WO2009033144A2

WO2009033144A2 - Focusing magnetic fields with attractor magnets and concentrator devices

Info

Publication number: WO2009033144A2
Application number: PCT/US2008/075575
Authority: WO
Inventors: David Mishelevich; M. Bret Schneider
Original assignee: Neostim, Inc.
Priority date: 2007-09-07
Filing date: 2008-09-08
Publication date: 2009-03-12
Also published as: WO2009033144A3

Abstract

Described herein are Transcranial Magnetic Stimulation (TMS) systems and methods configured to focus the applied magnetic fields generated by one or more primary TMS electromagnets using attractor magnets and/or magnetic concentrators having high-permeability regions. An attractor magnet is typically a secondary, phase-complimentary magnet that is configured to shape the field of the primary TMS electromagnet. A magnetic concentrator typically includes a region of high magnetic permeability that may shape a TMS magnetic field. Attractor magnets and concentrator devices can be used independently or in combination. The profile of the TMS field can be made narrower or wider than for an unfocused field using these devices, systems and methods.

Description

FOCUSING MAGNETIC FIELDS WITH ATTRACTOR MAGNETS AND

CONCENTRATOR DEVICES

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to the following provisional patent applications: U.S. Provisional Patent Application Serial No. 60/970532, filed on September 7, 2007, titled "FOCUSING MAGNETIC FIELDS WITH CONCENTRATION DEVICES"; U.S. Provisional Patent Application Serial No. 60/970534, filed on September 7, 2007, titled "FOCUSED MAGNETIC FIELDS USING ATTRACTOR MAGNETS"; and U.S. Provisional Patent Application Serial No. 60/975177, filed on September 26, 2007, titled "FOCUSING MAGNETIC FIELDS WITH ATTRACTOR MAGNETS AND CONCENTRATOR

DEVICES." Each of these applications is herein incorporated by reference in its entirety.

INCORPORATION BY REFERENCE

[0002] All publications and patent applications mentioned in this specification are herein incorporated by reference in their entirety to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference.

FIELD OF THE INVENTION

[0003] The devices and methods described herein relate generally to the focusing of magnetic fields generated by electromagnets used for Transcranial Magnetic Stimulation.

BACKGROUND OF THE INVENTION [0004] Transcranial Magnetic Stimulation (TMS) has been previously delivered from electromagnets positioned at the side of the head, the top of the head, or somewhere in between the side and the top of the head. Generally speaking, a single or double standard TMS coil placed on a patient's scalp and operated at a power level at, or slightly above, a patient's motor threshold will directly active neurons from the cortical crowns to the bottom of the cortical gyri- a depth of about 1-3 cm. Using this approach, deeper structures (herein referred to as

"subcortical", even when these deeper areas are histologically layered in nature) are activated only secondarily through intracerebral neural connections. Conventional approaches typically do not reach greater depths (for example, the cingulate gyrus, the insula and other subcortical structures). Deep brain modulation cannot be accomplished by simply turning up the power of the stimulating electromagnet, because the intervening tissue, for example superficial cortex, will be over-stimulated, causing undesired side effects such as seizures. [0005] Positive outcomes for treatment of depression refractory to drug treatment have been demonstrated with repetitive Transcranial Magnetic Stimulation (rTMS, Avery et al., 2005). rTMS works indirectly, because the superficial stimulation of the dorsolateral pre-frontal cortex is carried by nerve fibers to the deeper cingulate gyrus. More effective therapy of depression and treatment of a number of other conditions such as chronic pain, addiction, obesity, and obsessive compulsive disorder would be possible with focused brain stimulation capable of reaching depths below the cortex. Devices for providing deep brain stimulation with Transcranial Magnetic Stimulation are described in Schneider and Mishelevich, U.S. Patent Application No. 10/821,807 and Mishelevich and Schneider, U.S. Patent Application No. 11/429,504. Whether superficial or deep stimulation is being employed, focusing the applied magnetic field during TMS has the potential to improve clinical results. In particular, the ability to stimulate at depth could be facilitated by shaping the profile of the magnetic field of one or more primary stimulating electromagnets, thereby focusing their magnetic fields and more preferentially stimulating a given targeted neural structure. [0006] The magnetic fields used for Transcranial Magnetic Stimulation determine both the depth and size of the region of stimulation. Thus, a more focused magnetic field would be capable of stimulating an area that is also more tightly focused, and may be better controlled by the TMS system. [0007] Both deep-brain stimulation and direct stimulation of deeper brain regions could benefit from improved focusing of the magnetic field of the primary stimulating electromagnets. Described herein are systems, methods and devices for improving the focus of the primary electromagnets used for Transcranial Magnetic Stimulation allowing enhanced stimulation of targeted neural structures.

SUMMARY OF THE INVENTION [0008] The methods, devices and systems for controlling, focusing and/or modifying magnetic fields described herein are appropriate for use with Transcranial Magnetic Stimulation (TMS), including repetitive Transcranial Magnetic Stimulation (rTMS). In particular, described herein are devices, systems, and methods including one or more magnetic field modifiers such as attractor magnets and/or concentration devices. [0009] As used herein, an attractor magnet is typically a secondary magnet positioned separately from the primary TMS magnet(s) whose magnetic field the attractor magnet is configured to modify. An attractor magnet may be isolated from the primary TMS electromagnet(s) whose filed it is configured to modify. In particular the attractor magnet may be physically isolated, meaning that it may not be directly connected to a primary electromagnet. In some variations, the attractor magnet is separately maneuverable from the primary electromagnet, though it may be connected to the same gantry, framework, etc. as the primary electromagnet(s). For example, an attractor magnet may be positioned opposite from a primary TMS magnet and configured to direct, focus, or otherwise enhance the electromagnetic field emitted by the TMS magnet, which may aid in delivering deeper, more effective Transcranial Magnetic Stimulation (TMS). Typically, TMS involves uses a large electromagnet placed near the side of the patient's head to provide electromagnetic simulation. For the purposes of this document, the primary TMS (e.g., large) electromagnet is herein referred to as a "primary magnet," "primary electromagnet" or a "main electromagnet". The secondary magnets described herein, which may be located separately from the primary magnet but can be activated simultaneously or synchronously (in the case of active secondary magnets) with the primary magnet. For example, one or more attractor magnets may be located on the side of a patient's head opposite from the primary TMS magnet(s), or in the mouth or nasal cavity, and may act as active sink for the magnetic field from the magnet to help focus the field. [00010] The secondary magnets (or "attractor magnets") may be of opposite polarity in a phase-complementary manner at any given time within the course of synchronized TMS discharges from the primary TMS magnet(s). Consequently, the attractor magnet may draw in the primary electromagnet's magnetic field. Alternatively, the primary magnet may be described as drawing out or focusing the magnetic field of the attractor magnet(s). Although many of the attractor magnets described herein are active electromagnets (e.g., to which current may be applied to generate an electromagnetic field), attractor magnets may also be configured as permanent magnets, and the similar principles of operation may be applied to permanent magnets in addition to (or instead of) electromagnets. Thus, in some variations, an attractor magnet is (or includes) a permanent magnet. In some variations the attractor magnet is an electromagnet (also referred to as an active magnet).

[00011] Because the magnetic fields produced by TMS magnets have complex, 3- dimensional field strength profiles, the term "opposite" polarity may be relative. Consequently, the primary TMS magnet and an attractor magnet do not need to be positioned at 180 degrees with respect to one another. For example, a primary magnet and an attractor magnet may face 90 degrees relative to one another, and still produce the attractor effect as herein described. In some variations the attractor magnet maybe moved relative to the TMS magnet (or vice versa). In general, the attractor magnet may be positioned so that the effect of the attractor magnet on the magnetic field of the TMS magnet is predictable. [00012] One or more attractor magnets may be used simultaneously to modify the magnetic field of a primary magnet. In addition, attractor magnets may be used with one or more other magnetic field modification devices, including magnetic concentrators. A magnetic concentrator typically includes a shaped region of high magnetic permeability that may focus an externally applied magnetic field. One or more magnetic concentrators may help focus on neural-tissue targets in the brain (or spinal cord) during TMS. [00013] A magnetic concentrator typically includes one or more regions of high magnetic permeability. The material of high magnetic permeability may be shaped or formed into a shape to guide, concentrate, or limit the pathway of the magnetic field through the magnetic concentrator. A region of high magnetic permeability may be formed or high magnetic permeability alloys such as "Mu metal", which may draw and thus concentrate magnetic fields in these regions. The magnetic concentrators described herein (for use with TMS systems) can be disposable, or including one or more disposable components. A disposable concentrator can be customized to the appropriate shape for a given patient at a selected anatomical location. For example, a magnetic concentrator may be configured for use in a patient's oral cavity, nasal cavity, sinus cavities, external ear canals or on the surface of the body, and may be customized to fit a particular patient, or may be generic to patients (or categories of patients).

[00014] In general, the attractor magnets and magnetic concentrators (or "TMS concentrators") described herein may be used alone, or in any appropriate combinations. Systems including one or more of these magnetic modifiers may also include a control unit. The control unit may be part of the TMS system control unit, and may include logic to determine and account for the effect of the magnetic field modifier on the TMS magnet(s). The control unit may also control the attractor magnet; for example, the activation of the attractor magnet may be controlled by the control unit. The control unit (or a separate unit) may also position, suggest positions, and/or confirm the positioning of the attractor magnet(s) and/or magnetic concentrator(s).

BRIEF DESCRIPTION OF THE DRAWINGS

[00015] FIG.1 is a magnetic field profile of a primary TMS electromagnet alone, prior to addition of attractor magnet.

[00016] FIG 2 is a magnetic field profile with attractor magnet in place.

[00017] FIG.3A shows a figure-eight, double-coil electromagnet and magnetic-field profile.

[00018] FIG 3 B shows one configuration of figure-eight, double-coil TMS electromagnet, a high-permeability magnetic concentrator, and a target.

[00019] FIG 3 C illustrates a narrowed magnetic field profile for a figure-eight double-coil primary magnet in the presence of a high-permeability magnetic concentrator. [00020] FIG 4A shows three figure-eight, double-coil electromagnets and associated magnetic-field profiles and placement of target.

[00021] FIG 4B illustrates the configuration of FIG. 4A showing narrowing of magnetic- field profiles and impact on target due to a high-permeability magnetic concentrator. [00022] FIG. 5 A is a diagram of a patient's mouth including one variation of a high- permeability magnetic concentrator that is not tailored to the shape of the patient's hard palette. [00023] FIG. 5B is a diagram of a patient's mouth including a variation of a high- permeability magnetic concentrator that is tailored to the shape of the hard palette. [00024] FIG.6 A shows a figure-eight, double-coil electromagnet and magnetic-field profile.

[00025] FIG 6B illustrates one configuration of figure-eight, double-coil TMS electromagnet, a high-permeability magnetic concentrator, and a target. [00026] FIG. 6C illustrates the configuration of FIG. 6B during stimulation, showing a narrowing of the magnetic-field profile and the impact on the target due to presence of the attractor magnet and two high-permeability concentrators.

[00027] FIG 7A shows three figure-eight, double-coil TMS electromagnets and associated magnetic-field profiles and placement of target.

[00028] FIG 7B shows the configuration of FIG. 7A with the addition of an attractor magnet and two high-permeability concentrators, illustrating a focusing of the magnetic-field profiles.

DETAILED DESCRIPTION OF THE INVENTION

[00029] Described herein are Transcranial Magnetic Stimulation (TMS) systems, methods and devices that include one or more magnetic field (or flux) modifying elements, including magnetic concentrators and/or attractor magnets. These magnetic field modifying elements may be configured to focus the electromagnetic field applied by one or more primary TMS electromagnetic coils.

[00030] As described briefly above, an attractor magnet is typically a secondary magnet that is configured to produce a magnetic field that interacts with and modifies the electromagnetic field produced by the primary TMS electromagnet(s). The attractor magnet is typically positioned opposite of (or otherwise separate and across from) the primary TMS electromagnet. Thus, in some variations, the attractor magnet is opposite in polarity in a phase- complementary manner at any given time with the primary electromagnet magnet. [00031] Thus, described herein are systems for stimulating a subject's neuronal tissue, which may include a primary electromagnet configured to apply Transcranial Magnetic Stimulation to the subject, and an attractor magnet, wherein the attractor magnet is configured to be positioned opposite the primary electromagnet and to apply an electromagnetic field that is opposite in polarity in a phase-complementary manner at any given time with the primary electromagnet magnet. [00032] In general, these systems may also include one or more controllers. For example, the system may include a controller configured to coordinate activation of the primary electromagnet and the attractor magnet so that the TMS applied by the primary electromagnet is focused by the attractor magnet on the neuronal target. The controller may be part of an overall TMS system controller, or it may be a separate controller. The controller may include controls for actively positioning the primary electromagnet and/or the attractor magnet. The controller may sense or receive input on the position of the primary electromagnet and/or the attractor magnet and the target, and may control the energy applied to activate one or both the primary electromagnet and the attractor magnet so as to focus the applied TMS on the target in a desired manner. Thus, the controller may guide the system in applying the TMS to deeper tissue region or applying TMS in a more uniform and focused manner than TMS without the use of an attractor magnet. The controller may also help assure that the electromagnet field of the attractor magnet is opposite in polarity in a phase-complementary manner at any given time with the primary electromagnet magnet. [00033] Any of the systems described herein may also include a second (or additional) primary TMS electromagnets. Additional attractor magnets may also be used.

[00034] FIGS. 1 and 2 both illustrate a primary of primary magnet 10 (FIG. 1), 200 (FIG.

2). In FIG. 1, the primary TMS magnet 10 has magnetic field lobes 20 and 30, and a magnetic field flux density measured at point 40 of 1.54 x 10^"4 units. In FIG. 2, the primary magnet 200 has lobes 210 and 220, and also illustrates an attractor magnet 230. In FIG. 2, the magnetic field flux density measured at a location 240, which is equivalent to position 40 of FIG.1 , the measured field flux is 2.79 x 10^"4 units, with both the primary magnet and the attractor magnet in place. In comparison, the field strength measured with just the attractor magnet alone is 1.89 x 10^"4 units. This is because the attractor magnetic is of opposite and phase-complimentary (temporal and/or spatial) orientation with respect to primary magnet 200. This configuration and relationship operates similarly even if the primary and attractor magnets do not directly face each other.

[00035] Any appropriate magnet may be used as an attractor magnet as described herein.

Thus, the size, shape, and power of the attractor magnet may be configured to best modify the electromagnetic field emitted by the primary magnet(s). For example, coil or other shapes may be used. In operation, the attractor magnet may be positioned either opposite the primary magnet(s), or at an angle to the primary magnets. The system may be configured so that the relationship (e.g., angle and/or distance) between the attractor magnet and the primary magnet is consistent or stereotyped, hi some variations the attractor magnet is configured to be applied externally to the patient (e.g., around the patients head), or within the patient (e.g., within the mouth, ear, nasal regions, etc.).

[00036] Alternatively or in addition to the attractor magnets described herein, the system may also include one or more magnetic concentrators. A described briefly above, a magnetic concentrator is typically a device including a material having a relatively high magnetic permeability. Exemplary materials include nickel-iron alloys such as permalloy, and "mu- metal". Mu-metal is a nickel-iron alloy (75% nickel, 15% iron, plus copper and molybdenum) that has very high magnetic permeability.

[00037] A magnetic concentrator may be shaped to direct the magnetic flux lines of the primary magnet in a desired fashion. In some variations, the magnetic concentrator may direct the flux lines to focus the magnetic field applied by the primary electromagnet. Similarly, a magnetic concentrator may be applied to divert the magnetic field applied by the primary TMS electromagnet from non-target tissue regions. This may help prevent unwanted stimulation of non-target neuronal regions, for example.

[00038] FIG. 3 A shows a simplified schematic view of an electromagnetic field generated by a figure-eight shaped primary TMS electromagnet. The width of the generated magnetic field 310 is illustrated. Such figure-eight double coils are well known, for instance the 70 mm double- coil configuration from Magstim (e.g., Model 9925, Magstim Ltd., Wales, UK). The electromagnets can be powered by commercially available power sources such as the "Magstim Rapid²"(Magstim Ltd., Wales, UK) that provide electrical currents for pulsed magnetic fields. A controller may control the power source. [00039] FIG. 3B and 3C illustrate the effect of one variation of a magnetic concentrator on the primary electromagnet shown in FIG. 3A. In FIG. 3B, the same electromagnet 300 shown in FIG. 3 A is positioned opposite a target region 350 and a magnetic concentrator 320. The magnetic concentrator includes a high-permeability concentrator region 320 that is placed close to the target 350 and can augment the field strength due from the primary electromagnet 300 at the target of interest 350. FIG. 3 C illustrates the resulting narrower magnetic field 310 due to the concentration of the field generated by the primary electromagnet 300 and the magnetic concentrator 320. Thus, the magnetic concentrator results in a more intense magnetic field at target 350 than would otherwise be present. [00040] The concentrator's high-permeability concentration region can be a small region that may help focus the magnetic field at the given location. By reducing the dimension of the concentrator that is parallel to the primary magnet, while concurrently increasing the perpendicular dimension, the size and mass of the concentrator can be maintained, thereby preserving its magnetic properties, and increasing the focus from the concentrator. The high- permeability concentrator region of the magnetic concentrator acts to concentrate the applied magnetic field and thus augments the magnetic field at that target location compared to what it would have been if the high-permeability region were not present. The effect applies whether or not the electromagnet and high-permeability regions directly face each other or not. In FIG. 3 A- 3 C, the high permeability regions shown are in fixed configurations with the primary electromagnet. In an alternative embodiment, the primary electromagnet can move (for example, as described in U.S. Patent Application No. 10/821,807). The fixed-configuration high- permeability regions may be selected from a set of available alternatives. [00041] As mentioned, the high-permeability magnetic region can be made of one or more materials, including MuShield (MuShield Company, Londonderry, NH), NETIC® and CO- NETIC® alloys from Magnetic Shield Corporation (Bensenville, IL), and AD-MU alloys from Ad- Vance Magnetics, Inc. (Rochester, IN).

[00042] One or more source electromagnets (primary TMS electromagnets) and/or one or more targets may be used with one or more magnetic concentrators. For example, FIG. 4A shows a variation in which three figure-eight coil pairs 400, 410, and 420 generating magnetic- field profiles (405, 415, and 425, respectively) are aimed towards a target 440. In FIG. 4B, the same configuration is used, but also including a magnetic concentrator placed reasonably near the target. In comparison to the magnetic field profiles shown in FIG. 4B, the same electromagnets 400, 410, and 420 now generate narrower magnetic field profiles 407, 417, and 420 than the magnetic field profiles 405, 415, and 425 shown in FIG. 4A, because of the presence of the magnetic concentrator 420. The focused magnetic fields 407, 417, and 427 evoked with the concentrator have a greater magnetic-field impact on target 440 in FIG. 4B than would otherwise occur with unfocused magnetic fields. Thus, the focused magnetic fields applied may penetrate deeper, and over a smaller (or larger) target area than without a magnetic concentrator, depending on the configuration of the magnetic concentrator relative to the primary magnet(s). [00043] The magnetic concentrator may be configured as a re-useable or as a disposable device or system element. For example, the magnetic concentrator may be configured as an adhesive patch that is applied to the subject's head, or internally to the subject's head. In some variations the magnetic concentrator is configured as an implant that is temporarily or chronically implanted in the subject. The magnetic concentrator including the high-permeability region may be configured as a disposable or re-useable device whose shape is customized to each individual patient. Such concentration devices may be disposables in the sense that they are used for only one patient, but need not necessarily be disposed of between individual sessions with the same patient. Additionally these devices may become magnetically saturated over a period of use, and therefore require replacement with a fresh, unsaturated device. [00044] FIGS. 5 A and 5B show examples of magnetic concentrator devices configured to be held in a patient's mouth during TMS. For example, in FIG. 5A, component 500 is positioned vertically between the tongue 520 and the palette 530 of the subject's mouth. In FIG. 5A, the shape profile of high-permeability concentrator component 500 is lower to approximately match the shape of the underside of palette 530. In FIG. 5B, the magnetic concentrator component 510 extends noticeably higher to accommodate a high palette 530, because the magnetic concentrator has been custom formed to fit the patient's anatomy in this region. The target (not shown) in this example, is typically located superior to the palette 530. Other shapes for high-permeability magnetic concentrator components (disposable or re-usable) may fit other physical cavities, such as the nasal cavity, sinus cavities, the oral or nasal pharynx, or the external ear canal. The regions can incorporate passages for air or fluid to maintain physiological function including diagnostic and therapeutic elements. In addition, the shape may be configured to fit outside regions of the body, such as the head, neck or face. Different shapes in different cavities can be used simultaneously. For example nasal-cavity inserts can be used in conjunction with buccal component inserts. A variety of shapes can be employed, although some will be more effective at focusing than others. The third dimension of a given concentrator may be of the same or an alternate shape. The high-permeability region of the concentrator need not be symmetric. In some variation a single magnetic concentrator includes multiple sub-regions comprised of high magnetic permeability material, which may allow further shaping or refining of the applied electromagnetic field from the primary electromagnet. [00045] A magnetic concentrator (including the high-permeability region or regions of the magnetic concentrator) may be molded to fit the available space. In some variations, the magnetic concentrator may be compress-able, expandable, or otherwise anchorable, and may be configured for insertion, for example, it may include appendages or embodiments allowing for expansion and contraction (e.g., an umbrella-like). The component may be held in place by conformation with a cavity or with a suitable fixture. Examples of embodiments include filling up the rest of the space with resilient or non-resilient foam or placing a spring (which may be non-ferromagnetic) against an opposing surface.

[00046] A magnetic concentrator may also be used to control the flux pathway of a primary electromagnet and thereby protect non-target tissues. For example, in some variations, the system may include one or more magnetic concentrators with high-permeability regions that are placed on the same side of a primary electromagnet relative to a target, or are placed adjacent to the target. These positions may allow the magnetic concentrator to guide the flux pathway away from non-target regions, particularly regions that it would be desirable to avoid overstimulation of the target. Thus, a magnetic concentrator may be placed at any useful position or orientation relative to the source electromagnet(s) and the target(s).

[00047] As mentioned the magnetic field modifying elements described herein need not only be external, but may be applied internally as well. For example, external implementations may be placed under the chin or on the outside of the cheeks of the face or on the temples. Any suitable shape is appropriate. For example, a magnetic concentrator may include a high- permeability region may be configured as a horseshoe-shape which may be more effective than the rounded shape of a sphere. Components need not always match the shape of a cavity into which they are applied, such as the oral cavity, nasal cavity, etc., or the surface to which they are applied. As mentioned, a magnetic concentrator may be placed implanted with the patient, e.g., under anesthesia. For example this approach can be used in connection with a component placed in the nasal pharynx. In one embodiment, the high-permeability region can be constructed in liquid or paste form such that it can be injected into a cavity with a small opening such as a sinus cavity, the procedure performed, and then the high-permeability liquid form removed. Examples of such materials are found in Xiao et al., 2005 and Yoshida et al., 2005 (U.S. Patent 6,792,097). In another embodiment, the magnetic concentrator including a high-permeability component could be inserted into the cranium through an open-craniotomy procedure. Such an implant could be left in permanently or removed later. In some cases, the implant would be placed during open surgery not done for the sake of the implant alone but done for another purpose such as therapy for intra-cranial bleeding. The high-permeability component could then be used for therapy to restore function temporarily lost due to the lesion such as intra-cranial bleeding. [00048] External magnetic concentrators can draw magnetic field to an external location or through a volume at an intermediate position between the magnetic source and the magnetic region. In certain circumstances the high-permeability component may be used to concentrate magnetic field locally to prevent penetration of the field to sensitive underlying structures that need to be protected (say as a source electromagnet is rotating around the head). A typical embodiment may be an external shield or set of shields at the side or sides of the head or face. This use of shielding includes drawing away all or a portion of the magnetic field from superficial or other areas that, if over-stimulated, might generate seizures. [00049] FIG. 6A illustrates another example of a magnetic field 610 resulting from a figure-eight electromagnet 600. As mentioned above, such figure-eight double coils are well known. This double-coil electromagnet is used as only one example of a primary electromagnet; any appropriate primary TMS electromagnet may be used with the systems and methods described herein. The electromagnets can be powered by available power sources such as the Magstim Rapid² (Magstim Ltd., Wales, UK) that provides for pulsed magnetic fields, and may be controlled by a controller, as described. [00050] In some variation, a system may include both an attractor magnet and a magnetic concentrator. As described above, the attractor magnet may be any active or "source" electromagnet other than the primary source magnet, which is typically arranged at a position opposite the primary source magnet. The attractor magnet, owning to the opposite phase if its pulses relative to the primary source magnet, serves to pull magnetic field into the space interposed between the primary magnet and the attractor magnet. For example, FIG. 6B shows one variation of a system in which an attractor magnet 620 and two magnetic concentrators 630, 631 are used. In this configuration, which uses the same electromagnet 600 in FIG. 6A, for which an attractor magnet 620 and high permeability concentrator regions 630 and 631 are placed close to a target 650, can augment the field strength due to electromagnet 600 at the target of interest 650. FIG. 6C shows the narrower magnetic field 610 resulting from the focusing or concentration of the field generated by electromagnet 600 due to attractor magnet 620 and magnetic concentrators 630 and 631. Thus, a more intense magnetic field occurs at target 650 than there would be otherwise. In other embodiments attractor magnets and concentrator devices can be used to widen the magnetic-field profile of the primary magnet. [00051] In general, the attractor magnets and magnetic concentrators described herein concentrate the applied magnetic field and thus augment the magnetic field at a target location compared to what it would have been if these were not present. The effect applies whether or not the primary electromagnet and one or more attractor magnets and high-permeability regions directly face each other or not. As previously mentioned, although the attractor magnets and high-permeability regions shown in these embodiments are in fixed configuration relative to the primary electromagnet, the primary electromagnet may be mobile (for example as described U.S. Patent Application No. 10/821,807); in addition one or both of the magnetic concentrator(s) and/or attractor magnet(s) may also be mobile, and may move synchronously with the primary electromagnet. In other embodiments the attractor magnets, the concentrator devices or both can move, with or without movement of the primary source electromagnet.

[00052] One or more source electromagnets may be used or form a part of the systems described herein, and one or more targets may be stimulated with TMS using these stems and methods. For example, FIG. 7A, illustrates three figure-eight coil pairs 700, 710, and 720 generating magnetic-field profiles 705, 715, and 725 respectively aimed towards target 740. FIG. 7B illustrates a system with the same three primary electromagnets, but also including a pair of magnetic concentrators and an attractor magnet. In comparison to the magnetic field profiles shown in FIG. 7 A, the same electromagnets 700, 710, and 720 now generate narrower magnetic-field profiles 707, 717, and 727 than the profiles 705, 715, and 725 because of the presence of attractor magnet 720 and high-permeability concentrator regions 730 and 731. The combination of the magnetic fields 707, 717, and 727 has greater magnetic-field impact on target 740 in FIG. 7B than would otherwise occur with unfocused magnetic fields. [00053] Thus, described herein are Transcranial Magnetic Stimulation systems for stimulating a subject's neuronal tissue that may include a primary electromagnet configured to apply Transcranial Magnetic Stimulation to the subject and a magnetic concentrator comprising a shaped region of high magnetic permeability, wherein the concentrator is configured to modify the Transcranial Magnetic Stimulation applied by the primary electromagnet. In some variations, the system also includes an attractor magnet, wherein the attractor magnet is configured to be positioned opposite the primary electromagnet and to apply an electromagnetic field that is opposite in polarity in a phase-complementary manner at any given time with the primary electromagnet magnet.

[00054] As mentioned above, any of these systems may also include a controller configured to coordinate the positions of the primary electromagnet and the magnetic concentrator relative to a neuronal target.

[00055] In operation, any of the devices and systems described herein may be used to apply TMS to a patient in need thereof. For example, TMS may be used to treat one or more disorders (e.g., depression, chronic pain, addiction, obesity, and obsessive compulsive disorder, or other psychological disorders) using any of the devices and systems, including the attractor magnets and magnetic concentrators, described.

[00056] In general, a subject may be treated by providing TMS stimulation after first positioning the primary electromagnet(s) and any additional magnetic field modifying elements, such as attractor magnets and/or magnetic concentrators. The step of positioning either or both the primary electromagnet(s) and the additional magnetic field modifying elements may be guided, e.g., by the controller, which may determine an optimal position based in part on target position. For example, a controller may detect or be told (e.g., by direct input) the selected target(s) and the position of the system components such as the primary electromagnet(s), magnetic concentrator(s), and attractor magnet(s). After positioning these components, the system may then determine the desired stimulation protocol to achieve targeted stimulation without undesirably stimulating (or over stimulating) non-target tissues. [00057] For example, in variations in which the target selected is a deep-brain (e.g., non- cortical) target, it may be desirable to avoid stimulating neural tissue that is located superficially to the deep target. Thus, the controller (or other portion of the system) may determine the appropriate stimulation protocol to achieve stimulation at a desired frequency, rate and/or duration to activate or inhibit the target without stimulating (or overstimulation) non-target regions. In determining the stimulation protocol, the system may calculate the effect of any attractor magnet(s) and/or magnetic concentrator(s) including in the system. For example, the controller may receive input on the position and orientation, as well as the magnetic properties of the attractor magnet(s) and magnetic concentrator(s) (e.g., the field strength range of the attractor magnet(s) and the magnetic permeability of the magnetic concentrator(s)). This information may be used to determine the effect and optimize the treatment protocol. [00058] For example, described herein are Transcranial Magnetic Stimulation methods for stimulating a neuronal target tissue that include the steps of: selecting the neuronal target; positioning a primary electromagnet to apply electromagnetic energy to the target; positioning an attractor magnet opposite the primary electromagnet; emitting an electromagnetic field from the primary electromagnet; and emitting an electromagnetic field from the attractor magnet that is opposite in polarity in a phase-complementary manner at any given time with the electromagnetic field emitted from the primary electromagnet magnet, so that the magnetic field applied to the neuronal target from the primary electromagnet is focused by the electromagnet field from the attractor magnet. The method may also include the step of positioning a magnetic concentrator on or within the subject to enhance the electromagnetic energy applied to the target from the primary electromagnet. Alternatively (or additionally), the method may include the step of positioning a magnet concentrator on or within the subject to shield a region of the subject from the electromagnetic energy applied to the target.

[00059] In some variations, the method includes determining the energy applied to the primary electromagnet based on the positions of the target, primary electromagnet and attractor electromagnet.

[00060] Also described herein are Transcranial Magnetic Stimulation methods for stimulating a neuronal target tissue that include the steps of: selecting the neuronal target; positioning a primary electromagnet to apply electromagnetic energy to the target; positioning a magnetic concentrator on or within the subject to enhance the electromagnetic energy applied to the target from the primary electromagnet; and emitting an electromagnetic field from the primary electromagnet so that the emitted electromagnetic field is altered by the magnetic concentrator.

[00061] The step of positioning the magnetic concentrator may include positioning the concentrator within the subject's body (e.g., within the nose, mouth, ears, etc.). The magnetic concentrator may be a disposable magnetic concentrator, or a re-usable one. In some variations, the step of positioning the magnetic concentrator comprises applying the magnetic concentrator comprises applying the magnetic concentrator to the subject's head. [00062] Also described herein are Transcranial Magnetic Stimulation methods for stimulating a neuronal target tissue that include: selecting the neuronal target; positioning a primary electromagnet to apply electromagnetic energy to the target; positioning a magnetic concentrator on or within the subject to shield a region of the subject from the electromagnetic energy applied to the target by the primary electromagnet; and emitting an electromagnetic field from the primary electromagnet so that the emitted electromagnetic field is altered by the magnetic concentrator. [00063] The various embodiments described above are provided by way of illustration only and should not be construed to limit the invention. Based on the above discussion and illustrations, those skilled in the art will readily recognize that various modifications and changes may be made to the present invention without strictly following the exemplary embodiments and applications illustrated and described herein. Such modifications and changes do not depart from the true spirit and scope of the present invention, which is set forth in the following claims.

REFERENCES

Avery, D.H., Holtzheimer III, P.E., Fawaz, W., Russo, Joan, Neumaier, J. and Dunner, D.L., Haynor, D.R., Claypoole, K.H., Wajdik, C. and P. Roy-Byrne, "A Controlled Study of Repetitive Transcranial Magnetic Stimulation in Medication-Resistant Major Depression," Biological Psychiatry, 2005, 59: 187-194.

Chris Hovey C, Houseman P and Jalinous R. The New Guide to Magnetic Stimulation. The Magstim Company Ltd Carmarthenshire, United Kingdom 2003.

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Claims

CLAIMSWhat is claimed is:

1. A Transcranial Magnetic Stimulation system for stimulating a subject's neuronal tissue, the system including: a primary electromagnet configured to apply Transcranial Magnetic Stimulation to the subject; and an attractor magnet, wherein the attractor magnet is configured to be isolated from the primary electromagnet and to apply an electromagnetic field that is opposite in polarity in a phase-complementary manner at any given time with the primary electromagnet magnet.

2. The system of claim 1 , further comprising a controller configured to coordinate activation of the primary electromagnet and the attractor magnet.

3. The system of claim 1 , further comprising a controller configured to coordinate the positions of the attractor magnet and the primary electromagnet relative to a neuronal target.

4. The system of claim 1 , wherein the attractor magnet is configured to be positioned opposite the primary electromagnet by 180 degrees.

5. The system of claim 1 , wherein the attractor magnet is configured to be positioned opposite the primary electromagnet by 90 degrees.

6. The system of claim 1 , further comprising at least one magnetic concentrator comprising a shaped region of high magnetic permeability, wherein the concentrator is configured to modify the Transcranial Magnetic Stimulation applied by the primary electromagnet.

7. The system of claim 6, wherein the magnetic concentrator is isolated from the primary electromagnet.

8. The system of claim 1 , further comprising a second primary electromagnet configured to apply Transcranial Magnetic Stimulation to the subject.

9. A Transcranial Magnetic Stimulation system for stimulating a subject's neuronal tissue, the system including: a primary electromagnet configured to apply Transcranial Magnetic Stimulation to the subject; and a magnetic concentrator comprising a shaped region of high magnetic permeability, wherein the concentrator is configured to modify the Transcranial Magnetic Stimulation applied by the primary electromagnet, further wherein the magnetic concentrator is configured to be positioned on or within the subject separately from the primary electromagnet.

10. The system of claim 9, further comprising an attractor magnet, wherein the attractor magnet is configured to be positioned opposite the primary electromagnet and to apply an electromagnetic field that is opposite in polarity in a phase-complementary manner at any given time with the primary electromagnet magnet.

11. The system of claim 9, further comprising a controller configured to coordinate the positions of the primary electromagnet and the magnetic concentrator relative to a neuronal target.

12. The system of claim 9, wherein the magnetic concentrator is disposable or single-use.

13. The system of claim 9, wherein the magnetic concentrator is configured to be applied to the outside of the patient's head.

14. The system of claim 9, wherein the magnetic concentrator is configured to be inserted in a subject's body.

15. The system of claim 9, wherein the magnetic concentrator is configured to be held in the patient's mouth.

16. The system of claim 9, further comprising a plurality of magnetic concentrators.

17. A Transcranial Magnetic Stimulation method for stimulating a neuronal target tissue, the method comprising:

selecting the neuronal target; positioning a primary electromagnet to apply electromagnetic energy to the target; positioning an attractor magnet opposite the primary electromagnet; emitting an electromagnetic field from the primary electromagnet; and emitting an electromagnetic field from the attractor magnet that is opposite in polarity in a phase-complementary manner at any given time with the electromagnetic field emitted from the primary electromagnet magnet, so that the magnetic field applied to the neuronal target from the primary electromagnet is focused by the electromagnet field from the attractor magnet.

18. The method of claim 17, further comprising positioning a magnetic concentrator on or within the subject to enhance the electromagnetic energy applied to the target from the primary electromagnet.

19. The method of claim 17, further comprising positioning a magnet concentrator on or within the subject to shield a region of the subject from the electromagnetic energy applied to the target.

20. The method of claim 17, further comprising determining the energy applied to the primary electromagnet based on the positions of the target, primary electromagnet and attractor electromagnet.

21. A Transcranial Magnetic Stimulation method for stimulating a neuronal target tissue, the method comprising:

selecting the neuronal target; positioning a primary electromagnet to apply electromagnetic energy to the target; positioning a magnetic concentrator on or within the subject to enhance the electromagnetic energy applied to the target from the primary electromagnet; and emitting an electromagnetic field from the primary electromagnet so that the emitted electromagnetic field is altered by the magnetic concentrator.

22. The method of claim 21, wherein the step of positioning the magnetic concentrator comprises positioning the concentrator within the subject's body.

23. The method of claim 21, wherein the step of positioning the magnetic concentrator comprises positioning a disposable magnetic concentrator.

24. The method of claim 21, wherein the step of positioning the magnetic concentrator comprises applying the magnetic concentrator comprises applying the magnetic concentrator to the subject's head.

25. The method of claim 21, further comprising determining the energy applied to the primary electromagnet based on the position of the primary electromagnet, the target and the magnetic concentrator.

26. A Transcranial Magnetic Stimulation method for stimulating a neuronal target tissue, the method comprising:

selecting the neuronal target; positioning a primary electromagnet to apply electromagnetic energy to the target; positioning a magnetic concentrator on or within the subject to shield a region of the subject from the electromagnetic energy applied to the target by the primary electromagnet; and emitting an electromagnetic field from the primary electromagnet so that the emitted electromagnetic field is altered by the magnetic concentrator.