The general linear model used to calculate the individual BOLD contrast maps (drug epochs and neutral epochs) for each fMRI time series consisted of a box-car design convolved with the canonical hemodynamic response function (HRF) and a high-pass filter (cut-off frequency: 1/520 Hz). The BOLD signal strength was estimated without the removal of global effects (global normalization) to minimize false deactivation signals [30], [31]. The estimated BOLD maps, contrasting word epochs (drug or neutral) against baseline epochs, were included in a two-way (word type × group) repeated measures analysis of variance (ANOVA) model in SPM2. Four covariates (smoking status, urine results, gender, and age) were included in this random-effects model in an effort to control for potential confounds. Brain activation clusters were corrected for multiple comparisons using the continuous random field calculation implemented in SPM2. Clusters with at least 15 voxels (400 mm3) and pcorr <0.05, corrected for multiple comparisons at the cluster level, were considered significant in group analyses of brain activation.
