title: Behavioral and Neural Signatures of Reduced Updating of Alternative Options in Alcohol-Dependent Patients during Flexible Decision-Making.
abstract: 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 = 43) versus healthy volunteers (n = 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.
  
  
  
  In addiction, patients maintain substance use despite devastating consequences and often report having no choice but to consume. These clinical observations have been theoretically linked to disturbed mechanisms of inference, for example, to difficulties when learning statistical regularities of the environmental structure to guide decisions. Using computational modeling, we demonstrate disturbed inference on alternative choice options in alcohol addiction. Patients neglecting "what might have happened" was accompanied by blunted coding of inference regarding alternative choice options in the medial prefrontal cortex. An impaired integration of alternative choice options implemented by the medial prefrontal cortex might contribute to ongoing drug consumption in the face of evident negative consequences.
authors: Max Planck Fellow Group "Cognitive and Affective Control of Behavioral Adaptation", Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany, reiter@cbs.mpg.de.|International Max Planck Research School on the Neuroscience of Communication (IMPRS NeuroCom), 04103 Leipzig, Germany.|Chair of Lifespan Developmental Neuroscience, Department of Psychology, TU Dresden, 01602 Dresden, Germany.
authors: Andrea M F
authors: 0000-0002-5209-3996
authors: AM
authors: Reiter
authors: Max Planck Fellow Group "Cognitive and Affective Control of Behavioral Adaptation", Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.|Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, 10115 Berlin, Germany.|Department of Neurology, Otto-von-Guericke University, 39118 Magdeburg, Germany.
authors: Lorenz
authors: 0000-0001-7392-5280
authors: L
authors: Deserno
authors: Soteria Clinic Leipzig, Helios Park-Klinikum Leipzig, 04289 Leipzig, Germany.
authors: Thomas
authors: T
authors: Kallert
authors: Max Planck Fellow Group "Cognitive and Affective Control of Behavioral Adaptation", Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.|Department of Neurology, Otto-von-Guericke University, 39118 Magdeburg, Germany.|Department of Behavioral Neurology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany and.
authors: Hans-Jochen
authors: HJ
authors: Heinze
authors: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, 10115 Berlin, Germany.
authors: Andreas
authors: 0000-0001-7392-5280
authors: A
authors: Heinz
authors: Max Planck Fellow Group "Cognitive and Affective Control of Behavioral Adaptation", Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany.|Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, 10115 Berlin, Germany.
authors: Florian
authors: F
authors: Schlagenhauf
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000503:physiopathology*; D001931:Brain Mapping; D002755:Choice Behavior; D005260:Female; D006801:Humans; D007858:Learning; D008297:Male; D001523:Mental Disorders / Q000209:etiology / Q000503:physiopathology*; D009473:Neuronal Plasticity; D017397:Prefrontal Cortex / Q000503:physiopathology*; D013647:Task Performance and Analysis