Nicotinic receptor modulation of the default mode network
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ORIGINAL INVESTIGATION
Nicotinic receptor modulation of the default mode network Britta Hahn 1 & Alexander N. Harvey 1 & Marta Concheiro-Guisan 2 & Marilyn A. Huestis 2 & Thomas J. Ross 2 & Elliot A. Stein 2 Received: 16 July 2020 / Accepted: 10 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Previous neuroimaging studies of cognition involving nicotinic acetylcholine receptor (nAChR) agonist administration have repeatedly found enhanced task-induced deactivation of regions of the default mode network (DMN), a group of brain systems that is more active at rest and mediates task-independent thought processes. This effect may be related to pro-cognitive nAChR agonist effects Objectives The present study sought to test whether nAChR modulation of the DMN is bi-directional, i.e., whether a nAChR antagonist would reduce task-induced deactivation. Methods Eighteen healthy non-smokers underwent functional magnetic resonance imaging while performing a letter N-back task. Scans were performed after nicotine administration (7 mg/24 h, transdermally), after administration of the nAChR antagonist mecamylamine (7.5 mg, p.o.), and after double placebo, in counterbalanced sequence. Blood-oxygen-level-dependent (BOLD) signal was analyzed within ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC) regions of interest—central hubs of the DMN in which consistent nAChR agonist–induced changes had previously been identified. Results Nicotine enhanced hit rate in both the 0-back and 2-back condition, while mecamylamine slowed reaction time in the 2back condition. Mecamylamine reduced task-induced deactivation of vmPFC and PCC. Nicotine had no significant effects on the BOLD signal. Conclusions The finding that nAChR tone reduction by mecamylamine weakened task-induced DMN deactivation indicates that a constant tone of nAChR activation helps regulate DMN activity in healthy individuals. This suggests that low nAChR tone may play a causal role in DMN dysregulation seen in conditions such as mild cognitive impairment or Alzheimer’s disease. Keywords Cognition . Deactivation . Default mode network . fMRI . Mecamylamine . Nicotine . Nicotinic acetylcholine receptor . N-back
Introduction Much evidence has built up suggesting that nicotine and other nicotinic acetylcholine receptor (nAChR) agonists can enhance cognitive performance, as reported with particular consistency in tests of attention (Hahn 2015; Heishman et al. 2010; Newhouse et al. 2004; Stolerman et al. 1995). Several
* Britta Hahn [email protected] 1
University of Maryland School of Medicine, Maryland Psychiatric Research Center, P.O. Box 21247, Baltimore, MD 21228, USA
2
Neuroimaging Research Branch, National Institute on Drug Abuse Intramural Research Program, 251 Bayview Blvd, Suite 200, Baltimore, MD 21224, USA
disease states marked by cognitive deficits involve nAChR hypofunction, most prominently Alzheimer’s disease, mild cognitive impairment, and schizophrenia (Adams and Stevens 2007; Contest
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