Nicotinic modulation of salience network connectivity and centrality in schizophrenia

Abstract

Although functional abnormalities of the salience network are associated with schizophrenia, the acute effects of nicotine on its function and network dynamics during the resting state in patients are poorly understood. In this study, the effects of a 7 mg nicotine patch (vs. placebo) on salience network connectivity were examined in 17 patients with schizophrenia and 19 healthy subjects. We hypothesized abnormal connectivity between the salience network and other major networks (e.g. executive network) in patients under placebo administration and amelioration of this difference after nicotine. We also examined effects of nicotine on betweenness centrality (a measure of the influence of a region on information transfer throughout the brain) and local efficiency (a measure of local information transfer) of the network. A hybrid independent component analysis (ICA) / seed-based connectivity approach was implemented in which the salience network was extracted by ICA and cortical network peaks (anterior cingulate cortex (ACC), left and right insula) were used as seeds for whole-brain seed-to-voxel connectivity analysis. Significant drug X diagnosis interactions were observed between the ACC seed and superior parietal lobule and ventrolateral prefrontal cortex. A significant interaction effect was also observed between the left insula seed and middle cingulate cortex. During placebo conditions, abnormal connectivity predicted negative symptom severity and lower global functioning in patients. A significant drug X diagnosis interaction was also observed for betweenness centrality of the ACC. These results suggest that nicotine may target abnormalities in functional connectivity between salience and executive network areas in schizophrenia as well as affect the ability of the salience network to act as an integrator of global signaling in the disorder.

A modality‐specific dysfunction of pain processing in schizophrenia

“…Similar to LEP responses, vertex potentials elicited by intense stimuli belonging to different sensory modalities (Mouraux & Iannetti, ) largely reflect saliency‐related neural processes possibly related to the detection of relevant changes in the sensory environment (Downar, Crawley, Mikulis, & Davis, ). Considering that N2 wave is mainly generated from the insula that is an interoceptive integration brain structure playing a crucial role in the salience network, as it conveys multisensory information about internal body state and external surrounding environment (Craig, ), previous studies suggested that dysfunction of sensory information processing across modalities in SCZ patients could represent an epiphenomenon of salience network dysfunctions (Alustiza et al, ; Liddle et al, ; Minichino et al, ; Palaniyappan & Liddle, ; Potvin et al, ; Smucny, Wylie, Kronberg, Legget, & Tregellas, ). The salience network is involved in detecting and filtering salient stimuli and functions to segregate the most prominent information among internal and external stimuli in order to guide behavior (Legrain, Iannetti, Plaghki, & Mouraux, ; Mouraux, Diukova, Lee, Wise, & Iannetti, ).…”

Nicotine-induced activation of caudate and anterior cingulate cortex in response to errors in schizophrenia

“…We did not find any significant effects of nicotine on resting state functional connectivity measures, consistent with our prior research in smokers with and without schizophrenia in which there was no effect of nicotine on the strength of functional connectivity between dACC and striatal regions (Moran et al 2012). However, a recent study using graph theoretical methods found enhanced nicotine-induced connectedness of the ACC in individuals with schizophrenia but the opposite effect of nicotine in healthy individuals (Smucny et al 2017). Our finding of negative correlations between right caudate activation and connectivity between right caudate and dACC/DLPFC suggests that enhanced nicotine-induced caudate activation in response to errors served as a compensatory mechanism to overcome functional dysconnectivity in the cognitive control network in schizophrenia.…”

Targeting neuronal dysfunction in schizophrenia with nicotine: Evidence from neurophysiology to neuroimaging

“…Our laboratory has recently expanded upon this work by examining effects of acute nicotine on resting state SN connectivity and topology in nonsmoking schizophrenia patients and healthy controls (Smucny et al, 2017). The SN was extracted by independent component analysis, and peaks from the extracted network used as seeds in a functional connectivity analysis.…”