Time varying connectivity across the brain changes as a function of nicotine abstinence state

Abstract

Background:The Nicotine Withdrawal Syndrome (NWS) includes affective and cognitive disruptions whose incidence and severity vary across time during acute abstinence. However, most network-level neuroimaging employs static measures of resting state functional connectivity (rsFC), assuming time-invariance, and unable to capture dynamic brain-behavior relationships. Recent advances in rsFC signal processing allow characterization of "time varying connectivity" (TVC), which characterizes network communication between sub-networks that reconfigure over the course of data collection. As such, TVC may more fully describe network dysfunction related to the NWS. Methods:To isolate alterations in the frequency and diversity of communication across network boundaries as a function of acute nicotine abstinence we scanned cigarette smokers in the nicotine sated and abstinent states and applied a previously-validated method to characterize TVC at a network and nodal level within the brain. Results:During abstinence, we found brain wide decreases in the frequency of interactions between network nodes in different modular communities (i.e. temporal flexibility; TF). In addition, within a subset of the networks examined the variability of these interactions across community boundaries (i.e. spatiotemporal diversity; STD) also decreased. Finally, within two of these networks the decrease in STD was significantly related to NWS clinical symptoms. Conclusions:Employing multiple measures of TVC in a within subjects' design, we characterized a novel set of changes in network communication and link these changes to specific behavioral symptoms of the NWS. These reductions in TVC provide a meso-scale network description of the relative inflexibility of specific large-scale brain networks as a result of acute abstinence. Acute nicotine abstinence is a key early hurdle to smoking cessation as most cessation attempts fail within a week of their target quit day 1 . These poor treatment outcomes are due, in part, to components of the Nicotine Withdrawal Syndrome (NWS) precipitated by acute smoking abstinence. The aversive symptoms of the NWS both dissuade smokers from attempting to quit 2 and promote relapse via negative reinforcement-the relief of the withdrawal state 3-5 .The clinical presentation of the NWS includes increases in negative affect 6,7 , lapses of attention [8][9][10][11] , and punctate craving for nicotine 6 . Critically, across both subjective and objective measures of NWS symptoms, variability in onset, time course, and phenomenology is consistently observed 12-17 . For example, craving increases early and again late in the day 15 , and negative affect spikes intermittently following cessation 17 . Symptoms are more variable in withdrawn smokers after quitting than before, suggesting that smoking may buffer or constrain aversive symptoms, which are then "unleashed" by cessation 18 . The incidence of these NWS symptoms increases with increased acute psychosocial stress [19][20][21][22] . The volatility in affective disrupti...

Altered dynamic functional connectivity of insular subdivisions among male cigarette smokers

“…Furthermore, existing research has unveiled that smokers and non-smokers exhibit distinctive resting-state indices related to dynamic changes in localized neural activity, such as dynamic regional homogeneity (dReHo) and dynamic amplitude of low-frequency fluctuations (dALFF) (18). Previous studies employing dynamic functional connectivity (dFC) methods have found that smokers experience reduced temporal flexibility and spatiotemporal diversity in brain networks during acute withdrawal (19). However, there is a lack of systematic research on dFC of the insula subregions.…”