The extent of structural brain damage and related cognitive deficits has been little described in alcohol-dependent individuals with preserved social functioning. Thus, we investigated the relationship between regional alterations, executive performance, and drinking history. Volumes of gray and white matter were assessed using magnetic resonance imaging voxel-based morphometry in healthy men and in detoxified alcohol-dependent men with good psychosocial functioning. Their executive performance was assessed using neuropsychological tests. Regression analyses were carried out in the regions in which volume differences were detected. Decreases in gray matter were detected bilaterally in alcohol-dependents in the dorsolateral frontal cortex (up to 20% lower), and to a lesser extent in the temporal cortex, insula, thalamus, and cerebellum. Decreases in white matter volume were widespread, being up to 10% in corpus callosum. The degradation of neuropsychological performance correlated with gray matter volume decreases in the frontal lobe, insula, hippocampus, thalami and cerebellum, and with white matter decrease in the brainstem. An early age at first drinking was associated with decreased gray matter volumes in the cerebellum, brainstem (pons), and frontal regions. Regional alteration in gray and white matter volume was associated with impairment of executive function despite preserved social and somatic functioning in detoxified patients. Besides involving frontal regions, these findings are consistent with a cerebello-thalamo-cortical model of impaired executive functions in alcohol-dependent individuals.

Components of the corticocerebellar circuit and the midbrain individually play a central role in addictive processes and have been associated with altered volumes and impairment of cognitive flexibility in alcohol-dependent subjects. The microstructure of white matter bundles composing the corticocerebellar network and passing through the midbrain was studied using diffusion tensor imaging in a group of detoxified alcohol-dependent men (n ¼ 20) and a group of healthy men (n ¼ 24). The relationship between properties of these white matter bundles and cognitive flexibility performance was investigated in alcohol-dependent subjects. Bundles connecting two regions of interest were analyzed using a fiber-tracking quantitative approach, which provided estimates of the fractional anisotropy and the apparent diffusion coefficient, as well as the number of tracked fibers normalized by the volume of regions of interest. Within the bundles running between the midbrain and pons, a mean of 18% fewer fibers per unit volume were tracked in alcohol-dependent men than in healthy controls. In addition, the normalized number of these fibers correlated with the performance in the Trail-Making Test part-B. Even though the alcohol-dependent subjects were detoxified and apparently neurologically intact, their earlier excessive use of alcohol seems to be associated with altered neural microstructure of mesencephalic white matter bundles, which may contribute to their cognitive flexibility impairment.

Even though uncomplicated alcoholics may likely have episodic memory deficits, discrepancies exist regarding to the integrity of brain regions that underlie this function in healthy subjects. Possible relationships between episodic memory and 1) brain microstructure assessed by magnetic resonance diffusion tensor imaging (DTI), 2) brain volumes assessed by voxel-based morphometry (VBM) were investigated in uncomplicated, detoxified alcoholics.Diffusion and morphometric analyses were performed in 24 alcohol dependent men without neurological or somatic complications and in 24 healthy men. The mean apparent coefficient of diffusion (ADC) and grey matter volumes were measured in the whole brain. Episodic memory performance was assessed using a French version of the Free and Cued Selective Reminding Test (FCSRT). Correlation analyses between verbal episodic memory, brain microstructure, and brain volumes were carried out using SPM2 software.In those with alcohol dependence, higher ADC was detected mainly in frontal, temporal and parahippocampal regions, and in the cerebellum. In alcoholics, regions with higher ADC typically also had lower grey matter volume. Low verbal episodic memory performance in alcoholism was associated with higher mean ADC in parahippocampal areas, in frontal cortex and in the left temporal cortex; no correlation was found between regional volumes and episodic memory scores. Regression analyses for the control group were not significant.These findings support the hypothesis that regional microstructural but no macrostructural alteration of the brain might be responsible, at least in part, for episodic memory deficits in alcohol dependence.