ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY
THYROID HORMONE AND BRAIN FUNCTION II. C H A N G E S I N P H O T I C A L L Y E L I C I T E D E E G R E S P O N S E S FOLLOWING THE ADMINISTRATION OF TRIIODOTHYRONINE TO NORMAL SUBJECTS 1 W. P. WILSON, M.D. 2, J. E. JOHNSON, M.D. 3 AND F. W. FEIST, M.D. Departments of Psychiatry and Medicine, University of Texas Medical Branch, Galveston, Texas (U.S.A .) (Received for publication : June 13, 1962) (Resubmitted: February 4, 1963)
Among the changes frequently observed in a clinical study on the EEGs of hyperthyroid patients were a decrease in the duration of photically elicited arousal responses and an increase in susceptibility to intermittent photic stimulation. This latter finding was in many instances associated with potentiation (increase in voltage) of the response to intermittent photic stimulation (Wilson and Johnson 1960). Furthermore, patients with potentiated photic responses often found the procedure most disagreeable and noted that the light seemed quite intense (Wilson and Johnson 1963). The fact that the duration of the arousal response returned to normal or was increased above normal following treatment with radioactive iodine suggested that the observed changes resulted from the increased secretion of thyroid hormone. Because these findings also suggested a relationship between perception and the neurophysiologic variables associated with hyperthyroidism, this study was undertaken in an effort to determine whether the EEG changes arid perceptual distortions noted in thyrotoxic patients could be induced by the administration of thyroid hormone to normal subjects. MATERIAL AND METHOD
The eleven subjects included in this series were This work was supported by Grant M-2698, National Institute of Mental Health, U.S.P.H.S. 2 Associate Professor of Psychiatry and Director of Psychiatric Research. Present address: Box 3355, Duke University Medical Center, Durham, N. C. (U.S.A.). Assistant Professor of Medicine.
young medical students and technicians with normal EEGs. Nine subjects were male and two were female. All were known to the authors, and their basic personality patterns could be classified as within the range of normal. All had been used previously in similar studies, and were known to be suitable for these experiments. On the day that the ingestion of triiodothyronine was begun, a control EEG, using six electrodes placed in the left and right central, parietal, and occipital regions (C3-C4, P3-P4, and Ox-O~) was obtained on each subject. After a suitable control period of recording on a Grass [1I D electroencephalograph, single photic stimuli from a Grass PS-2 photic stimulator were randomly presented at intervals of 5-15 sec for a period of 5 min. The stimuli were of constant intensity. Intermittent photic stimuli were then presented at frequencies of l, 2, 4, 6, 8, 10, 12 and 15 flashes/sec for 20 sec periods, with a 30 sec rest period between each frequency. In order to obtain an accurate count of the pulse rate, lead 11 of the electrocardiogram was recorded on the same EEG tracing. Each subject's blood pressure was recorded, and a BMR was obtained when possible. After the control studies had been completed, the subject began the daily ingestion of 300 , g of triiodothyronine 4, divided into three doses of 100 ,,g each. After 72 h on this medication, the various procedures were repeated. The EEG records were analyzed for the pulse rate, duration of arousal response (determined 4 Supplied as Cytomel by the Smith, Kline and French Laboratories of Philadelphia.
Electroenceph. clin. Neurophysiol., 1964, 16:329-331
w . P . WILSON et al.
by the method of Wilson and Wilson 1959), responsiveness to intermittent photic stimulation, and alpha frequency. If an increase in the voltage of the responses to intermittent photic stimulation was observed which was 50 per cent greater than the responses occurring in the control record, this change was noted. To determine the duration of the mean arousal response, the responses to the three flashes presented at random intervals during 30 sec intervals were determined and a mean value obtained. However, to simplify the statistical analysis of data the mean response duration for the entire 5 min period was calculated from these values. The means for the 5 rain periods in the control and experimental EEG of each subject were then compared, and the t-test used to determine the statistical significance of the differences. RESULTS
All subjects reported marked changes in feeling tone (mood) after the ingestion of triiodothyronine, although these changes followed no obvious pattern (Wilson et al. 1962). Only two subjects noticed a tendency to withdraw and complained of being unable to think clearly. That the hormone affected body metabolism was TABLE 1 Duration of arousal responses obtained in eleven subjects before and after the administration of triiodothyronine
1 2 3 4 5 6 7 8 9 10 11
Mean duration (in seconds) of responses obtained over a period of 5 min Before
0.42 0.52 0.67 0.73 0.57 1.23 0.55 0.92 0.93 0.65 1.01
0.19 0.37 0.65 0.34 0.23 0.76 0.44 0.53 0.85 0.51 0.56
Mean 0.74 ( ! 0.24*) P 0.001 * Standard deviation,
0,49 (-4- 0.21")
documented by the changes in BMR in the five subjects with satisfactory tests; the mean increase in these five subjects was 30 per cent. While the pulse rate of the eleven subjects showed a mean increase of 16 (P -----0.001), blood pressure was essentially unchanged. Analysis of the E E G data demonstrated a decrease in the duration of the arousal response in all subjects (Table I). The mean decrease for the entire group was 0.25 sec (P ~-- 0.001). The alpha frequency was essentially unchanged, the mean value for the control records being 10.2 c/sec and for the experimental records, 10.3 (P--~ 0.1). In five subjects responsiveness to intermittent photic stimulation at some frequencies was increased by one level. Six subjects showed no changes in the responsiveness to intermittent photic stimulation. Perception was altered in eight of the eleven subjects. These eight described the after-images as being grossly distorted and intensified. Two found the experience most unpleasant. DISCUSSION
By the administration of triiodothyronine we have reproduced experimentally a decrease in the duration of the arousal response in all eleven subjects and an increase in the responses to photic stimulation in five subjects. Although the changes in the photic responses are inconsistent we can speculate that the data thus obtained afford evidence of physiological changes in the two systems through which the responses are mediated, namely, the specific afferent sensory system (visual) and the reticular system with its projections. When these findings are interpreted in the light of present knowledge (Killam and Killam 1958; King et al. 1957), it may be hypothesized that the changes i n cortical responsiveness are possibly secondary to a depression of the level of activity in the reticular system. Depression of the propagation of afferent stimuli through the reticular network could decrease the output of this system to the cortex, possibly shortening the duration of the arousal response. The inhibitory influence of the reticular system on the transmission of impulses in the primary afferent system would also be reduced, thus increasing the amount of information transmitted to the Electroenceph. clin. Neurophysiol., 1964, 16:329-331
THYROID HORMONE AND BRAIN FUNCTION. II
cortex and resulting in enhanced cortical responses. The increase in the amount of information reaching the cortex would also cause a distortion of perception, characterized by an increase in intensity and possibly by alteration in the quality of the perception. Further experiments designed to investigate this hypothesis are now in progress, and will be reported at a later date. In the present experiment, as in our clinical studies on thyrotoxic patients (Wilson and Johnson 1960, 1963), the parieto-occipital rhythms showed no increase in frequency. In contrast, Rubin et al. (1937) demonstrated a significant increase in the alpha frequency within 2-3 days following the administration of thyroid hormone to schizophrenic patients, and Ross and Schwab (1939) observed a significant correlation of alpha frequency with basal metabolic rate in hyperthyroid patients. It is quite possible that the short duration of the experiments reported here might account for the lack of increase in the alpha frequencies of our subjects, and that more prolonged administration of triiodothyronine might have resulted in a significant change. As triiodothyronine and thyroxine have similar effects on tissues, it seems unlikely that the difference is related to the use of this specific compound. SUMMARY
Electroencephalograms were made in nine normal male and two normal female subjects before and after the ingestion of 300 /zg of triiodothyronine daily for 3 days. Following the administration of the hormone,
the duration of the EEG arousal response was shortened in all subjects, and responsiveness to photic stimulation was increased in five of the eleven subjects. Eight of the eleven subjects reported perceptual distortion. No change in alpha frequency was observed.
REFERENCES KILLAM, K. F. and KILLAM, E. K. Drug action on p~thways involving the reticular system. In H. JttSPER et al. (Editors), Reticular .lbrmation of the brain, Little, Brown and Co., Boston, 1958:111-121. KING, E. E., NAQUET, R. and MAGOUN, H. W. Alterations in somatic afferent transmission through the thalamus by central mechanisms and barbiturates. J. Pharmacol. exp. Ther., 1957, 119: 48-63. Ross, D. A. and SCHWAB, R. S. The cortical alpha rhythm in thyroid disorders. Endocrinology, 1939, 25: 75-79. RUBIN, M. A., COHEN, L. H. and HOAGLAND,H. The effect of artificially raised metabolic rate on the electroencephalogram of the schizophrenic. Endocrinology, 1937, 21: 536-540. WILSON, W. P. and JOHNSON, J. E. Clinical laboratory and electroencephalographic correlations in hyperthyroidism. South. reed. J., 1960, 53: 606-610. WILSON, W. P. and JOHNSON, J. E. Thyroid hormone and brain function. I. The EEG hyperthyroidism with observations on the effect of age, sex, and reserpine in the production of abnormalities. Electroenceph. clin. Neurophysiol., 1964, 16: 321-328. WILSON, W, P., JOHNSON, J. E. and SMITH, R. B. Affective change in thyrotoxicosis and experimental hypermetabolism. Recent Advanc. biol. Psychiat., 1962, 4: 234-242. WZLSON, N. J. and WILSON, W. P. The duration of human electroencephalographic arousal responses elicited by photic stimulation. Electroenceph. clin Neurophysiol., 1959, II : 85-91.
Reference: WILSON,W. P., JOHNSON, J. E. and FEIST, F. W. Thyroid hormone and brain function. !1. Changes in photically elicited EEG responses following the administration of triiodothyronine to normal subjects. Electroenceph. clin. NeurophysioL, 1964, 16: 329-331.