Dorsolateral prefrontal cortex contributes to the impaired behavioral adaptation in alcohol dependence

Abstract

Substance-dependent individuals often lack the ability to adjust decisions flexibly in response to the changes in reward contingencies. Prediction errors (PEs) are thought to mediate flexible decision-making by updating the reward values associated with available actions. In this study, we explored whether the neurobiological correlates of PEs are altered in alcohol dependence. Behavioral, and functional magnetic resonance imaging (fMRI) data were simultaneously acquired from 34 abstinent alcohol-dependent patients (ADP) and 26 healthy controls (HC) during a probabilistic reward-guided decision-making task with dynamically changing reinforcement contingencies. A hierarchical Bayesian inference method was used to fit and compare learning models with different assumptions about the amount of task-related information subjects may have inferred during the experiment. Here, we observed that the best-fitting model was a modified Rescorla-Wagner type model, the “double-update” model, which assumes that subjects infer the knowledge that reward contingencies are anti-correlated, and integrate both actual and hypothetical outcomes into their decisions. Moreover, comparison of the best-fitting model's parameters showed that ADP were less sensitive to punishments compared to HC. Hence, decisions of ADP after punishments were loosely coupled with the expected reward values assigned to them. A correlation analysis between the model-generated PEs and the fMRI data revealed a reduced association between these PEs and the BOLD activity in the dorsolateral prefrontal cortex (DLPFC) of ADP. A hemispheric asymmetry was observed in the DLPFC when positive and negative PE signals were analyzed separately. The right DLPFC activity in ADP showed a reduced correlation with positive PEs. On the other hand, ADP, particularly the patients with high dependence severity, recruited the left DLPFC to a lesser extent than HC for processing negative PE signals. These results suggest that the DLPFC, which has been linked to adaptive control of action selection, may play an important role in cognitive inflexibility observed in alcohol dependence when reinforcement contingencies change. Particularly, the left DLPFC may contribute to this impaired behavioral adaptation, possibly by impeding the extinction of the actions that no longer lead to a reward.

The ease and sureness of a decision: evidence accumulation of conflict and uncertainty

“…In this case, what should be an easy decision perhaps more obvious to others is approached similar to a difficult decision. These findings are consistent with previous observations that AD show reduced discrimination of conflict (Beylergil et al, 2017) and risk levels (Zhu et al, 2016) with reported conflict-related deficits in dorso-lateral prefrontal cortex(DLPFC) (Boschin et al, 2016;Beylergil et al, 2017). In humans, the rate of evidence accumulation or the drift rate has been linked to the fronto-parietal network (Mulder et al, 2014).…”

A transdiagnostic dimensional approach towards a neuropsychological assessment for addiction: an international Delphi consensus study

“…Other shared dysfunctions include impaired self-control (e.g. reduced top-down, inhibitory control); linked to dysfunction in frontal-subcortical brain circuits ascribed to decision-making and goal-directed behaviour [22][23][24][25][26][27][28][29][30][31] which limit recovery [32][33][34][35][36]. While there may not be a single phenotype, or set of related neural processes, that confers vulnerability to addictions, impairment in these reward, stress and control-related processes may shape various pathways in and out of the addiction cycle.…”

Brain Network Underlying Executive Functions in Gambling and Alcohol Use Disorders: An Activation Likelihood Estimation Meta-Analysis of fMRI Studies

“…Our results suggested that individuals with AUD have difficulties in adapting their responses to the changing contingencies of reward-guided decision-making. Weaker activity in the bilateral DLPFC and the dorsal anterior cingulate, associated with loss of adaptive control of action selection, could be linked with cognitive inflexibility when reinforcement contingencies change [ 42 ]. In Wrase and colleagues [ 19 ], individuals with AUD showed weaker sensitivity in the putamen and in the caudate head during the anticipation of monetary gain.…”

“…Alcoholic brain damage seems to be partially reversible in some cases, although organic brain damage often remains permanent [ 40 , 41 ]. The neuropsychological consequences of AUD inevitably include a reduced control of behavior and the suppression of psychosocial adaptability skills [ 42 ]. Patients with AUD were found to show higher levels of impulsive choice than controls in a delay discounting task; also, higher delay discounting rates were markedly correlated with greater impulsivity trait scores [ 43 ].…”