Contingent negative variation (CNV) and drug effects

A classification of eye movements is proposed based on the observation that all types of version eye movements can be generated by 3 major oculomotor subsystems, called saccadic, smooth-pursuit and vestibule-ocular. Rapid and efficient assessment of oculomotor function should be based on such considerations. We have concentrated on visually-evoked smooth-pursuit and saccades, and on doll’s head eye movements. Impairment of the latter type in pharmacological experimental situations has not been demonstrated. Subjects follow horizontal displacement of a light spot which moves sjnusoidally to elicit smooth =1 pursuit and in square wave fashion to elicit saccades. Eye movements are recorded by electro-oculography and anatized by computer, for the determination of the velocity of smooth-pursuit as well as of the reaction time, peak velocity, duration and accuracy of saccades. It has been demonstrated that benzodiazepines and alcohol impair the velocity of both types of eye movement, in a manner related linearly to serum or blood drug concentration. The effect of carbamazepine on smooth-pursuit was similarly related to the serum concentration, while that on peak saccadic velocity was not, suggesting that two distinct effects of the same drug on the oculomotor system are being measured. Sodium valproate appeared to impair saccadic but not smooth-pursuit velocity, while phenytoin slowed smoothpursuit but not saccades. Barbiturates impaired both smooth-pursuit and saccadic velocity. These results indicate that psychoactive compounds often have effects on the oculomotor system, and these can be specific enough for a physiological profile of the drugs to be established. Practical implications are raised in terms of the relationship of these findings to impaired psychomotor performance. Studies of oculomotor function can be further used to clarify syndromes of drug toxicity, as in the case of carbamazepine.

CONTINGENT EFFECTS H. ASHTON,

NEGATIVE

V.R. MARSH

VARIATION

(CNV) AND DRUG

and .I.W,. THOMPSON

Clinical Fs_y~hophur~iac~lo~~Unit, The Unioersiy, Newcastle upon l@e,

NEi 7RU, U.K.

There are three main ways in which the effects of drugs on the CNV can be studied: (1) As a method to study the effects of centrally acting drugs on the humapl brain In normal subjects: Central stimulant drugs (caffeine, cannabis, LSD,

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ubstracts,

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methylamphetamine, nicotine (low dose), pemoline; see references) may increase the amplitude whilst central depressant drugs (atropine, carbon monoxide, chlorpromazine, diazepam, ethanol, flurazepam, metoclopramide, nicotine (high dose), nitrazepam; see references) may decrease it. But more recent work (Ashton, Golding, Marsh, Millman and Thompson, 1981b) has shown that many (possibly all) centrally active drugs, including benzodiazepines, nicotine (cigarette smoking) and cannabis, produce a biphasic effect, the direction and magnitude of the change depending on many factors including dose and time course of action of drug, personality, starting state and environmental factors. (2) As a method to study the effects of drugs on the brain during psychiatric illness: The CNV is altered in depression (and schizophrenia) and also by antidepressant drugs. A longitudinal study made in 10 patients (Ashton, Marsh, Thompson, Eccleston, Hassanyeh and Tyrer, 1981a) indicated that the CNV (and auditory evoked response (AER)) increased in magnitude after treatment with amitriptyline in some patients and corresponded with clinical improvement. (3) As tools to investigate the electrogenesis of the CNV: Limited studies of this type suggest that pharmacological antagonists of several putative central neurotransmitters, including acetylcholine and dopamine. are probably involved in the neuronal pathways which subserve the CNV (Thompson, Newton, Pocock, Cooper, Crow, McCallum and Papakostopoulos, 1978).

References Ashton, H., Marsh, V.R., Thompson, J.W., Eccleston, D., Hassanyeh, F. and Tyrer, S. (1981a). Cortical event-related potentials and clinical ratings in depression. Abstracts of Eighth International Congress of Pharmacology, Tokyo, p. 6 16. Ashton, H., Golding, J., Marsh, V.R.. Millman, J.E. and Thompson, J.W. (1981b). The seed and the soil: Effect of dosage, personality and starting state on the response to tetrahydrocannabinol in man. British Journal of Clinical Pharmacology. Thompson, J.W., Newton, P., Pocock, P.V., Cooper, R., Cros, H., McCallum, W.C. and Papakostopoulos, D. (1978). Preliminary study of pharmacology of contingent negative variation in man. Multidisciplinary Perspectives in Event-Related Brain Potential Research. (Proceedings of the Fourth International Congress on Event-Related Slow Potentials of the Brain (EPIC IV). (1976). 51-55.

4.2. BEHAVIOURAL

MEDICINE

Symposium

by Andrew

convened

MATHEWS