Biology subjects

Ross, T. J.

Publications and source records attributed to Ross, T. J..

3 recordsLinked to original sources

bioRxiv2020

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

BackgroundThe 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. MethodsTo 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. ResultsDuring 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. ConclusionsEmploying 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.

animal behavior and cognition↗

bioRxiv2019

Nicotine dependence (trait) and acute nicotinic stimulation (state) modulate attention but not cognitive control: converging fMRI evidence from Go-Nogo and Flanker tasks

AO_SCPCAPBSTRACTC_SCPCAPCognitive deficits during nicotine withdrawal may contribute to smoking relapse. However, interacting effects of chronic nicotine dependence and acute nicotine withdrawal on cognitive control are poorly understood. Here, we examine the effects of nicotine dependence (trait; smokers versus non-smoking controls), and acute nicotinic stimulation (state; administration of nicotine and varenicline, two FDA-approved smoking cessation aids, during abstinence), on two well-established tests of cognitive control, the Go-Nogo task and the Flanker task, during fMRI scanning. We compared performance and neural responses between these four pharmacological manipulations in a double-blind, placebo-controlled crossover design. As expected, performance in both tasks was modulated by nicotine dependence, abstinence and pharmacological manipulation. However, effects were driven entirely by conditions that required less cognitive control. When demand for cognitive control was high, abstinent smokers showed no deficits. By contrast, acutely abstinent smokers showed performance deficits in easier conditions and missed more trials. Go-Nogo fMRI results showed decreased inhibition-related neural activity in right anterior insula and right putamen in smokers and decreased dorsal anterior cingulate cortex activity on nicotine across groups. No effects were found on inhibition-related activity during the Flanker task, or on error-related activity in either task. Given robust nicotinic effects on physiology and behavioral deficits in attention, we are confident that pharmacological manipulations were effective. Thus, findings fit a recent proposal that abstinent smokers show decreased ability to divert cognitive resources at low or intermediate cognitive demand, while performance at high cognitive demand remains relatively unaffected, suggesting a primary attentional deficit during acute abstinence.

neuroscience↗

bioRxiv2019

Habenular and striatal activity during performance feedback are differentially linked with state-like and trait-like aspects of tobacco use disorder

Although tobacco use disorder is linked with functional alterations in the striatum, anterior cingulate cortex (ACC), and insula, preclinical evidence also implicates the habenula as a contributor to negative reinforcement mechanisms maintaining nicotine use. The habenula is a small and understudied epithalamic nucleus involved in reward and aversive processing that is hypothesized to be hyperactive during nicotine withdrawal thereby contributing to anhedonia. In a pharmacologic fMRI study involving administration of nicotine and varenicline, two relatively efficacious cessation aids, we utilized a positive and negative performance feedback task previously shown to differentially activate the striatum and habenula. By administering these nicotinic drugs (vs. placebos) to both overnight abstinent smokers (n=24) and nonsmokers (n=20), we delineated feedback-related functional alterations both as a function of a chronic smoking history (trait: smokers vs. nonsmokers) and as a function of drug administration (state: nicotine, varenicline). We observed that smokers showed less ventral striatal responsivity to positive feedback, an alteration not mitigated by drug administration, but rather correlated with higher trait-level addiction severity among smokers and elevated self-reported negative affect across all participants. Conversely, nicotine administration reduced habenula activity following both positive and negative feedback among abstinent smokers, but not nonsmokers; greater habenula activity correlated with elevated abstinence-induced, state-level tobacco craving among smokers and elevated social anhedonia across all participants. These outcomes highlight a dissociation between neurobiological processes linked with the trait of dependence severity and with the state of acute nicotine withdrawal. Interventions simultaneously targeting both aspects may improve currently poor cessation outcomes.\n\nOne-sentence teaserIn a pharmacological fMRI study, e dissociate brain alterations in the habenula linked with nicotine withdrawal and striatal alterations linked with addiction.

neuroscience↗