Chemosensory modulator system and method for the treatment of chemosensory dysfunction

Abstract

A system and method modify the neural pathways that determine how chemical vapors are perceived and interpreted by the brain. The perception of chemical stimuli is altered by modulating the activity in one or two primary chemosensory pathways: the olfactory and trigeminal systems. By adjusting the relative activity in these pathways, abnormal and unpleasant smell sensations are treated. The system can be used to treat certain parosmias (abnormal smell sensations) and other types of dysosmias by adjusting the ratio of neural activity in the olfactory and trigeminal pathways. For example, patients with impaired olfactory function (decreased olfactory input) often report that "everything smells bad or foul." By adjusting the relative activity in the trigeminal (unpleasant) vs olfactory (pleasant) pathways the unpleasant or foul odor sensation can be treated (e.g., by blocking signals from the trigeminal system or enhancing olfactory stimulation).

Description

[0001] CHEMOSENSORY MODULATOR SYSTEM AND METHOD FOR THE TREATMENT OF CHEMOSENSORY DYSFUNCTION

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003] This application claims the benefit of U.S. Provisional Patent App. No. 63 / 574,922, filed April 5, 2024, the complete contents of which are incorporated herein by reference.

[0004] FIELD OF THE INVENTION

[0005] The present invention generally relates to impaired chemosensory systems and, more particularly, to devices and methods for treatment of chemosensory dysfunction such as parosmia.

[0006] BACKGROUND

[0007] Chemicals are detected in the nose (intranasally) by two systems: (1) the olfactory receptors and (2) the trigeminal receptors. Both are capable of detecting chemical vapors and sending signals to the brain. Central perception of chemical vapors depend upon the relative influence and activity of these two input systems.

[0008] Any abnormal smell perception may be referred to as a dysosmia. This includes certain conditions such as parosmia (smelling something different than what it should be), phantosmia (smelling something that isn’t there), and cacosmia (smelling something foul / unpleasant). When an individual with cacosmia smells or sniffs something, the individual experiences an unpleasant sensation even when the stimulus is something healthy individuals would interpret as pleasant (e.g., various flowers, fresh foods, etc.). Cacosmia and other types of dysosmia may occur when the trigeminal input is greater than or overpowers the olfactory input. This may be the result of damage to the olfactory cells, for example. Trigeminal sensations are usually interpreted or perceived by the brain as unpleasant.

[0009] Devices to date intended to treat chemosensory disorders involving smell have focused on hyposmia (reduced sense of smell) and anosmia (lost sense of smell). For example, US9517342 describes a system for generating patterns of activity in the olfactory cortex which mimic the sense of smell in a subject. As another example, W02024200803A1 describes a system that stimulates the trigeminal system of a subject. The technology of W02024200803A1 is specifically designed to increase trigeminal neural activity which has the effect of increasing detection of sensory perceptions by the subject. A limitation of technologies like that which is described in W02024200803A1 is that they are not well suited for the treatment of chemosensory disorders which are not necessarily the result of inadequate neural activity, but rather the result of an imbalance in neural activity levels between the olfactory system and the trigeminal system. A need persists for devices and techniques for treating chemosensory disorders such as parosmia and other types of dysosmia.

[0010] SUMMARY

[0011] Some exemplary embodiments of this disclosure provide treatment of dysosmias such as parosmia (e.g., distorted sense of smell) and cacosmia (e.g., unpleasant smell sensations without odorant stimulus). Relatedly, the terms “smell” and “smell sensations” are used in this disclosure to refer to a subject’s sensory experience attributable to a combination of the subject’s olfactory system and trigeminal system. “Olfaction” is used in this disclosure to refer to a subject’s sensory experience attributable specifically to the olfaction system (to the exclusion of the trigeminal system). “Chemesthesis” is used in this disclosure to refer to a subject’s sensory experience attributable specifically to the trigeminal system (to the exclusion of the olfactory system).

[0012] Some exemplary embodiments generally relates to the detection and processing of chemical signals by the olfactory and trigeminal systems and how the relative activity in the two systems determines the pleasant and unpleasant nature of the perception of chemicals.

[0013] Exemplary embodiments include methods and apparatuses for treating chemosensory disorders and modulating chemosensory perceptions. Exemplary embodiments include methods to treat parosmia(s). Exemplary embodiments include methods to treat cacosmia. Exemplary embodiments include methods for altering the hedonic (pleasantness, unpleasantness) nature and perception of chemical vapors. Exemplary embodiments may be used with human subjects, non-human subjects (such as but not limited to swine, monkeys, dogs, turkeys, chickens, bovine, horses, etc.), and / or other animal subjects.

[0014] Chemosensory perception, the brain’s interpretation and processing of chemicals in the vapor phase, depends on two systems, the olfactory and trigeminal. By modulating the relative inputs from these two systems, exemplary embodiments make it possible to shift a subject’s perception toward a more pleasant or unpleasant experience.

[0015] Some exemplary methods comprise blocking neural activity in trigeminal chemosensory pathways. Some exemplary methods comprise changing the neural activity in olfactory pathways. What is unique about the chemosensory modulation approach is that by altering the inputs from two chemosensory systems exemplary embodiments are able to change the hedonic (pleasant vs unpleasant) quality of smell sensations and give patients relief from chronic unpleasant sensations.

[0016] Some exemplary systems and devices provide means of manipulating the inputs and pathways from two sensory systems (olfactory and trigeminal) to generate desired perceptions in the brain including the hedonic (pleasant vs unpleasant) value of chemical stimuli (vapors or odorants).

[0017] An exemplary system comprises a neurostimulator and electrodes that alter the relative activity of signals in one or both the olfactory and trigeminal pathways.

[0018] An exemplary chemosensory modulator is a neuro-stimulation device that is programmed to alter the activity in one or more trigeminal pathways for the purpose of reducing or blocking unpleasant sensations caused by stimulation from chemical vapors. The chemosensory modulator may be programmed to alter the activity in one or more olfactory pathways in addition to one or more trigeminal pathways. A processor such as a microprocessor may provide instructions for delivering patterns of electrical pulses to neural electrodes for stimulating olfactory and trigeminal pathways. The microprocessor is programmed or programmable to stimulate or block activity independently in either the olfactory or trigeminal pathway to achieve the desired outcome, for example, blocking a trigeminal pathway to reduce the unpleasantness of a chemical.

[0019] In exemplary systems, the one or more electrodes positioned to affect a subject’s trigeminal system may include one or more transcutaneous electrical nerve stimulation (TENS) electrodes, one or more implanted electrodes, or a combination of TENS and implanted electrodes. In exemplary systems, the one or more electrodes positioned to affect a subject’s olfactory system may include one or more transcutaneous electrical nerve stimulation (TENS) electrodes, one or more implanted electrodes, or a combination of TENS and implanted electrodes.

[0020] One purpose of some exemplary embodiments is to treat parosmia, altered odor sensations that result from an impaired chemosensory olfactory input and relative chemosensory trigeminal input resulting in unpleasant or foul odor sensations. Decreasing or blocking the activity in the trigeminal pathway or increasing the relative activity in the olfactory pathway can have a positive effect on the hedonic (pleasantness) value of the chemosensory perception within the brain.

[0021] An exemplary application of some embodiments is treatment of patients with parosmia and chronic unpleasant smell sensations. Another exemplary application of some embodiments is modulation of aromas of foods and beverages to increase their acceptance (pleasantness).

[0022] Distinct from parosmia, anosmia may be treated according to some embodiments. Anosmia entails diminished or no sense of smell. According to embodiments tailored to addressing anosmia in particular, an exemplary device and method may generate perceptions a subject with anosmia would otherwise not experience, including trigeminal unpleasant warning sensations in toxic or dangerous environments.

[0023] According to an exemplary embodiment, a system includes a sensor module that detects and identifies chemicals entering the nasal cavity, creating a digital fingerprint of the stimulus. A microprocessor receives input from the sensor module and compares its digital fingerprint to known / programmed information stored in memory (odor matrix). An algorithm determines the hedonic value that represents the degree of pleasantness to unpleasantness. Based on the hedonic value, stimulation parameters are sent to the receive-stimulator unit that in turn sends electrical pulses to the stimulation electrodes. User input can alter the stimulation outputs to obtain the optimal desired perception.

[0024] BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 is a diagram of olfactory and trigeminal pathways typical of human subjects. Figure 2 is a diagram illustrating the modulation of olfactory pathways (A) and trigeminal pathways (B) by an exemplary chcmoscnsory modulator, resulting in shifts in the A / B activity ratio and changes in pleasant and unpleasant sensory perceptions.

[0026] Figure 3 is a block diagram of components of another exemplary chemosensory modulator system.

[0027] Figure 4 is a flow diagram of an exemplary process to treat parosmia (e.g., unpleasant or foul odor sensations).

[0028] Figure 5 is illustration of trigeminal pathways in a human head and non-limiting exemplary placements of electrodes for adjusting activity of the trigeminal system.

[0029] DETAILED DESCRIPTION

[0030] Figure 1 is a diagram of olfactory and trigeminal pathways typical of subjects such as but not limited to human subjects. Chemicals in the vapor phase (gases) are detected in the nose and upper airway by specialized receptors. The olfactory receptors 111 in the nasal cavity 100 detect a wide variety of chemicals associated with the perception of odors or smells. These are often pleasant odors like the fragrances from foods, perfumes, and loved ones. The olfactory receptors 111 send their signals to the olfactory brain centers 116 via olfactory pathways such as the olfactory nerves 101, olfactory bulb 112, and olfactory tract 102.

[0031] Many of the chemesthetic sensations of the human body are mediated by the trigeminal nerves, large nerves which are also responsible for certain motor functions and sensation in the face. Another class of chemical sensors 113 located in the nose (nasal cavity 100) and upper airway are associated with specialized receptor cells connected to the trigeminal system and pathways (trigeminal nerve branches, trigeminal nucleus). The trigeminal receptors 113 have a high sensitivity to chemicals such as alcohols (cooling), capsaicin (hot and spicy), and ammonia (burning and stinging). They are also activated by many chemical odorants typically thought to be olfactory (e.g., coffee, perfumes, air fresheners). The anterior ethmoid nerve 103 and posterior ethmoid nerve 104 innervate the nasal cavity 100 (chemethesis). The external nasal nerve (ant ethmoid n.) 110 is also present. Within the trigeminal system, the ophthalmic nerve (VI) 105, maxillary nerve (V2) 106, mandibular nerve (V3) 107 converge at the trigeminal ganglion 114. The trigeminal nerve (V=V1+V2+V3) 108 connects the trigeminal ganglion 114 with chcmothcsis brain centers 115. The supraorbital nerve 109 connects with the ophthalmic nerve (VI) 105.

[0032] As exemplified by the depiction of the trigeminal system in Figure 1, a sensory system involves nerve bundles and branches. The branching is why in this disclosure the trigeminal system may be referred to as entailing trigeminal “pathways” in the plural. Depending on electrode placement, electrical pulses delivered by exemplary systems may directly affect the electrical properties of one or more such pathways which collectively constitute the trigeminal system. Likewise, though not as apparent from the simplified rendering of Figure 1, the olfactory system also involves nerve bundles and branches. The branching is why in this disclosure the olfactory system may be referred to as entailing olfactory “pathways” in the plural. Depending on electrode placement, electrical pulses delivered by exemplary systems may directly affect the electrical properties of one or more such pathways which collectively constitute the olfactory system.

[0033] In many cases, when chemicals activate receptors in the nose, both the olfactory and trigeminal pathways are activated. The brain receives input from both systems and creates an impression or perception of the stimulus. In general, olfactory system inputs are mostly associated with pleasant odor sensations while the trigeminal system input often contributes to an unpleasant or bad sensation. The relative input between these two systems determines the perception outcomes (pleasant or unpleasant) in the brain.

[0034] In cases of individuals who have impaired olfactory system function, the experience they report when confronted with odors is often an unpleasant or a foul smelling sensation, even when the external stimulus is something healthy subjects would register as pleasant. In subjects with parosmia, the sensation can range from annoying to repulsive. Moreover, the unpleasant sensation is persistent in some parosmia-afflicted subjects, continuing regardless of whether any particular external stimulus is present or absent. If this condition is persistent, patients seek help, and often there is no remedy. For many parosmia-afflicted subjects, this condition is likely due to an olfactory and trigeminal input imbalance in which the trigeminal system is dominant, and smell sensations are mostly unpleasant regardless of external stimuli.

[0035] Figure 2 is a diagram illustrating the modulation of (A) olfactory pathways and / or (B) trigeminal pathways by an exemplary chemosensory modulator system 200 for treatment of chemosensory disorders such as parosmia, the modulation resulting in shifts in the A / B activity ratio and changes in pleasant and unpleasant sensory perceptions.

[0036] The system 200 includes a chemosensory modulator 201. The chemosensory modulator 201 is a neuro stimulation device that functions to adjust the balance between the flow of olfactory and trigeminal pathway stimulation into the brain. The chemosensory modulator 201 may be interchangeably referred to as a chemosensory neuromodulator. Chemicals that activate the trigeminal pathways often result in unpleasant or foul odor sensations. By altering the activity in either the olfactory pathways (e.g., causing increased activity) or the trigeminal pathways (e.g., causing decreased activity) it is possible to change the perception in higher centers in the brain to shift subject perception towards more pleasant smell sensations.

[0037] As depicted in the right hand side of Figure 2, “chemical sensing”, “smell”, “smell sensations”, “smell perceptions” are terms used in this disclosure to refer to a subject’s sensory experience affected by both olfaction (from the olfactory system) and chemesthesis (from the trigeminal system). “Hedonic smell sensations” is used in this disclosure to refer to smell sensations which are characterizable on a scale of pleasantness vs unpleasantness. Generally speaking, different parts of the brain are responsible for processing signals from the olfactory pathways A versus processing signals from trigeminal pathways B. However, activity in these multiple brain centers result in a conscious experience of a human subject that is a more singular phenomenon which this disclosure refers to as “smell” 206. Moreover, it should be appreciated that a stimulus 205 is not strictly necessary for a subject to experience a smell 206. Particular in the case of certain chemosensory disorders, untreated subjects can report experiencing chronic unpleasant / foul smells which are not mitigated by elimination or introduction of any particular stimuli 205.

[0038] The chemosensory modulator 201 generates patterns of electrical current pulses that can activate or block activity in neural pathways such as the olfactory and trigeminal nerves. Stimulation parameters (such as one or more of current, duration, and frequency) are programmed into the chemosensory modulator 201 to activate or block nerve conductions in A or B pathways.

[0039] By modulating two major chemosensory pathways, olfactory and trigeminal, the modulator 201 is able to change the hedonic perception (e.g., pleasantness — unpleasantness) of chemical vapor stimuli 205. By adjusting A / B ratio, the system can modulate perceptions, for example, adjusting relative pleasantness / unpleasantness.

[0040] The exemplary chemosensory modulator 201 includes a neurostimulator 202 configured to generate electrical pulses with stimulation parameters for adjusting (e.g., modulating, regulating, shifting) relative neural activity between olfactory and trigeminal systems of a subject. The chemosensory modulator system 200 further includes at least one electrode 204 for delivering the electrical pulses to a trigeminal pathway B. The electrical pulses delivered to the trigeminal pathway B are configured to decrease activity in one or more trigeminal neural pathways affecting hedonic smell sensations. The act of decreasing neural activity and corresponding hedonic smell sensations may be interchangeably characterized as blocking, preventing, masking, or inhibiting.

[0041] For consistency of discussion, this disclosure frequently refers to an electrode like electrode 204 in the singular. However, it should be appreciated that in practice, the disclosed embodiments may use multiple electrodes, e.g., configured as an array. Accordingly, it should be understood that throughout this disclosure, “electrode” may be one or more electrodes, e.g., an array of electrodes, affecting one or more trigeminal pathways. Likewise, for consistency of discussion, this disclosure frequently refers to an electrode like electrode 203 in the singular. However, it should be appreciated that in practice, the disclosed embodiments may use multiple electrodes, e.g., configured as an array. Accordingly, it should be understood that throughout this disclosure, “electrode” may be one or more electrodes, e.g., an array of electrodes, affecting one or more olfactory pathways.

[0042] The precise pail of the trigeminal system where the at least one electrode 204 (which in some implementations is an array of multiple electrodes) delivers electrical pulses may or may not be the same part of the trigeminal system which has a decrease in neural activity. In general, the part (or parts) of the trigeminal system where activity is reduced may be “downstream” of electrode placement. For instance, in reference back to Figure 1, the electrode (or electrode array) 204 may be placed proximal to the ophthalmic (VI) branch 105 of the trigeminal system. The electrical pulses from electrode 204 may cause increased local neural activity in the nerve 105. However, the electrical pulse parameters are such that the local spike in electrical activity inhibits signal transmission (e.g., by preventing the recovery to resting potential of one or more nerve fibers which is necessary after an action potential before a subsequent action potential is possible). As another mechanism of desired reduction of neural activity in one or more trigeminal pathways downstream of electrode placement, the electrode 204 may be placed and the electrical pulses delivered may be configured to cause an increase in activity in large diameter fibers which are part of or become part of a nerve bundle which includes smaller trigeminal nerve fibers. By increasing activity in the larger diameter nerve fibers, the signals being carried by the smaller diameter trigeminal nerves of the same nerve bundle may be suppressed. This suppression may occur biologically at, for example, one or more ganglia or nuclei which fail to forward the signals of the smaller diameter trigeminal nerves owing to the heightened activity of the larger diameter nerves meeting at the same ganglia or nuclei. Accordingly, despite the electrode 204 causing increased neural activity in at least one nerve fiber, the end result is a reduction in the activity from at least one other nerve fiber reaching the chemesthesis brain center(s) 115. That is, reduced activity may be a reduction in activity associated with one or more particular nerves reaching a ganglion or nucleus, past a ganglion or nucleus, or in a particular region of the brain.

[0043] In exemplary configurations, system 200 involves transmission of electrical signals from the modulator 201 to the electrodes 203 and 204. One or more other signals pathways may be provided in some alternative configurations. For instance, some electrodes placed proximal to neural pathways may be configured to monitor activity in the olfactory and trigeminal systems, their passive signal readings being fed back to the modulator 201 to be used in determining the characteristics of the stimulatory electrical pulses that adjust / modulate relative activity in the two neural systems of the subject. As another feature which may be included in some configurations of system 200, a feedback subsystem may be included by which the modulator 201 measures its own outputs to ensure the actual electrical pulses being sent are consistent with the intended stimulation parameters and making adjustments to the outputs as necessary to minimize or eliminate errors such as drift.

[0044] Figure 3 is a block diagram of another exemplary chemosensory modulator 300, including some exemplary internal components, inputs, and outputs. The chemosensory modulator 300 comprises at least one processor such as a programmable microprocessor 301, a neural stimulator module 302, and leads 303 to electrodes for stimulating one or both A) chemosensory olfactory pathways such as the olfactory nerves or tract and B) the chemosensory trigeminal pathways such as the ophthalmic branch of the trigeminal nerve. By manipulating the ratio of A to B stimulation, the hedonic or pleasantness of smell sensations is adjusted. In this disclosure, “stimulating” refers to delivering current. Stimulating may have cither an excitatory or inhibitory effect depending on the stimulation parameters.

[0045] The modulator 300 further includes a memory unit 304 where specific treatment protocols and programs are storable. The processor 301 executes the program(s) stored in memory unit 304, issuing commands to the neural stimulator 302 including particular stimulation parameters for adjusting neural activity. The neural stimulator, using power from the power module 305, generates electrical pulses having the stipulated stimulation parameters. These electrical pulses carried by the leads 303 to the electrodes (not shown) placed to affect one or both of the trigeminal system and the olfactory system. The neural stimulator 302 may be configured to receive the commands from the processor 301 in a digital signal type and send out corresponding electrical pulses as an analog signal type deliverable to tissue by the electrodes.

[0046] The modulator 300 may be configured with an input buffer 306 for receiving data from one or more sensing modules 321. The input buffer may also be used to assign odor names to the sensor fingerprint patterns, or to enter hedonic values, and other programmed info that can be stored in memory 304.

[0047] Exemplary devices and systems may use values (e.g., hedonic values) to characterize user experiences and assist in replicating appropriate stimulation signals to achieve consistent user experiences with repeated use of the device / system. For instance, the device may be programmed to employ a rating system or scale (e.g., 1-10) where the value at one end of the scale (e.g., 1) represents “extremely pleasant” / “most pleasant” and the value at the opposite end of the scale (e.g., 10) represents “extremely unpleasant' ’ / “most unpleasant” with intermediate values representing scaled variations between these extremes. The middle value of the scale (e.g., 5) may represent “neither pleasant nor unpleasant”, for example.

[0048] An exemplary sensing module 321 is configured to detect at least one chemical vapor. In general, it is desirable for sensing module 321 to be configured to detect a plurality of different chemicals. Suitable sensors and sensor arrays known in the ail or developed in the future may be employed for this purpose. Some non-limiting examples are the sensors disclosed in US9517342 and PCT / US2024 / 052789, both of which are incorporated herein by reference to the extent they do not conflict with the expressly given details of this disclosure. The microprocessor 301 is configured to use sensor information from sensor module 321 to adjust instructions supplied to the neural stimulator 302 and thereby the electrical pulses generated by the neural stimulator 302 to generate normal smell perceptions, which is to say, smell perceptions more in keeping with healthy human experience which are less unpleasant than the status quo for a chemosensory disorder afflicted subject in the absence of the modulator 300. The memory unit 304 may store values of stimulation parameters for one or both the olfactory system A and trigeminal system B, the values varying for different chemical vapors detectable with sensing module 321. The stored values may vary not only for different chemical vapors but also for different subjects. That is to say, the values stored for stimulation parameters may be tailored to the needs of different subjects, each equipped with his or her own modulator 300 storing subject-specific stimulation parameter values. When a particular chemical vapor is detected by sensor module 321, corresponding data is conveyed to modulator 300 where it is used by processor 301 to select appropriate stimulation parameter values from memory unit 304 and command neural stimulator 302 to generate one or more electrical pulses in accordance with the selected stimulation parameter values. In cases of parosmia where a pleasant odor such as the aroma of a cup of coffee triggers an unpleasant sensation, the modulator can be alerted by a chemical sensor that activates the modulator. Once the program settings are adjusted and unwanted trigeminal input is suppressed and / or the olfactory input is enhanced, the subject can enjoy his or her cup of coffee.

[0049] The modulator 300 may be further configured with an input buffer 307 for receiving data from one or more user interfaces 322. Exemplary user interfaces include but are not limited to one or more of display devices, personal computers, mobile electronic devices, smartphones, tablets, microphones, and touch interfaces. The processor and memory may be configured with Bluetooth and / or Wi-Fi capability to communicate with external devices and interfaces without a hardwired connection. As a non-limiting example, esp32 chips may be employed in some embodiments for supplying such functionality. These or alternative chips may be configured according to the methods of this disclosure. The user input interface provides a way of programming and updating the processor 301 and / or memory unit 304 as well as real time adjustments of the A / B stimulation ratio. User input may allow for the user to adjust values saved in memory unit 304 based on the actual real time perceptions of the user. In addition to or as an alternative to receiving user input via one or mor user interfaces, exemplary processors of some embodiments may be configured to output signals and information to a user. Figure 4 is a flow diagram of an exemplary process to treat parosmia (unpleasant or foul odor sensations) using a chcmoscnsory modulator system such as that depicted in Figure 3. The remote sensor detects a chemical (or chemicals) in the environment and activates the chemosensory modulator. Prior to the chemosensory modulator activation, the subject may experience unpleasant or foul odor sensation. However, the activated modulator adjusts the A / B modulation ratio based on the detected chemical. Manipulating the balance of inputs to the brain (olfactory versus trigeminal) can alter the subject’s perception. By blocking certain trigeminal sensations or masking or inhibiting them, the brain is less likely to perceive unpleasant sensations. The concept of treating cacosmia requires manipulation of these sensory inputs and brain center modulations to alter the unpleasant sensations. The result is that the foul odor sensation is resolved, allowing the user of the modulator a neutral or pleasant smell sensation.

[0050] Figure 5 is an illustration of a human head including the arrangement of branches of the ophthalmic nerve VI, maxillary nerve V2, and mandibular nerve V3. Nerves VI, V2, and V3 converge together at the trigeminal ganglion 114. Signals continue to the brain (not illustrated) via the trigeminal nerve V. Dotted lines serve to delineate generally accepted areas of sensory innervation from VI, V2, and V3, respectively. Area 501 in innervated by ophthalmic nerve VI. Area 502 is innervated by maxillary nerve 502. Area 503 is innervated by mandibular nerve V3.

[0051] Some exemplary embodiments include non-invasive stimulation methods and associated hardware. In particular, some exemplary embodiments employ one or more electrodes configured as transcutaneous electrical nerve stimulation (TENS) electrodes. In Figure 5 solid black dots are used to represent TENS electrodes. TENS stimulator electrodes may be placed, for example, on the bridge of the nose as indicated by electrode(s) 513 and / or on the forehead (externally) as exemplified by electrode(s) 514 to modify the trigeminal pathway activity. Other placements of TENS electrodes besides the exemplary instances depicted by Figure 5 may be used in various embodiments. As yet another example, one or more TENS electrodes may be applied intranasally, e.g., positioned at an upper region of the nasal cavity. Such arrangements may be characterized as head- mounted TENS devices. The ophthalmic branch VI innervates upper regions of the nasal cavity. The position of TENS electrode 511 facilitates delivery of electrical pulses to VI which have the effect of reducing activity in the trigeminal system with corresponding reduction in unpleasant smell sensations. Electrodes may be placed proximal to olfactory receptor cells and / or trigeminal nerve endings, for example. TENS stimulation embodiments may be configured to activate large afferent fibers in the peripheral nervous system that send input to the central nervous system. This activity in turn activates descending inhibitory systems that reduce activity in trigeminal brain centers.

[0052] TENS embodiments according to this disclosure may use particular stimulation parameters to selectively activate large diameter Type A nerve fibers with one or more electrodes 511 positioned in or proximal to the nasal cavity. Chemical receptors in the nasal cavity transmit their information by small diameter fibers C fibers. TENS stimulation of ophthalmic nerve (VI) may reduce unpleasant chemosensory sensations originating in the nasal cavity since they share the same branch of the trigeminal nerve. Selective stimulation of large diameter fibers in mixed nerves (e.g., trigeminal nerves) inhibits the central effects of small diameter fibers (including chemoreceptors) that typically mediate pain or unpleasant sensations.

[0053] In the alternative to non-invasive embodiments, some exemplary embodiments involve a chemosensory implant system and devices. In Figure 5 black circles with white centers are used to represent implanted electrodes. As an exemplary non-limiting example, Figure 5 depicts an implanted electrode or electrode array 512 for stimulating the ophthalmic nerve VI. As further exemplary non-limiting examples, Figure 5 depicts implanted electrode or electrode array 515 for changing activity along the V2 nerve and implanted electrode or electrode array 516 for changing activity along the V3 nerve. As yet another non-limiting illustrative example, Figure 5 shows an implanted electrode 511 positioned at an upper region of the nasal cavity. Implanted devices offer the advantage of placing electrodes at positions of the trigeminal and / or olfactory systems which cannot be significantly influenced by electrical signals delivered only at the body surface (as is necessary in the case of a TENS system). One or more electrodes 512, 515, and / or 516 may be a strategically placed intracranial stimulating electrode or electrode array.

[0054] Be an embodiment non-invasive (e.g., employing one or more TENS electrodes 511) or invasive (e.g., employing one or more implanted electrodes 512), the overall system configuration may be consistent with the above descriptions and illustrations such as those provided with Figures 2 and 3. For example, an exemplary system may comprise at least one processor programmed to modulate the activation of central olfactory and / or trigeminal regions in the brain by way of electrodes 511 and / or 512. Some exemplary embodiments may employ a combination of implanted and TENS electrodes. In either case, the electrodes are strategically placed to influence olfactory pathways and / or trigeminal pathways based on electrical pulses supplied by a neural stimulator. The neural stimulator in turn bases its signals on commands from the processor that determine relative stimulation of the target regions.

[0055] Some embodiments of the present invention may be a system, a device, a method, and / or a computer program product. A system, device, or computer program product may include a computer readable storage medium (or media) having computer readable program instructions thereon for causing a processor to carry out aspects of the present invention, e.g., processes or parts of processes or a combination of processes described herein.

[0056] The computer readable storage medium can be a tangible device that can retain and store instructions for use by an instruction execution device. The computer readable storage medium may be, for example, but is not limited to, an electronic storage device, a magnetic storage device, an optical storage device, an electromagnetic storage device, a semiconductor storage device, or any suitable combination of the foregoing. A non-exhaustive list of more specific examples of the computer readable storage medium includes the following: 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), a static random access memory (SRAM), a portable compact disc read-only memory (CD-ROM), a digital versatile disk (DVD), a memory stick, a floppy disk, a mechanically encoded device such as punch-cards or raised structures in a groove having instructions recorded thereon, and any suitable combination of the foregoing. A computer readable storage medium, as used herein, is not to be construed as being transitory signals per se, such as radio waves or other freely propagating electromagnetic waves, electromagnetic waves propagating through a waveguide or other transmission media (e.g., light pulses passing through a fiber-optic cable), or electrical signals transmitted through a wire.

[0057] Processes described herein, or steps thereof, may be embodied in computer readable program instructions which may be paired with or downloaded to respective computing / processing devices from a computer readable storage medium or to an external computer or external storage device via a network, for example, the Internet, a local area network, a wide area network and / or a wireless network. The network may comprise copper transmission cables, optical transmission fibers, wireless transmission, routers, firewalls, switches, gateway computers and / or edge servers. A network adapter card or network interface in each computing / processing device receives computer readable program instructions from the network and forwards the computer readable program instractions for storage in a computer readable storage medium within the respective computing / proccssing device.

[0058] Computer readable program instructions for carrying out operations of the present invention may be assembler instructions, instraction-set-architecture (ISA) instructions, machine instructions, machine dependent instructions, microcode, firmware instructions, state-setting data, or either source code or object code written in any combination of one or more programming languages, including an object oriented programming language such as Java, Python, Smalltalk, C++ or the like, and conventional procedural programming languages, such as the "C" programming language or similar programming languages. The computer readable program instructions may execute entirely on the user's computer, partly on the user's computer, 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). In some embodiments, electronic circuitry including, for example, programmable logic circuitry, field-programmable gate arrays (FPGA), or programmable logic arrays (PLA) may execute the computer readable program instructions by utilizing state information of the computer readable program instructions to personalize the electronic circuitry, in order to perform aspects of the present invention.

[0059] Aspects of the present invention are described herein with reference to flowchart illustrations and / or block diagrams of methods, apparatus (systems), and computer program products according to embodiments of the invention. 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 readable program instructions and in various combinations.

[0060] These computer readable program instructions may be provided to one or more processors of one or more general purpose computers, special purpose computers, or other programmable data processing apparatuses to produce a machine or system, such that the instructions, which execute via the processor(s) 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. These computer readable program instructions may also be stored in a computer readable storage medium that can direct a computer, a programmable data processing apparatus, and / or other devices to function in a particular manner, such that the computer readable storage medium having instructions stored therein comprises an article of manufacture including instructions which implement aspects of the function / act specified in the flowchart and / or block diagram block or blocks.

[0061] The computer readable program instructions may also be loaded onto a computer, other programmable data processing apparatus, or other device to cause a series of operational steps to be performed on the computer, other programmable apparatus or other device to produce a computer implemented process, such that the instructions which execute on the computer, other programmable apparatus, or other device implement the functions / acts specified in the flowchart and / or block diagram block or blocks.

[0062] The flowchart and block diagrams in the Figures illustrate the architecture, functionality, and operation of possible implementations of systems, methods, and computer program products according to various embodiments of the present invention. In this regard, each block in the flowchart or block diagrams may represent a module, segment, or portion of instructions, which comprises one or more executable instructions for implementing the specified logical function(s). In some alternative implementations, the functions noted in the block may occur out of the order noted in the figures. For example, two blocks shown in succession may, in fact, be executed substantially concurrently, or the blocks may sometimes be executed in the reverse order, depending upon the functionality involved. It will also be noted that each block of the block diagrams and / or flowchart illustration, and combinations of blocks in the block diagrams and / or flowchart illustration, can be implemented by special purpose hardware-based systems that perform the specified functions or acts or carry out combinations of special purpose hardware and computer instructions.

[0063] Where a range of values is provided in this disclosure, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range, is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges and are also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits arc also included in the invention.

[0064] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, representative illustrative methods and materials are described.

[0065] It is noted that, as used herein and in the appended claims, the singular’ forms “a”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. It is further noted that the claims may be drafted to exclude any optional element. As such, this statement is intended to serve as antecedent basis for use of such exclusive terminology as “solely,” “only” and the like in connection with the recitation of claim elements, or use of a “negative” limitation.

[0066] As will be apparent to those of skill in the ail upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present invention. Any recited method can be carried out in the order of steps recited or in any other order which is logically possible. Alternative methods may combine different elements of specific detailed methods described above and in the figures.

[0067] While exemplary embodiments of the present invention have been disclosed herein, one skilled in the ail will recognize that various changes and modifications may be made without departing from the scope of the invention as defined by the appended claims.

Claims

CLAIMSWhat is claimed is:

1. A chemosensory modulator system for treatment of chemosensory disorders, comprising a neurostimulator configured to generate electrical pulses with stimulation parameters for adjusting relative neural activity between olfactory and trigeminal systems of a subject; and at least one first electrode for delivering the electrical pulses to a trigeminal pathway, wherein the electrical pulses are configured to decrease activity in one or more trigeminal neural pathways affecting hedonic smell sensations.

2. The chemosensory modulator system of claim 1, further comprising at least one second electrode for delivering further electrical pulses to an olfactory pathway.

3. The chemosensory modulator system of claim 2, wherein the further electrical pulses are configured to increase activity in one or more olfactory neural pathways affecting the hedonic smell sensations.

4. The chemosensory modulator system of claim 1, further comprising a processor configured to generate the stimulation parameters for the electrical pulses.

5. The chemosensory modulator system of claim 1, wherein the at least one first electrode is implantable.

6. The chemosensory modulator system of claim 1, wherein the at least one first electrode is a transcutaneous electrical nerve stimulation (TENS) electrode.

7. A method of treating a subject for chemosensory disorders, comprising generating electrical pulses with stimulation parameters for adjusting relative neural activity between olfactory and trigeminal systems of the subject; anddecreasing activity in one or more trigeminal neural pathways affecting hedonic smell sensations by delivering the electrical pulses to a trigeminal pathway of the subject using at least one first electrode.

8. The method of claim 7, wherein the electrical pulses are delivered by transcutaneous electrical nerve stimulation (TENS).

9. The method of claim 7, wherein the at least one first electrode is an implanted electrode.

10. The method of claim 7, further comprising generating further electrical pulses and increasing activity in one or more olfactory neural pathways affecting the hedonic smell sensations by delivering the further electrical pulses to an olfactory pathway of the subject using at least one second electrode.

11. The method of claim 7, wherein the electrical pulses are delivered proximal to the ophthalmic (VI) branch of the trigeminal system.

12. A method of using a chemosensory modulator system, comprising generating electrical pulses with stimulation parameters for adjusting relative neural activity between olfactory and trigeminal systems of a subject; and sending the electrical pulses to at least one first electrode for delivery to a trigeminal pathway, wherein the electrical pulses are configured to be capable of causing decreased activity in one or more trigeminal neural pathways affecting hedonic smell sensations.

13. The method of claim 8, further comprising generating further electrical pulses and sending the further electrical pulses to at least one second electrode for delivery to an olfactory pathway, wherein the further electrical pulses are configured to be capable of causing increased activity in one or more olfactory neural pathways affecting the hedonic smell sensations.

14. The method of claim 12, wherein the at least one first electrode is a transcutaneous electrical nerve stimulation (TENS) electrode.

15. The method of claim 12, wherein the at least one first electrode is an implantable electrode.

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