Demographics and group differences in impulsivity
The two groups were reasonably well matched in terms of age, gender and verbal intelligence (). Eighty-three per cent of the cocaine users had a high school education; although this level is comparable with other studies in cocaine dependence (e.g. Buchanan et al., 2006
), it is falling behind education levels in the control group, in which 98% of volunteers had a high school degree (Fisher's exact P
0.008). The cocaine users also reported more dysphoric mood compared with the healthy volunteers, which is not unusual for substance-dependent individuals (Buckley et al., 2001
). In keeping with previous research, the cocaine users reported increased trait-impulsivity and appetitive motivation (Moeller et al.
; Franken and Muris 2006
; Ersche et al., 2010
). However, these high levels of self-reported impulsivity were not reflected in their behavioural performance. On the Stop-Signal task, cocaine users showed an overall slowing of responses that was not limited to the stop-signal reaction time; latencies on both stop- and go-trials were prolonged. Their poor target detection accuracy on a test of sustained attention was due to the fact that cocaine users missed significantly more targets than controls. We found evidence for generally impaired attentional control rather than the more specific pattern of an increased rate of false alarms and speeded-up responding, which has traditionally been considered to be a marker of impulsive behaviour. Statistical details of all self-report and behavioural measures are shown in .
Demographic and impulsivity measures for healthy volunteers and cocaine-dependent individuals
We used principal component analysis to examine how the different task measures were related to each other in all participants. A five-component solution, comprising all components with standardized eigenvalues >1, accounted for 71% of the total variance/covariance. As shown in , the first component, labelled tentatively ‘inattention’, loaded on the behavioural measures of target detection during sustained attention (RVIP) and response latencies during the response inhibition task. The second component, ‘impulsive reward-seeking’, loaded strongly on self-report measures reflecting reward-driven behaviours (behavioural activation system items) as well as motor and cognitive impulsivity [Barratt Impulsiveness Scale-11 (BIS-11)]. The third component, ‘response slowing’, loaded strongly on prolonged response times on the stop-signal task. The fourth component, ‘impulsive responding’, summarized self-reported behaviours in anticipation of reward [Behavioural Activation System (BAS)] and lack of forward thinking (BIS-11). The fifth component, ‘anxious responding’, loaded highly on self-reported avoidance behaviour (Behavioural Inhibition/Activation System scale) and also on impulsive errors on the RVIP.
The eigenvector matrices of the principal component analysis including 16 impulsivity variables in all participants
Group comparisons on the five components were controlled for the between-group differences in years of education and dysphoric mood ratings. The analyses revealed significant group differences on the components reflecting inattention [F
0.001] and self-reported impulsive reward-seeking [F
0.001]; statistical details of the group comparisons are shown in .
Group differences in grey matter volume
There were significant differences in grey matter volume between the two groups (). There was widespread significant loss of grey matter in orbitofrontal cortex bilaterally in the cocaine user group. Grey matter volume was also abnormally reduced in the insula, the medial frontal and anterior cingulate cortex, temporoparietal cortex and the cerebellum. In contrast to this extensive system of decreased cortical grey matter volume, cocaine users also showed a significant increase of grey matter volume mainly localized to basal ganglia structures (including putamen, caudate nucleus and pallidum), and cerebellum.
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 (more ...)
Individual differences in impulsivity, compulsivity and grey matter volume
To investigate how the significant components of impulsivity were associated with the abnormal grey matter systems in the cocaine-dependent group, we separately regressed cocaine users’ individual scores on each of the two abnormal components (inattention and impulsive reward-seeking) on grey matter volume in each voxel of the corticostriatal system that was abnormal in the cocaine-dependent individuals group compared with healthy participants. This procedure identified a set of voxels where grey matter volume was significantly positively correlated with the first impulsivity component (inattention) in the cocaine users (coloured in red in ) in the left caudate nucleus [Montreal Neurological Institute coordinates (x, y, z; mm): −18, 18, 8], and negatively correlated with grey matter volume in the insula bilaterally [coloured in blue (38, −8, 18) and (−36, 0, 8)], and in the right middle temporal gyrus (56, 0, −18). The second component (impulsive reward-seeking) was not significantly correlated with grey matter volume variation in the cocaine-dependent group.
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 (more ...)
We also regressed the OCDUS score of cocaine-related compulsivity on those grey matter systems in the cocaine group that differed from control volunteers. As shown in , drug-related compulsivity was significantly associated with grey matter loss in the orbitofrontal cortex (−2, 32, −18). The OCDUS score was correlated with the inattention score (r
0.05) (), and the OCDUS-related decline in grey matter in the orbitofrontal cortex was correlated with the inattention-related decline in grey matter in the insula and middle temporal gyrus (r
Correlation matrix of impulsivity, compulsivity and duration of cocaine use in cocaine-dependent individuals
Relationship between duration of cocaine dependence and grey matter volume
To investigate whether or not altered grey matter volume was related to the duration of cocaine abuse, we regressed the number of years of cocaine abuse of each cocaine user on the map of grey matter volume differences. We found that the individuals who had been using cocaine for longer periods of time, had greater extent of grey matter volume reduction in the anterior and middle cingulate gyrus, middle frontal cortex (orbital part), rectus gyrus, supplementary motor area, superior temporal gyrus, insula, cerebellum and in the left caudate (r