Transcranial magnetic stimulation implants and methods of use

Abstract

Systems and methods for transcranial magnetic stimulation in accordance with embodiments of the invention are illustrated. One embodiment includes a transcranial magnetic stimulation system, including at least one implant, where the at least one implant includes at least one solenoid, a communication circuitry, and a power source, and a controller communicatively coupled to the at least one implant via the communication circuitry, including a processor, and a memory containing a stimulation application that configures the processor to direct the at least one implant to deliver transcranial magnetic stimulation to a brain. In some embodiments, high permeability magnetic cores are implanted in the skull, and magnetic field generating circuitry are external to the skull. Techniques described herein can be utilized for TMS and / or pharmacological investigations.

Description

Transcranial Magnetic Stimulation Implants and Methods of UseCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] The current application claims the benefit of and priority under 35 U.S.C. § 119(e) to U.S. Provisional Patent Application No. 63 / 556,818 entitled “Transcranial Magnetic Stimulation Implants and Methods of Use” filed February 22, 2024 and U.S. Provisional Patent Application No. 63 / 571 ,960 titled “Miniaturized External TMS Magnets” filed March 29, 2024. The disclosure of U.S. Provisional Patent Application Nos. 63 / 556,818 and 63 / 571 ,960 are hereby incorporated by reference in their entirety for all purposes.FIELD OF THE INVENTION

[0002] The present invention generally relates to miniature, implantable transcranial magnetic stimulation coils and their applications.BACKGROUND

[0003] Transcranial magnetic stimulation (TMS) is a type of neurostimulation that involves application of pulsed, / .e., time-dependent magnetic fields to brain tissue. Conventionally, TMS is delivered via large coils positioned above a patient’s head such that the resulting magnetic field penetrates a desired target region in the patient’s brain. There are many different protocols for TMS that involve various temporal modulations and geometries of the magnetic field. TMS has been shown to be effective for the treatment of a wide variety of neurological conditions, including depression, pain management, and obsessive-compulsive disorder. The development of TMS-based treatments for many other diseases, disorders and conditions of the nervous system is ongoing.SUMMARY OF THE INVENTION

[0004] Systems and methods for transcranial magnetic stimulation in accordance with embodiments of the invention are illustrated. One embodiment includes a transcranial magnetic stimulation system, including at least one implant, where the at least oneimplant includes at least one solenoid, a communication circuitry, and a power source, and a controller communicatively coupled to the at least one implant via the communication circuitry, including a processor, and a memory containing a stimulation application that configures the processor to direct the at least one implant to deliver transcranial magnetic stimulation to a brain.

[0005] In a further embodiment, the at least one implant includes a mount configured to attach to an interior of a skull above a dura surrounding the brain, but below an external surface of the skull surrounding the brain.

[0006] In still another embodiment, the at least one solenoid includes a 2 mm to 5mm diameter conical iron powder core surrounded by a triple layer of 0.1 to 0.7 mm diameter copper wire.

[0007] In a still further embodiment, the at least one implant includes between 1 and 5 solenoids.

[0008] In yet another embodiment, the between 1 and 5 solenoids are positioned to focus a magnetic field at a target location.

[0009] In a yet further embodiment, to deliver the transcranial magnetic stimulation, the at least one implant is configured to discharge the at least one solenoid to induce a flyback electromagnetic field.

[0010] In another additional embodiment, the method further includes steps for a micro-optic enabling viewing of a brain stimulated by the transcranial magnetic stimulation.

[0011] In a further additional embodiment, the micro-optic is an image relay gradient index lens.

[0012] In another embodiment again, the micro-optic is a fiber optic.

[0013] In a further embodiment again, the at least one implant includes a biocompatible pouch.

[0014] One embodiment includes a transcranial magnetic stimulation system, including a high permeability magnetic cylinder configured to be implanted into the skull of a patient, and a magnetic field generator coupled to the high permeability magnetic cylinder, and positioned external to a skull of the patient, and configured to stimulate a brain of the patient by directing therapeutic magnetic stimulation into the brain via the highpermeability magnetic cylinder, and a controller communicatively coupled to the magnetic field generator, including a processor, and a memory containing a stimulation application that configures the processor to deliver the therapeutic magnetic stimulation in accordance with a protocol.

[0015] In still yet another embodiment, to deliver the therapeutic magnetic stimulation, the magnetic field generator is configured to discharge a capacitor to induce a flyback electromagnetic field channeled via the high permeability magnetic cylinder.

[0016] In a still yet further embodiment, the method further includes steps for a plurality of high permeability magnetic cylinders configured to be implanted into the skull of the patient.

[0017] One embodiment includes a transcranial magnetic stimulation system, including at least one solenoid, where the at least one solenoid includes a high magnetic permeability core having a diameter between 1 and 5 cm, wrapped in a triple layer of 0.1 to 0.7 mm diameter copper wire, and a power source, where the power source is configured to provide current to the at least one solenoid in order to produce a magnetic field capable of providing transcranial magnetic stimulation.

[0018] In still another additional embodiment, the power source is configured to discharge a capacitor to induce a flyback voltage that drives the provided current to the at least one solenoid.

[0019] In a still further additional embodiment, the method further includes steps for a mounting configured to position the at least one solenoid external to a skull of a patient.

[0020] In still another embodiment again, the method further includes steps for an image relay gradient index lens enabling viewing of a brain stimulated by the transcranial magnetic stimulation.

[0021] One embodiment includes a transcranial magnetic stimulation research system, including a brain of a subject includes genetically modified neurons that change their fluoresce when their membrane potential change, at least one transcranial magnetic stimulation device including a high permeability magnetic core implanted near the brain, and a micro-optic element that enables viewing or sensing the neurons’ fluorescence of the brain from outside the subject.

[0022] In a still further embodiment again, the high permeability magnetic core is a core of an implanted solenoid.

[0023] In yet another additional embodiment, the high permeability magnetic core is a cylinder implanted into a skull of the subject, wherein the core is further coupled to a magnetic field generator external to the skull of the subject.

[0024] In a yet further additional embodiment, the method further includes steps for an imaging device configured to image at least stimulated neurons through the micro-optic.

[0025] In yet another embodiment again, the micro-optic is a GRIN lens.

[0026] In a yet further embodiment again, the micro-optic is a fiber optic.

[0027] In another additional embodiment again, the method further includes steps for a device for administering a drug to the subject.

[0028] In a further additional embodiment again, the subject is a FosTRAP mouse.

[0029] In still yet another additional embodiment, the genetically modified neurons are modified to fluoresce in response to a biological parameter.

[0030] In a further embodiment, the biological parameter is cell voltage.

[0031] In still another embodiment, the biological parameter is calcium concentration.

[0032] One embodiment includes a transcranial magnetic stimulation device, including at least one solenoid includes a 2 mm to 3 mm diameter conical iron powder core surrounded by a triple layer of 0.1 to 0.7 mm diameter copper wire, a communication circuitry, and a power source.

[0033] One embodiment includes a transcranial magnetic stimulation device, including at least one solenoid includes a 1 cm to 5cm diameter conical iron powder core surrounded by a triple layer of 0.1 to 0.7 mm diameter copper wire, a communication circuitry, and a power source.

[0034] Additional embodiments and features are set forth in part in the description that follows, and in part will become apparent to those skilled in the art upon examination of the specification or may be learned by the practice of the invention. A further understanding of the nature and advantages of the present invention may be realized by reference to the remaining portions of the specification and the drawings, which forms a part of this disclosure.BRIEF DESCRIPTION OF THE DRAWINGS

[0035] The description and claims will be more fully understood with reference to the following figures and data graphs, which are presented as exemplary embodiments of the invention and should not be construed as a complete recitation of the scope of the invention.

[0036] FIG. 1 illustrates an implantable coil TMS system in accordance with an embodiment of the invention.

[0037] FIG. 2 illustrates an implantable HMPC TMS system in accordance with an embodiment of the invention.

[0038] FIG. 3 is a block diagram for a controller of an implantable TMS system in accordance with an embodiment of the invention.

[0039] FIG. 4A and 4B illustrate a TMS coil implant and an example magnetic field, respectively, in accordance with an embodiment of the invention.

[0040] FIG. 5A and 5B illustrate a dual TMS coil implant and example magnetic field, respectively, in accordance with an embodiment of the invention.

[0041] FIG. 6 illustrates a 5 TMS coil implant in accordance with an embodiment of the invention.

[0042] FIG. 7A and 7B illustrate a TMS coil implant with a viewing port and an example magnetic field, respectively, in accordance with an embodiment of the invention.

[0043] FIG. 8 illustrates a mount for an implantable TMS system in accordance with an embodiment of the invention.

[0044] FIG. 9 illustrates a TMS coil implant with an integrated lens in accordance with an embodiment of the invention.

[0045] FIG. 10 illustrates a TMS coil array implant with integrated lens in accordance with an embodiment of the invention.

[0046] FIG. 11 is an example circuit diagram for a driver circuitry for a TMS coil implant in accordance with an embodiment of the invention.

[0047] FIG. 12 is a flow chart for delivering TMS using TMS implants in accordance with an embodiment of the invention.DETAILED DESCRIPTION

[0048] Transcranial magnetic stimulation (TMS) is an attractive option for treatment of pain and neuropsychiatric conditions, as it is non-invasive, does not require pharmaceuticals, and has minimal observed side effects. However, a significant drawback to conventional forms of TMS is that it is delivered using large, expensive TMS coils that are typically only available in clinics and hospitals. This means that patients must return to (or stay at) these facilities on a regular basis for treatment which can be problematic for longer courses of treatment, or for treatments that need regular periodic re-applications. Notably, certain treatment regimens with TMS are prolonged, requiring many hours of treatment within the course of a single day, which often prevents patients from attending to their jobs or other daily activities. Further, conventional TMS coil geometries that are most suitable for stimulating deeper brain structures require high currents and generate large-volume magnetic fields. This has an unintentional effect of delivering stimulation to regions of the brain adjacent to the target region.

[0049] To address at least these shortcomings, miniature TMS magnets suitable for focused excitation of brain regions near the surface of the brain (e.g., just beneath the inner surface of the skull) are described. In numerous embodiments, TMS coil implants are designed to stimulate small regions of the brain or spinal cord using significantly less energy than conventional TMS, and consequently have significantly smaller magnetic field volumes while still being able to effectively stimulate neurons. The small volumes further allow for much more selective stimulation than conventional TMS coils. In numerous embodiments, implantation location is predetermined to produce a magnetic field that stimulates the desired target brain region. In various embodiments, the implantation location is below the skull, but above the dura. By leaving the dura intact during implantation, the incidence of infection and physical damage to the brain or spinal cord is significantly reduced.

[0050] In various embodiments, instead of implantation of a TMS coil, a small diameter cylinder of high magnetic permeability material (hereinafter “HMPC”) can be implanted into the skull over which a magnetic field generator is placed. The HMPC can be made of a high magnetic permeability material that concentrates the magnetic field in the brain region with the required spatial precision to stimulate the target anatomical structure inthe brain or spinal cord. TMS coil implants tend to be less than 5 mm in diameter, whereas the HMPC approach can, alternatively, utilize larger magnets located exterior to the body. A further advantage of the HMPC approach is that ohmic heating is removed from the tissue, and only hysteresis heating occurs proximate to tissue. Both types of implants are described and are collectively referred to as “stimulation devices”. Further, while cylinder geometries are primarily discussed, other high magnetic permeability shapes can be used depending on desired magnetic field geometries as appropriate to the requirements of specific applications of embodiments of the invention.

[0051] TMS coil implants as well as HMPCs can be used as an array. That is, multiple different TMS coil implants and / or HMPCs can be implanted and synchronized to provide more complex stimulation to multiple regions of the brain. In many embodiments, a controller external to the body is used to orchestrate the stimulation. In numerous embodiments, multiple different implants can be positioned to increase penetrative depth when acting together. The use of multiple coils further enables the direction of the magnetic and electric fields to be modified and / or differently oriented, resulting in additional selectivity during stimulation. In various embodiments, viewing ports can be built into the implantable TMS coils and / or HMPCs in order to enable viewing of brain response to TMS pulses.

[0052] Implantable TMS systems have a wide range of applications from medical treatment to clinical research. In various embodiments, drugs can be co-administered with specific TMS protocols that enhance the efficacy of the administered drug. Turning now to the drawings, implantable TMS systems and their components are discussed in further detail below, followed by a discussion of various use-cases.Implantable TMS Systems

[0053] Implantable TMS systems utilize implantable devices to provide TMS to a patient. In numerous embodiments, TMS coil implants are used. In some embodiments, high magnetic permeability HMPCs are implanted through the skull in concert with external magnetic field generators. Depending on the patient’s specific needs (i.e. stimulation target, tolerance for surgery, etc.), either or both types of implants can be used. Turning now to FIG. 1 , an implantable TMS system utilizing a TMS coil implant inaccordance with an embodiment of the invention is illustrated. System 100 includes a TMS coil implant 110, a controller 120, and a medical server 130. Controllers are communicatively coupled to the TMS coil implants and are configured to receive stimulation protocols and trigger the implant to deliver magnetic stimulation in accordance with the stimulation protocol. Medical servers can be any computing device that stores stimulation protocols. Medical servers can be used for any of a wide variety of computing tasks, and in some embodiments, controllers can be manually programmed by a medical professional. The controller 120, and the medical server 130 are communicatively coupled via a network 140. In many embodiments, the network is the Internet. In some embodiments, the network is a wired network, a wireless network, or a combination of one or more thereof.

[0054] Turning now to FIG. 2, an implantable TMS system utilizing a HMPC implant in accordance with an embodiment of the invention is illustrated. System 200 includes a high magnetic permeability HMPC 210 implanted into the skull of the patient. A magnetic field generator 212 is positioned over the HMPC to direct the generated field into the brain via the HMPC. In many embodiments, the magnetic field generator is anchored to the head. In some embodiments, the magnetic field generator is incorporated into a headband or wearable headgear (not shown) for cosmetic and / or placement purposes. The field generator 212 is communicatively coupled to the controller 220, which in turn is connected to a medical server 230 via a network 240. In many embodiments, the field generator is integrated with the controller on the same hardware platform instead of being two separate hardware components. As can be readily appreciated, implantable TMS systems can incorporate more than one implant and / or more than one type of implant. The single implant examples of FIGs. 1 and 2 are non-limiting and are for illustrative purposes only. Further, the specific position of the implants can be at any location required to deliver stimulation to an arbitrary target region, and the position of the implants shown in FIGs. 1 and 2 are for illustrative purposes only. It is further appreciated that medical servers are not needed in many embodiments, and indeed field generators and / or TMS coil implants may operate without input from a controller.

[0055] Turning now to FIG. 3, a block diagram for a controller in accordance with an embodiment of the invention is illustrated. Controller 300 includes a processor 310.Processors can be any logic processing circuitry including (but not limited to) a central processing unit (CPU), a graphics processing unit (GPU), an application specific integrated circuit (ASIC), a field programmable gate array (FPGA), and / or any other logic circuit or combination thereof as appropriate to the requirements of specific applications of embodiments of the invention. Controller 300 further includes a communications interface 320. The communications interface can communicate with external devices and / or the TMS coil implants and / or magnetic field generators via appropriate communications protocols. In some embodiments, the communications protocols are wired, wireless, or a combination thereof.

[0056] A memory 330 of the controller 300 stores a TMS application 332. TMS applications configure the processor to perform various processes including (but not limited to) driving TMS coil implants and / or magnetic field generators to perform stimulation in accordance with a given protocol. In many embodiments, stimulation protocol data can be stored in the memory which defines the manner in which the magnetic fields should be generated by the various stimulation devices. As can be readily appreciated, controllers can be manufactured which are hardwired to perform stimulation processes and may not require an application to store instructions that configure the controller. Indeed, many different system architectures can be utilized that utilize the advantages of stimulation devices contemplated herein without departing from the scope or spirit of the invention. Implants are discussed in additional detail below.Stimulation Devices

[0057] Stimulation devices as contemplated herein can be TMS coil implants, or implanted HMPCs paired with a magnetic field generator exterior to the body. As noted above, these two modalities provide similar but different advantages. TMS coil implants are entirely internally implanted, and therefore no input from the patient is required, and cosmetic issues are minimized. However, the size restrictions of the implanted TMS coil required to fit above the dura while maintaining safe operating temperature may impact the total depth of stimulation that is possible. In contrast, the HMPC utilizes an external magnetic field generator, which may be less desirable cosmetically. Due to increased temperature thresholds outside the body, additional power can be used to generate themagnetic field. This alternative can generate less heat against the tissue for a given protocol while maintaining a narrow magnetic field, but still requires far less power (and generates less volume compared to penetrative depth) than a conventional TMS coil. Depending on the specific target(s) desired, different stimulation devices may be appropriate.

[0058] In many embodiments, TMS coil implants are packaged with a power source such as (but not limited to) a battery and / or a capacitor. In some embodiments, the TMS coil implant includes a wireless power transfer coil for inductive charging using an external charging device. In various embodiments, the TMS coil implant encapsulated in a biologically safe housing to protect surrounding tissue and the internal electronic components. The implant can include one or more coils and, depending on the specific target, different coil geometries can be used.

[0059] In various embodiments, the TMS coil implant uses a high permeability core surrounded by a tightly wound coil. In many embodiments, the coil is less than 5mm in diameter. In various embodiments, the coil is constructed using a narrow diameter wire of approximately 0.4mm diameter (gauge 28 to 32), around a high magnetic permeability core. A 3-5mm diameter core is sufficient to penetrate the human motor cortex when the coil is under the skull and above the dura. In many embodiments, the core is an iron powder core material, such as -52 material from Micrometals, Inc. of Anaheim, California. However, any material that has a high magnetic permeability as well as a good high- frequency response appropriate for TMS can be used as appropriate to the requirements of specific applications of embodiments of the invention. In many embodiments, the wire diameter allows for a high number of turns per unit length (e.g. 25 / cm), creating a field of approximately 1T at current levels of approximately 100A, while maintaining a relatively low resistance. This reduces the resistive heating of the assembly, and limits the temperature rise of the assembly to acceptable levels when used with many current theta burst TMS protocols.

[0060] Turning now to FIG. 4A, a coil for a TMS coil implant in accordance with an embodiment of the invention is illustrated. The illustrated coil uses a 2mm cylindrical iron powder core, 8mm long, surrounded by 3 layers of 0.4mm wire of approximately 30 wraps. This geometry generates a vertical magnetic field of about 1 T / 100 A at the surface of theiron core protruding from the bottom of the solenoid. The B field extends vertically down from the protrusion and expands horizontally as it descends. The depth of penetration of the high field region is about 1 mm, and, in general, for any diameter core the depth of the high field region is approximately equal to the diameter of the high permeability core. For greater depth penetration the diameter of the core can be increased. FIG. 4B illustrates the resulting magnetic field.

[0061] Solenoid geometries can also be constructed which use multiply closely spaced magnets. Turning now to FIG. 5A, two magnets with conical, beveled ends are spaced a few millimeters apart. The current through the coils flows in such a way that the facing ends have opposite polarities. As can be seen in FIG. 5B, the direction of the magnetic field between the two magnets is horizontal, which is perpendicular to the magnetic field direction of the single solenoid illustrated in FIGs. 4A and 4B. As can readily be appreciated, more complex geometries that allow different magnetic fields as well as the ability to vary the timing and sequence of current pulses to each magnet can be achieved. FIG. 6 illustrates 5 separate solenoids making up a single implant. In numerous embodiments, each magnet can be driven independently to achieve a wide variety of pulse configurations.

[0062] In many embodiments, a biocompatible compartment is permanently (or semipermanently) placed into a hole in the skull into which the implanted coil or HPMC can fit when applying TMS excitation. This removes the need for the implant to be permanently mounted in the head, which can aid in receiving MRIs, and reduce the chances of setting off magnetic alarms, for example during air travel.

[0063] Further, similar designs can be scaled up to the multi-centimeter range (i.e. 1- 10cm) to better enable external to the body use cases. Scaled up devices are less suitable for implantation, but retain advantages over conventional TMS coils, such as (but not limited to) conventional figure eight coils and other large coil windings. Scaling of HMPCs can be modeled relatively easily, as magnetic field intensity falls off with distance from the end of the face of the HMPC, and is reduced by a factor of 2 at approximately 3 / 5 the diameter distance from the end face. For example, if HMPCs are scaled to operate outside of the skull for a particular target desiring 0.5 to 1 Tesla at the inner surface of theskull, then an HMPC core diameter of between 1 and 4cm is appropriate having a wrap density of approximately 25 turns per cm / layer as with the millimeter scale designs.

[0064] HMPC configurations can be made that are similar to the TMS coil implant configurations, but without windings. Similar core materials can be used, but with increased diameter as needed.

[0065] In numerous embodiments, the ability to identify which neurons are responding in response to TMS in a research setting can be very useful. For example, genetically engineered neurons that fluoresce when firing. This enables monitoring of specific neural circuits that are activated by trial TMS excitation. In many embodiments, this experimentation occurs in model organisms and / or using cultured tissue to test protocols and / or calibrate implants. Imaging configurations of stimulation devices are also contemplated.

[0066] In many embodiments, a hole can be introduced through the solenoid (or magnetic HMPC). The hole acts as a viewport through which the effect of TMS excitation on the brain can be imaged using an image relay lens. FIG. 7A illustrates a solenoid with a viewport in accordance with an embodiment of the invention, and FIG. 7B illustrates the corresponding magnetic field. In some embodiments, a mount is provided through which a hole is positioned above the space between the magnets. The mount can be attached to the underside of the skull, with a lens material protruding through the skull to enable direct imaging. FIG. 8 illustrates an example mount with a viewport in accordance with an embodiment of the invention. As can be readily appreciated, mounts may take other forms such as clips or brackets attached to the skull, with or without micro-optic viewports such as an integrated image relay gradient index (GRIN).

[0067] FIGs 9 and 10 illustrate additional viewing configurations in accordance with two embodiments of the invention. FIG. 9 illustrates a magnet with an GRIN lens through the center. FIG. 10 shows a similar image relay GRIN lens placed above a thin transparent window over the brain to relay the image of the activated neurons to the top of the coil assembly. In numerous embodiments, an imaging system can be constructed using TMS coil implants with viewing windows as part of a research platform. As noted above, genetically modified neurons can be made to fluoresce, which can be used in conjunction with stimulation device assemblies with viewing ports to investigate theeffects of various stimulation protocols and coil geometries on live tissues. As can be readily appreciated, genetic modification is not a requirement, and systems and methods described herein can provide benefits to research on model organisms in a research environment without such modification.

[0068] In many embodiments, TMS coil implants additionally include control circuitry. A control circuitry in accordance with an embodiment of the invention is illustrated in FIG. 11. However, any number of different circuit architectures can be used to drive the magnets as appropriate to the requirements of specific applications of embodiments of the invention. For example, experimentation has been performed using a solenoid made of a 2 mm to 3 mm diameter powder conical iron core (Micrometals material -52), surrounded by a triple layer of 0.4 mm copper wire. A TMS electronic driver was designed to supply high current (up to ~120 A) current pulses to the electromagnets. The current through the magnet was controlled by a high-power IGBT transistor (30N135m DIGIKEY) driven by a high-current IGBT / FET transistor gate driver (TC4422, Microchip Technology). The amplitude of the flyback voltage spike generated by abruptly terminating the current flow through the TMS magnet was limited to approximately 900 V by two 440 V transient suppressor diodes placed in series across the source and drain of the IGBT transistor. The TMS pulse timing was controlled by a high-speed, 32 bit microprocessor (ESP32, Espressif Systems) which was programmed to provide TMS intermittent theta bursts or single pulses. The microprocessor receives timing instructions from a personal computer linked by Bluetooth. The measurement of the magnetic field intensity was performed using a stepper motor controlled micropositioning stage which translated a small Hall probe (Bestol A1302) across the active regions of both human and mouse TMS coils. The induced EMF magnitude was measured using a 2 mm diameter current loop similarly translated across the TMS coil active region.

[0069] Based on said experimentation, the flyback voltage spike generated by terminating current flow can be leveraged in numerous embodiments to drive a pulse of a magnetic field for stimulation. In numerous embodiments, this enables lower power requirements to generate stronger stimulation than would otherwise be possible. In various embodiments, wireless power transfer via induction is used instead of a wired power supply.

[0070] As can readily be appreciated, the TMS coil implants, HMPCs, and control circuitry can be modified without departing from the scope or spirit of the invention and can be used in a variety of ways. For example, while the above discusses particular coils in the context of an implant, similar designs can be used externally to the body or for any other application where small volume, low-energy magnetic fields are required.

[0071] Magnet designs discussed herein provide a high degree of configurability enabling very directional and precise targeting. Further, the small form factor is better suited to in-home use and requires significantly less bulky and expensive power supplies. Use of implantable TMS systems is discussed below.Stimulation Protocols

[0072] TMS stimulation using implantable TMS systems is similar to conventional TMS. However, because implantable TMS systems are capable of generating small volume magnetic fields, less energy is needed, and higher stimulation is achievable when the target is near the surface of the brain. Therefore, conventional TMS protocols can be adapted to be performed using implantable TMS systems with the understanding that operating power can be significantly lower to hit the target. Turning now to FIG. 12, a flowchart for a stimulation process in accordance with an embodiment of the invention is illustrated. Process 1200 includes obtaining (1210) a stimulation protocol and generating (1220) magnetic fields in accordance with the protocol. In many embodiments, certain pharmacological agents can be co-administered (1230) to the patient. For example, opioids and / or cannabinoids can be administered to the patient in order to increase the (focal response of specific circuits. In some embodiments, stimulation protocols and / or pharmacological effects on stimulation protocols can be tested using implants with integrated viewing optics as described above. In various embodiments, using GRIN lenses or other optics as described herein, neural circuits activated by the protocol can be optically observed.

[0073] As can be readily appreciated, the method of FIG. 12 and similar methods can be used for treating patients. However, they can also be used as a platform for drug discovery. By way of example, Crystal Skull imaging of mouse brain neurons can be performed during stimulation in conjunction with administration of any test molecule. Inthis way, neuron activation in response to the test molecule (or various test molecules) can be directly measured in a live setting. In many embodiments, the mouse is a FosTRAP (Fos Targeted Recombination in Active Populations) strain mouse or an ArcTRAP (Arc Targeted Recombination in Active Populations) strain mouse. In various embodiments, neurons are genetically modified such that in the presence of calcium, the neuron fluoresce. In some embodiments, neurons are genetically modified such that in response to voltage, the neuron fluorescence is optically changed such that the voltage response can be measured. Different mouse strains, for example rbp4-Cre, SST-cre, Cux2-Cre, PV-Cre, and / or any other strain can be used to investigate different cell types as appropriate to the requirements of specific applications of embodiments of the invention. Indeed, any number of different genetic combinations can be used as the subject in the platform in order to investigate TMS and / or chemical impact on tissue as appropriate to the requirements of specific applications of embodiments of the invention.

[0074] In various embodiments, instead of (or in conjunction with) optical imaging, other measurement techniques such as utilization of neuropixels can be performed in conjunction with research platforms described herein to record the activity of multiple neurons due to TMS stimulation with or without drug delivery. Further, the application is not limited to the brain, but can also be used to measure activity and responses of peripheral nerves. By measuring neurological responses to TMS, the effects of various molecules can be investigated.

[0075] An additional benefit of stimulation devices described herein is that due to low power requirements, back-EMF resulting from the rapid collapse of the magnetic field can be taken advantage of. In many conventional TMS systems, back-EMF is suppressed by cutting current at a zero-crossing of the stimulation pulse for safety reasons. In numerous embodiments, stimulation devices are charged to a steady state, and then discharged. The charging process slowly generates a magnetic field. Once the discharge occurs, the rapid change in current causes a back-EMF that is significantly higher, which can trigger action potentials in surrounding neurons.

[0076] Although specific implantable TMS coils and methods of use are discussed above, many different fabrication methods can be implemented in accordance with many different embodiments of the invention. It is therefore to be understood that the presentinvention may be practiced in ways other than specifically described, without departing from the scope and spirit of the present invention. Thus, embodiments of the present invention should be considered in all respects as illustrative and not restrictive. Accordingly, the scope of the invention should be determined not by the embodiments illustrated, but by the appended claims and their equivalents.

Claims

What is claimed is:1 . A transcranial magnetic stimulation system, comprising: at least one implant, where the at least one implant comprises: at least one solenoid; a communication circuitry; and a power source; and a controller communicatively coupled to the at least one implant via the communication circuitry, comprising: a processor; and a memory containing a stimulation application that configures the processor to: direct the at least one implant to deliver transcranial magnetic stimulation to a brain.

2. The transcranial magnetic stimulation system of claim 1 , wherein the at least one implant comprises a mount configured to attach to an interior of a skull above a dura surrounding the brain, but below an external surface of the skull surrounding the brain.

3. The transcranial magnetic stimulation system of claim 1 , wherein the at least one solenoid comprises a 2 mm to 5mm diameter conical iron powder core surrounded by a triple layer of 0.1 to 0.7 mm diameter copper wire.

4. The transcranial magnetic stimulation system of claim 1 , wherein the at least one implant comprises between 1 and 5 solenoids.

5. The transcranial magnetic stimulation system of claim 4, wherein the between 1 and 5 solenoids are positioned to focus a magnetic field at a target location.

6. The transcranial magnetic stimulation system of claim 1 , wherein to deliver the transcranial magnetic stimulation, the at least one implant is configured to discharge the at least one solenoid to induce a flyback electromagnetic field.

7. The transcranial magnetic stimulation system of claim 1 , further comprising a micro-optic enabling viewing of a brain stimulated by the transcranial magnetic stimulation.

8. The transcranial magnetic stimulation system of claim 7, where the micro-optic is an image relay gradient index lens.

9. The transcranial magnetic stimulation system of claim 7, where the micro-optic is a fiber optic.

10. The transcranial magnetic stimulation system of claim 1 , wherein the at least one implant comprises a biocompatible pouch.

11. A transcranial magnetic stimulation system, comprising: a high permeability magnetic cylinder configured to be implanted into the skull of a patient; and a magnetic field generator coupled to the high permeability magnetic cylinder, and positioned external to a skull of the patient, and configured to stimulate a brain of the patient by directing therapeutic magnetic stimulation into the brain via the high permeability magnetic cylinder; and a controller communicatively coupled to the magnetic field generator, comprising: a processor; and a memory containing a stimulation application that configures the processor to deliver the therapeutic magnetic stimulation in accordance with a protocol.

12. The transcranial magnetic stimulation system of claim 11 , wherein to deliver the therapeutic magnetic stimulation, the magnetic field generator is configured to discharge a capacitor to induce a flyback electromagnetic field channeled via the high permeability magnetic cylinder.

13. The transcranial magnetic stimulation system of claim 11 , further comprising a plurality of high permeability magnetic cylinders configured to be implanted into the skull of the patient.

14. A transcranial magnetic stimulation system, comprising: at least one solenoid, where the at least one solenoid comprises a high magnetic permeability core having a diameter between 1 and 5 cm, wrapped in a triple layer of 0.1 to 0.7 mm diameter copper wire; and a power source; where the power source is configured to provide current to the at least one solenoid in order to produce a magnetic field capable of providing transcranial magnetic stimulation.

15. The transcranial magnetic stimulation system of claim 14, wherein the power source is configured to discharge a capacitor to induce a flyback voltage that drives the provided current to the at least one solenoid.

16. The transcranial magnetic stimulation system of claim 14, further comprising a mounting configured to position the at least one solenoid external to a skull of a patient.

17. The transcranial magnetic stimulation system of claim 14, further comprising an image relay gradient index lens enabling viewing of a brain stimulated by the transcranial magnetic stimulation.

18. A transcranial magnetic stimulation research system, comprising: a brain of a subject comprising genetically modified neurons that change their fluoresce when their membrane potential change; at least one transcranial magnetic stimulation device comprising: a high permeability magnetic core implanted near the brain; and a micro-optic element that enables viewing or sensing the neurons’ fluorescence of the brain from outside the subject.

19. The system of claim 18, where the high permeability magnetic core is a core of an implanted solenoid.

20. The system of claim 18, wherein the high permeability magnetic core is a cylinder implanted into a skull of the subject, wherein the core is further coupled to a magnetic field generator external to the skull of the subject.

21. The system of claim 18, further comprising an imaging device configured to image at least stimulated neurons through the micro-optic.

22. The system of claim 18, wherein the micro-optic is a GRIN lens.

23. The system of claim 18, wherein the micro-optic is a fiber optic.

24. The system of claim 18, further comprising a device for administering a drug to the subject.

25. The system of claim 18, wherein the subject is a FosTRAP mouse.

26. The system of claim 18, where the genetically modified neurons are modified to fluoresce in response to a biological parameter.

27. The system of claim 26, where the biological parameter is cell voltage.

28. The system of claim 26, where the biological parameter is calcium concentration.

29. A transcranial magnetic stimulation device, comprising: at least one solenoid comprising a 2 mm to 3 mm diameter conical iron powder core surrounded by a triple layer of 0.1 to 0.7 mm diameter copper wire; a communication circuitry; and a power source.

30. A transcranial magnetic stimulation device, comprising: at least one solenoid comprising a 1cm to 5cm diameter conical iron powder core surrounded by a triple layer of 0.1 to 0.7 mm diameter copper wire; a communication circuitry; and a power source.

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