Functional alteration in frontolimbic systems relevant to moral judgment in cocaine-dependent subjects

• Published in: Addiction biology Vol. 19; no. 2; pp. 272 - 281
• Main Authors: Verdejo-Garcia, Antonio, Contreras-Rodríguez, Oren, Fonseca, Francina, Cuenca, Aida, Soriano-Mas, Carles, Rodriguez, Joan, Pardo-Lozano, Ricardo, Blanco-Hinojo, Laura, de Sola Llopis, Susana, Farré, Magí, Torrens, Marta, Pujol, Jesús, de la Torre, Rafael
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2014; John Wiley & Sons, Inc
• Subjects: Addiction; Adolescent; Adult; Brain; Brain Mapping - methods; Case-Control Studies; Cerebral Cortex - physiopathology; Cocaine; Cocaine-Related Disorders - physiopathology; Cocaine-Related Disorders - psychology; Data Interpretation, Statistical; Decision making; Female; frontolimbic systems; functional connectivity; Humans; Judgment - physiology; Limbic System - physiopathology; Magnetic Resonance Imaging - methods; Male; Middle Aged; moral dilemmas; Morals; Neural Pathways - physiopathology; Periaqueductal Gray - physiopathology; Photic Stimulation - methods; Prefrontal Cortex - physiopathology; Young Adult; moral dilemmas; functional connectivity; cocaine; frontolimbic systems
• DOI: 10.1111/j.1369-1600.2012.00472.x
• ISSN: 1355-6215; 1369-1600

Cocaine addiction is characterized by persistent decision‐making deficits, which are linked to structural and functional abnormalities in frontolimbic systems. Moral judgment is as a special instance of decision making, in which both cognitive and emotional signals must be adequately integrated to decide how to resolve moral dilemmas. Here, we employed a moral dilemmas functional magnetic resonance imaging (fMRI) task to explore possible alterations of frontolimbic systems in cocaine‐dependent subjects. We also explored if these alterations relate to more basic deficits in functional connectivity within these systems during spontaneous resting‐state activation. Ten cocaine‐dependent subjects and 14 non‐drug‐using controls participated in the study. Cocaine‐dependent subjects were carefully selected to discard potentially confounding co‐morbidities, and they underwent a uniform supervised abstinence period of 10 days. Both groups were scanned, and fMRI maps were generated to identify (1) brain response to moral dilemmas; and (2) the strength of functional connectivity within frontolimbic systems during resting‐state. During the moral dilemmas task, cocaine‐dependent subjects showed reduced activation involving frontolimbic structures as the anterior cingulate cortex (ACC), left insula and brain stem. Connectivity analyses showed that cocaine users had less resting‐state functional connectivity between ACC, thalamus, insula and brain stem. These results demonstrate that cocaine‐dependent subjects have functional alterations in the frontolimbic systems that support moral judgment and social decision making. During the functional resonance imaging moral decision‐making task (e.g., “would you throw a dying person into the sea to float a lifeboat full of survivors?”), cocaine dependent users displayed significantly reduced signal in brain regions involved in generating and instantiating emotions (i.e., insula, anterior cingulate cortex and brainstem periacqueductal gray). We reason that cocaine dependent users exhibit blunted responsiveness of the brain network that normally anticipates potentially aversive emotional consequences of complex social decisions.