
Dr. Hugh Myrick
Biographical Information
Pilot Grant - The Use of fMRI to Determine Response to Medication Treatment in Individuals 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.