Alterations in Structural and Functional Connectivity in ADHD: Implications for Theories of ADHD.

Attention-Deficit/Hyperactivity Disorder (ADHD) is increasingly viewed as a disorder of brain connectivity. We review connectivity-based theories of ADHD including the default mode network (DMN) interference and multiple network hypotheses. We outline the main approaches used to study brain connectivity in ADHD: diffusion tensor imaging and resting-state functional connectivity. We discuss the basic principles underlying these methods and the main analytical approaches used and consider what the findings have told us about connectivity alterations in ADHD. The most replicable finding in the diffusion tensor imaging literature on ADHD is lower fractional anisotropy in the corpus callosum, a key commissural tract which connects the brain's hemispheres. Meta-analyses of resting-state functional connectivity studies have failed to identify spatial convergence across studies, with the exception of meta-analyses focused on specific networks which have reported within-network connectivity alterations in the DMN and between the DMN and the fronto-parietal control and salience networks. Overall, methodological heterogeneity between studies and differences in sample characteristics are major barriers to progress in this area. In addition, females, adults and medication-naïve/unmedicated individuals are under-represented in connectivity studies, comorbidity needs to be assessed more systematically, and longitudinal research is needed to investigate whether ADHD is characterized by maturational delays in connectivity.