Adjustment of diffusion gradient direction Two corrections were applied to the diffusion gradients. The nominal diffusion gradient directions were prescribed in the magnet axis frame and rotated to correspond to the image slice orientation. No correction was required if the imaging slice was pure axial. A second correction accounted for any image AC220 rotation during the previous motion and eddy current correction step. The rotation part of the transformation found previously was extracted, and each gradient Inhibitors,research,lifescience,medical direction vector was corrected accordingly. Image registration

and transformations steps were done with FMRIB’s Linear Image Registration Tool (FLIRT), and the detection of outliers and data pruning was done with a custom program written in IDL (http://www.ittvis.com). Inhibitors,research,lifescience,medical Dtifit was used to calculate the diffusion tensor and the FA maps. FA values were obtained using FMRIB Software Library (FSL), tract-based spatial statistics (TBSS; Smith et al. 2006). Each FA image was aligned to the standard-space FMRIB58 FA image

(voxel size of 1 × 1 × 1 mm) with a nonlinear registration algorithm (FMRIB’s Nonlinear Image Registration Tool, Oxford, UK). Inhibitors,research,lifescience,medical Following transformation to the target and affine transformation to MNI152 space, all FA images were merged into a single 4D image file, from which the FA skeleton was calculated using a threshold value of 0.2. White matter tracts were defined using the Johns Hopkins University, International Consortium for Brain Mapping DTI-81 labels atlas, with highest probability thresholding at 25% and white matter tractography atlas (Mori et al. 2005; Wakana et al. 2007). White matter tracts were selected for analysis on the basis Inhibitors,research,lifescience,medical of previous studies summarized above and hypotheses regarding the involvement of self-regulation and reward networks.

Inhibitors,research,lifescience,medical These 18 tracts were as follows: genu, body, and splenium of corpus callosum; fornix; forceps minor; anterior, posterior, and retrolenticular limbs of internal capsule; anterior, superior, and posterior corona radiata; anterior and posterior thalamic radiations; sagittal striatum; external capsule; cingulate gyrus; superior longitudinal fasciculus; and inferior frontooccipital fasciculus. why Within individuals, FA values for the skeletonized voxels that intersected with the tract atlas were averaged to obtain a single value per tract to be used in subsequent correlations with fMRI data. Right and left hemispheres were averaged for the 13 bilateral tracts, as hypotheses did not stipulate differential effects based on hemisphere. fMRI task and analysis To measure cue-elicited responses to alcohol, we used a task described previously in which a small amount of the participant’s preferred alcoholic beverage was alternated with litchi juice, an appetitive control (Filbey et al. 2008; Claus et al. 2011).