Patent ID: 12207930

The figures are not necessarily to scale. Like numbers used in the figures refer to like components. However, it will be understood that the use of a number to refer to a component in a given figure is not intended to limit the component in another figure labeled with the same number.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

Embodiments of the disclosure are directed to systems and methods for recording neurostimulation data representative of patterns of stimulation of a specified region or regions of a subject's brain in response to exposing the subject to stimuli that stimulates one or more of a sensing organ or organs, vestibular system, and memory of the subject. The patterns of stimulation are stored in an electronic memory as pre-recorded neurostimulation data.

Embodiments of the disclosure are directed to systems and methods for delivering transcranial stimulation to a specified region or regions of a person's brain using pre-recorded neurostimulation data to recreate a sense of exposing one or more of a sensing organ or sensing organs, vestibular system, and memory of the subject to various stimuli.

Embodiments of the disclosure are directed to systems and methods for delivering transcranial stimulation to a specified region or regions of a person's brain using pre-recorded neurostimulation data to recreate a sense of exposing one or more of a sensing organ or sensing organs, vestibular system, and memory of the subject to various stimuli, and for transcranially sensing neural activity in the specified region or regions of the subject's brain caused by delivery of the transcranial stimulation and producing contemporaneous neurostimulation data developed using the transcranially sensed neural activity.

Past attempts to artificially stimulate the human sensory system and record the results of such artificial stimulation have seen limited success. For example, despite being one of the major five senses, the sense of olfaction has been difficult to artificially stimulate or record. Attempts at making an electronic nose, for example, have not yielded successful results. Developing a device that permits on-demand stimulation of one or more human senses (and in an advanced implementation, a device/method for recording and a closed-loop method for stimulating) is expected to have a range of applications in various industries such as perfumes and cosmetics, cognitive neuroscience, medical health, and as an extra dimension in entertainment. Embodiments of the disclosure address these and other market need by taking advantage of the high spatiotemporal resolution of neuromodulation possible through the skull using focused ultrasound, and the advantage of machine learning to permit customization of sensory organ (e.g., olfactory system) stimulation and recording for personalized sensory (e.g., fragrance) experiences.

FIG.1Aillustrates a system100aconfigured to record neurostimulation information acquired using transcranial sensing of a subject's brain in accordance with various embodiments. The system100aincludes a support structure102configured for placement on or about a subject's head. The support structure102is typically configured for placement on or about a human subject's head, but may alternatively be configured for an animal's head (e.g., a non-human primate). The system100aincludes an electronic recording apparatus103which includes a magnetic sensor arrangement104and an electronic memory110.

The magnetic sensor arrangement104is mounted to, or supported by, the support structure102. In various embodiments, the magnetic sensor arrangement104includes an array of magnetic sensors. In other embodiments, the magnetic sensor arrangement104can include a single magnetic sensor. The magnetic sensor arrangement104is configured for transcranial sensing of local magnetic fields emanating from a specific region of a subject's brain. The sensed local magnetic fields correspond to patterns of stimulation of the specified region of the subject's brain caused by stimulating one or more of the subject's sense organ or organs, vestibular system, and/or memory. It is understood that stimulation of a specified region of a subject's brain can refer to one or both of excitation and suppression of neural activity in the specified region of the subject's brain.

According to the embodiment shown inFIG.1A, the electronic memory110is physically distinct from, and not supported by or attached to, the support structure102. In the embodiment shown inFIG.1A, the electronic memory110is operatively coupled to the magnetic sensor arrangement104via a wired or wireless connection. The electronic memory110is configured to record neurostimulation data representative of patterns of stimulation of the specified region of the subject's brain sensed by the magnetic sensor arrangement104.

The electronic memory110is configured to store a multiplicity of patterns112of neurostimulation data associated with exposing one or more of the subject's senses to different stimuli and/or stimulating the subject's vestibular system and/or memory. The multiplicity of patterns112typically comprise spatiotemporal patterns of stimulation (e.g., patterns of excitation and/or suppression) recorded from the specified region of the subject's brain via the magnetic sensor arrangement104. The spatiotemporal patterns of stimulation (also referred to as spatiotemporal neural activity patterns) include both spatial features (e.g., relative distance) and temporal features (relative timing) of neural activity that together define a particular spatiotemporal neural activity pattern.

For example, the multiplicity of patterns112stored in the electronic memory110can comprise geometric and dynamic profiles that provide a spatiotemporal representation of neural activity patterns sensed by the magnetic sensor arrangement104. The various spatiotemporal patterns112stored in the memory110can be characterized in terms of a topographic mapping of an activity amplitude (geometric profile) and its associated temporal evolution (dynamic profile). These geometric and dynamic profiles can be used to define a spatiotemporal activity profile index to describe quantitatively each type of neural activity pattern112acquired by the magnetic sensor arrangement104and stored in the electronic memory110.

FIG.1Billustrates a system100bconfigured to record neurostimulation information acquired using transcranial sensing of a subject's brain in accordance with various embodiments. The system100bincludes a support structure102configured for placement on or about a subject's head. The system100bincludes an electronic recording apparatus103which includes a magnetic sensor arrangement104and an electronic memory110. The magnetic sensor arrangement104is mounted to, or supported by, the support structure102. The magnetic sensor arrangement104typically includes an array of magnetic sensors but can alternatively include a single magnetic sensor. The magnetic sensor arrangement104is configured for transcranial sensing of local magnetic fields emanating from a specific region of a subject's brain. As previously discussed, the sensed local magnetic fields correspond to patterns of stimulation of the specified region of the subject's brain caused by stimulating one or more of the subject's sense organ or organs, vestibular system, and/or memory.

According to the embodiment shown inFIG.1B, the electronic memory110is physically attached to, or supported by, the support structure102. The electronic memory110is operatively coupled to the magnetic sensor arrangement104typically via a wired connection, but may alternatively be coupled via a wireless connection. The electronic memory110is configured to record neurostimulation data representative of patterns of stimulation of the specified region of the subject's brain sensed by the magnetic sensor arrangement104. The electronic memory110is configured to store a multiplicity of patterns112of neurostimulation data associated with exposing one or more of the subject's senses to different stimuli and/or stimulating the subject's vestibular system and/or memory.

FIG.1Cillustrates a representative architecture of the electronic memory110shown inFIGS.1A and1Bin accordance with various embodiments. The electronic memory110includes a multiplicity of spatiotemporal patterns112shown as Pattern A through Pattern N. Each of the patterns112is associated with neural activity sensed from a specified region of a subject's brain via the magnetic sensor arrangement104in response to stimulating one or more of the subject's sense organ or organs, vestibular system, and/or memory to a particular stimulus or particular stimuli. Each of the patterns112includes stimulation parameters (e.g., a topographic mapping of neural activity amplitude) and a temporal pattern of stimulation (e.g., a temporal mapping of the neural activity).

FIG.2Aillustrates a magnetic sensor arrangement204ain accordance with various embodiments. The magnetic sensor arrangement204ashown inFIG.2Aincludes a single magnetic sensor205. In the embodiment shown inFIG.2B, the magnetic sensor arrangement204bincludes an array of magnetic sensors205. According to some embodiments, an individual magnetic sensor205can be implemented as a nitrogen-vacancy (NV) diamond magnetic sensor. In other embodiments, an individual magnetic sensor205can be implemented as an optically pumped magnetic (OPM) sensor. In further embodiments, an array of magnetic sensors205, such as that shown inFIG.2B, can include an array of NV diamond magnetic sensors, an array of OPM sensors, or a combination of NV diamond magnetic sensors and OPM sensors. Representative examples of an NV diamond magnetic sensor and an OPM sensor are described in more detail hereinbelow.

FIG.3Aillustrates a method of recording neurostimulation data generated by a magnetic sensor arrangement shown inFIGS.1A-2Band other figures in accordance with various embodiments. Although the method shown inFIG.3Acan be implemented using a single magnetic sensor, the following discussion assumes that an array of magnetic sensors are utilized. The method shown inFIG.3Ainvolves situating302a support structure on or about a subject's head, wherein an array of magnetic sensors is mounted on the support structure. The method involves exposing304the subject to a stimulus or stimuli to stimulate one or more of a sensing organ or sensing organs, a vestibular system, and a memory of the subject. The method also involves performing306, using the array of magnetic sensors, transcranial sensing of local magnetic field emanating from a specific region or regions of the subject's brain in response to the stimulus or stimuli. The method further involves recording308neurostimulation data generated by the array of magnetic sensors, the data representative of patterns of stimulation of the specific region or regions of the subject's brain in response to the stimulus or stimuli.

FIG.3Billustrates a method of recording neurostimulation data generated by a magnetic sensor arrangement shown inFIGS.1A-2Band other figures in accordance with various embodiments. The representative method shown inFIG.3Bis directed to recording neurostimulation data acquired from a subject's olfactory system. The method shown inFIG.3Binvolves situating322a support structure on or about a subject's head, wherein an array of a magnetic sensors is mounted on the support structure. The method involves exposing324the subject to one or more predetermined odors. The method also involves performing326, using the array of magnetic sensors, transcranial sensing of local magnetic fields emanating from the subject's olfactory system (e.g., olfactory cortex, piriform cortex, and/or olfactory bulb) in response to exposing the subject to the one or more predetermined odors. The method further involves recording328olfactory neurostimulation data generated by the array of magnetic sensors, the data representative of patterns of olfactory system stimulation in response to the predetermined odor exposure.

FIG.4Aillustrates a system400aconfigured to record neurostimulation information acquired using transcranial sensing of a subject's brain in accordance with various embodiments. In the embodiment shown inFIG.4A, the system400ais configured to be wearable by the subject and portable, which provides for real-time operation while the subject is ambulatory. The system400aincludes a support structure402aconfigured for placement on a subject's head. In the representative embodiment shown inFIG.4A, the support structure402ais implemented as a headband or other head-worn apparatus that extends generally from a location proximate the subject's left ear, across the left parietal ridge, over the top of the subject's head, across the right parietal ridge, and to location proximate the subject's right ear. Other configurations of the support structure402aare contemplated.

The support structure402ais configured to support a magnetic sensor arrangement404awhich, in the embodiment shown inFIG.4A, includes an array of magnetic sensors405. The magnetic sensor arrangement404acan comprise an arrangement of interlocking magnetic sensors405mounted to the support structure402a. The arrangement of interlocking magnetic sensors405can comprise magnetic sensors405configured to be mechanically interlocking, communicatively (e.g., electrically and/or optically) interlocking, or both mechanically and communicatively interlocking with one another. The magnetic sensors405preferably have a compact design, and can have a size less than or equal to about 2.5 cm2and/or a volume less than or equal to about 2 cm3. The magnetic sensors405are preferably mounted to the support structure402asuch that the magnetic sensors405are positioned relative to a specified region or regions of the subject's brain of interest. For example, the magnetic sensors405can be mounted to the support structure402arelative to specific regions of the subject's olfactory system, including the olfactory cortex and the piriform cortex.

FIG.4Billustrates a system400bconfigured to record neurostimulation information acquired using transcranial sensing of a subject's brain in accordance with various embodiments. The system400bshown inFIG.4Bcan be configured to be the same as or similar to the system400aillustrated inFIG.4A. The system400bincludes a support structure402bconfigured to support a magnetic sensor arrangement404bsimilar that shown inFIG.4A. The support structure402bis configured to support an array of magnetic sensors405and additional magnetic sensors405apositioned near the subject's temples and configured for sensing local magnetic fields emanating from a specified brain region or regions proximate the subject's temples. For example, the magnetic sensors405can be mounted to the support structure402brelative to specific regions of the subject's olfactory system, including the olfactory cortex and the piriform cortex, and the additional magnetic sensors405acan be mounted to the support structure402brelative to the olfactory bulb located near the front of the brain in both cerebral hemispheres.

FIG.5illustrates a support structure502configured to support a magnetic sensor arrangement504in accordance with various embodiments. The support structure502shown inFIG.5includes a helmet structure502within which an array of magnetic sensors504is mounted (individual magnetic sensors not shown). The helmet structure502is configured to be raised and lowered by an external mechanism relative to the subject's head when the subject is at a stationary (e.g., non-ambulatory) position. For example, the subject may be sitting in the chair of a test station and the helmet structure502can be lowered and raised relative to the subject's head via a coupling member505mechanically coupled to an external mechanism (e.g., a controllable manual or electromechanical lift mechanism).

FIG.6Aillustrates a magnetic sensor605suitable for use in any of the magnetic sensor arrangements disclosed herein in accordance with various embodiments. The magnetic sensor605shown inFIG.6Aincludes mechanical features configured to establish an interlocking relationship with one or more other magnetic sensors605of a magnetic sensor arrangement (e.g., magnetic sensor arrangement404a,404bshown inFIGS.4A and4B). The magnetic sensor605includes a chassis607within which a printed circuit board (PCB)606is disposed. One or more magnetic sensor elements612are positioned on or distributed about the PCB606. The magnetic sensor605can include one or more magnetic sensor elements612. Each of the magnetic sensor elements612can be configured to sense local magnetic fields emanating from a specified region of a subject's brain. The magnetic sensor elements612can operate independently or cooperatively with respect to one another. The magnetic sensor elements612are communicatively connected to other electronic circuitry (e.g., electronic memory and/or controller) via traces608disposed on the PCB606. The traces608can include any combination of signal, control, and power lines. Various passive and active electronic components610(e.g., resistors, capacitors, inductors, filters, amplifiers, switches) can be disposed on the PCB606and electrically connected to the magnetic sensor elements612via the traces608.

The chassis607of the magnetic sensor605shown inFIG.6Aincludes a multiplicity of interlocking members614. Typically, the chassis607incorporates at least two of the interlocking members614, but may include more than two interlocking members614(e.g., 3, 4, 5, or 6 interlocking members). Each of the interlocking members614is configured to be received by a corresponding interlocking member of an adjacent magnetic sensor605(not shown, but seeFIGS.6A and6B). For example, the interlocking members614are shown as male connectors inFIG.6A, which can be received by corresponding female interlocking members (e.g., female connectors) of an adjacent magnetic sensor605. In some implementations, some of the interlocking members614of the magnetic sensor605can be male connectors while others can be female connectors.

FIG.6Bis a front view of a connection interface614aof the interlocking members614shown inFIG.6Ain accordance with various embodiments. The connection interface614aincludes a number of connector elements (e.g., pins, ports, and/or receptacles) configured to provide electrical connectivity and optical connectivity (optional in some embodiments) between the PCB606of the magnetic sensor605and other electronic circuitry (e.g., PCBs606of adjacent magnetic sensors605, an electronic memory, and/or controller). The interlocking mechanical and electrical/optical features of the magnetic sensor605provide for enhanced flexibility in terms of the number, configuration, and positioning of a multiplicity of magnetic sensors605that define a magnetic sensor arrangement in accordance with various embodiments. For example, the interlocking mechanical and electrical/optical features of the magnetic sensors405shown inFIGS.4A and4Bprovide for the addition of two extra magnetic sensors405apositionable relative to a subject's left and right temples.

FIG.7illustrates a system700configured to record neurostimulation information acquired using transcranial sensing of a specific region or regions a subject's brain in accordance with various embodiments. The system700includes a support structure702configured for placement on or about a subject's head. The system700includes an electronic recording apparatus703which includes a magnetic sensor arrangement704and an electronic memory710. The electronic recording apparatus703also includes a controller707operatively coupled to the magnetic sensor arrangement704and the electronic memory710. The controller707is configured to control operation of the system700and, in some embodiments, effect communication and interaction with an external system or device (e.g., via a wired or wireless communication device (not shown) coupled to the controller707). As was previously discussed, the electronic memory710is configured to store various spatiotemporal patterns712.

The magnetic sensor arrangement704is configured for transcranial sensing of local magnetic fields emanating from a specific region of a subject's brain. For example, the magnetic sensor arrangement704can be configured for transcranial sensing of local magnetic fields emanating from any one or more of Regions A-n of a subject's brain720. Each of Regions A-n can be representative of a region associated with one or more of the subject's sense organ or organs, vestibular system, and/or memory. For example, each of Regions A-n can represent a region or regions of the brain720associated with one or more of the following sensory organs: eyes, ears, skin, vestibular system, nose, and mouth/tongue, which contribute, respectively, to the sensory perceptions of vision, hearing, touch, spatial orientation, smell, and taste. Regions A-n can also represent a region or regions of the brain720associated with short-term and/or long-term memory.

For example, Region A can represent regions of the brain720associated with a subject's nose/olfactory system and sensory perception of smell (e.g., frontal lobe, olfactory cortex, piriform cortex, olfactory bulb). Region B can represent regions of the brain720associated with a subject's eyes/vision system and sensory perception of vision (e.g., occipital lobe, parietal and temporal lobes). Region C can represent regions of the brain720associated with a subject's auditory system and sensory perception of hearing (e.g., temporal lobe, auditory cortex: primary A1, secondary A2, and tertiary A3 regions). Region D can represent regions of the brain720associated with a subject's somatosensory system and sensory perception of touch and pressure (e.g., somatosensory cortex primarily, parts of the prefrontal cortex and posterior parietal lobe secondarily).

Region E can represent regions of the brain720associated with a subject's gustatory system and sensory perception of taste and flavor (e.g., gustatory cortex, insular cortex, specific portions behind the neocortex, namely the anterior insula, located on the insular lobe, and the frontal operculum, on the frontal lobe). Region F can represent regions of the brain720associated with a subject's vestibular system and sensory perception of spatial orientation (e.g., vestibular cortex of the cerebellum, the core region, parietoinsular vestibular cortex (PIVC), located in the posterior insula and retroinsular region and including the parietal operculum). Other regions of the subject's brain720not specifically associated with one of the subject's senses can be subject to transcranial sensing of local magnetic fields using the system700. For example, Region G can represent regions of the brain720associated with short-term and/or long-term memory (e.g., hippocampus, amygdala, cerebellum, prefrontal cortex).

As is shown inFIG.7, a specified region or regions of a subject's brain720can be stimulated via a stimulation source730. The stimulation source730will vary depending on the subject's sensory system being evaluated using the system700. For example, the stimulation source730may involve manual or automated delivery of one or more odors, one or more visual stimuli (e.g., colors, images, video, graphics), one or more auditory stimuli (natural and man-made sounds, music, tones), different forms of touch and/or pressure to specific body locations, one or more flavors or tastes (e.g., sweet, sour, bitter, salty, umami), and various semantic and episodic memory tests (e.g., neuropsychological tests).

In response to delivery of a stimulus or stimuli by the stimulation source730, the magnetic sensor arrangement704senses local magnetic fields emanating from a specified region or regions of the subject's brain720. The sensed local magnetic fields acquired by the magnetic sensor arrangement704correspond to patterns of stimulation of the specified region or regions of the subject's brain720caused by stimulating one or more of the subject's sense organ or organs, vestibular system, and/or memory. The electronic memory710is configured to store a multiplicity of patterns712of neurostimulation data associated with delivery of the stimulus or stimuli by the stimulation source730. Each of the patterns712stored in the electronic memory710can correspond to neural activity responsive to a specific one of the stimuli delivered by the stimulation source730.

The controller707is configured to coordinate the operation of the system700including activation and deactivation of the magnetic sensor arrangement704and storing of neurostimulation data in the electronic memory710. The controller707can be configured to receive a manual activation input concurrently or shortly after manual or automated activation of the stimulation source730. Alternatively, the controller707can be configured to receive a control signal directly from the stimulation source730which causes activation of the system700concurrently with or shortly after manual or automated activation of the stimulation source730.

FIG.8illustrates a system800configured to record neurostimulation information acquired using transcranial sensing of a specific region or regions a subject's olfactory system820in accordance with various embodiments. The system800includes a support structure802configured for placement on or about a subject's head. The system800includes an electronic recording apparatus803which includes a magnetic sensor arrangement804and an electronic memory810. The electronic recording apparatus803also includes a controller807operatively coupled to the magnetic sensor arrangement804and the electronic memory810. The controller807is configured to control operation of the system800and, in some embodiments, to control communication and interaction with an external system or device (e.g., via a wired or wireless communication device (not shown) coupled to the controller807). As was previously discussed, the electronic memory810is configured to store various spatiotemporal patterns812.

The magnetic sensor arrangement804is configured for transcranial sensing of local magnetic fields emanating from the subject's olfactory system820of the brain. For example, the magnetic sensor arrangement804can be configured for transcranial sensing of local magnetic fields emanating from any one or more of the subject's olfactory bulb822, olfactory cortex824, and piriform cortex826.

As is further shown inFIG.8, the subject's olfactory system820can be stimulated via a stimulation source830. The stimulation source830can be configured to expose the subject to one or more predetermined odors. In response to delivery of each predetermined odor of odors via stimulation source830, the magnetic sensor arrangement804senses local magnetic fields emanating from one or more of the subject's olfactory bulb822, olfactory cortex824, and piriform cortex826. The sensed local magnetic fields acquired by the magnetic sensor arrangement804correspond to patterns of stimulation of the subject's olfactory bulb822, olfactory cortex824, and piriform cortex826caused by exposing the subject to one or more predetermined odors. The electronic memory810is configured to store a multiplicity of patterns812of neurostimulation data associated with delivery of the one or more predetermined odors. Each of the patterns812stored in the electronic memory810can correspond to neural activity response to a specific one of the predetermined odor or a combination of predetermined odors delivered by the stimulation source830.

The controller807is configured to coordinate the operation of the system800including activation and deactivation of the magnetic sensor arrangement804and storing of neurostimulation data in the electronic memory810. The controller807can be configured to receive a manual activation input concurrently or shortly after manual or automated activation of the stimulation source830. Alternatively, the controller807can be configured to receive a control signal directly from the stimulation source830which causes activation of the system800concurrently with or shortly after manual or automated activation of the stimulation source830.

FIG.9illustrates a system900configured to record neurostimulation information acquired using transcranial sensing of a specific region or regions a subject's brain (e.g., olfactory system) in accordance with various embodiments. The system900includes a support structure902configured for placement on or about a subject's head. The system900includes an electronic recording apparatus903which includes one or a multiplicity of magnetic sensor arrangements904, a digital logic module920(e.g., a controller, processor or other logic device), an electronic memory930, and a power source940(e.g., one or more lithium-ion batteries). As discussed previously, the system900can include a multiplicity of the magnetic sensor arrangements904arranged in the form of an array. In such embodiments, each of the multiplicity of magnetic sensor arrangements904is operatively coupled to the digital logic module920, the power source940, and the electronic memory930via the digital logic module920and a communication bus. It is understood that the electronic memory930can be separate from, or integral to, the digital logic module920.

The digital logic module920is configured to control operation of the system900and, in some embodiments, effect communication and interaction with an external system or device (e.g., via a communication device (not shown) coupled to the digital logic module920). As was previously discussed, the electronic memory930is configured to store various spatiotemporal patterns. The magnetic sensor arrangement904is configured for transcranial sensing of local magnetic fields emanating from one or more specified regions (e.g., the olfactory system) of the subject's brain.

The magnetic sensor arrangement904includes a light source910, such as a laser. Light generated by the light source910is directed to a magnetic sensor912. An imaging device (e.g., CCD sensor, active-pixel sensors (CMOS sensor), charge injection devices (CID device)) or photodetector914is configured to detect an optical response of the magnetic sensor912to the light generated by the light source910. In some embodiments, the magnetic sensor arrangement904is configured as an optically pumped magnetometer. In other embodiments, the magnetic sensor arrangement904is configured as an magnetometer arrangement comprising an NV center diamond crystal. The digital logic module920is configured to receive an output signal from the imaging device or photodetector914.

In the case of an imaging device914, the output signal is typically a digital signal. In the case of a photodetector914, the output signal may be an analog signal (e.g., output current signal), which can be converted to a digital signal via an analog-to-digital (ADC) circuit integral or coupled to the digital logic module920. The digital logic module920generates an output signal950representative of a local magnetic field measurement generated by the magnetic sensor arrangement904. The output signal950is communicated from the digital logic module920to the electronic memory930for storage as one of a multiplicity of patterns of stimulation of a specified region or regions of the subject's brain caused by stimulating one or more of the subject's sense organ or organs, vestibular system, and/or memory. The output signal950can also be communicated to a system or device external of the system900.

According to an embodiment of a magnetic sensor arrangement904configured as an OPM sensor, the light source910includes a laser, the magnetic sensor912includes a glass vapor cell containing sensing atoms in a gaseous state, and a photodetector914. The OPM sensor904can be configured as a Zero-Field OPM sensor or a Total-Field OPM sensor. The OPM904configured as a Zero-Field OPM sensor can exhibit extreme sensitivity when the magnetic background is small, works in low field environments, and measures the vector components of the field. When the field is nearly zero, the atoms in the vapor cell become mostly transparent allowing maximum light onto the photodetector914. Any change in the field induces a change in the transparency of the atoms. The resulting change in the photocurrent gives a measure of the magnetic field signal. The Zero-Field OPM sensor can measure field components along the sensitive axes and provides ultra-high sensitivity for detecting very weak magnetic fields, such as local magnetic fields emanating from one or more specified regions of the subject's brain indicative of activation and/or suppression of neuronal activities. A suitable Zero-Field OPM sensor for use in the magnetic sensor arrangement904is disclosed in U.S. Pat. No. 10,775,450, which is incorporated herein by reference.

The OPM sensor904configured as a Total-field OPM sensor can operate in Earth's field with high accuracy, measures the scaler amplitude of the field, and does not need calibration. The atoms in the vapor cell have a well-defined resonance frequency that is directly proportional to the magnitude of the field being measured. Internal coils apply a varying RF field to resolve this frequency by monitoring the transmitted light through the cell. Resonance is achieved when absorption is maximized. The output of the Total-Field OPM sensor is the value of this RF frequency, multiplied by a known scaling factor which directly converts frequency to magnetic field. A suitable Total-Field OPM sensor for use in the magnetic sensor arrangement904is disclosed in U.S. Published Patent Application No. 2018/0238974, which is incorporated herein by reference.

FIG.10Aillustrates a magnetic sensor arrangement1000comprising an NV center diamond crystal magnetic sensor in accordance with various embodiments. A nitrogen vacancy or NV center is an atomic-scale point defect in a diamond crystal lattice. A nitrogen atom substitutes for a carbon atom in the diamond lattice and forms a nearest neighbor pair with a lattice vacancy. In some cases, the NV center attracts an additional electron and it and an unbound electron from the vacancy form a spin 1 pair with quantized energy levels as shown in the example ofFIG.11. The photoluminescence intensity of the NV center diamond crystal is proportional to the relative population of the spin 1 and spin 0 energy levels because the excitation is spin conserving and the spin 1 first excited state has a non-radiative decay path. Microwave radiation at an energy equal to the splitting of the spin 1 and spin 0 ground states can change the population of each of these states driving spin 0 electrons into the spin 1 state.

An applied magnetic field splits the degeneracy in the spin +1 and spin −1 states which shifts the energy splitting between the spin 0 and spin −1 states. Consequently, by exciting the NV center diamond crystal with laser light (e.g. green laser light) and concurrently sweeping the applied microwave frequency, the local magnetic field can be measured at the NV center diamond crystal directly from the frequency value where the photoluminescence signal drops. In a luminescence vs microwave frequency graph, there will be two “dips” for each NV center, which correspond to the energy between the spin −1 and spin 0 states and the spin 1 and spin 0 states. In addition, regardingFIG.11, it should be understood that y represents a physical constant. It should further be understood that the frequency depends on the magnetic field parallel to the defect axis, represented by BII.

The magnetic sensor arrangement1000includes a green pumping laser1008configured to excite nitrogen vacancy centers of a diamond crystal (e.g., an NV center diamond crystal)1006. A long pass filter1010is configured to filter a red light1012caused by the excitation of the NV centers of the diamond crystal1006through to an image sensor1014which, in turn, creates a photoluminescence signal1018. In some embodiments, the image sensor1014is pixelated to provide a spatially resolved magnetic field image. The long pass filter1010is stacked between the NV center diamond crystal1006and the image sensor1014. For example, the long pass filter1010and the image sensor1014can be connected with an adhesive that is transparent for red light. It is noted that the long pass filter1010and the NV center diamond crystal1006can be glued together with an adhesive that blocks green laser light. It is further noted that the long pass filter1010can instead be configured as a bandpass filter, and absorption filter, or an interference filter. In some implementations, a red light reflector1004can be stacked on a surface of the NV center diamond crystal1006opposing a surface of the NV center diamond crystal1006stacked on the long pass filter1010. In some embodiments, a plurality of NV center diamond crystals1006can be attached across a face of the image sensor1014and arranged such that green laser light of the green pumping laser1008is totally internally reflected with a single crystal and transmitted with minimal loss to a neighboring crystal to make a large area magnetic imaging sensor.

A radio frequency source1002(e.g., an RF coil) is configured to apply radiation to the NV center diamond crystal1006. The RF source1002may also be configured to shift energy of the photoluminescence signal1018. In some implementations, the RF source1000can be stacked on a mirror stacked on the NV center diamond crystal1006. The RF source1000can be configured to drive electron population transitions and read out a local projection of a magnetic field along a center crystallographic axis of the NV center defects of the NV center diamond crystal1006. A magnet1016is configured to break a degeneracy of the NV centers. The components of the magnetic sensor arrangement1000shown inFIG.10Aadvantageously provide for a compact device, in large part due to stacking the long pass filter1010between the NV center diamond crystal1006and the image sensor1014.

The photoluminescence signal1018produced by the magnetic sensor arrangement1000can be communicated to a digital logic module1020which, in the embodiment shown inFIG.10A, includes a processor1022operatively coupled to memory1024. In some embodiments, the digital logic module1020is integral to the magnetic sensor arrangement1000. In other embodiments, the digital logic module1020is separate from, but operatively coupled to, the magnetic sensor arrangement1000. The memory1024is configured to store computer program code which, when executed by the processor1022, causes the digital logic module1022to measure a local magnetic field1026by measuring a frequency of a radiation where the photoluminescence signal drops.

FIG.10Bshows a compact magnetic sensor arrangement1001in accordance with one embodiment. As illustrated inFIG.10B, and with continued reference toFIG.10A, a diamond crystal1006with implanted NV center defects and an optical long pass filter1010are stacked directly on a pixelated image sensor1014. Green laser light is coupled in from a side1009of the diamond crystal1006via edge coupling and totally internally reflected within the diamond crystal1006to excite the NV center bound state electrons while minimizing the green background in the photoluminescence measurement. NV centers emit light isotopically in all directions. A red light reflector1004is included on the diamond crystal surface opposite the long pass filter1010to reflect light back towards the image sensor1014and double the collection efficiency. This reflector1004can optionally be omitted if spatial resolution is more critical that signal sensitivity. An integrated RF coil1002is included on top of the mirror diamond surface to drive the electron population transitions and readout the local projection of the magnetic field along the NV center's crystallographic axis. As the frequency is swept, a series of pairs of dips each corresponding to a NV center projection can be seen. In addition, a magnet1016(either permanent or electromagnet) is included to break the degeneracy of the NV ensemble projections and spectrally separate the dips in the photoluminescence vs. RF frequency plot.

Because the magnet1016may suitably be placed in different locations, a specific location of the magnet is not shown inFIG.10B. The device stack up includes: optional top red light reflector1004, NV center diamond crystal1006, long pass filter1010, and the image sensor1014. In some embodiments, any or all of the components can be connected with no gap either by direct deposition (e.g., sputtering an aluminum mirror on the top surface of the diamond substrate). In other embodiments, any or all of the components can be coupled with a high index adhesive that is transparent for red light. If an adhesive that is transparent for red light and opaque for other colors of light is used, this could combine the purpose of the long pass filter1010and the adhesive, and thus eliminate the need for using a long pass filter1010which would eliminate some thickness and thereby improve resolution.

Matching the index of the adhesive material to diamond crystal's index (n=2.4) can improve the spatial resolution and light collection efficiency. The highest possible index adhesive that still meets the transparency requirements should be used. In one example, an optically clear adhesive with an index of about 1.4 is used. It should be understood that if an adhesive is not used, there might be an air gap (e.g., where the adhesive would otherwise be between the various layers of diamond crystal1006, long pass filter1010, and image sensor1014) along at least a portion of contacting layers. In some embodiments, between layers where no adhesive is used, there is no purposely created space but air gap(s) still exist along certain portions of the edges. In some aspects, the airgap is a nuisance because its presence can create some diffusion in the light signal that decreases spatial resolution. Thus, in some exemplary embodiments, there is no airgap. In some embodiments, the long pass filter1010is pressed to the imager1014(instead of gluing it), in which case a small airgap may be unavoidable.

There are many options for the components described above, and the examples given are not meant to limit the design variations. For example, various long pass filters or other filters may be used. In this regard, a purpose of the long pass filter1010is to block the (532 nm) green laser light. For example, in some embodiments, the filter1010passes 639-800 nm light and blocks 532 nm light (e.g., the filter1010may be a bandpass filter). In another example, the filter1010may be a long pass filter. In one aspect, the filter1010can be an absorption filter or an interference filter. The filter1010can be directly deposited onto the NV center diamond crystal1006or glued to the diamond crystal1006with a high index adhesive that is also transparent in certain wavelength ranges (e.g., 639-800 nm) such that the green laser light is blocked.

Similarly, the top red light reflector1004can be implemented with a broad band reflector (mirror) or low frequency reflector that reflects light in a particular band such as the 639-800 nm band. The reflector1004can be deposited directly on the NV center diamond crystal1006or glued to the diamond crystal1006with a high index adhesive.

The image sensor1014can be any light-to-charge converter and can be pixelated or not. Examples include complementary metal-oxide semiconductor (CMOS) imagers, charge-coupled device (CCO) imagers, and large area thin film transistor/photodiode imagers. In some embodiments of this compact system1001, the spatial resolution will be limited by the larger of the thickness of the optical stack (diamond crystal1006and long pass filter1010) or the imager pixel. The diamond crystal1006minimum thickness is set by the mechanical stability of the diamond crystal1006and the thickness needed to achieve good coupling for the green excitation laser. A suitable NV center diamond crystal1006can have a thickness of about 250 um with a polished edge1009to serve as an edge coupling of the totally internally reflected laser light. If an imager1014with pixels smaller than the optical stack thickness is selected, pixel binning up to the size of the optical stack can be done to increase the signal size with no loss of resolution.

In some embodiments, the thickness of the diamond crystal1006is the same or about the same as the pixel size of the image sensor1014. The overall imaging area will also be limited by the size of the diamond crystal1006. NV diamond crystals1006as large as about 4 mm×4 mm have been demonstrated in the art, but larger crystals may be possible. The size of the available diamond crystal1006will impact the choice of image sensor1014used in the optical stack. If diamond substrate sizes remain small, a CMOS imager will likely be the best choice. A state of the art 4K 2.8 um pixel CMOS sensor is about 11 mm×11 mm. However, NV diamond crystals1006could also be tiled across the surface of an imager1014and connected with a high index adhesive to cover a large area. In this case, an a-Si thin-filmtransistor (TFT) imager can be selected as the image sensor1014to create a large area, portable, high sensitivity magnetic imager with high spatial resolution.

In some embodiments, the NV centers of the diamond crystal1006are near the top surface of the diamond crystal1006(e.g., near the red light reflector1004). In one example, the NV centers are about 5 nm-40 nm from the top surface of the diamond170. The precise distance depends on the energy of implementation. In other embodiments; the NV centers of the diamond crystal1006may be near a bottom surface of the diamond crystal1006(e.g., near the long pass filter1010).

Moreover, NV diamond magnetometers can operate at a room temperature (unlike superconducting quantum interference device (SQUIDs), can measure the vector projections of the magnetic field and, in an ensemble configuration, can provide natural 2-D imaging unlike other sensing technologies which are essentially 0-D point-like sensors.

Embodiments of the magnetic sensor arrangement1001illustrated inFIGS.10A and10Badvantageously add portability to the other benefits of the NV magnetometer imaging system and enable the image sensor1014to be used in field environments for non-destructive, non-invasive operation (e.g., in real-time by an ambulatory user) and/or in clinical environments for medical imaging. For example, some embodiments can be used to measure neuron activity (e.g., neurons firing) as described herein by use of a small portable device1001. In some embodiments, the small portable device1001is about 1 inch×1 inch by×1 inch, and uses three conductors, cables and/or traces (e.g., a digital cable for the imager/camera1014, an RF cable for the RF coil1002, and a fiber cable for the laser1008). The small portable device1001(e.g., an array of the devices1001) can easily be strapped to a patient at any suitable location on the patient (e.g., situated on a patient's head via a headband support arrangement as previously described). Embodiments directed to a magnetic sensor arrangement comprising an NV center diamond crystal magnetic sensor can include structures, hardware, software, functionality, and/or processes disclosed in commonly-owned U.S. patent application Ser. No. 16/665,375 filed Oct. 28, 2019, which is incorporated herein by reference in its entirety.

FIG.12illustrates a system1200configured to facilitate implementation of non-invasive transcranial sensing and recording in accordance with various embodiments. The system1200shown inFIG.12includes a digital assistant device1210configured to communicatively couple to a non-invasive transcranial neurorecording apparatus1202and a remote server1230via a network connection, such as the Internet1220. The digital assistant device1210can be any mobile or stationary communication device, such as a smartphone, tablet, laptop or desktop PC, for example. The digital assistant device1210can include a touchscreen1212and a number of conventional components such as a microphone, camera, CPU, memory, power source, one or more radios or wireless transceivers (e.g., WiFi®, Bluetooth®, Zigbee®). The digital assistant device1210can also include one or more wired communication ports, such as USB or Ethernet ports. The digital assistant device1210includes one or more applications (referred to herein as apps) which can be stored in the memory and are executable by the CPU. At least one of the apps comprises executable instructions or program code that causes the CPU to cooperate with the non-invasive transcranial neurorecording apparatus1202in accordance with any of the processes disclosed herein.

In some embodiments, the digital assistant device1210cooperates with the server1232at least to store data acquired or produced by the non-invasive transcranial neurorecording apparatus1202in cloud storage. A cloud processor can provide additional computing resources to process the data received from the digital assistant device1210in accordance with the processes (e.g., machine learning) and algorithms disclosed herein. In addition, the cloud processor can generate additional or variant neurorecording data, which can be transferred back to the digital assistance device1210.

FIGS.13A and13Billustrate apparatuses1300a,1300bconfigured to deliver transcranial stimulation to a specified region or regions of a person's brain in accordance with various embodiments. The apparatuses1300a,1300binclude a support structure1302configured for placement on or about a person's head. The support structure1302is configured to support at least a focused ultrasound (fUS) transducer arrangement1304. According to various embodiments, the fUS transducer arrangement1304includes an array of ultrasound transducers mounted to the support structure1302. An electronic memory1310is operatively coupled to the fUS transducer arrangement1304. In the embodiment shown inFIG.13A, the electronic memory1310is not a component of (e.g., not mounted to) the support structure1302, but is operatively coupled to the fUS transducer arrangement via a wireless or wired connection. In the embodiment shown inFIG.13B, the electronic memory1310is mounted to or supported by the support structure1302and operatively coupled to the focused or system transducer arrangement, typically via a wired connection but may alternatively include a wireless connection.

The electronic memory1310is configured to store pre-recorded neurostimulation data comprising a multiplicity of patterns1312of stimulation of a specified region or regions of a subject's brain. Each of the patterns1312is associated with neural activity sensed from a specified region of a subject's brain in response to stimulating one or more of the subject's sense organ or organs, vestibular system, and/or memory to a particular stimulus or particular stimuli as previously described. Each of the patterns1312can include stimulation parameters (e.g., a topographic mapping of neural activity amplitude) and a temporal pattern of stimulation (e.g., a temporal mapping of the neural activity).

It is understood that stimulation of a specified region of a subject's brain can refer to one or both of excitation and suppression of neural activity in the specified region of the subject's brain. In the case of suppression, for example, a combination of control over the phase and amplitude of the transcranial ultrasound stimulation can be selected to interfere with the neural activity in the specified region(s) of the subject's brain, such that the net resultant action is the closing of neuronal ion channels and thus the suppression of the region(s) of interest. It is noted that other stimulation modes can used, including a combination of ultrasound and magnetic stimulation, to cancel the potential excitation of a certain region(s) of interest. The patterns1312stored in the electronic memory1310can be any of the patterns previously described, such as patterns112shown inFIGS.1A-1C. It is also understood that the patterns1312stored in the electronic memory1310can be representative of patterns1312associated with a particular subject's neural activity or a multiplicity (e.g., population) of subjects' neural activity.

In accordance with various embodiments, the patterns1312can include neural activity data of various types. For example, the patterns1312can include neural activity data acquired from the same or different type of transcranial sensing arrangement. For example, and as previously described, the patterns1312can include neural activity data acquired by an NV (nitrogen-vacancy) diamond magnetic sensor arrangement. The patterns1312can include neural activity data acquired by an EEG (electroencephalogram) sensor arrangement. The patterns1312can include neural activity acquired by and an MEG (magnetoencephalography) sensor arrangement. The patterns1312can include neural activity data acquired by an MRI (magnetic resonance imaging) or fMRI (functional magnetic resonance imaging) arrangement. The patterns1312can include neural activity data acquired by an optically pumped magnetic (OPM) sensor arrangement. It is understood that the patterns1312can include neural activity data acquired from any one or any combination of these and other transcranial sensing arrangements.

According to various embodiments, at least the support structure1302and the fUS transducer arrangement1304(as well as an on-board power source) are configured to be wearable and portable by a user, such as during ambulatory activities. In some embodiments, the support structure1302, the fUS transducer arrangement1304, and the electronic memory1310(as well as an on-board power source) are configured to be wearable and portable by a user, such as during ambulatory activities.

FIGS.14A and14Billustrate methods which can be implemented using the apparatuses1300a,1300bshown inFIGS.13A and13Bin accordance with various embodiments. The method shown inFIG.14Ainvolves situating1402a support structure on or about a person's head, with an array of ultrasound transducers mounted to the support structure. The method also involves selecting1404, from an electronic memory, pre-recorded neurostimulation data developed to recreate a response by one or more of a sensing organ or organs, a vestibular system, and a memory of a subject. It is noted that the pre-recorded neurostimulation data can include neurostimulation data acquired from the subject or from person or persons other than the subject. The method further involves delivering1406, using the array of ultrasound transducers and the pre-recorded neurostimulation data, transcranial stimulation to a specified region or regions of the subject's brain to recreate the response by one or more of the sensory organ or organs, the vestibular system, and the memory of the subject.

FIG.14Billustrates methods which can be implemented using the apparatuses1300a,1300bshown inFIGS.13A and13Bin accordance with various embodiments. The method shown inFIG.14Binclude situating1420as support structure on or about a person's head, with an array of ultrasound transducers mounted to the support structure. The method also involves selecting1422, from an electronic memory, pre-recorded olfactory neurostimulation data developed to recreate one or more predetermined odors. The method further involves delivering1424, using the array of ultrasound transducers and the pre-recorded olfactory neurostimulation data, transcranial stimulation of the subject's olfactory system to recreate the one or more predetermined odors or variations of the one or more predetermined odors.

FIG.15Aillustrates a system1500aconfigured to deliver transcranial stimulation to a subject's brain in accordance with various embodiments. In the embodiment shown inFIG.15A, the system1500ais configured to be wearable by the subject and portable, which provides for real-time operation while the subject is ambulatory. The system1500aincludes a support structure1502aconfigured for placement on a subject's head. In the representative embodiment shown inFIG.15A, the support structure1502ais implemented as a headband or other head-worn apparatus that extends generally from a location proximate the subject's left ear, across the left parietal ridge, over the top of the subject's head, across the right parietal ridge, and to location proximate the subject's right ear. Other configurations of the support structure1502aare contemplated.

The support structure1502ais configured to support an fUS transducer arrangement1504awhich, in the embodiment shown inFIG.15A, includes an array of ultrasound transducers1505. The fUS transducer arrangement1504acan comprise an arrangement of interlocking ultrasound transducers1505mounted to the support structure1502a. The arrangement of interlocking ultrasound transducers1505can comprise ultrasound transducers1505configured to be mechanically interlocking, communicatively (e.g., electrically and/or optically) interlocking, or both mechanically and communicatively interlocking with one another. The ultrasound transducers1505preferably have a compact design, and can have a size less than or equal to about 2 to 2.5 cm2and/or a volume less than or equal to about 2 cm3. The ultrasound transducers1505are preferably mounted to the support structure1502asuch that the ultrasound transducers1505are positioned relative to a specified region or regions of the subject's brain of interest. For example, the ultrasound transducers1505can be mounted to the support structure1502arelative to specific regions of the subject's olfactory system, including the olfactory cortex and the piriform cortex.

FIG.15Billustrates a system1500bconfigured to deliver transcranial stimulation to a subject's brain in accordance with various embodiments. The system1500bshown inFIG.15Bcan be configured to be the same as or similar to the system1500aillustrated inFIG.15A. The system1500bincludes a support structure1502bconfigured to support an fUS transducer arrangement1504bsimilar that shown inFIG.15A. The support structure1502bis configured to support an array of ultrasound transducers1505and additional ultrasound transducers1505apositioned near the subject's temples and configured for delivering transcranial stimulation to a specified brain region or regions proximate the subject's temples. For example, the ultrasound transducers1505can be mounted to the support structure1502brelative to specific regions of the subject's olfactory system, including the olfactory cortex and the piriform cortex, and the additional ultrasound transducers1505acan be mounted to the support structure1502brelative to the olfactory bulb located near the front of the brain in both cerebral hemispheres.

FIG.16illustrates a support structure1602configured to support an fUS transducer arrangement1604in accordance with various embodiments. The support structure1602shown inFIG.16includes a helmet structure1602within which an array of ultrasound transducers1604is mounted (individual ultrasound transducers not shown). The helmet structure1602is configured to be raised and lowered by an external mechanism relative to the subject's head when the subject is at a stationary (e.g., non-ambulatory) position. For example, the subject may be sitting in the chair of a test station and the helmet structure1602can be lowered and raised relative to the subject's head via a coupling member1605mechanically coupled to an external mechanism (e.g., a controllable manual or electromechanical lift mechanism).

FIG.17Aillustrates an ultrasound transducer1705suitable for use in any of the ultrasound transducer arrangements disclosed herein in accordance with various embodiments. The ultrasound transducer1705shown inFIG.17Aincludes mechanical features configured to facilitate interlocking with one or more other ultrasound transducers1705of an ultrasound transducer arrangement (e.g., ultrasound transducer arrangement1504a,1504bshown inFIGS.15A and15B). The ultrasound transducer1705includes a chassis1707within which a PCB1706is disposed. One or more ultrasound transducer elements1712are positioned on or distributed about the PCB1706. Each of the ultrasound transducer elements1712can be configured to deliver transcranial stimulation to a specified region or regions of a subject's brain. The ultrasound transducer elements1712can operate independently or cooperatively with respect to one another. The ultrasound transducer elements1712are communicatively connected to other electronic circuitry (e.g., electronic memory and/or controller) via traces1708disposed on the PCB1706. The traces1708can include any combination of signal, control, and power lines. Various passive and active electronic components1710(see discussion of components610shown inFIG.6A) can be disposed on the PCB1706and electrically connected to the ultrasound transducer elements1712via the traces1708.

The chassis1707of the ultrasound transducer1705shown inFIG.17Aincludes a multiplicity of interlocking members1714. Typically, the chassis1707incorporates at least two of the interlocking members1714, but may include more than two interlocking members1714(e.g., 3, 4, 5, or 17 interlocking members). Each of the interlocking members1714is configured to be received by a corresponding interlocking member of an adjacent ultrasound transducer1705(not shown, but seeFIGS.15A and15B). For example, the interlocking members1714are shown as male connectors inFIG.17A, which can be received by corresponding female interlocking members (e.g., female connectors) of an adjacent ultrasound transducer1705. In some implementations, some of the interlocking members1714of the ultrasound transducer1705can be male connectors while others can be female connectors.

FIG.17Bis a front view of a connection interface1714aof the interlocking members1714shown inFIG.17Ain accordance with various embodiments. The connection interface1714aincludes a number of connector elements (e.g., pins, ports, and/or receptacles) configured to provide electrical (and optionally optical) connectivity between the PCB1706of the ultrasound transducer1705and other electronic circuitry (e.g., PCBs1706of adjacent ultrasound transducers1705, an electronic memory, and/or controller). The interlocking mechanical and electrical features of the ultrasound transducer1705provide for enhanced flexibility in terms of the number, configuration, and positioning of a multiplicity of ultrasound transducers1705that define a ultrasound transducer arrangement in accordance with various embodiments. For example, the interlocking mechanical and electrical features of the ultrasound transducers1505shown inFIGS.15A and15Bprovide for the addition of two extra ultrasound transducers1505apositionable relative to a subject's left and right temples.

FIG.18illustrates a transcranial stimulation system1800comprising an fUS transducer arrangement1804in accordance with various embodiments. The system1800includes a support structure1802configured for placement on or about a person's head. The fUS transducer arrangement1804is mounted to the support structure1802. A driver1806, a controller1808, and optional beamforming/steering electronics1810are also mounted to, or supported by, the support structure1802. The driver1806is operatively coupled to the fUS transducer arrangement1804and configured to drive and control each ultrasound transducer of the fUS transducer array in cooperation with the controller1808. The controller1808is configured to adjust one or more parameters impacting transcranial stimulation delivered by the fUS transducer arrangement1804Beamforming/steering electronics1810can be operatively coupled to the controller1808and the driver1806. The beamforming/steering electronics1810is configured to steer focusing of the fUS transducer arrangement1804towards specified region or regions (e.g., specified structures) of a subject's brain.

The fUS transducer arrangement1804is configured to deliver non-invasive (e.g., non-ionizing, non-destructive) neurostimulation to specified sites within a subject's brain. The fUS transducer arrangement1804can be configured for low-intensity fUS (LIFU). The fUS transducer arrangement1804delivers transcranial focused ultrasound (tFUS) having a higher spatial resolution, and capable of reaching deeper structures, when compared to conventional magnetic or electric non-invasive brain stimulation.

The fUS transducer arrangement1804can be configured to non-invasively deliver mechanical forces to structures deep within the brain in the form of an acoustic pressure wave, which can result in numerous bioeffects, both thermal and mechanical, depending on the specific pulsing regime. The acoustic waves can be focused to a particular location or region with a spatial resolution on the order of the wavelength of the driving frequency (e.g., approximately 3 mm at 0.5 MHz). As the focusing is achieved through constructive interference of the incident waves, a focal spot can be formed at a specified depth within the targeted brain tissue without affecting cells along the propagation path closer to the fUS transducer arrangement1804.

FIG.19illustrates a fUS transducer arrangement1904comprising an array of ultrasound transducers1905in accordance with various embodiments. The ultrasound transducer array1905includes a multiplicity of ultrasound transducer elements1907. The ultrasound transducer elements1907can be arranged in any suitable pattern along a single axis (e.g. a one-dimensional (1-D) array) or multiple orthogonal axes (e.g., a 2-dimensional (2-D) array).FIG.19shows a driver1906operatively coupled to the array of ultrasound transducers1905via beamforming/steering electronics1910. The fUS transducer arrangement1904can be implemented as a phased array of ultrasound transducer elements1907. The beamforming/steering electronics1910includes a divider1920operatively coupled to the driver1906. The divider1920can be a Wilkinson power divider, such as a compact multi-layer Wilkinson power divider. The divider1920is operatively coupled to a multiplicity of phase shifters1922and a multiplicity of variable gain amplifiers1924. Each ultrasound transducer element1907is operatively coupled to a corresponding variable gain amplifier1924and phase shifter1922.

A controller1908is operatively coupled to the driver1906and the beamforming/steering electronics1910. The controller1908is configured to control the phase shifters1922and variable gain amplifiers1924to steer focusing of the ultrasound transducer elements1907, such as by adjusting the phase shift of each of the phase shifters1922. The beamforming/steering electronics1910can be configured to shape the spatial distribution of the pressure field amplitude in the volume of interest within a subject's brain. A challenge to accurately targeting a specified brain region concerns acoustic reflection, refraction, and distortion due to the inhomogeneity of skull bone. This challenge can be solved by time shifting each single ultrasound wave, according to the related skull bone acoustical properties, in order to permit all the waves to reach the target at the same time.

An acoustic wave can be defined by two fundamental parameters: the intensity, defined as the amplitude of the wave, and the instantaneous period (T), defined as the time needed to complete one single oscillation cycle, which is used to calculate the Acoustic frequency (Af). In addition to these two parameters, the stimulus duration (StimD) is the total duration of one single sonication. During the stimulus duration, two paradigms of sonication are used: continuous or pulsed. Some of these protocols resemble those used for non-invasive brain stimulation based on repetitive transcranial magnetic stimulation. The more popular protocol for neuromodulation is the pulsed paradigm.

For the pulsed paradigm, two additional periods are defined: the pulse duration (PD), which is the period of acoustic sonication from the starting point of oscillation to the ending point, before the pause and the pulse repetition period (PRP), which is the period between the starting point of two consecutive sonications, or, in other terms, the sum of the pulse duration (PD) and the pause between two consecutive sonications. This period is used to calculate the pulse repetition frequency (PRF). For the pulsed paradigm, the duty cycle (DC) is the fraction of the pulsed repetition period (PRP) covered by the pulse duration (PD). The cycles per pulse (c/p) are the number of cycles during a single pulse; instead, the number of pulses (Np) is the number of pulses throughout the stimulus duration. The sonication delivered during the stimulus duration period can be repeated, without pauses, for the continuous stimulation protocol. Intermittent protocols are characterized by pauses between the sonications, defined as inter stimulation intervals (ISIs). The intermittent protocol is the most used for fUS neurostimulation.

For safety reasons, the indexes that describe the thermal and biomechanical effects of the sonication have been defined. These parameters are related to the instantaneous intensity of stimulation and its instantaneous acoustic pressure. The two main mechanisms that can induce tissue damage are: local heating, which through proteins denaturation leads to cell death, and inertial cavitation. The latter is thought to be mediated by the collapse of gas bubbles due to the pressure exerted by ultrasonic field sufficiently strong to allow tissue damage. Both animal histological studies and human neuroimaging studies have shown that it is possible to neuromodulate brain circuits without inducing tissue damage. The thermal index (TI) is the ratio of total acoustic power to the acoustic power required to raise tissue temperature by 1° C. under defined assumptions. Finally, the non-thermal, mechanical bioeffect is described by the mechanical index (MI), which is directly proportional to the ultrasound beam's peak negative pressure and inversely proportional to the frequency of the beam.

The intensity, spatial-peak pulse-average (ISPPA) is the value of the pulse-average intensity at the point in the acoustic field where the pulse-average intensity is a maximum or is a local maximum within a specified region. The intensity, spatial-peak temporal-average (ISPTA) is the value of the temporal-average intensity at the point in the acoustic field where the temporal-average intensity is a maximum, or is a local maximum within a specified region. FDA guidelines define the safety threshold for diagnostic usage of fUS for adult cephalic ultrasound, which can be applied to neuromodulation. These parameters are Isspa≤190 W/cm2, Ispta≤94 mW/cm2and a mechanical index ≤1.9.

FIG.20illustrates a system2000configured to facilitate implementation of non-invasive transcranial neurostimulation in accordance with various embodiments. The system2000shown inFIG.20includes a digital assistant device2010configured to communicatively couple to a non-invasive transcranial neurostimulation apparatus2002and a remote server2030via a network connection, such as the Internet2020. The digital assistant device2010can be any mobile or stationary communication device, such as a smartphone, tablet, laptop or desktop PC, for example. The digital assistant device2010can include a touchscreen2020and a number of conventional components such as a microphone, camera, CPU, memory, power source, one or more radios or wireless transceivers (e.g., WiFi®, Bluetooth®, Zigbee®). The digital assistant device2010can also include one or more wired communication ports, such as USB or Ethernet ports. The digital assistant device2010includes one or more apps which can be stored in the memory and are executable by the CPU. At least one of the apps comprises executable instructions or program code that causes the CPU to cooperate with the non-invasive transcranial neurostimulation apparatus2002in accordance with any of the processes disclosed herein.

In some embodiments, the digital assistant device2010cooperates with the server2032(e.g., via the Internet) at least to acquire pre-recorded neurostimulation data (e.g., stored in cloud storage) comprising patterns of stimulation of a type or types previously described. A cloud processor can provide additional computing resources to facilitate delivery of transcranial stimulation to a specified region or regions of the subject's brain using the pre-recorded neurostimulation data. For example, the cloud processor can generate additional or variant neurorecording data, which can be transferred back to the digital assistance device2010.

FIG.21illustrates a system2100configured to deliver transcranial stimulation to a specified region or regions of a subject's brain and to contemporaneously sense a response to the transcranial stimulation in accordance with various embodiments. The system2100includes a transcranial neurorecording sensor arrangement2104and a transcranial stimulation arrangement2140, each of which is operatively coupled to a controller2130. Components of the neurorecording sensor arrangement2104are mounted to a support structure2102configured for placement on or about a subject's head. The neurorecording sensor arrangement2104can have a configuration and functionality described previously with reference to the systems and methods shown inFIG.1AthroughFIG.12. Components of the transcranial stimulation arrangement2140are mounted to a support structure2142configured for placement on or about the subject's head. The transcranial stimulation arrangement2140can have a configuration and functionality described previously with reference to the systems and methods shown inFIG.13AthroughFIG.20. In some embodiments, components of the neurorecording sensor arrangement2104and the transcranial stimulation arrangement2140are mounted to a common support structure2102or2142configured for placement on or about the subject's head.

The transcranial stimulation arrangement2140includes an ultrasound transducer arrangement2144operatively coupled to an electronic memory2146and a controller (not shown, but seeFIGS.7-10A). The ultrasound transducer arrangement2144preferably includes an array of ultrasound transducers mounted to the support structure2142. The transcranial stimulation arrangement2140is configured to deliver transcranial stimulation to a specified region or regions of the subject's brain2120using pre-recorded neurostimulation data stored in the electronic memory2146. In addition or alternatively, the transcranial stimulation arrangement2140can be configured to deliver transcranial stimulation to a specified region or regions of the subject's brain2120using contemporaneous stimulation data acquired by the neurorecording sensor arrangement2104. The contemporaneous stimulation data comprises neural activity data acquired by the neurorecording sensor arrangement2104during concurrent stimulation of the specified region or regions of the subject's brain2120via the transcranial stimulation arrangement2140. The pre-recorded neurostimulation data comprises patterns2148of stimulation of the specified region or regions of the subject's brain or the brain of one or more persons other than the subject developed to recreate a response by one or more of the sensing organ or sensing organs, a vestibular system, and a memory of the subject.

The neurorecording sensor arrangement2104is configured to transcranially sense a response from a specified region or regions of the subject's brain initially cause by exposing the subject to stimuli and subsequently caused by delivery of transcranial stimulation by the transcranial stimulation arrangement2140using neurostimulation data recorded by the neurorecording sensor arrangement2104. A wide variety of neurorecording sensor arrangements2104can be used in the context of an open-loop system or a closed-loop system in accordance with various embodiments. In some embodiments, the neurorecording sensor arrangement2104includes an array of magnetic sensors (e.g., NV-diamond magnetic sensors, OPM sensors) mounted to a support structure2102/2142and configured to sense local magnetic fields emanating from the specified region or regions of the subject's brain. In other embodiments, the neurorecording sensor arrangement2104includes an EEG sensor arrangement configured to acquire electroencephalogram data from the subject's brain for recording by the neurorecording sensor arrangement2104.

In further embodiments, the neurorecording sensor arrangement2104includes a MEG sensor arrangement configured to acquire magnetoencephalography data from the subject's brain for recording by the neurorecording sensor arrangement2104. In some embodiments, the neurorecording sensor arrangement2104includes an MM sensor arrangement configured to acquire magnetic resonance imaging data from the subject's brain for recording by the neurorecording sensor arrangement2104. In other embodiments, the neurorecording sensor arrangement2104includes an fMRI sensor arrangement configured to acquire functional magnetic resonance imaging data (e.g., brain activity data detected by measuring small changes in cerebral blood flow) from the subject's brain for recording by the neurorecording sensor arrangement2104.

Controlling operation of the array of ultrasound transducers by the controller2130can involve determining a difference between the contemporaneous neurostimulation data2106and the pre-recorded neurostimulation data, and comparing the difference to a predetermined threshold or a predetermined neural activity template. The controller2130is configured to produce transcranial stimulation adjustments2136in response to the difference exceeding or falling below the threshold or in response to a lack of correlation (e.g., >97%) relative to the predetermined neural activity template. In response to the transcranial stimulation adjustments2136generated by the controller2130, the transcranial stimulation arrangement2140adjusts delivery of the transcranial stimulation. Adjusting delivery of the transcranial stimulation by the controller2130can involve one or more of adjusting a location or locations of the subject's brain subject to the transcranial stimulation, adjusting a spatiotemporal stimulation pattern of the transcranial stimulation, adjusting power of the transcranial stimulation, adjusting a frequency or a frequency range of the transcranial stimulation, adjusting a time duration or time parameter of the transcranial stimulation, adjusting a phase of the transcranial stimulation, and adjusting an amplitude of the transcranial stimulation. Adjustment of other parameters by the controller2130are contemplated.

According to some embodiments, a subject can be exposed to stimuli to stimulate one or more of a sensing organ or organs, a vestibular system, and a memory of the subject. The neurorecording sensor arrangement2104can be controlled by the controller2130to perform transcranial sensing of the specified region or regions of the subject's brain in response to the stimuli using any one or more of the sensor arrangements discussed above. The controller2130, alone or in cooperation with another controller or processor, can be configured to operate on the data acquired from the neurorecording sensor arrangement2104.

For example, the controller2130, alone or in cooperation with another controller or processor, can be configured to operate on the data acquired from the neurorecording sensor arrangement2104by algorithmically determining, via machine learning, a spatiotemporal pattern needed to recreate the response (and/or a variation of the response) of one or more of the sensing organ or sensing organs, the vestibular method, and the memory of the subject stimulated by the stimuli. By way of further example, the controller2130, alone or in cooperation with another controller or processor, can be configured to operate on the data acquired from the neurorecording sensor arrangement2104by algorithmically altering, via machine learning, the spatiotemporal pattern to produce an altered version of the spatiotemporal pattern. Various machine learning tools can be implemented by the controller2130, alone or in cooperation with another controller or processor, including one or more of neural networks, convolutional neural networks (CNNs), and generative adversarial networks (GANs).

In some embodiments, the controller2130, alone or in cooperation with another controller or processor, can be configured to algorithmically determine, via machine learning, one or both of the likelihood of stimulating the specified region or regions of the subject's brain in response to exposing the subject to the stimuli, and determine components of the stimuli that can be used as basis vectors to produce an altered spatiotemporal pattern that recreates an altered version of the response. Additionally, or alternatively, the controller2130, alone or in cooperation with another controller or processor, can be configured to algorithmically predict, via machine learning, which particular region or regions of the subject's brain will be stimulated when stimulating the subject's brain to recreate an altered version of the response. Additionally, or alternatively, the controller2130, alone or in cooperation with another controller or processor, can be configured to algorithmically determine, via machine learning, person-to-person variations of the transcranial stimulation based on physiology of a human head in order to infer properties for driving the array of ultrasound transducers needed to one or both of excite and suppress the particular region or regions of the subject's brain.

The spatiotemporal patterns needed to recreate the response (and/or a variation of the response) of one or more of the sensing organ or sensing organs, the vestibular method, and the memory of the subject stimulated by one of more stimuli are stored in the electronic memory2146. The patterns2148can include neural activity data acquired from the same or a different type of transcranial sensing arrangement. For example, and as previously described, the patterns2148can include neural activity data acquired by an NV-diamond magnetic sensor arrangement. The patterns2148can include neural activity data acquired by an EEG sensor arrangement. The patterns2148can include neural activity acquired by and an MEG sensor arrangement. The patterns2148can include neural activity data acquired by an MRI or fMRI arrangement. The patterns2148can include neural activity data acquired by an OPM sensor arrangement. It is understood that the patterns2148can include neural activity data acquired from any one or any combination of these and other transcranial sensing arrangements.

FIG.22illustrates a system2200configured to deliver transcranial stimulation to an olfactory system2220of a subject's brain and to contemporaneously sense a response to the transcranial stimulation in accordance with various embodiments. The system2200is a variant of the system2100shown inFIG.21. In the embodiment shown inFIG.22, the transcranial stimulation arrangement2140includes an ultrasound transducer arrangement2144comprising an array of ultrasound transducers which, under the control of the controller2130, delivers transcranial stimulation to the subject's olfactory system2220. As previously discussed, the transcranial stimulation arrangement2140can use one or both of pre-recorded and contemporaneous olfactory stimulation data acquired from the neurorecording sensor arrangement2104.

The transcranial stimulation arrangement2140shown inFIG.22is configured to deliver transcranial stimulation to one or more of the subject's olfactory cortex, piriform cortex, and olfactory bulb to recreate a sense of one or more of predetermined odors or variations of one or more of the predetermined odors. The transcranial neurorecording sensor arrangement2104is configured to transcranially sense and record local magnetic fields emanating from one or more of the subject's olfactory cortex, piriform cortex, and olfactory bulb caused by delivery of the transcranial stimulation.

FIGS.23and24illustrate a system2300a,2300bconfigured to transcranially record neural activity, process recorded neural activity data using processor-implemented algorithms and/or machine learning, and transcranially stimulate a subject's brain using the processed recorded neural activity data in accordance with various embodiments. The system2300ais configured as a relatively fast, but lower fidelity, system. The system2300bis configured as a relatively slow, but higher fidelity, system. Each of the systems2300a,2300bcan be configured to provide open-loop transcranial stimulation of a subject's brain or closed-loop transcranial stimulation/neurorecording of a subject's brain.

Many of the components of systems2300aand2300bare largely the same or similar, and largely have the same or similar functionality. However, system2300aincludes a faster, but lower fidelity, neurorecording sensor arrangement2302in the form of an array of magnetic sensors (e.g., NV-diamond or OPM sensors) and/or an EEG sensor arrangement. In the closed-loop implementation2320of system2300a, the neurorecording sensor2302can be the same sensor as that used in the neurorecording sensor arrangement2302.

The system2300bincludes a slower, but higher fidelity, neurorecording sensor arrangement2402in the form of an MRI sensor or an fMRI sensor. In the closed-loop implementation2320of system2300b, the neurorecording sensor2324is typically a different sensor from that used in the neurorecording sensor arrangement2402, such as an MEG sensor.

The systems2300a,2300bcan be configured to transcranially record neural activity in one or more of a sensing organ or organs, a vestibular system, and a memory of the subject's brain while exposing the subject to stimuli. In addition, the systems2300a,2300bcan be configured to transcranially stimulate, using previously recorded neural activity data, one or more of a sensing organ or organs, a vestibular system, and a memory of the subject. The transcranial stimulation can be used to recreate a response (and/or a variation of the response) of one or more of the sensing organ or sensing organs, the vestibular method, and the memory of the subject stimulated by the stimuli during the transcranial neurorecording process. The transcranial stimulation can also be used to convey and/or elicit abstract data (e.g., an order from a commanding officer, a memory) without use or stimulation of the subject's vision/ocular system.

The systems2300a,2300binclude a neurorecording sensor arrangement2302,2402of a type previously described. During a training phase, the subject is exposed to stimuli to stimulate one or more of a sensing organ or organs, a vestibular system, and a memory of the subject. For example, the subject can be exposed to one or more predetermined odors to stimulate the olfactory system of the subject. While the subject is exposed to the stimuli, the neurorecording sensor arrangement2302,2402is configured to record neurostimulation data representative of patterns of stimulation of the specified region or regions of the subject's brain in response to the stimuli. For example, the neurorecording sensor arrangement2302,2402can be configured to record neurostimulation data representative of patterns of stimulation of the subject's olfactory system including one or more of the subject's olfactory cortex, piriform cortex, and olfactory bulb in response to the subject smelling one or more predetermined odors.

A controller2304(shown as a computer system including a desktop PC comprising one or more processors operatively coupled to an optional display) is configured to operate on the data produced by the neurorecording sensor arrangement2302,2402by algorithmically determining, via machine learning, a spatiotemporal pattern needed to recreate the response (and/or a variation of the response) of one or more of the sensing organ or sensing organs, the vestibular method, and the memory of the subject stimulated by the stimuli. As previously discussed, various machine learning tools can be implemented by the controller2304, alone or in cooperation with another controller or processor, including one or more of neural networks, convolutional neural networks (CNNs), and generative adversarial networks (GANs). The controller2304generates a multiplicity of spatiotemporal patterns associated with the subject's response to a corresponding multiplicity of stimuli. The spatiotemporal patterns are stored in an electronic memory of, or operatively coupled to, the controller2304.

In an open-loop implementation2310and a closed-loop implementation2320of systems2300aand2300b, one or more selected spatiotemporal patterns stored in the memory of the controller2304are communicated to a transcranial stimulation arrangement2312(e.g., a focused ultrasound array). The transcranial stimulation arrangement2312delivers focused ultrasound to a specified region or regions of the brain to recreate a response (and/or a variation of the response) of one or more of the sensing organ or sensing organs, the vestibular method, and the memory of the subject stimulated by the stimuli associated with the one or more selected spatiotemporal patterns. In addition, or alternatively, the transcranial stimulation arrangement2312can deliver focused ultrasound to a specified region or regions of the brain to convey and/or illicit abstract data.

In the closed-loop implementation2320, the neurorecording sensor arrangement2302,2324is used to transcranially sense contemporaneous stimulation data and generate neural activity data during concurrent stimulation of the specified region or regions of the subject's brain via the transcranial stimulation arrangement2322. The contemporaneous stimulation data acquired or produced by the neurorecording sensor arrangement2302,2324can be used by the controller2304refine the spatiotemporal patterns needed to recreate the response of one or more of the sensing organ or sensing organs, the vestibular method, and the memory of the subject stimulated by the stimuli. This contemporaneous stimulation data can also be used to alter the spatiotemporal patterns to recreate a variation of the response of one or more of the sensing organ or sensing organs, the vestibular method, and the memory of the subject stimulated by the stimuli.

For example, the controller2304can be configured to produce a spatiotemporal pattern representative of the subject's olfactory response to a particular perfume. The controller2304can be further configured to produce a variant spatiotemporal pattern to recreate a variation of the subject's olfactory response to the particular perfume. As such, the subject believes that he or she is smelling a variation of the particular perfume, which can facilitate the rapid development of new and pleasing perfumes at a substantially reduces cost. Machine learning can be used to tailor the specific stimulation protocols for each subject, based on their physiology and prior training experiences. The closed-loop implementation2320improves stimulation in real-time by ensuring that the subject's olfactory system is activated in the same manner as if the subject user had a conventional olfactory experience by directly smelling the perfume.

The systems2300a,2300billustrated inFIGS.23and24advantageously provide for a completely non-invasive (e.g., non-ionizing, non-destructive) high-resolution stimulation technique accompanied by imaging (varying fidelity) to create closed-loop transcranial recording of neural activity from specified sites of a subject's brain, recreation of a response by one or more of a sensing organ or sensing organs, a vestibular system, and a memory of the subject via transcranial focused ultrasound, and a means to convey abstract data. The systems2300a,2300billustrated inFIGS.23and24advantageously provide for an enhanced HMI (Human Machine Interface), faster skill training, selective memory recollection, enhanced realistic experience, recreating personalized sensory (e.g., olfactory) experience, and ‘recording’ and ‘recreating’ sensed experiences without the need of physical stimuli (e.g., recreating smells without the need of chemicals). The systems2300a,2300billustrated inFIGS.23and24advantageously provide for integrated headgear to augment a virtual reality experience with recreated sensor experience.

FIG.25Aillustrates a method that can be implemented by the systems2300a,2300bshown inFIGS.23and24in accordance with various embodiments. The method shown inFIG.25Ainvolves situating2502a neurorecording sensor arrangement relative to a subject's head. The method involves exposing2504the subject to stimuli to stimulate one or more of a sensing organ or organs, of the stimulus system, and a memory of the subject. The method also involves associating2506the stimuli with a training objective or objectives, such as retaining/recalling a thought, an abstract idea, and memory, performing an action, or learning a new skill. The method further involves performing2508, using the neurorecording sensor arrangement, transcranial sensing of specified region or regions of the subject's brain in response to the stimuli and associated training objective(s). The method also involves recording2510neurostimulation data generated by the neurorecording sensor arrangement. The recorded data is representative of patterns of stimulation of the specified region or regions of the subject's brain in response to the stimuli and associated training objective(s).

FIG.25Billustrates a method that can be implemented by the systems2300a,2300bshown inFIGS.23and24in accordance with various embodiments. The method shown inFIG.25Binvolves situating250a neurorecording sensor arrangement relative to a subject's head. The method involves exposing2522the subject to one or more predetermined odors. The method also involves associating2524the one or more predetermined odors with one or more training objectives (e.g., see examples above). The method further involves performing2526, using the neurorecording sensor arrangement, transcranial sensing of a specified region or regions of the subject's olfactory system in response to the predetermined odor(s) and associated training objective(s). The method also involves recording2528olfactory neurostimulation data generated by the neurorecording sensor arrangement. The recorded data is representative of patterns of olfactory system stimulation in response to the predetermined odor(s) and associated training objective(s).

FIG.26Aillustrates a method that can be implemented by the systems2300a,2300bshown inFIGS.23and24in accordance with various embodiments. The method shown inFIG.26Ainvolves situating2602an array of ultrasound transducers relative to a subject's head. The method also involves selecting2604, from an electronic memory, pre-recorded neurostimulation data developed to recreate a response by one or more of a sensing organ or organs, a vestibular system, and a memory of the subject and a trained objective or objectives associated with the response. The method further involves delivering2606, using the array of ultrasound transducers and the pre-recorded neurostimulation data, transcranial stimulation to a specified region or regions of the subject's brain to recreate the response by the subject's one or more sensing organ or organs, vestibular system, and memory of the subject.

FIG.26Billustrates a method that can be implemented by the systems2300a,2300bshown inFIGS.23and24in accordance with various embodiments. The method shown inFIG.26Binvolves situating2620an array of ultrasound transducers relative to a subject's head. The method also involves selecting2622, from an electronic memory, pre-recorded olfactory neurostimulation data developed to recreate a response to one or more predetermined odors and one or more trained objectives associated with the one or more predetermined odors. The method further involves delivering2622, using the array of ultrasound transducers and the pre-recorded olfactory neurostimulation data, transcranial stimulation to the subject's olfactory system to recreate the one or more predetermined odors and cause the subject to initiate the one or more associated trained objectives.

It is understood that the controllers and processors shown in the figures can include or be operatively coupled to a main memory and a non-volatile memory. The controllers and processors can be implemented as one or more of a multi-core processor, a digital signal processor (DSP), a microprocessor, a programmable controller, a general-purpose computer, a special-purpose computer, a hardware controller, a software controller, a combined hardware and software device, such as a programmable logic controller, and a programmable logic device (e.g., FPGA, ASIC). The controllers and processors can include or be operatively coupled to main memory, such as RAM (e.g., DRAM, SRAM). The controllers and processors can include or be operatively coupled to non-volatile memory, such as ROM, EPROM, EEPROM or flash memory.

Although reference is made herein to the accompanying set of drawings that form part of this disclosure, one of at least ordinary skill in the art will appreciate that various adaptations and modifications of the embodiments described herein are within, or do not depart from, the scope of this disclosure. For example, aspects of the embodiments described herein may be combined in a variety of ways with each other. Therefore, it is to be understood that, within the scope of the appended claims, the claimed invention may be practiced other than as explicitly described herein.

All references and publications cited herein are expressly incorporated herein by reference in their entirety into this disclosure, except to the extent they may directly contradict this disclosure. Unless otherwise indicated, all numbers expressing feature sizes, amounts, and physical properties used in the specification and claims may be understood as being modified either by the term “exactly” or “about.” Accordingly, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached claims are approximations that can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings disclosed herein or, for example, within typical ranges of experimental error.

The recitation of numerical ranges by endpoints includes all numbers subsumed within that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5) and any range within that range. Herein, the terms “up to” or “no greater than” a number (e.g., up to 50) includes the number (e.g., 50), and the term “no less than” a number (e.g., no less than 5) includes the number (e.g., 5).

The terms “coupled” or “connected” refer to elements being attached to each other either directly (in direct contact with each other) or indirectly (having one or more elements between and attaching the two elements). Either term may be modified by “operatively” and “operably,” which may be used interchangeably, to describe that the coupling or connection is configured to allow the components to interact to carry out at least some functionality (for example, a radio chip may be operably coupled to an antenna element to provide a radio frequency electric signal for wireless communication).

Terms related to orientation, such as “top,” “bottom,” “side,” and “end,” are used to describe relative positions of components and are not meant to limit the orientation of the embodiments contemplated. For example, an embodiment described as having a “top” and “bottom” also encompasses embodiments thereof rotated in various directions unless the content clearly dictates otherwise.

Reference to “one embodiment,” “an embodiment,” “certain embodiments,” or “some embodiments,” etc., means that a particular feature, configuration, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of the disclosure. Thus, the appearances of such phrases in various places throughout are not necessarily referring to the same embodiment of the disclosure. Furthermore, the particular features, configurations, compositions, or characteristics may be combined in any suitable manner in one or more embodiments.

The words “preferred” and “preferably” refer to embodiments of the disclosure that may afford certain benefits, under certain circumstances. However, other embodiments may also be preferred, under the same or other circumstances. Furthermore, the recitation of one or more preferred embodiments does not imply that other embodiments are not useful and is not intended to exclude other embodiments from the scope of the disclosure.

As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” encompass embodiments having plural referents, unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and/or” unless the content clearly dictates otherwise.

As used herein, “have,” “having,” “include,” “including,” “comprise,” “comprising” or the like are used in their open-ended sense, and generally mean “including, but not limited to.” It will be understood that “consisting essentially of” “consisting of,” and the like are subsumed in “comprising,” and the like. The term “and/or” means one or all of the listed elements or a combination of at least two of the listed elements.

The phrases “at least one of,” “comprises at least one of,” and “one or more of” followed by a list refers to any one of the items in the list and any combination of two or more items in the list.