Brain atrophy in long-term abstinent alcoholics who demonstrate impairment on a simulated gambling task

Abstract

We recently demonstrated impairment on the Simulated Gambling Task (SGT) in long-term abstinent alcoholics (AbsAlc). Brain regions that have been shown to be necessary for intact SGT performance are the ventromedial prefrontal cortex (VMPFC) and the amygdala; patients with VMPFC or amygdalar damage demonstrate SGT impairments similar to those of substance abusing populations. We examined these brain regions, using T1-weighted MRIs, in the 101 participants from our previous study using voxel-based morphometry (VBM). VBM was performed using a modification we developed [Fein, G., Landman, B., Tran, H., Barakos, J., Moon, K., Di Sclafani, V., Shumway, R., 2006. Statistical parametric mapping of brain morphology: sensitivity is dramatically increased by using brain-extracted images as inputs. Neuroimage] of Baron's procedure, [], in which we use skull-stripped images as input. We also restricted the analysis to a ROI consisting of the amygdala and VMPFC as defined by the Talairach Daemon resource. Compared to the controls, the AbsAlc participants had significant foci of reduced gray matter density within the amygdala. Thus, SGT decision-making deficits are associated with reduced gray matter in the amygdala, a brain region previously implicated in similar decision-making impairments in neurological samples. This structurally based abnormality may be the result of long-term alcohol abuse or dependence, or it may reflect a pre-existing factor that predisposes one to severe alcoholism. From an image analysis perspective, this work demonstrates the increased sensitivity that results from using skull-stripped inputs and from restricting the analysis to a ROI. Without both of these methodological advances, no statistically significant finding would have been forthcoming from this work.

Figure 1

Figure 1 shows performance on the simulated gambling task (number of cards chosen from the good decks minus number of cards chosen from the bad decks) separately for males and females, and abstinent alcoholics and controls. Abstinent alcoholics performed worse on the gambling task when compared to controls (p < 0.05), and men performed poorer than women (p < 0.05). No gender by group interaction was observed.

Figure 2

Figure 2 shows the output from the SPM2 analysis on the glass brain. The results use p(fwe) < 0.05, where p(fwe) is family wise error corrected in order to determine significance. On the left (glass brain right), the cluster of significance has 370 voxels having a minimum p(fwe) value of 0.013. On the right (glassbrain left), the cluster of significance has 218 voxels having a minimum p(fwe) value of 0.015. The glass brain coordinates are given in Talaraich space.

Figure 3

Figure 3 depicts the gray MNI template rendered brain with overlay in colors. The coronal and axial views on the right show the amygdala (blue), the ventromedial prefrontal cortex (magenta), and the ROI mask (light pink). The coronal and axial views on the left show the SPM2 areas of significant reduced gray matter (orange) (SPM2 family wise error corrected p < 0.05), and the spatial uncertainty of focus (green). The spatial uncertainty of focus is the projection of the areas of significant focus smoothed with a Full Width Half Maximum (FWHM) 12 mm Gaussian Kernel.