From Psychotechnology:
Electronic Control of Mind and Behavior, edited by Robert L.
Schwitzgebel and Ralph K. Schwitzgebel, Chapter 15, Holt,
Rinehart and Winston, 1973.
.
Reprinted there from The Journal of Nervous and
Mental Disease, Vol. 147, No. 4, 1968. Research supported by
the United States Air Force 6571st Aeromedical Research
Laboratory, Unites States Public Health Service, and the
Office of Naval Research.
Diagnosis and treatment of focal brain dysfunction associated with
behavioral abnormalities are complex tasks which require more effective
exploratory techniques. Intracerebral electrodes,
electrocorticographical studies, and subsequent discrete neurosurgery
have given the epileptologist and stereotaxic surgeon new possibilities
for clinical investigation which as yet have been applied to only a
small percentage of the patients suffering from neurological disorders
including temporal-lobe epilepsy and related episodic behavior problems.
In these therapeutic studies, recordings and stimulations of any chosen
cerebral structure can be performed over a period of days or weeks, and
neuronal sites identified as triggers for abnormal electrical patterns
associated with behavioral disturbances can be destroyed by electrolysis
or resection.
Unfortunately, in some
patients episodic behavior disorders may be more disabling than their
epileptic seizures, and focal lesions may improve one syndrome without
modifying the other. Furthermore, recording and stimulation are usually
performed under conditions which qualify their usefulness, because the
patients' mobility is limited by connecting leads, and their behavior is
likewise altered by the stressful and artificial environment of the
recording room.
During the last few years, methodology has been developed to stimulate
and record the electrical activity of the brain in completely
unrestrained monkeys and chimpanzees (Delgado, 1967; Delgado & Mir, in
press). This procedure should be of considerable clinical interest
because it permits exploration of the brain for unlimited periods in
patients without disturbing their rest or normal spontaneous activities.
This paper reports instrumentation used and clinical application in four
patients with psychomotor epilepsy in whom electrodes had been implanted
in the temporal lobes. To our knowledge, this is the first clinical use
of intracerebral radio stimulation and recording in man.
METHODS
Implantation of Electrodes
Electrodes were constructed and stereotaxically implanted according to
methods previously described (Mark & Ervin, 1969). The electrode
assemblies, which were connected to a McPherson skull plug, consisted of
a plastic styled, 1.2mm in diameter, with 15 stainless steel 3mm wide
contacts attached at 3mm intervals, plus one thermistor and three other
contacts at the tip. Using a McPherson Type 2 stereotaxic machine (Mark
& Ervin, 1969), electrode assemblies were implanted bilaterally into the
anterior medial amygdala of each patient.
Radio Stimulation This system consists of two instruments: (1) the RF transmitter that
measures 30cm x 25cm x 15cm and includes the circuitry for controlling
the repetition rate, duration, and amplitude (intensity) of the
stimulating pulse. The repetition rate may be varied in steps between 10
and 200Hz and the duration between 0.1 and 1.5msec. Single pulses may
also be generated. Intensity control is accomplished by varying the
frequency of the three subcarrier oscillators that operate in the 100 to
500 kHz frequency range. A 100mHz oscillator is turned on and off by the
pulse train from the subcarrier oscillators. The duration of this pulse
train is determined by the pulse-duration switch. These bursts of 100mHz
RF energy are received by (2) the receiver-stimulator which is carried
by the subject, measures 3.7cm x 3.0cm x 1.4cm, and weighs 20g. The
solid-state circuitry is encapsulated in epoxy resin which provides it
with very good mechanical strength and makes it waterproof. Space for
the 7-volt Mercury battery is included in the size mentioned above.
After RF detection, the resulting subcarrier frequency is demodulated
into an amplitude. This amplitude controls the current intensity of the
stimulation pulse by means of a constant current transistor in the
output circuit of the receiver. This method makes the pulse intensity
independent of biological impedance changes over a wide range. Under
average stimulation conditions, the battery life is approximately one
week. Operating range is up to 100ft. Three channels of stimulation are
available. The pulse intensity of each channel can be controlled
individually from the transmitter. The pulse duration and repetition
rate are the same for all three channels.
Electroencephalographic (EEG) Telemetry A miniature FM-FM amplifier-transmitter combination and a telemetry
receiver are used for this purpose. (1) The transmitting circuitry,
carried by the subject, consists of an EEG amplifier with a gain of 100,
input impedance of 2 megohms, frequency response from 2 to 200Hz, and a
voltage-controlled oscillator (VCO) for each channel. The VCO operates
in one of the frequency bands assigned for subcarrier oscillators by the
IRIG standards. In these studies, a three-channel system was used which
operated on IRIG channels (Delgado & Hamlin, 1962; Delgado & Mir, in
press; Fonberg and Delgado, 1961). The outputs of all three subcarrier
oscillators were summed and connected to the single RF transmitter
module. The miniaturized RF transmitter operates at 216mHz and its range
is 50 to 200 ft, depending on the environment. The size of the
three-channel unit, including the battery, is 4.5cm x 4.5cm x 1.5cm, and
it weighs 50g. The signals from the depth electrodes are received by the
amplifier. The output signal of the amplifier controls the frequency of
the subcarrier oscillator, and the oscillator output in turn controls
the frequency of the transmitter. (2) After amplification of the
received signal from the transmitter has been demodulated, the composite
subcarrier signals are connected to the inputs of the three
discriminators, which then separate and demodulate their respective
subcarriers to obtain the telemetered analogue information. In the
instrumentation used in this instance, a 100uV signal at the input of
the EEG amplifier resulted in a 1-volt output from the corresponding
discriminator in the receiver.
The analogue output signals from the receiver were connected to the
inputs of an EEG recorder and a magnetic tape recorder. A microphone was
also mounted in the room with the subjects and conversation was recorded
along with the EEG on magnetic tape.
Stimoceiver
The integration of the three-channel units for radio stimulation and EEG
telemetry constitutes the stimoceiver (stimulator and EEG receiver).
Several tests were conducted to ensure proper electronic and biological
operation, as explained later. The complete instrument, which weighs
only 70g, can easily be taped onto the patient's head bandage (Figure
1). During part of her treatment, one patient wore a wig which covered
her stimoceiver and all evidence of instrumentation.
Additional Equipment Conversations with the patients were taperecorded and synchronized
with the EEG recordings and the moments of stimulation. During
interviews with the first two patients, time-lapse photography was used
to record possible changes in facial expression or behavior, according
to a method employed for studies in monkey colonies (Delgado, 1964).
Physical Location of
the Studies
The first two
patients were under treatment at the Boston General Hospital, and radio
stimulations and recordings were performed in a curtained, shielded, 12
x 12 ft room in which the patients could walk around or remain seated.
The other two cases were studied in their customary quarters within a
closed psychiatric ward at Massachusetts General Hospital, and they
could move freely around their bedrooms, bathroom, sittingroom, or
diningroom. Nurses and other patients were present during some of the
recording and stimulation sessions, as seen in Figure 1.
[<FIGURE OMITTED> Figure 1 Two patients instrumented for intracerebral
radio stimulation and recording engage in spontaneous activities (one is
playing the guitar) in the psychiatric ward in the presence of the
doctor (VM). Explorations of the brain can be performed for as long as
necessary without disturbing the patients.]
Experimental
Design
The purpose of this study was to identify sites of abnormal
intracerebral electrical activity and to test brain excitability in
order to guide contemplated therapeutic surgery. Patterns of electrical
activity were correlated with behavioral performance, and alterations of
conduct evoked by brain stimulation were evaluated. Many hours of EEG
recordings were taped and analyzed to determine the frequency, severity,
and propagation of spontaneous electrical discharges which could have
pathological significance. Interviews were structured in order to elicit
the patient's verbal expression without unduly influencing the
ideological content. During these sessions, two intracerebral points
were selected for more extensive study, and they were randomly
stimulated at 3- to 5-minute intervals according to a predetermined
schedule. Neither the patient nor the therapist was informed of the
exact moments of stimulation, and each point was stimulated seven times
during three 60- to 90-min sessions. Tape-recorded conversations were
transcribed, analyzed for number of words per minute and for ideological
and emotional content, and correlated with the EEG activity recorded
continuously during control periods and stimulations (Higgins, Mahl,
Delgado, & Hamlin, 1956; Mahl, Rothenburg, Delgado, & Hamlin, 1964).
Instrumenting the patient for telestimulation and recording is a simple
and rapid procedure requiring only connection of the stimoceiver to the
electrode assembly plug. The stimoceiver is so small and light that it
can be concealed within the head bandage, as shown in Figure 1. The
patient is thus continuously available, day and night, for brain
exploration, and there is no interference with spontaneous behavior.
The entire instrumentation for these studies consisted of the
stimoceiver, radio transmitter, FM receiver, electroencephalograph, tape
recorder, and oscilloscope. This equipment can be rapidly assembled in a
small space and operates without any special physical or electrical
requirements. These aspects are emphasized to indicate the feasibility
of this type of research within minimum facilities of a hospital ward.
Controls and
Functional Characteristics of the Stimoceiver
Fidelity of
recording: As demonstrated in previous animal experimentation
(Delgado & Mir, in press), the traces obtained by means of direct
wire connections with the brain were identical with tracings
obtained from the same points by telemetry. In the present study
this fact was also confirmed.
Noise of open input: Tests were made by disconnecting the
instrumentation from the terminals of the implanted electrodes on
the patient's head without removing the instrumentation. In this
electrically adverse situation of open input, the noise level was
below 15uV. When the input of the EEG transmitter was connected with
the calibrator, the noise level was below 5uV, as shown in Figure 2.
Movement artifacts:
The leads connecting the terminal plug of the intracerebral
electrodes with the telemetric unit were multistrand,
Teflon-covered, unshielded copper wires about 80mm long, attached to
the patient's bandage. Normal activities, including walking around,
did not produce observable artifacts.
Interference by extraneous noise: Most of the recordings, as
in Figures 2, 3, and 4, were reasonably free of electrical
interference in spite of the fact that no special precautions had
been taken in the ward, and the rooms were unshielded. From time to
time, however, brief periods of electrical noise appeared in the
telemetric recordings, probably related to motors of other
instrumentation in use at the hospital. These disturbances sometimes
lasted for 10 to 15 sec.
Walls and obstacles: Suitable tests demonstrated that radio
stimulation and telemetry could be performed through walls and
closed doors that did not obstruct the transmission of RF energy. As
an added precaution, receiving and emitting antennae were attached
to the ceiling of the ward.
Cross-talk: Tests were performed to ensure the lack of
cross-talk between the telemetric recording channels, and also
between the channels of radio stimulation. During application of
radio stimulations, however, artifacts appeared in the recordings,
as seen in Figure 2B.
Blocking time after stimulation: The amplifiers of the
telemetric units recovered from the over-voltage block immediately
after stimulation, and the delay in onset of EEG recording was very
brief, as shown in Figure 2B. In general, recordings were obtained
from points adjacent to the stimulated leads to avoid direct
interference between inputs and outputs of the instrumentation. One
cerebral contact could be shared by recording and stimulating units.
Monitoring of stimulation: In animal experimentation, prior
to releasing the subject for telestimulation, we always monitor on
the oscilloscope the voltage and milliamperage of cerebral radio
stimulations. In two patients we performed similar oscillographic
monitoring. It should be clarified that in the completely free
situation there is no direct monitoring of the actual intensity
used, but as the output is constant current reliability of
electrical parameters is ensured.
Safety in stimulations: In patients walking around while
instrumented with stimoceivers, there is a theoretical risk that
they might receive extraneous electrical signals. In our stimulators
this risk is avoided because of the specificity of the
frequency-modulated coding needed to activate them. In addition, by
construction the maximum amount of current that the stimoceiver can
deliver is 2uA.
Clinical Applications of
the Stimoceiver
1. L. K. This
35-year-old white male design engineer had experienced attacks of
staring and automatisms for 10 to 12 years. He also had frequent
episodes of rage during which he assaulted and injured his wife and
children. His driving was precarious because he became enraged if
other cars cut in front of him and he would go miles out of his way
to force them off the road.
The EEG revealed temporal lobe spiking more prominent on the right
side. Pneumoencephalograms disclosed dilation of the right lateral
ventricle, and recording from inlying temporal lobe electrodes
showed marked EEG abnormalities. Telemetered recordings were done to
correlate the results of amygdala stimulation, EEG recording, and
behavior without risking the danger of displacing the intracerebral
electrodes by sudden, untoward movements of the patient which could
not be compensated for with the usual method of EEG recording by
means of direct leads.
2. M. R. This 25-year-old white male suffered from
encephalitis as an infant and a severe head injury in the Navy.
Following this he had four years of staring spells and automatisms.
He was the driver of a car involved in a serious accident and had a
police record for vagrancy and violence. He began assaulting his
medical attendants on the neurology service of a local veterans'
hospital and had to be confined in a mental institution while
awaiting surgical evaluation.
The EEG showed bilateral temporal-lobe abnormalities. Electrodes
were implanted in both amygdalas and depth recordings revealed
abnormalities particularly prominent on the right side. The clinical
problem here was to decide if and where in the amygdala a focal
destructive lesion should be made. The telemetered recording and
stimulation allowed us to correlate the patient's behavior and
electrical abnormalities without the structured rigidity of the EEG
recording room.
3. J. P. This 20-year-old white female had a history of
encephalitis at the age of 18 months. In addition, she had
experienced temporal-lobe seizures and occasional grand mal seizures
for 10 years. She also had frequent rage attacks which on more than
a dozen occasions resulted in an assault on another person. On one
occasion she inserted a knife into a stranger's myocardium, and
another time she inserted scissors into the pleural cavity of a
nurse.
The EEG showed occasional temporal lobe spikes and depth recordings
revealed dramatic electrical abnormalities in both amygdala and
hippocampus. The use of stimoceivers proved to be of crucial
importance in selection of the temporal lobe site for a destructive
lesion because it was difficult to confine the patient in the EEG
recording room during a rage attack while recordings were easily
made by telemetry.
4. G. C. This 14-year-old Negro girl was brought up in a
foster home and was of borderline intelligence. On two separate
occasions her violent behavior resulted in the death of a young
foster sibling, and she subsequently assaulted a 7-year-old child at
the state hospital where she was confined.
The EEGs, ventriculograms, and arteriograms appeared normal, and
extradural plates beneath the temporal lobes recorded normal brain
waves. Depth electrodes were placed in each amygdala through the
posterior approach. Recordings from the hippocampus showed marked
focal electrical abnormalities. Telerecordings and telestimulations
were used because of this patient's unpredictable behavior. She
could not be relied on to sit quietly with the conventional EEG
recording system. Stimulation in her right hippocampus produced a
clinical and electrical temporal-lobe seizure. In retrospect, the
patient claimed to have had a number of these before electrode
implantation but she had not communicated this information to her
physicians.
Recording and Stimulation
In the four patients, recording of spontaneous electrical activity
showed typical patterns which in general permitted the identification of
each linkage in different recordings, indicating the reliability of the
information. The activity of each linkage indicates the existence of
autochthonous electrical generators rather than the predominance of
widespread pacemakers. This fact is demonstrated in Figures 2, 3, and 4,
which show the lack of synchrony among the waves in the three channels,
contrasting with the simultaneous detection of single-shock stimulus
artifact that appeared in Figure 2C and also contrasting with the
correlation of patterns during the evoked after-discharges that spread
to the three channels (Figure 2D). We do not know the extension of the
electrical fields generated within each cerebral structure but
recordings indicate that the localization is rather precise because a
clear pattern, such as the 12-cps bursts in Figure 4A, was detected
exclusively in Channel 1.
One of the main objectives in telemetric recording of intracerebral
activity is the search for correlations between electrical patterns and
behavioral manifestations. Computer analysis of the tape-recorded
information is the best method for this purpose, and its results will be
reported in the future. Visual inspection of ink writing recording may
also give valuable data, as indicated in the following examples.
In patient J. P., spontaneous, brief periods of aimless walking around
the room coincided with an increase in high-voltage sharp waves, as
shown in Figure 3B. At other times, spontaneous inhibition of speech
lasting for several minutes was accompanied by a burst of spike activity
localized to Contacts 15-16, as seen in Figure 4B. Psychological
excitement of the same patients was related to an increase in the number
and duration of 16-cps bursts (see Figure 4). Emotionally charged
conversation often modified the recordings from the amygdala, but this
result was not as evident as the above-mentioned changes. The possible
significance of these correlations was increased by the fact that other
behavioral manifestations did not produce detectable electrical changes.
The patient walked around the room, used the toiled, read papers, and
conversed without visible alterations in the telemetered depth
recordings.
Radio stimulation of different points in the amygdala and hippocampus in
the four patients produced a variety of effects including pleasant
sensations, elation, deep, thoughtful, concentration, odd feelings ,
super relaxation, colored visions, and other responses. In this article
we will discuss only the following selected results:
During a recorded interview in patient G. C., Point 9, located in the
left hippocampus, was radio-stimulated for 5 sec with 100Hz, 0.5 msec,
and 1uA, resulting in an electrical after-discharge (Figure 2D)
involving the amygdala, hippocampus, and optic radiation that lasted for
25 sec. During this time the patient's conversation stopped completely,
and she was unresponsive, without exhibiting motor convulsions,
automatisms or other visible disturbances. When the after-discharge was
over, the patient resumed conversation, remembered her speech arrest,
but was not able to explain it. Spontaneous electrical activity of the
brain was considerably modified for more than 2 min after stimulation,
as shown in Figure 2 (E, F, G). During this period, the patient
expressed the successive sensations of fainting, fright, and floating
around. These "floating" feelings were repeatedly evoked on different
days by stimulation of the same point even in the absence of
after-discharges. Single shocks applied to the hippocampus induced
bursts of high-voltage activity in the optic radiation and were
accompanied by the perception of "funny feelings."
In patient J. P., crises of assaultive behavior reminiscent of her
spontaneous bursts of anger could be elicited by radio stimulation of
Contact 3 in the right amygdala. Seven seconds after the onset of radio
stimulation with 50Hz, 1.0msec, and 1.2uA, the patient interrupted
spontaneous activities such as guitar playing, and in a fit of rage
threw herself against the wall (never attacking the interviewer), paced
around the room for several minutes, and then gradually resumed her
normal behavior. This effect was repeated on two days with similar
results. During this elicited rage, no seizure activity was evident in
the depth recording. The fact that only one contact gave this type of
response suggested that the surrounding neuronal field was involved in
the behavioral problems of the patient.
DISCUSSION
Important limitations of standard electroencephalographic recordings are
as follows:
(1)
psychological stress of the recording room
(2) time
required to attach leads to the patients
(3)
restrictions imposed on individual mobility by the
connecting leads
(4)
limited period for the acquisition of data
(5) the
slim likelihood of taking recordings during spontaneous
electrical or behavioral crises, which could provide the
most important information for the patient's diagnosis and
treatment.
These handicaps are
eliminated by using telemetry. Extensive information has been published
about different systems for radio telemetry in biological studies (Barwick
& Fullagar, 1967; Caceres, 1965; Geddes, 1962; Slater, 1963). The
disparity between the large number of technical papers and the few
reports of results indicates the existence of methodological problems.
There are some data on telemetered EEG obtained during space flights (Adey,
1963; Simmons & Prather, 1964); preliminary descriptions of scalp EEG
studies in humans have been reported (Breakell, Parker, & Christopherson,
1949; Kamp & Van Leeuwen, 1961); and there is also a technical reference
paper on telemetered scalp EEG in disturbed children (Vreeland, Collins,
Williams, Yeager, Gianascol, & Henderson, 1963). Data are presented here
to demonstrate that telemetry of EEG has already attained a degree of
sophistication, miniaturization and reliability that tender it suitable
for widespread clinical application in both standard scalp and
intracerebral electrical studies.
In the last decade, depth recording in man has become a major
therapeutic tool in various medical centers (Alberts, Feinstein, Levin,
& Wright, 1966; Ajmone, Marson, & Van Buren, 1964; Bickford, Dodge, &
Uihlein, 1960; Heath, 1963; Sem-Jacobsen, 1964; Walker & Marshall, 1964;
White & Sweet, 1969). The usefulness of intracerebral electrodes would
be significantly increased if stimulations and recordings were performed
by remote control. This technique, in addition to being more comfortable
for the patients, would permit more detailed exploration and prolonged
studies including periods of normal sleep.
Electrical stimulation of the brain, which is a standard procedure in
neurosurgery, has been proposed by some authors as a therapeutic
technique (Heath, 1963; Sem-Jacobsen, 1964; Walter & Crow, 1964). For
this purpose, programmed radio stimulation of ambulatory patients would
be obviously advantageous.
The combination of both stimulation and EEG recording by radio telemetry
offers a new tool for the two-way clinical exploration of the brain, and
it may be predicted that in the near future microminiaturization and
more refined methodology will permit the construction of instruments
without batteries and small enough to be permanently implanted
underneath the patient's skin, for transdermal reception and
transmission of signals through several channels. Part of the basic
circuitry for this purpose has already passed satisfactory testing in
our laboratory. While the use of cardiac pacemakers is well-established
in clinical medicine, methodological problems in the development of a
similar instrument for cerebral pacemaking are far more difficult
because of the requirements of multichanneling, external control of
several parameters of stimulation, and the far greater functional
complexity of the brain in comparison with the heart. These technical
problems, however, are soluble, and the possibility of clinical
application should attract the interest of more electronic and medical
investigators.
Experimentation in animals has demonstrated the practicality of
long-term, programmed stimulation of the brain to inhibit episodes of
assaultive behavior (Delgado, 1967), to increase or decrease appetite (Fonberg
& Delgado, 1961), to modify drives (Delgado, 1967), and to modulate
intracerebral reactivity (Delgado 1964). Some of these findings may be
applicable to the treatment of cerebral disturbances in man.
With respect to the electrical information obtained in our four
patients, analysis of their telemetered EEG supports the assumption that
depth recordings reveal local activity rather than diffuse volume
conductor fields in the brain, in agreement with previous work obtained
by direct leads (Delgado & Hamlin, 1958). The considerable independence
of the electrical activity of different intracerebral points indicates
that this electrographic information has anatomical significance.
Caution is necessary, however, in a calculation of the origin of
apparently abnormal waves, such as the burst recorded from Channel 1 in
Figure 2A, which could originate in the neuronal field around the
contacts of could reflect merely the activity transmitted from a distant
cerebral area, as demonstrated in animal experiments (Delgado & Hamlin,
1962). The distinction between reactive and propagated activity that can
be made by studying recorded electrical patterns may help to evaluate
the origin of abnormal intracerebral activity.
SUMMARY
A new instrument called a "stimoceiver" has been developed for the
simultaneous multichannel recording and stimulation of the brain by FM
radio waves in completely unrestrained subjects. This instrument is
small enough to be worn comfortably and permanently by the patient.
Clinical application of the stimoceiver is reported in four patients
with psychomotor epilepsy who had electrodes implanted in the amygdala
and hippocampus for therapeutic reasons. the advantages of this
methodology are:
(1) the
patient is instrumented for the telestimulation and recording
simply by plugging the stimoceiver into the electrode socket on
the head
(2) the
instrumentation does not limit or modify spontaneous behavior
(3) the
patient is continuously available, day and night, for
intracerebral recording or treatment
(4) studies
are performed, without introducing factors of anxiety or stress,
in the relatively normal environment of the hospital ward and
during spontaneous social interactions
(5) cerebral
explorations may be conducted in severely disturbed patients who
would not tolerate the confinement of the recording room
(6) the lack
of connecting wires eliminates the risk that during
unpredictable behavior or convulsive episodes the patient may
dislodge or even pull out the implanted electrodes
(7)
programmed stimulation of the brain for therapeutic reasons may
be continued for as long as necessary
In four patients, telemetric
information obtained supports the following conclusions:
(1) depth
recordings reveal local activity rather than diffuse
volume-conductor fields, giving anatomical significance to the
data
(2)
abnormality in spontaneous behavior, including aimless walking,
speech inhibition, and psychological excitement, coincided with
abnormal EEG patterns
(3) arrest
reaction accompanied by an after-charge was evoked in one
patient by radio stimulation of the hippocampus, and, during the
subsequent 2 min, abnormalities in brain waves coincided with
successive sensations of fainting, fright, and floating around
(4)
assaultive behavior, reminiscent of spontaneous crises, was
elicited in another patient by radio stimulation of the amygdala,
and this fact was important in orienting therapeutic surgery