Functional connectivity changes associated with fMRI neurofeedback of right inferior frontal cortex in adolescents with ADHD.

Attention Deficit Hyperactivity Disorder (ADHD) is associated with poor self-control, underpinned by inferior fronto-striatal deficits. We showed previously that 18 ADHD adolescents over 11 runs of 8.5 min of real-time functional magnetic resonance neurofeedback of the right inferior frontal cortex (rIFC) progressively increased activation in 2 regions of the rIFC which was associated with clinical symptom improvement. In this study, we used functional connectivity analyses to investigate whether fMRI-Neurofeedback of rIFC resulted in dynamic functional connectivity changes in underlying neural networks. Whole-brain seed-based functional connectivity analyses were conducted using the two clusters showing progressively increased activation in rIFC as seed regions to test for changes in functional connectivity before and after 11 fMRI-Neurofeedback runs. Furthermore, we tested whether the resulting functional connectivity changes were associated with clinical symptom improvements and whether they were specific to fMRI-Neurofeedback of rIFC when compared to a control group who had to self-regulate another region. rIFC showed increased positive functional connectivity after relative to before fMRI-Neurofeedback with dorsal caudate and anterior cingulate and increased negative functional connectivity with regions of the default mode network (DMN) such as posterior cingulate and precuneus. Furthermore, the functional connectivity changes were correlated with clinical improvements and the functional connectivity and correlation findings were specific to the rIFC-Neurofeedback group. The findings show for the first time that fMRI-Neurofeedback of a typically dysfunctional frontal region in ADHD adolescents leads to strengthening within fronto-cingulo-striatal networks and to weakening of functional connectivity with posterior DMN regions and that this may be underlying clinical improvement.