阅读说明：本技术 瞄准的可操纵经颅干预以加速记忆巩固 (Targeted steerable transcranial intervention to accelerate memory consolidation ) 是由 M·D·霍华德 P·K·皮利 于 2018-05-25 设计创作，主要内容包括：描述了一种使用可操纵的经颅干预来加速记忆巩固的系统。在操作期间,所述系统生成独特的经颅且可操纵的刺激标记,以与任务或事件的记忆相关联。一旦生成了所述标记,在要巩固的事件或任务发生期间,所述系统就激活多个电极(例如,少至四个)以施加所述独特的经颅刺激标记。(A system for accelerating memory consolidation using steerable transcranial intervention is described. During operation, the system generates unique transcranial and manipulable stimulation markers to correlate with the memory of the task or event. Once the markers are generated, the system activates multiple electrodes (e.g., as few as four) to apply the unique transcranial stimulation markers during the event or task to be consolidated.)

1. A system for steerable transcranial intervention to accelerate memory consolidation, the system comprising:

one or more processors and memory, the memory being a non-transitory computer-readable medium encoded with executable instructions such that, when executed, the one or more processors perform the following:

generating a unique transcranial and manipulable stimulation marker to correlate with a memory of a task or event; and

activating at least a plurality of electrodes to apply the unique transcranial stimulation marker during the occurrence of the event or task to be consolidated.

2. The system of claim 1 wherein the unique transcranial and manipulable stimulation marker is a targeted, localized, transcranially applied pattern of electrical stimulation in a three-dimensional region of the brain with at least four electrodes during the occurrence of the event or task to be consolidated.

3. The system of claim 1, wherein a unique transcranial and steerable stimulation marker is generated for each memory to be consolidated.

4. The system of claim 1, wherein the unique transcranial and manipulable stimulation marker activated during the occurrence of the event or task to be consolidated is activated during a positive phase of slow wave oscillations during non-REM sleep of a subject.

5. The system of claim 1, wherein each unique transcranial stimulation marker is generated according to a change in a stimulation pattern that includes a three-dimensional starting location of stimulation, frequency, intensity, and a temporal trajectory through the subject's brain that changes frequency, intensity, and location as a function of time.

6. The system of claim 1, wherein the duration of the task or event to be consolidated is pre-estimated, and the generated unique transcranial and steerable stimulation indicia is clipped if the actual task or event is shorter than the estimated task or event, or repeated if the actual task or event is longer than the estimated task or event.

7. The system of claim 1, wherein the rate at which the trajectory of the unique transcranial and manipulable stimulation marker traverses the brain can increase at least ten times during sleep application.

8. The system of claim 1, wherein, in activating the plurality of electrodes, includes activating at least four electrodes to apply the unique transcranial and steerable stimulation marker, and in doing so, the area of stimulation changes during application of the electrical stimulation.

9. A computer program product for steerable transcranial intervention to accelerate memory consolidation, the computer program product comprising:

a non-transitory computer-readable medium encoded with executable instructions such that, when the instructions are executed by one or more processors, the one or more processors perform the following:

generating a unique transcranial and manipulable stimulation marker to correlate with a memory of a task or event; and

activating at least a plurality of electrodes to apply the unique transcranial stimulation marker during the occurrence of the event or task to be consolidated.

10. The computer program product of claim 9 wherein the unique transcranial and manipulable stimulation marker is a targeted, localized, transcranially applied pattern of electrical stimulation in a three-dimensional region of the brain with at least four electrodes during the occurrence of the event or task to be consolidated.

11. The computer program product of claim 9, wherein a unique transcranial and manipulable stimulation marker is generated for each memory to be consolidated.

12. The computer program product of claim 9, wherein the unique transcranial and manipulable stimulation marker activated during the occurrence of the event or task to be consolidated is activated during a positive phase of slow wave oscillation during non-REM sleep of a subject.

13. The computer program product of claim 9, wherein each unique transcranial stimulation marker is generated according to a change in stimulation pattern, the stimulation pattern including a three-dimensional starting location of stimulation, frequency, intensity, and a temporal trajectory through the subject's brain that changes frequency, intensity, and location as a function of time.

14. The computer program product of claim 9, wherein the duration of the task or event to be consolidated is pre-estimated, and the generated unique transcranial and steerable stimulation indicia is clipped if the actual task or event is shorter than the estimated task or event, or repeated if the actual task or event is longer than the estimated task or event.

15. The computer program product of claim 9, wherein the rate at which the trajectory of the unique transcranial and manipulable stimulation marker traverses the brain can increase at least ten times during sleep application.

16. The computer program product of claim 9, wherein activating the plurality of electrodes includes activating at least four electrodes to apply the unique transcranial and steerable stimulation marker, and in doing so, the area of stimulation changes during application of the electrical stimulation.

17. A computer-implemented method for steerable transcranial intervention to accelerate memory consolidation, the computer-implemented method comprising the acts of:

causing one or more processors to execute instructions encoded on a non-transitory computer-readable medium such that, when executed, the one or more processors perform the following:

generating a unique transcranial and manipulable stimulation marker to correlate with a memory of a task or event;

activating at least a plurality of electrodes to apply the unique transcranial stimulation marker during the occurrence of the event or task to be consolidated.

18. The method of claim 17 wherein said unique transcranial and manipulable stimulation marker is a targeted, localized, transcranially applied pattern of electrical stimulation in a three-dimensional region of the brain with at least four electrodes during the occurrence of said event or task to be consolidated.

19. The method of claim 17, wherein a unique transcranial and steerable stimulation marker is generated for each memory to be consolidated.

20. The method of claim 17, wherein the unique transcranial and manipulable stimulation marker activated during the occurrence of the event or task to be consolidated is activated during a positive phase of slow wave oscillations during non-REM sleep of a subject.

21. The method of claim 17, wherein each unique transcranial stimulation marker is generated according to a change in stimulation pattern, the stimulation pattern including a three-dimensional starting location of stimulation, frequency, intensity, and a temporal trajectory through the subject's brain that changes frequency, intensity, and location as a function of time.

22. The method of claim 17, wherein the duration of the task or event to be consolidated is pre-estimated, and the generated unique transcranial and steerable stimulation indicia is clipped if the actual task or event is shorter than the estimated task or event, or repeated if the actual task or event is longer than the estimated task or event.

23. The method of claim 17 wherein the rate at which the trajectory of the unique transcranial and manipulable stimulation marker traverses the brain can increase at least ten times during sleep application.

24. The method of claim 17, wherein activating the plurality of electrodes includes activating at least four electrodes to apply the unique transcranial steerable stimulation marker, and in doing so, the area of stimulation is changed during application of the electrical stimulation.

Technical Field

The present invention relates to brain stimulation systems, and more particularly, to systems for targeted and steerable transcranial intervention to accelerate memory consolidation.

Background

In operational tasks (as in many business and educational scenarios), it is vital that information be quickly integrated and accurately recalled based on limited contact with the information. To assist with this need, some prior art stimulation systems have been developed to promote memory consolidation. Such stimulation systems are based on the widely supported idea that when a person sleeps, the memory system "replays" the memory, which means that it is recalled from short-term hippocampal memory and transmitted to the slower-learning cortical structures, where it slowly integrates, without loss, into long-term memory storage. Although any memory in the hippocampus may be replayed during sleep, there is a greater probability of replaying a particular memory if it is recently learned and is associated with certain emotional content or high immediate returns. Unfortunately, many things that a person needs to learn are boring or boring, and the return for learning such things can be a long way to go.

One prior art technique applies a unique high-definition transcranial current stimulation (HD-tCS) clip (montage), i.e., a spatiotemporal amplitude modulation pattern (STAMP) of current, including intrinsic rhythms, applied across the scalp during a unique experience or skill learning period to "flag" the unique experience or skill by causing the STAMP to become associated with the unique experience or skill in short-term memory. Then, during quiet wakeful or slow wave sleep (especially during cortical UP states), the same STAMP flag is later applied offline to prompt the specific memory associated with that STAMP flag for replay, thereby consolidating in long-term memory. The STAMP method has the advantage of not degrading task performance or distracting the learning of the task, unlike other methods that use audio or olfactory associated with memory to mark the memory and later prompt playback of the memory. Unfortunately, the STAMP method may require that many (e.g., at least 64) and possibly up to 256 electrodes must be applied to the scalp of a subject in order to make possible a variety of unique STAMP patterns. Each electrode must be in good contact with the scalp and therefore one electrode at a time should be applied and tested to ensure that the electrical characteristics match each other electrode (see description of the process of applying such electrodes in reference No.2 of the list of references incorporated). This process is lengthy and tedious, often requiring a professional who can test and adjust each electrode. Furthermore, the life of the electrodes is limited, so it is recommended to keep a record of use and replace the old electrodes. In addition, the high-density electrodes must be coated with gel, which is troublesome; sponge electrodes that can be applied on their own by laymen have a large footprint and cannot be arranged closely. If this memory consolidation method can be made easier to apply, it can be used regularly by a business in a meeting, a patrolling or training soldier, or a student in a daily class. However, to convert this technology into a widely accepted and adopted product that will be used by a wider family of non-professionals, even outside the clinical setting, it is crucial to reduce the number of electrodes to at least six, which will reduce time and trouble by a factor. Another disadvantage of the prior art is: in order to create the same STAMP pattern when learning a particular memory, and then recreate the same pattern every night later to consolidate during sleep, all the large volume electrodes must be applied exactly at the same location and with exactly the same conductivity characteristics.

Thus, there is a continuing need for a transcranial stimulation system that requires only a desired small number of electrodes (e.g., as few as four) during task acquisition while awake and during operation to create a marker or STAMP to be associated with memory, which is a localized and steerable 3D stimulation region that may be deep below the cortical surface.

Disclosure of Invention

The present disclosure provides a system for steerable transcranial intervention to accelerate memory consolidation. In various embodiments, the system includes one or more processors and memory. The memory is a non-transitory computer-readable medium encoded with executable instructions such that, upon execution of the instructions, the one or more processors perform operations such as generating unique transcranial and steerable stimulation markers to associate with a task or event's memory; and activating at least a plurality of the electrodes to apply a unique transcranial stimulation signature during the occurrence of the event or task to be consolidated.

In another aspect, the unique transcranial and manipulable stimulation marker is a targeted, localized, transcranially applied pattern of electrical stimulation in a three-dimensional region of the brain with at least four electrodes during an event or task to be consolidated.

In yet another aspect, unique transcranial and steerable stimulation markers are generated for each memory to be consolidated.

In yet another aspect, the unique transcranial and manipulable stimulation marker activated during the occurrence of the event or task to be consolidated is activated during the positive phase of slow wave oscillations during non-REM sleep of the subject to stimulate replay of the memory and prompt consolidation of the memory to long-term memory.

In another aspect, each unique transcranial stimulation marker is generated from a change in a stimulation pattern that includes a three-dimensional starting location of stimulation, frequency, intensity, and a temporal trajectory through the subject's brain that changes frequency, intensity, and location as a function of time.

In another aspect, the duration of the task or event to be consolidated is estimated in advance, and the generated unique transcranial and steerable stimulation indicia is clipped if the actual task or event is shorter than the estimated task or event, or repeated if the actual task or event is longer than the estimated task or event.

In yet another aspect, the rate of trajectory of the unique transcranial and manipulable stimulation marker may be increased at least ten times during sleep application to increase the efficacy of induced memory reactivation, since sleep replay is known to be temporally compressed relative to brain dynamics while awake.

In another aspect, activating the plurality of electrodes includes activating at least four electrodes to apply the unique transcranial and steerable stimulation marker, and in so doing, the area of stimulation changes during application of the electrical stimulation.

Finally, the invention also includes a computer program product and a computer implemented method. The computer program product includes computer-readable instructions stored on a non-transitory computer-readable medium that are executable by a computer having one or more processors such that, when the instructions are executed, the one or more processors perform the operations listed herein. Alternatively, the computer-implemented method includes acts of causing a computer to execute such instructions and perform the resulting operations.

Drawings

The objects, features and advantages of the present invention are apparent from the following detailed description of the various aspects of the invention, taken in conjunction with the accompanying drawings, in which:

FIG. 1 is a block diagram depicting components of a system in accordance with various embodiments of the present invention;

FIG. 2 is an exemplary diagram of a computer program product embodying an aspect of the present invention;

FIG. 3 is an illustration of two operational stages, awake and sleep;

FIG. 4 is an illustration of a steerable STAMP mode;

FIG. 5 is an exemplary illustration of a pattern of moving a stimulated sphere region (sphere) up or down in a linear motion, but changing the size of the stimulation region and possibly other parameters;

fig. 6 is an exemplary illustration of a steerable STAMP mode in which a stimulated sphere region may be moved in a non-linear trajectory that may be used across the prefrontal area of the brain;

FIG. 7 is a block diagram depicting control of an apparatus according to various embodiments; and

FIG. 8 is an illustration of a hood according to various embodiments of the present invention.

Detailed Description

The present invention relates to brain stimulation systems, and more particularly, to systems for targeted and steerable transcranial intervention to accelerate memory consolidation. The following description is presented to enable any person skilled in the art to make and use the invention and is incorporated in the context of a particular application. Various modifications and applications of the aspects will be apparent to those skilled in the art, and the generic principles defined herein may be applied to a wide range of aspects. Thus, the present invention is not intended to be limited to the aspects shown, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

In the following detailed description, numerous specific details are set forth in order to provide a more thorough understanding of the present invention. However, it will be apparent to one skilled in the art that the present invention may be practiced without limitation to these specific details. In other instances, well-known structures and devices are shown in block diagram form, rather than in detail, in order to avoid obscuring the present invention.

The reader's attention is directed to all papers and documents which are filed concurrently with this specification and which are open to public inspection with this specification, and the contents of all such papers and documents are incorporated herein by reference. All functions disclosed in this specification (including any accompanying claims, abstract, and drawings) may be replaced by alternative features serving the same, equivalent or similar purpose, unless expressly stated otherwise. Thus, unless expressly stated otherwise, each feature disclosed is one example only of a generic series of equivalent or similar features.

Moreover, any element in the claims that does not explicitly recite "a means for performing a specified function" or "a step for performing a particular function" is not to be construed as an "means" or "a step" clause as specified in section 6 of 35 u.s.c.112. In particular, the use of "step …" or "action … …" in the claims herein is not intended to refer to the provisions of section 6 of 35 u.s.c.112.

Before describing the present invention in detail, a list of incorporated references is first provided. Next, a description is provided of various main aspects of the present invention. The reader is then directed to provide a general understanding of the invention. Finally, specific details of various embodiments of the invention are provided to gain an understanding of the specific aspects.

(1) List of references

The following references are cited throughout this application. For clarity and convenience, these references are listed herein as the central resource of the reader. The following references are incorporated by reference as if fully set forth herein. These references are incorporated by reference into this application as follows:

1.Nir Grossman,David Bono,Nina Dedic,Suhasa B.Kodandaramaiah,Andrii Rudenko,Ho-Jun Suk,Antonino M.Cassara,Esra Neufeld,Niels Kuster,Li-Huei Tsai,Alvaro Pascual-Leone,Edward S.Boyden(2017).Noninvasive Deep Brain Stimulation via Temporally Interfering Electric Fields.Cell 169,1029–1041June 1,2017。

2.Woods et al.(2016).A technical guide to tDCS,and related non-invasive brain stimulation tools.Clinical Neurophysiology,127:1031-1048。

3.Santostasi,Giovanni,et al."Phase-locked loop for precisely timed acoustic stimulation during sleep."Journal of neuroscience methods 259(2016):101-114。

4.Liu,Hechen,and Markus Schneider."Similarity measurement of moving object trajectories."Proceedings of the third ACM SIGSPATIAL internationalworkshop on geostreaming.ACM,2012。

https://www.cise.ufl.edu/～mschneid/Research/papers/LS12IWGS.pdf

(2) main aspects of the invention

Various embodiments of the present invention include three "primary" aspects. The first main aspect is a system for performing transcranial stimulation. The system typically takes the form of computer system operating software or in the form of a "hard coded" instruction set and may include all of the electrodes and/or sensors as may be required in accordance with the present disclosure. The system may be incorporated into a wide variety of devices that provide different functions. The second main aspect is a method, usually in the form of software, which operates with a data processing system (computer). A third main aspect is a computer program product. The computer program product generally represents computer readable instructions stored on a non-transitory computer readable medium such as an optical storage device (e.g., a Compact Disc (CD) or a Digital Versatile Disc (DVD)) or a magnetic storage device (e.g., a floppy disk or a magnetic tape). Other non-limiting examples of computer readable media include: hard disks, Read Only Memories (ROMs), and flash memory type memories. These aspects will be described in more detail below.

A block diagram depicting an example of the system of the present invention (i.e., computer system 100) is provided in fig. 1. The computer system 100 is configured to perform calculations, processes, operations, and/or functions associated with a program or algorithm. In one aspect, certain processes and steps discussed herein are implemented as a series of instructions (e.g., a software program) residing in a computer readable memory unit and executed by one or more processors of the computer system 100. The instructions, when executed, cause the computer system 100 to perform particular actions and exhibit particular behaviors, as described herein.

Computer system 100 may include an address/data bus 102 configured to communicate information. In addition, one or more data processing units, such as a processor 104 (or multiple processors), are coupled to the address/data bus 102. The processor 104 is configured to process information and instructions. In an aspect, the processor 104 is a microprocessor. Alternatively, the processor 104 may be a different type of processor, such as a parallel processor, an Application Specific Integrated Circuit (ASIC), a Programmable Logic Array (PLA), a Complex Programmable Logic Device (CPLD), or a Field Programmable Gate Array (FPGA).

Computer system 100 is configured to utilize one or more data storage units. The computer system 100 may include a volatile memory unit 106 (e.g., random access memory ("RAM"), static RAM, dynamic RAM, etc.) coupled to the address/data bus 102, wherein the volatile memory unit 106 is configured to store information and instructions for the processor 104. The computer system 100 may also include a non-volatile memory unit 108 (e.g., read only memory ("ROM"), programmable ROM ("PROM"), erasable programmable ROM ("EPROM"), electrically erasable programmable ROM ("EEPROM"), flash memory, etc.) coupled to the address/data bus 102, wherein the non-volatile memory unit 108 is configured to store static information and instructions for the processor 104. Alternatively, the computer system 100 may execute instructions retrieved from an online data storage unit, such as in "cloud" computing. In an aspect, computer system 100 may also include one or more interfaces, such as interface 110, coupled to address/data bus 102. The one or more interfaces are configured to enable computer system 100 to connect with other electronic devices and computer systems. The communication interfaces implemented by the one or more interfaces may include wired (e.g., serial cable, modem, network adapter, etc.) and/or wireless (e.g., wireless modem, wireless network adapter, etc.) communication technologies.

In one aspect, computer system 100 may include an input device 112 coupled to address/data bus 102, wherein input device 112 is configured to communicate information and command selections to processor 100. According to one aspect, the input device 112 is an alphanumeric input device (e.g., a keyboard) that may include alphanumeric and/or function keys. Alternatively, the input device 112 may be other input devices besides alphanumeric input devices. In one aspect, the computer system 100 may include a cursor control device 114 coupled with the address/data bus 102, wherein the cursor control device 114 is configured to communicate user input information and/or command selections to the processor 100. In one aspect, cursor control device 114 is implemented with a device such as a mouse, a trackball, a trackpad, an optical tracking device, or a touch screen. Notwithstanding the foregoing, in one aspect, cursor control device 114 is directed and/or enabled via input from input device 112, for example, in response to using special keys and key sequence commands associated with input device 112. In an alternative aspect, cursor control device 114 is configured to be directed or guided by voice commands.

In one aspect, computer system 100 may also include one or more optional computer usable data storage devices, such as storage device 116 coupled to address/data bus 102. Storage device 116 is configured to store information and/or computer-executable instructions. In one aspect, storage device 116 is a storage device such as a magnetic or optical disk drive (e.g., hard disk drive ("HDD"), floppy disk, compact disk read only memory ("CD-ROM"), digital versatile disk ("DVD")). According to one aspect, a display device 118 is coupled with the address/data bus 102, wherein the display device 118 is configured to display video and/or graphics. In one aspect, display device 118 may include: a cathode ray tube ("CRT"), a liquid crystal display ("LCD"), a field emission display ("FED"), a plasma display, or any other display device suitable for displaying video and/or graphic images, as well as alphanumeric characters recognizable to a user.

Computer system 100 presented herein is an example computing environment in accordance with an aspect. However, a non-limiting example of computer system 100 is not strictly limited to being a computer system. For example, one aspect provides that computer system 100 represents a type of data processing analysis that may be used in accordance with various aspects described herein. Other computing systems may also be implemented. Indeed, the spirit and scope of the present technology is not limited to any single data processing environment. Thus, in one aspect, computer-executable instructions, such as program modules, executed by a computer are used to control or implement one or more operations of various aspects of the present technology. In one implementation, such program modules include routines, programs, objects, components, and/or data structures that are configured to perform particular tasks or implement particular abstract data types. In addition, one aspect provides for implementing one or more aspects of the technology by utilizing one or more distributed computing environments, where tasks are performed by remote processing devices that are linked through a communications network, for example, or where various program modules are located in both local and remote computer storage media including memory-storage devices.

An illustrative diagram of a computer program product (i.e., a storage device) embodying the present invention is depicted in FIG. 2. The computer program product is depicted as a floppy disk 200 or an optical disk 202 such as a CD or DVD. However, as previously mentioned, the computer program product generally represents computer readable instructions stored on any compatible non-transitory computer readable medium. The term "instructions," as used with respect to the present invention, generally indicates a set of operations to be performed on a computer, and may represent a fragment of an entire program or a single, separate software module. Non-limiting examples of "instructions" include computer program code (source or object code) and "hard-coded" electronic devices (i.e., computer operations encoded into a computer chip). The "instructions" are stored on any non-transitory computer readable medium, such as on a floppy disk, CD-ROM, and flash drive or in the memory of a computer. Regardless, the instructions are encoded on a non-transitory computer readable medium.

(3) Introduction to

The present disclosure provides a system and method for accelerating memory consolidation by applying targeted, localized, transcranial applied electrical stimulation patterns in a particular regime. In contrast to the prior art which describes a weak, widely distributed "high density" pattern of transcranial stimulation applied across the scalp with a large number of electrodes (e.g., at least 64, and as many as 256), the system of the present disclosure utilizes as few as four electrodes to apply stimulation to the focal region, thereby creating a highly localized stimulation region that can potentially be located deeper below the cortex and can move over time, thereby changing the intensity and size of the stimulated spot. It should be noted that although it is sufficient to describe as few as four electrodes, the invention is not so limited as it requires only a minimum number of electrodes to create a pattern of stimulation by interference patterns between multiple electrodes, each emitting an AC current at a possibly different frequency, where the current periods interact constructively or destructively. Thus, although a system employing four electrodes has been described and has proven to work (see reference No.1), the system may also be implemented, for example, with three electrodes, where areas are triangulated using triangulation.

In operational tasks (as in many business and educational scenarios), it is vital that information be quickly integrated and accurately recalled based on limited contact with the information. The object of the invention is to promote memory consolidation to make it possible. The present invention is based on the widely supported idea that when a person sleeps, the memory system "replays" the memory, which means that it is recalled from short-term hippocampal memory and transmitted to the slower-learning cortical structure, where it slowly integrates, without loss, into long-term memory storage. Although any memory in the hippocampus may be replayed during sleep, there is a greater probability of replaying a particular memory if it is recently learned and is associated with certain emotional content or high immediate returns.

One prior art (us application No.15/227,922 filed on 8/3/2016 (' 922 application), which is incorporated herein by reference) applies a unique HD-tCS clip, a spatiotemporal amplitude modulation pattern (STAMP) including an intrinsic rhythm of current applied across the scalp during a unique experience or skill learning period to "flag" the unique experience or skill by causing the STAMP to become associated with the unique experience or skill in short-term memory. Then, during quiet wakeful or slow wave sleep (especially during cortical UP states), the same STAMP flag is later applied offline to prompt the specific memory associated with that STAMP flag for replay, thereby consolidating in long-term memory. The advantage of the STAMP approach is that it does not degrade task performance or distract from learning the task, unlike other approaches that employ audio or olfactory associated with memory to mark the memory and later prompt playback of the memory. Unfortunately, the prior art requires that a large number of electrodes (e.g., 64 to 256 electrodes) must be applied to the scalp of a subject in order to make possible a wide variety of unique STAMP modes.

The system and method of the present disclosure improves upon the prior art (as taught in the' 922 application) by significantly reducing the number of electrodes required to double the time and effort involved in setting up and implementing the system. The reduction in the number of electrodes (e.g., only four) also makes the article more portable for mobile and field applications. Another advantage of the system of the present disclosure is that this new reduced electrode (e.g., four) technique does not place strict constraints on the electrode layout (as is the case with prior art devices) because the area of stimulation can be manipulated. This means that if the location at which the stimulus was first applied is calculated, it can be recreated at a later time regardless of where the several (e.g., four) electrodes are placed on the scalp. Compared to the prior art, the system of the present disclosure improves the use of as few as four electrodes to target the brain's focal region, as the intervention of the present system moves the position of the movable stimulation region during a certain time and changes the intensity of the intervention over time. The intervention may be spatially controlled to focus on or avoid the most task-related regions of the brain. I.e. if the task is of the type that has been found to strongly activate brain region a, the person skilled in the art can design a stimulation pattern to focus on brain regions other than a in order to avoid interfering with the normal functioning of brain region a. Thus, the system described herein not only targets a particular static location, but can be used to move the targeted location during the duration of an event to be remembered while also changing the intensity and size of the stimulation site, thereby associating the moving stimulation pattern with the memory, and then using the same pattern again during slow wave sleep to prompt recall of the memory, thereby facilitating consolidation of the memory.

The systems and methods may be implemented in products that provide a targeted and personalized closed loop system for enhancing memory in normal subjects as well as those subjects with learning difficulties related to memory consolidation. Interventions employing closed-loop high-density electroencephalography (HD-EEG) sensing and Focal-tACS (transcranial alternating current stimulation) stimulation may be incorporated into existing stimulation systems, such as those produced by neuroelectronics, sourix Medical, and/or EGI. Neuronectics is located at 210Broadway, Suite 201, Cambridge 02139, Massachusetts, USA. Soterix Medical is located at 237W 35th St, New York, NY 10001, and EGI (OR electric Geodesics, Inc.) is located at 500East 4th Ave., Suite 200, Eugene, OR 97401. An integrated brain monitoring and transcranial stimulation system would have wide applicability in research and rehabilitation relating to both commercial and military applications.

The products resulting from this work will enable people to enhance episodic memory and gain skills more quickly as they sleep. As an additional benefit, if the stimulation is applied in an oscillating manner at the same frequency and phase as the slow wave oscillations during sleep (as disclosed in U.S. provisional application No.62/570,669, which is incorporated herein by reference), the intervention will increase overall cognitive alertness by promoting longer periods of Slow Wave Sleep (SWS) (or deep sleep). The system of the present disclosure provides a number of advantages for a number of reasons and as will be apparent to those skilled in the art. The enhancement techniques and treatment procedures are safe and non-invasive; the system does not require medication or surgery. In the case of a subject-identified event, the system may be trained either before the event occurs or at some time after the event occurs (in which case the user turns on the system as clearly as possible to recall the event). In addition, the therapy targets specific memory, while other memory is not affected. Specific details are provided below.

(4) Details of various embodiments

The systems and methods described in this disclosure are designed to improve consolidation of specific memories (referred to herein as "events"). For further understanding, fig. 3 provides an illustration of two operational phases of the system, an awake intervention phase 301 for event coding and an offline intervention phase 303 for consolidation. The ideal implementation is that when the event 300 is first experienced (e.g., when the user is learning something new), he/she wears an intervention system that includes at least four steerable STAMP stimulation electrodes 302 (more electrodes can be employed to generate more complex patterns of more than one simultaneously steerable stimulation site). Steerable STAMP employs the latest prior art time-perturbation approach (see reference No.1, or any other suitable technique) that can target the stimulation area for transcranial application of alternating current stimulation (tACS) intervention without physically moving the electrodes by varying the respective frequencies of the AC currents delivered to a fixed set of electrodes. In other words, the area of stimulation is manipulated by varying the frequency and amplitude of the current delivered to the fixed set of electrodes 302.

With this capability, highly targeted and localized brain regions deep within the brain can be stimulated by electrical intervention. Intervention module 304 generates a unique steerable STAMP clip 306 that brain associates with the task or event when the brain encodes the STAMP clip through selectively activated electrodes 302. By varying the spatiotemporal trajectory of the region being stimulated (via the electrodes 302), varying the size of the region over time as it moves, and the power being stimulated over that time, an infinite number of patterns are possible.

A manipulable STAMP clip 306 is generated to become associated with an event to be remembered and is then used during slow wave sleep to prompt recall of the event's memory, thereby facilitating consolidation of the memory. The purpose of moving the stimulated region is to provide another dimension for creating a unique stimulation cue associated with memory, and also to allow the unique cue to focus on or avoid certain task-related brain regions (regions that are highly activated during memory to be consolidated).

For example, fig. 4 provides an illustration depicting an extreme example in which a stimulation site 400 moves rapidly around the brain 402 in a spiral pattern, changing in size as it moves. This is a manipulable STAMP marker, and the STAMP marker should be unique relative to any other marker used for different memories being learned. In this non-limiting example, a spherical stimulation region moves through the brain volume in a spiral trajectory that changes size over time according to a unique pattern determined as a basic idea of a steerable stimulation pattern.

Some other examples of steerable STAMP markers are depicted in fig. 5 and 6. Fig. 5 is an exemplary illustration of a pattern 500 of linear motion moving a stimulated sphere up or down but changing the size of the stimulation area and possibly other parameters. Fig. 6 is an example illustration of a steerable STAMP mode 600 in which a stimulated sphere may be moved across a non-linear trajectory directed across a brain region such as the prefrontal area (e.g., across the cortical region behind the forehead).

Once the event has been flagged in this manner, the flag used must be stored for later use during sleep to prompt consolidation of memory. Later, during sleep or quiet waking (i.e., during the offline intervention phase for consolidation 303), the user again wears the intervention system, but this time with an EEG array. The intervention system 304 monitors EEG data to detect stages of sleep and during the transcranial sensed positive ("UP") phase of Slow Wave Sleep (SWS), applies the same steerable STAMP flag to prompt the memory, and the clipping becomes a prompt that facilitates replay (some kind of recall) of the memory, speeding UP consolidation of the memory into long-term memory.

U.S. application No.15/947,733, which is incorporated herein by reference, discloses a method for sensing the UP phase of Slow Wave Oscillations (SWO) and applying transcranial stimulation in a closed loop. The steerable STAMP can be applied using similar techniques. Sleep intervention may be applied daily overnight until memory is consolidated. The degree of consolidation of memory is judged from the recall of the task execution or event within days or weeks after the task or event is encoded.

A unique signature must be generated for each memory to be consolidated. As mentioned above, the markers are localized tACS stimulation regions, and are generated from a unique temporal trajectory through the brain that changes intensity, velocity, spatial extent, and location over time. The duration must be limited to the expected length of the task or event to be consolidated (e.g., based on historical data of, for example, the subject or others performing such task or event). The flag may be generated for the estimated duration if the duration cannot be predicted in advance, clipped if the task is shorter than the estimated duration, or repeated if the task is longer than the estimated duration. If the duration of the event is extended, the trajectory may be reversed multiple times. The speed of movement is another parameter that can be varied. In either case, the marker used to consolidate memory during sleep must equal any clipped or extended markers used during waking. When the flag is used during sleep, the flag is applied in the UP phase, each UP phase lasting only 400 milliseconds to 1 second. The duration of the marked awake event is likely longer than the UP phase, there are two approaches: (1) accelerating the application of the mark thus takes less than 1 second to apply the mark; or (2) the flag is applied at the rate at which it is applied during wakefulness, so that the UP phase may be exceeded. Both options are acceptable and depending on the type of event learned, one or the other may achieve better results. However, during sleep, memory replay will typically be accelerated by a factor of 10 or more, so it may be preferable to increase the rate of manipulation of the stimulated region across the trajectory of the brain by a factor of 10 or more during the off-line intervention phase 303 for consolidation.

In associating a manipulable STAMP with the memory to be consolidated, the manipulable STAMP can be applied during the actual event to be remembered, or can be applied during the viewing of the event from a body camera playback event so that the user can learn of an unexpected event after it has occurred. If a camera view of an event is not available, the user may still sit still quiet after the event occurs and recall as much detail of the event as possible while the system marks the episode. The system needs to ascertain whether the dynamically generated steerable STAMP trace used to mark the new event is sufficiently unique given the library of previously used steerable STAMP traces. Uniqueness can be judged by maximizing the distance metric according to all parameters of the steerable STAMP; e.g. (time trajectory, time intensity, temporal spatial range), and these factors may be weighted. Preferred weights are [3, 1, 2] times the mentioned functional parameters. The trajectory or the distance between two vectors is a well-known process. For example, reference No.4 describes how two tracks are compared. The present invention may be combined with sensory cues (e.g., auditory or olfactory based targeted memory reactivation) and other forms of cues with electromagnetic and mechanical stimuli. For example, a particular sound may be combined with a haptic pattern on the manipulatable STAMP or a skill area (e.g., forearm or tongue). The present invention can be combined with closed-loop auditory stimulation during sleep (see reference No.3) to enhance the slow oscillations in order to provide a more window of opportunity to apply a steerable STAMP. The application of the steerable STAMP during sleep can be optimized and scheduled based on behavioral predictions of the personalized memory model to prioritize cues for weaker memory.

(5) And (4) controlling the device.

As shown in fig. 7, the processor 104 can be used to control a device 700 (e.g., an electrode array of multiple electrodes (e.g., four or more electrodes located on the scalp of a subject)) based on determining when to apply the steerable STAMP clip or the focused transcranial stimulation clip. Apparatus 500 is any suitable apparatus that may be used to provide a steerable focused transcranially-applied stimulation pattern to a subject, non-limiting examples of which include an array of electrical stimulation electrodes (e.g., the electrodes depicted as component 302 in fig. 3, and/or including a high resolution array employing a hood or separate application to the subject), magnetic fields, or ultrasound. Thus, in this example, the processor 104 activates the device 700 (electrode array (e.g., element 302 in fig. 3)) to provide transcranial stimulation to the subject based on the processes described herein. The apparatus 700 may also be an article that provides sensory cues (e.g., warnings for memory reactivation based on auditory or olfactory targeting) as well as other forms of cues with electromagnetic and mechanical stimuli.

Although not limited thereto, fig. 8 provides another example of an apparatus 700, wherein the apparatus 700 is a hood 1000 that includes one or both of: 1) a sensor 1002, the sensor 1002 detecting high resolution spatiotemporal neurophysiological activity (e.g., EEG data); and 2) a stimulation clipping component 1004 (i.e., electrodes) that can be used to direct current to a particular cortical sub-region in accordance with the processes described herein. While the electrodes are shown in fig. 3 as being applied separately to the subject, fig. 8 depicts another aspect of incorporating the electrodes into the headgear 1000. It should be understood that additional headgear (headgear) configurations may also be implemented so long as they include the sensor and/or stimulation component, additional non-limiting examples including inelastic headgear, mesh (e.g., hair or head net), straps, face shields, helmets or other headwear, and the like.

In some embodiments, the hood 1000 is formed of an elastic material containing a sensing component that records neurophysiologic activity (electroencephalogram (EEG)) via an electrical potential on the scalp and backscattered near infrared light (functional near infrared spectrum, FNIRS) that detects cortical blood flow. In some embodiments, there are desirably two sensors in the hood to delineate cortical activity at high spatiotemporal resolution, and the headgear has elasticity (compression fittings 1006) to secure sensitive recording components to ensure clean, artifact-free signal feed to the system (and provide consistency of sensors and stimulators). Stimulation component 1004 also resides in the same head shield 1000 device that includes multiple sets of surface electrodes (e.g., as few as four) that are precisely controlled to direct current through the scalp in accordance with the process described above. In some embodiments, these stimulation components 1004 maintain a consistent electrical environment (particularly impedance values) in order to provide proper stimulation throughout the cognitive enhancement process. The control software of the electrodes (i.e., the system as described herein) also enables modification of the injected current, as different effects on the neural tissue can be achieved with varying stimulation protocols. In the same way, in some embodiments, the head cover 1000 itself is configurable, that is, the head cover 1000 is configured such that all of the sensing and recording components are modularly configurable to enable recording from distinct areas of the scalp and to apply stimulation to a wide variety of brain structures. For example, the hood 1000 is depicted as having a plurality of configurable harness positions for housing the sensors 1002 and/or stimulators 1004. The sensor 1002 and stimulator 1004 may be formed and combined in a single harness for attachment to a harness location, or the sensor 1002 and stimulator 1004 may be attached separately. The sensor 1002 and stimulator 1004 may also be spring loaded to maintain sufficient contact with the skin of the wearer. For various embodiments, one, some, or all of these components are present in the hood 1000, and these features of the device are helpful for the application of transcranial stimulation for cognitive enhancement.

Finally, while the invention has been described in terms of several embodiments, those of ordinary skill in the art will readily recognize that the invention can have other applications in other environments. It should be noted that many embodiments and implementations are possible. Furthermore, the following claims are in no way intended to limit the scope of the present invention to the specific embodiments described above. Additionally, any statement that "means (means) for …" is intended to evoke a means and means-plus-function interpretation of the claims, and no specific use of any element that recites "means (means) for …" is intended to be interpreted as a means-plus-function element, even if the claims otherwise include the word "means (means)". Moreover, although specific method steps have been set forth in a particular order, these method steps may occur in any desired order and fall within the scope of the invention.