TMARC Pilot Studies - Completed

Intraindividual Neurocognitive Variability in Acute METH Users (Morgan)

Agency: TMARC
PI: Morgan, Erin E., Ph.D.

Abstract

Acute methamphetamine toxicity produces significant central nervous system changes, including hyperthermia, edema, reduction in blood brain barrier integrity, and cellular changes in the brain, which may result in lasting neuropathological and neurocognitive effects observed in chronic MA users that is largely consistent with prefronto-striatal circuit dysfunction. Study of the neuropsychological sequelae of acute MA intoxication presents a challenge because of the relative improvement in performance that may result from recent use when traditional neuropsychological summary scores based on average level of performance are used. However, there is evidence to suggest that individuals with MA intoxication may be more variable in their performance, and as such a method for directly measuring within-person fluctuations in performance secondary to MA use may be useful for elucidating the neurocognitive changes that occur in the context of MA intoxication. A theory-based approach to directly measuring these within-person fluctuations that can occur within a single session or across time is known as intraindividual variability (IIV), and increases in IIV are purportedly related to cognitive dyscontrol such as that observed in frontal systems dysfunction. The current proposal aims to gather pilot data to investigate IIV in acute MA toxicity, hypothesizing that greater IIV will be demonstrated among MA dependent individuals with recent MA use (as evidenced by urine toxicology screen results that are positive for MA; n = 30) relative to MA dependent individuals without recent use (n = 25), who in turn will evidence greater IIV relative to nonMA-using comparisons (n = 25). The study will also evaluate executive mechanisms purportedly underlying IIV using a theoretical model, and will examine factors that may influence this relationship (e.g., task complexity). The functional impact of IIV related to recent MA use will also be explored. The resource economy of this proposed pilot project is enhanced by enrolling TMARC participants, and the findings will support a planned NIMH R01 application to examine the effects of acute and chronic MA use, as well as their conceptual (e.g., cognitive mechanisms), neurobiological (e.g., biomarkers of inflammation), and expanded functional implications in a larger, comprehensive cohort. This nascent line of research has the potential to inform future study of IIV in MA dependence, including neural correlates (e.g., multimodal neuroimaging), effects of medical and psychiatric comorbidities, and potential rehabilitation strategies to improve IIV and daily functioning.

Sponsored by NIH/NIDA P50DA026306

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