United States Patent |
5,899,922
|
Loos
|
May 4, 1999
|
Manipulation of nervous systems by electric fields
Abstract
Apparatus and method for manipulating the nervous system of a subject
through afferent nerves, modulated by an externally applied weak electric
field. The field frequency is to be chosen such that the modulation causes
excitation of a sensory resonance. The resonances found so far include one
near 1/2 Hz which affects the autonomic nervous system, and a resonance
near 2.4 Hz that causes slowing of certain cortical processes. Excitation
of the 1/2 Hz autonomic resonance causes relaxation, sleepiness, ptosis of
the eyelids, or sexual excitement, depending on the precise frequency
used. The weak electric field for causing the excitation is applied to
skin areas away from the head of the subject, such as to avoid substantial
polarization current densities in the brain. Very weak fields suffice for
bringing about the physiological effects mentioned. This makes it possible
to excite sensory resonances with compact battery powered devices that
have a very low current consumption. The method and apparatus can be used
by the general public as an aid to relaxation, sleep, or sexual arousal,
and clinically for the control and perhaps the treatment of tremors and
seizures, and disorders of the autonomic nervous system, such as panic
attacks.
Inventors:
|
Loos; Hendricus G. (3019 Cresta Way, Laguna Beach, CA 92651)
|
Appl. No.:
|
970747 |
Filed:
|
November 14, 1997 |
Current U.S. Class: |
607/2 |
Intern'l Class: |
A61N 001/36 |
Field of Search: |
607/2,39,45
600/26
|
U.S. Patent Documents
3441136 | Mar., 1976 | Buealo | 607/39.
|
3678337 | Jul., 1972 | Graunogel | 128/419.
|
3840020 | Oct., 1974 | Smith | 128/419.
|
3886932 | Jun., 1975 | Suessmilch | 128/908.
|
4084595 | Apr., 1978 | Miller | 178/422.
|
4197851 | Apr., 1980 | Fellus | 128/422.
|
4297980 | Oct., 1981 | Suzuki | 128/419.
|
4611599 | Sep., 1986 | Bentall et al. | 128/422.
|
4856526 | Aug., 1989 | Liss et al. | 128/422.
|
5169380 | Dec., 1992 | Brennan | 600/26.
|
Foreign Patent Documents |
0285415 | Dec., 1965 | AU | 607/2.
|
3327126 | Apr., 1984 | DE | 607/2.
|
2164563 | Mar., 1986 | GB | 607/2.
|
Primary Examiner: Kamm; William E.
Parent Case Text
Division of Ser. No. 08/788582, Jan. 24, 1997, now U.S. Pat. No. 5,782,874,
Jul. 21, 1998, which is a continuation-in-part of Ser. No. 08/447394, May
23, 1995, abandoned, which is a continuation of Ser. No. 08/068748, May
28, 1993, abandoned.
Claims
I claim:
1. Apparatus for modulating cutaneous nerves in areas of sparsely
innervated skin away from the head of the subject, comprising:
field-applying means for applying, predominantly to the said areas of the
skin, an external periodic electric field with a frequency in the range
0.1 to 2 Hz and such that, over the said areas, the field amplitude is
between 1 and 25 V/m, for modulating cutaneous nerves in the said areas of
the skin without causing classical stimulation of cutaneous nerves; and
frequency tuning means for tuning the frequency of the field-applying
means.
2. Apparatus according to claim 1, in which the said field-applying means
comprises field electrode means, generator means for generating a periodic
voltage, and conductor means for connecting said generator means to said
field electrode means, further including:
switching means for interrupting polarization currents through the said
conductor means, caused by a 60 Hz house field when the apparatus is
inactive.
3. In electrical apparatus for inducing at least one of a plurality of
results, namely relaxation, sleep, and sexual excitement, and control of
tremors, seizures, and panic attacks, comprising:
generator means for generating a periodic voltage with a peak-to-peak
variation less than 10 V and a frequency in the range 0.1 to 2 Hz;
field electrode means, electrically connected to the generator means, for
applying, predominantly to areas of sparsely innervated skin away from the
head of a subject an external periodic electric field, with an amplitude
over the said areas between 1 and 25 V/m, for modulating cutaneous nerves
in the said areas without causing classical stimulation of cutaneous
nerves; and
frequency-tuning means for tuning the frequency of the generator means.
4. In an apparatus according to claim 3, and wherein the field electrode
means comprise one field electrode to be placed adjacent to skin area on
the hips, buttocks, and lower back of the subject, and another field
electrode to be placed adjacent to the skin area on the back side of the
thighs and knees of the subject.
5. Apparatus for manipulating the nervous system of a subject, comprising:
generator means for generating a periodic voltage with a peak-to-peak
variation less than 16 V, and a frequency less than 45 Hz; and
field electrode means, electrically connected to the generator means, for
inducing an electric field on the skin of the subject to modulate afferent
nerves, without causing classical nerve stimulation, and without causing
substantial polarization current densities in the brain of the subject.
6. Apparatus for manipulating the nervous system of a subject, comprising:
generator means for generating a periodic voltage with a frequency less
than 45 Hz and a peak-to-peak variation less than 16 V;
at least two field electrodes, connected to the generator means, for
producing an electric field;
one casing for containing the generator means and the field electrodes.
7. A method for manipulating the nervous system of a subject, comprising:
selecting, on the subject, a skin area away from the head;
generating a periodic voltage with frequency less than 45 Hz, and a
peak-to-peak variation less than 16 V;
applying the periodic voltage to field electrodes for producing an electric
field; and
administering the electric field predominantly to said skin area, for
modulating afferent nerves without causing classical nerve stimulation,
and without causing substantial polarization current densities in the
brain of the subject.
8. The method of claim 7 for exciting in the subject a sensory resonance
with a resonance frequency below 45 Hz, further including the step of
setting the voltage frequency to the resonance frequency.
Description
BACKGROUND OF THE INVENTION
The invention relates to electrical neurostimulation, wherein electric
currents are passed to the brain, the spinal cord, an organ, or peripheral
nerves ›1-3!. Such stimulation has been used with various degrees of
success for anesthesia, induction of relaxation and sleep, as well for the
treatment of pain, intractable epilepsy, behavioral disorders, movement
disorders, and cardiac arrythmia. The electric current is usually
delivered by contact electrodes i.e., electrodes that are in Ohmic contact
with the biological tissue. An exception is the capacitor electrode of
Guyton and Hambrecht ›4!, which consists of an implanted porous tantalum
disc with a thin insulating coating of tantalum pentoxide. After
implantation, the pores fill with extracellular fluid and thus present a
large capacitive interface to the fluid. The electrode is capable of
delivering sizable currents to tissue without causing accumulation of
electrochemical byproducts. Mauro ›5! has proposed another capacitor
electrode in which one of the "plates" is formed by an electrolyte that is
in Ohmic contact with the tissue, via a thin tube. In both these cases the
capacitance employed is large, such as to pass currents of a magnitude and
duration large enough to cause firing of the nerves, as expressed by the
strength-duration curve with typical times of 0.1 ms and currents of the
order of 1 mA ›6,7!. The nerves fire as a result of substantial
depolarization of the nerve membrane by the applied electric current, a
process here called classical nerve stimulation.
An area of neurostimulation that has attracted much attention is the
induction of relaxation and sleep. One method, called Cranial Electric
Stimulation (CES) involves passing an alternating current through the
brain via contact electrodes attached to the head or held in the mouth.
With properly chosen strength and frequency, these currents may excite or
support brain waves that accompany deep sleep. The method has been
explored extensively in the Former Soviet Union, under the name
"Electrosleep".
A commercially available device is the Japanese "Sleepy" ›8!, which
generates for one hour square pulses of 4 V and 0.2 ms duration, with a
frequency that sweeps from 14 to 0 Hz, every 3 minutes. The device
requires contact electrodes placed on the head. Other commercial CES
devices ›9! are Alpha Stim, Mindman, and Endo Stim, which all require
contact electrodes attached to the head.
Electric currents in biological tissue may also be induced by an electric
field that is generated in the space outside the subject. The external
electric field is set up by applying an electric potential between field
electrodes that do not have Ohmic contact with the tissue. Of course the
arrangement may be seen as a form of capacitive coupling, but the
capacitances are very much smaller than in Mauro ›5! or Guyton and
Hambrecht ›4!. There is also an important practical difference, in that no
bodily contact with any part of the apparatus is required for the electric
field application by the field electrodes.
A neurological effect of external electric fields has been mentioned by
Norbert Wiener ›10!, in discussing the bunching of brain waves through
nonlinear interactions. The electric field was arranged to provide "a
direct electrical driving of the brain" ›10!. Wiener describes the field
as set up by a 10 Hz alternating voltage of 400 V applied in a room
between ceiling and ground.
Brennan ›11! describes an apparatus for alleviating disruptions in
circadian rythms of a mammal, in which an external alternating electric
field is applied across the head of a subject. The voltage applied to the
electrodes is specified as at least 100 V, and the peak-to-peak value of
the electric field as at least 590 V/m in free air before deploying the
electrodes across the head of the subject. The frequency of the
alternating electric field is in the range from 5 to 40 Hz. Brennan states
that the method is aimed at subjecting at least part of the subject's
brain to an alternating electric field, in the belief that this would
stimulate an influx of Ca.sup.2+ ions into nerve endings, which in turn
would "regulate and facilitate the release of neurotransmitters".
Embodiments mentioned include electrodes arranged in a head cap, in a bed,
or mounted on the walls of a room. It should be noted that electric
polarization of the head causes the field strength in the narrow space
between electrode and skin to be about a factor h/2d larger than the
free-air field strength, h being; the distance between the electrodes and
d the spacing between electrode and skin. For h=17 cm and d=5 mm the
factor comes to 17, so that with the specified free-air field of at least
590 V/m the field in the gap between electrode and skin is at least 10
KV/m peak to peak.
A device involving a field electrode as well as a contact electrode is the
"Graham Potentializer" mentioned in Ref. ›9!. This relaxation device uses
motion, light and sound as well as an external alternating electric field
applied predominantly to the head. The contact electrode is a metal bar in
Ohmic contact with the bare feet of the subject; the field electrode is a
hemispherical metal headpiece placed several inches from the subject's
head. According to the brief description in ›9!, a signal less than 2 V at
a frequency of 125 Hz is applied between the field electrode and the
contact electrode. In this configuration the contact electrode supplies to
the body the current for charging the capacitor formed by the field
electrode and the apposing skin area. The resulting electric field stands
predominantly in the space between the head piece and the scalp.
In the three external field methods mentioned, viz. Wiener ›10!, Brennan
›11!, and Graham ›9!, the electric field is applied to the head, thereby
subjecting the brain to polarization currents. These currents run through
the brain in a broad swath, with a distribution influenced by
nonuniformities of conductivity and permittivity. The scale of the current
density can be conveniently expressed by the maximum value, over the skin
of the head, of its component perpendicular to the local skin. This scale
is easily calculated for sinusoidal fields as the product of radian
frequency, permittivity, and maximum amplitude of the external field on
the head. Using Brennan's ›11! lowest frequency of 5 Hz, his minimum
required free-air field strength of 590 V/m, and the factor 17 as
estimated above to account for the polarization of the head by the applied
field, the scale of the polarization current density in the brain comes to
about 280 pA/cm.sup.2. Without understanding the neurological effects
involved, it is prudent to avoid exposing the brain to current densities
of such scale, and impose as a limit 1/4000 times the scale calculated for
Brennan's patent. Polarization current densities in the brain with a scale
in excess of 70 fA/cm.sup.2 are henceforth considered substantial.
It is the object of the present invention to obtain a method and apparatus
for manipulating the nervous system by external electric fields without
causing substantial polarization currents in the brain.
The use of electric fields raises concerns about possible health effects.
Such concerns have been widely discussed in the media in regard to
electric power lines and electric apparatus ›12!. Answering the pertinent
questions by objective research will take time, but meanwhile governments
have been setting guidelines for safe limits on field strengths. At
present, the strictest limits of this sort are the Swedish MPRII
guidelines. Magnetic fields are of no concern here, because the currents
involved are so small. However, the electric field strengthy must be
considered, since even at low voltages strong electric fields can result
from electrodes placed close to the skin. For extremely low frequency
fields, the MPRII guidelines limit the field strength to 25 V/m in the
frequency range from 5 Hz to 2 KHz. In the Brennan patent ›11! the minimum
field strength of 590 V/m violates the guidelines by a factor 23; when the
polarization effects are accounted for, the factor is about 400.
It is a further object of the present invention to manipulate the nervous
system by external electric fields that are in compliance with the MPRII
guidelines.
Brennan ›11! stipulates voltages of at least 100 V, and as high as 600 V
for his preferred embodiment. Generation of such voltages requires a
voltage multiplier stage, if practical battery operation is desired. This
increases the current drain and the size of the generator. The large
voltages also raise safety concerns.
It is yet a further object of the present invention to manipulate the
nervous system by external electric fields, using low voltages that are
generated by a small and safe battery-powered device with low current
consumption.
SUMMARY
Experiments have shown that weak electric fields of frequency near 1/2 Hz
applied externally to the skin of a subject can cause relaxation,
doziness, ptosis of the eyelids, or sexual excitement, depending on the
precise frequency used. In these experiments the electric field was
applied predominantly to skin areas away from the head, thereby avoiding
substantial polarization current densities in the brain. Apparently, the
external electric field somehow influences somatosensory or visceral
afferent nerves, which report the effect to the brain. Although the
mechanism whereby the field acts on the afferents is unknown, the effect
must take the form of a slight modulation of the firing patterns of the
nerves, because the polarization current densities induced by the field
are much too small to cause firing of the nerve. If the applied external
field is periodic, so will be the modulation of the firing patterns of
affected afferent fibers, and the brain is then exposed to an evoked
periodic signal input. Apparently, this signal input influences certain
resonant neural circuits, the state of which has observable consequences.
Since the resonances are excited through somatosensory or visceral
afferents, they are here called "sensory resonances".
Besides the resonance near 1/2 Hz that affects the autonomic nervous
system, we have also found a resonance near 2.4 Hz which slows certain
cortical processes. For both resonances the external electric field on the
skin must lie in a certain range of values for the physiological effects
to occur. This "effective intensity window" can be determined accurately
for the 2.4 Hz resonance, by measuring the time needed to count silently
backward from 100 to 70.
The effective intensity window depends on the number of afferents modulated
by the field. This "bulk effect" is important for the proper use of the
invention, and has therefore been explored in preliminary experiments. At
the lower boundary of the window the external field strengths are very
small, down to 10 mV/m when a large skin area is exposed to the field. The
fact that very small external field strengths suffice for the excitation
of sensory resonances through modulation of afferents allows the use of
small battery-powered electric field generators that can be used
conveniently by the general public as an aid to relaxation, sleep, or
sexual excitement, and clinically for the control and perhaps a treatment
of tremors and seizures, and disorders of the autonomic nervous system
such as panic attacks.
Compliance of the devices with the MPRII guidelines on field limits in the
ELF and VLF frequency bands is easily achieved.
The field generators shown involve simple low voltage generators based on
555 type timer chips, and field electrodes that are small enough to fit in
a single small casing, such as a powder box.
Although the mechanism of electric field modulation is unknown, candidates
for cutaneous receptors that may be susceptible to this modulation are
indicated.
DESCRIPTION OF THE DRAWINGS
FIG. 1 depicts a preferred embodiment, and shows the deployment of field
electrodes external to the body of the subject.
FIG. 2 illustrates the electric field generated between the field
electrodes and the subject's body.
FIG. 3 shows an embodiment which generates an electric field that
fluctuates as a rounded square wave, and includes an automatic shutoff.
FIG. 4 shows an embodiment which generates an electric field that
fluctuates as a rounded square wave, and which includes an automatic
frequency shift and automatic shutoff.
FIG. 5 shows an embodiment which generates an electric field that
fluctuates as a rounded square wave with a chaotic time dependence, and
which includes an automatic shutoff.
FIG. 6 shows the map of time intervals between consecutive transitions of
the chaotic square wave generated by the circuit of FIG. 5.
FIG. 7 shows an embodiment in which the field electrodes and generator are
contained in a powder box.
FIG. 8 shows schematically a shielded pair of electrodes.
FIG. 9 shows the effective intensity window for currents passed by contact
electrodes to the skin overlying the vagus nerve.
FIG. 10 shows the effective intensity window for large skin area exposure
to the field from a small electrode pair placed some distance from the
subject.
FIG. 11 is a replot of the data of FIG. 10, to serve in a comparison with
the data of FIGS. 12 and 13.
FIG. 12 shows the effective intensity window for an experiment using a
shielded electrode pair placed on the thighs.
FIG. 13 shows the effective intensity window for an experiment using a
shielded electrode pair placed on the finger tips.
DETAILED DESCRIPTION
The invention is based on the discovery, made in our laboratory, that
neurological effects can be induced by weak external electric fields of a
precisely tuned frequency near 1/2 Hz, when applied to skin areas away
from the head. The observed effects include ptosis of the eyelids,
relaxation, drowziness, the feeling of pressure at a centered spot on the
lower edge of the brow, seeing moving patterns of dark purple and greenish
yellow with the eyes closed, a tonic smile, a tense feeling in the
stomach, and sexual excitement, depending on the precise frequency used.
These effects were observed initially for external field strengths in the
range from 1 to 25 V/m, but recent experiments have shown effects with
much weaker and stronger fields.
In these experiments the polarization current densities produced in
biological tissue by the applied external electric field are much too
small to cause classical nerve stimulation, yet a central nervous system
response is evoked. Experiments have shown that signal pathways other than
afferent nerves are not involved. It follows that weak external electric
fields can evoke some sort of signal that is carried by afferent nerves.
Since classical nerve stimulation cannot occur, these signals must have
the form of a modulation of spontaneous firing patterns. The simplest such
modulation is frequency modulation (fm), but more subtle modulation modes
›26! may be involved. For simplicity of description however, we will refer
to the modulation as fm. In our experiments the modulation depth is very
small, but for field frequencies close to the resonance frequency of
receptive neural circuits the weak incoming fm signal can evidently cause
excitation of the resonance with observable consequences. Since the
applied fields are much too weak to cause nerves to fire, the sensory and
visceral receptors and afferents susceptable to modulation must exhibit
spontaneous firing.
Since the resonances are excited through somatosensory or visceral afferent
nerves, they are here called sensory resonances. The sensory resonance
near 1/2 Hz involves the autonomic nervous system and is therefore
sometimes called the 1/2 Hz autonomic resonance.
Exploitation of sensory resonances and reliance on modulation of
spontaneous firing patterns rather than classical nerve stimulation makes
it possible to manipulate the nervous system with very small electric
fields, induced by low voltages. Moreover, employing the natural pathways
of afferent nerves into the brain allows application of the field to skin
areas away from the head. The invention thereby meets the stated objects
of providing manipulation of the nervous system without causing
substantial polarization current densities in the brain, compliance with
MPRII field limits, and use of a low voltage battery powered generator
with small current assumption.
The invention provides a method and apparatus for maniplating the nervous
system of human subjects. Such manipulation comprises relaxation and the
induction of sleep or arousal, as well as the control and perhaps a
treatment of tremors, seizures, and disorders resulting from a malfunction
of the autonomic nervous system, such as panic attacks.
In the early experiments the excitation of the sensory resonance occurred
through the modulation of cutaneous nerves by the applied electric field.
In later experiments with larger field strengths, similar physiological
effects have been obtained by applying the field to the skin overlying the
vagus nerve or the sciatic nerve. It appears that excitation of sensory
resonances can be achieved through any afferent pathway, provided that it
is broad.
A new sensory resonance has been found at 2.4 Hz, characterized by a
pronounced increase in the time needed for silently counting backward from
100 to 70. Prolonged exposure to the excitation was found to have a
sleep-inducing and dizzying effect. Recent experimental results will be
discussed towards the end of the specification.
The equipment suitable for the generation of the weak electric fields used
for the modulation of afferent nerves consists of field electrodes and a
voltage generator. The field electrodes can be conductive foils, wires or
meshes that may optionally be covered on one or both sides with an
insulating layer. The field electrodes are to be electrically connected to
the generator, but insulated from the subject. The voltage generator is to
produce a low flucuating voltage. Harmonic content needs to be considered
for compliance with MPRII guidelines, if the amplitude of the field
applied to the skin is large. An automatic shutoff can be provided, such
as to limit the duration of the field administration.
It has been found that a single half hour application of the field is
usually sufficient to induce sleep, if the frequency is tuned correctly
for the individual to a frequency near 1/2 Hz. Shorter application times
are typically sufficient for inducing relaxation.
A preferred embodiment is shown in FIG. 1, where the voltage generator 1,
labelled as GEN, is connected to the field electrodes 2 by wires 3; the
field electrodes 2 are positioned away from the subject 4. The voltage
generator may be tuned manually by the user with the tuning control 21. As
an option, sheet conductors 43 and 43' such as aluminum foils may be
placed near the subject in order to diminish interference from a 60 Hz or
50 Hz house field, to be discussed. Referring to FIG. 2, application of a
voltage between the field electrodes 2 produces an electric field 5
between field electrodes 2 and the subject 4, for the case that the sheet
conductors 43 and 43' of FIG. 1 are absent. The field is applied
predominantly to skin areas away from the head of the subject; in the
setup of FIG. 1 these areas comprise skin area 36 on the hips, buttocks,
and lower back, and skin area 36' on the back side of the thighs and
knees.
A suitable voltage generator, built around two RC timers, is shown in FIG.
3. Timer 6 (Intersil ICM7555) is hooked up for astable operation; it
produces a square wave voltage with a frequency determined by resistor 7
and capacitor 8. The square wave voltage at the output 9 drives the LED
10, and appears at one of the output terminals 11, after voltage division
by potentiometer 12. The other output terminal is connected to an
intermediate voltage produced by the resistors 13 and 14. As a result, the
voltage between the output terminals 11 alternates between positive and
negative values. Automatic shutoff of the voltage that powers the timer,
at point 15, is provided by a second timer 16 (Intersil ICM7555), hooked
up for monostable operation. The shutoff occurs after a time interval
determined by resistor 17 and capacitor 18. Timer 16 is powered by a 3 V
battery 19, controlled by the switch 20. The output terminals 11 are
connected to the field electrodes 2 by conductors 3. The resistors 13 and
14 not only serve as a voltage divider that gives the intermediate voltage
needed to produce an alternating square wave, but these resistors also
provide current limitation. A further decrease of the currents induced in
the subject is caused by the output capacitor 22, in a manner to be
discussed. There is the option of including a switch 44 in the output
circuit, in order to prevent polarization of the electrode assembly by a
60 Hz or 50 Hz house field when the device is inactive, to be discussed.
A time variation of frequency may be accomplished by manipulating the
control voltage of one section of a dual timer with the output of the
other section. An embodiment for this type of operation is shown in FIG.
4. The dual timer 23 (Intersil ICM7556) is powered at point 24 by voltage
from the output 15 of timer 16 (Intersil ICM7555), which serves as an
automatic shutoff after a time interval determined by resistor 17 and
capacitor 18. The timer operation is started by closing switch 20. The
voltage at output 25 of the dual timer 23 drives the LED 10, and is
applied, via the variable resistor 12, to one of the outputs 11 of the
voltage generator. Resistors 14 and 13 serve to provide an intermediate
voltage at the other output terminal 11, such as to result in a potential
difference between the output terminals that alternates between positive
and negative values of substantially equal magnitudes. The frequency of
the square wave voltage at point 25 depends on resistor 7 and capacitor 8.
The frequency is also influenced by the control voltage applied to the
timer. A frequency upshift can be obtained by applying the output of the
second section of the dual timer 23 to the control voltage pin of the
first timer section, via resistor 26. This second timer section is hooked
up for monostable operation. The output terminals 11 are connected by
conductors 3 to the field electrodes 2, which are pieces of aluminum foil,
covered by insulating tape on both sides.
The automatic shutoff and time variation of the frequency are examples of
automatic control of the fluctuating voltage generated by the generator.
Low frequencies can be monitored with an LED 10 of FIG. 3. The LED blinks
on an off with the square wave, and doubles as a power indicator. The
frequency can be determined by reading a clock and counting LED light
pulses. For higher frequencies a monitoring LED can still be used, if it
is driven by a wave obtained by frequency division of the generator output
wave .
The voltage generators discussed above have oscillators of the RC type, but
other types of low-voltage oscillators can be used as well. For instance,
the voltage generator can be built as a digital device, in which a square
wave output is derived from a clock signal by means of frequency division.
Chaotic signals, time variation of frequency, programmed frequency
sequences, automatic turn on and shutdown, frequency adjustment, and
frequency monitoring may also be accomplished digitally. A computer that
runs a simple timing program can be used for the generation of all sorts
of square waves that can be made available at a computer port. An economic
and compact version of such arrangement is provided by the Basic Stamp
›30!, which has an onboard EEPROM that can be programmed for the automatic
control of the fluctuating voltage generated, such as to provide desired
on/off times, frequency schedules, or chaotic waves. In the interest of
controlling polarization current peaks or complying with MPRII guidelines,
the square waves can be rounded by RC circuits, and further smoothed by
integration and filtering. In this manner, near sinusoidal output can be
achieved. Such output can also be obtained with a digital sine wave
generator based on a walking-ring counter ›31!, or with a waveform
generator chip such as the Intersil ICL8038. Analog circuits for tunable
sine wave generators based on LC oscillators with passive inductance and
capacitance are not practical because of the very large component
parameter values required at the low frequencies involved. Large
inductances can be produced by a compact active stage, or one can use two
separate RC phase shift circuits connected in a loop with an amplitude
limiter ›32!. Tuning may be done with a single potentiometer.
Applications are envisioned in which the field electrodes are driven with a
fluctuating voltage that is chaotic. Such a voltage is here defined as a
signal for which the times of zero crossings or peaks, or both, form a
pseudo-random sequence. A simple example is provided by a square wave for
which the transition time intervals form a pseudo-random sequence, within
upper and lower limits. The brain is adaptive, but the chaotic transitions
are difficult to learn and anticipate, and therefore a field with a
slightly chaotic square wave can thwart habituation. A sensory resonance
can still be excited by such a wave, if the average frequency of the wave
is close to the resonant frequency. The chaotic wave can also be used to
upset pathological oscillatory modes in neural circuitry, such as to
control tremors in Parkinson patients.
An embodiment which involves a chaotic square wave electric field is shown
in FIG. 5. The dual timer 23 (Intersil ICM7556) is powered, at point 24,
by the output 15 of timer 16 (Intersil ICM7555), hooked up for monostable
operation, such as to provide automatic shutoff after a time determined by
resistor 17 and and capacitor 18. Operation of timer 16 is started by
closing switch 20. Both sections of the dual timer 23 are hooked up for
bistable operation, with slightly different RC times. The voltage at
output 25 of the first timer section is used to drive the LED 10; after
voltage division by the variable resistor 12, the voltage is applied to
one of the outputs 11. The other output 11 is an intermediate voltage from
the voltage divider formed by resistors 14 and 13. The ouputs 11 are
connected to the field electrodes 2 through conductors 3. The RC time of
the first timer section is determined by resistor 7 and capacitor 8. The
RC time of the second timer section is determined by resistor 27 and
capacitor 28. The two timer sections are coupled by connecting their
outputs crosswise to the control voltage pins, via resistors 29 and 30,
with capacitors 31 and 32 to ground. For a proper range of component
values, easily found by trial and error, the square wave output of each of
the timer sections is chaotic.
An example for chaotic output is shown in FIG. 6, where the points plotted
correspond to transitions (edges) of the square wave. Abscissa 33 and
ordinates 34 of a plotted point are time durations between consecutive
transitions of the square wave output; for any transition, the abscissa is
the time to the preceding transition, and the ordinate is the time to the
next transition. Starting with transition 35, consecutive transitions are
found by following the straight lines shown. The transition times follow a
pseudo random sequence, with some order provided by the oval attractor.
The results shown in FIG. 6 were measured for the device of FIG. 5, with
the following component values: R.sub.7 =1.22 M.OMEGA., R.sub.27 =1.10
M.OMEGA., R.sub.29 =440 K.OMEGA., R.sub.30 =700 K.OMEGA., C.sub.8 =0.68
.mu.f, C.sub.28 =1.0 .mu.f, C.sub.31 =4.7 .mu.f, and C.sub.32 =4.7 .mu.f.
In the above list, R.sub.i is the resistance of component i in FIG. 5, and
C.sub.j is the capacitance of component j.
Tests with a subject who is not a Parkinson patient, but who has a hand
tremor of another origin, have shown good control of the tremor by a
square wave electric field with the chaotic time dependence shown in FIG.
6. The device of FIG. 5 was used in these tests, with electrodes placed
vertically on two opposite vertical sides of the seat cushion of an easy
chair.
In the present invention, the external field is applied predominantly to
certain selected areas of the skin of the subject, such as the areas as 36
and 36' in FIG. 2. Areas of predominant field application are here defined
to consist of all points of the skin at which the absolute value of the
resultant field strength is at least twice the average over the skin. The
resultant field includes the field produced by polarization charges on the
skin of the subject. The resultant field is perpendicular to the skin when
the polarization keeps up with changes in the applied field, as is the
case for the low frequencies involved, if sharp transitions are avoided.
Of convenience in social settings is an embodiment in which the two field
electrodes and the signal generator are contained in a single casing such
as a small box, purse, powder box, or wallet. An embodiment is shown in
FIG. 7, where the generator 1' with tuning control 21' is placed inside a
powder box casing 45 with hinge 49. The field electrodes 2 and 2' are
contained in the casing 45. The field electrodes 2 are connected to the
generator 1' by conductors 3. For brevity, field electrodes mounted on the
outside surface of a casing are considered as contained in the casing.
The peak-to-peak variation of the output voltage of the voltage generators
discussed above cannot exceed 16 V, because of supply voltage limitations
for the CMOS timer chip. However, much lower output voltages suffice for
most applications. An output voltage of 2.4 V peak to peak is adequate for
the setup of FIG. 1. Such an output voltage is provided by the signal
generators of FIGS. 3 and 4, when powered by a 3 V battery. Such small
voltages suffice even for embodiments in which the generator and field
electrodes are mounted in a single small casing, in spite of the small
area available for the electrodes.
An electric field outside the body of the subject is called an external
electric field.
In applications of modulation of cutaneous nerves by an external electric
field there is usually also present a 60 Hz or 50 Hz house field, i.e., an
electric field emanating from house wiring, electric apparatus and
electric power lines. House fields can have considerable strength; Becker
and Marino ›15, table 10.4! list the electric field, at 1 ft distance from
an electric blanket, broiler, refrigerator, food mixer, hairdryer, and
color TV, respectively as 250, 130, 60, 50, 40, and 30 V/m. The electric
field 1 ft away from a light bulb is listed as 2 V/m. The house field may
cause inadvertent modulation of cutaneous nerves. In distinction with this
inadvertent modulation, there is the purposeful modulation which is the
subject of the present invention. The house field intensities mentioned
above suggest that the house field may interfere with the purposeful
modulation. The interference can be diminished by reducing the strength of
the house field incident on the subject. This may be done by placing near
the subject a sheet conductor oriented roughly parallel with the local
house field. An example is shown in FIG. 1, where a sheet conductor in the
form of aluminum foils 43 is placed against the underside of the bed, and
a continuation 43' of the aluminum foil covers the back of the headboard.
The house-field-diminishing effect of a properly placed and oriented sheet
conductor can be readily understood as due to electric polarization of the
sheet conductor by the house field.
There further is concern about the effect of house field induced electric
polarization of the electrode assembly, that may occur at times when no
external electric field is being generated by the apparatus, although the
field electrodes are electrically connected through the device. This state
occurs during most of the night, if the apparatus of FIGS. 3 or 4 is used
as a sleeping aid with permanently placed field electrodes, after the
automatic shutoff has cut the power to the oscillator. Of concern is the
circuit comprised of the two field electrodes, their connections to the
signal generator, and pertinent output circuitry in the signal generator.
Referring to FIG. 3, it is seen that this circuit includes the capacitor
22 and part of the potentiometer 12. The house field generally induces
polarization currents in this circuit. The resulting polarization charges
on the field electrodes induce an electric field with a nonuniformity
scale comparable to the electrode spacing. This 60 Hz field may cause
modulation of the same afferent nerves as those involved in the purposeful
modulation by the apparatus field. The inadvertent modulation may cause
weak fm signals of 60 Hz frequency in receptive neural circuitry, and the
signals may be so weak as to sneak by nuisance-guarding circuitry. The
unwanted signals may be diminished by using the house-field-diminishing
sheet conductor described above. Alternatively, or in addition,
polarization of the electrode assembly by the house field may be prevented
by breaking the electric connection between the field electrodes by means
of a switch (44 in FIG. 3) in one of the output leads of the signal
generator. This switch may be ganged with the power switch.
The external electric field must be predominantly applied to skin regions
away (at least 10 cm) from the head of the subject. Furthermore,
substantial polarization current densities in the subject's brain must be
avoided. The scale of these current densities is expressed here as the
product of permittivity, radian frequency of the field, and maximum
external electric field amplitude on the head; this product should not
exceed 70 fA/cm.sup.2. Satisfying this condition and that of predominant
field application to skin areas away from the head requires calculation of
external field strengths on the subject's skin, for the field electrode
configuration and deployment considered. This can be done along the
following lines.
First, the electric field produced by a field electrode at distance r is
given by the well known Coulomb formula, for r considerably larger than
the electrode dimensions. For elongated electrodes, the two-dimensional
Coulomb formula can be used for intermediate distances that are large
compared to a significant dimension of the cross section but small
compared to the electrode length. The presence of the subject can be
accounted for by the well-known method of images ›27!. The field produced
by a field electrode in its immediate vincinity can be calculated with
simple models that are appropriate to the situation at hand, and are well
known to those skilled in the art. Of course, these calculations need only
be approximate or furnish reliable upper bounds of the field strength
considered. Field calculations will be shown here for several field
electrode configurations and settings of practical interest.
Presently, the experiments that underlie the invention will be discussed.
The experiment setup used was much like the one shown in FIG. 1, with
variations as to the skin area of predominant field application. The
voltage applied between the field electrodes was usually a square wave
with a frequency that can be manually tuned from 0.1 to 3 Hz, by adjusting
the tuning control 21 on the generator 1 of FIG. 1; the voltage of the
square wave was about 3 V. Frequencies at which a physiological effect
occurs were found by manual frequency scanning. We needed a way to tell
whether the nervous system of the subject was being affected by the
external electric field. Invasive procedures were ruled out. Extensive EEG
measurements were done on the scalp over appropriate points on the
postcentral gyrus, using the method of averaging over many sweeps, in
order to recover evoked potentials ›13!. No evoked potentials showed up,
even after averaging over 8000 sweeps, which brought the sensitivity to
100 nV. This showed that if anything is going on with the cutaneous nerves
in the skin areas exposed to the field, it is not classical nerve
stimulation. It was noticed that, at frequencies of about 1/2 Hz, the
subject became drowsy and the EEG eventually showed increased amplitudes
of slow waves, as judged by the signal waveform. The experiments need to
be repeated, using hardware or software that provides for fast spectral
analysis. Lacking this equipment, we looked for another indicator and
found one in the form of ptosis of the eyelids.
When voluntary control of the eyelids is relinquished, the eyelid position
is determined by the state of the autonomic nervous system ›13!. There are
two ways in which this indicator may be used. In the first the subject
simply relaxes control over the eyelids, and makes no effort to correct
for any drooping. The more sensitive second method requires the subject to
first close the eyes about half way. While holding this eyelid position,
the subject rolls the eyes upward, while giving up voluntary control of
the eyelids. With the eyeballs turned up, ptosis will decrease the amount
of light admitted into the eyes, and with full ptosis the light is
completely cut off. The second method is very sensitive because the
pressure exerted on the eyeballs by partially closed eyelids increases
parasympathetic activity. As a result the eyelid equilibrium position
becomes labile, as characterized by a slight flutter. The labile state is
sensitive to small shifts in the activities of the sympathetic and
parasympathetic nervous system. The method works best when the subject is
lying flat on the back and is viewing a blank wall that is dimly to
moderately illuminated.
With this arrangement maximum ptosis occurred at a frequency near 1/2 Hz,
with external electric field amplitudes on the skin ranging from 1 V/m to
25 V/m, where field amplitude is defined as half the peak-to-peak
variation of the field strength. Immediately after onset, the ptosis
frequency, defined as the frequency for maximum ptosis, slowly decreases
until a steady frequency is reached in 5 to 10 minutes. It is believed
that this is due to changes in the chemical environment of the resonating
neural circuitry, caused by changes in the concentration of
neurotransmitters or hormones that accompany or result from the resonance
or from the subsequent shift in the autonomic nervous system state. The
effect is here called "chemical detuning" of the ptosis frequency. The
slow shift of ptosis frequency initially is so large that ptosis is lost
if the frequency is not adjusted. The ptosis is accompanied by a state of
deep relaxation, and a slight dull pressure at a spot about 1 cm above the
point midway between the eyes.
As directed demonstrated by the ptosis experiments, the method of the
present invention can be used for inducing relaxation in a subject. In
further experiments with the device of FIG. 3 it has been found that, in a
narrow range of frequencies around the ptosis frequency, the subject
became very relaxed after a few minutes of field application, using peak
field strengths on the subject's skin of about 1 V/m. The field was
induced by field electrodes placed on the sides of the seat cushion of an
easy chair. The ptosis frequency is higher in the evening than in the
morning, just after awakening. For the subject tested, the evening ptosis
frequency was 0.512 Hz at the onset, slowly shifting downwards to 0.465 Hz
in about 10 minutes. Other autonomic responses can be obtained as well;
tuning to a frequency of 0.540 Hz brings forth a tonic smile, provided
that the subject gives up voluntary control of the facial muscles
involved, so that the smile is controlled by the autonomic nervous system.
Relaxation was experienced in the frequency range from 11% below to 4%
above ptosis frequency. In the morning, the ptosis frequency at the onset
was 0.490 Hz initially, shifting downwards to 0.460 Hz in about 7 minutes.
The method can also be used for the induction of sleep. Long-term tests
running for about 400 nights were conducted on a subject who had trouble
sleeping due to prolonged severe situational stress. In these tests, an
external electric field was set up by applying a square-wave voltage of 20
V peak to peak between two field electrodes placed directly underneath the
bed sheet on both sides of the hips. Good results were obtained with
frequencies of about 1/2 Hz. More recently, the device of FIG. 4 with a 3
V battery has been used successfully by the same subject for about 300
nights, under the same stressful conditions. Among the various electrode
positions tried, the placement depicted in FIG. 1 was found to be most
effective for inducing peaceful sleep. In this configuration the field
electrodes 2 are located directly under the mattress, in the vertical mid
plane through the longitudinal axis. The maximum electric field amplitude
on the subject's skin is estimated as about 1 V/m. Two modes of operation
were used. In the first mode, the unit was turned on at bedtime, at a
frequency of 0.545 Hz, and thereafter left alone. After 15 minutes, the
device automatically shifts the frequency upward by 3%, and turns off the
oscillator after another 15 minutes. The subject usually fell asleep
before automatic shutoff had occurred. A second mode of operation involves
initial tuning for ptosis, followed by manual tracking of the slowly
downshifting ptosis frequency, using the tuning control 21 shown in FIG.
1. About 5 minutes after a steady ptosis frequency is reached, the device
is shut off manually. Tracking the ptosis frequency during its downward
shift brings an increasingly deep state of relaxation and detachment.
Sleep usually follows shortly after the device is shut off manually.
In regard to electrode placement there is a fundamental neurological
difference between antisymmetric and symmetric excitation, in which the
skin polarization is respectively antisymmetric and symmetric with respect
to the sagittal plane. In antisymmetric excitation, the weak fm signals
from the modulated afferents act antisymmetrically on the brain. As a
consequence, resulting resonances in neural circuits exhibit antisymmetry
in left and right hemispheres, and the corpus callosum is "caught in the
middle". In symmetric excitation, resonant modes occur synchronously in
both hemispheres, and the corpus callosum is less involved, if at all.
Experiments have shown that induction of sleep occurs with both
excitations, but the symmetric excitation gives a somewhat softer feeling.
At frequencies somewhat different from the ptosis frequency, sexual arousal
has been observed. In a male subject 67 years of age, the incidence of
morning erections increased considerably when a square wave voltage was
applied to field electrodes 2 placed as shown in FIG. 1, at a frequency of
0.563 Hz, and also, to a lesser extent, at a frequency of 0.506 Hz. These
frequencies were found by manual scanning the range fron 0.1 to 3 Hz. The
signal generator of FIG. 3 was used, powered by a 3 V battery. For
frequencies near 0.55 Hz, rather intense sexual excitement lasting for up
to an hour has been induced in a male subject 70 years of age, by applying
the external electric field predominantly to a skin area that includes the
perinaeum skin.
Cutaneous receptors are particularly dense in glabrous skin, such as found
on the palms of the hand, footsoles, areas of the genitals, nipples,
areola, and lips. In the somatosensory map between areas of skin, the
thalamus, and sensory cortex, the representation of these glabrous skin
areas is greatly amplified. As a consequence, external electric field
modulation of cutaneous nerves in glabrous skin is expected to excert a
particularly strong effect on the central nervous system. We feel that
this should be avoided by the general public; the effects are already
ample when the field is applied predominantly to areas of the skin which
are innervated sparsely, such as the thighs and the back. In particular,
the lips should not be exposed strongly to the field, so that the areas of
predominant application of the electric field by the general public should
be away (say, at least 10 cm) from the head. Another reason for such
choice is the avoidance of substantial polarization current densities in
the brain, as discussed above.
Fixing experiment parameters except for the field strength, the described
physiological effects are observed only for field intensities in an
interval, called here "the effective intensity window". This feature of
sensory resonances may be understood as due to nuisance-guarding neural
circuitry that blocks impertinent repetitive sensory signals from higher
processing. For the guarding circuitry to spring into action, the
amplitude of the nuisance signal needs to exceed a certain threshold. This
explains the upper boundary of the effective intensity window. The lower
boundary of the window is due to the detectibility threshold of the
sensory signals.
There needs to be concern about kindling ›13, 18! of epileptic seizures in
susceptable individuals. Kindling has traditionally involved the passage
of electric currents of the order of 0.1 mA directly to a part of the
brain, such as the amygdala. Although in the present invention substantial
polarization current densities in the brain are avoided, an effect similar
to kindling might occur if critical neural circuits are subjected to
repeated sessions of periodic fm signals from somatosensory or visceral
afferents. To guard against such an effect, the frequency of modulation of
afferents for use by the general public should be chosen away from the
frequencies involved in epileptic seizures. Frequencies below 2 Hz appear
to qualify in this regard.
The pathological oscillatory neural activity involved in epileptic seizures
›13! is influenced by the chemical milieu of the neural circuitry
involved, specifically through concentrations of GABA, glutamate, and
aspartate ›18!, and perhaps .beta.-endorphin. Since excitation of the 1/2
Hz sensory resonance may cause a shift in some of these neurotransmitter
concentrations, the application of external electric fields may be useful
for control and perhaps treatment of seizures. For this purpose, the
patient wears compact field electrodes and a generator, to be manually
activated upon experiencing a seizure precursor or aura. For patients with
infrequent seizures, a small unit that contains the field electrodes as
well as the generator, in the form of a small box, wallet, purse, or
powderbox, may be particularly suitable.
The modulation of afferents by external electric fields may also be used
for the control of tremors in Parkinson patients, by interfering with the
underlying pathological oscillatory activity. According to Ref. ›14!,
Scientific American of 1892 contains an article about controlling
Parkinson symptoms by means of a vibrating helmet placed on the patient's
head. For a 10 Hz vibration frequency, the subject is reported to
experience, within a few minutes, a general lassitude and a tendency to
sleep. Modulation of afferent nerves by a properly tuned periodic external
electric field affords another and far less conspicuous excitation method,
which is expected to have a similar result. The method of upsetting
pathalogical oscillatory activity by applying an external electric field
for modulating afferent nerves in skin areas away from the head may also
be used for the control of seizures.
The method may be applied for the control of panic attacks, when these
involve an abnormally high activity of the sympathetic nervous system. The
experiments on ptosis, relaxation, and sleep show that the application of
alternating external electric fields can diminish the activity of the
sympathetic nervous system. The apparatus of FIG. 3 may be used, tuned to
a frequency just below ptosis, or, for severe cases, right at ptosis. In
this application it is convenient to use a generator and field electrodes
mounted in a small single casing, such as a small box, wallet, purse, or
the powder box of FIG. 7.
The question arises whether in the weak-field experiments discussed above
the observed physiological effects are perhaps due to mechanisms other
than the response of afferent nerves to the applied field. Candidates for
such alternate mechanisms are polarization currents induced in the brain,
and currents carried along high-conductivity paths provided by the
cerebrospinal fluid, blood, and lymph, and subsequently detected by
receptors. These alternate mechanisms are ruled out by experiments in
which a sharply localized electric field is applied to the dorsum of the
feet. The usual array of physiological responses was found in these
experiments. It is therefore concluded that for weak aplied electric
fields the observed physiological effects are indeed instigated by a
response of afferent nerves to the external electric field.
The manipulation of the nervous system by external electric fields tuned to
a sensory resonance frequency is subject to habituation, sensitization,
classical conditioning, and the placebo effect. To minimize habituation in
the use as a sleeping aid, the field should be predominantly applied to a
different skin area each night. Sensitization, the placebo effect, and
positive classical conditioning enhance the efficacy of the method.
Clinical trials can be designed such that the placebo effect does not
contribute to the statistical mean. This is done by arranging the
generator output to the field electrodes to be passed or blocked by
computer, according to a pseudo-random sequence with a seed that is
changed from run to run, as determined for instance by date and time.
Whether the field was on or off is unknown until the run is complete and
the response of the subject has been entered into the computer. The
arrangement is equivalent to a trully double-blind study.
The following considerations are important for proper design and use of the
field generator, as well as for the planning and interpretation of
experiments.
When an external electric field is applied to an isolated conductor,
electric currents will flow that drive charges to the conductor surface.
In steady state, these charges are distributed in such a way that the
total electric field inside the conductor vanishes and the conductor
surface is equipotential. These surface charges and electric currents are
here called respectively "polarization charges" and "polarization
currents". Although mainly used in the context of dielectrics, the wording
is proper for isolated conductors as well.
Since the human body is a good conductor of electricity, exposure of an
isolated subject to an alternating external electric field will cause
polarization currents to flow broadly through the subject's body. The
currents are of course accompanied by an ("internal") electric field,
which turns out to be a very small fraction of the applied external field.
In principle the polarization current and accompaning internal electric
field may act on receptors, axons, synapses, and dendrites. As a purely
electrical effect, the polarization current causes a polarization of the
body, in which electric charges accumulate on the skin, if the latter is
dry and the body is substantially insulated from its surroundings. The
polarization charge density on the skin tracks the fluctuations in the
applied external field. For an external electric field that varies as a
square wave, the polarization currents flow only as brief pulses in
response to the edges of the square wave. The polarization current pulses
then have sharp leading edges, followed by an exponential decay with an
e-folding time
T.sub.c =(.epsilon./.epsilon..sub.o).epsilon..sub.o .eta., (1)
where .epsilon..sub.o is the permittivity of free space
(8.85.times.10.sup.-12 farads/m), .epsilon./.epsilon..sub.o the average
dielectric constant of the biological tissue, and .eta. the average
resistivity. T.sub.c is called the charge relaxation time. Using the
dielectric constant .epsilon./.epsilon..sub.o and resistivity .eta. for
muscle tissue ›16, FIG. 3--3!, we find the estimate
T.sub.c =710 ns. (2)
After each square wave edge, the current flow in the subject's body becomes
negligibly small after a few times T.sub.c. For square wave edges that are
rounded with a rise time considerably larger than T.sub.c, the
polarization current pulses are broadened to the rise time of the edges.
If spatial averages are used for the dielectric constant and resistivity,
the charge relaxation time expressed by (1) is a spatial average. However,
local relaxation times can differ substantially from the spatial average;
for instance, the relaxation time of membranes ranges from 0.7 ms to 24 ms
for the cases listed by Katz ›17, table 1!.
For external electric fields that vary slowly compared to the charge
relaxation time (2), the polarization keeps up with the field. The
resultant electric field, i.e., the sum of the applied field and the field
due to polarization, is then essentially always perpendicular to the skin
of the subject, and the electric field on the skin is proportional to the
surface density of electric polarization in the skin. As will be
discussed, experiments have shown that weak external field modulation of
cutaneous nerves is due to electric polarization of the skin.
The polarization currents are subject to the skin effect ›19, p. 5-85!, in
which the current density falls of exponentially, from the skin into the
body, with e-folding distance
.delta..sub.s =.sqroot.(.eta./(.pi.f.mu.)), (3)
where f is the frequency of the applied field, .mu. the permeability, and
.eta. the resistivity of the body tissue. Calculation of the skin depth
.delta..sub.s for the frequencies involved in the present invention gives
values in excess of 1 m. It follows that the polarization current paths
are not restricted by the skin effect.
The scale of the polarization current densities can be determined from the
peak polarization current induced in the subject's body by the applied
external field. This peak current can easily be calculated for the case
that the applied electric field varies as a rounded square wave. The
calculation is illustrated here for the field generator of FIG. 3. Let the
resistors 13 and 14 and the potentiometer 12 all have the same resistance
R.sub.o, and let the potentiometer wiper be set at fraction .alpha. of the
total resistance R.sub.o. With a 3 V battery, the output voltage of timer
16 at point 15 is 2.5 V. Therefore, timer 6 produces a square wave with a
voltage of V.sub.o =2.5 V. A short calculation shows that the voltage
between the two output terminals 11 swings from .alpha.V.sub.o /3 to
-.alpha.V.sub.o /3, and that the output impedance, in the absence of
output capacitor 22, is
R.sub.out =.alpha.(3-2.alpha.)R.sub.o /3. (4)
Hence, with an output capacitor C.sub.o, the peak polarization current
through the body of the subject is
##EQU1##
where C.sub.eb is the part of the capacitance between the field electrodes
calculated from electrode charges at the end of electric field lines that
go to the subject's body, and C.sub.ee is the remaining part of the
capacitance between the field electrodes. Eq. (5) holds, provided that
R.sub.o is much larger than the impedance of the subject's body, a
condition that is satisfied in practice. The rise time of the external
electric field is
##EQU2##
provided that T.sub.f is much larger than the charge relaxation time (2)
of the subject's body. This condition is satisfied in practice, unless
.alpha. is very small. For the device of FIG. 3, with an output capacitor
C.sub.o =1000 pf, R.sub.o =1 M.OMEGA., .alpha.=1, V.sub.o =2.5 V, and the
electrode configuration of FIG. 1, with the estimates C.sub.eb =1 pf,
C.sub.ee =1 pf, the peak current I.sub.max of (5) becomes
I.sub.max =5.0 nA, (7)
and the rise time T.sub.f of (6) is found to be
T.sub.f =0.33 ms. (8)
Although these results were derived for the generator of FIG. 3, under the
assumption that the timer produces a square wave with sharp edges, they
will remain valid for rise times up to 100 ns. Comparison of the peak
polarization current (7) with the 1 mA or so required for classical nerve
stimulation ›6,7! shows that the latter does not occur in the experiments
under discussion. Estimating, for the setup of FIG. 1, the area of the
skin that is subjected to appreciable field strengths as 2A=600 cm.sup.2,
the peak polarization current density has over this area a spatial average
<j>=I.sub.max /A, which comes to
<j>=17 pA/cm.sup.2 (9)
Using .eta.=400 Ohm cm as an average tissue resistivity ›16, FIG. 3--3!,
the spatial average peak internal electric field strength <E.sub.i > that
accompanies the average peak current density <j> of (9) is
<E.sub.i >=6.8 nV/cm, (10)
for the case considered. These results are spatial averages of temporal
peaks. In order to estimate the deviations from the average caused by
nonuniformities in conductivity, consider a membrane with surface
resistivity of 4000 Ohm cm.sup.2 ›17, table 1! subject to the
perpendicular density (9). The potential difference across the membrane is
then perturbed by a mere 68 nV. Even if a factor 10 is used to account for
the local nonuniformities in current density, the resulting peak membrane
potential perturbation of 680 nV is orders of magnitude below the membrane
depolarization required for firing. This again shows that classical nerve
stimulation does not occur. Since the applied field acts on the nerves, as
evidenced by the observed physiological effects, the action must be a
modulation of the spontaneous firing pattern of the nerve. The question
remains whether the modulation is caused by the polarization currents or
by the polarization charges on the skin.
In order to investigate this question, two experiments were performed. The
field generator of FIG. 3 was used in both, with a 1000 pf output
capacitor 22, V.sub.o =2.5 V, and R.sub.o =1 M.OMEGA., where R.sub.o is
the resistance of resistors 13 and 14, and potentiometer 12. The field
electrodes were aluminum foil rectangles of 8.times.17 cm, placed over the
upper skin of the subject's feet, with 1.5 cm insulation between the skin
and the foils. The field electrodes were shielded on the outside with
8.5.times.20 cm rectangular pieces of grounded aluminum foil, separated
from the field electrodes by a 0.5 cm thick layer of insulation. The
subject's feet, fitted with the shielded field electrode assemblies, were
placed in a 36.times.31.times.53 cm cardboard box, covered on the outside
with grounded aluminum foil; the front opening of the box was shielded by
a curtain of grounded insulated strips of aluminum foil. With this
arrangement, the electric field was mainly confined to the 1.5 cm space
between each field electrode and the opposing area of skin; any field
spilling out from this space was essentially kept in the box by the
grounded shield on the outside of the box and by the grounded curtain in
front. The capacitance between the field electrodes via the subject's body
is estimated as C.sub.eb =11 pf, using a dielectric constant of 2.6 for
the styrofoam insulation. The remaining capacitance between the field
electrodes is estimated as C.sub.ee =33 pf. With the output capacitor
C.sub.o =1000 pf, V.sub.o =2.5 V and R.sub.o =1 M.OMEGA., Eq. (5) gives a
peak polarization current of I.sub.max =53 nA, multiplied by a factor that
ranges from 1/3 to 1, as the intensity control potentiometer is advanced
from small .alpha. to .alpha.=1. Full ptosis was observed with intensity
control potentiometer settings from .alpha.=1 to .alpha.=0.06, at a
frequency near 0.53 Hz.
Next, the experiment was repeated with one modification: the upper skin of
the subject's feet, in the area opposite the field electrodes, was covered
with a layer of conductive jelly, followed by a thin layer of overlapping
strips of aluminum foil, and a thin insulating plastic sheet. In this
arrangement, the polarization currents in the subject's body end up not on
the subject's skin opposite the field electrodes, but on the aluminum foil
covering of that skin area. The conductive jelly between skin and aluminum
foil assures that the polarization charges make their way to the foil
without delay beyond the charge relaxation time T.sub.c of (2). As a
result, the polarization currents that flow in the subject 's body are the
same as in the previous experiment, but during the plateaus of the square
wave, after a few times T.sub.c, the skin is not subjected to an electric
field. With intensity control settings .alpha. ranging from 1 down to
0.06, and tuning through the frequency range from 0.490 to 0.589 Hz, only
very faint and fleeting ptosis was sporadically experienced for very short
times; it could not be tracked in the usual manner by slowly tuning to
lower frequencies. This result is to be compared with the full ptosis
occurring in the previous experiment in which the feet were not covered
with the highly conductive layer.
Varying the intensity control settings .alpha. in the two experiments gave
pairs of settings in which the polarization current densities on the skin
in the areas opposite the field electrodes is the same for the two
experiments. For each of these pairs, the values of .alpha. are somewhat
different, because the metal covering of the skin used in the second
experiment extends to border areas for the purpose of capturing the edge
field flux; therefore, the effective area of skin involved in the second
experiment is slightly larger than in the first experiment. Considering
the existence of these pairs of .alpha. settings for which the
polarization current densities on the skin are the same for the two
experiments, and the essential absence of ptosis in the second experiment,
it is concluded that ptosis is essentially not caused by polarization
currents in the skin. Moreover, settings with the same .alpha. give about
the same polarization currents in the rest of the subject's body, away
from the skin area opposite the field electrodes. It is therefore
concluded that ptosis is essentially not due to stimulation or modulation
of nerves other than cutaneous nerves, and it is not due to polarization
currents in the brain either. It also follows that the ptosis is
essentially not due to any stray electric field standing on the scalp or
any other part of the skin other than the skin area lying directly across
the field electrodes. It is concluded that the ptosis is essentially due
to external electric field effects other than the polarization current,
and that ptosis occurs essentially through cutaneous sensory nerves.
What are the effects of the external electric field, besides the
polarization current? One such effect is the force exerted by the external
field on hairs. However, experiments in which the field is exclusively
applied to glabrous skin also give ptosis; hence, hairs are not involved
in an essential way. The only possibility remaining is a shallow
penetration of the external electric field into the subject's skin. Two
such mechanisms have come to mind.
The first mechanism is due to thermal motion of the ions, that cause a
smearing of the polarization charges through a Debye layer at the skin
surface. The scale of such penetration in an electrolyte with monovalent
ions of opposite charge is given by the Debye length ›20!
##EQU3##
where .epsilon. is the permittivity, e the elementary electric charge, n
the concentration of one of the ion species deep in the electrolyte, and
V.sub.T =kT/e is the thermal voltage (26 mV at the normal skin temperature
of 34.degree. C.); k is the Boltzmann constant and T the absolute
temperature. If the electrolyte is exposed to an external electric field
E.sub.o perpendicular to its boundary, then at thermodynamic equilibrium
the potential at depth z in the electrolyte is approximately
V(z)=E.sub.o .delta..sub.d e .sup.-/.delta..sbsp.d, (12)
where .delta..sub.d is the Debye length given by (11), and the voltage is
taken with respect to points deep in the electrolyte. The approximation
(12) is good if E.sub.o .delta..sub.d <<V.sub.T. From (12) one has for the
electric field
E(z)=E.sub.o e.sup.-z/.delta..sbsp.d. (13)
These results are easily derived from balancing conduction and diffusion
currents, together with the Poisson equation that relates the potential to
the charge distribution. The calculation can be readily extended to the
case of bivalent ions, and to mixtures of ions with different valences.
The above considerations for an electrolyte are applicable to the dermis,
because of its considerable fluid content. But one may apply the theory
also to the epidermis. This outer layer of the skin contains horny cells
that suppress the mobility of ions. However, the relation between mobility
and diffusivity of ions is still given by the Einstein relation.
Therefore, the equilibrium thermodynamics of ions in the epidermis is the
same as in an electrolyte. Since the ion concentration in the epidermis is
relatively small, the Debye length is relatively large; for example, for
an ion density of 10.sup.7 per cm.sup.3 and a dielectric constant of 4,
the Debye length (11) is 0.54 mm. Sensory receptors in dermal papilla that
protrude into the base of the epidermis are then subjected to the remnant
of the electric field as it penetrates from the outside, in the manner
shown by Eq. (13). If the cytoplasm of the receptor is at the same
potential as the deep body tissue, then the membrane potential at the tip
of the receptor is perturbed by the about the voltage (12), using for z
the thickness of the epidermis. Taking 0.2 mm for that thickness, and
parameters of the epidermis as in the above example, an external field of
1 V/m on the skin is found to perturb the membrane potential of the
receptor tip by about 0.4 mV.
Such a change in membrane potential is much too small to fire the nerve.
However, as pointed out by Terzuolo and Bullock in a classical paper ›25!,
modulation of the frequency of an already active neuron can be achieved
with voltages very much lower than those needed for the excitation of a
quiet neuron. Voltage gradients as small as 1 V/m across the soma were
sufficient to cause a marked change of firing of adaptive stretch
receptors of crayfish. Terzuolo and Bullock further remark that the value
of the critical voltage gradient for this effect may actually be much
smaller than 1 V/m. The 0.4 mV membrane voltage perturbation calculated
above for the example may be sufficient to cause frequency modulation of
the firing pattern of the receptors investigated by Terzuolo and Bullock.
Perhaps the same behavior occurs for other slowly adapting
mechanoreceptors that exhibit spontaneous firing, such as Ruffini endings
and Merkel cells, which are found roughly at a depth of 0.2 mm in the skin
›21-23!.
A second mechanism for penetration of the external field into the epidermis
is provided by sweat ducts. These narrow ducts are normally kept at least
partially filled by the sweat glands and capillary action. The higly
conducting thin sweat column in the duct will be polarized by the external
electric field. As a result the field will be severely distorted, causing
the equipotential surfaces to crowd together near the tips of the columns,
and dip deep into the epidermis in between the sweat ducts. As a result, a
local field that is a small fraction of the external field E.sub.o acts on
cutaneous receptors which lie in papilla that protrude into the base of
the epidermis. The associated potential must be added to that due to the
first mechanism.
Cold receptors also lie at shallow depths ›22! and exhibit spontaneous
firing, so that they need to be considered as candidates for modulation by
externally applied weak electric fields. Therefore, an experiment was
performed in which steady electric fields of up to 1 KV/m were applied to
the skin. If modulation occurs, these electric fields may induce a
sensation of skin temperature change. No such sensation was experienced.
However, there may have been rapid adaption to the electric field
stimulus, and the effect of the field on the firing pattern of cold
receptors may differ in nature from the pattern change due to temperature.
The latter possibility is suggested by the complicated coding of
temperature information, which is much more intricate than mere frequency
modulation ›26!. Therefore, the observed absence of a temperature
sensation in steady-state electric field application does not quite rule
out modulation of cold receptors by the applied external electric field.
There have been further developments, as follows.
It has been observed that lower field strengths suffice for the excitation
of sensory resonances when the skin area of dominant field application is
increased. This "bulk" effect is important for the proper use of the
invention, and can be understood as follows. The field causes a frequency
modulation of the stochastic firing of the affected afferent fibers. If
these fibers synapse, either directly or indirectly, upon a summing
neuron, then the sequence of current injection spikes into the dendrite of
the neuron will be a slightly modulated Poisson stream. For zero
modulation a Poisson distribution is expected on theoretical grounds if
the number N of synapsing afferents is large, since the afferent spike
trains add and interlace. This results in a high-frequency sequence of
charge injections, in which the features of the individual afferent spike
trains are substantially washed out, in much the same way is density
nonuniformities of a substance suspended in a fluid are removed by
stirring. The Poisson distribution is found to be a good approximation in
computer simulations with N of the order of 4000, substantially
independent of the details of the firing probability distributions for the
individual afferents. As a consequence of the Poisson distribution, the
variance as well as the mean of the number of injection spikes into the
summing neuron that occurs in a fixed time interval .DELTA.t is
.lambda.=Nf.sub.o .DELTA.t, (14)
where f.sub.o is the average frequency of the afferent spike train, assumed
to be the same in each afferent, for simplicity. For large N the
excitatory synaptic current needs to be balanced with an inhibitory
current, lest the integrated signal by far exceeds the firing threshold
and the summing neuron is locked into a maximal firing state. The balance
requires that, in addition to N excitatory neurons, roughly N inhibitory
neurons also synapse on the summing neuron The inhibitory current spikes
contribute to the noise, thus increasing the variance by about a factor 2.
Balanced excitatory and inhibitory activity has been recently considered
as a mechanism for rendering cortical neurons sensitive to small
fluctuations in their synaptic current; see ›24! and the references
contained therein. With modulation present, the Poisson distribution still
stands short-term, but .lambda. has now a slow sinusoidal variation with
the frequency of the applied electric field. All modulated afferents
contribute coherently to this sine wave. As a result, the signal-to-noise
ratio of the fm signal that is present in the temporal density of the
current injection spikes is proportional to mNf.sub.o /.sqroot.(2f.sub.o
N)=m.sqroot.(f.sub.o N/2), where m is the depth of the frequency
modulation. The latter is expected to be proportional to the applied
external field amplitude E. Hence, one expects the signal-to-noise ratio
to be proportional to E.sqroot.(f.sub.o N). The fm signal is somehow
demodulated by subsequent neural circuitry. The matter contains or is
followed by nuisance-guarding circuits, with the result that the
observable response to the field application exhibits an effective
intensity window. One expects the ultimate response to be a function of
the signal-to-noise ratio of the current injections into the summing
neuron, so that
observable response=function of (E.sqroot.(f.sub.o N). (15)
Eq. (15) shows the bulk effect. For excitation of sensory resonances
through modulation of cutaneous nerves, N is roughly proportional to the
skin area A.sub.s over which the field is predominantly applied, and also
to the surface density p of the affected nerves, so that in (15) one has
N=cpA.sub.s, (16)
where c is a constant. If the fm detection circuitry receives inputs from M
similar summing neurons, the results (15) and (16) still hold if N is
replaced by MN. Very shallow frequency modulation can be detected amidst
the large fluctuations occurring in the spontaneous firing of the
individual afferents, if the product MN is large. This result is helpful
in understanding the exquisite sensitivity of the human electroception
observed and discussed here. Stochastic resonance ›33! perhaps contributes
to the sensitivity as well.
The peak value (10) of the internal electric field induced by an external
field of 1 V/m with rounded square wave time dependence at a frequency
near 1/2 Hz shows that the internal field is a very small fraction of the
external field. The same conclusion holds for sinusoidal fields, for which
the internal field is easily found to be
E.sub.i =2.pi.fT.sub.c E.sub.o, (17)
where T.sub.c is the relaxation time (1), f the field frequency, and
E.sub.o the external electric field. For f=1/2 Hz, and the value T.sub.c
given by (2), Eq. (17) gives for the internal electric field
E.sub.i =2.2.times.10.sup.-6 E.sub.o. (18)
It follows that, for the purpose of calculating the field induced on the
skin by field electrodes, the internal electric field may be neglected, so
that the subject's skin is an equipotential surface. For the configuration
of FIG. 2, the skin voltage is then determined by a capacitive voltage
divider with two capacitors, one formed by the left electrode 2 and the
apposing skin area 36', and the other formed by the right electrode 2 and
the skin area 36. If both electrodes are placed opposite the skin by a
small separation d, the electric field on the skin in the areas 36 and 36'
is approximately
E=V/2d, (19)
where V is the voltage applied between the field electrodes.
In certain experiments and clinical applications there is a need for an
external electric field that is strictly confined to two selected skin
regions. Such a field can be set up with a shielded electrode pair as
depicted in FIG. 8, where field electrodes 2 and 2' of identical shape and
size are closely apposed, in parallel fashion, respectively by electrodes
38 and 39 called shield electrodes. The latter have the same size and
shape as the field electrodes 2 and 2', and are positioned and oriented
such as to bring their contours in registration with those of the
corresponding electrodes 2 and 2'. Furthermore, a conductor 40 connects
the shield electrodes, so that they have the same potential. Electrodes 2
and 2' are connected by wires 41 to the input port 55 which is to receive
a voltage from the generator. With the generator voltage applied to the
input port 55, the voltage on the field electrodes 2 and 2' is
respectively V.sub.1 and V.sub.2. Although not shown, insulation is
applied between electrodes 2 and 38, and between electrodes 2' and 39.
Optionally, insulation is applied to the top and bottom of the two
resulting structures as well, resulting in two 5-layer sandwiches. The
latter are positioned in close proximity of the skin 37 of the subject, in
the orientation shown in FIG. 8. If the sandwiches are placed parallel and
at equal distances to the skin 37, then both the skin and the shield
electrodes have the potential (V.sub.1 +V.sub.2)/2, so that no field lines
stand between the shield electrodes 38 or 39 and the subject. It follows
that the external electric field is then confined to four narrow spaces,
viz., the space between electrode 2 and the skin 37, between electrode 2'
and the skin, between electrode 2 and the shield electrodes 38, and
between electrode 2' and shield electrode 39, except for edge fields
pouring from the edges of the narrow spaces. These edge fields extend over
a distance of the order of the electrode separation or the distance from
electrode 2 or 2' to the skin. If these separations are very small, so
will be the spatial extents of the edge fields, and the external field on
the skin then will be essentially confined to the skin areas directly
apposed by the electrodes 2 and 2'. Electrodes 2 and 2' need not be
positioned in close proximity to each other.
In the foregoing discussion the field electrodes 2 and 2' were assumed to
have the same shape, size, and distance to the skin. One can deviate from
these conditions by making adjustments in the distances at which the
shield electrodes are applied over the field electrodes 2 and 2', such as
to assure that the shield electrodes are at the same potential as the
skin. The shield electrodes 38 and 39 may be conductive foils or
conductive meshes. The conductor 40 may be a conductive foil, which may
simply be the continuation of the shield electrodes 38 and 39. If the
field electrodes 2 and 2' are deployed at a short distance from each
other, the shield electrodes 38 and 39, together with the conductor 40 may
be implemented as a single conductive foil.
A well-designed and deployed shielded pair of field electrodes limits the
field application essentially to the skin area directly apposing the field
electrodes. Therefore, the shielded pair can be used on skin areas very
close to the head, without causing substantial polarization currents in
the brain. An important example of such deployment is localized field
application to the skin overlying the vagus nerve in the neck.
A new sensory resonance has been found near 2.4 Hz. The resonance shows up
as a sharp increase in the time of silently counting backward from 100 to
70, as fast as possible, with the eyes closed. The counting is done with
the "silent voice" which involves motor activation of the larynx
appropriate to the numbers to be uttered, but without the passage of air,
or movement of mouth muscles. The motor activation causes a feedback in
the form of a visceral stress sensation in the larynx. Counting with the
silent voice must be distinguished from merely thinking of the numbers,
which does not produce a stress sensation, and is not a sensitive detector
of the resonance. The larynx stress feedback constitutes a visceral input
into the brain and thus may influence the amplitude of the resonance. This
unwanted influence is kept to a minimum by using the count sparingly in
experiment runs. The protocol adapted in our laboratory, after extensive
trial and error, is to have experiment runs of 40 minutes duration, with
counts taken at times 0, 20, and 40 minutes into the run. In early
experiments the count was done from 100 to 70, but as experience was
gained, we switched to the more sensitive 100-60 counts. Since counting is
a cortical process, the 2.4 Hz resonance is here called a cortical sensory
resonance, in distinction to the autonomic resonance that occurs near 1/2
Hz. In addition to affecting the silent counting, the 2.4 Hz resonance is
expected to influence some other cortical processes as well. It was found
that in the long run the resonance has a sleep inducing effect. Very long
exposures cause dizziness. The frequency of 2.4 Hz raises concerns about
kindling; therefore, the general public should not use the 2.4 Hz
resonance until this concern has been addressed properly in experiments.
The sensitivity and numerical nature of the silent count makes it a very
suitable detector of sensory resonance, thereby affording several
experiments which clarify somewhat the processes involved, and provide
guidance for the proper use of the invention.
First, the experiment aimed at resolving the question whether it are the
polarization currents or the polarization charges that cause the
excitation of the 1/2 Hz autonomic resonance has been repeated for the 2.4
Hz cortical resonance, using the same field strengths applied in the same
manner to the same areas of skin, but with a sine wave instead of a
rounded square wave. The amplitude of the voltage applied to the field
electrodes was 1.45 V, resulting in an external electric field at the skin
with a maximum amplitude of 48 V/m. A frequency of 2.407 Hz was used, and
the counts were done from 100 to 60. As for the 1/2 Hz experiments
discussed, the electric field was applied to the dorsum of the feet in a
localized manner. In the first experiment the silent counts were 37 s at
the start t=0 of the run, 53 s at t=20 minutes, and 75 s at t=40 minutes,
the end of the run. The pronounced increase of counting time shows
excitation of the 2.4 Hz resonance. In the second experiment the
conditions and parameters were the same, except that the skin of the
dorsum of the feet was covered with conductive jelly and aluminum foil,
all insulated from the field electrodes. This arrangement removes the
polarization charges from the skin, whereas the polarization currents in
the skin and the body are the same as before. The counts were 32 s at t=0,
34 s at t=20 minutes, and 33 s at t=40 minutes, so that the resonance was
not excited. Comparison of the two experiments shows that the excitation
of the resonance is not due to polarization currents, but rather to
polarization charges on the skin, in agreement with the conclusion reached
above for the 1/2 Hz autonomic resonance experiments.
The magnitude of the polarization current densities in the subject is
calculated as follows. With an estimated 11 pf capacitance between the
field electrodes via the subject's body, the polarization current
amplitude comes to 241 pA. Assuming that this current is spread over a
skin area that is 10% larger than the area of the nearby field electrode,
the maximum current density in the subject's body is found to be 1.6
pA/cm.sup.2. The experiment shows that such a small current density
applied to cutaneous nerves in the dorsum of the foot is not capable of
exciting the 2.4 Hz resonance, but the accompanying polarization charges
can.
In the described experiments the polarization current through the skin is
concentrated in the skin area S immediately apposing the field electrodes,
fanning out from there into deeper lying tissue. A similar current
distribution can be set up by means of contact electrodes attached to the
skin in the area S. This affords another check on the conclusion that the
resonance is not excited by the currents, in the parameter range
considered. To perform this check, the output of the sinusoidal voltage
generator was connected to the contact electrodes via a small capacitor
which at the low frequencies presents an impedance very much larger than
that of the subject's body. The generator thereby becomes effectively a
current source. The two contact electrodes had the same size and shape as
the field electrodes in the field experiments described above, and each
was attached to the dorsum of the foot through a layer of conductive
jelly. Passing in this manner a sinusoidal current with an amplitude of 48
nA at 2.417 Hz gave rise to a 100-60 count of 35 s at t=0, 36 s at t=20
minutes, and 34 s at t=40 minutes, showing that the resonance was not
excited. The maximum current density in the skin was 321 pA/cm.sup.2,
considerably larger than in the field application discussed. Yet, the
current did not cause excitation of the 2.4 Hz resonance. It may be
remarked that the current density of 321 pA/cm.sup.2 perhaps falls outside
the effective intensity window, but that is not the case, as follows from
the next experiment discussed.
Thus far arrangements have been discussed where the modulation of afferents
by the field occurs in the receptors of afferent fibers. An essentially
different situation of interest occurs when the tissue underlying the skin
area of predominant field application is traversed by a nerve that has no
receptors in the skin area. The question then arises whether the spike
trains carried by the afferent fibers in the nerve can be modulated
without causing classical nerve stimulation. Since polarization charges on
the skin cannot have an effect in this case, any modulation occurring must
be due to the polarization currents. The origin of the currents does not
matter, so that they may as well be introduced by contact electrodes,
since this arrangement affords easier control of the current magnitude for
research purposes. An experiment was done in which currents in the tissue
were produced by contact electrodes (3M red dot.TM., 22.times.22 mm)
placed on the skin at the back of the right knee, with a center-to-center
separation of 45 mm, such as to expose the underlying sciatic nerve to
longitudinal currents. For a sinusoidal current with a peak density
amplitude of 3.4 nA/cm.sup.2 at a frequency of 2.410 Hz, the 100-60 counts
were 33 s at t=0, 54 s at t=20 minutes, and 67 s at t=40 minutes, showing
excitation of the 2.4 Hz resonance. The current density of 3.4 nA/cm.sup.2
is much too small for causing classical nerve stimulation. No excitation
was found for a similar current injection transverse to the nerve. The
experiments show that indeed, afferent fibers in a nerve can be modulated
by electric currents without undergoing classical nerve stimulation. The
current densities at which modulation occurred were a factor 10 larger
than in the previously discussed experiment with the dorsum of the foot,
wherein the 2.4 Hz resonance was not excited. The finding that transverse
currents do not excite the resonance shows that the modulation is really
done on the afferent fibers, and not on receptors.
Similar results were found for sinusoidal current applications to the skin
over the right vagus nerve in the neck. Exposure to longitudinal currents
in the range from 200 pA/cm.sup.2 to 60 nA/cm.sup.2 caused excitation of
the 2.4 Hz resonance, but transverse currents showed no effect. The fact
that the current density of 200 pA/cm.sup.2 caused excitation of the
resonance while 321 pA/cm.sup.2 applied to the dorsum of the foot was
ineffective is understandable as due to the bulk effect discussed above;
the afferents are much more numerous in the vagus nerve than in the
affected region in the foot experiment. To get further data on this issue,
we measured the effective intensity window for excitation of the 2.4 Hz
resonance through vagal modulation with longitudinal currents applied by
contact electrodes attached to the overlying skin. The contact electrodes
used were again a pair of 3M red dot.TM. electrodes with centers 45 mm
apart. To provide longitudinal currents, the electrodes were placed on the
skin of the neck over the right vagus nerve, one above the other along the
direction of the underlying nerve. The results are shown in FIG. 9, where
the time needed for the silent count from 100 to 70 is plotted versus the
amplitude of the total current passed through the subject by the contact
electrodes placed on the neck. The current was sinusoidal with frequency
of 2.466 Hz. For a fixed current amplitude, the 100-70 counting time was
measured at the beginning, t=0, of the current application, at t-20
minutes into the experiment run, and at t=40 minutes at the end of the
run. In FIG. 9 the measured counting times are shown as graph 73 for t=0,
graph 74 for t=20 minutes, and graph 75 for t=40 minutes. The effective
intensity window is clearly seen to extend from about 100 pA to about 200
nA. The apparant anomaly near point 74 is attributed to chemical detuning.
Dividing by the electrode area of 484 mm.sup.2, the window for the peak
current density in the subject is found to range from 21 pA/cm.sup.2 to 41
nA/cm.sup.2. These current densities are much too small to cause classical
nerve stimulation. The previously discussed modulation mechanism involving
the Debye layer in the epidermis does not apply in this case since the
modulation does not involve receptors, but rather afferent fibers in a
nerve that runs in the tissue underlying the skin region of the current
injection. It must be that longitudinal electric currents in the tissue
surrounding the vagus nerve can affect the propagation velocity of action
potentials in the afferents; fluctuating applied currents would then
result in frequency modulation of the spike trains received by the brain.
Since the propagation velocity of action potentials along an axon is
influenced by the membrane conductance, and the latter is a sensitive
function of the membrane potential ›29!, the propagation speed can indeed
be modulated by perturbations of the membrane potential brought about by
longitudinal currents superimposed on the currents that accompany the
action potential propagation, considering the nonuniformities of
conductivity in the current path distribution. The modulations of
propagation speed brought on by the currents are very small, but they can
produce a fm of signals received by the brain that suffices for the
excitation of a sensory resonance, if the frequency of the current is
chosen properly. The influencing of the action potential propagation speed
along an axon by an external electric field is of great importance to
neural science and needs to be investigated further.
Further experimentation has shown that sensory resonances can be excited by
external fluctuating electric fields with amplitudes on the skin much
lower than 1 V/m. This was already known from experiments with the 1/2 Hz
resonance which shows ptosis of the eyelids occurring at field amplitudes
of 20 mV/m on the skin, using a closely spaced electrode pair placed some
distance from the subject, such as to expose a large area of skin to the
weak field. The discovery of the 2.4 Hz resonance with the more sensitive
and quantitative detector in the form of the silent count made
measurements at even lower field strengths possible. In these experiments
we used a closely spaced pair of rectangular field electrodes measuring
59.times.44 cm, oriented parallel to the line to the nearest point on the
subject's body. The electrodes were driven by a sine wave with amplitude
of 1.25 V:, at frequency near 2.4 Hz. The electrode pair was placed at
various distances from the subject, about at hip height. The distances
were large enough to expose a large skin area to the field. The maximum
field induced on the subject's skin was estimated from a model wherein the
subject is represented as a 24 cm radius conductive sphere. The results
for the silent 100-60 count are shown in FIG. 10, where the counting time
at the beginning, t=0, of the run, at t=20 minutes, and t=40 minutes is
shown respectively by graphs 76, 77, and 78. The crossover of graphs 77
and 78 is attributed to chemical detuning. A pronounced slowing of the
counting is seen to occur already at a peak field external field amplitude
of 10 mV/m. FIG. 10 shows an effective intensity window that extends from
about 8 to 190 mV/m field amplitude. Using the model mentioned above, the
effective intensity window was expressed in terms of the polarization
current in the subject's body; the window is found to extend from 0.25 to
5.9 pA.
Since in the experiments the distance s from the center of the electrode
pair to the subject's body varied from 64.5 cm to 208 cm, there was
considerable variation of the skin area A.sub.s of predominant field
application, which in first approximation is proportional to s.sup.2.
Therefore it is of interest to consider the bulk effect discussed above.
Using Eqs. (15) and (16), ignoring the effect of the surface density p of
cutaneous nerves, and taking .sqroot.A.sub.s as the distance s, the graphs
of FIG. 10 may be replotted in terms of the quantity E.sub.max s. The
result is shown in FIG. 11, where the graphs for t=0, 20, and 40 minutes
are shown respectively as 79, 80, and 81. The effective intensity window
is seen to extend from about 17 to 123 mV, in terms of E.sub.max s. That
the voltages are comparable to membrane potentials is deemed fortuitous.
In the above experiment, different field strengths were obtained by putting
the electrode pair at different distances s from the subject. This
resulted of course in different areas A.sub.s of predominant field
application. As a check on the validity of Eq. (15), an experiment was
performed in which A.sub.s is fixed, and the field strength is varied by
changing the voltage applied to the field electrodes. The latter were a
shielded pair as in FIG. 8, with field electrodes of 223.times.230 mm
applied to the thighs of the subject at a distance of 5 mm from the skin.
A sinusoidal generator voltage was used with frequency of 2.408 Hz and an
amplitude of 1.25 V. Before application to the electrodes, the generator
output voltage was reduced by an adjustable voltage divider. Silent counts
from 100 to 60 were done at times t=0, 20, and 40 minutes into the
experiment run. The resulting counting times are plotted as function of
E.sqroot.A.sub.s, where A.sub.s is the skin area of predominant field
application, which here is equal to the electrode area of 513 cm.sup.2. E
is the electric field on the skin apposing the field electrode; E is
uniform and equal to E.sub.max introduced above. The resulting plots are
shown in FIG. 12, where 82, 83, and 84 are respectively the counting time
plots for t=0, 20, and 40 minutes. The anomaly at the data points with
E.sqroot.A.sub.s =79.5 may perhaps be attributed to chemical detuning that
depresses the counting times, but the matter needs further investigation.
The data reveal an effective intensity window that extends from 18.2 to
158 mV in terms of E.sqroot.A.sub.s. Comparison with FIG. 11 shows that
the windows for the two experiments are in rather good agreement,
considering the crudeness of the model used, and the neglect of
differences in surface density p of cutaneous nerves in the skin areas
involved; see Eqs. (15) and (16).
In order to see the effect of surface density p of cutaneous receptors,
another experiment was done in which a shielded pair of small field
electrodes was applied to the tip of the index and middle fingers of the
left hand. Since the receptor density p is larger on the finger tips than
on the thighs, the values for E.sub.max .sqroot.A.sub.s in the window are
expected to be less than for the thighs experiment. The field electrode
area was 15.times.20 mm, and both field electrodes were applied at an
average distance d=0.5 mm from the skin, accounting for the distance
variation due to the ridges on the fingerprint skin. The voltage applied
to the field electrodes (2 and 2' of FIG. 8) was sinusoidal with an
amplitude of 1.15 V, reduced by a resistive divider, so that different
field electrode voltages can be applied from run to run. Counting times
from 100 to 60 are plotted in FIG. 13 versus E.sub.max .sqroot.A.sub.s.
The graphs 85, 86, and 87 show respectively the counting times at t=0, 20,
and 40 minutes into the run. The data reveal an effective intensity window
that extends from 6.6 to 54 mV, in terms of E.sub.max .sqroot.A.sub.s. The
bimodality of graphs 86 and 87 does not appear to be due to chemical
detuning, and needs to be investigated further. Comparison with FIG. 12,
where the window extends from 18.2 to 158 mV, and use of Eqs, (15) and
(16), gives for the surface densities the ratio
p.sub.f /p.sub.t =2.9, (20)
where p.sub.f and p.sub.t are respectively the receptor densities of the
affected cutaneous nerves on the finger tips and on the thighs. The upper
window limits have been used in calculating the ratio (20).
The small ratio (20) is surprising, and it may help in identifying which
type afferents are modulated. There are four different kinds of nerve
endings in fingerprint skin: bare intraepidermal terminals, intrapapillary
coils, Merkel cells, and Meissner corpuscles ›34!. The latter have poor
low frequency response. The Merkel cells are mechanoreceptors that are
innervated by slow-adapting (SA) afferents with good low frequency
response, which makes them candidates for electric field modulation with
the frequencies used. The cells sometimes are found to be most profuse
near the entry of sweat ducts into the underside of the epidermis ›34!.
Nearby Merkel cells are thus subjected to a field that is concentrated by
the conductive sweat ducts, so that they may get modulated. The matter
needs further investigation.
It is of interest to compare the ratio of upper to lower limit of the
windows, as it is independent of the receptor density p; this ratio is
here called the span of the window. For FIGS. 11, 12, and 13, the span is
found to be respectively 7.2, 8.7, and 8.2. The good agreement of the
spans of the effective intensity windows for the three experiments with
different skin areas of predominant field application supports the notion
that the nuisance-guarding circuitry is the same in all three cases. In
contrast, the window span is about 2000 in FIG. 9 which pertains to
excitation not by external electric fields, but by longitudinal currents
applied with contact electrodes to the skin overlying the vagus nerve in
the neck. Our comments on this large span of 2000 are as follows. First,
the afferents in the vagus nerve report visceral information, whereas the
cutaneous nerve signals are somatosensory. Since the latter are much more
prone to nuisance signals coming from the environment, the
nuisance-guarding circuitry involved is expected to be more sensitive. It
is even somewhat surprising that such activity is indicated at all for
visceral information. Second, our modulation of the vagus nerve and
cutaneous nerves are of different nature, as evidenced by the large
current densities needed in the former case. Perhaps the modulation of the
propagation speed along the afferents involved is a strongly nonlinear
function of the applied longitudinal current density.
Although an effective intensity window has been noticed in the 1/2 Hz
experiments, the window has not been measured, mainly because we lacked a
sensitive quantitative indicator. Ptosis of the eyelids, the leading
indicator for the 1/2 Hz resonance, is not nearly as suitable a detector
as the 100-60 counting time for the 2.4 Hz resonance. In the absence of
the full window information, one can still see whether effective
intensities for the 1/2 Hz resonance fit the 2.4 Hz windows, in terms of
E.sub.max .sqroot.A.sub.s. For the 1/2 Hz cases we take two experiments
with setups that have given satisfactory results as sleeping aids. The
first of these is illustrated by FIG. 1, with the peak external electric
field amplitude on the skin estimated as 1 V/m. With the area A.sub.s of
predominant field application estimated as 400 cm.sup.2, the product
E.sub.max .sqroot.A.sub.s comes to 200 mV. The second experiment involves
a closely spaced electrode pair of 16 cm.sup.2 area driven by 3 V peak to
peak, and placed at a distance s=30 cm from the subject's thighs. Use of
the model mentioned above gives for the maximum electric field on the skin
E.sub.max =12 mV/m, so that one has E.sub.max .sqroot.A.sub.s =4 mV, using
.sqroot.A.sub.s =s. The E.sub.max .sqroot.A.sub.s values of 200 mV and 4
mV for these 1/2 Hz resonance cases can perhaps be reconciled with the 2.4
Hz resonance window of FIG. 11, considering differences in the density p
of affected cutaneous receptors in the skin areas of predominant field
application involved. This result supports the notion that the
nuisance-guarding circuitry is the same for the 1/2 Hz and 2.4 Hz
resonances. Further experiments are needed to settle the question.
For a sinusoidal external field the polarization current density in the
skin has approximately the amplitude
j=2.pi.f.epsilon..sub.o E.sub.o, (21)
where E.sub.o is the external field on the skin, f the field frequency, and
.epsilon..sub.o the permittivity of free space. For the 1/2 Hz experiment
discussed in regard to Eqs. (4)-(9), the current density amplitude (21)
comes to 2.8 fA/cm.sup.2. This value is of course very much smaller than
the peak current density of 17 pA/cm.sup.2 given by (9) for the rounded
square wave. It has been observed that, in weak field experiments with
cutaneous nerves, sine waves excite the resonance just as well as square
waves of the same amplitude, rounded or not. This is consistent with our
conclusion that it are the polarization charges that cause the modulation
of the cutaneous nerves, not the polarization currents. Since the
polarization currents constitute a foreign intrusion, sine waves, with
their mimimum polarization currents, are to be preferred from a
neurological point of view.
Excitation of the 1/2 Hz resonance is possible with large external electric
fields, up to 10 KV/m, produced by placing insulated field electrodes
directly on the skin of the thighs. In this arrangement, a sweat layer
quickly develops between the skin and the field electrode insulation. This
highly conductive layer removes the polarization charges from the skin so
that the mechanism that relies on the Debye smearing of the polarization
charges in the epidermis cannot operate. Therefore, the modulation of
cutaneous nerves in this case must be due to polarization currents. For
the rounded square wave used, the peak polarization current density in the
skin apposing the field electrodes is found to have an amplitude of about
100 nA/cm.sup.2. This current density lies somewhat outside the window of
FIG. 9, which ranges from 21 pA/cm.sup.2 to 41 nA/cm.sup.2, in terms of
the current density. The discrepancy is believed to be due to the
difference in the density of afferents for the two cases. Since the
afferents of the cutaneous nerves in the dermis are oriented roughly
perpendicular to the skin surface, the local polarization current is
longitudinal with respect to the afferent fibers, so that one expects the
afferents to be subject to modulation by the currents, at least by virtue
of the action potential propagation speed effect discussed. In addition,
the cutaneous receptors may also respond to the large polarization
currents. The modulation of cutaneous nerves by the large external field
of 10 KV/m in the presence of a sweat layer between skin and field
electrode insulation is thereby understood to about the same extent as the
other modulation situations. It is emphasised that the polarization
current density of 100 nA/cm.sup.2 is still much too small to cause
classical nerve stimulation.
Frequencies appropriate for the excitation of sensory resonances discussed
lie near 1/2 Hz and 2.4 Hz. Additional sensory resonances may be found,
with frequencies up to perhaps 45 Hz.
Strong fields applied to areas of skin overlying nerves may be used for
modulating afferent fibers in these nerves, thereby providing a method for
manipulation of the nervous system via visceral afferents, as in the vagus
nerve. The method differs from that of Wernicke et al. ›35! and from that
of Terry et al. ›28!, in that it employs field electrodes rather than
contact electrodes, so that it is noninvasive, and there is no reliance on
classical nerve stimulation, so that current densitites smaller by a
factor 50000 suffice. Furthermore, the present invention uses excitation
of sensory resonance. In our experiments, a shielded pair of insulated
field electrodes is placed on or adjacent to the skin such that the line
connecting their centers is roughly parallel to the underlying nerve,
afferents of which are to be modulated. The field strength needed for the
excitation of sensory resonances can be calculated from (21) if the
necessary current densities are known. For the excitation of the 2.4 Hz
resonance through the vagus nerve, these current densities can be
determined from FIG. 9; accounting for the electrode area of 484 mm.sup.2,
the window extends from 21 pA/cm.sup.2 to 41 nA/cm.sup.2. Using (21), the
corresponding field strengths for a sine wave are found to range from 3.8
KV/m to 7.6 MV/m. A low voltage sine wave generator suffices for the
production of fields in a low part of this range, if the insulated field
electrodes are placed directly on the skin. For instance, with insulating
tape 0.076 mm thick (3M Scotch.TM. Mailing Tape), a voltage amplitude of 1
V gives a field of 13.2 KV/m.
Strong-field experiments have been conducted on the sciatic nerve
underlying the skin on the back of the knee, using an insulated doublet of
60.times.42 mm area. With the doublet positioned in the skin fold of the
bent knee, and an 162.times.135 mm insulation sheet provided such that the
polarization currents cannot be shortened by apposing skin of calf and
thigh, the sciatic nerve was exposed to longitudinal polarization currents
of the order of 50 pA/cm.sup.2, caused by fields of about 3.7 KV/m set up
by a sine wave voltage of 1.13 V amplitude at a frequency of 2.414 Hz. The
100 to 60 counting times were 34 s at t=0, 54 s at t=20 minutes, and 59 s
at T=40 minutes, showing that the 2.4 Hz resonance was excited.
A similar experiment was done in the right armpit, exposing the ulnar nerve
to longitudinal polarization currents that were caused by the 60.times.42
mm doublet imbedded in the 162.times.135 mm insulation sheet discussed
above, using the same voltage amplitude and frequency as before. The
100-60 counting times were 33 s at t=0, 57 s at t=20 minutes, and 57 s at
t=40 minutes, showing excitation of the 2.4 Hz resonance.
Finally, a strong-field experiment was done on the right vagus nerve in the
neck, using a shielded pair of field electrodes of 22.times.22 mm area, at
a center-to-center distance of 45 mm, oriented such as to expose the nerve
to longitudinal polarization currents. The field electrodes were driven by
a sinusoidal voltage with an amplitude of 1.13 V and a frequency of 2.414
Hz. The 100-60 counting times were 34 s at t=0, 68 s at t=20 minutes, and
74 s at t=40 minutes, showing excitation of the 2.4 Hz resonance. In spite
of the rather close proximity of the skin area of predominant field
application, the brain was not subjected to substantial polarization
current densities, by virtue of the strict field localization by the
shielded field electrode pair.
The experiments discussed show that there are two regimes of afferents
modulation by an electric field applied to a selected skin area. The first
regime involves modulation of cutaneous sensory receptors by polarization
charges in the skin, and is therefore called charge modulation. In the
second regime the polarization currents are strong enough to cause
modulation of the propagation speed of action potentials along axons
exposed to the currents, so that the regime is called current modulation.
In both regimes, the polarization currents are much too weak to cause
classical nerve stimulation. Sensory resonances can be excited in both
regimes, but the effective intensity windows have different spans. In the
charge modulation regime, the window extends roughly from 20 mV to 140 mV
in the parameter E.sub.max .sqroot.A.sub.s, to be adjusted for different
densities of the affected cutaneous receptors. In the current modulation
regime, the effective intensity window extends roughly from 21 pA/cm.sup.2
to 41 nA/cm.sup.2, to be adjusted for the number of affected afferents in
the nerve exposed to the polarization currents. The span of about 2000 for
this window compared to about 8 for the charge modulation regime shows
that different mechanisms operate in the two regimes. Current modulation
is suitable for manipulation of the nervous system through visceral or
somatosensory afferents in large nerves that are, at places, capacitively
accessible through the skin, such as vagus and sciatic nerves. In these
cases, the application of external fields can be done with a shielded pair
of field electrodes, placed on the overlying skin in the direction of the
nerve. When used properly, the shielded electrode pair assures that the
field is applied strictly to the underlying skin, without exposing more
distant regions of the body, such as the brain, to substantial
polarization currents. The field strengths appropriate for exitation of
sensory resonances in the two regimes differ by a large factor; for charge
modulation, typical fields on large skin areas range from 10 to 200 mV/m,
whereas for the current modulation the fields, naturally for localized
small skin area exposure, are of the order of kilovolts per meter. For
both regimes, the proper fields can be produced by the same low-voltage
generator, simply by using different field electrodes and deployment. The
doublet placed some distance from the subject is particularly suitable for
charge modulation of cutaneous receptors over large skin areas, whereas
the shielded pair is the field electrode configuration of choice in the
current modulation regime, although a single small electrode pair may be
used for the special case where it can be completely surrounded by the
subject's skin.
The method is expected to be effective also on certain animals, and
applications to animal control are therefore envisioned. The nervous
system of mammals is similar to that of humans, so that sensory resonances
are expected to exist, albeit with somewhat different frequencies.
Accordingly, in the present invention, subjects are mammals.
The invention is not limited by the embodiments shown in the drawings and
described in the specification, which are given by way of example and not
of limitation, but only in accordance with the scope of the appended
claims.
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* * * * *