(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
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`(19) World Intellectual Property Organization
`International Bureau
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`25 November 2010 (25.11.2010) (10) International Publication Number
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`(43) International Publication Date
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`WO 2010/135425 Al
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`G1)
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`QD
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`International Patent Classification:
`A6IN 1/02 (2006.01)
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`(81)
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`International Application Number:
`PCT/US2010/035401
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`(22)
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`International Filing Date:
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`(25)
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`(26)
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`(30)
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`(7)
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`(74)
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`Filing Language:
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`Publication Language:
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`19 May 2010 (19.05.2010)
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`English
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`English
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`Priority Data:
`61/179,590
`61/225,644
`
`19 May 2009 (19.05.2009)
`15 July 2009 (15.07.2009)
`
`US
`US
`
`Applicant (for all designated States except US): THE
`TRUSTEES OF COLUMBIA UNIVERSITY IN THE
`CITY OF NEW YORK [US/US]; 412 Low Memorial
`Library, 535 West 116th St., Mail Code 4308, New York,
`NY 10027 (US).
`
`Inventor; and
`Inventor/Applicant (for US only): PETERCHEV, An-
`gel, Vladimirov [BG/US]; 495 West End Avenue, #6E,
`New York, NY 10024 (US).
`
`Agents: CATAN, Mark, A.et al.; Miles & Stockbridge
`P.C., 1751 Pinnacle Drive, Suite 500, McLean, VA
`22102-3833 (US).
`
`Designated States (unless otherwise indicated, for every
`kind of national protection available): AE, AG, AL, AM,
`AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ,
`CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO,
`DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT,
`HN,HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP,
`KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD,
`ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI
`NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD,
`SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, TR,
`TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW.
`
`(84)
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`Designated States (unless otherwise indicated, for every
`kind of regional protection available): ARIPO (BW, GH,
`GM, KE, LR, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG,
`ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU,TJ,
`TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, DK,
`EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU,
`LV, MC, MK, MT, NL, NO, PL, PT, RO, SE, SL SK,
`SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ,
`GW, ML, MR,NE,SN, TD, TG).
`Published:
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`with international search report (Art. 21(3))
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`(54) Title: SYSTEMS AND METHODSFOR INDUCING ELECTRIC FIELD PULSES IN A BODY ORGAN
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`POWERLINE pACITOR
`CHARGER!
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`DISC-IARGER
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`FIG. 22
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`(57) Abstract: Systems and methods for providing controllable pulse parameter magnetic stimulation are described. One aspectis
`directed to a magnetic stimulation system for inducing approximately rectangular electric field pulses in a body organ, comprising
`an electrical energy storage device, a stimulating coil, and a switching meansfor electrically coupling said electrical energy stor-
`age device to said stimulating coil to produce current pulses in said stimulating coil which generates, in response to the current
`pulses, magnetic field pulses that can induce approximately rectangular electric field pulses in the body organ.
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`wo2010/135425A1IMITINIININMTNIACINTTTAAT
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`WO 2010/135425
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`PCT/US2010/035401
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`SYSTEMS AND METHODSFOR INDUCING ELECTRIC FIELD PULSESIN A
`
`BODY ORGAN
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`Cross-Reference to Related Applications
`
`[0001]
`
`This application claimspriority to, and the benefit of, U.S. Provisional
`
`Application No. 61/225,644,filed on July 15, 2009, and U.S. Provisional Application No.
`
`61/179,590,filed on May 19, 2009, the entireties of both of which applications are hereby
`
`incorporated herein by reference.
`
`Field
`
`[0002]
`
`The disclosed subject matter relates to systems and methodsfor providing
`
`controllable pulse parameter magnetic stimulation that induceselectric field pulses in a
`
`body organ.
`
`Background
`[0003] Magnetic stimulation is a noninvasive tool for the study of the human brain
`and peripheral nerves that is being investigated as a potential therapeutic agentin
`
`psychiatry and neurology. When appliedto the brain, this technique is commonly referred
`
`to as Transcranial Magnetic Stimulation (TMS). However, the term "TMS"is often used
`to refer to magnetic stimulation of other body organs as well. Therefore, the term TMS
`will be used hereinafter to refer to magnetic stimulation of the brain or other body organs.
`
`In TMS, a pulsed current sent through a coil produces a magnetic field that
`[0004]
`induces an electric field in the brain, which can affect neuronal activity. A single TMS
`pulse can activate a targeted brain circuit. For example, a TMS pulse delivered to the
`motor cortex can result in a twitch of the associated muscles in the body. Further, a single
`
`TMS pulse can also disrupt neural activity. For example, a TMS pulse delivered to the
`
`occipital cortex can maskthe perception of a visual stimulus. This allows researchers to
`
`probe brain circuits on a millisecond timescale.
`(0005)
`A train of TMS pulses, referred to as repetitive TMS (rTMS), can produce
`excitatory or inhibitory effects which last beyond the stimulation interval. Repetitive
`TMSprovides a means to study higher cognitive functions, and it could potentially be
`
`used as a therapeutic intervention in psychiatry and neurology.
`
`[0006]
`
`The neural response to TMSis sensitive to the parameters of the stimulating
`
`TMSpulse. The pulse width (PW), shape (e.g., sinusoidal vs. rectangular), and the
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`relative amplitude of the positive and negative phases (degree of bidirectionality) of the
`
`inducedelectric field affect the physiological response to TMS, the powerefficiency of
`
`the stimulator, and the heating of the stimulating coil. Existing TMS systems are capable
`
`of inducing only damped cosineelectric field pulse shapes, with a lirnited set of discrete
`
`choices of pulse width and degree of bidirectionality. Further, in existing TMS systems,
`monophasic magnetic field pulse shapes are associated with very low powerefficiency of
`the stimulator in r™MSapplications.
`
`Description
`
`.
`
`[0007]
`
`Systems and methods are disclosed for providing controllable pulse parameter
`
`magnetic stimulation that induceselectric field pulses in a body organ. Oneaspectis
`
`directed to a magnetic stimulation system for inducing approximately rectangular electric
`
`field pulses in a body organ, comprising an electrical energy storage device, a stimulating
`coil, and a switching means for electrically coupling said electrical energy storage device
`to said stimulating coil to produce current pulses in said stimulating coil which generates,
`
`in responseto the current pulses, magnetic field pulses that can induce approximately
`
`rectangularelectric field pulses in the body organ.
`
`[0008]
`
`Anotheraspectis directed to a magnetic stimulation system for inducing
`
`approximately rectangularelectric field pulses in a body organ, comprising a first and a
`
`second electrical energy storage device, a stimulating coil, a first switching means to
`
`electrically couple said first electrical energy storage device to the stimulating coil to
`
`produce current pulses with a positive rate of change in the stimulating coil, and a second
`switching means to electrically couple said second electrical energy storage device to said
`
`stimulating coil to produce current pulses with a negative rate of changein the stimulating
`
`coil, wherein the stimulating coil produces, in response to a combination of the current
`
`pulses with the positive and negative rates of change, magnetic field pulses that can
`
`induce approximately rectangular electric field pulses in the body organ.
`
`[0009]. Another aspectis directed to a method of inducing approximately rectangular
`
`electric field pulses in a body organ with a magnetic stimulation system. The method
`
`comprises providing a first and a second energy storage device, providing a stimulating
`
`coil, providing a first switching meanselectrically coupled to the first energy storage
`
`device and the stimulating coil, providing a second switching meanselectrically coupled
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`to the second energy storage device and the stimulating coil, actuating the first switching
`
`means to électrically couple the first energy storage device to the stimulating coil for a
`
`first period of time to produce current pulses with a positive rate of change in the
`
`stimulating coil, actuating the second switching meansto electrically couple the second
`
`energy storage device to the stimulating coil for a second period. of time to produce
`
`current pulses with a negative rate of change in the stimulating coil, and thereby causing
`
`the stimulating coil to produce, in response to a combination of the current pulses with the
`
`positive and negative rates of change, magnetic field pulses that can induce
`approximately rectangularelectric field pulses in the body organ, and positioning the
`
`stimulating coil proximate to the body organ and exposing the body organ to the magnetic
`
`field pulses thereby inducing the approximately rectangular electric field pulses in the
`
`body organ.
`
`[0010] Another aspect is directed to a magnetic stimulation system for inducing
`
`adjustable pulse width electric field pulses in a body organ, comprising an electrical
`
`energy storage device, a stimulating coil; and a switching meansfor electrically coupling
`
`said electrical energy storage device to said stimulating coil to produceselectively-
`
`adjustable-width current pulses in said stimulating coil which generates, in response to
`
`the current pulses, magnetic field pulses that can induce selectively-adjustable-width
`
`electric field pulses in the body organ.
`
`{0011} Another aspect is directed to a method of inducing adjustable pulse width
`
`electric field pulses in a body organ. The method comprises providing an electrical energy
`
`storage device, providing a switching means, providing a stimulating coil, and electrically
`
`coupling said electrical energy storage device to said stimulating coil with said switching
`meansto produceselectively-adjustable-width current pulsesin said stimulating coil
`
`which generates, in response to the current pulses, magnetic field pulses that can induce
`
`selectively-adjustable-width electric field pulses in the body organ.
`
`(0012) Another aspect is directed to a magnetic stimulation system for inducing
`
`electric field pulses with an adjustable degree of bidirectionality in a body organ,
`
`comprising a first and a second electrical energy storage device, a charging means
`
`electrically coupled to the first and second electrical energy storage devices for charging
`
`the first electrical energy storage device to a selectable first voltage and charging the
`
`secondelectrical energy storage device to a selectable second voltage, a stimulating coil,
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`a first switching means to electrically couple the first electrical energy storage device to
`
`the stimulating coil to produce current pulses with a positive rate of change in the
`
`stimulating coil, and a second switching means to electrically couple the second electrical
`
`energystorage device to said stimulating coil to produce current pulses with a negative
`
`rate of changein the stimulating coil, wherein the stimulating coil produces, in response
`
`to a combination of the current pulses with the positive and negative rates of change,
`magnetic field pulses that can induce electric field pulses in the body organ, the degree of
`
`bidirectionality being determined bytheratio of the selectable first voltage and the
`
`selectable second voltage.
`
`[0013] Another aspectis directed to a method ofinducingelectric field pulses with an
`adjustable degree of bidirectionality in a body organ. The method comprises providing a
`
`first and a second electrical energy storage device, providing a charging means
`
`electrically coupled to the first and second electrical energy storage devices for charging
`
`the first electrical energy storage device to a selectable first voltage and charging the
`
`second electrical energy storage device to a selectable second voltage, providing a
`
`stimulating coil, providing a first switching means electrically coupledto thefirst
`
`electrical energy storage device and the stimulating coil, providing a second switching
`
`meanselectrically coupled to the second electrical energy storage device and the
`
`stimulating coil, setting a desired degree of bidirectionality by selecting respective
`
`amplitudes for the first and second voltages, the degree of bidirectionality being
`
`determined bythe ratio of the selected first voltage and the selected second voltage,
`
`actuating said first switching means to electrically couple the first electrical energy
`
`storage device to the stimulating coil for a first period of time to produce current pulses
`
`with a positive rate of change in the stimulating coil, actuating said second switching
`meansto electrically couple the secondelectrical energy storage device to the stimulating
`
`coil for a second period of time to produce current pulses with a negative rate of change
`
`in the stimulating coil, and thereby causing the stimulating coil to produce magnetic field
`
`pulses in response to a combination of the current pulses with the positive and negative
`
`rates of change; and positioning the stimulating coil proximate to the body organ and
`
`exposing the body organ to the magnetic field pulses thereby inducing electric field
`
`pulses in the body organ with the desired degree of bidirectionality.
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`[0014] Another aspectis directed to a magnetic stimulation system for inducing
`
`electric field pulses in a body organ, comprising an electrical energy storage device, a
`
`stimulating coil, a switching means for electrically coupling said electrical energy storage
`
`device to said stimulating coil to produce current pulses in said stimulating coil which
`
`generates, in responseto the current pulses, magnetic field pulses that can induceelectric
`
`field pulses in the body organ, the electric field pulses having a plurality of selectively
`
`adjustable parameters from a group consisting of amplitude, pulse width, degree of
`
`bidirectionality and pulse repetition frequency; and an operator-controlled apparatus
`
`including means for independently controlling at least two of said parameters.
`
`[0015] Another aspect is directed to a method for inducing electric field pulses in a
`
`body organ with a magnetic stimulation system. The method comprises providing an
`
`electrical energy storage device, providing a stimulating coil, electrically coupling said
`
`electrical energy storage device to said stimulating coil with a switching meansto
`
`produce current pulses in said stimulating coil which generates, in response to the current
`
`pulses, magnetic field pulses that can induceelectric field pulses in the body organ, the
`
`electric field pulses having a plurality of selectively adjustable parameters from a group
`
`consisting of amplitude, pulse width, degree of bidirectionality and pulse repetition
`
`frequency, detecting physiological effects induced in the body organ bythe electric field”
`
`pulses, and controlling at least two of said parameters based on the detected physiological
`
`effects.
`[0016] Another aspect is directed to a magnetic stimulation system for inducing
`approximately rectangularelectric field pulses in a body organ, comprising an electrical
`energy storage device, a stimulating coil, and a switching circuit configured for
`
`electrically coupling said electrical energy storage device to said stimulating coil to
`
`produce current pulses in said stimulating coil which generates, in response to the current
`
`pulses, magnetic field pulses that can induce approximately rectangularelectric field
`
`pulses in the body organ.
`
`[0017]
`
`Anotheraspectis directed to a method for inducing approximately rectangular
`
`electric field pulses in a body organ, comprising storing electrical energy M in an
`
`electrical energy storage device, generating with a stimulating coil magnetic field pulses
`
`that can induceelectric field pulses in the body organ, and switchably electrically
`
`coupling the electrical energy storage device to the stimulating coil to produce current
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`pulses in the stimulating coil which generates, in response to the current pulses, magnetic
`
`field pulses that can induce approximately rectangular electric field pulses in the body
`
`organ.
`
`[0018]
`
`Ina first embodiment, two energy storage capacitors are connected to a
`
`commonground. A positive pulse is created in a transcranial magnetic stimulation
`
`(TMS)coil by connecting it between a first of two capacitors and groundfora first
`
`interval of time and then disconnecting thefirst capacitor and permitting a current to
`
`continue to flow through the TMScoil through a first diode connected between the coil
`
`and ground and a second diode connected betweenthe coil and a second capacitor,
`
`thereby charging the second capacitor using the magnetic field energy stored in the TMS
`
`coil.
`
`[0019]
`
`Ina second embodiment, two energy storage capacitors are connectedto a
`
`common ground. A positive pulse is created in a transcranial magnetic stimulation
`
`(TMS) coil by connecting it betweena first of two capacitors and a second of the two
`
`capacitors for a first interval of time and then disconnecting the first capacitor and
`
`permitting a current to continue to flow through the TMScoil througha first diode
`
`connected between the coil and ground and a second diode connected betweenthecoil
`
`and the second capacitor, thereby charging the second capacitor using the magnetic field
`
`energy stored in the TMS coil. In this embodiment, the first capacitor voltage may be
`
`higher than the second.
`
`[0020]
`
`In either of the above two embodiments, the coil can be short-circuited by
`
`closing respective switcheson either side of the TMS coil to connect either side of the
`
`TMScoil together.
`to ground.
`[0021]
`
`In a variation this causes both sides of the TMS coil to be connected
`.
`In either of the embodiments, a negative voltage is applied across the TMS
`
`coil by closing third and fourth switches.
`(0022) Another aspectis directed to a magnetic stimulation system for inducing
`approximately rectangularelectric field pulses in a body organ, comprising a first and
`
`second electrical energy storage device, a stimulating coil, a first and second switching
`
`meansto electrically couple said first electrical energy storage device to the stimulating
`
`coil to produce current pulses with a positive rate of change in the stimulating coil, and a
`
`third and fourth switching meansto electrically couple said second electrical storage
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`device to said stimulating coil to produce current pulses with a positive rate of change in
`the stimulating coil, wherein the stimulating coil produces, in response to a combination
`of the current pulses with the positive rates of change, magnetic field pulses that can
`
`induce approximately rectangular electric field pulses in the body organ.
`
`[0023] Another aspectis directed to a method of inducing approximately rectangular
`
`electric field pulses in a body organ with a magnetic stimulation system. The method
`
`comprises providing a first and second energy storage device, providing a stimulation
`
`coil, providing a first and second switching means coupled to thefirst energy storage
`
`device and the stimulating coil, providing a third and fourth switching meanselectrically
`
`coupled to the second energy storage device andthe stimulating coil, actuating thefirst
`
`and second switching meansto electrically couple the first energy storage device to the
`
`stimulating coil for a first period of time to produce current pulses with a positive rate of
`
`changein the stimulating coil, actuating the third and fourth switching meansto
`
`electrically couple the second energy storage device to the stimulating coil for a second
`
`period of time to produce current pulses with a negative rate of changein the stimulating
`
`coil, and thereby causing the stimulating coil to produce, in response to a combination of
`
`the current pulses with the positive rates of change, magnetic field pulses that can induce
`
`approximately rectangular electric field pulses in the body organ, and positioning the
`
`stimulating coil proximate to the body organ and exposing the body organ to the magnetic
`
`field pulses thereby inducing the approximately rectangular electric field pulses in the
`
`body organ.
`
`[0024]
`In a variation of the above, the two energy storage devices include two
`capacitors, each chargedto a different voltage level relative to a common ground. The
`
`circuit common groundcan bedirectly connected to earth ground. Fora positive phase of
`
`a pulse sequence,a first capacitor with a voltage V1 is applied to the coil with a polarity
`
`relative to ground to generate a forward current. Then thefirst capacitor is disconnected
`
`allowing currentin the coil to decline over an interval. Then a voltage from the second
`
`capacitoris applied to the coil to generate a negative current opposite to the direction of
`
`the forward current for another interval after which the voltage from the second capacitor
`
`is disconnected causing the current to decline for anotherinterval.
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`Brief Description of the Drawings
`
`[0025]
`
`Fig.
`
`| is an illustrative component diagram of a controllable pulse parameter
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`transcranial magnetic stimulation system, according to some embodiments of the
`
`disclosed subject matter.
`[0026]
`Fig. 2Ais anillustrative block diagram of an embodimentof the power
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`electronics circuitry for the controllable pulse parameter transcranial magnetic stimulation
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`system ofFig. 1.
`
`[0027]
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`Fig. 2B is an illustrative block diagram of an embodimentof the control
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`computerelectronics for the controllable pulse parameter transcranial magnetic
`
`stimulation system of Fig. 1.
`
`[0028]
`
`Fig. 3Ais anillustrative schematic diagram of another embodimentofthe
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`powerelectronics circuitry for controllable pulse parameter transcranial magnetic
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`stimulation circuit.
`
`[0029]
`
`Fig. 3B is anillustrative schematic diagram of an insulated-gate bipolar
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`transistor switch with an anti-parallel diode.
`
`[0030]
`
`Fig. 3C is an illustrative schematic diagram of a gate turn-off thyristor with an
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`anti-parallel diode.
`
`[0031]
`
`Figs. 3D-3Fare illustrative schematic diagrams of snubbercircuits.
`
`[0032]
`
`Fig. 4Ais anillustrative graph of a positive magnetic pulse generated by using
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`the controllable pulse parameter transcranial magnetic stimulation circuit of Fig. 3A.
`
`[0033]
`
`Fig. 4B is an illustrative graph of a negative magnetic pulse generated using
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`the controllable pulse parameter transcranial magnetic stimulation circuit of Fig. 3A.
`
`[0034]
`
`Fig. 5A showsillustrative waveforms of a monophasic magnetic field pulse
`
`(B), an associated electric field (E), and neuronal membrane voltage (V,,) induced in the
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`brain by a controllable pulse parameter transcranial magnetic stimulation system,
`
`according to one embodimentof the disclosed subject matter.
`
`[0035]
`
`Fig. 5B showsillustrative waveformsof a biphasic magnetic field (B), an
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`associated electric field (E), and neuronal membrane voltage (V,,) inducedin the brain by
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`a controllable pulse parameter transcranial magnetic stimulation system, according to one
`
`embodiment of the disclosed subject matter.
`
`[0036]
`
`Fig. 6 is an illustrative waveform depicting user-adjustable pulse parameters,
`
`according to one embodimentof the disclosed subject matter.
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`[0037]
`
`Fig. 7 showsillustrative waveforms of approximately rectangular induced
`
`electric field pulses with pulse widths adjustable over a continuousrangeof values,
`generated by a controllable pulse parameter transcranial magnetic stimulation circuit,
`according to one embodimentof the disclosed subject matter.
`
`[0038}
`
`Fig. 8 showsillustrative waveforms of approximately rectangular induced
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`electric field pulses with bidirectionality adjustable over a continuous range, generated by
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`a controjlabie pulse parameter transcranial magnetic stimulation circuit, according to one
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`embodimentof the disclosed subject matter.
`
`[0039]
`
`‘Fig. 9 is an illustrative waveform of repetitive TMS with predominantly
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`unipolar induced electric field pulses, with adjustable pulse repetition frequency,
`
`according to one embodimentof the disclosed subject matter.
`
`Fig. 10 is an illustrative simulation circuit for producing controllable pulse
`(0040)
`parameter transcranial magnetic stimulation, in accordance with the disclosed subject
`matter.
`
`[0041]
`
`Fig. 11 is a table of pulse performance metrics used to evaluate the efficiency
`
`of controllable pulse parameter transcranial magnetic stimulation pulses.
`
`[0042]
`
`Fig. 12A showsanillustrative waveform of a coil current produced by the
`
`simulation circuit of Fig. 10.
`
`[0043]
`
`Fig. 12B showsanillustrative waveform of a peak induced electric field
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`producedbythe simulation circuit of Fig. 10.
`
`[0044]
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`Fig. 12C showsanillustrative waveform of a neuronal membrane voltage
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`change producedby the simulation circuit of Fig. 10.
`
`[0045]
`
`Fig. 13A is an illustrative block diagram of powerelectronics circuitry for a
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`controllable pulse parameter transcranial magnetic stimulation system, according to
`
`another embodiment of the disclosed subject matter.
`
`[0046]
`
`Fig.
`
`13B is an illustrative block diagram of another embodimentof the control
`
`computerelectronics for the controllable pulse parameter transcranial magnetic
`
`stimulation system.
`
`[0047]
`
`Fig. 14 is an illustrative schematic of a controllable pulse parameter
`
`transcranial magnetic stimulation circuit, according to another embodiment of the
`
`invention.
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`[0048]. Fig. 15A showsillustrative waveformsof voltage across capacitor C5 for
`
`different pulse widths of the controllable pulse parameter transcranial magnetic
`
`stimulation circuit of Fig. 14.
`
`[0049]
`
`Fig. 15B showsillustrative waveforms of voltage induced in a search coil by
`
`the stimulating coil L for different pulse widths of the controllable pulse parameter
`
`transcranial magnetic stimulation circuit of Fig. 14.
`
`[0050]
`
`Fig. 15C showsillustrative waveforms of estimated shape of neuronal
`
`membrane voltage changefor different pulse widths induced with the controllable pulse
`
`parametertranscranial magnetic stimulation circuit of Fig. 14.
`
`(0051]
`
`Fig. 16 is an illustrative schematic diagram of an active snubbercircuit in
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`parallel with a magnetic stimulation coil.
`
`(0052)
`
`‘Fig. 17 is an illustrative schematic diagram of an active snubbercircuit.
`
`[0053]
`
`Figs. 18A-18E are illustrative schematic diagrams of switch implementations
`
`in an active snubbercircuit.
`
`(0054)
`
`‘Fig. 19 is an illustrative schematic diagram of an active snubbercircuit with
`
`switches connectedin series.
`
`[0055]
`
`Fig. 20 showsanillustrative schematic of activating a positive current
`
`conducting active snubber switch.
`
`[0056]
`
`Fig. 21 showsanillustrative schematic of activating a negative current
`
`conducting active snubber switch.
`[0057]
`Fig. 22 is an illustrative schematic diagram of another embodiment of the
`powerelectronics circuitry for the controllable pulse parameter transcranial magnetic
`f
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`stimulation circuit.
`
`Detailed Description
`
`[0058]
`
`The disclosed subject matter provides, among otherthings, a controllable
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`pulse parameter transcranial magnetic stimulation (CTMS) system that induces
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`approximately rectangular electric field pulses in an organ of a body, such as a human
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`brain for example. The amplitude, pulse width, and degree of bidirectionality of the
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`induced electric field pulses are adjustable over a continuous range of values. The degree
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`of bidirectionality is defined as the ratio of the positive phase amplitude to the negative
`
`phase amplitude of the inducedelectric field pulse. By adjusting the degree of
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`bidirectionality, the induced electric field pulse can be varied from bipolar (i.e., equal
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`amplitudes of the positive and negative phases) to predominantly unipolar(i.e., a large
`
`amplitude of one phase for one polarity and a small amplitude of the other phase for the
`
`opposite polarity).
`
`[0059]
`
`In some embodiments, the cTMSsystem disclosed herein switches a
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`stimulating coil between positive-voltage and negative-voltage energy storage capacitors
`
`or capacitor banks using high-power semiconductor devices. Controlling the pulse
`
`parameters facilitates enhancement of TMSas a probeofbrain function and as a potential
`
`therapeutic intervention. Independent control over the pulse parameters (e.g., pulse width,
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`pulse amplitude, degree of bidirectionality, pulse repetition frequency) facilitates defining
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`dose-responserelationships for neuronal populations and producingclinical and
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`physiological effects. For example, dose-response relationships for specific neuronal
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`populationscan be defined, and selected clinical and physiological effects can be
`
`enhanced. Moreover, the cTMSsystem disclosed herein also enables high-frequency (> 1
`
`Hz) repetitive TMS (rTMS) with predominantly unipolar induced electric fields.
`
`Referring to Fig. 1, in one embodiment, an illustrative component diagram of
`(0060]
`a controllable pulse parameter transcranial magnetic stimulation system 100 is shown.
`The cTMSsystem 100 includes a powerelectronics housing 120, a positioning arm 130, a
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`stimulating coil L, and a digital data processing device, such as control computer
`
`electronics 110. The control computerelectronics 110 includes a control computer
`
`electronics housing 102 with analog-digital interface devices, a digital data processing
`device, and a storage device (e.g., a hard disk), a keyboard 104, a monitor 106, and a
`mouse 105 (or trackball), and/or other data entry devices. The power electronics circuitry
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`in housing 120 includes cTMS system powerelectronics that supply currentto the
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`stimulating coil L, which can be positioned and held proximateto a patient's head by the
`positioning arm 130. The powerelectronics circuitry in the powerelectronics housing 120
`is controlled by the control computer electronics 110. An operator, operating the control
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`computer electronics 110, controls the power electronics in power electronics housing
`
`120 to produce one or more adjustable current pulses that are passed through the
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`stimulating coil L held by positioning arm 130. During a medical treatment, the
`
`stimulating coil L is positioned proximate to a patient’s head. The adjustable current
`
`pulses that are passed throughthe stimulating coil L result in the stimulating coil L
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`generating adjustable magnetic field pulses, which induce adjustable electric field pulses
`
`which, in turn, induce adjustable current pulses in the patient's brain.
`
`[0061]
`
`Referring to Figs. 2A and 2B, illustrative block diagrams of embodiments of
`
`the powerelectronics circuitry in housing !20 and the contro! computer electronics in
`
`housing 102 are respectively shown. The powerelectronics housing 120 houses
`
`electronics used to drive the stimulating coi] L. The electronics in the housing 120 include
`
`a charger 210, a first capacitor Cl, a second capacitor C2,a first capacitor discharger 215,
`a second capacitor discharger 216, a first semiconductor switch Q1, a second
`semiconductor switch Q2, a first snubber circuit 222, a second snubbercircuit 223, a third
`
`snubbercircuit 224, a fourth snubbercircuit 225, a fifth snubber circuit 226, a first gate
`
`drive 220, and a second gate drive 221.
`
`The control computer housing 102 housesa typical central processing unit
`[0062]
`(CPU) (not shown), and various standard printed circuit board slots (not shown). Inserted
`into one of the slots is a controller board 205 that provides contro] signals used to control
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`the cTMSsystem 100,and is discussed in further detail below.
`
`[0663]
`
`In one embodiment, capacitor Cl and capacitor C2 are single capacitors. In
`
`another embodiment, capacitor Cl and capacitor C2 each represent a separate bank of
`
`capacitors. The capacitors in each separate bank are connectedin parallel and/orin series
`
`with each other.
`
`[0064]
`
`Referring to Fig. 3A, an illustrative schematic diagram of the controllable
`
`pulse parametertranscranial magnetic stimulation circuit for driving the stimulation coil
`
`Lis shown. As previously described in connection with the block diagram of Figs. 2A
`
`_and 2B,the controllable pulse parameter transcranial magnetic stimulation circuit for
`driving the stimulation coil L includes energy storage capacitor (or bank of capacitors) Cl,
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`energy storage capacitor (or bank of capacitors) C2, controllable semiconductor switch
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`QI, controllable semiconductor switch Q2, the first and second gate drives 220, 221, and
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`charger 210. The circuit of Fig. 3A additionally includes a