Neurocircuitry of impaired insight in addiction: relevance to aberrant self-related processing

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 DESCRIPTION (provided by applicant): Impaired self-awareness of illness severity (insight) is associated with increased morbidity and poorer treatment outcome across multiple neuropsychiatric diseases. Although the study of insight has traditionally been limited to psychotic disorders (e.g., schizophrenia, mania), emerging theory and evidence suggest that this construct may also be highly relevant to drug addiction. In particular, addicted individuals often overestimate their addiction-related self-control, underestimate their neurocognitive impairments, and fail to seek treatment when it is warranted. In this R21 application, we provide the first direct investigation of insight impairment in drug addiction and its underlying neurobiology. Individuals with cocaine use disorder (CUD) and matched healthy controls (HC) will complete a brand-new functional magnetic resonance imaging (fMRI) insight task, during which they will respond to probes about the severity of their drug use. Specific Aims include uncovering the behavioral and neural correlates (both task and baseline resting-state) of impaired insight in CUD, and then validating this task via measures of social-cognitive functioning (self-awareness and emotional awareness) and drug use. We hypothesize that this fMRI insight task will identify a subpopulation of CUD with impaired insight into their addiction severity, which in these individuals will be associated with focal- and network-related deficits of the rostral anterior cingulate cortex extending into the ventromedial prefrontal cortex (rACC/vmPFC). This region, insofar as it mediates personal relevance and is disrupted in addiction and other psychopathologies, indeed provides a plausible candidate region for studying insight. We further hypothesize that this insight impairment and its underlying functional deficits will correlate with reduced social-cognitive functioning and increased drug use. Taken together, in this project we map a newly appreciated addiction- related symptom (insight) onto functional deficits of corticolimbic circuitry that mediate self-related processing. This approach can then be applied to other diseases of impaired insight (e.g., schizophrenia, mania), with the goal of identifying a common thread (insight) that links drug addiction with these other disorders. Even more broadly, studying impaired insight vis-à-vis general abnormalities of core social-cognitive functioning (i.e., tagging behavior and emotions with personal relevance and emotional salience in association with rACC/vmPFC function) could even help illuminate the basic science of social-cognitive processing in health.