A cholinergic mechanism of impulsive response in young adult cigarette smokers

Yale University, New Haven CT

Investigators

Linked publications & trials

Abstract

Abstract/Summary Cigarette smokers experience cognitive deficits when they refrain from smoking, reflecting the chronic effects of nicotine on the brain. Nicotine influences cerebral functions by way of its action on nicotinic receptors and the basal nucleus of Meynert (BNM) provides the primary source of cholinergic inputs to the cerebral cortex. Brain regions critical to cognitive control, including the medial frontal cortex (MFC), are reciprocally connected to the BNM. In preclinical studies BNM neurons respond to salient stimuli to support motivated behavior and MFC control of BNM activity may interrupt these fast, habitual responses. It is possible that the MFC BNM circuit functions are compromised such that smokers exhibit attentional bias to smoking cues and inability to abstain from smoking. However, this cholinergic circuit has received little attention in extant imaging literature of nicotine addiction. Employing a chemically defined stereotaxic template of the BNM, we recently characterized whole-brain functional connectivity of the BNM and how BNM-MFC connectivity is related to dependence level in cigarette smokers. The present study builds on this work and proposes to investigate how BNM and MFC respond to attentional bias and control of impulsive response to smoking cues in young adult cigarette smokers in overnight abstinence vs. in satiation. We hypothesized higher BNM responses to smoking cues and diminished MFC responses and MFC-BNM functional connectivity during responses to smoking cues in abstinence vs. satiation. We also hypothesized that the neural markers may exhibit individual variation in association with nicotine dependence level and will explore sex differences in these behavioral and neural markers. We will test these hypotheses in a within-subject experiment of 40 young adult smokers (half women) in two sessions, when they are either sated or abstinent, with the order counter-balanced across participants. The specific aims are to 1) examine attentional bias (reaction time difference between smoking and neutral cues) and the neural bases of attentional bias in a dot probe task; 2) examine inhibitory control (as indexed by stop signal reaction time) of response to smoking vs. neutral cues and the neural bases of impulse control in a stop signal task. Successful cessation requires self control to resist smoking urges. The study may provide data to shed light on how the cholinergic basal forebrain and MFC interacts to regulate smoking behavior.