Microstructural alterations of an orbital and medial prefrontal network in patients with alcohol dependence as detected by voxel-based Diffusion Tensor Imaging

Aims: To comprehensively assess the microstructural integrity of white matter pathways, we performed voxel-based Diffusion Tensor Imaging (DTI) in subjects with alcohol dependence undergoing detoxification. In contrast to a predefined region approach the whole brain was assessed in an exploratory fashion without a priori assumptions about the structures to be investigated.

Methods: 21 adult alcoholics (16 men) and 22 age-matched control subjects were enrolled in the study. DTI (25 directions) was performed on a 1.5T neuro-optimized GE-scanner at least one week after the detoxification had been started. Images were pre-processed and analyzed using a new approach by SPM2. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were compared using t-tests (p<0.05, corrected).

Results: Compared with controls, alcoholics showed extensive decreases in FA in the white matter of the orbital and medial prefrontal cortex, the corpus callosum, the cingulate gyrus, the uncinate fasciculus, and the brainstem bilaterally compared with controls. Comparison of ADC maps revealed widespread increased diffusivity in gray matter of the frontal and parietal lobes bilaterally.

Conclusions: The findings of our DTI study identified disturbances of associational and commissural fibers in the orbital and medial prefrontal network of patients with alcohol dependence. This network is thought to be involved in emotional and other self-referential processes. Linking neuropathological abnormalities with clinical characteristics in vivo, the results contribute to constraining the prevailing biological models of alcohol dependence extending the results of previous structural MRI studies with a region of interest approach. Furthermore, voxel-based DTI opens a window to study manifestations of early brain recovery associated with abstinence from alcoholism and could help to characterize brain endophenotypes of patients with alcohol dependence.