James L. Grisell

Relationship of EEG background rhythms to photic evoked responses

Abstract Photic evoked responses were obtained in twenty normal male and twenty normal female subjects. It was demonstrated that females tend to have larger amplitude evoked responses than males. Intercorrelations of aspects of the evoked response curve with results of the frequency analysis of the EEG background showed highly significant correlations between amplitude of the photic response and energy amount of the EEG. Individuals with large amplitude evoked response curves showed a greater abundance of actitivity in all frequency bands than those who had small amplitude evoked response curves. The complexity of the evoked response curve — as reflected in the total number of positive peaks — was found to be significantly correlated with the amount of fast activity in the basic EEG.

sleep Deprivation: Effects on Behavior, Thinking, Motor Performance, and Biological Energy Transfer Systems

&NA; The effect of sleep deprivation on behavior, thinking, motor performance, and biological energy transfer systems was studied in a single subject who remained awake without drugs for 220 hours. Behavioral changes included irritability, paranoid thinking, expansiveness, grandiosity, hypnagogic states, visual hallucinations, and episodic rage. Deficits in thinking and visual‐motor performance occurred cyclically across days of wakefulness, with gradual deterioration finally resulting in virtual untestability on the ninth day. Energy transfer systems responded to sleep deprivation as a stressor with a marked increase in the specific activities of ATP, AMP, and F‐1,6‐P; this was eviden on the fourth day. For the first time in out laboratories, radioactive phosphorus was observed in AMP, a reflection of increased synthesis of this substance from adenine ribose‐I‐phosphate, and phosphate. This emergency energy mobilization began to fail by the seventh day, when the specific activities of all the adenylic phosphates fell appreciably. Conceivably the energy transfer system respond to a stressor in a manner similar to the pituitary adrenal axis, passing through stages of alarm, resistance, and exhaustion. The relationship of disturbances in these systems (associated with the most fundamental cellular processes) to various disease mechanisms is under investigation in our laboratories.

BIOCHEMICAL, PSYCHOLOGICAL, AND BEHAVIORAL RESPONSES TO SLEEP DEPRIVATION

The psychosis of sleep deprivation is one of the more useful models in the study of induced psychopathology in humans. I ts gradual development and comparatively long duration allow for the investigation of a number of response systems. Biochemical changes were not demonstrated in sleep deprivation until Luby et ~ 1 . ~ 3 ~ studied the energy transfer systems. Two subjects reacted to the stress of prolonged yvakefulness by a considerable increase in energy production, as measured by the specific activity of adenosine triphosphate (ATP) in their red cells. Such an increase was followed by a fall a t about 100 hours that continued even after completion of the experiment. Ax and Lubyl investigated the autonomic functioning of 5 subjects who were kept awake for 120 hours and reported that prolonged wakefulness produced a marked decline in central sympathetic responsivity. Decrease in palmar sweating was particularly significant in this respect and the trend was further substantiated by a fall in galvanic skin response (GSR) and a paradoxical drop in diastolic blood pressure to a pain stimulus at 100 hours. Psychopathological changes in sleep deprivation have been extensively described and include irritability, illusions, visual hallucinations, paranoid thinking, and dissociative s t a t e ~ . ~ z ~ ~ Performance on psychological tests has also been thoroughly investigated, particularly by Williams et d.1° Both the psychopathology and the performance deficits in this state have been interpreted by this group within the framework of the “lapse” hypothesis, with a lapse defined as ‘(a period of no response accompanied by extreme drowsiness and a decline in EEG alpha amplitude.” During this lapse period external sensory input is cut off and responses occur only to internal stimuli. Electroencephalographic changes have been highly variable but generally demonstrate a progressive decline in alpha rhythm. After 50 hours, stimuli that normally block alpha rhythm were found to elicit it; the so-called paradoxical alpha.I0 E. Rodin and E. D. Luby (unpublished data) recently found that in certain subjects paroxysmal activity was evoked early in the course of sleep deprivation, disappearing at 48 to 72 hours. This would suggest initial stimulation of energy production in brain, followed by depletion. Bliss et aZ.2 found that some acute schizophrenic reactions were seemingly precipitated by sleep loss and that sleep-deprived subjects were more sensitive to the hallucinogenic effects of lysergic acid diethylamide. These observations suggest that metabolic changes in this state may afford a biological setting favorable to the development of psychosis. Koranyi and Lehman5 provide additional evidence for this hypothesis in an experiment in which they sleepdeprived 6 schizophrenic patients. Progressive deterioration occurred after 72 hours, and 5 of the 6 subjects again manifested their acute psychotic picture “as it had been observed a t the time of their admission to the hospital.”

Biologic responsiveness to environmental stimuli in schizophrenia

Summary Evidence has previously been presented that a plasma factor, measured by the chicken-cell lactate-pyruvate ratio method, is at a higher level in the blood of schizophrenic subjects than control subjects after exercise. The present study examined the question of whether this difference was also present after a cold pressor test or 80 reaction time trials. It was found that after each of these two stress situations the groups could be significantly distinguished (p An explanatory hypothesis is presented which considers the schizophrenic subject as more sensitive than control subjects to the unfamiliar and new in his environment. This maladaptive sensitivity makes him unpredictably responsive to relatively minor environmental stimulation. Studies are now underway to discover the specific biologic mechanism responsible for this response.

EFFECTS OF AUDITORY INTENSITY ON SIMPLE REACTION TIME OF SCHIZOPHRENICS

Previous studies (Rosenbaum, Mackavey, & Grisell, 1957; Rosenbaum, Grisell, & Mackavey, 1957) have shown that aversive shock motivation seems to normalize the simple reaction times ( R T ) of chronic schizophrenics. Lang (1959) and Karras (1962) found that aversive auditory stimulation improved disjunctive R T in chronic schizophrenics, but none of their groups approached normal levels. This study investigated the effects of five levels of auditory intensity on the simple RT of 2 3 chronic male schizophrenic patients and 2 8 control Ss. The mean age of the schizophrenics was 31.04 (range = 25-40); of the controls, 28.39 (range = 20-39). The educational backgrounds for last grade completed were: schizophrenics, Af = 11.22 (range 9-18) ; controls, 1M = 12.57 (range 8-20) . All Ss were required to lift a finger from a telegraph key as rapidly as possibIe at the onset of an 800-cps tone presented through a set of earphones. The tone followed a 2-sec. preparatory interval initiated by a ready light. Eighty R T trials consisting of 1 6 trials at each of the 5 auditory inrensities were administered ro all Ss. Each intensity occurred once in every 5 trials, but was randomly ordered within each 5-trial block. The 5 intensity levels employed ranged in approximately equal steps from minimally audible (approximately 15 db) to just below the pain threshold (approximately 90 db) . A Lindquist Type I analysis of variance showed that increases in auditory inrensity resulted in linear increases in speed of simple R T for the schizophrenics, but mean RTs were significantly slower than for the controls at all intensity levels. Normal Ss showed a rapidly decelerated RT curve which approaches an asymptote with small increases in auditory intensity. It is concluded that aversive auditory stimulation has motivating effects on performance by schizophrenics, but that shock srimulation is significantly more effective in activating the biological systems required to normalize simple R T in chronic schizophrenic paciencs.