion of a fragrance substance in the air and / or the intensity thereof for determining said intervals.

[0337] In some embodiments, the pattern is determined based on statistical data (e.g., based on literature, other patients, and / or a control group, comprising a population with similar characteristics to the patient). For example, once REM sleep is detected, the scent is released for a duration of 10 to 60 seconds every 3 to 6 minutes optionally, until the REM stage is no longer detected. In another example, once a deep sleep stage is detected the scent is released for about 1 minute every 4 minutes. For example, about 0.5-2 minutes every 2-6 minutes, or 1-5 minutes every 2-10 minutes, or 1-15 minutes every 5-20 minutes, or about 1.2 minutes every 5 minutes or lower or higher, or intermediate numbers of minutes. In another example, if a shallow sleep is detected, for example, based on an indicatin of elevated heart rate, the at least one scent is released for 30 to 60 seconds, with breaks of 3-6 minutes between each activation, optionally from upon detecting the elevated heart rate until monitoring a decrease in heart rate.

[0338] In some embodiments, the pattern is personalized and is determined based on patientspecific data, having the potential advantage of reducing and / or avoiding habituation of the olfactory system.

[0339] In some embodiments, the at least one scent is first delivered according to a default delivery pattern, optionally based on statistical data (based on literature and / or historical data of other patients, or based on a tested control group), and during operation, the system learns the patient's reaction to stimulations and adjusts the delivery pattern accordingly.

[0340] In some embodiments, alternatively or additionally to intermittent delivery, the at least one scent can be delivered continuously, for at least a portion of a sleep stage and / or sleep course.

[0341] In some embodiments, the at least one scent comprises a plurality of scents. In some embodiments, the transition between different scents occurs randomly. For example, the same scent may be released during a following release pulse, while at other times, each release pulse introduces a different scent compared to the previous scent. This randomization potentially reduces brain adaptation to a scent order, having the potential advantage of increasing brain stimulation.

[0342] At 418, the at least one scent is provided to the patient during at least a portion of a detected sleep stage, optionally, from the detection of the sleep stage until the end thereof. The synchronization between providing the at least one scent and a sleep stage, when the effect of the scent is desirable and / or enhanced, has the potential advantage of improving the influence of the treatment and / or reducing smell habituation.

[0343] At 420, the patient's reaction to the olfactory stimulus is monitored.

[0344] In some embodiments, the olfactory stimulus is provided until a change in at least one of the patient’s physiological parameters is detected. At 422, In some embodiments, if after a time period, the patient’s physiological parameter(s) indicates an insufficient effect of the provided scent(s), the stimulation is modified, optionally by a controller. In some embodiments, a patient's reaction to an olfactory stimulation can be detected about 0.1-1 minute from being exposed to the stimulation. For example, 0.1-2 minutes, or 1-5 minutes, or about 0.5 minutes, or about 1.5 minutes or lower or higher, or intermediate numbers of minutes.

[0345] In some embodiments, the patient's reaction is evaluated after about a minute after exposing the patient to the olfactory stimulus. For example, 1-5 minutes, or 5-15 minutes, or about 1.1 minutes, or about 4.5 minutes or lower or higher, or intermediate numbers of minutes. In some embodiments, the scent(s) type, order, release pattern, and / or treatment duration are adjusted to potentially enhance the stimulation effectin some embodiments, if after a time period, the patient’s physiological parameter(s) indicates an insufficient effect of the provided scent(s), the system wakes up the patient. Such waking is optionally provided, if the patient is in a life-threatening situation, or poses a danger to others. For example, if a high heart rate requires immediate lowering is detected. In another example, if vocalizations, and / or aggressive behaviors are detected (e.g., during nightmares) which might endanger the patient and / or others, such as the patient’s spouse.

[0346] In some embodiments, the patient is awakened by exposure to intensity and / or type of olfactory stimulus, which leads to arousal from sleep. Alternatively or additionally, the patient is awakened by light, sound, and / or vibration stimulation, actuated by the controller.

[0347] At 424, repeating acts 406-422 during at least a portion of the course of the patient’s sleep.

[0348] At 426, optionally, the patient provides feedback while awake regarding the influence of treatment.

[0349] In some embodiments, if additional people are exposed to the olfactory stimulus, the feedback can include information regarding their reaction thereto. For example, if a selected scent and / or intensity has an unwanted effect, such as an arousing effect on the patient's partner (e.g., spouse). In some embodiments, one or more of the selected scents can be omitted and / or replaced. Alternatively or additionally, the patient receives recommendations and / or instructions for repositioning the stimulator to potentially reduce the effect on the patient’s partner. In some embodiments, the stimulator position is adjusted automatically, to be directed toward the patient, by the controller, optionally, according to image processing detecting the patient's location in bed and the partner's location in bed.At 428, long-term effects of the olfactory treatment are evaluated. Without being bound to theory, since the olfactory system has direct projections to the brain’s limbic system, the olfactory treatment may affect the brain’s structure and / or function. The olfactory stimulation can potentially induce structural changes in the brain through a phenomenon known as neuroplasticity (the brain's ability to reorganize its structure and function in response to, for example, sensory experiences, learning, and / or environmental factors)

[0350] Without being bound to theory, synchronizing between an olfactory stimulus and a particular sleep stage has the potential advantage of enhancing long-term effects, optionally, since the effect on brain activity is enhanced and / or maximized. An additional potential advantage of this synchronization is improving long-term effects while reducing and / or avoiding habituation of the olfactory system and / or the brain

[0351] In some embodiments, the evaluation comprises, for example, assessing changes in the patient’s sleep pattern over time, and / or assessing changes in the patient's function and health during daytime, over time. For example, prolonging deep sleep during the night, for example by 10% or more. Another example, a change in the rating of nightmare questionnaires which indicates a reduction in nightmares.

[0352] In some embodiments, this evaluation comprises, presenting the patient with questionnaire(s) regarding the mental and / or cognitive state thereof. Optionally, a caregiver, alternatively or additionally an application (e.g., application of system 100). In some embodiments, the questionnaires are automatically sent to the patient's email, optionally, each period.

[0353] In some embodiments, alternatively or additionally, structural changes in the patient's brain can be measured by neuroimaging techniques and histological analyses, such as but not limited to MRI (Magnetic Resonance Imaging).

[0354] At 430, in some embodiments, the olfactory treatment plane is adjusted according to the patient’s reaction during treatment, long-term effect(s), and / or a patient’s feedback.

[0355] In some embodiments, the treatment is adjusted periodically, based on collected data during a period. Alternatively or additionally, the treatment is adjusted each morning, according to the data and / or feedback last night.

[0356] In some embodiments, the match between a sleep stage and a scent(s) is adjusted. In some embodiments, the types and / or number of scent(s), order of providence, intensity, and / or pattern release are adjusted. In some embodiments, the data processing is adjusted according to learning patient-specific physiological parameter(s) during sleep. Alternatively or additionally, the processing is adjusted according to new statistical data obtained from a patient population with a common or similar disorder to that of the patient. In some embodiments, the system learns how periodic changes affect the olfactory abilities or the effect of different smells, and adjust the treatment accordingly . For example, hormonal changes smell during different parts of the menstrual cycle and / or during pregnancy.

[0357] A method for influencing dream content by olfactory stimulation.

[0358] The method for influencing dream content by olfactory stimulation may be as described in Figs. 4A-B with the following differences and / or elaboration:

[0359] In Act 402, the patient selection comprises selecting a patient suffering from sleep disorders and / or nightmares. In some embodiments, the patient is diagnosed with PTSD (Post- Traumatic Stress Disorder) which nightmares are a common symptom thereof.

[0360] According to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), 1 nightmares are “typically lengthy, elaborate, story-like sequences of dream imagery that seem real and that incite anxiety, fear, or other dysphoric emotions, and usually terminate with awakening and rapid return of full alertness.”

[0361] In some embodiments, the nightmare level is evaluated by prompting the patient to complete nightmare questionnaire(s), such as the disturbing dream and nightmare severity index (DDNSI), which is a questionnaire that rates the level of nightmares based on nightmare frequency and nightmare distress. Another example is the nightmare distress questionnaire (NDQ) with 13 items to capture different aspects of nightmare distress, which assesses nightmare frequency, using an 8-point rating scale for example, “How often have you experienced nightmares recently [in the past several months]?”: 0 = never, 1 = less than once a year, 2 = about once a year, 3 = about 2 to 4 times a year, 4 = about once a month, 5 = 2 to 3 times a month, 6 = about once a week, 7 = several times a week. In both exemplary questionnaires, the rating is proportional to the nightmares level.

[0362] Alternatively or additionally, the patient is prompted to complete other questionnaires, such as the modified Nightmare Effects Survey (mNES) which includes self-report questions, including the effect of nightmares on sleep, work, relationships, daytime energy, school, mood, sex life, diet, mental health, physical health, and leisure activities.

[0363] Regarding acts 410-414. In some embodiments, olfactory stimulation is provided when a REM sleep stage is detected. Without being bound to theory, approximately 95% of dreams, and the most vivid dreams (including vivid nightmares) occur during the REM sleep stage so potentially influencing dream content and / or reducing and / or mitigating nightmares is performed by providing at least one olfactory stimulation during at least a portion of a REM sleep stage. In some embodiments, the at least one olfactory stimulation is provided from the detection of and until the end of the detected REM sleep stage.

[0364] In some embodiments, the at least one scent provided to the patient having a positive effect thereof, potentially influencing the content of the dream to be more and / or to reduce and / or prevent nightmares. Herein, a positive effect is defined by a decrease in the rating of the nightmare questionnaire index.

[0365] When a patient is experiencing a nightmare the physiological reaction thereto can include increased heart rate, increased breathing rate, increased blood pressure, sweating, increased body movements, sleep-talking, and / or sleep-acting. In some embodiments, a positive effect during sleep is defined by a decrease in the physiological reaction, such as a decrease in heart rate, breathing rate, blood pressure, sweating, body movements, sleep-talking, and / or sleep-acting.

[0366] In some embodiments, alternatively or additionally to providing olfactory stimulation during a REM sleep stage, olfactory stimulation is provided during a deep sleep stage. Without being bound to theory, during this stage of the sleep cycle, there is a relatively significant operation of the brain's memory mechanisms so that providing at least one scent during at least a portion of a deep sleep stage can alleviate stress, anxiety, and fear. In some embodiments, the at least one scent provided to the patient is a scent having a calming and / or relaxing effect thereon. Relaxation allows the parasympathetic nervous system to become active by down-regulating the sympathetic nervous system, relaxation leads to ceasing the release of stress hormones such as cortisol and / or adrenaline. Herein relaxation is defined by physiological responses associated with relaxation and / or a state of calmness, for example, one or more of a decrease in heart rate, Lower blood pressure, reduced muscle tension, slower and deeper breathing (e.g., decrease in respiratory rate), a decrease in body (e.g., skin) temperature and / or a decrease in sweating.

[0367] In some embodiments, at least one scent having a relaxing effect on the patient can be provided during a light sleep stage, to potentially enhance and / or promote the following deep sleep stage.

[0368] In some embodiments, alternatively or additionally to identifying a sleep stage and providing olfactory stimulation accordingly, a nightmare and / or mental distress during sleep can be detected.

[0369] For example, a patient experiencing active dreaming, nightmares and / or mental distress during sleep can be identified by detecting an elevated heart rate, elevated blood pressure, elevated respiratory rate, changes in body temperature and / or in the amount of sweat, increased movements, talking while sleeping, and / or any combination thereof. In some embodiments, such indication(s) promote exposing the patient to at least one scent which is perceived by the patient as a positive scent, for potentially modifying the dream content to be more pleasant for the patient. This exposure has the potential advantage of reducing the severity and / or duration of a nightmare. Alternatively or additionally, the indication promotes providing at least one scent having a relaxing effect on the patient for potentially alleviating stress, anxiety, and / or fear that might be caused by a nightmare.

[0370] In some embodiments, a set of scents, optionally four scents are selected, for example, Lavander (from the fresh scents family), Jasmine (from the floral), Vanilla (from the oriental scents family) and Sandalwood (from the woody scents family), in this order and / or in another order.

[0371] In another example, the four scents are Camomile (from the fresh scents family), Rose (from the floral scents family), Amber (from the oriental scents family), and Patchuli (from the woody scents family), in this order and / or in another order, determined and / or random.

[0372] In some embodiments, the selection of the at least one scent is based on historical data of the patient. The collected measurements of the patient’s physiological parameters are analyzed to identify scents with a positive effect on the patient, scents with changing effects over time, and / or scents with no actual effect and / or undesired effect. In some embodiments, during the selection scents whose positive effect fades over time and / or scents that did not actually produce a positive effect are replaced with other smells.

[0373] In some embodiments, a process of experimentation and learning (e.g., trial and error) is performed, different stimulation is selected and the effect thereof on the patient is evaluated. Based on said effect the controller (e.g., controller 104) determines whether to select said stimulation again.

[0374] In acts 420-422, the patient's reaction to the olfactory stimulus is monitored. In some embodiments, the olfactory stimulus is provided until a change in at least one of the patient’s physiological parameters is detected. For example, if it is identified that the patient is experiencing a nightmare and / or emotional distress while sleeping, for example by measuring an increase in heart rate and / or breathing rate, and / or according to any other physiological index previously specified, the system will provide the stimulus until the measurements indicate an improvement in the patient mental state and / or end of the nightmare.

[0375] In some embodiments, if after a time period, such as a minute from providing the at least one scent to the patient, the patient’s physiological parameter(s) indicates that the patient is still experiencing nightmares and / or mental distress, and / or indicates no mental distress reduction, the stimulation is modified. This modification has the potential advantage of enhancing the influence of treatment. For example, the intensity of the scent is modified, the pulses of the scent release are prolonged, the scent is replaced or combined with other scents, as a mixture and / or in turns.

[0376] In some embodiments, if after a time period, the patient’s physiological parameter(s) indicates that the patient is still experiencing nightmares and / or mental distress, the system wakes up the patient. For example, if a decrease in heart rate is not detected, or if the patient continues to talk and / or move while asleep, the patient may be awakened. In some embodiments, the effect of olfactory stimulation is evaluated using threshold values, fixed and / or personalized. For example,

[0377] In act 426, optionally, the patient provides input regarding the sleep thereof which can indicate the treatment influence. For example, the number of remembered dreams, number of nightmares, content of the dreams, number of awakenings through the night, the level of alertness and / or fatigue during the following day optionally along with an overall general feeling.

[0378] In act 428, long-term effects of the olfactory treatment on the patient's sleep are evaluated.

[0379] In some embodiments, this evaluation comprises, for example, assessing over time changes in the patient’s sleep pattern, sleep duration, number of awakenings, amount of dreams, number of sleep-talking events and / or sleep-acting events, level of fatigue and / or mood during daytime.

[0380] In some embodiments, this evaluation comprises evaluating the patient’s physical health by assessing a long-term effect on the patient's physiological parameters. For example, reducing nightmares can potentially lower the average heart rate during sleep and / or daytime, stabilize blood pressure levels during both night and day, and / or regulate stress hormones production, such as cortisol and / or adrenaline (which can be measured by blood test).

[0381] A method for lowering heart rate by olfactory stimulation during sleep.

[0382] The method for lowering heart rate by olfactory stimulation may be as described in Figs. 4A-B with the following differences and / or elaboration:

[0383] At Act 402, the patient selection comprises selecting a patient suffering and / or potentially suffering from a high heart rate, optionally during sleep. Herein, an elevated heart rate refers to a heart rate that is higher than the typical resting rate for an individual (e.g., regular heart rate), for example, 5% or more increase in heart rate compared to the patient's heart rate while the patient is at rest and awake. Resting heart rate varies between individuals but is statistically considered to be between 60 to 100 beats per minute (bpm) for adults.

[0384] At Act 404, in some embodiments, the learning comprises learning the baseline heart rate of a patient during sleep and / or during the different sleep stages, for potentially identifying heart rate abnormalities. Herein heart rate abnormalities can include, a decrease or increase relative to resting heart rate (RHR), for example of at least 5% and / or deviations from the regular pattern of heart rate variability (HRV), where a regular pattern is the pattern during RHR.

[0385] In some embodiments, the learning comprises distinguishing heart rate during sleep and / or wakefulness for potentially detecting when the patient enters sleep.

[0386] In some embodiments, the learning comprises collecting medical history related to the patient’s heart rate.

[0387] At Act 406, the heart rate and / or the HRV of the patient is monitored. In some embodiments, the heart rate and / or HRV are measured for detecting sleep stages as well as for identifying heart rate abnormalities. Alternatively or additionally, sleep monitoring can be measured by a different parameter, for example as described in this document.

[0388] At Act 412, at least one heart rate abnormality (e.g., deviation from regulated heart rate) is detected. For example, an increase in heart rate can indicate stress and / or anxiety, since emotional stress or anxiety can stimulate the release of hormones such as adrenaline, which can cause the heart rate to increase. In another example, a medical condition, such as heart disease(s) and / or heart arrhythmias can lead to increases in heart rate. In some embodiments, a scent that activates the sympathetic system is provided to the patient, to potentially increase the heart rate thereof.

[0389] In Acts 410-416, in some embodiments, the olfactory stimulation and / or the release thereof is selected based on the identified sleep stage. Without being bound to theory, according to studies, the highest average heart rate during sleep occurs in the REM sleep stage. In some embodiments, when a REM sleep stage is identified, one or more scents that are perceived by the patient as positive and / or relaxing are selected and provided to the patient.

[0390] Alternatively or additionally, at least one scent having a positive and / or relaxing effect on the patient is selected and / or provided when a heart rate elevation is detected.

[0391] In some embodiments, if a decrease in heart rate is detected, at least one scent having an activating effect on the patient is selected, for potentially increasing heart rate. In Act 418, the at least one scent is provided to the patient. In some embodiments, the at least one scent is provided during at least a portion of a detected sleep stage, such as a REM sleep stage, optionally from the detection until the end of the stage.

[0392] Alternatively or additionally, the at least one scent is provided throughout at least a portion of the patient’s sleeping course, regardless of the sleep stage, optionally throughout all night and / or sleep duration. In some embodiments, to potentially reduce and / or avoid olfactory habituation, the provided scent is replaced every period optionally, during the course of a sleep stage, for example, about every 20 minutes. For example, about every 5-20 minutes, or 20-30 minutes, or 15-25 minutes, or about 22 minutes or lower or higher, or intermediate numbers of minutes.

[0393] In some embodiments, when heart rate abnormally is detected, the at least one scent is provided until a regularity, and / or sufficient improvement in heart rate is detected.

[0394] At 420, the patient’s heart rate reaction to the olfactory stimulation is monitored. In some embodiments, if a time period after providing the olfactory stimulation, the heart rate abnormality is still detected, the stimulation is modified to potentially enhance the influence of the olfactory stimulations. For example, the type of scent, number of scents, order of scents, release duration, duration between scent(s) release pulses, and / or intensity of scent(s) are adjusted.

[0395] In some embodiments, if a period after providing the olfactory stimulation and / or modifying thereof, the heat rate abnormality is still detected, the patient is woken, optionally by the system (e.g., system 100). In some embodiments, the patient is woken and referred to medical treatment to treat the heart rate abnormality, for example, to lower heart rate. In some embodiments, the patient is awakened by exposure to an intensity and / or type of olfactory stimulus, which leads to arousal from sleep. Alternatively or additionally, the patient is woken by light, sound, and / or vibration stimulation, optionally actuated by a controller (e.g., controller 104).

[0396] In some embodiments, the period of time after which the effectiveness of the stimulation is evaluated can be fixed and / or personalized and / or learned. In some embodiments, said period of time can be reviewed and / or changed remotely for example by a caregiver and / or the patient via the application.

[0397] At Act 428, the long-term effect of the olfactory treatment on the patient’s heart rate is optionally evaluated. In some embodiments, this evaluation comprises monitoring the patient’s heart rate when an olfactory stimulation is not provided. In some embodiments, this evaluation comprises assessing long-term changes (e.g., long-term decrease) in the patient's heart rate during sleep, optionally during REM sleep stage(s). In some embodiments, this evaluation comprises assessing short-term and / or long-term changes (e.g., long-term decrease) in the patient's heart rate during daytime.In some embodiments, providing olfactory stimulation during a REM sleep stage has the potential advantage of reducing heart rate during other sleep stages during the night sleep when stimulation is no longer provided. An additional potential advantage is reducing the heart rate for a longer period, for example, a month from the stimulation administration, during sleep and / or while awake.

[0398] A method for lowering heart rate using olfactory stimulation while a patient is awake.

[0399] In some embodiments, the method for lowering heart rate by olfactory stimulation can be utilized while a patient is awake.

[0400] In some embodiments, heart rate abnormalities during waking time are detected, and the patient is instructed to approach an odorant delivery device to be exposed to released scent(s). In some embodiments, the device is wearable and automatically provides the scent(s). In some embodiments, the device is placed next to the patient, for example on a desk thereof.

[0401] In some embodiments, the patient can inform the system about a situation that is a trigger for an increase in heart rate. For example, noisy situations or crowded events can trigger a person suffering from PTSD and result in an increased heart rate. The information regarding the trigger optionally leads the system to provide stimulation, optionally during sleep, alternatively or additionally during and / or not long after the trigger (e.g., using a portable and / or a wearable scent diffuser), for potentially lowering the heart rate and / or preventing heart rate increase.

[0402] A method for deepening and improving sleep by olfactory stimulation during sleep

[0403] Referring now to Fig 5. showing a simplified flowchart of a method for deepening and improving sleep by olfactory stimulation, in accordance with some exemplary embodiments of the invention.

[0404] The method of Fig. 5 comprises:

[0405] Selecting a patient suffering from sleep disturbances (502);

[0406] Decreasing sleep latency, by exposing the patient to olfactory stimulation (504); and Extending deep sleep, by exposing the patient to olfactory stimulation (506); A more detailed method for lowering heart rate by olfactory stimulation may be as described in Figs. 4A-B with the following differences and / or elaboration:

[0407] In Act 402, the patient selection comprises selecting a patient suffering and / or at risk from suffering from sleep disturbances such as but not limited to insomnia.

[0408] In some embodiments, the patient suffers from disease(s) and / or medical condition(s) that affect the autonomic nervous system’s (ANS) ability to achieve and maintain correct activation levels, resulting in disrupting the body's ability to transition into a relaxed state conducive to sleep (e.g., by activating the parasympathetic system and / or diactivting the sympathetic system).

[0409] For example, anxiety disorders such as generalized anxiety disorder (GAD) or post- traumatic stress disorder (PTSD), depression, and / or neurological conditions, such as Parkinson's disease or multiple system atrophy, can affect autonomic function and disrupt sleepwake cycles. In another example, medical conditions, such as, but not limited to, gastrointestinal disorders, respiratory disorders, and / or chronic pain conditions can activate the autonomic nervous system and / or interfere with the body's ability to relax.

[0410] In Act 406, the monitoring comprises monitoring the patient during a pre-sleep period.

[0411] In Acts 410-414, the identifying comprises first identifying arousal state and / or sleep entrance.

[0412] In some embodiments, when the patient is identified as awake, olfactory stimulation to promote sleep is provided. In some embodiments, the olfactory stimulation comprises at least one scent having a relaxing and / or calming effect on the patient, having the potential advantage of reducing the time required for the patient to fall asleep, alternatively or additionally, other stimulations such as sound stimulation (for example, white and / or pink noise) can be provided for prompting sleep entrance, allowing to reduce patient exposure to the olfactory stimulus and potentially reducing adaptation of the olfactory system at an initial stage of treatment.

[0413] In some embodiments, upon detecting sleep entrance and / or a light sleep stage, the olfactory stimulation comprises at least one scent having a relaxing and / or calming effect on the patient, for potentially promoting relaxation and reducing stress and anxiety during a predeep sleep period (e.g., during a light sleep stage). This stimulation has the potential advantage of reducing the time for the patient to enter into a deep sleep stage.

[0414] In some embodiments, olfactory stimulation is provided when a deep sleep stage is detected. Without being bound to theory, olfactory stimulation during a deep sleep stage, (e.g., slow-wave sleep, SWS) can enhance the depth, duration, and quality of sleep. In some embodiments, upon detecting a deep sleep stage, the patient is exposed to at least one scent 13 perceived thereby as relaxing.In Act 420, the patient's reaction to the olfactory stimulation which indicates sleep quality is monitored. For example, time to fall asleep, light sleep duration, deep sleep duration, and / or number of awakenings.

[0415] In acts 414-416, in some embodiments, a set of scents, optionally four scents are selected, as described for the method of influencing dream content, for potentially reducing and / or avoiding olfactory habituation.

[0416] In Act 426, optionally, the patient provides feedback regarding the sleep quality and / or fatigue level during the day.

[0417] In Act 428, long-term effects of the olfactory treatment on the patient's sleep are evaluated. Improving sleep has the potential advantage of improving the patient’s physical health, mental well-being, and / or cognitive function, such as memory consolidation, physical restoration, longevity, weight management, immune function, emotional regulation, and / or energy restoration. In some embodiments, these parameters are tested periodically, for example using questionnaires and / or medical tests, and an improvement over time is evaluated.

[0418] In some embodiments, the evaluation comprises receiving feedback from the patient, regarding the physical health, mental well-being, and / or cognitive function thereof. Optionally, the patient is prompted to answer periodic questionnaires, alternatively or additionally, the patient is evaluated during periodic tests. For example, in some embodiments, the patient’s memory consolidation is evaluated, optionally by memory tests and / or neuroimaging techniques such as MRI and / or EEG.

[0419] A method for treating mental health conditions

[0420] Referring now to Fig 6. showing a simplified flowchart of a method for treating mental health conditions by olfactory stimulation during sleep, in accordance with some exemplary embodiments of the invention.

[0421] The method of Fig. 6 comprises:

[0422] Selecting (602) a patient suffering from anxiety disorder such as post-traumatic stress disorder (PTSD), and / or generalized anxiety disorder (GAD). Alternatively or additionally, the patient is suffering from mood disorders such as depression. In some embodiments, the patient is suffering from sleep disorders such as insomnia.

[0423] Reducing (604) sleep latency, optionally by providing an olfactory stimulation having a relaxing effect on the patient, as described in this document, during at least a portion of a predeep sleep stage, optionally, during at least a portion of a light deep stage. In some embodiments, the olfactory stimulation is provided prior to falling asleep and optionally continues during at least a portion of a light sleep stage, optionally until a deep sleep stage is detected.

[0424] Without being bound to theory, anxiety disorders such as PTSD can lead to heightened sympathetic arousal and / or hyperarousal, making it challenging to relax and fall asleep. Providing an olfactory stimulation, and optionally a relaxing noise such as white noise and / orlight music, having a relaxing effect on the patient's autonomic nervous system has the potential advantage of reducing sleep latency and promoting entrance into a deep sleep stage. In addition, one reason individuals with PTSD experience insomnia is due to their parasympathetic system's difficulty in achieving and maintaining high activation levels, resulting in shallow sleep resembling wakefulness. Providing a relaxing olfactory stimulation has the potential advantage of deepening the patient’s sleep.

[0425] In some embodiments, the stimulation is provided according to specific detected sleep stages.

[0426] Alternatively or additionally, the stimulation is provided based on an indication. For example, elevated heart rates can indicate a need to provide an olfactory stimulation having a calming effect on the patient (604);

[0427] Extending deep sleep, for potentially improving sleep quality and / or reducing fatigue during daytime (606);

[0428] Reducing nightmares by influencing dreams contact (608); and Lowering heart rate, optionally during sleep (610).

[0429] A method for treating dementia by olfactory stimulation during sleep.

[0430] The method for influencing dream contact by olfactory stimulation may be as described in Figs. 4 A-B with the following differences and / or elaboration:

[0431] In Act 402, the patient selection comprises selecting a patient suffering and / or potentially suffering from cognitive loss. In some embodiments, the patient is suffering and / or is at risk of suffering from dementia and / or other neurodegenerative diseases. In some embodiments, the patient is an older adult, which is usually prone to suffer from cognitive and / or memory loss. Alternatively or additionally, the patient is an individual aiming to improve the memory and / or cognition thereof.

[0432] In some embodiments, the treatment is provided as a preventive treatment, optionally for elder patients, and / or patients with a genetic predisposition to neurodegenerative diseases.

[0433] Refering now to Acts 410-416. Without being bound to theory, the critical memory storage processes (e.g., declarative memory consolidation process) occur during deep sleep, specifically during the slow wave sleep (SWS) phase of the non-REM sleep cycle. In some embodiments, when a light sleep stage is identified, one or more scents that can promote deep sleep are selected and provided to the patient. Alternatively or additionally, another deep sleep promoter can be provided to the patient, such as a sound stimulus, for example, sound(s) having a relaxing effect, such as a white and / or a pink noise, and / or a song having a calming effect on the patient.

[0434] In some embodiments, when a deep sleep stage is identified, at least one scent, intended for increasing brain activity (e.g. stimulating brain regions involved in emotion and memory, such as the amygdala and hippocampus, which are part of the limbic system) is selected and provided to the patient. Herein, a scent that stimulates the brain (or substantially stimulates the brain) can be defined as a scent that activates the olfactory bulb and / or regions of the brain associated with memory, such as the hippocampus and amygdala (as shown for example in Fig. 20) and / or leads to increased activity in the brain, which can be detected by brain imaging (such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG)), and / or evaluated for example, by neuropsychological tests and / or patient’s report for example, questionnaires and / or interviews.

[0435] Without being bound to theory, REM sleep is associated with emotional memory processing and / or procedural memory consolidation. In some embodiments, when a REM sleep stage is identified, at least one scent, intended for increasing brain activity is selected and provided to the patient.

[0436] Without being bound to theory, in some embodiments of the invention a way of treating dementia and / or other memory disorders is to stimulate the brain sufficiently. Providing olfactory stimulus during at least a portion of a deep sleep stage and / or a REM sleep stage when memory components are most active has the potential advantage of increasing brain stimulation and / or the effectiveness of the treatment. In some embodiments, a plurality of scents is selected, having the potentially enhancing brain stimulation. An additional potential advantage of a plurality of scents, provided to the patient in turn and / or with some overlap is reducing and / or preventing adaptation of the olfactory system to the scents and / or adaptation of the brain to the olfactory stimulation.

[0437] In some embodiments, a set of scents, optionally four scents are selected, for example, Rosemary (from the fresh scents family), Jasmine (from the floral scents family), Cinnamon (from the oriental scents family) and Cedarwood (from the woody scents family). In Act 418, the at least one scent is provided to the patient during at least a portion of a detected sleep stage, optionally, until the end thereof, as described in Act 416. For example, in some embodiments, a relaxing scent(s) is provided during at least a portion of a light sleep stage, optionally, from the detection of light sleep until the end of the stage.

[0438] In some embodiments, brain activity arousing scent(s) are provided during a portion of a deep sleep stage, optionally from detection of deep sleep until the end of the stage, alternatively, during a slow wave sleep (SWS) phase of the non-REM sleep cycle.

[0439] At 420-422, the reaction of the patient's exposure to the at least one scent is monitored. In some embodiments, at least one of the patient's physiological parameters is measured to detect an undesired effect of the treatment. For example, detecting awakening effects and / or negative effects such as nightmares and / or emotional distress during sleep.

[0440] In some embodiments, the olfactory treatment is adjusted according to the patient reaction.

[0441] In Act 426-428, a long-term effect of the olfactory treatment is evaluated. In some embodiments, the memory and / or cognitive function of the patient is assessed by receiving feedback from the patient. In some embodiments, the feedback comprises periodic questionnaires, such as comprehension and / or memory questionnaires that can indicate improvement and / or deterioration of dementia and / or memory.

[0442] In some embodiments, the evaluation comprises physical abilities tests such as walking test, executive function, activity spaces test, balance test, and / or fear of falling test (fear from falling is a common concern among patients with dementia).

[0443] In some embodiments, alternatively or additionally, structural changes relating in the patient's brain optionally relating with memory and / or cognitive function, can be measured by neuroimaging techniques and histological analyses, such as but not limited to MRI (Magnetic Resonance Imaging). For example, evaluating the size of the hippocampus (for example by MRI and / or CT), such that enlargement thereof can indicate an improvement in cognitive ability. In some embodiments, the effectiveness of scents on the patient is evaluated using this information.

[0444] A method for identifying dementia by olfactory stimulation.

[0445] Referring now to Fig. 7, showing a simplified flowchart of a method for identifying dementia by olfactory stimulation, in accordance with some exemplary embodiments of the invention.

[0446] The method of Fig. 7 includes: Creating a scent response indicator, by collecting data regarding the patient’s response to sensing an olfactory stimulus, and training a system (e.g., system 100) to detect said response and / or the lack thereof (702); and

[0447] Using the scent response indicator for detecting a decrease in the patient’s sense of smell, optionally, relative to a personal baseline, alternatively or additionally, relative to a general baseline (704);

[0448] Without being bound to theory, there is often a correlation between decreased sense of smell and dementia or other cognitive disorders. By establishing a personal scent response indicator (SRI), optionally a patient-specific scent response indicator, changes in the patient’s sense of smell can be monitored over time and indicate cognitive changes.

[0449] In some embodiments, the method of Fig. 7 can be used for diagnosing olfactory decrease. Early detection of olfactory decrease, or anosmia (impaired sense of smell), can be used for identifying underlying medical conditions and / or environmental contributing to medical conditions. For example, olfactory decrease can be one of the early symptoms of the disease caused by COVID-19, such that olfactory decrease has the potential advantage of facilitating early detection of COVID-19. In addition, an olfactory decrease can occur in the absence of other symptoms such that monitoring the patient's sense of smell has the potential advantage of facilitating the detection of asymptomatic patients.

[0450] Referring now to Figs. 8A-B, showing a more detailed flowchart of a method for identifying dementia by olfactory stimulation, in accordance with some exemplary embodiments of the invention. In some embodiments, acts 802-810 are details of Act 702 and acts 814- 826 are details of Act 704.

[0451] At 802, a patient suffering from dementia and or at risk of suffering from dementia is selected.

[0452] At 804, one or more of the patient’s physical parameters are monitored, while the patient is awake and exposed to olfactory stimulation (e.g., Act 802), optionally or additionally, the patient is monitored while not exposed to stimulation, optionally for establishing a base line.

[0453] At 806, an input from the patient is received, indicating whether the patient is able to smell the provided olfactory stimulation. For example, the patient answers a questionnaire in an application while smells are provided, optionally, the application is synchronized with the stimulator (e.g., scent diffuser 900)

[0454] In some embodiments, the input comprises information regarding the intensity with which the patient senses the smell, indicating the sensitivity of the patient's sense of smell. In some embodiments, the olfactory stimulation comprises releasing scent(s) pulses with various intensities (e.g., amplitude), optionally, in ascending order of intensity, and / or variable order for detecting the patient's level of sensitivity to olfactory stimulations. Alternatively or additionally, the system comprises the patient's reaction to different types of scents and / or release patterns (e.g., intensities, length of pulses, and / or intervals therebetween), for example, pleasant and / or unpleasant scents.

[0455] At 808, the patient's physiological response to sensing an olfactory stimulus is identified. For example, if a patient can smell a scent having a relaxing effect thereon, slower breathing rate, decreased heart rate, and / or lower blood pressure can be detected. In another example, if a patient smells a strong and / or unpleasant scent, faster breathing rate, increased heart rate, and / or higher blood pressure can be detected.

[0456] At 810, Acts 802-804 are repeated for data collection. In some embodiments, the repetition is performed by the patient at different times. In some embodiments, an application of the system (e.g., system 100) periodically prompts the patient to activate a scent diffuser while wearing a monitor (e.g., patient monitor 106) and indicates whether can smell a diffused scent. In some embodiments, alternatively or additionally to collecting data while the patient is awake, data regarding the patient’s physiological parameters is collected while the patient is asleep.

[0457] At 812, the data collected at act 810 is used for training the system, optionally, an Al component of the system.

[0458] In some embodiments, the training is based on patient-specific data. Alternatively or additionally, the training is based on data collected from a plurality of patients, optionally, with a common risk of dementia, and optionally, then the training is personalized based on patientspecific data. This has the potential advantage of reducing the amount of measurements required for training the system.

[0459] At 814, the patient’s one or more physiological parameters are monitored, optionally, during sleep, alternatively or additionally, while the patient is awake.

[0460] At 816, the patient is exposed to an olfactory stimulus.

[0461] At 818, the patient's ability to smell the olfactory stimulus is evaluated. In some embodiments, The scent response indicator detects changes in the patient’s physiological parameters which indicates that the patient is sensing the olfactory stimulation, while lack of change indicates that the patient can not smell the olfactory stimulation.

[0462] At 820-822, optionally, the olfactory stimulation is modified and then introduced to the patient. In some embodiments, if the patient's physiological parameters indicate that the patient can’t smell the previous stimulus, the next stimulus can be stronger, longer by time, and / or less pleasant for potentially distinguish between loss of smell and decreased sense of smell. Alternatively or additionally, a set of monotonous stimuli (e.g., in intensity and / or type) is provided, having the potential advantage of reducing and / or avoiding habituation.

[0463] In some embodiments, if the patient's physiological parameters indicate that the patient can smell the previous stimulus, the next stimulus can be weaker, shorter by time, and / or more pleasant for potentially detecting the sensitivity of the sense of smell and / or improvement in the sense of smell.

[0464] At 824, the patient, a caregiver, and / or a treatment center is informed if changes in the sense of smell thereof are detected. In some embodiments, upon detection of a decrease in the patient’s sense of smell or a loss of the sense of smell, the patient is recommended to consult a medical professional.

[0465] At 826, optionally, olfactory treatment for treating dementia and / or improving the sense of smell can be provided, for example as described in this document.

[0466] Exemplary device

[0467] Referring now to Figs. 9A-C, showing side views of a scent diffuser 900, in accordance with some exemplary embodiments of the invention.

[0468] Referring also to Fig. 9D, showing an exploded views of scent diffuser 900, in accordance with some exemplary embodiments of the invention.

[0469] Referring also to Fig. 9E, showing an aerosolizer 902 of ascent diffuser 900, in accordance with some exemplary embodiments of the invention.

[0470] Referring also to Fig. 9F showing a perspective view of scent diffuser 900 for releasing a plurality of scents, in accordance with some exemplary embodiments of the invention.

[0471] Scent diffuser 900 can be a detailed embodiment of stimulator 102 and / or odorant delivery device 202.

[0472] In some embodiments scent diffuser 900 comprises an aerosolizer 902, such as an atomizer and / or a nebulizer that transforms a liquid scent substance into inhalable droplets, spray, mist, and / or aerosol. For example, in some embodiments, scent diffuser 900 comprises a piezoelectric disk for fluid atomization, as shown for example in Figs. 9C-E.

[0473] In some embodiments, scent diffuser 900 comprises at least one cartridge 904 for continuing a liquid scent substance. In some embodiments, piezoelectric disk 902 is connected to a tube for liquid therewithin. In some embodiments, cartridge 904 is refillable, alternatively or additionally, cartridge 904 is removable. In some embodiments, cartridge 904 is removable and optionally, disposable. In some embodiments, cartridge 904 comprises piezoelectric disk 902, for example, located at the bottom there (as shown for example in Fig. 9F). Upon placing cartridge 904 within scent diffuser 900 piezoelectric disk 902 is connected electrically thereto. In some embodiments, cartridge 904 is recognized by scent diffuser 900, optionally using a QR code reader and / or RFID. This disposable cartridge, including a disposable piezoelectric disk, has the potential advantage of reducing scent substance contamination and / or undesired mixing of scent. In some embodiments, scent diffuser 900 comprises an opening mechanism for a cartridge, such as a puncher.

[0474] In some embodiments, scent diffuser 900 comprises a housing 906 with an outlet aperture 908 for scent release therefrom. In some embodiments, the aerosolizer 902 is located within housing 906 near the outlet aperture 908 such that there is a fluid communication between the at least one cartridge 904 and the aerosolizer 902. In some embodiments, outlet aperture 908 comprises a valve, controlled by controller 104, such that there is a fluid communication between the at least one cartridge 904 the aerosolizer 902 and said valve.

[0475] In some embodiments, scent diffuser 900 is configured to be automatically operated by a controller (e.g., controller 104 of system 100). In some embodiments, scent diffuser 900 comprises a PCB (Printed Circuit Board) 910 and a microprocessor 912 which controls the control the operation of scent diffuser 900. In some embodiments, microprocessor 912 comprises controller 104, alternatively or additionally, microprocessor 912 comprises a transceiver (e.g., transmitter-receiver) allowing thereof to communicate and be controlled by controller 104, such that controller 104 optionally, is positioned externally to scent diffuser 900.

[0476] In some embodiments, outlet aperture 908 is a selectively closable aperture allowing further control of scent release timing, pattern, and / or intensity. In some embodiments, aperture 908 is rotatable, and optionally comprises a motor that can controlled by controller 104 allowing to modify release angle. This modification has the potential advantage of improving the scent release orientation in relation to the patient. In some embodiments, outlet aperture 908 can be a closed loop with a camera, such that the motor thereof is operated (e.g., by controller 104) to adjust the orientation of the scent release to be toward the patient.

[0477] In some embodiments, outlet aperture 908 is defined by piezoelectric disk 902, such that when not activated, is sealed to scent release and / or entrance. Alternatively or additionally, the valve of outlet aperture 908 opens and / or closes to allow scents to release. In some embodiments, the valve is located between cartridge 904 and piezoelectric disk 902. In other embodiments, the valve is located near and / or incorporated within aperture 908. In some embodiments, piezoelectric disk 902 is positioned within container 904, optionally at the bottom thereof. This positioning potentially reduces the noise resulting from liquid atomization at the outlet, having the potential advantage of reducing noise disturbance to the patient sleep. This directionality potentially reduces scent saturation in the room, allowing the evacuation of scents and / or altering scents while reducing and / or preventing scents from blending undesiredly. This directionality potentially reduces the effect on other persons in the room, which are not the patient. In addition, this directionality has the potential advantage of saving costs of scent substances.

[0478] In some embodiments, scent diffuser 900 comprises a power source 914. In some embodiments, power source 914 is a portable power source, such as a battery. In some embodiments, the portable power source is rechargeable and / or removable. Alternatively, or additionally, to a portable power source, power source 914 can be a conductivity to an external power supply, such as an AC (alternating current) power supply.

[0479] In some embodiments, scent diffuser 900 comprises one or more operation buttons 916, 918, for activating thereof. In some embodiments, a first power button 916 is a power button (e.g., an Off-On button), and a second operation button 918 is configured for controlling scent diffusion 900, for example, changing the device’s modes, altering scent release intensities and / or controlling connectivity through WIFI and / or Bluetooth., alternatively or additionally scent diffuser 900 can be activated and / or operated automatically and / or remotely, optionally by controller 104.For example, scent diffuser 900 can be activated and / or operated remotely via a touch screen of a smartwatch, and / or a smartphone.

[0480] In some embodiments, scent diffuser 900 is constructed to have a separation between the device’s electronics (e.g., PCB 910, microprocessor 912, and / or power source 914) and the liquid scent substances within at least one cartridge 904. This separation potentially prventing liquid leakage causing electrical shorts and / or corrosion of the electronics

[0481] In some embodiments, scent diffuser 900 comprises a tank 920, optionally positioned below at least one cartridge 904, for collecting and / or storing leaks of liquid scent substances for at least one cartridge 904. In some embodiments, tank 920 is positioned above the electronics of scent diffuser device 900 (e.g., PCB 910, microprocessor 912, power source 914), for potentially protecting thereof from exposure to liquid scent substance(s).

[0482] In some embodiments, scent diffuser 900 comprises a leak outlet 922, allowing leaking liquids from tank 920 to be drained out form scent diffuser 900. In some embodiments, scent diffuser 900 is configured to release more than one scent, as shown for example is shown in Fig. 9F which depicts a scent diffuser configured for providing up to four base scents.

[0483] In some embodiments, scent diffuser 900 comprises a cartridge 904 for each scent substance and optionally, aerosolizer 902, such as a piezo disk for fluid atomization for each cartridge 904, for potentially reducing undesired mixing and / or contamination of liquid substances contained in cartridge(s) 904. In some embodiments, scent diffuser 900 comprises a separate outlet aperture 908 for each scent, potentially further reducing undesired mixing and / or contamination of liquid scent substances. In addition, the separate aperture allows the release of more than one scent simultaneously if required, and / or the release of the same liquid scent substance, from more than one outlet aperture 908, optionally, simultaneously. Releasing the same liquid scent substance from more than one outlet aperture 908 allows to increase an intensity of the stimulus, controlling the direction of the stimulus release, and / or releasing the liquid scent substance in more than one direction, having the potential advantage of improving the exposure effectiveness on the patient if required.

[0484] In some embodiments, scent diffuser 900 comprises at least one fan and / or motor (not shown) used to disperse the scent into the air. In some embodiments, a fan is located near the electronics (e.g., PCB 910, microprocessor 912, power source 914), for cooling the electronics in addition to or instead of scent dispersion. In some embodiments, scent diffuser 900 comprises an additional fan, located next to the outlet of piezo disk 902. An additional fan potentially improves the scent dispersion. More than one fan allows for the fans to be smaller, while not impairing the scent dispersion. Smaller fans are potentially less loud and / or less noisy, having the potential advantage of reducing disturbances to the patient's sleep. In some embodiments, scent diffuser 900 comprises a fan for each cartridge 904 and / or for each piezo disk 902. In some embodiments scent diffuser 900 comprises a mixing tank (not shown) for scent mixing. The mixing tank is located at the outlet of the piezo disks, for allowing scent aerosols to mix, if required, while reducing and / or avoiding contaminating the liquid substances contained in cartridge(s) 904. In some embodiments, scent diffuser 900 is configured to blend scent in a controlled manner. In some embodiments, scent diffuser 900 releases more than one scent according to pre-set ratios, optionally, considering the relative dispersion thereof.

[0485] Referring now to Figs. 10A-B showing perspective side views of a positioned scent diffuser 900, in accordance with some exemplary embodiments of the invention. Referring also to Fig. IOC, showing a side view of a positioned scent diffuser with an adaptor for installing thereof, in accordance with some exemplary embodiments of the invention.

[0486] In some embodiments, scent diffuser 900 is positioned 50 cm above the patient’s bed (e.g., above the mattress surface). For example, about 40-60 cm, or 10-50 cm, or 40-100 cm, or about 55 cm, or about 70 cm, or lower or higher, or intermediate numbers of distances.

[0487] In some embodiments, the scent diffuser 900 is positioned in line with the center of the patient, optionally, 50 cm above the patient center.

[0488] In some embodiments, scent diffuser 900 is configured to be placed on a bedside table and / or on a windowsill next to the bed.

[0489] In some embodiments, scent diffuser 900 is configured to be mounted on a wall next to the bed, optionally above the patient's head and / or on the side of the patient’s bed. In some embodiments, scent diffuser 900 comprises an adaptor 1000, such as a holder, shaped and / or sized to contain scent diffuser 900 and to be mounted on a surface, optionally, a vertical surface such as said wall. In some embodiments, adaptor 1000 comprises a connector such as an adhesive tape, suction cup and / or a screw for anchoring thereof to the surface.

[0490] In some embodiments, scent diffuser 900 and / or adaptor 100 comprise at least one sensor for identifying the patient’s location (e.g., distance and / or orientation) relative to scent diffuser 900, such as, a speaker, a microphone, network signal sensor, IR sensors, and / or a camera. For example, in some embodiments controller 104 can identify deviation from a desired position by image processing of camera signals.

[0491] Alternatively or additionally, the patient can input the location thereof relative to scent diffuser 900, for example, by using a user interface of monitor 106.

[0492] In some embodiments, if scent diffuser 900 is positioned otherwise than instructed, controller 904 adjusts the amplitude and / or frequency of the scent release to provide a desired stimulus intensity to the patient.

[0493] In some embodiments, adaptor 1000 comprises a movable arm, which allows the adjustment of the location and / or orientation of scent diffuser 900. In some embodiments, the arm is an electric arm that can be remotely adjusted, having the potential advantage of allowing the patient to reposition scent diffuser 900 without leaving the bed. In some embodiments, the arm is automatic, optionally, controlled by controller 104. Alternatively or additionally, scent diffuser 900 is rotatable (e.g., around a longitudinal axis thereof), optionally, controlled by controlled by controller 104. Referring now to Fig. 11 A, showing an illustration of a controller 900 of a system for providing olfactory stimulation during sleep, in accordance with some exemplary embodiments of the invention.

[0494] Referring also to Fig. 11B, showing an illustration of software of controller 1100, in accordance with some exemplary embodiments of the invention.

[0495] Controller 900 can be a detailed embodiment of controller 104 described in Figs. 1A- B.

[0496] Control 900 is configured to control a system for providing olfactory stimulation (e.g., system 100).

[0497] In some embodiments, Controller 1100 comprises a processor 1102, connected to a memory 1108 and to a software 1110.

[0498] In some embodiments, controller 1100 is connected to a patient monitor (e.g., monitor 106) and / or to at least one sensor (e.g., at least one sensor 108) thereof via communication link 912. Alternatively or additionally, controller 900 is incorporated into the patient monitor.

[0499] In some embodiments, controller 1100 is further connected to external devices, via communication link 1112, such as to a camera, microphone, light sensor, temperature sensor, and / or humidity sensor, positioned in the room.

[0500] In some embodiments, processor 1102 comprises a CPU (Central Processing Unit) portion 1104, and optionally an Al component 1106. In some embodiments, Al component comprises a neural network, optionally of LSTM type (Long Short-Term Memory). Alternatively or additionally, Al component 1106 comprises a SARIMAX network. In some embodiments, the Al component is used for machine learning and / or running a trained model. Alternaternatively or additionally, the learning is performed remotely and / or external to controller 1100, for example on a cloud.

[0501] In some embodiments, processor 1102 is configured to produce a classification and / or identification output of the patient’s sleep stage for example, about every minute, utilizing data collected during the preceding minute as well as historical data, optionally, stored in memory 1108. For example, about every 0.5-2 minutes, or 1-5 minutes, or 0.8-1.5 minutes, or about 1.1 minutes or lower or higher, or intermediate numbers of minutes. Alternatively or additionally, processor 1102 is configured to produce an identification output of a patient’s irregular state, In some embodiments, processor 1102 is configured to identify sleep stages by considering one or more factors, including the patient’s physiological parameters and / or environmental information. In some cases, identifying a sleep stage and / or an irregular state requires considering a relatively increased number of factors, optionally, by using Al component 1106. For example, when there is no significant change in one of the patient's physiological parameters in the transition between sleep stages, sleep stage classification can be performed by considering a plurality of physiological parameters as well as additional parameters such as a stage during the night, and / or historical data, and / or processing image signals from a camera and / or sounds signals form a sound sensor. In some embodiments, memory 1108 is a part of controller 1100, alternatively or additionally, memory 1108 is external to controller 1100, for example, located in a cloud. Code for applying the methods and / or embodying various modules of system 100 is optionally stored, temporarily and / or permanently in memory 1108, for execution by processor 1102 (e.g., CPU portion 1104 and / or Al component 1106).

[0502] In some embodiments, software 1110 comprises an input receiver module 1114, a sleepstage identifier module 1116, an abnormality identifier module 1118 , a stimulus selector module 1120, and / or an output transmitter module 1122.

[0503] In some embodiments, input receiver module 1114 receives input from a patient monitor (e.g., monitor 106) and / or directly from at least one sensor (e.g., sensor 108) via communication 1112 by processor 1102. In some embodiments, input receiver module 1114 parses the input and transmits a signal to sleep-stage identifier module 1116 and / or abnormality identifier module 1118. In some embodiments, sleep-stage identifier module 1116 obtains information from memory 1108 and identifies a current sleep stage. In some embodiments, abnormality identifier module 1118 obtains information from memory 1108 and identifies an abnormality in the patient’s physiological parameters. In some embodiments memory 1108 stores baseline values of the patient’s physiological parameters and / or threshold values defining which deviation from the baseline is considered as an abnormality. In some embodiments, the baseline and / or threshold values are personalized, optionally by pre-treatment learning of the patient, and / or learned during treatment.

[0504] In some embodiments, stimulus selector module 1120 first determines if providing stimulation is required, considering the current sleep stage and / or the presence of an abnormality. If stimulation is required, stimulus selector module 1120 selects the olfactory stimulus parameters, optionally based on treatment tables for each disease, data on other patients from the same diseasewhile considering a patient’s medical history 1124 and / or historical data 1126, stored in memory 1108. In some embodiments, memory 1108 comprises selection data which comprises stimulations to select from.

[0505] In some embodiments, memory 1108 comprises treatment protocols. For example, protocols of pulsed release (e.g, pulse intensity, pulse length, and / or intervals between pulses), protocols for sleep stages, protocols for sleep sessions (e.g., night sleep and / or a day napping), protocols for a week, protocols for a week for a month, and / or protocols for a week to accompany a chronic disease and / or a chronic mental conditions.

[0506] In some embodiments, stimulus selector module 1120 selects an olfactory stimulation according to treatment guidelines 1128, optionally statistical guidelines, alternatively or additionally, patient-specific guidelines. In some embodiments, stimulus selector module 1120 selects the type of scents, number of scents in a series, order of scents, release pattern (e.g., intensity, duration of release pulses, duration between release pulses), and / or duration of stimulation. In some embodiments, stimulus selector module 1120 applies the treatment methods described in this document.

[0507] In some embodiments, output transmitter module 1122 obtains a selected stimulus from stimulus selector module 1120 and transmits signals, optionally to an odorant delivery device (e.g., odorant delivery device 102). Alternatively or additionally, output transmitter module 1122 transmits signals to other external devices, for example, an alarm for waking up the patient if needed, and / or to an electric arm that moves and / or directs the odorant delivery device.

[0508] Referring now to Fig. 12, showing an exemplary flow diagram of an olfactory treatment using system 100 for providing olfactory stimulation, in accordance with some exemplary embodiments of the invention.

[0509] In some embodiments, a patient is monitored during sleep, optionally by a patient monitor (e.g., patient monitor 106) in the form of a smartwatch with an application of system 100 installed thereon. The smartwatch monitors the patient's physiological parameters as described in this document, such as vital signs (e.g., pulse rate (heart rate) and / or HRV, respiratory rate, blood pressure, and / or body temperature) and / or accelerometer measurements.

[0510] The data is transmitted to a controller (e.g., 104, 1100) optionally, located in the scent diffuser microprocessor (e.g., microprocessor 912) and / or in a cloud. Then, a processor (e.g., processor 1102) of the controller analyzes the data to identify a mental and / or physiological state of the patient that requires olfactory stimulation. Alternatively or additionally, the processor identifies a current sleep stage optionally, that requires an olfactory stimulation. Then an olfactory stimulation is selected, as shown for example in Fig. 12. In some embodiments, once a light sleep is identified, at least one scent having a relaxing effect on the patient is selected, for potentially enhancing deep sleep. In some embodiments, upon identifying a deep sleep stage, at least one scent having a relatively high cognitive effect is selected, having the potential advantage of reducing the risk of waking the patient as a result of the exposure to the stimulation. In some embodiments, once a REM sleep stage is identified, at least one scent having a cognitive effect and is less likely to cause awakening is selected. In some embodiments, the cognitive effectiveness is evaluated prior to treatment, optionally, during a personalization procedure of the treatment plane. In some embodiments, this evaluation comprises testing one or more of the following and / or any combination thereof: REM sleep duration; Deep sleep duration; Total sleep duration; Heart rate; and Awakening frequency and / or duration, such that a relatively prolonged deep sleep duration and / or total sleep duration and / or relatively reduced heart rate and / or and Awakening frequency and / or duration, indicated on relatively high effectiveness of a scent.

[0511] In some embodiments, the selected at least one scent is provided to the patient using a smart scent diffuser (e.g., scent diffuser 900), located in proximity to the patient.

[0512] Exemplary system training

[0513] Referring to Fig. 13, showing a simplified flowchart of a method for training a system for providing olfactory stimulation to a patient during sleep, in accordance with some exemplary embodiments of the invention.

[0514] The method of Fig. 13 includes:

[0515] Training of the system to provide an olfactory treatment based on statistical data (e.g., literature, data from a control group, and / or data of other patients), where the training comprises first identifying sleep stages during the course of a patient's sleep and / or identifying a patient state, such as medical condition abnormality, and then selecting whether to provide an olfactory stimulus and / or which stimulus to provide (1302); and

[0516] Personalizing the treatment based on patient-specific data, optionally by tuning the learning by patient-specific data, optionally, regarding the patient's sleep patient's sleep characteristics and / or regarding the patient's response to olfactory stimulation(s) (1304).

[0517] Referring now to Figs. 14A-B, showing a flowchart of a method for training a system to classify sleep stages, in accordance with some exemplary embodiments of the invention.

[0518] In some embodiments, the method of Figs. 14A-B implement act 1302.

[0519] In some embodiments, the system training is based on data from a sleep tracker. Alternatively or additionally, the training is based on polysomnography measurement. In some embodiments, as shown in Figs, 14A-B, the system is trained based on sleep tracker data and tuned by polysomnography measurement. At 1402 data from at least one sensor which monitors the patient during sleep, is collected. In some embodiments, the at least one sensor measures one or more of a patient's physiological parameters. In some embodiments, the at least one sensor is one or more of the sensors previously described in this document. For example, a heart rate meter. In some embodiments, the monitoring is performed while a patient is wearing a wearable monitor (e.g., patient monitor 106) which comprises the at least one sensor.

[0520] At 1404, data from a sleep tracker is collected, at the same time the at least one sensor is monitoring the patient.

[0521] At 1406, the patient’s night's sleep is categorized into distinct sleep stages and each sleep stage is identified, based on the data collected by the sleep tracker, and performed retroactively optionally, based on data collected throughout all and / or most night sleep.

[0522] In some embodiments, the data collection of acts 1402 and 1404 are collected from a plurality of patients experiencing common disorder(s) and / or symptoms during sleep.

[0523] At 1408, the measurements from at least one sensor are labeled with the corresponding sleep stages.

[0524] At 1410, acts 1402-1408 are repeated for data augmentation. In some embodiments, the data is collected from a population of patients, optionally a diverse population.

[0525] In some embodiments, the population numbers about 100 patients or more, optionally, divided by demographics, for example, age, gender, life experience, disorder, optionally, such that each category about 100 patients or more. For example, 50-100 patients, or 100-200 patients, or 20-50 patients, or about 150 patients, or about 300 patients, or lower or higher or intermediate numbers of patients. In some embodiments, the patients’ ages are between 20 to 60 years old. For example, 18-62 years old, or 25-50 patients, or 40-70 patients, or lower or higher or intermediate numbers of ages. In some embodiments, the measurements are repeated over the course of about 10 nights each. For example, 5-10 nights, or 10-30 nights, or about 15 nights, or about 25 nights, or lower or higher or intermediate numbers of nights.

[0526] At 1412, the labeled data is modeled. In some embodiments, the model learns from the input-output pairs provided thereto and the model parameters are automatically adj us ted to minimize the difference between its predictions and the true labels. For example, neural network, optionally, LSTM type, and / or SARIMAX network, as described in this document.

[0527] At 414, the patient’s brain waves during sleep are monitored, at the same time the at least one sensor is monitoring the patient. In some embodiments, the patient's sleep is classified into sleep stages based on monitoring brain activity during sleep, optionally, in a sleep laboratory using PSG (polysomnography) and / or EEG (Electroencephalogram) measurements, and the data is collected. At 1416, the patient’s night's sleep is categorized into distinct sleep stages and each sleep stage is identified, based on the brain waves data.

[0528] At 1418, the course of sleep is categorized into distinct sleep stages and each sleep stage is identified, according to the brain wave measurements.

[0529] At 1420, the measurements from at least one sensor are labeled with the corresponding sleep stages, classified according to brain wave measurements.

[0530] At 1422, acts 1402-1408 are repeated for data augmentation. In some embodiments, the data is collected from a population of patients, optionally a diverse population, optionally, the same population of Act 1410. In some embodiments, the population numbers about 30 patients. For example, 5-25 patients, or 10-33 patients, or 20-60 patients, or about 35 patients, or about 25 patients, or lower or higher or intermediate numbers of patients.

[0531] At 1424, the model is tuned using the input-output pairs based on the brain wave measurements.

[0532] Referring now to Figs. 15A-B, showing a flowchart of a method for training a system to select an olfactory stimulation, in accordance with some exemplary embodiments of the invention.

[0533] At 1502, one or more of a patient's physiological parameters are monitored during sleep thereof. In some embodiments, the monitoring comprises the classification of the patient’s sleep into sleep stages.

[0534] At 1504, an olfactory stimulus is introduced to the patient while asleep.

[0535] At 1504, data regarding the timing of providing the stimulation and / or the sleep stage of providing the stimulation is collected.

[0536] At 1508, data regarding the patient's physiological parameters as a response to the olfactory stimulation is detected and collected, for example, the patient’s heart rate and / or breathing rate.

[0537] At 1510, data regarding the patient’s sleep, and / or changes in the patient sleep as a response to the stimulus is collected. For example, time to fall asleep, number of awakenings, duration of light, deep, and / or REM sleep stages. At 1512, the olfactory stimulation is modified. In some embodiments at least one of the following stimulation parameters is modified: type of scent, number of scents, order of scent dispersion intensity, dispersion duration, time elapsed since the previous dispersion, timing of introduction of a scent (e.g., sleep stage).

[0538] At 1514, acts 1502-1512 are repeated for data collection. At 1516, acts 1502-1514 are repeated for a plurality of patients. For example, a population of about 100 or more patients, or 75-100 patients, or 80-150 patients, or 150-300 patients, or about 120 patients, or about 200 patients, or lower or higher or intermediate numbers of patients.

[0539] At 1518, the stimulus parameters are labeled with the corresponding patient’s parameters: timing (e.g., sleep stage), patient’s physiological parameters, and / or patient’s sleep parameters.

[0540] In some embodiments, the labeling further comprises a correlation between a patient’s physiological abnormality such as elevated heart rate and / or talking while sleeping with corresponding stimulus parameters.

[0541] At 1520, the labeled data is modeled. For example, using neural network, optionally, LSTM type, and / or SARIMAX network, as described in this document.

[0542] In some embodiments, the model learns from the input-output pairs of stimulus parameters-patient’s parameters provided thereto and the model parameters are automatically adjusted to minimize the difference between its predictions and the true labels.

[0543] Exemplary personalization method

[0544] Referring to Fig. 16, showing a flowchart of a method for personalizing an olfactory treatment, in accordance with some exemplary embodiments of the invention.

[0545] At act 1602, a patient is selected, as described in this document. In some embodiments, the patient reacts differently to olfactory stimulation than described in the literature or by other patients. Personalization has the potential advantage of improving the effectiveness of olfactory treatment for said patient.

[0546] At act 1604, in some embodiments, the sleep-stages classification procedure is personalized, optionally, by employing the method of Figs. 14A-B for an individual patient, e.g., by using patient-specific data for training a system (e.g., system 100) to identify the patient’s sleep stages. In some embodiments, one or more of the patient’s physiological parameters are monitored during a pre-treatment period. In some embodiments, the patient sleeps with a monitor (e.g., patient monitor 106) for about 7-14 nights before treatment. For example, 5-15 nights, or 3-14 nights, or 15-20 nights, or about 10 nights, or about 20 nights, or lower or higher or intermediate numbers of nights.

[0547] In some embodiments, the system learns the characteristics of the patient's sleep, for example, the physiological parameter values during sleep and / or different sleep stages. For example, characteristic heart rate and / or breathing rate during sleep and / or a certain sleep stage. This patient-specific information has the potential advantage of improving the sleep stages classification for the individual patient.

[0548] In some embodiments, the information regarding the patient's sleep characteristics can be used as a baseline to detect patient-specific physiological abnormalities, such as elevated heart rate and / or elevated breathing rate. In some embodiments, this base-line can be used to detect physiological characteristics indicating that the patient experiences a nightmare and / or anxiety while sleeping

[0549] At act 1606, in some embodiments, the stimulation selection procedure is personalized, optionally, by employing the method of Figs. 15A-B for an individual patient, e.g., by using patient-specific data for training a system (e.g., system 100) to select stimulus parameters.

[0550] In some embodiments, the patient undergoes positive conditioning to at least one scent, for example by exposing the patient to the at least one scent during a positive experience, as described in this document.

[0551] In some embodiments, the patient receives an odor preference questionnaire during which a plurality of scents is introduced and the patient indicates which odor is perceived thereby as pleasant.

[0552] In some embodiments, the patient’s historical data is collected and used for tuning the system model, having the potential advantage of improving accuracy and / or efficiency thereof. In some embodiments, this data comprises scent diffuser information such as dispersion time, power usage, dispersion duration, and scent type during the course of sleep.

[0553] In some embodiments, information regarding the medical history and / or medical conditions of the patient is provided for adjusting the olfactory treatment accordingly.

[0554] At 1608, in some embodiments, the personalization comprises enhancing and / or improving the exposure to the olfactory stimulation, for example, as described in Fig. 17.

[0555] At 16010, a personal Scent Response Indicator (SRI) is optionally established, for example as described with reference to Fig. 8A-B. In some embodiments, the patient is required to approach and activate the scent diffuser of the system and / or use a separate scent diffuser, optionally, portable, optionally, wearable, such as on the patient’s wrist, during daytime while monitored by the patient monitor. For example, for about 5-15 minutes, for about 10-30 minutes, or 1-5 minutes, or 9-12 minutes, or about 7 minutes or lower or higher, or intermediate numbers of minutes.

[0556] The scent diffuser initiates a sequence of scent dispersals with varying characteristics. At the end of each dispersion, the monitor records the patient’ s physiological parameters and / or environmental measurements, and the patient indicates optionally using an application of the system if the scent is detected and to what extent. In some embodiments, the patient repeats this process, optionally, for at least 5-6 days, during the initial period of treatment, for example, during the initial two weeks. Subsequently, the application encourages the patient to perform this process periodically, for example, once every 2-3 weeks, to potentially enhance the SRI indicator.

[0557] Referring now to Fig. 17, showing a flowchart of a method for improving olfactory expousre effectiveness, in accordance with some exemplary embodiments of the invention.

[0558] At 1702, at least one of a patient’s physiological parameters is monitored, optionally, during a pre-treatment period, alternatively or additionally, periodically between and / or during treatments.

[0559] In some embodiments, the monitoring is performed during a patient’s sleep. Alternatively or additionally, the patient activates the system (e.g., system 100) while awake. In some embodiments, an application of the system prompts the patient to activate a scent diffuser (e.g., scent diffuser 900) optionally while wearing a monitor (e.g., patient monitor 106). In some embodiments, the scent diffuser is located near the patient’s bed and the patient is lying awake in bed.

[0560] At 1704, an olfactory stimulus is introduced to the patient.

[0561] At 1706, whether the patient can sense (e.g., smell) the olfactory stimulation is evaluated. In some embodiments, a change in at least one of the patient’s physiological parameters, optionally during sleep, indicates that the patient can sense (e.g., smell) the stimulus with sufficient intensity. Alternatively or additionally, a decrease in the patient's physiological response, optionally during sleep, indicates an olfactory decrease.

[0562] Alternatively or additionally, the patient is awake and aware that an olfactory stimulus is introduced. Then, input is provided by the patient regarding the ability thereof to smell the provided scent(s). For example, in some embodiments, the patient user indicates if the stimulus is sensed and to what extent.

[0563] At 1708, the olfactory stimulation and / or the delivery thereof is adjusted for potentially increasing the ability of the patient to smell the olfactory stimulation. For example, the dispersion intensity is increased, the dispersion duration is extended, the diffuser placement and / or orientation in the room is adjusted. Alternatively or additionally, the number of scents in a scent series and / or the order thereof and / or the scent(s) types are modified. In some embodiments, the olfactory stimulation is adjusted to analyze which stimulus leads to a significant decrease in heart rate. For example, which scent(s), delivery patterns and / or the combination thereof.

[0564] Experimental results

[0565] Various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below find experimental support in the following validation experiment.

[0566] Referring now to Figs. 18A-C, showing an example of patients' feedback on olfactory treatment during sleep, in accordance with some exemplary embodiments of the invention.

[0567] Referring also to Fig. 19A, showing a table with average results of heart rate, during the entire night's sleep or during REM sleep, of nights free from olfactory stimulation versus nights when the patient was exposed to olfactory treatment, in accordance with some exemplary embodiments of the invention.

[0568] Referring also to Fig. 19B, showing a table with average results of heart rate change resulting from exposure to olfactory treatment, during the entire night's sleep or during REM sleep, , in accordance with some exemplary embodiments of the invention.

[0569] Referring also to Fig. 19C, a graph showing an example of changes in the heart rate of one patient during sleep, as a result of exposing thereof to olfactory stimulation, in accordance with some exemplary embodiments of the invention.

[0570] To obtain this data, 20 participants between the ages of 25-70 were exposed to olfactory stimulation during sleep. All the participants were healthy, meaning not diagnosed with sleep disorders and / or mental conditions, and did not consume and do not regularly consume sleeppromoting substances such as sleeping pills, and / or cannabis. Each participant was provided with a smartwatch (Fitbit smartwatch) with an application installed thereon (e.g., an application of system 100).

[0571] In the experiment and in some embodiments of the invention, for example at block 1604 in Fig. 16, first, learning of the patient's sleep was performed. Each participant was required to wear the smartwatch during sleep, for three weeks during which each participant was monitored by the system’s application to collect measurements of heart rate (e.g., BPM (beats her minute)), HRV (heart rate variability) and sleep stage classification based on the smartwatch program (based on retrospective analysis of the night sleep). The sample rate was one minute for each measurement. The collected data from the three weeks was analyzed for statistically predicting REM sleep stages. The timing and duration where each participant was in REM sleep were analyzed to obtain a sleep stages timeline, based on at least 70% of the nights of each participant.

[0572] In addition to the measurements from the smartwatch, each participant answered a questionnaire regarding the sleep and feelings thereof, each morning, for control.

[0573] In the experiment and in some embodiments of the invention, for example at block 1606 in Fig. 16, each participant was introduced to 5 scents: rose, lavender, vanilla, camomile, and Jasmine. Each participant chose two scents that were perceived as positive.

[0574] At night, each participant was requested to turn on a scent diffuser located next to the bed thereof, upon entering into bed for night sleep, and then each diffuser started scent release according to an individual release program. The scent diffuser was programmed to release a scent for a minute and stop for 4 minutes during each REM interval, potentially avoiding habituation. The first scent was provided for 10 days and then switched to the other selected scent, for additional 10 days.

[0575] During night sleep, the system’s application collects measurements of heart rate (e.g., BPM) and HRV and sleep stage classification based on the smartwatch program. In addition to the measurements from the smartwatch, each participant answered a questionnaire regarding the sleep and feelings thereof, each morning, as performed during the control period.

[0576] Results summary: The measurements and participants' feedback with and without being exposed to olfactory stimulation during sleep were compared.

[0577] When asked “How was your sleep at night” an increase was observed in the number of participants who answered “Well, better than usual” after a night of exposure to olfactory stimulation (28.69% of the participants) compared to a night free of olfactory stimulation (17.3% of the participants), and a decrease was observed in the number of participants who answered “worse than usual” after a night of exposure to olfactory stimulation (11.95% of the participants) compared to a night free of olfactory stimulation (18.8% of the participants), as shown in Fig. 18 A.

[0578] When asked “What are your feelings from the night” an increase was observed in the number of participants who answered “moderate positive feeling” after a night of exposure to olfactory stimulation (25.9% of the participants) compared to a night free of olfactory stimulation (10.3% of the participants), and a decrease was observed in the number of participants who answered “moderate negative feelings” after a night of exposure to olfactory stimulation (12.35% of the participants) compared to a night free of olfactory stimulation (19.56% of the participants), and a decrease observed in the number of participants who answered “very negative feelings” after a night of exposure to olfactory stimulation (1.59% of the participants) compared to a night free of olfactory stimulation (2.95% of the participants), as shown in Fig. 18B.

[0579] When asked “What was the nature of your dreams” an increase was observed in the number of participants who answered “realistic and good” after a night of exposure to olfactory stimulation (26.24% of the participants) compared to a night free of olfactory stimulation (22.49% of the participants), and a decrease was observed in the number of participants who answered “realistic and bad” after a night of exposure to olfactory stimulation (4.94% of the participants) compared to a night free of olfactory stimulation (8.3% of the participants, as shown in Fig. 18C.

[0580] Referring now to Figs. 19A-B, for 16 of the 20 participants, a decrease in heart rate was observed, as a result of the olfactory treatment, on average for the whole night's sleep, when compared to night's lack of olfactory treatment . A total of 2.9% decrease for all 20 participants and a 4.2% decrease for the 16 participants.

[0581] For 15 of the 20 participants, a decrease in heart rate was observed, as a result of the olfactory treatment, through the REM sleep. A total of 1.85% decrease for all 20 participants and a 3.02% decrease for the 15 said participants. For some of the participants, a trend of a decrease in heart rate was observed when comparing the nights when the patient was exposed to olfactory stimulation with the prior nights when free from olfactory stimulation, for example, as shown in Fig. 19C (for patient number 6) and Fig 19D.

[0582] Exemplary protocolsln some embodiments, a pulse of scent release is provided upon identifying a particular sleep stage (such as REM and / or deep sleep), and / or upon detecting a physiological state (such as high heart rate and / or a physiological state indicating a nightmare.

[0583] In some embodiments, the pulse is released for about a minute and repeats itself after a 4-minute interval between pulses. In another example, at least one scent is released for a duration of 10 to 60 seconds every 3.

[0584] In some embodiments, the pulsed release (e.g., intermittent release) is provided, until the end of the sleep stage, and / or until the detected physiological state stabilizes (e.g., improved and / or regulated).

[0585] In some embodiments, the scent release is provided continuously until the end of the sleep stage.

[0586] In some embodiments, the scent release (pulsed and / or continues) is provided any time the specific sleep and / or patient’s state is detected. In some embodiments, the patient is prompted to activate the system before every sleep.

[0587] It is noted that - on an ongoing basis - it is desirable for the stimulus provided to a patient to maintain a balance between creating enough stimulation but not creating habituation.

[0588] It is further noted that - in some examples - stimulus should be avoided while a patient is awake, as e.g. the noise associated with the stimulus might interfere with the patient’s attempt to go back to sleep. Thus, in some examples, system 100 (e.g. controller 104) can halt a stimulus in response to determining that the patient has awakened, and restore the stimulus after the patient has been detected as (or estimated to have fallen) back asleep.

[0589] In some examples, system 100 (e.g. controller 104) can be configured to perform particular protocols for patient treatment. By way of non limiting example: a) In some examples, system 100 (e.g. controller 104) can provide (e.g. via a stimulator such as scent diffuser 900) a first scent of a stimulus up to e.g. 5 minutes following detection or estimation of pending sleep onset state in the patient. In this manner, the scent can create a calming effect, thereby enabling the beginning of patient sleep. It is noted that system 100 (e.g. controller 104) can then terminate the diffusion, so that the noise of the diffusion does not disturb the patient falling asleep.

[0590] In some examples, the duration of this initial diffusion can be between 10 and 90 seconds (for example: 40 seconds). b) In some examples, system 100 (e.g. controller 104) can provide (e.g. via scent diffuser 900) a scent to the patient, responsive to detecting deep sleep (or upon an estimation of onset of deep sleep e.g. 20 to 60 minutes after beginning of pending sleep onset state in the patient). The duration of this diffusion can be between 10 and 90 seconds (for example: 40 seconds), or a different duration.

[0591] During deep sleep, system 100 (e.g. controller 104) can provide (e.g. via scent diffuser 900) one or more diffusions of the scent. The time between the diffusions (i.e. “interval”) can be a value (or series of values) in a first interval range - for example - an interval between 5 and 15 minutes. c) In some examples, subsequent to the diffusions during deep sleep, system 100 (e.g. controller 104) can identify a change in the patient’s sleep state from deep sleep to Rapid Eye movement (REM) sleep (or estimate that such a change has occurred). In response to the change of sleep state, system 100 (e.g. controller 104) can lengthen the scent diffusion interval, so as to prevent the patient from waking from REM sleep. For example, system 100 (e.g. controller 104) can diffuse in accordance with a second release interval which is 50% longer (or has an average duration that is 50% longer) than the first release interval. d) In some examples, the stimulus provided in deep sleep can include scents of three (or more) different families in succession. Such a stimulus can stimulate different parts of the brain, and can improve patient cognition as described above (also cf. James D., Howard et. al. “Odor quality coding and categorization in human posterior piriform cortex”). In some examples, the families are be selected from:

[0592] • Floral

[0593] • Fruity, non-citrus

[0594] • Citrus

[0595] • Woody

[0596] • Minty

[0597] • Sweet / Gourmand

[0598] • Spicy e) In some examples, system 100 (e.g. controller 104) can provide (e.g. via scent diffuser 900) a scent (e.g. a non-trigeminal scent), responsive to detecting REM sleep (or upon an estimation of onset of REM sleep). Such a stimulus can improve the mental state of patient and / or reduce patient nightmares (for example, in patients with post-traumatic stress disorder or other mental conditions). f) In some examples, system 100 (e.g. controller 104) can provide (e.g. via scent diffuser 900) one or more scents, responsive to detecting elevated heart rate or shortened the patient (or upon an estimating onset of elevated heart rate based on time-of-day and previous patient measurement). System 100 (e.g. controller 104) can continue to provide the scent (e.g. in release intervals of between 5 and 15 minutes) e.g. until the patient’s heart rate is identified non-elevated or BBI is non- shortened.

[0599] In some such examples, the one or more scents can include one or more of: linalool, nerolidol, bornyl acetate, bisabolol, myrcene, terpinen-4-ol, linalyl acetate, perillyl alcohol, camphor, beta caryophyllene, and / or alpha-pinene. g) In some examples, system 100 (e.g. controller 104) can provide (e.g. via scent diffuser 900) one or more scents, responsive to detecting deep sleep (or upon an estimating onset of deep sleep). System 100 (e.g. controller 104) can continue to provide the scent (e.g. in release intervals of between 5 and 15 minutes) in order to lengthen and / or deepen the patient’s deep sleep.

[0600] In some such examples, the one or more scents can include one or more of: linalool, nerolidol, bornyl acetate, bisabolol, myrcene, terpinen-4-ol, linalyl acetate, perillyl alcohol, camphor, beta caryophyllene, and / or alpha-pinene.

[0601] It is noted in this context that pending sleep onset refers to a period wherein the patient is attempting to fall asleep (indicated e.g. by closed eyes, dark room etc.) but is not yet asleep.

[0602] System 100 (e.g. controller 104) can be configured to end the stimulation at a certain time or in response to a certain event, so as to avoid waking the patient. In some examples, system 100 (e.g. controller 104) is configured to end the stimulation after e.g. 5.5 hours of sleep. In some other examples, system 100 (e.g. controller 104) is configured to end the stimulation a certain amount of time in advance of an alarm clock setting (e.g. on a phone associated with system 100).

[0603] It is noted that system 100 (e.g. controller 104) can utilize various methods to identify a patient’s sleep stage. Identified sleep states can include, for example: wakefulness, pending sleep onset, abnormal / elevated heart rate, disturbed sleep (e.g. nightmare), shortened BBI, rapid-eye movement (REM) sleep, and / or deep sleep. Shortened BBI and abnormal / elevated heart rate are regarded as sleep states, as - for example - these states can be inferred from historical patient data (as for other sleep states)

[0604] In some examples, system 100 (e.g. controller 104) utilizes a method which operates upon data obtained from a patient monitor. These data can include patient physiological parameters, e.g. e.g.: heart rate respiration rate accelerometer motion measurement, beat-to-beat-interval (BBI).

[0605] These data can also include environmental parameters, e.g.: light level time-of-day noise level distance of a patient’s phone from system 100, as detected e.g. using bluetooth or similar signals

[0606] In some examples, system 100 (e.g. controller 104) utilizes one or more physiological and / or environmental parameters - in conjunction with a trained machine learning model (e.g. a transformer, long-short term memory(LSTM), or tree-based model) - to identify the patient’s sleep stage. In some other examples, system 100 (e.g. controller 104) utilizes one or more physiological and / or environmental parameters - in conjunction with a different method - to identify the patient’s sleep stage.

[0607] In some examples utilizing a trained machine learning model, the model can be trained using a number of training samples, where each sample includes one or more physiological and / or environmental parameters of a real or simulated human subject, as well as a ground truth sleep state of the human subject. In some such examples, the ground truth of the sample is derivative of, at least, performing polysomnography performed on the human subject.

[0608] In some examples, system 100 (e.g. controller 104) identifies the sleep state of the patient based on previous tracking of sleep states of the patient. In some examples, system 100 (e.g. controller 104) identifies the sleep state of the patient based on given typical sleep state transitions of human subjects.

[0609] In some examples, system 100 (e.g. controller 104) utilizes personalized scents in a stimulus. To personalize scents, system 100 (e.g. controller 104) can e.g. expose a patient to one of some number of families (e.g. 3 families) for a duration of time (e.g. 3 to 7 days) and analyzing which scent family is the most effective. In some such examples, system 100 (e.g. controller 104) can employ a real-time personalization machine learning model to determine scent is the most effective at a particular time (i.e. when certain physiological and / or environment parameters are received), or for a patient with particular characteristics.

[0610] In some examples, system 100 (e.g. controller 104) utilizes a real-time identification model for detecting habituation of a patient to particular scents. In some such examples, system 100 (e.g. controller 104) successively monitors a patient’s reactivity to a scent e.g. the detected physiological parameters (heart rate, heart rate variability, movement, respiration rate etc.). System 100 (e.g. controller 104) can then accordingly select a particular scent or scents.

[0611] General

[0612] It is expected that during the life of a patent maturing from this application many relevant olfactory stimulation and scent will be developed; the term scent intended to include all such new technologies a priori.

[0613] As used herein with reference to quantity or value, the term “about” means “within ±10% of’.

[0614] The terms “comprises”, “comprising”, “includes”, “including”, “having” and their conjugates mean: “including but not limited to”.

[0615] The term “consisting of’ means: “including and limited to”.

[0616] The term “consisting essentially of’ means that the composition, method or structure may include additional ingredients, steps and / or parts, but only if the additional ingredients, steps and / or parts do not materially alter the basic and novel characteristics of the claimed composition, method or structure.

[0617] As used herein, the singular form “a”, “an” and “the” include plural references unless the context clearly dictates otherwise. For example, the term “a compound” or “at least one compound” may include a plurality of compounds, including mixtures thereof.

[0618] The words “example” and “exemplary” are used herein to mean “serving as an example, instance or illustration”. Any embodiment described as an “example” or “exemplary” is not necessarily to be construed as preferred or advantageous over other embodiments and / or to exclude the incorporation of features from other embodiments.

[0619] The word “optionally” is used herein to mean “is provided in some embodiments and not provided in other embodiments”. Any particular embodiment of the present disclosure may include a plurality of “optional” features except insofar as such features conflict.

[0620] As used herein the term “method” refers to manners, means, techniques and procedures for accomplishing a given task including, but not limited to, those manners, means, techniques and procedures either known to, or readily developed from known manners, means, techniques and procedures by practitioners of the chemical, pharmacological, biological, biochemical and medical arts.

[0621] As used herein, the term “treating” includes abrogating, substantially inhibiting, slowing or reversing the progression of a condition, substantially ameliorating clinical or aesthetical symptoms of a condition or substantially preventing the appearance of clinical or aesthetical symptoms of a condition.

[0622] Throughout this application, embodiments may be presented with reference to a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of descriptions of the present disclosure. Accordingly, the description of a range should be considered to have specifically disclosed all the possible subranges as well as individual numerical values within that range. For example, description of a range such as “from 1 to 6” should be considered to have specifically disclosed subranges such as “from 1 to 3”, “from 1 to 4”, “from 1 to 5”, “from 2 to 4”, “from 2 to 6”, “from 3 to 6”, etc.', as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

[0623] Whenever a numerical range is indicated herein (for example “10-15”, “10 to 15”, or any pair of numbers linked by these another such range indication), it is meant to include any number (fractional or integral) within the indicated range limits, including the range limits, unless the context clearly dictates otherwise. The phrases “range / ranging / ranges between” a first indicate number and a second indicate number and “range / ranging / ranges from” a first indicate number “to”, “up to”, “until” or “through” (or another such range-indicating term) a second indicate number are used herein interchangeably and are meant to include the first and second indicated numbers and all the fractional and integral numbers therebetween.

[0624] Although descriptions of the present disclosure are provided in conjunction with specific embodiments, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims.

[0625] It is appreciated that certain features which are, for clarity, described in the present disclosure in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination or as suitable in any other described embodiment of the present disclosure. Certain features described in the context of various embodiments are not to be considered essential features of those embodiments, unless the embodiment is inoperative without those elements.

[0626] It is the intent of the applicant(s) that all publications, patents and patent applications referred to in this specification are to be incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually noted when referenced that it is to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present disclosure. To the extent that section headings are used, they should not be construed as necessarily limiting. In addition, any priority document(s) of this application is / are hereby incorporated herein by reference in its / their entirety.

Claims

CLAIMS1. A system of providing therapeutic stimulation to a patient during sleep, the system comprising: a) a stimulator, configured to release one or more scents; b) a patient monitor, comprising at least one sensor configured to measure at least one physiological parameter or environmental parameter of the patient; and c) a controller, configured to:(i) identify a sleep state of the patient, and(ii) responsive to, at least, the identified sleep state, provide a stimulus to the patient, the stimulus being based on, at least, an ordering of one or more scents, and a respective intensity and respective release pattern of each of one or more scents.

2. The system of claim 1, wherein the controller is configured to identify the sleep state of the patient based on, at least, physiological parameters and / or environmental parameters of the patient.

3. The system of claim 2, wherein the physiological parameters comprise: heart rate, respiration rate, accelerometer motion measurement, and / or beat-to-beat- interval (BBI).

4. The system of claim 2, wherein the environmental parameters comprise: light level, time-of-day, distance of a patient device, and / or noise level.

5. The system of claim 2, wherein the controller is further configured to identify the sleep state of the patient based on, at least, a machine learning model that was trained utilizing a plurality of training samples, wherein each training sample of the plurality comprises: a. data indicative of a heart rate, respiration rate, accelerometer motion measurement, noise level, time-of-day, distance of patient-held device, and / or beat-to-beat-interval (BBI) of a human subject; and b. a ground truth sleep state of the human subject.

6. The system of claim 5, wherein the ground truth sleep state is derivative of, at least, polysomnography performed on the human subject.

7. The system of claim 1, wherein the controller is configured to identify the sleep state of the patient based on, at least, previous tracking of sleep states of the patient.

8. The system of claim 1, wherein the controller is configured to identify the sleep state of the patient based on, at least, given typical sleep state transitions of human subjects.

9. The system of claim 1, wherein the controller is configured to identify one or more sleep states selected from: wakefulness, pending sleep onset, abnormal / elevated heart rate, shortened BBI, rapid-eye movement (REM) sleep, and / or deep sleep.

10. The system of claim 1, wherein the controller is further configured to: responsive to the identified sleep state being pending sleep onset state:providing the stimulus to the patient, the stimulus comprising a first release of a scent, the release of the stimulus being within five minutes of the identification of pending sleep onset state, thereby providing a calming effect to enable the patient’s sleeping.

11. The system of claim 1, wherein the controller is further configured to: c) responsive to the identified sleep state being deep sleep: provide two or more releases of the stimulus, at a first release interval, and d) responsive to subsequently identifying a sleep stage of the patient as being REM sleep: provide two or more releases of the stimulus, at a second release interval that is at least 50% longer than the first release interval, thereby enabling the patient to remain in sleep.

12. The system of claim 11, wherein the stimulus comprises scents of three different families, the families being selected from a list consisting of: floral, fruity noncitrus, citrus, woody, minty, sweet, and spicy, thereby stimulating a plurality of parts of the patent’s brain, and improving cognition in the patient.

13. The system of claim 1, wherein the controller is further configured to:responsive to the identified sleep state being REM sleep: provide the stimulus; thereby improving patient mental state and / or reducing patient nightmares.

14. The system of claim 13, wherein the controller is further configured to: provide the stimulus in two or more releases, at release intervals of between 5 and 15 minutes.

15. The system of claim 13, wherein the stimulus is non-trigeminal.

16. The system of claim 1, wherein the controller is further configured to: responsive to identifying a period of elevated heart rate of the patient: providing the stimulus to the patient until the patient’s heart rate is identified as non-elevated.

17. The system of claim 16, wherein the controller is further configured to: provide the stimulus in two or more releases, at release intervals of between 5 and 15 minutes.

18. The system of claim 16, wherein the stimulus comprises one or more of scents based on: linalool, nerolidol, bornyl acetate, bisabolol, myrcene, terpinen-4-ol, linalyl acetate, perillyl alcohol, camphor, beta caryophyllene, and / or alphapinene, thereby creating a relaxing effect in the patient.

19. The system of claim 1, wherein the controller is further configured to:responsive to identifying a period of shortened BBI of the patient: providing the stimulus to the patient until the patient’s BBI is identified as non-shortened.

20. The system of claim 19, wherein the controller is further configured to: provide the stimulus in two or more releases, at release intervals of between 5 and 15 minutes.

21. The system of claim 19, wherein the stimulus comprises one or more of scents based on: linalool, nerolidol, bornyl acetate, bisabolol, myrcene, terpinen-4-ol, linalyl acetate, perillyl alcohol, camphor, beta caryophyllene, and alpha-pinene, thereby creating a relaxing effect in the patient.

22. The system of claim 1, wherein the controller is further configured to: responsive to the identified sleep state being deep sleep: provide two or more releases of the stimulus, at intervals of between 5 and 15 minutes; thereby lengthening and / or deepening the patient’s deep sleep.

23. The system of claim 22, wherein the stimulus comprises one or more of scents based on: linalool, nerolidol, bornyl acetate, bisabolol, myrcene, terpinen-4-ol, linalyl acetate, perillyl alcohol, camphor, beta caryophyllene, and alpha-pinene, thereby creating a relaxing effect in the patient.

24. The system of claim 1 , wherein the one or more scents are selected based on a personalization model.

25. The system of claim 1, wherein the one or more scents are selected based on a habituation avoidance model.

26. A controller-based method of providing therapeutic stimulation to a patient during sleep, the method comprising: a) identifying a sleep state of the patient, and b) responsive to, at least, the identified sleep state, controlling a stimulator to provide a stimulus to the patient, the stimulus comprising one or more scents, and being based on, at least, an ordering of one or more scents, and a respective intensity and respective release pattern of each of one or more scents.

27. A computer program product comprising a computer readable non-transitory storage medium containing program instructions, which program instructions when read by a processor, cause the processing circuitry to perform a method of providing therapeutic stimulation to a patient during sleep, the method comprising: a) identifying a sleep state of the patient, and b) responsive to, at least, the identified sleep state, controlling a stimulator to provide a stimulus to the patient, the stimulus comprising one or more scents, and being based on, at least, an ordering of one or more scents, and a respective intensity and respective release pattern of each of one or more scents.