Neurobiological Impact of Nicotinic Acetylcholine Receptor Agonists: An Activation Likelihood Estimation Meta-Analysis of Pharmacologic Neuroimaging Studies

Abstract

Background Nicotinic acetylcholine receptor (nAChR) agonists augment cognition among cigarette smokers and nonsmokers, yet the systems-level neurobiological mechanisms underlying such improvements are not fully understood. Aggregating neuroimaging results regarding nAChR agonists provides a means to identify common functional brain changes that may be related to pro-cognitive drug effects. Methods We conducted a meta-analysis of pharmacological neuroimaging studies within the activation likelihood estimation framework. We identified published studies contrasting a nAChR drug condition versus a baseline and coded each contrast by activity change direction (decrease or increase), participant characteristics (smokers or nonsmokers), and drug manipulation employed (pharmacological administration or cigarette smoking). Results When considering all studies, nAChR agonist administration was associated with activity decreases in multiple regions, including the ventromedial prefrontal cortex (vmPFC), posterior cingulate cortex (PCC), parahippocampus, insula, and the parietal and precentral cortices. Conversely, activity increases were observed in lateral frontoparietal cortices, the anterior cingulate cortex (ACC), thalamus, and cuneus. Exploratory analyses indicated that both smokers and nonsmokers showed activity decreases in the vmPFC and PCC, and increases in lateral frontoparietal regions. Among smokers, both pharmacological administration and cigarette smoking were associated with activity decreases in the vmPFC, PCC, and insula, and increases in the lateral PFC, dorsal ACC, thalamus, and cuneus. Conclusions These results provide support for the systems-level perspective that nAChR agonists suppress activity in default-mode network regions and enhance activity in executive control network regions in addition to reducing activation of some task-related regions. We speculate these are potential mechanisms by which nAChR agonists enhance cognition.

Encephalography Connectivity on Sources in Male Nonsmokers after Nicotine Administration during the Resting State

“…Since this study used simultaneous fMRI/EEG, the authors were able to correlate the functional connectivity of the default-mode network (by fMRI) with an objective measure of sedation (by EEG). Taking the fMRI studies together, the nicotine-induced decrease in the default-mode network activity found by Sutherland et al [60] indicates a possible nicotine-induced increase of vigilance. Anticipating our discussion, our EEG results suggest that nicotine does increase the neural signature of vigilance.…”

“…Furthermore, a meta-analysis of brain imaging data regarding nicotine appeared recently [60]. Although the authors did not specifically assess vigilance, they observed that nicotine decreases the activity in the default-mode network (a resting-state network), while increasing task-related brain regions.…”

SNAP-25a/b Isoform Levels in Human Brain Dorsolateral Prefrontal Cortex and Anterior Cingulate Cortex

“…Nicotinic acetylcholinergic receptors are widely distributed throughout the brain [36,37]. Smoking activates both the prefrontal cortex (BA9) and ACC (BA24) [38,39]. It is possible that the reduced pan (total) SNAP-25 BA9/BA24 ratio reflects smoking-induced alteration of the brain's acetylcholinergic distribution.…”

How neuroscience can inform the study of individual differences in cognitive abilities

“…Likewise, Rasmusson et al (2007) found that inactivation of prefrontal cortex inhibited sensory-evoked acetylcholine release in somatosensory cortex. In a meta-analysis of effects on neuroimaging, Sutherland et al (2015) concluded that nicotinic acetylcholine agonists reduce default-mode network activity and enhance executive control network regions. The basal forebrain thus appears to be an important efferent for the cortical regulation of the activity of central networks.…”