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Bibliography of Animal Studies
Cat:
1, 17
Dog:
4, 6, 7, 8
Horse:
2
Monkey:
3, 9, 10, 11, 12, 16, 18
Rabbit:
13, 14, 15
Rat:
5
II. Pysiological Measure:
-endorphin:
5
Blood Pressure:
4
Brain histology:
4, 11, 12, 13
Brain implanted electrodes:
1, 3
Electrocardiogram (ECG):
4, 9, 18
Electroencephalogram (EEG):
4, 17
Electromylogram (EMG):
9, 16, 18
Electroretinogram:
4, 9
Evoked potentials:
9, 18
Gastric acidity:
9, 10, 16
Hematology:
4, 6
Metenkephalin:
5
Respiration:
4
Synaptic vesicles:
11, 12
Temperature:
4
III. Behavioral Measure or Observation:
Alcohol withdrawal syndrome:
5
Epileptic activity:
14
Parkinson-like state:
8
Relaxation:
9
Reaction time:
6, 16
Sleep:
1, 13
IV. Intrabrain Electrical Passage:
1, 3
V. Safety Addressed, No Problem:
2, 4, 11
VI. Locus of CES Measurement:
Basal ganglia:
7
Brainstem:
15
Caudate nucleus:
4
Hypothalamus:
1
Limbic system:
10
Motor Cortex:
3
Septum:
4
Striate cortex:
4
Subcortex:
15
Thalamus:
3
1. Austen, Burton G. Current distribution in subcortical regions of the cat's brain during electrosleep. In Reynolds, David V., and Anita Sjorberg (Eds), Neuroelectric Research. Springfield, Charles Thomas. 28:262-266, 1971.
Following up on earlier researchers who said that when the hypothalamus was electrically stimulated "natural sleep" resulted, the author stimulated the caudate nucleus and the preoptic region of the hypothalamus in five adult female cats. The stimulus was a 15 second train of rectangular pulses, each with a width of 0.3 msec., frequency of 5 Hz, and an amplitude of between 0.1 and 2 V. The resulting current density and distribution in the cats' brain was discussed.
2. Geddes, L.A., Hoff, H.E., McCrady, J.D. Electroanesthesia in the horse. In Wageneder, F.M. and St. Schuy (Eds). Electrotherapeutic Sleep and Electroanaesthesia. International Congress Series No. 136. Excerpta Medica Foundation, N.Y., Pages 73-80, 1967.
The authors demonstrated the parameters of electrode size and current density necessary to produce burns via electrical stimulation of the skin. With electrodes similar to or smaller than those of most CES electrodes and with much greater current loads across the skin, they observed no burns. The discussion centered around the heat dissipation to be expected from polarized impedance's when constant or controlled current sources are used.
3. Jarzembski, William B., Sanford J. Larson, Sances, Anthony, Jr. Evaluation of specific cerebral impedance and cerebral current density. Annals of the New York Academy of Sciences, 170:476-490, 1970.
Sensor electrodes were chronically implanted in the sagittal planes in the region of the medial thalamus and in sagittal and coronal planes in the region of the motor cortex of the brains of 30 monkeys. Electrodes were placed externally at the nasion and inion. Currents varying from 0.1 to 100 mA were generated with frequencies ranging from 10 to 5,000 Hz. They found that the current densities in the brain at all frequencies tested were linearly proportional to the applied currents, but with the thalamic current density slightly higher than the cortical current density. Calculations indicated that from 42% to 46% of the total applied current entered the brain.
4. Jordan, Eric J., Morris, David. Evaluation of the electrosleep machine. Diseases of the Nervous System. 36(12):661-665, 1975.
9 littermate-male Beagle dogs were given 13 daily 31 hour treatments under anesthesia with eye to occipital electrodes and measured with EEG's, ERG's, blood pressure, temperature, respiration, blood and urine analysis. Photic stimulation was applied in addition to the CES. 3 dogs were given "normal" levels of 1 mA AC and .33 mA DC, another 3 received "high" levels of 5 mA AC and 1.33 mA DC, the third group of 3 had sham treatment. After the course of treatment, the dogs were sacrificed and examined. 2 dogs suffered direct trauma from the citernal puncture, causing spinal cord lesions. No neurologic signs were noted from the CES. It was noted that CES may cause mild EEG slowing. Suspicious findings were found in the striate cortex, caudate nucleus, and septum. Except for 1 case, these were small and of questionable significance. There were no changes which were unequivocally pathological. No acute or chronic changes were noted in BP, EKG, temperature or respiration. The authors concluded that evidence of ES-induced pathology is inconclusive.
5. Krupisky, E.M., Katznelson, Ya.S., Lebedev, V.P., et al. Transcranial electrostimulation (TES) of brain opioid structures (BOS): experimental treatment of alcohol withdrawal syndrome (AWS) and clinical application. Presented at the Society for Neuroscience Annual Meeting, New Orleans, November 10-15, 1991.
Alcohol withdrawal syndrome (AWS) was induced in rats. Noninvasive CES increased the -endorphin level in rat cerebrospinal fluid from 15.93 2.17 to 53.25 6.1 pmol/ml and met-enkephalin from 3.61 1.39 to 7.86 0.94 pmol/ml. Marked therapeutic effect of CES was also demonstrated in this animal model. Clinical double-blind placebo-controlled studies showed CES of brain opiod structures showed that CES was an effective method in the treatment of AWS in pts. After the CES treatment in AWS pts, the -endorphin concentration in plasma rose from 5.86 0.72 to 10.66 0.65 pmol/L. There was a threefold increase in -endorphin concentration just after 1 CES treatment.
6. Pocta, J., Lebl, M., Hanka, R. The autonomic and stress reactions during electrosleep. In Wageneder, F.M and St. Schuy (Eds) Electrotherapeutic Sleep and Electroanaesthesia. International Congress series, No. 136. Excerpta Medica Foundation, N.Y., Pages 342-344, 1967.
The authors completed 45 experiments in dogs, saying that dogs are known to respond to exogenous stimuli by developing disturbances of the autonomic system. The oculocardiac reflex, the carotid sinus reflex, the solar plexus reflex, leukocyte count, hemoglobin, hematocrit, segmented cells, and eosinophil count were obtained. They found that electrosleep elicited firm and reliable stabilization of the organism. No features of instability of the autonomic nervous system were observed.
7. Pozos, Robert S., Richardson, Alfred W., Kaplan, Harold M. Electroanesthesia: A proposed physiologic mechanism. In Reynolds, David V., and Anita Sjoberg (Eds.) Neuroelectric Research. Springfield, Charles Thomas, Pages 110-113, 1971.
The authors used both electoanesthesia and electrosleep current levels along with reserpine, anoxia, L-dopa, atropine and physostigmine in mongrel dogs to elucidate the mechanisms of action from electrical stimulation to the head. Their findings suggested that CES releases dopamine in the basal ganglia, and that the overall physiological effects appear to be anticholinergic and catecholamine-like in action, and that some form of acidosis or a concomitant of this state is implicated in the mechanism of action.
8. Pozos, Robert S., Strack, L.E., White, R.K., Richardson, Alfred W. Electrosleep versus electroconvulsive therapy. In Reynolds, David V. and Sjoberg, Anita E. (Eds), Neuroelectric Research. Charles Thomas: Springfield, 23:221-225, 1971.
This is a report of a series of 5 studies which involved a complex examination of physiologic changes in pharmacologically altered experimental animals (dogs), 20 experimental and 20 controls. The animals were prepared with 0.2 mg/kg reserpine intramuscularly. After 1 hour those given either electrosleep stimulation, electroconvulsive stimulation or lithium chloride, developed Parkinson-like symptoms. Dogs given electroconvulsive levels of stimulation while in the Parkinson-like state experienced evoked hypersynchrony persisting for 3 - 7 minutes, while stimulated controls showed a discharge pattern lasting for only 20 - 40 seconds. The evoked hypersynchrony in the electroconvulsively stimulated animals could be returned to the duration of hypersynchrony found in the control dogs by giving them atropine (0.4 mg/kg), L-dopa (2.5 mg/kg), or electrosleep stimulation. The authors conclude: "It is proposed that electrosleep, electroconvulsive stimulation, and lithium salts may share a common mechanism... Based on this study alone, the net effects of electrosleep stimulation and electroconvulsive stimulation seem quite similar."
9. Reigel, D.H., Dallmann, D.E., Christman, N.T., Hamilton, L.H., Zuperku, E.J., Henschel, E.O., Larson, S.,J., Sances, A., Jr. Physiological effects of electrotherapeutic currents in the primate and man. In Wageneder, F.M., and St. Schuy (Eds.), Electrotherapeutic Sleep and Electroanesthesia. Vol. II, Amsterdam, Excerpta Medica, Pages 158-165, 1970.
Studies were completed on squirrel monkeys, macaque monkeys and 15 human volunteers. Measures studied were somatosensory evoked potentials, visual evoked potentials, electroretinograms, electrocorticograms, electromyographic potentials, electrocardiograms, respiratory rate, and gastric acid. For the animal studies pulse type currents from 2.5 to 80 Hz were used. For the human studies, pulsed currents of 100-200 A intensity and 5 Hz were used. They summarized: "Neurophysiologic, cardiorespiratory and gastric secretory physiology was observed in man and primate during ESC. Visual and somatosensory evoked potentials were not significantly altered during and after ESC in the primates. The EMG and ECG suggested changes compatible with relaxation in the primates. Respiration and EKG remained stable in both humans and primates. Total gastric acid output in primates is significantly reduced by ESC. These studies suggest that ESC may be of therapeutic value." Abstract courtesy of Ray B. Smith, Ph.D., M.P.A.
10. Reigel, D.H., Larson, Sanford J., Sances, Anthony, Jr., Christman, Norbert, Dallmann, Donald, Henschel, Ernest O. Effects of electrosleep currents on gastric physiology. In Reynolds, David V. and Sjoberg, Anita (Eds.) Neuroelectric Research. Springfield, Charles Thomas. 24:226-229, 1971.
Gastric cannulas were placed in the dependent portion of the stomach of seven stump-tailed monkeys. After recovery from surgery, electrosleep currents of 20 to 100 A, 2.5 to 70 Hz, were applied between the nasion and inion for periods of one hour. The maximal change in gastric secretion occurred during the last half of the 60 minute period of ESC. The mean volume decreased 28.3%, the mean concentration decreased 38%, and acid production decreased 60%. Acid production returned to normal within 1 to 2 hours after ESC. The authors found that nocturnal gastric acid levels without ESC were similar to those during application of ESC or during in-depth stimulation of various limbic structures, and concluded that these two types of stimulation may affect similar structures.
11. Richter, Ward R., Zouhar, Raymond L., Tatsuno, Jiro, Smith, Robert H., and Cullen, Stuart C. Electron microscopy of the macaca mulatta brain after repeated applications of electric current. Anesthesiology. 36(4):374-377, 1972.
2 immature Rhesus monkeys and a control were studied to assess safety of electric currents applied to the brain. 1 monkey received only sine wave current up to 50 mA, another received only square wave, up to 13 mA. They received 10, 1 hour treatments. Following the course of treatment, the monkeys were sacrificed and brain tissue was analyzed. They examined neurons, neuroglia, myelinated and nonmyelinated fibers, capillaries and nearby astrocytes, synaptic endings and the general architecture of the neurophil. Special attention was given to the structure of the synapse and the size, location, and distribution of synaptic vesicles. The authors concluded that all of these structures were within normal limits, that there is no generalized evidence of injury, and that they have greatly increased their confidence in the safety of repeated application of electric currents.
12. Siegesmund, K.A., Sances, A., Jr., Larson, S.J. The effects of electrical currents on synaptic vesicles in monkey cortex. In Wageneder, F.M. and St. Schuy (Eds.) Electrotherapuetic Sleep and Electroanaesthesia. International Congress Series No. 136. Excerpta Medica Foundation, N.Y., Pages 31-33, 1967.
Biased rectangular current pulses of 2.5 msec duration, 75 Hz, and 5 mA were delivered through electrodes on the nasion and inion of 4 squirrel monkeys. Electron photomicrographs were made of neural tissue biopsies prior to, during, and post stimulation and the number of synaptic vesicles in close apposition to the presynaptic membranes were counted for at least 200 synapses in each group. They found that in the control specimen 65% of the presynaptic terminals contained 14 +/-2 vesicles near the cleft. Shortly after maximum stimulation was reached, there was an increase of terminals with less than 9 vesicles and corresponding decrease in those with 14. After 5 minutes at an applied current of 5 mA, a further decrease in terminals with 14 vesicles and a corresponding increase in terminals with more than 24 vesicles were found. Shortly after discontinuation of stimulation, the number of terminals with 24 or more vesicles returned to control levels while the number with 9 vesicles or less remained at a higher level than in the controls.
13. Sommer, H., Kriebel, J. Neuropathological investigations of electrosleep in animal experiments (Rabbits). In Wageneder, F.M., and St. Schuy (Eds.) Electrotherapeutic Sleep and Electroanesthesia. Vol. II, Amsterdam, Excerpta Medica, Pages 169-174, 1970.
Finding that the electrical parameters indicated for electrosleep in humans did not produce sleep in rabbits, they gave 700 Hz square-wave pulses with a pulse width of 0.4 msec, an average current of 0.5 mA, with a peak value of 4 mA. The animals were put into a sleep-like state 5 times per week for 15, 30, 45, or 60 minutes. Histological sections of the brains were made after 20 sessions. They found numerous pathological changes that were related to intensity of stimulation. One discussant noted that he had found such pathological changes in cats following ECS experiments. At the end of the conference discussion, the authors stated that these results cannot be extrapolated to humans because these current parameters are not usually used in humans, and the conditions within the human brain are quite different from those encountered in the rabbit brain. No control animals were used.
14. Tatsuno, Jiro, Marsoner, Hermann J., Fukuda, Hiroshi. The effects of diffuse currents on focal epileptic discharges. In Wageneder, F.M., and St. Schuy (Eds.) Electrotherapeutic Sleep and Electroanesthesia. Vol. II, Amsterdam, Excerpta Medica, Pages 93-101, 1970.
In a study using 15 rabbits in which the skull was exposed via a burr hole and focal discharges engendered by painting the exposed brain surface with penicillin solution, the authors found that no currents of electrosleep intensity were effective in suppressing epileptic activity, but some evidence was obtained which suggested that the more intense currents (30 mA, 1,000 Hz) altered the frequency of firing in the epileptic focus. They noted that while no CES study had found problems in grand mal epilepsy patients with CES (often finding positive results instead), this study suggested that focal epilepsy may react differently to CES, though the authors admit that "from the intensity of the currents used in this experiment it was not possible to conclude that the current in the electrosleep therapy has such effects on the seizure activity of the epileptic patients. Abstract courtesy of Ray B. Smith, Ph.D., M.P.A.
15. Titaeva, M.A. Changes in the functional state of the central nervous system under the influence of a pulse current as used in electrosleep: In Wageneder, F.M. and St. Schuy (Eds.) Electrotherapeutic Sleep and Electroanaesthesia. International Congress Series, No. 136. Excerpta Medica Foundation, N.Y., Pages 175-180, 1967.
This was an uncontrolled set of clinical observations of 110 pts, including 85 with schizophrenia and 25 with "asthenohypochondriacal syndromes of varied aetiology." For CES they used a pulsed current of 5-10 Hz, and duration of 0.2 msec, at an unspecified amperage. Treatment lasted from 40 minutes to 2 hours and continued for 16-25 days. They deduced that their observations indicated that the principal changes arising during electrosleep can be attributed most probably to its direct action on the brain. They then did a series of 35 experiments on 9 rabbits with the same pulse characteristics but with 0.7 to 2.0 V current intensity. Again they concluded that their observations indicated that CES has its effects via the stimulation of the nonspecific structures of the subcortex and brain stem.
16. Wilson, A.S., Reigel, D., Unger, G.F., Larson, S.J., and Sances, A., Jr. Gastric secretion before and after electrotherapeutic sleep in executive monkeys. In Wageneder, F.M., and St. Schuy (Eds.), Electrotherapeutic Sleep and Electroanesthesia. Vol. II, Amsterdam, Excerpta Medica, Pages 198-206, 1970.
The authors produced a demonstrable increase in gastric acid secretion as a result of learned avoidance behavior in 6 stump-tailed macaques. Electrosleep (100 A, 15 Hz) markedly reduced the gastric hypersecretion (50% - 75%) associated with shock avoidance behavior in these animals. The authors concluded that CES may be of clinical importance in acid hypersecretion in humans. There was no alteration in efficient behavioral performance during or after electrosleep in these animals.
17. Wulfsohn, N.L., Waldron, L. The importance of trains of current producing electrosleep. In Wageneder, F. M., and St. Schuy (Eds.), Electrotherapeutic Sleep and Electroanesthesia. Vol. II, Amsterdam, Excerpta Medica, Pages 212-216, 1970.
In an early attempt to see what parameters of electrosleep would more likely yield sleep in subjects, 5 cats were implanted subdurally bitemporally and occipito-frontally. The researchers applied numerous stimulation parameters, and concluded that EEG modulated trains produced better sleep effects than non-modulated trains, and were better than EEG modulated current without trains when compared with controls.
18. Zuperku, E.J., Hosek, R.S., Larson, Sanford J., Reigel, D.H., Sances, Anthony, Jr, Henschel, Ernest O. Studies during electrotherapeutic sleep. In Reynolds, David V., and Anita Sjoberg (Eds.) Neuroelectric Research. Springfield, Charles Thomas, Pages 235-241, 1971.
CES currents from 2.5 to 80 Hz, with amplitudes from 20 A to 1.5 mA were applied to stump-tail macaque and squirrel monkeys and various physiological recordings made. It was found that visual and somatosensory evoked potentials were not significantly altered during and after CES. A reduction in EMG amplitude occurred during CES, and the ECG showed a greater tendency toward slower, high-voltage activity. Respiration and EKG were stable.
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