William Hoffman, M.D., Ph.D., Principal Investigator
Marilyn Huckans, Ph.D., Jennifer Loftis, Ph.D., co-investigators
Damien Fair, Ph.D. and Suzanne Mitchell, Ph.D., collaborators

This component has three aims

1. Quantify and characterize the parametric variation of cerebral response to delay, probability, and reward magnitude during decision making in methamphetamine dependent individuals vs Controls.
2. Quantify disruptions in cerebral connectivity as a factor in the development of increased impulsivity in methamphetamine dependence using diffusion-tensor imaging (DTI and voxel based morphometry (VBM).
3. Investigate, in humans and rodents, the hypothesis that neuroimmune disruption of network connectivity contributes to impulsive choice in methamphetamine dependence

Methods

Forty-five actively using methamphetamine (MA) dependent individuals, 45 MA dependent patients in early (1 to 6 months) remission and 45 controls will be recruited from local residential treatment programs and by advertisement. Subjects will be evaluated with functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI) and voxel based morphometry (VBM) in order to identify the anatomical and functional networks that underlie impulsive choice.

Component 9 will expose mice from two lines selected for high and low MA drinking (Component 9), to chronic MA administration, chronic administration followed by abstinence and saline vehicle (total of 120 mice) and then train them to perform an animal version of the delay discounting task.  Component 9 will provide brains of these mice to this component for ex-vivo MRI scanning.  We will perform parallel analyses in mouse and human brains.

Measures of immune dysregulation and differential gene expression (from Component 8) will be investigated as factors responsible for disruption of decision networks in humans and in animals performing impulsivity tasks.