Action Monitoring, Action Observation and Dopamine Genes as Predictors of Substan

The Mind Research Network, Albuquerque NM

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Abstract

DESCRIPTION (provided by applicant): The purpose of the present study is to characterize the integrity of neural processes underlying the monitoring of one's own and another's behavior within cocaine-dependent individuals, and to explore the relationship between the functionality of these processes and dopamine transporter and receptor polymorphisms. The ability to monitor one's own behavior serves as a central component of executive control, promoting adaptation in accord with environmental concerns, and preventing perseveration on dysfunctional action patterns. Cocaine dependent populations show deficits in executive control that may underlie their difficulty remaining abstinent by reducing the efficacy of top-down control mechanisms to guide appropriate goal-direction. Electrophysiological indicators of error monitoring have been localized within the anterior cingulate and are believed reliant on appropriate mesolimbic dopaminergic flow to the anterior cingulate. Chronic cocaine use has been linked to reduced dopaminergic tone in the anterior cingulate, potentially due to increased dopamine transporter availability and/or reduced D2 receptor binding. Chronic cocaine use may, then, attenuate error processing by interfering with dopamine-mediated monitoring performance. A similar error-related electrophysiological signature has been documented that occurs when one views another person make a mistake. This observer error-related negativity (oERN) appears well positioned to act as an underlying indicator of empathic concern. The ability to monitor another's behavior, in turn, may serve as the basis for observational learning, and may be influenced by characteristics such as perspective-taking ability and level of empathic concern. Low empathic concern may explain the high comorbidity with externalizing disorders within drug-abusing populations. The Mind Research Network has recently acquired a state-of-the-art mobile MRI scanner, which has been used to collect brain imaging data from over 700 inmates in the first two years of deployment. Clinical data indicates that over 65% of inmates suffer from serious substance abuse issues. The deployment of this mobile MRI system thus provides unprecedented access to a population of serious cocaine abusers with comorbid externalizing characteristics. With this access, we propose to collect multimodal (EEG/fMRI) data on 300 incarcerated participants, stratified into cocaine-abusing and non-cocaine-abuse groups, during performance of, and the observation of, a go/no-go response-inhibition task designed to elicit errors. Electrophysiological indicators of error monitoring will be computed from brain potential data, while hemodynamic activity from the anterior cingulate will be computed from the fMRI data. Saliva samples will also be collected from cocaine-dependent and matched healthy participants for investigation of dopamine transporter (SLC6A3) and receptor (DRD2 and DRD4) genotypes. Six-, 12- 18- and 24-month follow-up appointments will be used to evaluate relapse through analysis of hair and urine samples. The data obtained through this project will serve as the largest and most comprehensive investigation of cognitive and affective abnormalities within a sample of serious cocaine abusers, and the first major investigation into the relationship between these cognitive/affective abnormalities and dopaminergic polymorphisms. The research will thus provide important information regarding the neurocognitive and genetic underpinnings of cocaine dependency, and will serve as a gateway towards the development of future clinical treatment protocols. The ultimate mission of The Mind Research Network is the development of novel treatment programs for serious psychological and mental disorders, and our group envisions the data collected from this research as an important step towards future work focused on therepeutic and treatment applications.