Prevailing neuropsychological models of attention-deficit/hyperactivity disorder (ADHD) propose that ADHD arises from deficits in executive functions such as working memory, but accumulating clinical evidence suggests a dissociation between ADHD and executive dysfunctions. This study examined whether ADHD and working memory capacity are behaviorally and neurobiologically separable using functional magnetic resonance imaging (fMRI). Participants diagnosed with ADHD in childhood who subsequently remitted or persisted in their diagnosis as adults were characterized at follow-up in adulthood as either impaired or unimpaired in spatial working memory relative to controls who never had ADHD. ADHD participants with impaired spatial working memory performed worse than controls and ADHD participants with unimpaired working memory during an n-back working memory task while being scanned. Both controls and ADHD participants with unimpaired working memory exhibited significant linearly increasing activation in the inferior frontal junction, precuneus, lingual gyrus, and cerebellum as a function of working-memory load, and these activations did not differ significantly between these groups. ADHD participants with impaired working memory exhibited significant hypoactivation in the same regions, which was significantly different than both control participants and ADHD participants with unimpaired working memory. These findings support both a behavioral and neurobiological dissociation between ADHD and working memory capacity.

Statistical models employed to test for group differences in quantized diffusion-weighted MRI white matter tracts often fail to account for the large number of data points per tract in addition to the distribution, type, and interdependence of the data. To address these issues, we propose the use of Generalized Additive Models (GAMs) and supply code and examples to aid in their implementation. Specifically, using diffusion data from 73 periadolescent clinically anxious and no-psychiatric-diagnosis control participants, we tested for group tract differences and show that a GAM allows for the identification of differences within a tract while accounting for the nature of the data as well as covariates and group factors. Further, we then used these tract differences to investigate their association with performance on a memory test. When comparing our high versus low anxiety groups, we observed a positive association between the left uncinate fasciculus and memory overgeneralization for negatively valenced stimuli. This same association was not evident in the right uncinate or anterior forceps. These findings illustrate that GAMs are well-suited for modeling diffusion data while accounting for various aspects of the data, and suggest that the adoption of GAMs will be a powerful investigatory tool for diffusion-weighted analyses.