Brain dysfunction changes in abstinent cocaine abusers.

Objectives To assess the changes in brain dysfunction during abstinence in cocaine dependent subjects

Methods Twenty-two active cocaine users (less than 10 days of abstinence), 20 abstinent users (more than 1 month of abstinence, range 1-8, mean 2.6 months) and 22 normal controls were subjected to resting 99mTc-ECD SPECT. Age and gender did not differ statistically between groups (range 18-35 years). Six subjects in both groups used inhaled cocaine hydrochloride and the rest used smoked cocaine basic paste. A history of at least 2 years of cocaine abuse was required. ANOVA was performed in SPM8. P<0.001 unc. was considered significant at the voxel level. Trends were also reported at p<0.01 unc. Cluster threshold was set to p<0.05 unc. Regression analysis between scans of abstinent subjects and time of abstinence was also performed.

Results Active users showed mesial frontal, anterior cingulate, medial orbitofrontal, thalamic and midbrain hypoperfusion, as well as cerebellar hyperactivity. Abstinent subjects showed bilateral anterior temporal, right lateral temporal, medial orbitofrontal, midbrain and cerebellar hypoperfusion, and left frontoparietal hyperactivity. Abstinent subjects had lower occipital and cerebellar perfusion that active users and greater bilateral dorsolateral prefrontal and left posterior parietal perfusion. No significant correlations were found with time of abstinence.

Conclusions Dysfunction of limbic prefrontal cortex and subcortical connections described in active users of cocaine partially reverse during abstinence. Dorsal prefrontal cortex increases its activity and may become hyperactive. These findings may reflect an improvement in limbic balance, responsible for emotional control and adapted behaviour. Brain dysfunction changes during abstinence but it is still present and has to be evaluated following longer periods to assess if complete reversibility is achieved. These factors are extremely important for rehabilitation programs.