Response Perseveration in Stimulant Dependence Is Associated with Striatal Dysfunction and Can Be Ameliorated by a D2/3 Receptor Agonist

Ersche, Karen D.; Roiser, Jonathan P.; Abbott, Sanja; Craig, Katy; Müller, Ulrich; Suckling, John; Ooi, Cinly; Shabbir, Shaila; Clark, Luke; Sahakian, Barbara J.; Fineberg, Naomi; Merlo‐Pich, Emilio; Robbins, Trevor W.; Bullmore, Edward T.

doi:10.1016/j.biopsych.2011.06.033

Cited by 119 publications

(169 citation statements)

References 56 publications

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“…Ropinirole acted as, albeit a weak, reinforcer in nonhuman primates (Freeman, Heal, McCreary, & Woolverton, 2012), which partly supports clinical data, suggesting that ropinirole marginally reduced craving in humans (Meini et al, 2012) and reduced the subjective intensity for the "cocaine rush" (Maremmani et al, 2011). Treatment with another dopamine D 2 agonist, pramipexole, caused perseverated responding in a reversal learning task, which was associated with stimulant dependence, rather than compulsive measures, suggesting additional efficacy for the potential treatment of SUD (Ersche et al, 2011). Together, these data support the dopamine replacement hypotheses, suggesting that clinically approved dopaminomimetic compounds might have clinical utility.…”

Section: L-dopasupporting

confidence: 56%

Psychostimulants

McCreary

Müller

Filip

2015

International Review of Neurobiology

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Section: L-dopasupporting

confidence: 56%

Psychostimulants

McCreary

Müller

Filip

2015

International Review of Neurobiology

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“…Deficits in cognitive flexibility are known in patients experiencing addiction (Bechara and Damasio, 2002;Garavan and Stout, 2005;Ersche et al, 2011;Goldstein and Volkow, 2011). In line with this, we demonstrate that alcohol-dependent patients show diminished behavioral adaptation in a dynamic environment.…”

Section: Disrupted Behavioral Adaptation In Addictionmentioning

confidence: 99%

“…Groups differed in terms of general cognition, smoking status, and gray matter density even though our results were robust when adjusting for these variables. Crosssectional studies in at-risk populations (Ersche et al, 2010;Reiter et al, 2016), and longitudinal designs are warranted to track the influence of dysfunctional behavioral control systems across different stages in the development of addiction. It is to be noted that our model was not able to capture one specific aspect of the observed choice behavior, namely the group ϫ phase interaction on correct choices due to particularly reduced performance in the middle and last phase.…”

Section: Neurochemical Considerationsmentioning

confidence: 99%

Behavioral and Neural Signatures of Reduced Updating of Alternative Options in Alcohol-Dependent Patients during Flexible Decision-Making

et al. 2016

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Addicted individuals continue substance use despite the knowledge of harmful consequences and often report having no choice but to consume. Computational psychiatry accounts have linked this clinical observation to difficulties in making flexible and goal-directed decisions in dynamic environments via consideration of potential alternative choices. To probe this in alcohol-dependent patients (n ϭ 43) versus healthy volunteers (n ϭ 35), human participants performed an anticorrelated decision-making task during functional neuroimaging. Via computational modeling, we investigated behavioral and neural signatures of inference regarding the alternative option. While healthy control subjects exploited the anticorrelated structure of the task to guide decision-making, alcohol-dependent patients were relatively better explained by a model-free strategy due to reduced inference on the alternative option after punishment. Whereas model-free prediction error signals were preserved, alcohol-dependent patients exhibited blunted medial prefrontal signatures of inference on the alternative option. This reduction was associated with patients' behavioral deficit in updating the alternative choice option and their obsessive-compulsive drinking habits. All results remained significant when adjusting for potential confounders (e.g., neuropsychological measures and gray matter density). A disturbed integration of alternative choice options implemented by the medial prefrontal cortex appears to be one important explanation for the puzzling question of why addicted individuals continue drug consumption despite negative consequences.

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“…Thus, intact episodic memory may be required to support the cognitive effort required in psychotherapies for CD. Whereas functional disturbances in habit learning systems are reported in substance use disorders (SUD) (Chiu et al, 2008;Ersche et al, 2011;Ghahremani et al, 2011;Park et al, 2010;Rose et al, 2012), the functioning of neural systems for episodic memory have not been assessed in CD. Additional disturbances in these systems would further support the learning model of human addiction, point to a putative mechanism of action for psychotherapies for CD, and offer additional targets for treatment development.…”

Section: Introductionmentioning

confidence: 99%

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

Tau

Marsh

Wang

et al. 2013

Neuropsychopharmacol

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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.

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Response Perseveration in Stimulant Dependence Is Associated with Striatal Dysfunction and Can Be Ameliorated by a D2/3 Receptor Agonist

Cited by 119 publications

References 56 publications

Psychostimulants

Psychostimulants

Behavioral and Neural Signatures of Reduced Updating of Alternative Options in Alcohol-Dependent Patients during Flexible Decision-Making

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

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