Neural Correlates of Reward-Based Spatial Learning in Persons with Cocaine Dependence

Abstract

Dysfunctional learning systems are thought to be central to the pathogenesis of and impair recovery from addictions. The functioning of the brain circuits for episodic memory or learning that support goal-directed behavior has not been studied previously in persons with cocaine dependence (CD). Thirteen abstinent CD and 13 healthy participants underwent MRI scanning while performing a task that requires the use of spatial cues to navigate a virtual-reality environment and find monetary rewards, allowing the functional assessment of the brain systems for spatial learning, a form of episodic memory. Whereas both groups performed similarly on the reward-based spatial learning task, we identified disturbances in brain regions involved in learning and reward in CD participants. In particular, CD was associated with impaired functioning of medial temporal lobe (MTL), a brain region that is crucial for spatial learning (and episodic memory) with concomitant recruitment of striatum (which normally participates in stimulus-response, or habit, learning), and prefrontal cortex. CD was also associated with enhanced sensitivity of the ventral striatum to unexpected rewards but not to expected rewards earned during spatial learning. We provide evidence that spatial learning in CD is characterized by disturbances in functioning of an MTL-based system for episodic memory and a striatum-based system for stimulus-response learning and reward. We have found additional abnormalities in distributed cortical regions. Consistent with findings from animal studies, we provide the first evidence in humans describing the disruptive effects of cocaine on the coordinated functioning of multiple neural systems for learning and memory.

Reward-Based Spatial Learning in Teens With Bulimia Nervosa

“…42 Dopaminergic dysfunction in reward circuits is documented in adults with both SUDs 24 and BN. 43 Cocaine-dependent men also show altered functioning of reward circuitry on our spatial task, 25 further pointing to dopaminergic, reward-circuit dysfunction in both disorders. Such functional abnormalities may influence the initial learning of binge-purge behaviors, consistent with the role of VS in the early stages of reinforcement-based learning 8 (in drug addiction 7 ).…”

“…25 These findings from adolescents with BN point to functional abnormalities within anterior hippocampus and fronto-striatal regions associated with reward-based learning and suggest that an increased sensitivity to positive PEs, together with deficient engagement of inferior frontal cortices, may contribute to the purported imbalance between top-down control and more bottom-up reward circuits that characterizes eating disorders. 44 Indeed, abnormal activation of anterior hippocampus and VS during the receipt of unexpected rewards (and increased sensitivity to positive PEs) in adolescents with BN suggests altered bottom-up representations of action–outcome associations that may contribute to the learned associations between food cues and maladaptive binge-eating behaviors.…”

“…24 Conversely, adults with severe cocaine use disorder over-engage limbic areas (VS and amygdala) when receiving unpredicted monetary rewards on our reward-based spatial learning task. 25 Whereas these findings from adults with SUD may be confounded by the chronic effects substance exposure and habitual drug-seeking behaviors, 26 the long-term effects of binge-eating and purging on mesolimbic circuits are less clear. 5 Thus, we sought to explore the functioning of these circuits in adolescents with BN, early in the course of illness and un-confounded by significant chronicity.…”

Reward Contingencies Improve Goal-Directed Behavior by Enhancing Posterior Brain Attentional Regions and Increasing Corticostriatal Connectivity in Cocaine Addicts

“…The third goal of the current study was to test whether ACD prefrontal impairment was related to an altered frontostriatal connectivity pattern, as previous studies have suggested [32,33]. We computed a psychophysiological analysis using the left DLPFC as a seed region because it was the only area that showed between-group differences in sensitivity to reward gradients in the PFC.…”

Disrupted Resting-State Brain Functional Architecture in Amphetamine-Type Stimulant Abusers

“…A previous study also discovered that in students who were referred to a college alcohol and drug assistance program, polydrug (containing club drugs such as methamphetamine, LSD and ketamine) cues produced significantly greater left inferior temporal gyrus activity compared with neutral cues [94]. Cocaine-dependent participants had increased neural functioning of the left inferior Disrupted Resting-State Brain Functional Architecture in Amphetamine-Type Stimulant Abusers temporal gyrus in the "reward" compared to the "no-reward" condition during reward-based spatial learning (a form of episodic memory) [95]. In comparison to a placebo, the left inferior temporal gyrus of those who used designer drugs containing benzylpiperazine (a worldwide safe and legal alternative to illicit recreational drugs, such as MDMA and methamphetamine) showed decreased activation in a Stroop task, especially during the incongruent condition [96].…”