Liam Nestor

Abstract:
Addiction to cigarettes presents with considerable health risks and induces high costs on healthcare resources. While the majority of cigarette smokers endorse the desire to quit, only a small percentage of quit attempts lead to full abstinence. Failure to achieve abstinence may arise from maladaptive reactivity in fronto-striatal regions that track positive and negative valence outcomes, thus biasing the choice to smoke in the presence of alternative, non-drug reinforcement. Alternatively, long-term nicotine abstinence may reveal neural substrates of adaptive valence outcome processing that promote and maintain smoking cessation. The present study set out to examine the neural correlates of operant response outcomes in current smokers, ex-smokers and matched controls using a monetary incentive delay task during functional MRI. Here we report that compared to controls, both current smokers and ex-smokers showed significantly less activation change in the left amygdala during positive response outcomes, and in the anterior cingulate cortex, during both positive and negative response outcomes. Ex-smokers, however, demonstrated significantly greater activation change compared to smokers and controls in the right amygdala during negative response outcomes. Activation change in the anterior cingulate cortex and middle frontal gyrus of smokers was significantly negatively correlated with nicotine dependence and cigarette pack-years. These results suggest a pattern of shared and divergent reactivity in current smokers and ex-smokers within corticolimbic regions that track both positive and negative operant response outcomes. Exaggerated adaptive processing in ex-smokers may promote long-term smoking cessation through amplified negative valence outcome monitoring.

Abstract:
Despite an increased understanding of nicotine addiction, there is a scarcity of research comparing the neural correlates of non‐drug reward between smokers and ex‐smokers. Long‐term changes in reward‐related brain functioning for non‐drug incentives may elucidate patterns of functioning that potentially contribute to ongoing smoking behaviour in current smokers. Similarly, examining the effects of previous chronic nicotine exposure during a period of extended abstinence may reveal whether there are neural correlates responsible for non‐drug reward processing that are different from current smokers. The current study, therefore, sets out to examine the neural correlates of reward and loss anticipation, and their respective outcomes, in smokers, ex‐smokers and matched controls using a monetary incentive delay task during functional magnetic resonance imaging. Here, we report that in the absence of any significant behavioural group differences, both smokers and ex‐smokers showed a significantly greater activation change in the lateral orbitofrontal/anterior insular cortex compared with smokers when anticipating both potential monetary gains and losses. We further report that ex‐smokers showed a significantly greater activation change in the ventral putamen compared with both controls and smokers and in the caudate compared with controls during the anticipation of potential monetary losses only. The results suggest that smoking may sensitize striato‐orbitofrontal circuitry subserving motivational processes for loss avoidance and reward gain in nicotine addiction.

Abstract:
Background The chronic use of cannabis has been associated with error processing dysfunction, in particular, hypoactivity in the dorsal anterior cingulate cortex (dACC) during the processing of cognitive errors. Given the role of such activity in influencing post-error adaptive behaviour, we hypothesised that chronic cannabis users would have significantly poorer learning from errors. Methods Fifteen chronic cannabis users (four females, mean age = 22.40 years, SD = 4.29) and 15 control participants (two females, mean age = 23.27 years, SD = 3.67) were administered a paired associate learning task that enabled participants to learn from their errors, during fMRI data collection. Results Compared with controls, chronic cannabis users showed (i) a lower recall error-correction rate and (ii) hypoactivity in the dACC and left hippocampus during the processing of error-related feedback and re-encoding of the correct response. The difference in error-related dACC activation between cannabis users and healthy controls varied as a function of error type, with the control group showing a significantly greater difference between corrected and repeated errors than the cannabis group. Conclusions The present results suggest that chronic cannabis users have poorer learning from errors, with the failure to adapt performance associated with hypoactivity in error-related dACC and hippocampal regions. The findings highlight a consequence of performance monitoring dysfunction in drug abuse and the potential consequence this cognitive impairment has for the symptom of failing to learn from negative feedback seen in cannabis and other forms of dependence.