1111111111111111 IIIIII IIIII 1111111111 11111 111111111111111 111111111111111 IIIIII IIII 11111111
`US 20110190569Al
`
`c19) United States
`c12) Patent Application Publication
`Simon et al.
`
`c10) Pub. No.: US 2011/0190569 Al
`Aug. 4, 2011
`(43) Pub. Date:
`
`(54) NON-INVASIVE METHODS AND DEVICES
`FOR INDUCING EUPHORIA IN A PATIENT
`AND THEIR THERAPEUTIC APPLICATION
`
`(75)
`
`Inventors:
`
`Bruce Simon, Mountain Lakes, NJ
`(US); Joseph P. Errico, Warren, NJ
`(US); John T. Raffle, Austin, TX
`(US)
`
`(73) Assignee:
`
`ElectroCore, LLC, Morris Plains,
`NJ (US)
`
`(21) Appl. No.:
`
`13/024,727
`
`(22) Filed:
`
`Feb.10,2011
`
`Related U.S. Application Data
`
`(63) Continuation-in-part of application No. 13/005,005,
`filed on Jan. 12, 2011, which is a continuation-in-part
`of application No. 12/964,050, filed on Dec. 9, 2010,
`which is a continuation-in-part of application No.
`12/859,568, filed on Aug. 19, 2010, said application
`No. 12/859,568 is a continuation-in-part of application
`
`No. 12/408,131, filed on Mar. 20, 2009, which is a
`continuation-in-part of application No. 12/612,177,
`filed on Nov. 4, 2009.
`(60) Provisional application No. 61/415,469, filed on Nov.
`19, 2010.
`Publication Classification
`
`(51)
`
`Int. Cl.
`(2006.01)
`A61N 1136
`(52) U.S. Cl. ............................................. 600/26; 607/45
`ABSTRACT
`(57)
`
`A novel non-invasive magnetic stimulator is used to modulate
`electrical activity of a patient's vagus nerve. Parameters of the
`stimulation are selected in such a way as to induce a state of
`euphoria in the patient. The methods and devices may be used
`for anesthesia, or to treat insomnia, depression, or premen(cid:173)
`strual syndromes. They may be used as substitution with(cid:173)
`drawal tools for individuals who otherwise would depend on
`substances and behaviors to achieve a euphoric state of mind,
`particularly individuals who abusively consume drugs, alco(cid:173)
`hol or food, or who exhibit behavioral disorders such as
`compulsive gambling. The devices and methods may also be
`used to prevent, manage, or relieve stress.
`
`36
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`35
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`37 37
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`35
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`34
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`33
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`34
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`32
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`LUMENIS EX1047
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`Patent Application Publication
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`Aug. 4, 2011 Sheet 1 of 7
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`US 2011/0190569 Al
`
`FIG. 1
`
`NS Dev'ice 300
`
`Impulse
`Generator
`3i0
`
`Control
`Unit
`330
`
`Pov1er
`Source
`320
`
`FIG. 2
`
`400
`
`Current
`
`Time
`
`~,,.---------~---...."--.... ...., .. _.,_ --~ .....
`
`420
`
`I
`
`Current r 4:,_
`
`r
`
`___ , m""-
`
`Time
`
`LUMENIS EX1047
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`Patent Application Publication
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`Aug. 4, 2011 Sheet 2 of 7
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`US 2011/0190569 Al
`
`FIG. 3A
`
`FIG. 3B
`
`30
`
`FIG. 3C
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`30
`
`FIG. 3D
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`30-
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`34
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`34
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`34
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`34
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`32
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`30
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`Patent Application Publication
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`Aug. 4, 2011 Sheet 3 of 7
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`US 2011/0190569 Al
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`FIG.4A
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`FIG.4D
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`FIG.4E
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`Patent Application Publication
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`Aug. 4, 2011 Sheet 4 of 7
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`US 2011/0190569 Al
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`FIG. 5
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`30
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`39
`
`--38
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`Patent Application Publication
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`Aug. 4, 2011 Sheet 5 of 7
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`US 2011/0190569 Al
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`FIG. 6
`
`"'■,l'.·5
`~--===i.-----4.---J ..
`----=-:------=-r------"k-- 7 6
`---------77
`
`30
`
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`Patent Application Publication
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`Aug. 4, 2011 Sheet 6 of 7
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`US 2011/0190569 Al
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`FIG. 7
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`66 67 68
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`76
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`Patent Application Publication
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`Aug. 4, 2011 Sheet 7 of 7
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`US 2011/0190569 Al
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`FIG. 8
`
`Vagal
`Nerve
`Stimulation
`
`81
`
`82
`
`84
`
`!
`
`92
`
`TGF-P
`
`Retinoic
`Acid
`97
`tas
`96
`-~
`,.,
`I
`I Pro-Inflammatory
`Anti-Inflammatory
`Cytokine. e.g., RI Inflammation I...,.._
`--
`Cytokine, e.g.,
`86 TNF-(L
`--
`--
`
`93
`
`--
`
`Neurotrophic
`Factor. e.g.,
`BDNF
`
`83 ..
`
`91
`
`94
`
`95
`
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`US 2011/0190569 Al
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`Aug. 4, 2011
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`1
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`NON-INVASIVE METHODS AND DEVICES
`FOR INDUCING EUPHORIA IN A PATIENT
`AND THEIR THERAPEUTIC APPLICATION
`
`CROSS REFERENCE TO RELATED
`APPLICATIONS
`
`[0001] This application is a continuation-in-part applica(cid:173)
`tion of U.S. patent application Ser. No. 13/005,005 filed Jan.
`12, 2011, which is a continuation-in-part application of U.S.
`patent application Ser. No. 12/964,050 filed Dec. 19, 2010,
`which claims the benefit of priority ofU.S. Provisional Patent
`Application No. 61/415,469 filed Nov. 19, 2010 and is a
`continuation-in-part application of U.S. patent application
`Ser. No. 12/859,568 filed Aug. 9, 2010, which is a continua(cid:173)
`tion-in-part of co-pending U.S. patent application Ser. No.
`12/408,131 filed Mar. 20, 2009 and a continuation-in-part
`application of co-pending U.S. patent application Ser. No.
`12/612,177 titled Electrical Treatment of Hypertension, filed
`Nov. 9, 2009, the entire disclosure of which is hereby incor(cid:173)
`porated by reference.
`
`BACKGROUND OF THE INVENTION
`
`[0002] The field of the present invention relates to the deliv(cid:173)
`ery of energy impulses (and/or fields) to bodily tissues for
`therapeutic purposes. It relates more specifically to the use of
`non-invasive methods and devices, particularly methods that
`make use of magnetic stimulation devices, to treat depression
`and/or induce in a patient a euphoric affect or sense of well(cid:173)
`being, using energy that is delivered by such devices. The
`disclosed methods involve stimulation of the vagus nerve to
`induce euphoria, for example, in individuals needing relief
`from mental and physical stress, depression, premenstrual
`syndrome, substance abuse and withdrawal including over(cid:173)
`eating, and behavioral disorders including compulsive gam(cid:173)
`bling. The disclosed methods and devices may also be used
`for purposes of anesthesia or as a sleep aid for insonmia.
`[0003] Treatments for various infirmities sometime require
`the destruction of otherwise healthy tissue in order to produce
`a beneficial effect. Malfunctioning tissue is identified and
`then lesioned or otherwise compromised in order to produce
`a beneficial outcome, rather than attempting to repair the
`tissue to its normal functionality. A variety of techniques and
`mechanisms have been designed to produce focused lesions
`directly in target nerve tissue, but collateral damage is inevi(cid:173)
`table.
`[0004] Other treatments for malfunctioning tissue can be
`medicinal in nature, but in many cases the patients become
`dependent upon artificially synthesized chemicals. In many
`cases, these medicinal approaches have side effects that are
`either unknown or quite significant. Unfortunately, the ben(cid:173)
`eficial outcomes of surgery and medicines are often realized
`at the cost of function of other tissues, or risks of side effects.
`[0005] The use of electrical stimulation for treatment of
`medical conditions has been well known in the art for nearly
`two thousand years. It has been recognized that electrical
`stimulation of the brain and/or the peripheral nervous system
`and/or direct stimulation of the malfunctioning tissue holds
`significant promise for the treatment of many ailments,
`because such stimulation is generally a wholly reversible and
`non-destructive treatment.
`[0006] Nerve stimulation is thought to be accomplished
`directly or indirectly by depolarizing a nerve membrane,
`causing the discharge of an action potential; or by hyperpo-
`
`larization of a nerve membrane, preventing the discharge of
`an action potential. Such stimulation may occur after electri(cid:173)
`cal energy, or also other forms of energy, are transmitted to the
`vicinity of a nerve [F. RATTAY. The basic mechanism for the
`electrical stimulation of the nervous system. Neuroscience
`Vol. 89, No. 2, pp. 335-346, 1999; Thomas HEIMBURG and
`Andrew D. Jackson. On soliton propagation in biomem(cid:173)
`branes and nerves. PNAS vol. 102 (no. 28, Jul. 12, 2005):
`9790-9795]. Nerve stimulation may be measured directly as
`an increase, decrease, or modulation of the activity of nerve
`fibers, or it may be inferred from the physiological effects that
`follow the transmission of energy to the nerve fibers.
`[0007] Electrical stimulation of the brain with implanted
`electrodes has been approved for use in the treatment of
`various conditions, including movement disorders such as
`essential tremor and Parkinson's disease. The principle
`underlying these approaches involves disruption and modu(cid:173)
`lation of hyperactive neuronal circuit transmission at specific
`sites in the brain. Unlike potentially dangerous lesioning pro(cid:173)
`cedures in which aberrant portions of the brain are physically
`destroyed, electrical stimulation is achieved by implanting
`electrodes at these sites. The electrodes are used first to sense
`aberrant electrical signals and then to send electrical pulses to
`locally disrupt pathological neuronal transmission, driving it
`back into the normal range of activity. These electrical stimu(cid:173)
`lation procedures, while invasive, are generally conducted
`with the patient conscious and a participant in the surgery.
`[0008] Brain stimulation, and deep brain stimulation in par(cid:173)
`ticular, is not without some drawbacks. The procedure
`requires penetrating the skull, and inserting an electrode into
`brain matter using a catheter-shaped lead, or the like. While
`monitoring the patient's condition (such as tremor activity,
`etc.), the position of the electrode is adjusted to achieve sig(cid:173)
`nificant therapeutic potential. Next, adjustments are made to
`the electrical stimulus signals, such as frequency, periodicity,
`voltage, current, etc., again to achieve therapeutic results. The
`electrode is then permanently implanted, and wires are
`directed from the electrode to the site of a surgically
`implanted pacemaker. The pacemaker provides the electrical
`stimulus signals to the electrode to maintain the therapeutic
`effect. While the therapeutic results of deep brain stimulation
`are promising, there are significant complications that arise
`from the implantation procedure, including stroke induced by
`damage to surrounding tissues and the neuro-vasculature.
`[0009] One of the most successful applications of modem
`understanding of the electrophysiological relationship
`between muscle and nerves is the cardiac pacemaker.
`Although origins of the cardiac pacemaker extend back into
`the 1800's, it was not until 1950 that the first practical, albeit
`external and bulky, pacemaker was developed. The first truly
`functional, wearable pacemaker appeared in 1957, and in
`1960, the first fully implantable pacemaker was developed.
`Around this time, it was also found that electrical leads could
`be connected to the heart through veins, which eliminated the
`need to open the chest cavity and attach the lead to the heart
`wall. In 1975 the introduction of the lithium-iodide battery
`prolonged the battery life of a pacemaker from a few months
`to more than a decade. The modern pacemaker can treat a
`variety of different signaling pathologies in the cardiac
`muscle, and can serve as a defibrillator as well (see U.S. Pat.
`No. 6,738,667 to DENO, et al., the disclosure of which is
`incorporated herein by reference).
`[0010] Another application of electrical stimulation of
`nerves has been the treatment of radiating pain in the lower
`
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`extremities by stimulating the sacral nerve roots at the bottom
`of the spinal cord (see U.S. Pat. No. 6,871,099 to WHITE(cid:173)
`HURST, et al., the disclosure of which is incorporated herein
`by reference).
`[0011] Yet another application of electrical stimulation of
`nerves has been the treatment of epilepsy and depression by
`vagus nerve stimulation (VNS) [U.S. Pat. No. 4,702,254
`entitled Neurocybernetic prosthesis, to ZABARA; U.S. Pat.
`No. 6,341,236 entitled Vagal nerve stimulation techniques for
`treatment of epileptic seizures, to OSORIO et al; U.S. Pat.
`No. 5,299,569 entitled Treatment of neuropsychiatric disor(cid:173)
`ders by nerve stimulation, to WERNICKE et al]. For these
`procedures, the left vagus nerve is ordinarily stimulated at a
`location on the neck by first implanting an electrode there,
`then connecting the electrode to an electrical stimulator.
`[0012] Despite the clinical use ofVNS in treating epilepsy
`and depression, a specific mechanism underlying VNS relief
`of symptoms is not currently known. Vagus afferent fibers
`innervate several medullary structures, with the nucleus of the
`tractus solitarius (NTS) receiving bilateral inputs totaling
`approximately eighty percent of all vagal afferents. The NTS
`has widespread projections, including direct or multiple syn(cid:173)
`aptic projections to the parabrachial nucleus, vermis, inferior
`cerebellar hemispheres, raphe nuclei, periaquaductal gray,
`locus coeruleus, thalamus, hypothalamus, amygdala, nucleus
`accumbens, anterior insula, infralimbic cortex, and lateral
`prefrontal cortex, making it difficult to determine the area or
`neuronal pathway mediating VNS effects. However, func(cid:173)
`tional imaging studies have concluded that VNS may bring
`about changes in several areas of the brain, including the
`thalamus, cerebellum, orbitofrontal cortex, limbic system,
`hypothalamus, and medulla. The stimulation of particular
`areas of the brain has been suggested as a mechanism for the
`effects of VNS, but such localized stimulation of the brain
`may depend upon the parameters of the stimulation ( current,
`frequency, pulse width, duty cycle, etc.). Those parameters
`may also determine which neurotransmitters are modulated
`(including norepinephrine, seratonin, and GABA) [Mark S.
`GEORGE, Ziad Nahas, Daryl E. Bohning, Qiwen Mu, F.
`Andrew Kozel, Jeffrey Borckhardt, Stewart Denslow. Mecha(cid:173)
`nisms of action of vagus nerve stimulation (VNS). Clinical
`Neuroscience Research 4 (2004) 71-79; Jeong-Ho Chae, Ziad
`Nahas, Mikhail Lomarev, Stewart Denslow, Jeffrey P. Lorb(cid:173)
`erbaum, Daryl E. Bohning, Mark S. George. A review of
`functional neuroimaging studies of vagus nerve stimulation
`(VNS). Journal of Psychiatric Research 37 (2003) 443-455;
`G. C. Albert, C. M. Cook, F. S. Prato, A. W. Thomas. Deep
`brain stimulation, vagal nerve stimulation and transcranial
`stimulation: An overview of stimulation parameters and neu(cid:173)
`rotransmitter release. Neuroscience and Biobehavioral
`Reviews 33 (2009) 1042-1060; GROVES DA, Brown VJ.
`Vagal nerve stimulation: a review of its applications and
`potential mechanisms that mediate its clinical effects. Neu(cid:173)
`rosci Biobehav Rev (2005) 29:493-500; Reese TERRY, Jr.
`Vagus nerve stimulation: a proven therapy for treatment of
`epilepsy strives to improve efficacy and expand applications.
`Conf Proc IEEE Eng Med Biol Soc. 2009; 2009:4631-4].
`[0013] To date, the selection of stimulation parameters for
`VNS has been highly empirical, in which the parameters are
`varied about some initially successful set of parameters, in an
`effort to find an improved set of parameters for each patient.
`A more efficient approach to selecting stimulation parameters
`might be to select a stimulation waveform that mimics elec(cid:173)
`trical activity in the regions of the brain that one is attempting
`
`to stimulate, in an effort to entrain the naturally occurring
`electrical waveform, as suggested in U.S. Pat. No. 6,234,953,
`entitled Electrotherapy device using low frequency magnetic
`pulses,
`to THOMAS et al. and application number
`US20090299435, entitled Systems and methods for enhanc(cid:173)
`ing or affecting neural stimulation efficiency and/or efficacy,
`to GLINER et al. However, some effects ofVNS stimulation,
`such as effects described herein, are simply discovered by
`serendipity, then improved upon deliberately.
`
`SUMMARY OF THE INVENTION
`
`[0014] Applicants have discovered methods for treating
`depression and/or inducing euphoria in a patient that are
`novel, as compared with methods and natural causes that
`were summarized above. The methods that are disclosed
`herein are preferably non-invasive, and they comprise stimu(cid:173)
`lating selected nerve fibers, such as those in the vagus nerve,
`with particular stimulation parameters, preferably using the
`nerve stimulator devices that are also described herein. The
`disclosed methods and devices may also be used for purposes
`of anesthesia or as a sleep aid for insomnia. They may also be
`useful therapeutically as a controlled substitute and with(cid:173)
`drawal tool for individuals who otherwise would depend on
`unsafe substances and behaviors to achieve an elevated state
`of mind, particularly individuals who abusively consume
`food, alcohol, tobacco or drugs, or who exhibit behavioral
`addictions such as gambling. The methods and devices may
`also be useful to prevent, manage, or relieve mental or physi(cid:173)
`cal stress, depression and/or premenstrual syndromes,
`thereby reducing the likelihood or severity of consequent
`health problems such as hypertension, strokes, heart attacks,
`diabetes, ulcers, and neck or low back pain.
`[0015]
`In one aspect of the invention, methods and devices
`are described to induce a euphoric affect in a patient by
`utilizing an energy source that transmits energy non-inva(cid:173)
`sively to nervous tissue. In particular, the disclosed devices
`can transmit energy to, or in close proximity to, a vagus nerve
`of the patient, in order to temporarily stimulate, block and/or
`modulate electrophysiological signals in that nerve.
`[0016]
`In one of the preferred embodiments, a magnetic
`stimulator is used to modulate electrical activity of the vagus
`nerve. The stimulator comprises a source of electrical power,
`a magnetically permeable toroidal core, and a coil that is
`wound around the core. The device also comprises a continu(cid:173)
`ous electrically conducting medium in which the coil and
`core are in contact, wherein the conducting medium has a
`shape that conforms to the contour of a target body surface of
`a patient when the medium is applied to the target body
`surface. For the present medical applications, the device is
`ordinarily applied to the patient's neck. The source of power
`supplies a pulse of electric charge to the coil, such that the coil
`induces an electric current and/or an electric field within the
`patient. The stimulator is configured to induce a peak pulse
`voltage sufficient to produce an electric field in the vicinity of
`a nerve such as the vagus, to cause the nerve to depolarize and
`reach a threshold for action potential propagation. By way of
`example, the threshold electric field for stimulation of nerve
`terminals may be about 8 V/m at 1000 Hz. For example, the
`device may induce an electric field within the patient of about
`10 to 600 V /m and an electrical field with a gradient of greater
`than 2 V/m/mm.
`[0017] The preferred magnetic stimulator comprises two
`toroidal coils and corresponding cores that lie side-by-side,
`each containing a high-permeability material, wherein cur-
`
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`rent passing through a coil produces a magnetic field within
`the core ofabout 0.1 to 2 Tesla. Current passing through a coil
`may be about 0.5 to 20 amperes, typically 2 amperes, with
`voltages across each coil of 10 to 100 volts. The current is
`passed through the coils in bursts of pulses. The burst repeats
`at 1 Hz to 5000 Hz, preferably at 15-50 Hz. The pulses have
`duration of 20 to 1000 microseconds, preferably 200 micro(cid:173)
`seconds and there may be 1 to 20 pulses per burst. The
`preferred magnetic stimulator shapes an elongated electric
`field of effect that can be oriented parallel to a long nerve,
`such as the vagus nerve.
`[0018] By selecting a suitable waveform to stimulate the
`nerve, the magnetic stimulator produces a correspondingly
`selective physiological response in an individual patient. In
`general, the induced electrical signal has a frequency between
`about 1 Hz to 3000 Hz and a pulse duration of between about
`10-1000 microseconds. By way of example, at least one
`induced electrical signal may be of a frequency between
`about 15 Hz to 35 Hz. By way of example, at least one induced
`electrical signal may have a pulsed on-time of between about
`50 to 1000 microseconds, such as between about 100 to 300
`microseconds. The induced electrical signal may have any
`desired waveform, which may comprise one or more of: a full
`or partial sinusoid, a square wave, a rectangular wave, and
`triangle wave.
`[0019] Teachings of the present invention demonstrate how
`non-invasive stimulators may be positioned and used against
`body surfaces, particularly at a location on the patient's neck
`under which the vagus nerve is situated. Those teachings also
`describe the induction of a euphoric affect in a patient, as well
`as methods for using that induced euphoric affect for pur(cid:173)
`poses of anesthesia, or as a sleep aid for insonmia, or for
`treating individuals needing relief from mental and physical
`stress, depression, premenstrual syndromes, substance abuse
`withdrawal and behavioral addictions. However, it should be
`understood that application of the methods and devices is not
`limited to the examples that are given.
`[0020] The novel systems, devices and methods for treating
`conditions using the disclosed magnetic stimulator or other
`non-invasive stimulation devices are more completely
`described in the following detailed description of the inven(cid:173)
`tion, with reference to the drawings provided herewith, and in
`claims appended hereto. Other aspects, features, advantages,
`etc. will become apparent to one skilled in the art when the
`description of the invention herein is taken in conjunction
`with the accompanying drawings.
`
`INCORPORATION BY REFERENCE
`
`[0021] Hereby, all issued patents, published patent applica(cid:173)
`tions, and non-patent publications that are mentioned in this
`specification are herein incorporated by reference in their
`entirety for all purposes, to the same extent as if each indi(cid:173)
`vidual issued patent, published patent application, or non(cid:173)
`patent publication were specifically and individually indi(cid:173)
`cated to be incorporated by reference.
`
`BRIEF DESCRIPTION OF THE DRAWINGS
`
`[0022] For the purposes of illustrating the various aspects
`of the invention, there are shown in the drawings forms that
`are presently preferred, it being understood, however, that the
`invention is not limited by or to the precise data, methodolo(cid:173)
`gies, arrangements and instrumentalities shown, but rather
`only by the claims.
`
`[0023] FIG. 1 is a schematic view of a nerve or tissue
`modulating device according to the present invention, which
`supplies controlled pulses of electrical current to a magnetic
`stimulator coil that is continuously in contact with a volume
`filled with electrically conducting material.
`[0024] FIG. 2 illustrates an exemplary electrical voltage/
`current profile for a blocking and/or modulating impulses that
`are applied to a portion or portions of a nerve, in accordance
`with an embodiment of the present invention.
`[0025] FIG. 3 illustrates a dual-toroid magnetic stimulator
`coil according to an embodiment of the present invention,
`which is shown to be situated within a housing that contains
`electrically conducting material.
`[0026] FIG. 4 illustrates different embodiments of cores
`according to the present invention, around which magnetic
`stimulator coil wires may be wound.
`[0027] FIG. 5 illustrates the housing and cap of the dual(cid:173)
`toroid magnetic stimulator coils of FIG. 3, attached via cable
`to a box containing the device's impulse generator, control
`unit, and power source.
`[0028] FIG. 6 illustrates the approximate position of the
`housing of the magnetic stimulator coil according one
`embodiment of the present invention, when the coil is used to
`stimulate the vagus nerve in the neck of a patient.
`[0029] FIG. 7 illustrates the housing of the magnetic stimu(cid:173)
`lator coil according one embodiment of the present invention,
`as the coil is positioned to stimulate the vagus nerve in a
`patient's neck via electrically conducting gel (or some other
`conducting material), which is applied to the surface of the
`neck in the vicinity of the identified anatomical structures.
`[0030] FIG. 8 illustrates mechanisms or pathways in the
`brain through which stimulation of the vagus nerve may pro(cid:173)
`duce euphoria in a patient.
`
`DETAILED DESCRIPTION OF THE PREFERRED
`EMBODIMENTS
`
`[0031]
`In the present invention, energy is transmitted non(cid:173)
`invasively to a patient. The invention is particularly useful for
`inducing applied electrical impulses that interact with the
`signals of one or more nerves to achieve a therapeutic result.
`In particular, the present disclosure describes devices and
`methods to treat depression and/or induce euphoria in a
`patient by stimulating the vagus nerve, for example, through
`non-invasive stimulation at a location on the patient's neck.
`[0032]
`In certain preferred embodiments, the present dis(cid:173)
`closure involves devices and medical procedures that stimu(cid:173)
`late nerves by transmitting energy to nerves and tissue non(cid:173)
`invasively. A medical procedure is defined as being non(cid:173)
`invasive when no break in the skin ( or other surface of the
`body, such as a wound bed) is created through use of the
`method, and when there is no contact with an internal body
`cavity beyond a body orifice (e.g, beyond the mouth or
`beyond the external auditory meatus of the ear). Such non(cid:173)
`invasive procedures are distinguished from invasive proce(cid:173)
`dures (including minimally invasive procedures) in that inva(cid:173)
`sive procedures do involve inserting a substance or device
`into or through the skin or into an internal body cavity beyond
`a body orifice.
`[0033] Potential advantages of such non-invasive medical
`methods and devices relative to comparable invasive proce(cid:173)
`dures are as follows. The patient may be more psychologi(cid:173)
`cally prepared to experience a procedure that is non-invasive
`and may therefore be more cooperative, resulting in a better
`outcome. Non-invasive procedures may avoid damage ofbio-
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`US 2011/0190569 Al
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`Aug. 4, 2011
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`4
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`logical tissues, such as that due to bleeding, infection, skin or
`internal organ injury, blood vessel injury, and vein or lung
`blood clotting. Non-invasive procedures are sometimes pain(cid:173)
`less or only minimally painful and may be performed without
`the need for even local anesthesia. Less training may be
`required for use of non-invasive procedures by medical pro(cid:173)
`fessionals. In view of the reduced risk ordinarily associated
`with non-invasive procedures, some such procedures may be
`suitable for use by the patient or family members at home or
`by first-responders at home or at a workplace, and the cost of
`non-invasive procedures may be reduced relative to compa(cid:173)
`rable invasive procedures.
`[0034] For example, transcutaneous electrical nerve stimu(cid:173)
`lation (TENS) is non-invasive because it involves attaching
`electrodes to the surface of the skin (or using a form-fitting
`conductive garment) without breaking the skin. In contrast,
`percutaneous electrical stimulation of a nerve is minimally
`invasive because it involves the introduction of an electrode
`under the skin, via needle-puncture of the skin. Both TENS
`and percutaneous electrical stimulation can be to some extent
`unpleasant or painful, in the experience of patients that
`undergo such procedures. In the case of TENS, as the depth of
`penetration of the stimulus under the skin is increased, any
`pain will generally begin or increase.
`[0035] The form of non-invasive electrical stimulation with
`which the present application is primarily concerned is mag(cid:173)
`netic stimulation. It involves the induction, by a time-varying
`magnetic field, of electrical fields and current within tissue, in
`accordance with Faraday's law ofinduction. Magnetic stimu(cid:173)
`lation is non-invasive because the magnetic field is produced
`by passing a time-varying current through a coil positioned
`outside the body, inducing at a distance an electric field and
`electric current within electrically-conducting bodily tissue.
`Because the induced electric field and induced current depend
`not only upon current being passed through wire of the coil,
`but also upon the permeability of core material around which
`the coil may be wound, the term coil as used herein refers not
`only to the current-carrying wire, but also to the core material,
`unless otherwise indicated. Large, pulsed magnetic fields
`(PMF) can induce significant electric fields in conducting
`media, including human tissue. Particular waveforms and
`amplitudes can stimulate action potentials in nerves, both in
`vitro and in vivo. Due to the noninvasive nature of the stimu(cid:173)
`lation, PMF devices have found utility in several clinical
`applications, both therapeutically, e.g., for treating depres(cid:173)
`sion via transcranial magnetic stimulation (TMS), and diag(cid:173)
`nostically, for peripheral nerve stimulation. It is an objective
`of the present invention to use magnetic stimulation to pro(cid:173)
`duce significantly less pain or discomfort, as compared with
`that experienced by the patient undergoing a treatment with
`TENS, for a given depth of stimulus penetration. Or con(cid:173)
`versely, for a given amount of pain or discomfort on the part
`of the patient ( e.g., the threshold at which such discomfort or
`pain begins), an objective of the present invention is to
`achieve a greater depth of penetration of the stimulus under
`the skin.
`[0036] The principle of operation of magnetic stimulation,
`along with a description of commercially available equip(cid:173)
`ment and a list of medical applications of magnetic stimula(cid:173)
`tion, is reviewed in: Chris HOVEY and Reza Jalinous, The
`Guide to Magnetic Stimulation, The Magstim Company Ltd,
`Spring Gardens, Whitland, Carmarthenshire, SA34 OHR,
`United Kingdom, 2006. The types of the magnetic stimulator
`coils that are described there include circular, parabolic, fig-
`
`ure-of-eight (butterfly), and custom designs. Additional types
`of the magnetic stimulator coils are described in U.S. Pat. No.
`6,179,770, entitled Coil assemblies for magnetic stimulators,
`to MOULD; as well as in Kent DAVEY. Magnetic Stimula(cid:173)
`tion Coil and Circuit Design. IEEE Transactions on Biomedi(cid:173)
`cal Engineering, Vol. 47 (No. 11, November 2000): 1493-
`1499 and in HSU K H, Nagarajan S S, Durand D M. Analysis
`of efficiency of magnetic stimulation. IEEE Trans Biomed
`Eng. 2003 November; 50 (11):1276-85.
`[0037] The circuits that are used to send pulses or other
`waveforms through magnetic stimulator coils are also
`described by HOVEY and Jalinous in The Guide to Magnetic
`Stimulation that was cited above. Custom magnetic stimula(cid:173)
`tor circuits for control, impulse generator and power supply
`have also been described [Eric BASHAM, Zhi Yang, Natalia
`Tchemodanov, and Wentai Liu. Magnetic Stimulation of
`Neural Tissue Techniques and System Design. pp 293-352,
`In: Implantable Neural Prostheses 1, Devices and Applica(cid:173)
`tions, D. Zhou and E. Greenbaum, eds., New York: Springer
`(2009); U.S. Pat. No. 7,744,523, entitled Drive circuit for
`magnetic stimulation, to EPSTEIN; U.S. Pat. No. 5,718,662,
`entitled Apparatus for the magnetic stimulation of cells or
`tissue, to JANILOUS; U.S. Pat. No. 5,766,124, entitled Mag(cid:173)
`netic stimulator for neuro-muscular tissue, to POLSON].
`[0038] As described in the above-cited publications, the
`circuits for magnetic stimulators are generally complex and
`expensive. They use a high current impulse generator that
`may produce discharge currents of 5,000 amps or more,
`which is passed through the stimulator coil, and which
`thereby produces a magnetic pulse. Typically, a transformer
`charges a capacitor in the impulse generator, which also con(cid:173)
`tains circuit elements that limit the effect of undesirable elec(cid:173)
`trical transients. Charging of the capacitor is under the control
`of a control unit, which accepts information such as the
`capacitor voltage, power and other parameters set by the user,
`as well as from various safety interlocks within the equipment
`that ensure proper operation, and the capacitor is then dis(cid:173)
`charged through the coil via an electronic switch ( e.g., a
`controlled rectifier) when the user wishes to apply the stimu(cid:173)
`lus. Greater flexibility is obtained by adding to the impulse
`generator a bank of capacitors that can be discharged at dif(cid:173)
`ferent times. Thus, higher impulse rates may be achieved