There are no effective treatments for cocaine use disorder (CUD), a chronic, relapsing brain disease characterized by dysregulated circuits related to cue reactivity, reward processing, response inhibition, and executive control. Transcranial magnetic stimulation (TMS) has the potential to modulate circuits and networks implicated in neuropsychiatric disorders, including addiction. Although acute applications of TMS have reduced craving in urine-negative cocaine users, the tolerability and safety of administering accelerated TMS to cocaine-positive individuals is unknown. As such, we performed a proof-of-concept study employing an intermittent theta-burst stimulation (iTBS) protocol in an actively cocaine-using sample. Although our main goal was to assess the tolerability and safety of administering three iTBS sessions daily, we also hypothesized that iTBS would reduce cocaine use in this non-treatment seeking cohort. We recruited 19 individuals with CUD to receive three open-label iTBS sessions per day, with approximately a 60-min interval between sessions, for 10 days over a 2-week period (30 total iTBS sessions). iTBS was delivered to left dorsolateral prefrontal cortex (dlPFC) with neuronavigation guidance. Compliance and safety were assessed throughout the trial. Cocaine use behavior was assessed before, during, and after the intervention and at 1- and 4-week follow-up visits. Of the 335 iTBS sessions applied, 73% were performed on participants with cocaine-positive urine tests. Nine of the 14 participants who initiated treatment received at least 26 of 30 iTBS sessions and returned for the 4-week follow-up visit. These individuals reduced their weekly cocaine consumption by 78% in amount of dollars spent and 70% in days of use relative to pre-iTBS cocaine use patterns. Similarly, individuals reduced their weekly consumption of nicotine, alcohol, and THC, suggesting iTBS modulated a common circuit across drugs of abuse. iTBS was well-tolerated, despite the expected occasional headaches. A single participant developed a transient neurological event of uncertain etiology on iTBS day 9 and cocaine-induced psychosis 2 weeks after discontinuation. It thus appears that accelerated iTBS to left dlPFC administered in active, chronic cocaine users is both feasible and tolerable in actively using cocaine participants with preliminary indications of efficacy in reducing both the amount and frequency of cocaine (and other off target drug) use. The neural underpinnings of these behavioral changes could help in the future development of effective treatment of CUD.
Age is one of the best predictors of antisocial behavior. Risk models of recidivism often combine chronological age with demographic, social and psychological features to aid in judicial decision-making. Here we use independent component analyses (ICA) and machine learning techniques to demonstrate the utility of using brain-based measures of cerebral aging to predict recidivism. First, we developed a brain-age model that predicts chronological age based on structural MRI data from incarcerated males (n = 1332). We then test the model's ability to predict recidivism in a new sample of offenders with longitudinal outcome data (n = 93). Consistent with hypotheses, inclusion of brain-age measures of the inferior frontal cortex and anterior-medial temporal lobes (i.e., amygdala) improved prediction models when compared with models using chronological age; and models that combined psychological, behavioral, and neuroimaging measures provided the most robust prediction of recidivism. These results verify the utility of brain measures in predicting future behavior, and suggest that brain-based data may more precisely account for important variation when compared with traditional proxy measures such as chronological age. This work also identifies new brain systems that contribute to recidivism which has clinical implications for treatment development.
