Identification and Modulation of Electrophysiological Markers of Reward Sensitivity, Relevance to Drug Addiction

Abstract

Drug addiction is primarily a disease of the brain's reward system. The resulting compromise in reward sensitivity traces its roots to the striatal reward circuitry, where excess dopamine is released by the acute administration of the drug of abuse; chronic use is in turn associated with a hypodopaminergic state. In individuals with cocaine use disorder (CUD), these maladaptive changes in striatal dopamine are shown to be predictive of the choice for cocaine over other non-drug rewards. This deficit in reward sensitivity may therefore be bi-pronged, such that CUD manifest hyposensitivity to non-drug-related rewards (e.g. money) as well as hypersensitivity to drug-related rewards, as associated with cue-induced craving. This thesis aims to study the electrocortical markers of reward sensitivity in healthy controls and compare them to CUD to highlight the electrophysiological manifestations of this dichotomous impairment in reward sensitivity, using electroencephalogram (EEG) and event-related potentials (ERP). Moreover, using multimodal neuroimaging techniques, their underlying neuroanatomical correlates are also explored. Finally, a proof-of-concept study is presented to show that the EEG/ERP markers associated with motivated attention (i.e. drug seeking) can be modulated using cognitive control. These findings establish the ground work for potential interventional and therapeutic use of EEG/ERP methods to reinforce cognitive control over craving and other drug-seeking behavior in CUD. Instead of using positron emission tomography (PET) or functional magnetic resonance imaging (both modalities are costly and location/facility specific; PET adds the additional cost of subjecting research participants to radiation), we demonstrate the use of non-invasive, portable, substantially less expensive and high temporal resolution EEG and ERP methods to track (and possibly correct) deficits in reward sensitivity in drug addiction.