Chronic Cocaine Use and White Matter Coherence: A Diffusion Tensor Imaging Study.

OBJECTIVE: Chronic substance use and its effects on brain function and structure has long been of interest to clinicians and researchers. Prior cross-sectional comparisons of diffusion tensor imaging (DTI) metrics have suggested deleterious effects of chronic substance use (i.e., cocaine use) on white matter coherence. However, it is unclear how these effects may replicate across geographic regions when examined with similar technologies. In this study, we sought to conduct a replication of previous work in this area and determine whether there are any patterns of persistent differences in white matter microstructure between individuals with a history of cocaine use disorder (CocUD, according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) and healthy controls. METHOD: A total of 46 participants (21 healthy controls, 25 chronic cocaine users) were recruited from the Richmond, Virginia metropolitan area. Information regarding past and current substance use was collected from all participants. Participants also completed structural and DTI scans. RESULTS: Consistent with previous DTI studies, significant differences were found between fractional anisotropy (FA) and axial diffusivity (AD) CocUD and controls, with CocUD showing lower FA and AD in the right inferior and superior longitudinal fasciculus, the genu, body, and splenium of the corpus callosum, and the anterior, posterior, and superior corona radiata, among several other regions. These differences were not significant for other diffusivity metrics. Lifetime alcohol consumption was greater in the CocUD group, but lifetime alcohol consumption did not show a significant linear relationship with any of the DTI metrics in within-group regression analyses. CONCLUSIONS: These data align with previously reported declines in white matter coherence in chronic cocaine users. However, it is less clear whether comorbid alcohol consumption results in an additive deleterious effect on white matter microstructure.

Blunted prefrontal signature of proactive inhibitory control in cocaine use disorder.

BACKGROUND: Impulsivity is an established risk factor for substance use disorder (SUD). Integral to SUD recovery is proactive control (leveraging information about a potential need for behavioral restraint to marshal increased cognitive resources toward inhibition) when cues for drug use are unavoidable. However, proactive control is little studied in SUD, and is merely inferred from post-error performance adjustments. METHODS: We probed covert neurocircuit signatures of proactive control in persons with SUD, as well as the moderating effects of incentives for successfully exerting proactive control. We administered a Monetary Incentive Stop Task (MIST) during functional magnetic resonance imaging of adults with cocaine use disorder (CUD; n = 21) and healthy controls (n = 21). The MIST blended the reward and loss-anticipatory cues of the Monetary Incentive Delay (MID) Task with a variant of the Stop-Signal Task, in which target color signaled whether or not withholding a response might be necessary. RESULTS: In controls, but not in CUD participants, targets that signaled a potential need to stop (as a contrast with targets that signaled no need to stop) activated portions of right operculum akin to activation commonly elicited by stop signals, despite no actual stop signal. Across all participants, this proactive control activation did not relate to task behavior or to questionnaire impulsivity. Anticipatory incentive cues did not recruit ventral striatum. CONCLUSIONS: These data suggest that persons with CUD show blunted covert signatures of attention and proactive control. This potentially accounts in part for the role of poor executive function in relapse vulnerability.

Cingulo-hippocampal effective connectivity positively correlates with drug-cue attentional bias in opioid use disorder.

Individuals with opioid use disorder (OUD) often relapse when exposed to opioid-related cues. Previous functional magnetic resonance imaging (fMRI) studies have identified neuronal corticolimbic changes related to drug cue reactivity in OUD. However, the corresponding manner in which brain regions interact is still unclear. Effective (directional) connectivity was analyzed using dynamic causal modeling of fMRI data acquired from 27 OUD participants (13 with OUD and 14 with OUD and cocaine use disorder [OUD+CUD]), while performing an opioid-word Stroop task. Participants were shown opioid and neutral words presented in different colors and were instructed to indicate word color but ignore word meaning. The effects of opioid words relative to neutral words on effective connectivity and on behavioral reaction time were defined as modulatory change and attentional bias, respectively. For all the 27 participants, left anterior cingulate cortex (ACC) to right hippocampus effective connectivity exhibited the largest modulatory change, which was positively correlated with attentional bias. The findings for the ACC to hippocampus EC were consistent across OUD and CUD found in a previous study.

Diffusion tensor imaging and decision making in cocaine dependence.

BACKGROUND: Chronic stimulant abuse is associated with both impairment in decision making and structural abnormalities in brain gray and white matter. Recent data suggest these structural abnormalities may be related to functional impairment in important behavioral processes. METHODOLOGY/PRINCIPAL FINDINGS: In 15 cocaine-dependent and 18 control subjects, we examined relationships between decision-making performance on the Iowa Gambling Task (IGT) and white matter integrity as measured by diffusion tensor imaging (DTI). Whole brain voxelwise analyses showed that, relative to controls, the cocaine group had lower fractional anisotropy (FA) and higher mean of the second and third eigenvalues (lambda perpendicular) in frontal and parietal white matter regions and the corpus callosum. Cocaine subjects showed worse performance on the IGT, notably over the last 40 trials. Importantly, FA and lambda perpendicular values in these regions showed a significant relationship with IGT performance on the last 40 trials. CONCLUSIONS: Compromised white matter integrity in cocaine dependence may be related to functional impairments in decision making.

Diffusion tensor imaging in cocaine dependence: regional effects of cocaine on corpus callosum and effect of cocaine administration route.

Recent studies demonstrated that diffusion tensor imaging (DTI) can provide information regarding white matter integrity of the corpus callosum (CC). In this study, DTI parameters were compared between cocaine dependent subjects (CDs) and non-drug using controls (NCs) in midsagittal CC. DTI images were acquired from 19 CDs and 18 age-matched NCs. The midsagittal CC was segmented into: genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. Linear mixed models analyses showed that, relative to NCs, CDs had lower fractional anisotropy (FA), higher radial diffusivity (lambda(perpendicular)), and higher mean diffusivity (D(av)) in the isthmus; higher lambda(perpendicular) and D(av) in the rostral body; and lower FA in the splenium. After including mass of lifetime alcohol use in the mixed model analysis of covariance (ANCOVA) as a covariate, significant between group differences in lambda(perpendicular) in the rostral body and isthmus remained. These results suggest that alterations in lambda(perpendicular) in the rostral body and isthmus were mainly due to cocaine use, consistent with previous studies showing that cocaine may alter myelin integrity. Between group differences in FA in the isthmus and splenium, and D(av) in the rostral body and isthmus became non-significant after inclusion of alcohol use as a covariate. This is suggestive of alcohol influencing these values, or may be related to the decreased degrees of freedom for these effects. Consistent with clinical data of greater severity of drug use in smoked versus intranasal cocaine, subjects who smoked cocaine showed lower FA and higher lambda(perpendicular) compared to intranasal CDs.