Using Real-Time fRMI to Facilitate Neuromodulation to Drug-Cues in Adolescent Abu

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DESCRIPTION (provided by applicant): Recent neurocognitive theories of adolescent substance abuse posit differences in the developmental trajectories of cortical and limbic regions as contributing to the increased initiation of drug use during adolescence. A growing literature indicates that maturation of limbic regions occurs early in adolescence, and precedes that of cortical regions, which continue to develop through adolescence and into early adulthood. These differing maturation trajectories may lead the adolescent's reward centers to develop faster than the frontal regions capable of constraining them. As such, the administration of drugs may elicit an intensely rewarding experience, that the adolescent has a difficult time managing, with their still limited capacity for effective top-down control. This coincides with current models of cocaine abuse in adults, which propose that cocaine may alter sensitivity within mesocorticolimbic, leading to increased sensitivity to drug-related reward, yet decreased sensitivity to nondrug-related reward, and decreased executive control processes. One implication of this perspective is that the ability to recalibrate these altered reward sensitivities may serve as a viable treatment strategy for individuals with serious cocaine dependency. Emerging technology, such as real-time functional magnetic resonance imaging (rt-fMRI), affords the opportunity to provide individuals with online feedback regarding the current state of their neural activity. One valuable use of this technology may be to provide cocaine-dependent individuals with information regarding their neural response to drug-related and nondrug-related reward, and to utilize this "neuro-feedback" approach to train participants to gain control over their neural activity, and to rebalance altered reward sensitivities. Our team proposes to use the R21 mechanism to demonstrate efficacy of rt-fMRI technology within a sample of 40 adolescent cocaine-abusers while they perform a fairly standard cue-elicited craving paradigm. Prior to presentation of drug, nondrug and neutral pictures, participants will be provided with an aural instruction to either INCREASE, DECREASE, or WATCH, and will be instructed to try to increase or decrease activity within either nucleus accumbens or anterior cingulate. An on-screen "thermometer" will display to participants the current state of activity within the region of interest, which participants will be instructed to use as an aid for facilitating successful neuromodulation. Detailed data regarding subjective levels of reward and craving, and of the neuromodulatory strategies employed, will be collected. The primary aim is to demonstrate feasibility of this protocol in substance abusing adolescents, while simultaneously increasing our understanding of developmental characteristics that could influence this neuromodulatory process. Evidence supporting feasibility of rt-fMRI as a facilitator of neuromodulation would represent a critical step toward development of comprehensive substance abuse treatment programs for adolescent abusers, and may serve as a gateway for future work to achieve these treatment goals. PUBLIC HEALTH RELEVANCE: Recent models of substance abuse argue that the substance abuser may experience decreased neural activity in response to nondrug rewards, yet increased neural activity in response to drug rewards. Adolescent abusers, in particular, may be particularly susceptible to this imbalance, due to incomplete maturation of cortical regions capable of regulating these rewarding impulses. The present study will utilize rt-fMRI to test the feasibility of a "neurofeedback" approach for facilitating voluntary modulation of reward-related neural activity in adolescent cocaine abusers. The ability to undertake such voluntary neuromodulate may prove a viable treatment option for substance abuse disorders. The present work will provide a fundamental evaluation of this emerging technology, and will serve as a gateway for future work to conduct larger-scale clinical studies in substance-abusing populations.