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Zilverstand, A1, Parvaz, MA1, Moeller, SJ1, Alia-Klein, N1, Goldstein, RZ1

1Icahn School of Medicine at Mount Sinai, New York, New York, USA

Resting-state functional connectivity has emerged as a reliable marker of abnormal brain functioning in addiction. However, resting-state connectivity has rarely been investigated using a whole-brain approach and whole-brain resting-state-behavior studies are yet to be performed in individuals with cocaine use disorder (iCUD). By tapping into individual differences in brain connectivity at rest and in baseline cognitive functioning we aim to advance the study of the neurocognitive deficits underlying drug addiction, to ultimately develop targeted trainings for preventing relapse.

We assessed neuropsychological functioning with the Cambridge Neuropsychological Test Automated Battery (CANTAB) and acquired resting-state functional scans in iCUD (N=44) and gender-/race-matched healthy controls (N=31), covarying for age. Factor analysis on ten CANTAB variables (DMS, SSP, VRM, IED, SST) revealed a group difference (controls>iCUD) in an Inhibitory Control factor (three SST variables, loadings >0.70). We employed complex network analysis (graph theory) to regress connectivity onto Inhibitory Control scores. Measure of interest was functional integration, both locally (within-region: local efficiency) and globally (across large-scale brain networks: global efficiency). Within iCUD, we compared individuals with non-recent [iCUD- (urine negative; N=26)] and recent drug use [iCUD+ (urine positive; N=17)].

Individuals with drug addiction demonstrated linearly decreased global functional integration of the executive control network (e.g., cingulate/supplementary motor area), hippocampal region and subcortical brain regions (e.g., putamen) as a function of recency of use (iCUD+<iCUD-<Controls). The local functional integration in the visual stream (e.g., visual cortex, inferior/superior parietal) was linearly increased (iCUD+>iCUD->Controls). Global disintegration of the executive control network and increased local connectivity within visual regions were correlated (r=-0.61), indicating a shift in balance from frontal (and global) to sensory (and local) brain networks. Impaired Inhibitory Control partially overlapped with these effects, being linked to both decreased global functional integration and increased local connectivity within executive/memory circuit and visual cortex. In individuals with non-recent drug use (iCUD-) worse performance was associated with stronger abnormalities in resting-state connectivity.

These results extend previous reports to show that whole-brain connectivity states are altered as a function of Inhibitory Control and recency of cocaine use in iCUD. Targeting these whole-brain states by cognitive training may lead to development of novel interventions grounded in neuroscience.