Method of treating amygdala related transitory disorders

The invention relates to a method for diagnosing and treating Amygdala Related Transitory Disorders, comprising selecting a patient who has symptoms suggesting ARTD, stimulating said patient's amygdala with a magnetic field, and determining whether said stimulus with a magnetic field is capable of inducing or aggravating symptoms of ARTD. Additional embodiments include a method to determine the lowest dose of an anticonvulsant that will effectively control ARTD, and methods of using electromagnetic stimuli to treat ARTD by interfering with kindling or desensitizing the amygdala.

FIELD OF THE INVENTION 
The present invention generally relates to the treatment of neurological 
disorders. In particular, it relates to the use of electromagnetic 
stimulation to diagnose and treat neuropsychiatric disorders. More 
specifically, it relates to methods for diagnosing and treating patients 
afflicted with Amygdala Related Transitory Disorders. 
BACKGROUND OF THE INVENTION 
The limbic system (comprising the amygdala, hypothalamus, anterior thalamic 
nuclei, gyrus cynguli, hippocampus, temporal lobe and their 
interconnections), in particular the amygdala, have been implicated in a 
variety of neuropsychiatric disorders. Patients suffering from Amygdala 
Related Transitory Disorders ("ARTD") exhibit a wide range of seemingly 
unrelated symptoms, which include (but are not limited to): mood changes 
(e.g., anxieties, dominating thoughts, impaired alertness, fatigue, 
hallucinations, irritability, low threshold for frustration, chronic and 
recurring depressions, panic attacks of varying intensity); thirst and 
appetite disorders; bodily pain, especially focal, bilateral or 
generalized headaches, including migraine headaches; muscle tension; 
addictions to alcohol, cigarettes or drugs and bulimia; writing, speech, 
and learning disabilities; perceptual dysfunctions (i.e., problems in 
integrating sensory--visual or auditory input); paranoid thinking; 
peripheral neuropathies (e.g., paresthesia or hypoesthesis in one or more 
extremities, usually episodic); seizure-like phenomena (e.g., blackouts, 
trances or impaired consciousness, myoclonic twitches); self-destructive 
behavior (including cutting, burning, biting self, hitting self or walls). 
Little is known of the physiological basis for symptoms of ARTD. In 
addition to any possible permanent neurological damage of the hypothalamus 
limbic temporal lobe and brain stem areas, it is believed that ARTD may be 
characterized by periodic, episodic or paroxysmal dysfunctions in the 
amygdala. Typically, the dysfunction manifests itself as a group of 
symptoms, often occurring in periodic bursts. Different ARTDs may map to 
different positions in the limbic systems. 
The symptoms of ARTD can be effectively treated with anticonvulsants. 
However, ARTD is often misdiagnosed and therefore mistreated. 
A principal reason for the difficulty in diagnosing ARTD is the wide 
variation of symptoms: a defined set of observable symptoms may 
characterize ARTD in one patient, whereas a different set of symptoms may 
predominate in another ARTD patient. For example, one patient may become 
very fearful when suffering from an ARTD, while another patient may 
experience obsessive thoughts or hallucinations, while still a third 
patient may engage in stalking, alcoholism, violent behavior, etc. 
Furthermore, while ARTD is almost always manifested by more than one 
symptom or sign, be it psychiatric or neurological, current treatments 
tend to focus on and treat only the predominant or most incapacitating 
one. For example, a physician may focus on depression and thus fail to 
recognize other symptoms of ARTD such as obsessions or excessive thirst. 
This may mistakenly lead to treatment with antidepressants, instead of to 
a diagnosis of ARTD and treatment with anti-convulsants. Without the use 
of the anticonvulsant medication, the use of the antidepressant or 
neuroleptic medication is usually ineffective or may actually exacerbate 
(especially with antidepressants) the ARTD. 
Clearly, there is need for a method of reliably diagnosing ARTD. There is 
also need for safer treatment. 
In the past, the interrelationship between certain disorders and neural 
activity has been determined by activating specific neural centers by a 
variety of means, mainly chemical stimuli and electrical impulses. 
For example, neurologists have successfully used electrical stimuli to map 
the regions of the cortex that are involved in specific cognitive 
functions (e.g., spatial recognition, color perception, etc.) and to form 
the basis for, or confirm, clinical diagnoses. The Food and Drug 
Administration (FDA) has approved a number of Cranial Electrotherapy 
Stimulation (CES) devices for the treatment of anxiety, insomnia and 
depression. 
U.S. Pat. No. 5,342,410 discloses a method and apparatus for increasing 
electrical brain activity, thereby decreasing cravings for addictive 
substances. The invention comprises a cranial electrotherapy stimulation 
device which generates a substantially periodic current waveform having a 
frequency approximately between 50 and 300 Hz, a current amplitude in the 
range of 0 to 400 mA, a voltage of approximately 40-60 volts, a pulse 
width in the range of 0.20 to 2 milliseconds and a duty cycle of about 
20%. The patient is stimulated with the device for between 20 minutes and 
two hours. Such stimulation results in an increase in the amplitude of 
P300 waves in the brain, which in turn reportedly results in a decrease in 
cravings for alcohol and drugs. Patent No. 1274693 from the Soviet Union 
claims a method for treating depressions wherein an anode is positioned on 
the occipital-mastoidal region (behind the ear) and a cathode is 
positioned on the frontal region. The sensory threshold is gaged by 
increasing current intensity until the individual first senses the 
current. An electric current with a pulse repetition rate ranging from 1 
to 100 Hz is then applied to the right or the left hemisphere of the brain 
for 7 to 15 minutes once every 2-3 days (8-10 times altogether). Treatment 
of the right side of the brain is recommended to treat emotional disorders 
characterized by prevalence of anxiety and treatment of the left side of 
the brain is recommended to treat anguish and apathy. 
U.S. Pat. No. 5,215,086 discloses methods and an apparatus for treating and 
controlling migraine by selectively stimulating a patient's vagus nerve, 
using an implantable neuro-stimulating device. The signal is a pulse 
waveform designed to desynchronize the patient's electroencephalogram 
(EEG) if paroxysmal activity is detected in the EEG, or to synchronize the 
EEG if low voltage fast wave activity is detected. Alternatively, the 
application of the stimulating signal to the vagus nerve may be initiated 
manually by the patient upon recognition of the onset of a migraine 
attack. 
Patent No. 725671 from the Soviet Union discloses a method for treating 
depressions with electrical stimuli, wherein an anode is placed on the 
palm of a hand and a cathode is placed on the lower third of the forearm 
of the same arm, and electric pulses are applied with a voltage 2-3 times 
the sensitivity threshold at a pulse repetition rate from 10 to 100 Hz. 
The treatment lasts for 2 to 10 minutes with intervals of 3 to 7 days. The 
treatment is repeated once every 3 to 4 months once or twice to prevent 
the relapse of depressions. 
Certain electrical stimuli can produce self-maintaining independent seizure 
foci. This phenomenon, known as "kindling", is optimally produced by 
intracortical stimulation at stimulation rates of 50/s. A rate of less 
than 3/s will generally not suffice. Trains of repetitive stimuli are 
often required. Repetition rates of less than 3/s are reportedly safe. 
However, there are significant counterindications to the use of electrical 
currents. Electrical currents can be painful, and their application often 
requires the use of anesthetics. The sensitivity threshold mainly depends 
on the electrical conductance properties of the skin. This threshold may 
vary substantially during the course of treatment of one and the same 
individual, depending on his emotional condition. It may also vary as a 
function of a number of subjective factors (e.g., fear of pain). Moreover, 
the usefulness of methods that rely on electrical stimulation is limited 
by its inability to penetrate into deep peripheral nerves, nerve plexi, 
and subcranial nerves. Finally, in chronic electrical stimulation of the 
brain using electrodes, reversible injury to the blood-brain barrier may 
occur if the charge exceeds 45 .mu.C and neuronal injury occurred as 
charged densities increased from 40-400 .mu.C/cm2 per phase. 
The intravenous administration of the anesthetic procaine has been reported 
to suppress neocortical structures while selectively stimulating the 
limbic system. Procaine induces patients to experience the symptoms or 
ARTD; this induction is called "kindling". The effect of procaine on the 
limbic system has been likened to the treadmill stress test in cardiology. 
The treadmill stimulates the heart muscle, unmasks abnormal cardiac 
patterns and is used to evaluate the effect of drugs on the abnormal 
patterns. Similarly, procaine has been used to unmask limbic 
electroencephalogram dysrhythmia, to occasionally recreate the concomitant 
behavior disorder, and to evaluate pharmacological treatment. 
U.S. Pat. No. 5,176,145 to Ryback and Gardner and also Ryback and Gardner, 
J. Neuropsychiatry 3: 321-329 (1991) disclose and claim a method for 
diagnosing whether a patient suffers from limbic system dysrhythmia 
("LSD"), involving studying electroencephalogram patterns for focal 
abnormalities in the temporal parietal areas. If there are none, the 
patient is administered a local anaesthetic, procaine, and the 
electroencephalogram is evaluated for omega band activity (30-50 Hz). A 
patient exhibiting either focal abnormalities in the temporal-parietal 
areas on the standard electroencephalogram or, after procaine, exhibiting 
omega band activity of at least about three times the baseline voltage 
above normal and exhibiting symptoms in at least four groups of twelve 
groups of defined symptoms is diagnosed as having LSD and being capable of 
treatment by administering an anticonvulsant medication. 
A time-varying (pulsed) magnetic field applied to a tissue capable of 
conducting electrical currents will result in an induced current as though 
the current had been applied via electrodes. The induced current will flow 
in planes parallel to the plane of the inducing magnetic coil, and in 
opposite directions. Good conductors, e.g., neurons, blood, and 
cerebrospinal fluid, will have larger currents than skin, fat, or bone, 
which present high resistance to electrical currents. 
The brain has a relatively high conductivity, whereas the electrical 
resistance of the skull is 8 to 15 times greater than that of soft tissue. 
While bone structures and cavities would limit currents generated with 
electrodes, they would not significantly attenuate a magnetic field. Thus, 
magnetic fields may induce currents in deeper tissues and over broader 
ranges than an electrical stimulus produced by electrodes. Accordingly, 
transcranial magnetic stimulation has been used instead of electrical 
currents to stimulate or detectably alter neural activities. See, e.g., 
Eisen, Meth. Clin. Neurophys. 3: 65-84 (1992). Pascual-Leone et al., 
Neurology 41: 697 (1991) reported that stimulation rates of up to 25 Hz 
for ten seconds using a coil held flat on the scalp induced speech arrest 
in patients without detectable damage to the brain tissue. 
Magnetic stimulators may not substitute for electrical stimuli in all 
cases. For example, it has been reported that cardiac muscle cannot be 
stimulated with a magnetic coil. Eisen at 66. 
SUMMARY OF THE INVENTION 
The ability to reasonably predict whether a patient would be successfully 
treated by a particular course of medication is of great importance; an 
incorrect diagnosis could not only result in an ineffective treatment but 
in one that might be harmful to the patient. Accordingly, it is an object 
of this invention to provide a diagnostic method for ARTD that has a very 
high probability of success and is relatively easy and safe to carry out. 
It is a principal object of the present invention to detect and treat ARTD 
by selectively stimulating nerve activity within the amygdala, by exposing 
a patient to subcranial magnetic fields using a magnetic neurostimulator 
device, in order to induce at least one but preferably more than one 
symptom from a group of defined symptoms of ARTD. 
In one embodiment, a magnetic coil (or coils), movably joined to and 
exposed at the top surface of a mouthpiece, is (are) held in place against 
the nasopharynx of a patient. The coil(s) is (are) held in place, for 
example, by reversibly affixing it (them) to the mouthpiece, and having 
the patient "clamp down" on the mouthpiece assembly comprising the coil 
and the mouthpiece without biting through any component of this assembly. 
The mouthpiece is preferably a wax or plastic mold of the patient's mouth. 
The coil or coils may be reversibly affixed to different positions on the 
mouthpiece. 
The magnetic stimulation is preferably a "sub-threshold stimulation", i.e., 
of a magnitude insufficient to elicit either the behavioral or brain wave 
manifestations of an ARTD in non-ARTD control subjects. If kindling is 
observed after a number of repetitive sub threshold stimuli, then the 
patient is diagnosed as having an ARTD. Of equal importance, the absence 
of symptoms following such stimulation indicates that the cause of the 
patient's symptoms is not an ARTD, and the patient should not be treated 
for such disorder. 
Once the diagnostic embodiment of the invention indicates that the patient 
is suffering from an ARTD, the physician can prescribe an appropriate 
treatment. For example, anticonvulsants that counteract kindling can be 
prescribed for patients who manifest several symptoms or signs 
concurrently. In another embodiment of the present invention, a physician 
can determine the lowest dose of the anticonvulsant that will effectively 
control ARTD. 
In other embodiments of the invention, electromagnetic forces such as rapid 
rate subcranial stimulation may be used to interfere with kindling or 
desensitize certain areas in the brain.

DETAILED DESCRIPTION OF THE INVENTION 
The various publications referenced herein are incorporated by reference in 
this application in order to more fully describe the state of the art to 
which the present invention pertains. All technical and scientific terms 
used herein, unless otherwise defined, are intended to have the same 
meaning as commonly understood by one of ordinary skill in the art, with 
the proviso that the terms used herein are not intended to be limiting of 
the invention. The term "amygdala" encompasses not only the amygdala 
proper, but also other components of the limbic system. Although the 
invention focuses preferentially on human patients exhibiting symptoms of 
ARTD, the invention also encompasses the analysis of asymptomatic 
relatives of persons exhibiting these symptoms who may be "at risk" for 
developing ARTD, and the treatment of other mammals having similar 
symptoms. 
The published methods for treating neural disorders by stimulating neural 
activity relied on electrical stimulation or, in the case of the method 
for diagnosing limbic disorders disclosed in U.S. Pat. No. 5,176,145, 
procaine administration, both of which have a number of significant 
drawbacks. On the one hand, localized electrical stimulation is severely 
limited by its inability to penetrate into deep peripheral nerves, nerve 
plexi, and subcranial nerves. Deeper penetration may be obtained by 
increasing the current, but this approximates electroshock treatment, 
which is painful and may cause grand mal convulsions. Also, medication and 
general anesthesia are required with stronger currents. On the other hand, 
intravenous procaine administration is invasive and its effects are 
systemic rather than localized, with a known potential for side-effects. 
The present invention utilizes subcranial electromagnetic fields to 
stimulate the amygdala/limbic system. It is less invasive and simpler to 
carry out than either electrical stimulation or procaine. It affords 
better penetration and more specific targeting of regions of the brain. It 
offers the advantages of electroconvulsive therapy (ECT) (e.g., potential 
for deliberate controlled stimulus of localized tissues), but not its 
disadvantages. It is painless and easier and safer than ECT. Selective 
magnetic probing of the limbic system by evoking the patients own symptoms 
is more reliable than the general kindling induced by intravenous 
procaine. The patient need not be anesthetized or worry about pain, as 
with ECT. This assures better patient acceptance of the treatment. 
In fact the patient is usually fully aware and capable of describing the 
effects of the neurostimulation as it takes place. This enormously 
simplifies the task of correlating field strength and orientation to 
neuropsychiatric phenomena, and greatly facilitates the fine structural 
mapping of the locus of the physical dysfunctions that give rise to an 
ARTD. 
While magnetic neurostimulation has been reported in the literature to 
study neurological functions, its use to diagnose and treat ARTD has 
neither been suggested nor disclosed in the prior art. 
Procedurally, the invention comprises the steps of: 
a. selecting a patient who has symptoms of ARTD and/or whose EEG indicates 
abnormal omega band activity three times baseline upon subcranial magnetic 
stimulation (SMS), 
b. stimulating said patient's amygdala with a magnetic field, and 
c. determining whether said stimulus with a magnetic field induces symptoms 
of ARTD. 
A. Selecting a Patient 
To select a patient, the physician performs a symptom inventory. In such a 
symptom inventory, the physician investigates the patient's past history 
with respect to: moods, anxieties, dominating thoughts, thirst, appetite, 
impaired alertness, fatigue, pain, hallucinations, irritability, writing, 
speech, frustration, etc. If the patient reports symptoms in these 
categories, then the patient may be suffering from ARTD, especially if the 
reported group of symptoms occur in periodic bursts. 
1. Questionnaire 
The most efficient way to perform the symptom inventory is through a 
questionnaire. The following is a model questionnaire used by the 
inventor: 
MOOD 
Do you experience depressions or mood swings? 
Could the depressions start suddenly? 
Do you have crying spells? 
Are your depressions short lived? 
Would they come and go within the same day or last for just a few days? 
Is there a reason to become depressed? 
Are they triggered by certain things? 
Are they totally unpredictable or do you feel them coming on? 
If so what do you feel? 
ANXIETY 
Do you have panic attacks, a sudden overwhelming fear? Do you have phobias, 
or fears from certain things or situations? 
Do you anticipate anxiety? 
Do you have anxiety in social situations? 
THOUGHTS 
Do you suffer from obsessive thoughts, recurrent or unwanted thoughts? 
Do you dwell on things, keep thinking about things of the past? 
Do you ever have racing thoughts, that is, do your thoughts ever go 100 mph 
or you can't put them still? 
Do these racing thoughts ever keep you up at night? 
DRINKING 
Are you a thirsty person? 
Do you drink more fluids than the average person, any fluid, water, soda, 
not necessarily alcohol? 
Do you drink a lot of alcohol? 
Are you a volume drinker? 
Do you drink beer? 
Do you drink mostly in the evening? 
Do you drink in order to sleep? 
Do you ever experience drinking binges? 
A sudden urge to drink, even at night? 
Is your thirst easily quenched by drinking? 
FOOD 
Do you have a good morning appetite? 
Do you feel nauseous in the morning? 
Does your appetite improve as the day progresses? 
Do you suddenly loose appetite while you eat? 
Do you suddenly have a craving for food? Is this irresistible to the point 
you just have to eat, i.e. impulsive eating or food-binging? 
Is your appetite ever satiated by eating? 
Does it occur at night, wake you up and make you go to the refrigerator? 
SLEEP 
Do you have trouble sleeping? 
Do you have trouble falling asleep? 
Do you have trouble staying asleep? 
Do you have to pace at night? 
Do you have vivid dreams? 
Do you have jerky movements in bed? 
Do you get up tired in the morning? 
Do you have trouble with yawning, do you yawn a lot during the day? 
Do you grind your teeth at night? 
Do you sleepwalk or experience night terrors? 
COGNITION 
Do you ever feel clouded or dazed, half asleep, or with a decreased 
awareness? In other words, do you ever feel that you are not fully alert? 
Do you feel this in the morning? 
Does it clear at the day progresses? 
At what time are you fully awake? 
Do you sometimes bump into things, for example, run into a doorjamb? 
Are you at your best in the evening? Are you sharp then? 
Do you daydream a lot? When does it occur, in the morning, or in the 
evening? 
Do you have trouble with your memory or concentration? 
Are you a night person, do you think more clearly in the evening? 
PAIN 
Do you have headaches or migraines? 
Do you have a sudden pain in the pit of your stomach and would that pain go 
upwards, in the chest, to your neck? 
Do you have sudden pain in your throat? 
FATIGUE 
Do you sometimes feel tired or exhausted? Suddenly and for no reason? 
Do you wake up tired in the morning? 
HALLUCINATIONS 
Visual: Do you ever see black dots, lightning, stardust, small objects or 
people? 
Auditory: Do you have ringing in the ears, or do you hear bells ringing? or 
a buzzing sound? 
Do you hear voices or hold conversations within yourself? or a humming 
sound? 
Olfactory: Do you ever smell anything that's not there? Do you ever smell 
anything unusual, something burning, burning rubber, corpses? Do you ever 
have no smell at all? 
Taste/Gustatory: Do you ever have no taste? Do you ever have an unusual 
taste, such as metallic or foul taste? 
IRRITABILITY 
Visual: Does strong light ever bother you or irritate you, such as 
sunlight, T.V., fluorescent lights? 
Does bright light hurt? 
Do you have to wear sunglasses, use shades excessively? 
Can you tolerate light some days and other days not? 
Auditory: Do loud noises bother you? Does it hurt or irritate you? Can you 
tolerate noises some days and other days not? Can you hear things at a 
great distance? 
WRITING 
Do you ever write too much or a lot, more than usual? 
Do you ever write a lot of poems, letters to important people? 
SPEECH 
Do you ever talk too much? 
Do people tell you to stop talking? 
Are you sometimes speechless? 
Do you ever feel you have nothing to say and would just remain silent as if 
there were no need to talk? 
Do you ever stutter? 
Do you ever have trouble finding your words? 
Do you find it difficult to terminate a conversation? 
FRUSTRATION 
Do you ever become intolerant, for no reason? 
Do you ever become very frustrated, unable to tolerate it? 
Would you then be very angry and lash out? 
Do you ever experience strong negative feelings, even hatred, when you feel 
there may be no real reason for that? 
Would you say that overall this anger, frustration, intolerance, etc. are 
not really you, that you are basically a different person? 
SEXUAL 
Do your symptoms get worse towards your periods? 
Do you have an increased or decreased sexual drive? 
Is there some degree of promiscuity? 
PERSONALITY 
Do you feel you may have several personalities? 
Are you a routine person? Do you feel it is difficult to change or adapt? 
Do you feel you are a unique person, an outsider, or someone who doesn't 
blend with the crowd? 
Do you have times you loose self confidence, yet at other moments you may 
be quite self confident? 
Are you overly sensitive at times, even to the point of becoming paranoid? 
Are you very concerned with what's right and wrong in life or with 
injustices in the world? 
Do you dread going to work in the morning but once you get started you are 
more or less OK? 
Do you find yourself clinging to people? 
PERCEPTIONS 
Do you ever experience cold or hot flashes? 
Do you ever experience numbness in your arms, legs, body? 
Do you experience deja vu or deja entendu, already heard? Do you feel you 
have a 6th sense, that is, do you have premonitions or can make 
predictions? 
2. Electroencephalogram 
The results of the questionnaire are based on the patient's subjective 
answers, and may be subject to error because of the patient's 
misperception, miscommunication, or misrepresentation, or the physician's 
bias or misunderstanding. An electroencephalogram may provide an objective 
criterion in the diagnosis of ARTD. The presence of either focal 
abnormalities in the temporal-parietal areas in a standard 
electroencephalogram or of omega band activity of at least about three 
times the normal baseline voltage (as described in U.S. Pat. No. 
5,176,145) may bolster an initial diagnosis of ARTD that results from the 
above-defined symptoms inventory. 
The measure of objectivity provided by EEG analysis may prove useful in 
ruling out hypochondriasis and malingering. It may further confirm cases 
of, for example, irresistible impulse in homicide cases, which then could 
plead an insanity defense on a more scientific basis, bypassing the 
subjectivity of neuropsychiatric experts. 
Patients having an abnormal EEG (including focal abnormalities) should not 
be tested. These patients typically would suffer from epilepsy. 
B. Magnetic Stimulation 
Once a patient is identified as apparently suffering from ARTD, his 
amygdala is probed with a subcranial magnetic stimulator. The goal is to 
identify and focus on the anatomical region that is prone to kindling and 
is causing the patients' neuropsychiatric symptoms and/or signs. This 
region will become the target of symptom suppression in a later treatment 
phase. 
A block diagram of the basic components of a neurostimulator and their 
interrelationship is illustrated in FIG. 1. The main components are a 
power source connected to a means, usually a coil, of generating a 
magnetic field, and also means for controlling the strength, shape, 
duration and direction of the magnetic field. Further details of a 
preferred embodiment involving a mouthpiece and the lead/magnetic coil 
system are shown in FIGS. 2a and 2b. The neurostimulator device is usually 
external to the body, but a portion of the circuitry (e.g., coils and 
associated leads) may be optionally implanted. 
The following is a brief summary of the functions of the main elements of a 
preferred magnetic neurostimulator. 
The neurostimulator utilizes a power supply which determines the peak 
charging voltage (and thus its intensity) and also limits the rate at 
which the stimulator charges (and thus its repetition rate). It is 
important that the power supply be designed so that failure modes will not 
significantly increase either of these parameters. 
The power supply is preferably equipped with a microprocessor, a computer 
and associated software for adjustment of parameters and control of 
communication between the generator and other standard electrical and 
electronic components for generating and modulating the desired magnetic 
field or indicating states of the device. In conjunction with its 
microprocessor-based logic and control circuitry, the stimulus generator 
circuitry may include detection circuitry for sensing an event indicative 
of an abnormality that triggers an automatic delivery of the stimulating 
signal. For example, specific characteristics of the patient's EEG could 
trigger the therapy. 
Magnetic stimulators produce magnetic fields by pulsing an intensive 
current through a suitable coil. This current is generated when a high 
value capacitator is suddenly discharged by a switching device 
(thyristor). 
When the magnetic coil and the capacitor are connected through a solid 
state switch, the energy moves rapidly from the capacitor to the coil 
creating a magnetic field, the strength of which is measured in Teslas (T; 
one T =10,000 gauss). A magnetic stimulator may deliver pulses of between 
1-10 T. Most experimentation for peripheral and central stimulation has 
used field strengths of about 1 to about 2.5 T. 
Thus, a magnetic stimulator's electrical circuit preferably comprises an 
inductor (stimulating coil) and, because it is necessary to obtain a rapid 
increase in excitation coil current and to deliver a high peak current to 
the coil, an energy storage capacitor with a very low equivalent series 
resistance (ESR). The capacitor provides the energy of stimulation. 
The capacitors deliver large currents for short durations. The intensity of 
stimulation is proportional to the voltage, which is set by the power 
supply, and to the square root of the capacitance. For current magnetic 
stimulators, the duration is generally fixed by the capacitors and the 
coil inductance, and so generally only the amplitude of the stimulus is 
varied. 
The capacitance is set by the charge energy allocated, approximately 500 J 
being wanted in many applications. This would require 4000 mfd at 500 V or 
250 mfd at 2000 V. The latter combination is preferable because the much 
lower currents involved not only allow finer gauge and therefore more 
compact coils, but system efficiency is also greatly improved. 
The capacitor is discharged into the coil by a solid state switch. 
Typically, the peak current is in the kiloampere range. The resulting 
pulse of current induced into the tissue is of short duration, typically 
in the fractional multi-second range. The voltage drop across these parts 
decreases the stimulus by approximately 0.5%. Changes with temperature or 
age have little effect on stimulus intensity. The main requirement of the 
switches is surviving the high surge requirements. 
The coil transfers the energy back to the capacitor, and if the switch 
remains closed, the energy moves again from the capacitor to the coil, 
back and forth, until it is entirely consumed by resistive losses. 
In a prototypical stimulator, a current pulse of up to 5000 A (peak 
current) is passed through a flat 45 mH copper coil of 10 cm diameter. The 
peak magnetic field strength is approximately 1-3 T and the duration of 
the induced current pulse is approximately 100 ms. The energy storage 
capacitator bank is charged to 4 kv and discharged into the coil (2 kV is 
adequate for superficial nerves) resulting in a brief magnetic field, 
peaking at 160 ms. The maximum frequency of stimulation is once every 3 
seconds. The power can be turned up until the desired response has been 
obtained. 
The production of heat by the coil is a limiting factor of the rate of 
repetitive pulses. The coil is designed for minimum resistance with enough 
inductance (i.e., amount that the coil resists the changing current 
measured in Henries) to protect the switching elements from over-current. 
Computer modeling shows a 0.7-1.0% change in the effectiveness of the 
stimulation with a 100% increase in coil inductance. 
An underdamped condition is preferred in magnetic field stimulators, to 
keep the resistance low and to favor low heating in the coil. In this 
condition the current is oscillatory and the induced current or stimulus 
pulse resembles a damped cosine wave. The output is a damped oscillation 
lasting about 800 .mu.S. 
Coil design is key to providing localized stimulation, as design affects 
the shape and intensity of the magnetic field. Circular coils and double 
circular ("butterfly") coils have been used, but any geometric shape 
(oval, ellipsoid, triangular, square, figure-eight, parallel wires, etc.) 
or combination of geometric shapes is possible, depending on the desired 
shape, strength and application. The magnetic field intensity and the 
shape of the field can be easily measured and mapped, if desired. 
A preferred embodiment in this invention is a magnetic coil shaped as an 
ellipse measuring about 7 cm wide and 9 cm long. The elliptical shape 
generates a narrower, more focused magnetic field. 
At present, a number of neurostimulators suitable for use in embodiments of 
the present invention are commercially available. For example, the Cadwell 
laboratories, Inc. High Speed Magnetic Stimulator features rapid firing 
capability and adjustable intensity. Maximum stimulation rate is 25 Hz at 
100% intensity and 50 Hz at 50% intensity. It generates a magnetic field 
of up to 2.2 T. In addition, Dantec markets its Mag Pro stimulator with a 
built-in trigger source offering a train duration from about 0.2 to about 
10 seconds with repetition rates of about 5-30 pulses per second. Manual 
operation and external trigger is provided, as well as the capability of 
selecting a biphasic or monophasic stimulation waveform, and the current 
direction can be reversed. 
C. Use of Magnetic Neurostimulator 
To stimulate excitable tissue, a threshold current needs to be induced in 
that tissue, generally sufficient to reduce the transmembrane potential by 
approximately 30%. Nerves respond to an appropriate stimulus by 
depolarizing. The appropriate time scale of the stimulus is relative to 
the neuron's ability to pump sodium ions in an attempt to maintain 
equilibrium, typically 100-300 ms. A charge density of 1-2 .mu.C/cm2 is 
sufficient to depolarize myelinated nerves. For a convenient electrical 
stimulator this would be 10 mA, 100 .mu.S. Increasing either the duration 
or the amplitude of the stimulator will increase the effectiveness of the 
stimulation. 
For magnetic stimulators the duration is fixed by the capacitors and the 
coil inductance. Typically, the induced current is only 1/100,000 the size 
of the inducing current. The stimulus is 1000 times smaller than that used 
for ECT and the energy is about 1 million times smaller. 
Up to 460 J of energy is needed to depolarize the brain. This large amount 
is required because the brain is almost transparent to magnetic fields. 
Which region of the brain is stimulated depends on the strength, shape and 
direction of the magnetic field. These parameters are strongly influenced 
by the shape, current flowing through, and placement of the coil. 
A magnetic field that originates outside the skull would likely stimulate 
cortical structures a well as the amygdala. Thus, preferably the magnetic 
coils are positioned subcranially such that they are adjacent to the 
amygdala. More preferably, they are positioned adjacent to the nasopharynx 
or the posterior region of the soft palate. 
In one embodiment the magnetic field strength is about 0.1 to about 4 
Tesla, the magnetic field is administered in trains of pulses, wherein 
each train lasts from about 5 seconds to about 10 minutes, each train 
comprising 1-20 second pulses, with an interval of 1-20 seconds between 
pulses. 
Consistency of coil positioning and orientation relative to the targeted 
structures are essential for reproducible results. This is especially true 
where the physician wishes to stimulate only a particular region of the 
amygdala or the limbic system. For the sake of accuracy and 
reproducibility, it is preferable to control the position and angle of the 
coil. This is preferably achieved by affixing the coil to a stable solid 
support. It is further preferable that this affixation be reversible. In 
other words, it is preferable that the physician or patient be able to fix 
the coil to a given position at will, and also change this position at 
will. A preferred embodiment for such a support is a mouth piece molded 
after the patient's mouth, as illustrated in FIGS. 1 and 2. Such a 
custom-molded piece has the double advantage that it fits snugly and 
comfortably in the patient's mouth, without slippage. It also makes it 
easier to position the coil. The mouthpiece may by made of a semisoft 
material capable of holding its shape, such as soft dental wax, or it may 
be made of non-toxic plastic. The plastic mouthpiece may be made by first 
making a template of a semisoft material such as dental wax, for example 
by directly applying the soft wax into the patient's mouth, as the patient 
firmly bites into the wax. The wax template may then be used to make a 
mold patterned after the template. The mold thus made may be filled with a 
polymerizable or solidifiable material such as plastic. 
In an alternate embodiment, the lead wire is threaded through the nasal 
passage of a patient, an the coil is positioned adjacent to the 
nasopharynx. The position and angle of the coil prior to magnetic 
stimulation are monitored with an imaging device, such as ultrasound or 
X-rays. 
The stimulus generator is designed, implemented and programmed to deliver a 
selectively patterned stimulating signal to modulate limbic activity in a 
manner designed to treat the specific neuropsychiatric disorder of 
interest. The magnetic stimulus is applied continuously, periodically or 
intermittently. 
The diagnostic stimulation starts off at low stimulation rate, say 1 to 3 
pulses per second at low power, and a magnetic field strength of 1 to 2 T, 
lasting for about 5-30 seconds. The stimulation rate, field strength, and 
duration are increased until magnetically induced kindling is achieved, 
either as reported by the patient, or by measuring the omega band activity 
on an EEG display. Kindling may be optimized by progressively changing the 
position and angle of the coil, for example, by moving the probe from left 
to right about a frontal-posterior axis. Regions from different depths of 
the limbic system may be scanned, the penetration depth being controlled 
by increasing the magnetic field strength. 
The patient himself may participate by varying the depth and direction of 
the field by using hand controls while the stimulating coil is in his 
mouth. The patient could not only control direction and depth of the field 
but also, for example, the rate of stimulation which would trigger his own 
symptoms or exacerbate them. The patient would thus be able to find his 
own kindling-sensitive spot within the limbic system. 
If upon this diagnostic stimulation, either 1) a concurrent EEG monitoring 
discloses Omega band activity of three times the baseline value or 2) the 
patient experiences symptoms or signs which are typical of his condition, 
then the patient suffers from ARTD. He can then be treated with 
anticonvulsants and/or rapid rate subcranial magnetic stimulation (RRSMS). 
If RRSMS is administered in the treatment phase, it will be desirable to 
stimulate at a rapid rate that area of the limbic system that was 
activated in the diagnostic stimulation test. Maintaining the same angles 
and penetration depth, stimulation will be provided at a rapid rate of 
about 25 pulses per second in 10 second trains for about 2 minutes twice a 
week for a month. 
Once an optimal stimulation is obtained, subsequent treatment would utilize 
the same position, angle, field strength, pulse rate, and duration. 
The magnetic stimulation is preferably given to the patient at a level 
insufficient to elicit either the behavioral or brain wave manifestations 
of an ARTD in non-ARTD control subjects, hereinafter a "sub-threshold" 
stimulation. If kindling is observed after a number of repetitive 
sub-threshold stimuli, then the patient is diagnosed as having an ARTD. 
The diagnostic method of the present invention makes it possible to 
distinguish a category of patients who are most likely to show positive 
responses to treatment with an anticonvulsant medication. 
D. Treatment of ARTD 
Patients who meet the above-described criteria are diagnosed as having 
ARTD. They are then treated by administration of an anticonvulsant 
medication such as Tegretol (carbamazepine), Depakene or Depakote 
(valproic acid), or Klonopin (clonazepam), alone or in combination with 
other medications, as appropriate (e.g., antidepressants or neuroleptic 
medication). 
The anticonvulsant medication is generally orally administered. Recommended 
dosages are listed in the Physician's Desk Reference, 1995 Edition, 
Medical Economics Company, or they may directly obtained from the 
manufacturer of the anticonvulsant medication. 
ARTD patients who are treated with anticonvulsants on a regular basis 
exhibit a decrease in the frequency and intensity of the symptoms 
characteristic for this particular patient. The patient's response to 
stimulation, both above and below the threshold decline, i.e., fewer 
symptoms are perceived nd the EEG is normalized. 
The present invention not only provides a method for identifying patients 
who can benefit from anti-convulsant therapy, but it also provides methods 
for determining the most effective dose of a given medication for a 
specific patient. Dosages can then be tailored to the individual 
tolerances of a particular patient, and dosage can be reduced or increased 
from the prescribed dosage as needed (e.g., 25-200% of recommended dose.) 
The present invention also provides a method for ascertaining which among 
alternative medications works best for a given patient. 
Accordingly, in one embodiment of the present invention, a physician 
determines the lowest dose of the anticonvulsant that will effectively 
control an ARTD. To do so, a patient is administered a predetermined dose 
of an anticonvulsant, preferably the recommended dose, and then her 
amygdala is probed with the magnetic neurostimulator, with the coil 
positioned and the magnetic field parameters set to values previously 
determined to induce an ARTD in that patient. If the patient does not 
exhibit kindling following magnetic stimulation of the amygdala, then the 
dose is progressively reduced, until the minimum dosage that determines 
kindling is ascertained. If on the other hand the patient exhibits 
kindling at the initial dose following magnetic stimulation of the 
amygdala, then the patient is administered progressively higher doses 
until the medication effectively inhibits kindling. 
The invention is useful also to determine whether and to what extent a 
patient may have become habituated to the medication. After a patient with 
such a disorder is receiving a dose of anticonvulsant for a while or if 
other medications are also taken that would affect bio availability of the 
anticonvulsant, such test could be used to determine proper dosage. 
Treatment with anticonvulsants may be contra-indicated in certain patients. 
Anticonvulsant medications typically have undesirable side effects such as 
depression of bone marrow proliferation, with a subsequent drop in white 
blood cell count. Also, the anticonvulsant Tegretol is teratogenic, and it 
is not suitable for use with pregnant women or in children. In these 
instances, a less invasive, safer treatment is indicated. Rapid Rate 
Subcranial Magnetic Simulation (RRSMS) is such a treatment. 
Once the region of the limbic system has been identified that undergoes 
kindling in response to magnetic neurostimulation, patients are treated 
with Rapid Rate Subcranial Magnetic Simulation (RRSMS) as an alternative 
to anticonvulsants. The RRSMS is delivered by placing the magnetic coil in 
the same position and orientation, and exposing the patient to a magnetic 
field having the same strength, shape, direction, train frequency and 
depth, as that shown to induce kindling in that patient. The frequency of 
the magnetic stimulation is the major parameter to be adjusted when 
passing from the diagnostic probing phase to the therapeutic RRSMS phase. 
Repeated kindling over extended periods desensitizes the patient and 
allays the ARTD. 
E. Other Uses 
The present invention contemplates that localized and selective stimulation 
of certain areas within the brain by magnetic stimulation will enhance or 
decrease the concentration and/or effect of neurotransmitters such as 
acetylcholine, dopamine, endorphins, norepinephrine or serotonin. Their 
levels in or outside the limbic system will be manipulated when desired. 
It is desirable, for example, to increase acetylcholine in the nucleus 
basalis to improve an Alzheimer's condition. Or it would be desirable to 
increase Dopamine in the substantia nigra of Parkinson's patients. Or it 
would be desirable to increase endorphin levels in pain control (such as 
was done with TENS). 
Magnetic stimulation of the limbic system is also useful to combine with 
and enhance the effects of neuropsychiatric medications. By activating the 
corresponding centers, it may also promote relaxation and induce sleep. 
Magnetic stimulation may also be used to treat suicidal ideation or 
homicidal ideation. Also recidivism of compulsive rapists, serial 
murderers, even arsonists, could be curtailed significantly. 
In addition, the methods of this invention permit a precise determination 
of structure-function correlations in affected areas of the limbic system. 
The magnetic stimulation as taught herein allows the physician to pinpoint 
with some accuracy the locus of the limbic system that correlates with a 
give patient's ARTD. This locus may then be studied in greater detail 
(e.g., a subsequent post mortem examination of the brain tissues would 
focus on the affected area and allow for more specific research than is 
now possible. 
It will be apparent to those skilled in the field from the foregoing 
description that variations and modifications of the above embodiments, 
methods and techniques may be made without departing from the true spirit 
and scope of the invention. For example, the use of transplantable coils 
and a portable power source is fully contemplated by the invention. The 
invention also fully contemplates an embodiment wherein the patient 
himself decides when to apply the magnetic stimulus (e.g., when he feels 
the onset of an ARTD).