EEG Mapping During Cholinergic Drug Challenge with RS-86

Abstract

The cholinergic-adrenergic balance hypothesis of affective disorders postulates cholinergic overactivity in depression (Janowsky et al. 1972, 1985). Indeed, patients suffering from affective disorders have been found supersensitive to cholinergic drugs like physostigmine and arecoline in behavioral, neuroendocrine, and electrophysiological parameters. Cholinomimetics inducing an anergic-anhedonic syndrome in healthy volunteers elicited full-blown depressive symptoms even in the euthymic interval. Following cholinomimetics the rise of ACTH/β-endorphin/cortisol secretion has been found greater than in controls. The reduction of REM sleep latency was more pronounced. Thus, cholinergic supersensitivity was proposed to represent a trait marker. Findings in split-brain patients suggest REM sleep to be generated primarily in the right hemisphere, i.e., the one not dominant for speech (Gazzaniga and LeDoux 1978). Based on various lines of evidence, including electrophysiological findings, the lateralization hypothesis suggests the right hemisphere to be overactive and dysfunctioning in depression (Coffey 1987; Flor-Henry 1983; Nasrallah 1982). Attempting to establish a bridge between the cholinergic and lateralization hypotheses, the present study investigated whether topographic changes of electrical brain activity under cholinergic drug challenge might mimic some of the lateralized findings in depression.