The general goal of this project is to extend our recent findings of brain abnormalities and neuropsychologicaldeficits in chronic cocaine abusing subjects through the study of putative brain mechanisms of impulsivity incocaine dependence. As described in the Preliminary Findings section, we observed white matterabnormalities in frontal areas that contain anatomical regions known to be associated with impulse control.We also observed disinhibition on neurocognitive tests including a measure of impulsive decision-making inthe cocaine users. Self-reported impulsivity traits, as measured by the Barratt Impulsiveness Scale (BIS),were associated with measures of white matter integrity. In our sample, cocaine users with longer duration ofuse showed more white matter abnormalities than those with fewer years of use. Together, these datasuggest that cocaine abuse may be associated with changes in the brain that result in increased impulsivity.In this project we will build on this preliminary work by collecting more specific assessments of impulsivity andcombine this information with neuroimaging measures of white matter integrity using Diffusion TensorImaging(DTI) and GABA, the major inhibitory brain neurotransmitter, using Magnetic ResonanceSpectroscopy(MRS). Recent findings suggest that impaired prefrontal inhibitory control may not be solely aresult of drug use, but may also reflect a preexisting condition that increases the vulnerability to using drugsand becoming addicted. Accordingly, an important goal of this project is to compare cocaine abusers directlywith participants in Project 3 (BED), who are not substance abusers yet have an addictive behavior, todetermine whether neurobiological findings present in cocaine users are also found in subjects with non-drugaddictive behavior. This will allow us to differentiate neurobiological and neurocognitive markers ofimpulsivity from the neurobiological and neurocognitive effects of drug use. Where possible, we haveselected our tasks and measures to overlap with what is being done in the Animal experiments in Project 1,which will allow us address questions difficult to study in humans.The proposed project also promises togenerate new findings relating brain GABA levels, white matter microstructure and neurocognitiveperformance in cocaine abusers. We have three aims: 1) Measure impulsivity in cocaine abusers usingbehavioral tasks and self-report instruments. 2) Use DTI measures to assess frontal white matter integrity andits relationship to impulsivity measures. 3) Using MRS, determine if cocaine abusers have abnormalities inbrain GABA levels.
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