Hugh Myrick, M.D.
Psychiatry & Behavioral Sciences
BS, Microbiology, 1988, Clemson University, Clemson, SC
M.D., 1992, Medical University of SC, Charleston, SC
The Use of fMRI to Determine Response to Medication in People with Cocaine Dependence.
Several neuroimaging studies have shown that specific regions of the brain become active when people are stimulated to crave drugs or alcohol. During the Phase 1 safety trial comparing N-acetylcysteine (NAC) to placebo described in the body of the proposal, we used functional magnetic resonance imaging (fMRI) to measure brain activity during the presentation of visual cues (pictures) designed to illicit craving for cocaine at baseline and after treatment with NAC in eleven individuals. Subjects were treated with NAC in a double-blind, crossover design in which the medication or placebo was administered over a four-day inpatient hospitalization and readmitted one-week later for the alternate medication condition. Imaging sessions took place the day prior to discharge (N = 12 for completed crossover plus fMRI). In a Philips 3.0 Tesla MRI scanner, the subjects viewed a 12 minute randomized presentation of pictures of cocaine, neutral objects, and two different visual control tasks. Figure 1 shows that in the cocaine vs object condition there was a decrease in anterior cingulate activation during NAC treatment as compared to placebo treatment. The anterior cingulated has been identified in neuroimaging studies in addicts, as well as in reinstatement animal models of addiction as a critical neurosubstrate underlying relapse. These date indicate that NAC may blunt the responsiveness of the anterior cingulated to the cocaine cue, which could contribute to a positive clinical outcome in the proposed clinical trials.