Reduced Anterior Corpus Callosum White Matter Integrity is Related to Increased Impulsivity and Reduced Discriminability in Cocaine-Dependent Subjects: Diffusion Tensor Imaging

Abstract

Brain imaging studies find evidence of prefrontal cortical dysfunction in cocaine-dependent subjects. Similarly, cocaine-dependent subjects have problems with behaviors related to executive function and impulsivity. Since prefrontal cortical axonal tracts cross between hemispheres in the corpus callosum, it is possible that white matter integrity in the corpus callosum could also be diminished in cocainedependent subjects. The purpose of this study was to compare corpus callosum white matter integrity as measured by the fractional anisotropy (FA) on diffusion tensor imaging (DTI) between 18 cocaine-dependent subjects and 18 healthy controls. The Barratt Impulsiveness Scale (BIS-11) and a continuous performance test: the Immediate and Delayed Memory Task (IMT/DMT) were also collected. Results of the DTI showed significantly reduced FA in the genu and rostral body of the anterior corpus callosum in cocainedependent subjects compared to controls. Cocaine-dependent subjects also had significantly higher BIS-11 scores, greater impulsive (commission) errors, and reduced ability to discriminate target from catch stimuli (discriminability) on the IMT/DMT. Within cocaine dependent subjects there was a significant negative correlation between FA in the anterior corpus callosum and behavioral laboratory measured impulsivity, and there was a positive correlation between FA and discriminability. The finding that reduced integrity of anterior corpus callosum white matter in cocaine users is related to impaired impulse control and reduced ability to discriminate between target and catch stimuli is consistent with prior theories regarding frontal cortical involvement in impaired inhibitory control in cocainedependent subjects.

Attentional deficits in cocaine-dependent patients: Converging behavioral and electrophysiological evidence

“…In a comparison of 17 individuals with current cocaine-dependence and 14 controls, the cocaine-dependent subjects had significantly higher behavioral laboratory scores of impulsivity, operationally defined as proportion of hit-corrected false alarms, than controls (Moeller et al, 2004). In a later study (Moeller et al, 2005) 18 cocaine-dependent patients and 18 normal controls in were administered a questionnaire measure of impulsivity, namely, the Barratt Impulsivity Scale-11 (BIS-11), and the Immediate and Delayed Memory Task, and underwent diffusion tensor imaging (DTI). Compared to the controls, the cocaine-dependent patients displayed significantly fewer hits and greater commission errors on the continuous performance test, as well as greater impulsivity on the questionnaire measure.…”

“…Using a co-twin control research design, Toomey et al (2003) observed that in their sample of 50 twin pairs discordant for abuse of cocaine and/or amphetamines , the drug-abusing co-twin displayed significantly better performance on the CPT, though impaired performance on other attentional measures. On the other hand, two more recent investigations (Moeller et al, 2004;Moeller et al, 2005) suggest that cocaine dependence may be associated with attentional impairments. In a comparison of 17 individuals with current cocaine-dependence and 14 controls, the cocaine-dependent subjects had significantly higher behavioral laboratory scores of impulsivity, operationally defined as proportion of hit-corrected false alarms, than controls (Moeller et al, 2004).…”

Expression of Transcripts for Myelin Related Genes in Postmortem Brain from Cocaine Abusers

“…Decreased expression of PLP1 in these regions therefore might represent more chronic effects of cocaine abuse on myelin structure. Interestingly, recent studies using diffusion tensor imaging, which measures diffusion of water in the CNS and can be used as a marker for myelination, have reported evidence for reduced integrity of myelin sheets in cocaine dependent subjects [56,57].…”

Brain macrostructural and microstructural abnormalities in cocaine dependence

“…Recent magnetic resonance (MR) imaging studies have provided strong evidence that cocaine abuse is associated with structural brain abnormalities in both gray matter (GM) and white matter (WM) (Bartzokis et al, 2002;Fein et al, 2002;Franklin et al, 2002;Lim et al, 2002;Moeller et al, 2005). Evidence from functional neuroimaging studies and investigations of neuropsychological deficits also point to long-term changes in brain status associated with cocaine abuse (Bolla et al, 2000;Goldstein et al, 2004;Volkow et al, 2005).…”

“…No significant group differences were observed in temporal WM or in corpus callosum. Moeller and colleagues used DTI to examine WM in the corpus callosum of cocaine dependent subjects and control subjects (Moeller et al, 2005). Cocaine dependent subjects showed lower FA in the genu and rostral body compared with control subjects.…”