Abnormal structure of frontostriatal brain systems is associated with aspects of impulsivity and compulsivity in cocaine dependence

Abstract

A growing body of preclinical evidence indicates that addiction to cocaine is associated with neuroadaptive changes in frontostriatal brain systems. Human studies in cocaine-dependent individuals have shown alterations in brain structure, but it is less clear how these changes may be related to the clinical phenotype of cocaine dependence characterized by impulsive behaviours and compulsive drug-taking. Here we compared self-report, behavioural and structural magnetic resonance imaging data on a relatively large sample of cocaine-dependent individuals (n = 60) with data on healthy volunteers (n = 60); and we investigated the relationships between grey matter volume variation, duration of cocaine use, and measures of impulsivity and compulsivity in the cocaine-dependent group. Cocaine dependence was associated with an extensive system of abnormally decreased grey matter volume in orbitofrontal, cingulate, insular, temporoparietal and cerebellar cortex, and with a more localized increase in grey matter volume in the basal ganglia. Greater duration of cocaine dependence was correlated with greater grey matter volume reduction in orbitofrontal, cingulate and insular cortex. Greater impairment of attentional control was associated with reduced volume in insular cortex and increased volume of caudate nucleus. Greater compulsivity of drug use was associated with reduced volume in orbitofrontal cortex. Cocaine-dependent individuals had abnormal structure of corticostriatal systems, and variability in the extent of anatomical changes in orbitofrontal, insular and striatal structures was related to individual differences in duration of dependence, inattention and compulsivity of cocaine consumption.

Figure 1

Whole-brain maps of significant differences in grey matter volume between healthy volunteers and cocaine users. Voxels coloured blue indicate brain areas in which cocaine users have reduced grey matter volume compared with healthy volunteers, and voxels coloured red indicate brain areas in which cocaine users have abnormally increased grey matter volume. These results were generated by permutation testing of voxel cluster statistics with cluster-wise P < 0.001, at which level we expect less than one false positive cluster per map. The statistical results are overlaid on the FSL MNI152 standard T₁ image and the numbers beneath each section of the image refer to its position (mm) relative to the intercommissural plane in standard stereotactic space. L = left; R = right.

Figure 2

Maps of brain regions demonstrating significant association between grey matter volume and measures of duration of cocaine use, compulsivity and impulsivity in the group of cocaine users. Regions where grey matter volume correlated significantly with the duration of cocaine use in drug users are indicated in orange. Regions that correlated significantly with compulsive cocaine-taking (as assessed by the OCDUS) are coloured in green. Regions where grey matter volume correlated significantly with the inattention component of impulsivity in cocaine users are indicated in red (if the correlation was positive) and blue (if the correlation was negative). The scatter plots beneath each section of the brain image show the correlation between these measures and the total grey matter volume for each drug user in those regions found to be significantly correlated by permutation testing of cluster-level statistics in the restricted search volume or mask defined by the areas of significant between-group difference in grey matter anatomy (Fig. 1). The probability threshold for significance was P ∼ 0.002 for each analysis, at which level we expect less than one false positive cluster per map. The statistical results are overlaid on the FSL MNI152 standard T1 image and the numbers above each section of the image refer to its plane position (mm) relative to the origin in MNI stereotactic space. L = left; R = right.