Neuroimaging studies provide evidence of functional (5,6,7,8) and structural abnormalities in orbitofrontal cortex (OFC) in substance dependence. Liu et al. found smaller prefrontal, but not temporal cortex, in poly-substance abusers compared to controls (9). Studies using voxel based morphometry (VBM) have found reduced medial OFC, anterior cingulate, and insular gray matter in cocaine addicts (10) and prefrontal and temporal gray matter in opiate addicts (11). In a study of methamphetamine addiction and HIV infection, methamphetamine was associated with an increase in lentiform gray matter volume, but complicated by opposing effects of HIV infection on brain volume. A limitation of these studies has been the recency of illicit drug use compared to the time of MR scanning. This is important because a) some drug effects on neural substrate may be reversible as has been shown for alcohol (12,13,14) and b) the neural substrates involved in acute drug effects likely differ from those underlying end-stage addiction (2). Thus, the current study sought to determine the pattern of gray matter loss in substance dependent individuals (SDI) after prolonged abstinence.
