Cortical acetylcholine, reality distortion, schizophrenia, and Lewy Body Dementia: too much or too little cortical acetylcholine?

Brain Cogn. 1998 Dec;38(3):297-316. doi: 10.1006/brcg.1998.1035.


Aberrations in cortical cholinergic transmission have been hypothesized to mediate the development and manifestation of psychotic cognition. Based primarily on hypotheses about mesolimbic dopaminergic hyperactivity in schizophrenia, the actions of antipsychotic drugs, the trans-synaptic regulation of the excitability of basal forebrain corticopetal cholinergic neurons, and the role of cortical cholinergic inputs in attentional functions, we hypothesized that persistent disinhibition of cortical cholinergic inputs mediates the fundamental cognitive dysfunctions which form the basis for the development of positive symptoms in schizophrenia. In contrast to this hypothesis, Perry and Perry (1995), based on evidence from hallucinating patients with Lewy Body Dementia (LBD), concluded that the extensive loss of cortical acetylcholine allows irrelevant information to enter "conscious awareness" and thus hallucinations to emerge. The discussion of these contrasting hypotheses highlights the need for more dynamic and precise theories describing the cognitive variables and neuronal processes which contribute to the development and manifestation of psychotic cognition. While the hypothesis that a disinhibited cholinergic system mediates the evolution of psychotic symptoms corresponds more convincingly with current theories about the cognitive functions of cortical cholinergic inputs, both hypotheses stress the critical role of cortical acetylcholine in the highest levels of cognitive functioning.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Acetylcholine / physiology*
  • Aged
  • Cerebral Cortex / physiopathology*
  • Cognition Disorders / diagnosis
  • Hallucinations / psychology
  • Humans
  • Parkinson Disease / physiopathology*
  • Perceptual Disorders / diagnosis*
  • Schizophrenia / physiopathology*


  • Acetylcholine