(12) INTERNATIQNAL APPLICATIGN FUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT)
`
`(19) W'III‘ICI InteIIectuaI Propert‘y Organizatien .
`Imemaucnal Bureau
`
`(43) Inlterlmfirmai I’IIBIIICREIIIII Bate
`
`25 NEH/ember 29H} {25. ELENA?) (10) lntematlmnal Publicatlma Number
`
`WI} EMS/@5425 Al.
`
`(51,)
`
`(21.
`~
`3
`
`Internatirmal Patent CIassiflcaleIm:
`AMA" [7/92 (2006.0J)
`b ..
`N
`I I:
`_ “6
`IA I"- ,
`,
`j
`I, M .I
`n 5”” “ma 5 W ““3"“ “m e“) ,
`KK'T’UM'0‘041J54‘“
`
`(22)
`
`IIIteI'rIatIeInaI Filing Date:
`
`(25} Filing “WWW
`(26;) Publicatima Language:
`
`19 Maj/2010 (19.05.2010)
`7
`(
`English
`English
`
`(30) Pricrity Data:
`o,r1/179590
`(II/225,644
`
`19 \Iay 2mg (I9 (35 20%)
`I.5 IIJIY 2909 (15.072039)
`
`
`
`(SI) Designated} States (unless 0. ,,erw...e indicated, for every
`kind afmztz‘omil protection available): AE, AG, AL, AM,
`AC), AT AU, AZ BA BB B: BII BR BW BY BZ.
`CA CII CI CN, CO, C. CZ DE, DK, DM DO
`DZ, EC, EE. EG, ES, FI, CIR, GI). GELII, GM. GT.
`HNI HR.» IIU, 1D; H'a IN) IS, JP.» KEI KGI KM.» KNI KP,
`KR. KZ, LA, LC, LK, LR, IS LT, LU, LY. MA. MD,
`ME, MG, MK, MN, M‘W. MIX, MY, MZ, NA, NG, NI,
`NO,NZ, OMIE. PG PH. PL, ET. RO, RS RU SC. SD
`SE SG .SLK’ 81> 534, ST, 8V5 SY TH TJ TM TN TR!
`TT, TZ -IA US I_T'S,I_'Z VC, VN ZA ZM Zv
`
`,
`.
`.
`Y.
`US (84) Designated States Izmless Othernessmazcated, for evenv
`US
`find 0‘ regwrza/ prazecnorz available/z ARIN) IB'W, (3H,
`GM. KE, LR LS, WV, MZ, NA, SD, SL. SZ, TZ. UG.
`25M, 25w); Eurasian (AM, AZ, By? KG.) {42.53 MI), RU, TJ,
`(71) Applicant (for all designated States may)! US): THE
`TM): £11“ngqu (AL AT} BE BG, CH, CY, CZ, DE, DK,
`TRUSTEES (IF COLUMBIA UNIVERSITY IN THE
`EE ES, FI, FR, GB, GR, HR, HU, IE, 13, If, LE LU,
`CITY OF NEW YORK [US’US]; 412 Low MemCII'IaI
`IN, MC, MK, MT, ml? N0, pL, PT, RO, SE 3}, SK.
`Li‘m313:.53-5 WestII 6th 81., Mail Cede 4:08 Ne 'York,
`8le TR) OAIIIIBF BI, CF, CG, CI, CM, GA. GN, GQ,
`NY 100270.5)
`GW MI... MR NE, SN. TI), TO)
`lm'enmr; and
`lm'eIItCIr/Apgslicaflt (for US" only): I’E'I‘ERCHEV, An— Pubfished;
`girl, Vladimimv [BS/US}; 495 West End Avenue, RGE, _
`New York. NY 10024 (US).
`(74) Agents: CAT/TN, Mark, A. et aI.; Miles & Stockbridge
`RC, 1751 Pinnacle Drive, Suite 500. McLean, VA
`22102-3833 (US).
`
`(72)
`(75)
`
`,.
`I
`.
`. , m,
`,.
`.
`wzm Inlematzona: 5“:an regal; (Art, 41(3))
`
`(54} Title: ST SIIEMS AND METHODS FOR INIDUCING I CLCII’:C I I:ILI) I’IILSES lN 25‘ BODY ORGAN
`
`
`
`(57) AI3§tractz Systerm aIId methodg"III prCIvidIng chII1CIIl211)‘Ie pulse paIaIneteI‘ magnetic SLIIIIU,latiCII are described. 0118 aspec‘w'
`
`Llil’ccted-I0 a magnetic stIIrIulaIICIII systemIor inducing approximater rectangular electric field pulses Inc body Organ ccmprising
`an electrical energy smrage de\Ice, a stimulating coil. and a swithIuIg means {or ClCCtrICaII).
`CIIJpIIIIlg saIdelectri'cal energy RIIII—
`age device to said stimulating
`chI to produce cm‘r’em pulses In said stimuIating chI which generates, III response to the current
`pulses, magnetic field palms that can Induce approximately rectangular electric field pulhes in the burly organ.
`
` m ~
`
`63
`
`mNV
`
`ein
`if;
`mW
`
`\C
`
`:W
`3:
`N
`
`S»
`
`

`

`‘WO EMS/135425
`
`PC'l‘lUSlelll/llfilfiéllll
`
`SYSTEMS AND ME'l’flOD-S FUR lND‘UClNG ELECTRIC FIELD PULSES EN A
`
`BQDY ORGAN
`
`
`
`[iltltlll
`
`This application claims prierity tn, and the benefit of, US. Pruvisional
`
`Application No. 61l225,644,. tiled nn luly l5, 2009, and US Provisional Application No,
`
`til/”9,590, filed en May 199 2009, the entireties of both at which applications are hereby
`
`incorpnrated herein by reference.
`
`
`Field
`
`llltlllZl
`
`The disclosed subject matter relates to systems and methods for providing
`
`controllable pulse parameter magnetic stimulation that induces electric field pulses in a
`
`hudy organ.
`
`Backgruund
`
`{$983} Magnetic stimulation is a neninvasive tocl for the study ni‘ the human brain
`
`and peripheral nerves that is being investigated as a petential therapeutic agent in
`
`psychiatry and neurology. When applied to the brain, this technique is commonly referred
`
`to as 'l‘ranscranial Magnetic Stimulation (FMS). However, the term “Tit/i3" is Often used
`
`to refer to magnetic stimulation of other body organs as well 'l'herefore, the term TMS
`
`will be used hereinafter tn refer to magnetic stimulation of the brain or other body organs.
`
`llltliltl}
`
`in This, a pulsed current sent through a cell pruduces a magnetic'l’ield that
`
`induces an electric field in the brain, which can affect neuronal activity. A single ”rs/rs
`
`pulse can activate a targeted brain circuit. For example, a 'l'MS pulse delivered tn the
`
`meter cortex can result in a twitch of the associated muscles in the hndy. Further; a single
`
`TMS pulse can also disrupt neural activity. For example“ a 'l‘lviS pulse delivered to the
`
`occipital cortex can mask the perception of a visual stimulus. This allows researchers to
`
`probe brain circuits on a millisecond time scale.
`[@865]
`A train at TMS pulses, referred tn as repetitive TMS (r’l‘MS), can preduce
`
`excitatory or inhibitory effects which last heynntl the stimulation interval. Repetitive
`
`TMS provides a means to study higher cognitive functions, and it could potentially be
`
`used as a therapeutic intervention in psychiatry and neurnlogy.
`
`[illliltfi
`
`The neural respunse to 'l‘l‘vlS is sensitive tn the parameters of the stimulating
`
`TMS pulse. The pulse width (PW), shape (rag, sinuseidal vs. rectangular), and the
`
`

`

`W'O film/135425
`
`PCT/llSZtlltlIll354lll
`
`relative amplitude of the positive and negative phases (degree of hidircctionality) of the
`
`induced electric field affect the physiological response to TMS, the power efficiency of
`
`the stimulator, and the heating of the stimulating coil. Existing TMS systems are capable
`
`of inducing only damped cosine electric field pulse shapes, with a limited set of discrete
`
`choices of pulse width and degree of hidirectionality. Further? in existing TMS systems,
`monophasic magnetic field pulse shapes are associated with very low power efficiency of
`
`the stimulator in r'l'MS applications.
`
`Description
`
`\
`
`[noon
`
`Systems and methods are disclosed for providing controllable pulse parameter
`
`magnetic stimulation that induces electric field pulses in a body organs One aspect is
`
`directed to a magnetic stimulation system for inducing approximately rectangular electric
`field pulses in a body organt 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 response to the Current pulses, magnetic field pulses that can induce approximately
`
`rectangular electric field pulses in the body organ.
`
`[lllllllll Another aspect is directed to a magnetic stimulation system for inducing
`
`approximately rectangular electric 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 change in 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.
`
`[9899}. Another aspect is 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 means electrically coupled to the first energy storage
`
`device and the stimulating coil, providing a second switching means electrically coupled
`
`is.)
`
`

`

`‘WO Emil/135425
`
`PC'l‘.’USlelli/ll$54iil
`
`to the second energy storage device and the stimulating coil, actuating the first switching
`
`means to'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 oi’change in the
`
`stimulating coil; actuating the second switching means to electrically couple the second
`
`energy storage device to the stimulating coil for a second periodof 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 lield pulses that can induce
`
`approximately rectangular eiectric 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 puises in the
`
`body organ.
`
`{litiiiill 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 means for electrically coupling
`
`said electrical energy storage device to said stimulating coil to produce selectively—
`
`acljustabienwitith current pulses in said stimulating coil which generates, in response to
`
`the current pulses, magnetic field pulses that can induce selectively-adjustable-width
`
`el chic field pulses in the body organ“
`
`{till} 1} 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
`
`means to produce selectiveiy~adjustablenwidth current pulses in said stimulating coil
`
`which generates, in response to the current pulses, magnetic field pulses that can induce
`
`seiectively-adjustahle-wirilh eiectric field pulses in the body organ.
`
`lilillZ} 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
`
`second electrical energy storage device to a selectable second voltage, a stimulating coil,
`
`

`

`‘WO EMS/135425
`
`PC'l‘.’USZtlltl/tl$54tll
`
`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 coupie the second electrical
`
`energy storage device to said stimulating coil to produce current pulses with a negative
`
`rate of change in the stimulating coil, wherein the stimulating coil produces, in response
`
`to 2t combination of the current pulses with the positive and negative rates of change,
`
`magnetic field pulses that can induce electric fieid pulses in the body organ, the degree of
`
`hidirectionaiity being determined by the ratio of the seiectahie first voltage and the
`
`selectable second voltage.
`
`[Gillie] Another aspect is directed to a method of inducing electric field pulses with tin
`
`adjustable degree of bidirectionaiity in a body organ. The method comprises providing a
`
`first and it second electrical energy storage device, providing it 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, oroviding a
`
`stimulating coil, providing a first switching means electrically coupled to the first
`
`electrical energy storage device and the stimulating coil, providing a second switching
`
`means electrically coupled to the second eiectrical energy storage device and the
`
`stimulating coil, setting a desired degree of hidirectionality by selecting respective
`
`amplitudes for the first and second voltages, the degree of hidirectionelity being
`
`etennined by the ratio of the selected first voltage and the selected second voltage,
`
`actnating said first switching means to electrically couple the first electrical energy
`
`storage device to the stimulating coil for it first period of time to produce current pulses
`
`with a positive rate of change in the stimulating coil, actuating said second switching
`
`means to electrically couple the second electrical 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 coii proximate to the body organ and
`
`exposing the body organ to the magnetic field pulses thereby inducing electric field
`
`guises in the body organ with the desired degree of bidirectionelity.
`
`

`

`W0 rein/issue
`
`PCP/U820ill/llSSallll,
`
`llitlldl Another aspect is 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 response to the current pulses, magnetic field pulses that can induce electric
`
`field pulses in the hotly organ, the electric field pulses having a plurality of selectively
`
`adjustable parameters from a group consisting of amplitude, pulse width, degree of
`
`hidirectionality and pulse repetition frequency; and an operatormcontrolled apparatus
`
`including means for independently controlling at least two of said parameters.
`
`{9915} 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 means to
`
`produce current pulses in said stimulating cell which generates, in response to the current
`
`pulses, magnetic field pulses that can induce electric 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 lay the electric ticld
`
`pulses, and controlling at least two of said parameters based on the detected physiological
`
`effects.
`
`{Mild} Another aspect is 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 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 rectangular electric field
`
`pulses in the body organ,
`
`[9017} Another aspect is 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 induce electric field pulses in the body organ, and switchahly electrically
`
`coupling the electrical energy storage device to the stimulating coil to produce current
`
`

`

`‘WO EMS/135425
`
`PC'l‘lUSlelll/lifilfiéllll
`
`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 hotly
`
`organ.
`
`{9918}
`
`in a first embodiment, two energy storage capacitors are connected to a
`
`common ground. A positive pulse is created in a transcranial magnetic stimulation
`
`(TMS) coil by connecting it between a ti rst of two capacitors and ground for a first
`
`interval of time and then disconnecting the first capacitor and permitting a current to
`
`continue to flow through the "EMS coil through a first diode connected between the coil
`
`and ground and a second diode connected between the coil and a second capacitor,
`
`therehy charging the second capacitor using the magnetic field energy stored in the TMS
`
`coil.
`
`{£13919}
`
`in a second embodiment, two energy storage capacitors are connected to a
`
`common ground. A positive pulse is created in a transcrani' l magnetic stimulation
`
`(TMS) coil by connecting it between a lirst 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 TMS coil through a first diode
`
`connected between the coil and ground and a second diode connected between the coil
`
`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.
`
`{@929}
`
`in either ol" the above twoernbodirnents, the coil can he short-circuitod by
`
`closing respective switches on either side of the TMS coil to connect either side of the
`
`'l'MS coil together.
`
`in a variation this causes both sides of the TMS coil to be connected
`
`to ground.
`
`I
`
`{9821}
`
`in either of the embodiments, a negative voltage is applied across the TMS
`
`coil by closing third and fourth switches.
`
`@022} Another aspect is directed to a magnetic stimulation system for inducing
`
`approximately rectangular electric field pulses in a hotly organ, comprising a first and
`
`second electrical energy storage device, a stimulating coil, a first and second 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
`
`third and fourth switching means to electrically couple said second electrical storage
`
`6
`
`

`

`‘WO Emil/135425
`
`PC'i‘lUSZtlltl/llilfiélill
`
`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 iield pulses in the body organ
`
`{9923] Another aspect is directed to a method oi 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 the first energy storage
`
`device and the stimulating coil, providing a third and fourth switching means electrically
`
`coupled to the second energy storage device and the stimulating coil, actuating the first
`
`and second switching means to 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
`
`change in the stimulating coil, actuating the third and fourth switching means to
`
`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 oi'change in the stimulating
`
`coil, and thereby causing the stimuiating 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 hotly organ and exposing the body organ to the magnetic
`
`field pulses thereby inducing the approximately rectangular electric field pulses in the
`
`hotly organ.
`
`[90243
`
`in a variation of the above, the. two energy storage devices include two
`
`capacitors, each charged to a different voltage level relative to a common ground. The
`
`circuit common ground can be directly connected to earth ground. For a 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 the first capacitor is disconnected
`
`allowing current in the coil to decline over an intervalr Then a voltage from the second
`
`capacitor is 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 another intervai.
`
`

`

`‘WO EMS/135425
`
`PC'i‘lUSZiiw/liiiifiéiiii
`
`Brief Deserintion 9f the Drawings
`
`{8925]
`
`Fig. i is an iiiustrative component diagram of a controiiabie pulse parameter
`
`transerania‘i magnetic stimuiation system. according to some emhttdiments of the
`
`diseiesed snbjeet matter.
`
`[9926]
`
`Fig. 2A is an iiiustrative bioek diagram of an embndiment of the power
`
`eieetronics circuitry for the contreiiabie pulse parameter transeraniai magnetic stitnuiation
`
`system of Fig. i.
`
`[8027]
`
`Fig. 2B is an iiinstrative biock diagram of an embodiment of the control
`
`cementer eieetronies for the centroiiahie puise parameter transcrnniai magnetic:
`
`stimuiation system of Fig. i.
`
`HERE}
`
`Fig. 3A is an iiiustrative schematic diagram of another embodiment (if the
`
`power eieetronics circuitry for emitroiiabie puise parameter transcraniai magnetic
`
`stimuiation circuit.
`
`[@929]
`
`Fig“ 3B is an iiiustrative schematic diagram of an insuiated—gate bipoiar
`
`transistor switch with an anti~paraiiei diode.
`
`[$030]
`
`Fig. 3C is an iiinstrative schematic diagram of a gate turn—off thyristor with an
`
`antivparaiiei diode.
`
`[iiiifiii
`
`Figs. 333—3?” are iiiustrative schematic diagrams of snubber circuits.
`
`{9932}
`
`Fig. 4A is an iiittstrative graph of a positive magnetic ptiise generated by using
`
`the controllabie puise parameter transeraniai magnetic stimulation circuit of Fig. 3A.
`
`[9333]
`
`Fig. 4B is an iiinstrative graph of a negative magnetic: guise generated using
`
`the controllable puise parameter transcraniai magnetic stimuiation circuit of Fig. 3A.
`
`[@934]
`
`Fig. 5A shows iiiustrative wavefnnns of a menophasie magnetic fieiti puise
`
`(B), an associated electric fieid (E). and neurnnni membrane voitage (Vm) induced in the
`
`brain by a eontrniiahie puise parameter transetaniai magnetic stimuiation system,
`
`according to one embodiment of the disclosed subject matter.
`
`[0935]
`
`Fig. 53 shows iiiustrative waveforms at a biphasie magnetic fieiti (B), an
`
`associated eieetric iieiti (E), and neurons} membrane voitage (Vm) indueeti in the brain by
`
`a enntrniiabie puise parameter transeraniai magnetic stimuiation system, according to one
`
`embodiment of the diseiosett subject matter.
`
`[9936]
`
`Fig. 6 is an iiiustrative waveform depicting user~adjustabie puise parameters,
`
`according to one embodiment of the diseiosed subject matter.
`
`

`

`W0 anions-5425
`
`PCP/U821}lil/ll354ll‘i
`
`{@037}
`
`Fig. 7 shows illustrative waveforms; of anproximately rectangular induced
`
`electric field pulses with pulse widths adjustable over a continuous range of values,
`
`generated by a controllable pulse parameter transcranial magnetic stimulation circuit,
`
`according to one embodiment of the disclosed subject matter.
`
`[9038}
`
`Fig. 8 shows illustrative waveforms of approximately rectangular induced
`
`electric field pulses with bidirectionality adjustable over a continuous range, generateti by
`
`a controllable pulse parameter transcranial magnetic stimulation circuit, according to one
`
`embodiment of the disclosed subject matter.
`
`{093%}
`
`Fig. 9 is an illustrative waveform of repetitive TMS with predominantly
`
`unipolar induced electric field pulses. with adjustable pulse repetition frequency,
`
`according to one embodiment of the disclosed subject matter.
`
`{liliéllll
`
`Fig. it} is an illustrative simulation circuit for producing controllable pulse
`
`parameter trnnscranial magnetic stimulation, in accordance with the disclosed subject
`matter.
`
`{09%}
`
`Fig. l l is a table of pulse performance metrics used to evaluate the efficiency
`
`of controllable pulse parameter transcranial magnetic stimulation pulses.
`
`{06242}
`
`Fig. lZA shows an illustrative waveform of a coil current produced by the
`
`simulation circuit of Fig. it).
`
`{@9633}
`
`Fig. 123 shows an illustrative waveform of a peak induced electric field
`
`produced by the simulation circuit of Fig. 10.
`
`{$944}
`
`Fig. 12C shows an illustrative waveform of a neuronal membrane voltage
`
`change produced by the simulation circuit of Fig. it).
`
`[llllifiifil
`
`Fig.
`
`l3i-‘r is an illustrative block diagram of power electronics circuitry for a
`
`controllable pulse parameter transcraniai magnetic stimulation system. according to
`
`another embodiment of the disclosed subject matter.
`
`[£39463
`
`Fig. 133 is an illustrative block diagram of another embodiment of the control
`
`computer electronics for the controllable poise parameter transcranial magnetic
`
`stimulation system.
`
`{6M7}
`
`Fig. 14 is an illustrative schematic of a controllable pulse parameter
`
`transcraniai magnetic stimulation circuit. according to another embodiment of the
`
`invention.
`
`

`

`‘WO EMS/135425
`
`PC'i‘lUSlelli/iifilfidill
`
`{99%}
`
`Fig. 15A shows iliuatrative waveforms cf voltage acrcss capacitor C5 for
`
`different pulse widths of the contrailahle pulse parameter transcranial magnetic
`
`stimulation circuit cf Fig l4.
`
`{@9453}
`
`Fig“ HEB shows illustrative 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.
`
`[tidfiiij
`
`Figi EEC shows illustrative wavetcrms cf estimated shape of neuronal
`
`membrane voltage change for different pulse widths induced with the controllable pulse
`
`parameter transcranial magnetic stimulation circuit of Fig. l4.
`
`‘
`
`[9651}
`
`Fig. i6 is an illustrative schematic diagram of an active snubber circuit in
`
`parallel with a magnetic stimulation coil.
`
`[9952}
`
`Fig. i7 is an illustrative schematic diagram of an active snubbcr circuit.
`
`[@0533
`
`Figs.
`
`lSA—lttfi are illustrative schematic diagrams cf switch implementations
`
`in an active sntthber circuit
`
`{@054}
`
`Fig. i9 is an illustrative schematic diagram of an active snubber circuit with
`
`switches connected in series.
`
`{@055}
`
`Fig. 2G shews an illustrative schematic of activating a positive current
`
`conducting active snubber switch.
`
`{@3056}
`
`Fig. 21 shows an illustrative schematic of activating a negative current
`
`ccnducting active snuhher switch.
`{@957}
`Fig. 22 is an illustrative schematic diagram of another embodiment of the
`
`newer electrcnica circuitry for the controllable praise parameter transcranial magnetic
`
`stimulation circuit.
`
`Detailed Descriggticn
`
`[9958}
`
`The disclosed subject matter provides, among other things, a controllable
`
`pulse parameter transcranial magnetic stimulation (cTMS) system that induces
`
`approximately rectangular electric field pulses in an organ of a body, such as a human
`
`brain for example. The amplitude, pulse width, and degree of hidirecticnality cf the
`
`induced electric field pulses are adjustable over a continuous range of values. The degree
`
`cf hidirectionality is defined as the ratio of the positive phase amplitude to the negative
`
`phase amplitude at the induced electric field pulse. By adjusting the degree (if
`
`it)
`
`

`

`W0 tarsus-5425
`
`PCP/U820lil/il354lll.
`
`hidirectionality, the induced electric field pulse can be varied from bipolar (i.e., equal
`
`amplitudes of the positive and negative phases) to predominantly unipolar tie, a large
`
`amplitude of one phase for one polarity and a small amplitude of the other phase for the
`
`opposite polarity).
`
`{0659}
`
`in some embodiments, the CTMS system disclosed herein switches a
`
`stimulating coil between positive-voltage and negativemvoltage energy storage capacitors
`
`or capacitor hanks using high~power semiconductor devices. Controlling the pulse
`
`parameters facilitates enhancement of TMS as a probe of brain function and as a potential
`
`therapeutic intervention. independent control over the pulse parameters {or}, pulse width,
`
`pulse amplitude, degree of bidirectionality, pulse repetition frequency) facilitates defining
`
`dose—response relationships for neuronal populations and producing clinical and
`
`physiological effects. For example, (loser-response relationships for specific neuronal
`
`populations can be defined, and selected clinical and physiological effects can he
`
`enhanced. Moreover, the cTMS system disclosed herein also enables high~frequency (> l
`
`lie) repetitive TMS (rTMS) with predominantly unipolar induced electric fields.
`
`{dildo}
`Referring to Fig. l, in one embodiment, an illustrative component diagram of
`a controllable pulse parameter transcranial magnetic stimulation system lllO is shown
`
`The cTMS system it'll} includes a power electronics housing l20, a positioning arm l30, a
`
`stimulating coil L, and a digital data processing device, such as control computer
`
`electronics ill}. The control computer electronics lit) includes a control computer
`
`electronics housing lClZ with analogdigltal interface devices, a digital data processing
`
`device, and a storage device (cg, a hard disk), a keyboard NM, a monitor lflo, and a
`
`mouse lOS (or trackball), and/or other data entry devices. The power electronics circuitry
`
`in housing tilt) includes chVlS system power electronics that supply current to the
`
`stimulating coil L, which can he positioned and held proximate. to a patient’s head lay the
`
`positioning arm l30. The power electronics circuitry in the power electronics housing l2il
`
`is controlled by the control computer electronics llfl. An operator, operating the control
`
`computer electronics lit), controls the power electronics in power electronics housing
`
`lEiIi to produce one or more adjustahle current pulses that are passed through the
`
`stimulating coll L held by positioning arm l30. filming a medical treatment, the
`
`stimulating coil is is positioned proximate to a patient's head. The adjustable current
`
`pulses that are passed through the stimulating coil L result in the stimulating coil L
`
`ll
`
`

`

`‘WO EMS/135425
`
`PC'l‘.’USlelll/ll$54lll
`
`generating adjustable magnetic field pulses, which induce adjustable electric field pulses
`
`which, in turn, induce adjustable current pulses in the patients brain.
`
`{nest}
`
`Referring to Figs. 2A and 2 , illustrative block diagrams of embodiments of
`
`the power electronics circuitry in housing l20 and the control computer electronics in
`
`housing lGZ are respectively shown. The power electronics housing ill) houses
`
`electronics used to drive the stimulating coil L. The electronics in the housing l20 include
`
`a charger 2 it), a first capacitor Cl, a second capacitor C2, a first capacitor dischargcr 215,
`a second capacitor discharger 216, a first semiconductor switch Ql, a second
`
`semiconductor switch Q2, a first snuhher circuit 222, a second snuhher circuit 223, a third
`
`snubber circuit 224? a fourth snuhher circuit 2.25, a fifth snuhher circuit 226, a first gate
`
`drive 220, and a second gate drive 22L
`
`{@621
`
`The control computer housing l02 houses a typical central processing unit
`
`(CPU) (not shown}, and various standard printed circuit board slots {not shown). inserted
`
`into one of the slots is a controller hoard 205 that provides control signals used to control
`
`the c’l‘MS system lilil, and is discussed in further detail below.
`
`{tillfifil
`
`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 hank are connected in parallel and/or in series
`
`with each other.
`
`{nest}
`
`Referring to Fig. 3A, an illustrative schematic diagram of the controllable
`
`pulse parameter transcranial magnetic stimulation circuit for driving the stimulation coil
`
`L is shown. As previously described in connection with the blo