@article{3660a2f4bd5140c3b0b373e96990e4c4,
title = "Nucleus basalis stimulation enhances working memory by stabilizing stimulus representations in primate prefrontal cortical activity",
abstract = "Acetylcholine plays a critical role in the neocortex. Cholinergic agonists and acetylcholinesterase inhibitors can enhance cognitive functioning, as does intermittent electrical stimulation of the cortical source of acetylcholine, the nucleus basalis (NB) of Meynert. Here we show in two male monkeys how NB stimulation affects working memory and alters its neural code. NB stimulation increases dorsolateral prefrontal activity during the delay period of spatial working memory tasks and broadens selectivity for stimuli but does not strengthen phasic responses to each neuron's optimal visual stimulus. Paradoxically, despite this decrease in neuronal selectivity, performance improves in many task conditions, likely indicating increased delay period stability. Performance under NB stimulation does decline if distractors similar to the target are presented, consistent with reduced prefrontal selectivity. Our results indicate that stimulation of the cholinergic forebrain increases prefrontal neural activity, and this neuromodulatory tone can improve cognitive performance, subject to a stability-accuracy tradeoff.",
keywords = "acetylcholine, basal forebrain, cognition, monkey, neurophysiology",
author = "Qi, {Xue Lian} and Ruifeng Liu and Balbir Singh and David Bestue and Albert Compte and Vazdarjanova, {Almira I.} and Blake, {David T.} and Christos Constantinidis",
note = "Funding Information: Research reported in this paper was supported by NIH grants R01 MH097695 and RF1 AG060754 to C.C. and D.T.B. A.I.V. was supported by VA grant I01 BX003890. D.B. and A.C. were supported by the Spanish Ministry of Science and Innovation and European Regional Development Fund (Ref: RTI2018-094190-B-I00) and by the CERCA Programme/Generalitat de Catalunya. We wish to thank James Daunais, Kristopher Bunting, Austin Lodish, Sihai Li, and Junda Zhu for technical help; Alvin Terry for guidance with the design of the study; and John Murray and Joost Maier for valuable comments on the manuscript. The contents of this publication do not represent the views of the VA or the US Government. C.C. and D.T.B. designed the experiments. R.L. C.C. X.-L.Q. and D.T.B. performed surgeries. X.-L.Q. and C.C. conducted behavioral and neurophysiological experiments. X.-L.Q. B.S. D.B. A.C. and C.C. performed data analysis. A.I.V. conducted immunohistochemistry experiments. C.C. X.-L.Q. and D.T.B. wrote the manuscript, with input from all authors. The authors declare no competing interests. Funding Information: Research reported in this paper was supported by NIH grants R01 MH097695 and RF1 AG060754 to C.C. and D.T.B. A.I.V. was supported by VA grant I01 BX003890 . D.B. and A.C. were supported by the Spanish Ministry of Science and Innovation and European Regional Development Fund (Ref: RTI2018-094190-B-I00 ) and by the CERCA Programme/Generalitat de Catalunya . We wish to thank James Daunais, Kristopher Bunting, Austin Lodish, Sihai Li, and Junda Zhu for technical help; Alvin Terry for guidance with the design of the study; and John Murray and Joost Maier for valuable comments on the manuscript. The contents of this publication do not represent the views of the VA or the US Government. Publisher Copyright: {\textcopyright} 2021 The Author(s)",
year = "2021",
month = aug,
day = "3",
doi = "10.1016/j.celrep.2021.109469",
language = "English (US)",
volume = "36",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "5",
}