Human flash-VEP and quantitative EEG are independently affected by acute scopolamine.

Scopolamine in acute intramuscular doses of 0.25-0.75 mg reduced the P2-N3 flash-VEP amplitude and, in the quantitative EEG, the 8.5-12.0 Hz power and total power in 8 healthy young male volunteers. The effects on flash-VEP and EEG total power were dose dependent and were evident 30 min and 90 min respectively after drug administration, regardless of dose. The reduction in 8.5-12.0 Hz power was limited to the 0.50 and 0.75 mg doses. No systematic effects on the pattern-VEP were observed. Possible interferences with flash- or pattern-VEP amplitude of the scopolamine-induced EEG changes were identified and removed by regression analysis and computation of VEP residuals from the regression function. The P2-N3 flash-VEP residuals proved EEG independent and showed relationships with dose and time after drug administration that were superimposable on those of the original data, with comparable significance levels at the drug/placebo and pre/postdrug statistical comparisons. The results indicate that VEP estimates of drug effects which are independent from EEG changes can be identified in human studies and allow some inference on the cholinergic specificity of the systems affecting late flash-VEP components. The statistical approach used in this study is suitable for application in VEP studies when effects of interacting factors are to be expected.

[1]  E. Hulme,et al.  Multiple Classes of Muscarinic Receptor Binding Sites in the Brain , 1979 .

[2]  B. J. Winer Statistical Principles in Experimental Design , 1992 .

[3]  M. Fink EEG and psychopharmacology. , 1978, Electroencephalography and clinical neurophysiology. Supplement.

[4]  M. Ghilardi,et al.  The importance of stimulus selection in VEP practice: the clinical relevance of visual physiology , 1986 .

[5]  H G Vaughan,et al.  Inhibitory processes in the flash evoked potential of the monkey. , 1990, Electroencephalography and clinical neurophysiology.

[6]  F. Ratliff,et al.  Bicuculline enhances a negative component and diminishes a positive component of the visual evoked cortical potential in the cat. , 1980, Proceedings of the National Academy of Sciences of the United States of America.

[7]  A. S. Schwartz,et al.  Neural mechanisms involved in the critical flicker frequency of the cat. , 1966, Brain research.

[8]  V. Skrebitsky,et al.  Reticular suppression of flash-evoked IPSPs in visual cortex neurons , 1976, Brain Research.

[9]  A. Rouck,et al.  Electrodiagnosis, Toxic Agents and Vision , 1978, Documenta Ophthalmologica Proceedings Series.

[10]  U. Eysel,et al.  Cholinergic excitation and inhibition in the visual thalamus of the cat — influences of cortical inactivation and barbiturate anesthesia , 1988, Brain Research.

[11]  W. Morton Grant,et al.  Toxicology of the eye , 1962 .

[12]  Wolf Singer,et al.  Acetylcholine-induced inhibition in the cat visual cortex is mediated by a GABAergic mechanism , 1989, Brain Research.

[13]  T. Ogawa,et al.  Does the ascending cholinergic projection inhibit or excite neurons in the rat thalamic reticular nucleus? , 1986, Journal of neurophysiology.

[14]  TATSUYA KANAI,et al.  Mesencephalic Reticular Activating System and Cortical Acetylcholine Output , 1965, Nature.

[15]  W. Sannita,et al.  Effects of scopolamine (0.25-0.75 mg i.m.) on the quantitative EEG and the neuropsychological status of healthy volunteers. , 1987, Neuropsychobiology.

[16]  H. Spekreijse,et al.  Principal components analysis for source localization of VEPs in man , 1987, Vision Research.

[17]  C E Wright,et al.  Changes in the human visual evoked potential caused by the anticholinergic agent hyoscine hydrobromide: comparison with results in Alzheimer's disease. , 1986, Journal of neurology, neurosurgery, and psychiatry.

[18]  H. Hinrichs,et al.  International Pharmaco-EEG Group (IPEG) , 1987 .

[19]  R. Lévy,et al.  Visual evoked potentials in Alzheimer's disease: correlations with age and severity. , 1990, Electroencephalography and clinical neurophysiology.

[20]  B. Katz,et al.  A study of the ‘desensitization’ produced by acetylcholine at the motor end‐plate , 1957, The Journal of physiology.

[21]  D. Tolhurst,et al.  Psychophysical evidence for sustained and transient detectors in human vision , 1973, The Journal of physiology.

[22]  M. Fink EEG and human psychopharmacology. , 1969, Annual review of pharmacology.

[23]  M. Brandt,et al.  The effect of the phase of prestimulus alpha activity on the averaged visual evoked response. , 1991, Electroencephalography and clinical neurophysiology.

[24]  M. Brandt,et al.  Pre-stimulus spectral EEG patterns and the visual evoked response. , 1991, Electroencephalography and clinical neurophysiology.

[25]  A. Ducati,et al.  Neuronal generators of the visual evoked potentials: intracerebral recording in awake humans. , 1988, Electroencephalography and clinical neurophysiology.

[26]  U. Mitzdorf Current source-density method and application in cat cerebral cortex: investigation of evoked potentials and EEG phenomena. , 1985, Physiological reviews.

[27]  T. Harding,et al.  A cholinergic-sensitive channel in the cat visual system tuned to low spatial frequencies. , 1983, Science.

[28]  T. Harding,et al.  Recovery of the visual evoked response in the cat following administration of diisopropylfluorophosphate, an irreversible cholinesterase inhibitor. , 1987, Life sciences.

[29]  C. E. Wright,et al.  Pathology of the optic nerve and visual association areas. Information given by the flash and pattern visual evoked potential, and the temporal and spatial contrast sensitivity function. , 1987, Brain : a journal of neurology.

[30]  J. Raz,et al.  Noise and signal power and their effects on evoked potential estimation. , 1988, Electroencephalography and clinical neurophysiology.

[31]  D. Hubel,et al.  Effects of sleep and arousal on the processing of visual information in the cat , 1981, Nature.

[32]  N. Birdsall,et al.  Muscarinic receptor subclasses , 1983 .

[33]  D. Guha,et al.  Effects of nicotine on eeg and evoked potentials and their interactions with autonomic drugs , 1976, Neuropharmacology.

[34]  Y. Kuroiwa,et al.  Visual function of the extrageniculo-calcarine system in man: relationship to cortical blindness. , 1980, Archives of neurology.

[35]  M. Kuhar,et al.  Muscarinic cholinergic receptors: Autoradiographic localization of high and low affinity agonist binding sites , 1980, Brain Research.

[36]  I. Bodis-Wollner Visual deficits related to dopamine deficiency in experimental animals and Parkinson's disease patients , 1990, Trends in Neurosciences.

[37]  L. Demisch,et al.  Changes in flash but not pattern evoked cortical potentials after subchronic application of a monoamine oxidase (MAO) type A inhibitor in man. , 1985, Electroencephalography and clinical neurophysiology.

[38]  D M Parker,et al.  The Spatial Selectivity of Early and Late Waves within the Human Visual Evoked Response , 1977, Perception.

[39]  J. Christophe,et al.  Muscarinic receptor heterogeneity in rat central nervous system. II. Brain receptors labeled by [3H]oxotremorine-M correspond to heterogeneous M2 receptors with very high affinity for agonists. , 1987, Molecular pharmacology.

[40]  D. Regan,et al.  Human brain electrophysiology , 1989 .

[41]  E. Hulme,et al.  Correlation Between the Binding Properties and Pharmacological Responses of Muscarinic Receptors , 1978 .

[42]  U. Aguglia,et al.  Different susceptibilities of the geniculate and extrageniculate visual pathways to human Creutzfeldt-Jakob disease (a combined neurophysiological-neuropathological study). , 1991, Electroencephalography and clinical neurophysiology.

[43]  J. Lance,et al.  Brain-stem facilitation of electrically evoked visual cortical response in the cat. Source, pathway and role of nicotinic receptors. , 1988, Electroencephalography and clinical neurophysiology.

[44]  J. Kulikowski,et al.  The effect of nitrous oxide on the relation between the evoked potential and contrast threshold. , 1973, Vision research.

[45]  M. Wright,et al.  Evidence for "sustained" and "transient" neurones in the cat's visual cortex. , 1974, Vision research.

[46]  J. Grisell,et al.  Relationship of EEG background rhythms to photic evoked responses. , 1965, Electroencephalography and clinical neurophysiology.

[47]  G. Harding,et al.  VISUAL EVOKED POTENTIALS IN PRE-SENILE DEMENTIA , 1981 .

[48]  R. Hichwa,et al.  In vivo Muscarinic Cholingeric Receptor Imaging in Human Brain with [11C]Scopolamine and Positron Emission Tomography , 1992 .

[49]  L. Ciganek The EEG response (evoked potential) to light stimulus in man. , 1961, Electroencephalography and clinical neurophysiology.

[50]  A. G. Karczmar,et al.  Brain Acetylcholine and Animal Electrophysiology , 1979 .

[51]  E. Garcı́a-Austt Influence of the states of awareness upon sensory evoked potentials. , 1963, Electroencephalography and clinical neurophysiology.

[52]  D. Purpura,et al.  Selective Blockade of Excitatory Synapses in the Cat Brain by γ-Aminobutyric Acid , 1957, Science.

[53]  Edward V. Evarts,et al.  PHOTICALLY EVOKED RESPONSES IN VISUAL CORTEX UNITS DURING SLEEP AND WAKING , 1963 .