Effects of cholinergic enhancement on visual stimulation, spatial attention, and spatial working memory

Neuron. 2004 Mar 25;41(6):969-82. doi: 10.1016/s0896-6273(04)00145-x.


We compared behavioral and neural effects of cholinergic enhancement between spatial attention, spatial working memory (WM), and visual control tasks, using fMRI and the anticholinesterase physostigmine. Physostigmine speeded responses nonselectively but increased accuracy selectively for attention. Physostigmine also decreased activations to visual stimulation across all tasks within primary visual cortex, increased extrastriate occipital cortex activation selectively during maintained attention and WM encoding, and decreased parietal activation selectively during maintained attention. Finally, lateralization of occipital activation as a function of the visual hemifield toward which attention or memory was directed was decreased under physostigmine. In the case of attention, this effect correlated strongly with a decrease in a behavioral measure of selective spatial processing. Our results suggest that, while cholinergic enhancement facilitates visual attention by increasing activity in extrastriate cortex generally, it accomplishes this in a manner that reduces expectation-driven selective biasing of extrastriate cortex.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / metabolism*
  • Adult
  • Attention / drug effects*
  • Attention / physiology
  • Brain Mapping
  • Cholinesterase Inhibitors / pharmacology*
  • Double-Blind Method
  • Female
  • Functional Laterality / drug effects
  • Functional Laterality / physiology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory, Short-Term / drug effects*
  • Memory, Short-Term / physiology
  • Photic Stimulation
  • Physostigmine / pharmacology
  • Reference Values
  • Space Perception / drug effects*
  • Space Perception / physiology
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • Visual Cortex / anatomy & histology
  • Visual Cortex / drug effects*
  • Visual Cortex / metabolism
  • Visual Fields / drug effects
  • Visual Fields / physiology


  • Cholinesterase Inhibitors
  • Physostigmine
  • Acetylcholine