Development of MRI Techniques for Drug-Abuse Applications

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

1. Functional connectivity of dorsolateral prefrontal cortex predicts cocaine relapse: implications for neuromodulation treatment Relapse is one of the most perplexing problems of addiction. The dorsolateral prefrontal cortex is crucially involved in numerous cognitive and affective processes that are implicated in the phenotypes of both substance use disorders and other neuropsychiatric diseases and has become the principal site to deliver transcranial magnetic stimulation for their treatment. However, the dorsolateral prefrontal cortex is an anatomically large and functionally heterogeneous region, and the specific dorsolateral prefrontal cortex locus and dorsolateral prefrontal cortex-based functional circuits that contribute to drug relapse and/or treatment outcome remain unknown. We systematically investigated the relationship of cocaine relapse with functional circuits from 98 dorsolateral prefrontal cortex regions-of-interest defined by evenly sampling the entire surface of bilateral dorsolateral prefrontal cortex in a cohort of cocaine dependent patients (n = 43, 5 Fr) following a psychosocial treatment intervention. Cox regression models were utilized to predict relapse likelihood based on dorsolateral prefrontal cortex functional connectivity strength. Functional connectivity from only 3 of the 98 dorsolateral prefrontal cortex loci, one in the left and two in the right hemisphere, significantly predicted cocaine relapse with an accuracy of 83.9%, 84.6% and 85.4%, respectively. Combining all three loci significantly improved prediction validity to 87.5%. Protective and risk circuits related to these dorsolateral prefrontal cortex loci were identified that have previously been implicated to support 'bottom up' drive to use drug and 'top down' control over behaviour together with social emotional, learning and memory processing. (Zhai et al., Brain Communication, 2021) 2. Temporal dynamic interaction between the large-scale brain networks predicts cocaine dependence level Addiction has been conceptualized, from a neurocircuitry perspective, as a neuropsychiatric disease with disrupted interactions between large-scale brain networks underlying its multifaceted phenotypes. While current understanding on the interaction of brain networks is mostly based on static functional connectivity, accumulating evidence began to reveal the role of temporal dynamics of these networks in brain function and dysfunction. We herein investigate temporal dynamics between salience, default-mode, and executive-control networks in cocaine use disorder and their relationship with the level of cocaine dependence. Using an innovative time-frame analysis approach on resting-state fMRI, we examined altered dynamic configurations in the aforementioned three large-scale brain systems with a temporal resolution of 2s in a cohort of 54 cocaine users (42M, 12F) and 54 healthy controls (37M, 17F). Two composite dynamic indices were developed to quantify occurrence rate and transfer probability of brain states. In addition, we assessed association between the altered dynamics of these brain networks and cocaine dependence. We successfully identified three dynamic brain states that resemble the canonical large-scale networks of the salience, default-mode, and executive-control. Compared to healthy controls, cocaine users exhibited higher occurrence rate in default-mode state and higher transition probability from salience state to default-mode state. Furthermore, the composite index of state transition probability depicting the dynamic interaction between these three large-scale brain states showed significant negative correlation with cocaine dependence. Our study identified abnormal state occurrence rate and state transition probability in cocaine use disorder, and the composite index of state transition probability was associated with cocaine dependence. These results provide novel evidence of the disrupted temporal dynamics of large-scale brain networks in substance use disorder. (Under submission) 3. High-frequency TMS combined with fMRI reveals site differences at the dorsolateral prefrontal cortex Transcranial magnetic stimulation (TMS) has been extensively used for the treatment of certain neurological and psychiatric disorders. Despite promising treatment efficacy, the fundamental neural mechanism of TMS remains elusive. In the present study, we used simultaneous TMS and functional magnetic resonance imaging (fMRI) to map the modulatory effect of TMS when it was applied over three different sites in the dorsolateral prefrontal cortex. The results showed that TMS affected the stimulus sites, as well as, remote brain areas, with some areas/networks (posterior insula, superior temporal gyrus, salience network, amygdala, hippocampus, occipital lobe, angular gyrus) being commonly affected by TMS regardless of the stimulus sites, but other areas/networks (dorsal anterior cingulate cortex, dorsomedial prefrontal cortex, striatum, thalamus, executive control network, rostral anterior cingulate cortex, ventromedial prefrontal cortex, temporal pole, medial orbitofrontal cortex) showing TMS effects specific to the sites of the stimulation. Our findings support the notion that TMS could act through a top-down mechanism, affecting deeper subcortical areas by directly stimulating cortical regions. (Under submission)