Medical magnetic non-convulsive stimulation therapy

A medical device includes a magnetic stimulator having a magnetic induction coil which is placed next to the scalp of a patient. A pulse train of high energy electrical waves is flowed through the induction coil to produce a sufficiently strong magnetic field to generate currents in the patient's brain for the therapy of psychiatric illnesses. These currents induced in the brain are below the minimum needed to induce a convulsive brain seizure. The device includes an ECG (electrocardiograph) to monitor the electrical activity of the patient's heart and an EEG (electroencephalograph) to monitor the patient's electrical brain waves.

FIELD OF THE INVENTION 
The present invention relates to medical methods and more particularly to a 
method of generating electrical currents inside the brain of a human 
patient without inducing brain seizures in order to treat certain 
psychiatric disorders, especially psychotic depression. 
DESCRIPTION OF THE RELAYED ART 
The related art discloses various methods used in the past for inducing 
brain seizures in patients for the treatment of certain neurologic and 
psychiatric disorders ("neuropsychiatric disorders"), particularly certain 
types of psychotic depression. For example, brain seizures may be induced 
in human patients by the injection of chemical convulsant agents 
(pentylenetetiazol), the inhalation of gaseous convulsant agents (e.g. 
flurothyl, Regan U.S. Pat. No. 3,976,788), or by the application of 
electric currents to the scalp in a procedure termed electroconvulsive 
therapy (ECT), sometimes referred to as "shock therapy". Only ECT is still 
used to induce therapeutic brain seizures. 
In addition, various pharmacological agents (drugs) such as imipramine, 
lithium, perphenazine, etc. have often been used to treat psychotic 
depression. However, sometimes such pharmacological agents have adverse 
side effects, deadly overdose risks, or are not reliably effective. 
In a present method of ECT, a pulsed or varying current of controlled 
amperage or controlled voltage is applied through electrodes to the 
patient's head for a period of 1-10 seconds. There are several hazards and 
risks with ECT, however; these include: 
1) The electrical resistance of the skull to the passage of current greatly 
attenuates the amount of current that actually reaches the brain. The rest 
of the current is shunted through the skin and scalp. Increasing the 
amount of current applied to the head, to reach the minimum required to 
induce seizures, may result in burns to the scalp and skin from the 
shunted current. 
2) Because the direct passage of electric current through the relatively 
high-impedance skin during ECT can cause skin burns, the doctor must 
reduce the impedance of the electrode-to-skin interface by first cleansing 
the skin, then wiping the skin dry, and applying conductive gel over the 
metal electrode surfaces and their application sites on the skin. Special 
effort is then required of the doctor to ensure that the metal disc 
electrodes are applied firmly to the skin, either by holding them in place 
with a rubber headstrap, or holding them with manually-applied 
nonconductive electrode handles. Alternatively, self-adherent, solid-gel 
disposable stimulus electrodes can be used, after first cleansing the skin 
and then wiping the skin dry. Metal disc electrodes, rubber headstraps, 
nonconductive electrode handles, and disposable self-adherent stimulus 
electrodes are all costly to purchase and time-consuming to maintain and 
use. 
3) The attenuated current that finally penetrates the skull is often 
capable only of stimulating seizures over the surface (cortex) of the 
brain. These seizures must then spread by secondary means to the deeper 
brain structures where the therapeutic effects of a seizure are believed 
to occur. Often these secondary means of spreading are insufficient to 
induce therapeutic remission of the disorder. 
4) It has been reported that memory loss may accompany the passage of 
current through the temporal lobes of the brain as part of the procedures 
of ECT. 
5) Leakage currents from defective equipment may reach the patient through 
the electrodes. Such leakage currents are dangerous to patients with 
cardiac arrhythmias or pacemakers. This requires that the ECT equipment 
undergo regular, and expensive, inspections and calibration checks. 
6) The negative feelings, stigma, and fear held by much of the public to 
the phrase "hock therapy" causes many patients to refuse the treatment 
although it would be beneficial to them. 
7) All convulsive therapies, including ECT, induce generalized brain 
seizures that stimulate superficial and deep subcortical brain structures 
indiscriminately. In some neuropsychiatric disorders for which ECT is 
used, however, it appears that only the deep brain structures (e.g. the 
diencephalon) that function abnormally and therefore require stimulation. 
Unnecessary stimulation of brain structures accordingly increases only the 
possibility of undesired effects (see next paragraph). 
8) Generalized seizures have hemodynamic consequences (hypertension, 
tachycardia, increased intracranial pressure) that can present undesired 
and sometimes unacceptable risks to patients with pre-existing cerebral, 
cardiovascular, or cerebrovascular conditions (e.g. myocardial infarction, 
hypertension, stroke, brain tumor). These result from the spread of 
seizure activity into brain areas that control cardiovascular excitation, 
such as the medulla. Patients with brain lesions, as from cerebrovascular 
disease, can suffer substantial confusion and memory loss from the spread 
of seizure activity into brain regions that contain those lesions. 
NCEST (nonconvulsive electrical stimulation therapy) applies a pulsed 
current of constant low amperage or voltage. This stimulates surface and 
deep brain structure, but does not induce brain seizures because of the 
low energy used. When used at particularly low current it may act by 
direct stimulation of tissues only outside the central nervous system 
(CNS) and only indirect stimulation of the CNS. However, NCEST suffers 
from many of the drawbacks that appear in ECT, and, in addition: 
1) The low energy current often fails to penetrate the bony skull in 
sufficient dosage to stimulate the deep subcortical brain structures that 
are believed to require the most stimulation. Any increase in the amount 
of current used increases the risk of the undesirable side-effects of 
generalized brain seizures that occur in ECT. 
2) The electric currents used in NCEST (and also in ECT) tend to diffuse 
through the brain as in a volume conductor. 
This means the current is dispersed fairly evenly throughout the brain and 
cannot be focused, or concentrated, in a specific deep brain region, such 
as the diencephalon, to cause a therapeutic stimulation in just that 
region. 
3) Even the low energy currents used in NCEST may cause painful sensations 
in the skin and scalp that require the use of general anesthesia. The use 
of general anesthesia has been reported to cause mortality rates of 
approximately 0.001% consequent to gastric paresis with vomiting and 
aspiration pneumonitis, hypotensive cardiovascular collapse, or cardiac 
ischemia or cerebral anoxia from laryngospasm. 
In U.S. Pat. No. 5,066,272 to Eaton et al, incorporated by reference, a 
magnetic nerve stimulator produces rapid chain high amplitude voltage 
discharges to a coil placed near a patient's scalp to generate a magnetic 
field. The patent asserts that the brain's high-level cognitive functions 
are disrupted for diagnostic purposes, i.e., to map functional areas of 
the brain. 
In U.S. Pat. No. 4,940,453 to Cadwell, incorporated by reference, a coil 
placed on a patient's head is electrically pulsed to produce magnetic 
stimulation. The magnetic stimulation generates an evoked potential. The 
evoked potentials are detected by electrodes connected to the arm and 
hand. The device is intended as a substitute for an electrical stimulator. 
In U.S. Pat. No. 5,092,835 to Schurig et al a subject wears a hat having 
permanent magnets. The subject watches a monitor which provides audio and 
visual stimulation and holds electrodes in his hands to provide electrical 
pulses. The asserted purpose is to stimulate and repair nerve cells. 
BRIEF SUMMARY OF THE INVENTION 
The present invention comprises a method for stimulating surface, 
intermediate, or deep brain structures by the application of pulsed 
magnetic fields near the outside surface of the patient's head, e.g., 
transcranial magnetic stimulation therapy for the relief of psychiatric 
disorders, especially depression. There is no attempt to treat or diagnose 
neurologic disorders. The generated magnetic fields induce corresponding 
electrical fields in surface and deep brain structures, thereby 
depolarizing nerve cells and raising their level of excitation closer to 
the point of neuronal discharge. In nonconvulsive magnetic stimulation 
(NCMS), the intended therapeutic agent is low-energy excitation of one or 
more brain structures without the induction of a generalized brain 
seizure. This might be given under circumstances of pretreatment of the 
patient with one or more anticonvulsant pharmaceutical agents to inhibit 
the development or spread of partial or generalized seizure activity. 
The nonconvulsive TMS device has electrodes which are connected to the 
chest of the patient to detect the patient's heart beat. They are 
preferably conventional ECG (electrocardiogram) electrodes. The device 
also has EEG (electroencephalograph) electrodes which are connected to the 
scalp of the subject. The device consequently is a combination of (i) a 
magnetic stimulator, (ii) an ECG monitor, and (iii) an EEG monitor. The 
ECG and EEG preferably include analog-to-digital converters, a CPU 
(Central Processing Unit) and a software program which detects the onset 
of a convulsion or calculates the risk of development of a convulsion and 
which automatically halts the magnetic stimulation before the convulsion 
occurs. 
One important reason for incorporating an EEG monitor in a nonconvulsive 
TMS device is to be able to monitor the progress of an 
inadvertently-generated focal or generalized seizure in the occasional 
patient who is so predisposed. To date, there are five published 
instances, of which we are aware, regarding unanticipated seizures 
occurring in patients receiving nonconvulsive TMS for neurological 
evaluation. It is logical that there have been additional instances of 
focal seizures which were not detected because no EEG monitor was used. It 
is expected that the risk of seizure may be even greater with the 
prolonged stimulation required for treatment of psychiatric disturbances. 
In addition to causing fractures, dislocations, cardiac arrhythmias, 
cerebral anoxia, cardiac ischemia, and mental confusion, an unprotected 
grand mal seizure might progress to status epilepticus, with potentially 
severe--even permanent--sequelae. Termination of such a seizure requires 
administration of intravenous anticonvulsant agents under EEG control. 
An ECG monitor is also important because nonconvulsive brain stimulation 
has been associated, in the ECT literature, with cardiac slowing 
(bradycardia), and even cardiac standstill (arrest). This occurs because 
nonconvulsive electrical stimulation can have a direct inhibiting effect 
on the heart via the vagus nerve. In addition, the ECT demonstrates 
evidence of seizure activity affecting the medulla, by tachycardia through 
right medullary stimulation or bradycardia through let medulla 
stimulation. Accordingly, heart rate disturbances seen on the ECG monitor 
can indicate seizure activity. 
The EEG monitor is sensitive to electromagnetic interference (noise) as it 
detects brain waves at the microvolt level. The pulsed magnetic coil, 
potentially, is a source of such noise. There are a number of possible 
solutions of this problem. First, the EEG monitor is equipped with a notch 
filter which filters out wave forms at the frequency of the magnetic 
pulses. The notch filter preferably is automatically changed, under CPU 
control, if the pulse rate is changed. For example, if the pulse rate is 
in the frequency 25-50 Hz the notch filter would cancel all waveforms 
above 20 Hz. Secondly, the pulse frequency may be raised to above 50 Hz 
and a notch filter used to eliminate waveforms above 50 Hz. Thirdly, the 
pulse train to the magnetic coil may be halted and the EEG monitor 
activated only during pauses in the pulse train. For example, a pulse 
train of 5 seconds, a pulse of 1 second for the EEG detection, and another 
pulse train of 5 seconds, pause of 1 second and a third pulse train of 5 
seconds. 
In the method of the present invention a storage capacitor is discharged 
into a stimulating coil by means of one or more solid-state switches. The 
coil is positioned next to the head of the patient. The current in the 
coil generates a magnetic field pulse that induces a secondary current in 
the brain tissue. This secondary current may be focused on a specific 
region in the brain by selectively manipulating the position of the coil 
three dimensionally around the patient's head. 
The voltage waveshape of the secondary current induced in the brain tissue 
is proportional to the rate of change of the magnetic field pulse. The 
delivered pulse, in NCMST, for example, may be a biphasic sine or cosine 
pulse with a duration of preferably 100 to 300 microseconds (usec). The 
pulse repetition rate is preferably 3 to 90 Hz and most preferably about 5 
to 20 Hz. The pulse train is preferably applied for about 0.1 to 60 
seconds, most preferably for about 10-20 seconds. The primary coil current 
is in the preferred range of 2000-5000A and the power is in the preferred 
range of 500-1500 watts. The magnetic flux density of the primary coil is 
preferably in the range of 1 to 5 Tesla, and most preferably about 2 
Tesla. 
The most preferred stimulus for nonconvulsive magnetic stimulation therapy 
(NCMT) is a 10 to 20 second biphasic pulse train at a frequency of about 3 
to 20 Hz (pulsewidth in the range of about 50-300 microseconds). The 
several advantages of the method of the present invention are as follows: 
1. Because the present method does not apply electric currents to the skin, 
NCMST does not expose the subject to the risk of skin burns. 
2. Because the magnetic fields require no direct contact with the skin, 
time-consuming skin preparation is unnecessary and no costly stimulus 
electrodes or accessories are required. 
3. Because the bony skull does not significantly impede the transmission of 
magnetic fields, there is no attenuation of the therapeutic stimulus 
before it reaches the deep brain structures: the intended strength 
electrical field current is directly induced in the brain region specified 
with NCMST. 
4. Because magnetic fields can be oriented in three dimensions, to induce 
focused electrical field currents in deep brain structures, there is no 
necessity for the spread, and consequent attenuation, of brain tissue 
excitation from superficial to deep structures during the application of 
such magnetic fields. 
Similarly, in patients with brain lesions, as from cerebrovascular disease, 
the brain stimulation can be focused in the selected areas, and 
unnecessary stimulation of brain regions near the lesions can be avoided, 
thereby decreasing risks of confusion and memory loss. 
5. Because the invented method does not pass external electric currents 
through the temporal lobes, its use would not cause the same deleterious 
memory effects that have been reported in some cases from ECT. 
6. Because the present method does not apply electric currents to the skin, 
the patient receiving NCMST does not experience the painful electrical 
sensations or shocks possible with ECT, thus avoiding the need for general 
anesthesia with its consequent morbid and mortal risks. 
7. Because the invented method requires no patient electrical or mechanical 
contact, the patient receiving NCMST is not subjected to the risks of 
leakage currents, thereby eliminating the need for costly and 
time-consuming leakage current tests of the device. 
8. Because no electrical stimuli or shocks are applied to the subject's 
head and the subject is not subject to a seizure, the method of NCEST is 
not "shock therapy", thus avoiding the prejudicial implications to some 
members of the public of this term.

DETAILED DESCRIPTION OF THE INVENTION 
The magnetic stimulator circuit of FIG. 1 is suitable for a device to 
induce sufficient electrical currents in the living tissue of the brain of 
a human patient. Capacitor 1 (C1) is initially charged by a power supply 2 
that is connected to capacitor 1 (C1) by solid state switches 3. When 
capacitor 1 (C1) reaches a sufficient charge, these switches 3 open and 
the power supply 1 is disconnected from the circuit. Switch 4 (S1) is then 
closed, completing a circuit loop containing capacitor 1 (C1) switch 4 
(S1), inductor coil 5 (L) and resistor 8 (R). Resistor 8 (R) represents 
the combined resistance of the cables, switches, capacitors, and coil L, 
and ideally is very low. The closing of switch 4 (S1) allows the charge on 
capacitor 1 (C1) to be discharged through the coil 5 (L). The current, i, 
in the coil 5 reaches its maximum when the voltage on capacitor 1 (C1) 
reaches zero. At that moment, switch 4 (S1) is opened and the inductive 
force of coil 5 (L) turns on diode 6 (D2) and charges capacitor 7 (C2). 
Most of the initial charge on capacitor 1 (C1) will thus be transferred to 
capacitor 7 (C2) with relatively small losses due to the stimulation 
pulse. The power supply used to charge capacitor 1 (C1) is also switchable 
and is connected to capacitor 7 (C2) to "top off" capacitor 7 (C2). When 
capacitor 7 (C2) is fully charged, switch 9 (S2) closes and capacitor 7 
(C2) discharges through the coil 5 (L) opening switch 9 (S2). When the 
voltage on capacitor 7 (C2) reaches zero inductor coil 5 (L) turns on 
diode 10 (D1) to "recharge" capacitor 1 (C1) and capacitor 7 (C2). The use 
of the inductive coil 5 (L) to recharge each capacitor 1 (C1) and 7 (C2) 
allows the capacitors to be recharged faster than using the power supply 
by itself. This allows for a higher pulse repetition rate. Having the coil 
5 (L) discharge its inductive energy by charging the capacitor 1 (C1) and 
7 (C2), whenever switches 4 (S1) and 9 (S2) are opened, avoids having the 
coil 5 (L) dissipate that inductive energy as heat. This allows the device 
to have low heat dissipation and requires little, if any, external 
cooling. 
The inductor current, shown in FIG. 2, is proportional to the magnetic 
field induced by the coil 5 (L). This magnetic field generates an induced 
voltage in the brain tissue (also shown in FIG. 2) that is proportional to 
the rate of change (i.e., the first derivative) of the magnetic field. 
This results in the single monophasic cosine induced voltage pulse of FIG. 
2. 
The method of the present invention applies the induced voltage pulses to 
selected focus points within the brain. By proper selection of pulse 
repetition rate, amplitude and duration, therapeutic results in the 
treatment of neuropsychiatric disorders may be achieved. In nonconvulsive 
magnetic stimulation (NCMST), the intended therapeutic agent is low energy 
excitation of surface and deep brain structures without inducing a 
generalized brain seizure. In magnetoconvulsive therapy (MCT), which is 
the subject of U.S. patent application Ser. No. 08/231,307 (allowed), 
incorporated by reference, high energy electrical fields are generated in 
the brain at selected foci to induce therapeutic brain seizures. 
The strength of the magnetic field flux created by the coil 5 (L) will 
preferably be in the range of from 1 to 5 Teslas, and most preferably 
about 2 Teslas. For magnetic fluxes above 1 Tesla it may be necessary and 
more practical to use super-conducting magnets to minimize the size of the 
coil and power requirements. The superconductor magnet may be of the type 
used in magnetic resonance imaging (MRI) systems in which a liquid helium 
cryostat is used to refrigerate a Low-Te superconductive magnet. 
As shown in FIG. 3, the magnetic stimulation device may be housed in a 
Dewar container 20 that moves around the head on a semicircular track 21. 
The semicircular track 21 can then be pivotally mounted to allow the track 
to rotate about an imaginary axis 22 around the patient's head. This three 
dimensional positioning of the coil and the variance of the strength of 
the induced voltage allow the operator to induce electrical currents at a 
particular focal point within the brain. 
In the embodiment shown in FIG. 4 the ECG signal (electrocardiograph), 
which detects heart activity, is sensed via three disposable or reusable 
electrodes 30a, 30b and 30c pasted on the chest 32 of the patient. The ECG 
signal is amplified with a low-noise differential amplifier 33 (less than 
one microvolt of noise) having a band width of 0-300 Hz. For patient 
safety the signal is isolated with optoelectronic isolator 34. The ECG 
signal is then further amplified by amplifier 35 and its frequency is then 
limited with a 2-50 Hz filter 36. 
In one embodiment, to remove electomagnetic noise caused by the pulse train 
to the magnetic coil, a notch filter is used at the frequency of the pulse 
train. For example, if the pulse train is at 30 Hz a notch filter at 25-35 
Hz is employed. Alternatively, or in addition, as explained below, ECG 
readings are taken only during pauses in the pulse train. 
The signal is then passed through a shaper circuit 37 which detects the 
R-wave of the ECG and provides a square wave output compatible with 
detection by the digital circuitry of the computer system 38. The pulse 
output of shaper circuit 37 is connected to a digital input-output circuit 
39 which provides a digital interrupt signal with every heartbeat, i.e., 
it is a rate detector. The heart rate is determined beat-to-beat by timing 
the interval between successive R-waves. The system will calculate heart 
rates and rates of change in heart rate and it will report these via the 
electronic alphanumeric display 60, or alternatively via a moving paper 
record. The system will calculate the time of the steepest drop in the 
heart rate. The pre-stimulus (baseline) frequency is determined over a 
5-second period as a point of reference. After the operator delivers the 
treatment stimulus, by triggering a treatment switch on the device 41, the 
heart rate is followed. The time of occurrence of greatest deceleration is 
identified by comparing the beat-to-beat changes in heart rate. This time 
is then reported to the operator via the electronic alphanumeric display 
60, or alternatively via a moving paper record. If the heart rate 
increases by a user selectable threshold value, such as at least 5% over 
prestimulus (baseline) frequency during or after the stimulus, or it 
accelerates positively or negatively by a user selectable threshold value 
such as 10 bpm per 5 sec, the operator is informed that there was observed 
effect on the heart rate. 
In the embodiment shown in FIG. 4 the EEG signal is determined from two 
disposable or reuseable scalp electrodes 50 and 51 pasted over sites on 
the head 52, e.g., on the forehead, typically above the eyes, or over the 
mastoid processes, or above one eye and over one mastoid process. The EEG 
signal is then amplified with a differential instrumentation amplifier 53. 
To minimize unintended current exposure for patient safety, the signal is 
isolated with optoelectronic isolator 54. The EEG signal is then further 
amplified by amplifier 55 and its frequency is limited with a 2-25 Hz 
filter 56. 
The pulsing of the coil 20 may cause electromagnetic radiation which is 
detected as noise by the EEG electrodes. It is helpful, to avoid such 
noise, that (i) the electrodes are shielded, and (ii) a notch filter is 
used at the frequency of the pulse train. For example, if the pulse train 
is at 30 Hz a notch filter at 25-35 Hz may be used. 
Alternatively, or in addition, the EEG monitor is switched on only during 
pauses in the pulse train to the magnetic coil. For example, the pulse 
train is interrupted by 2-6 pauses. The computer system 61 controls the 
automatic switching (on and off) of the EEG monitor and controls the pulse 
train generated by the pulse train generator 62 to the magnetic coil 20. 
For example, the magnetic coil 20 is pulsed for 5 seconds, there is a 
pause of 1 second during which the EEG monitor is switched on and off for 
0.9 second and this sequence is repeated 2-4 times. 
The signal is then passed through an absolute value circuit 57 and an 
integrator 58 to provide the mean value of the EEG. The mean analog value 
is then sampled and digitized by an analog-to-signal (A/D) converter 59. 
The system will calculate the time of the steepest drop in the EEG 
voltage. 
The patient's brain waves, as detected by the EEG electrodes 50, 50a, 51 
and amplified and digitized by the EEG system, shown in FIG. 3, may be 
used to provide additional information to the operator. The EEG signal may 
be divided, by filters, into selected frequency bands within the 2-25 Hz 
band of filter 56. The Delta band is 2-3.5 Hz, the Theta band is 3.5-7.5 
Hz, the Alpha band is 7.5-12.5 Hz and the lower portion of the Beta band 
is 12.5-25 Hz. Preferably the "absolute power" in the Delta band (2-3.5 
Hz) is measured, although alternatively or in addition absolute power 
across the entire 2-25 Hz spectrum may be measured or absolute power in 
the other bands may be measured. The "absolute power" is the mean 
integrated voltage in the selected band taken over the duration of the 
treatment. The absolute power in the Delta band is called the "Delta 
Energy Index". The "energy" is power times the number of seconds. That 
index is displayed to the operator at the end of the treatment and printed 
in an end-of-treatment report. Alternatively, a "Total Energy Index" may 
be obtained, displayed and printed-out, based upon the absolute power 
measured by the mean integrated voltage across the entire band 2-25 Hz and 
taken over the duration of the treatment. 
The pulse train to the coil is halted, either automatically under computer 
control, or manually by the operator, if the ECG or EEG monitors indicate 
an incipient EEG seizure. Preferably an age-related norm (normal 
population group) is obtained for the power in each EEG band and total 
power. These norms are used to set predetermined threshold values. If 
there is (i) an increase in coherence, and/or (ii) an increase in EEG 
voltage, in any band, or total EEG power; and/or (iii) an increase in 
individual EEG spikes, which is beyond the predetermined threshold values, 
there may be an indication of incipient seizure. For example, if the EEG 
power in the Delta band of the patient is 20% above the mean normal power, 
in view of the patient's age, and there are EEG spikes, there may be an 
incipient seizure and the pulse train is halted. Preferably a computer 
software program recognizes the indications of incipient seizure by 
comparison of the patient's EEG with the predetermined threshold values 
and generates a control signal to halt the pulse train when one, or more, 
of the EEG signals exceed the predetermined threshold values. 
As shown in FIG. 5, the magnetic stimulation device 70 includes a magnetic 
stimulator, EEG monitor, ECG monitor, computer system 61 and display 60. 
The ECG monitor has three electrode leads 30a-30c; the EEG monitor has 
three electrode leads 50, 51, 50a, and the magnetic stimulator has two 
leads to the coil 20. The computer system 61 controls the magnetic 
stimulation and performs the EEG and ECG analysis and presents results on 
the display 60. The dial 73 is used to control time (seconds of magnetic 
stimulation) and the seconds are shown on number display 64. The alarm 66 
is lighted, and a buzzer sounds, if the patient shows signals of an 
adverse effect. The light 72 is lit during treatment periods.