Determining the Effects of Active Methamphetamine Dependence on Grey Matter Structure and Function of the Human Brain using Magnetic Resonance Imaging

Methamphetamine dependence is a worldwide problem for which no effective treatment currently exists. Magnetic resonance imaging (MRI) allows the non-invasive study of the brains of methamphetamine-dependent individuals; however, most MRI studies have been conducted following varying periods of abstinence. This thesis focuses on the effects of active methamphetamine dependence on the human brain and examines changes associated with the use of methylphenidate, an agonist replacement therapy, versus placebo using structural and functional MRI (1.5 T); the former coupled with neuropsychological testing and the latter with the colour-word Stroop task. Active methamphetamine-dependent subjects (n=17) were compared to control subjects (n=20) at baseline, and following an acute oral methylphenidate (18mg) versus placebo challenge. Active methamphetamine-dependent subjects continued treatment with methylphenidate (54mg/day) or placebo and underwent testing again during their tenth week of treatment (n=8). At baseline, methamphetamine-dependent subjects showed increased right putamen volumes in comparison to control subjects, which correlated with improved performance during the Go/No-go task of response inhibition. Following 10 weeks of treatment with methylphenidate, right putamen volumes of methamphetamine-dependent subjects were decreased without worsening of cognitive function in comparison to placebo. This suggested a normalisation process whereby the underlying methamphetamine-induced putamen enlargement is reversed following treatment with methylphenidate. In general, methamphetamine-dependent subjects showed similar behavioural performance of the colour-word Stroop task to control subjects. However, they exhibited different patterns of fMRI activation. Increased activation of frontal, parietal and temporal regions of methamphetamine-dependent subjects during the incongruent and Stroop effect conditions was suggested to be essential for successful conflict resolution. After a methylphenidate (18mg) challenge, methamphetamine-dependent subjects exhibited deactivation of the insula in comparison to control subjects, a possible methylphenidate-induced adaptive effect to the incongruent condition which presents a higher cognitive load than the congruent condition. Following 10 weeks of treatment with methylphenidate (54mg/day), methamphetamine-dependent subjects showed faster responding during the Stroop task combined with increased activation of frontal and cingulate regions. These preliminary findings suggest that normalisation, at least in part, of brain function during cognitive control may occur following long-term methylphenidate treatment of methamphetamine-dependent subjects. Future studies are recommended to use a larger sample size and eliminate the confounding effects of other drug use. Finally, larger studies of active methamphetamine dependence using higher doses of methylphenidate for longer periods are recommended to consolidate the preliminary findings from this study.

Topic: Hermeneutics and Narrative Identity
Subfield: Philosophy
Field: Arts and Humanities
Domain: Social Sciences