Intermittent Stimulation of the Nucleus Basalis of Meynert Improves Working Memory in Adult Monkeys

Ruifeng Liu, Jonathan Crawford, Patrick M. Callahan, Alvin V. Terry, Christos Constantinidis, David T. Blake

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Acetylcholine in the neocortex is critical for executive function [1–3]. Degeneration of cholinergic neurons in aging and Alzheimer's dementia is commonly treated with cholinesterase inhibitors [4–7]; however, these are modestly effective and are associated with side effects that preclude effective dosing in many patients [8]. Electrical activation of the nucleus basalis (NB) of Meynert, the source of neocortical acetylcholine [9, 10], provides a potential method of improving cholinergic activation [11, 12]. Here we tested whether NB stimulation would improve performance of a working memory task in a nonhuman primate model. Unexpectedly, intermittent stimulation proved to be most beneficial (60 pulses per second, for 20 s every minute), whereas continuous stimulation often impaired performance. Pharmacological experiments confirmed that the effects depended on cholinergic activation. Donepezil, a cholinesterase inhibitor, restored performance in animals impaired by continuous stimulation but did not improve performance further during intermittent stimulation. Intermittent stimulation was rendered ineffective by either nicotinic or muscarinic receptor antagonists. In the months after stimulation began, performance also improved in sessions without stimulation. Our results reveal that intermittent NB stimulation can improve working memory, a finding that has implications for restoring cognitive function in aging and Alzheimer's dementia.

Original languageEnglish (US)
Pages (from-to)2640-2646.e4
JournalCurrent Biology
Volume27
Issue number17
DOIs
StatePublished - Sep 11 2017

Keywords

  • Alzheimer's
  • Nucleus Basalis of Meynert
  • deep brain stimulation
  • executive function
  • nonhuman primate
  • working memory

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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