The executive control network and symptomatic improvement in attention-deficit/hyperactivity disorder

• Published in: Cortex 2015-12, Vol.73, p.62-72
• Main Authors: Francx, Winke, Oldehinkel, Marianne, Oosterlaan, Jaap, Heslenfeld, Dirk, Hartman, Catharina A., Hoekstra, Pieter J., Franke, Barbara, Beckmann, Christian F., Buitelaar, Jan K., Mennes, Maarten
• Format: Article
• Language: English
• Subjects: ADHD; Adolescent; Attention Deficit Disorder with Hyperactivity - physiopathology; Brain Mapping; Cerebellum - physiopathology; Development; Executive control; Executive Function - physiology; Female; Follow-Up Studies; Humans; Hyperactivity/impulsivity; Magnetic Resonance Imaging - methods; Male; Neural Pathways - physiopathology; Remission; Resting state; Young Adult
• ISSN: 0010-9452; 1973-8102
• DOI: 10.1016/j.cortex.2015.08.012

One neurodevelopmental theory hypothesizes remission of attention-deficit/hyperactivity disorder (ADHD) to result from improved prefrontal top-down control, while ADHD, independent of the current diagnosis, is characterized by stable non-cortical deficits (Halperin & Schulz, 2006). We tested this theory using resting state functional MRI (fMRI) data in a large sample of adolescents with remitting ADHD, persistent ADHD, and healthy controls. Participants in this follow-up study were 100 healthy controls and 129 adolescents with ADHD combined type at baseline (mean age at baseline 11.8 years; at follow-up 17.5 years). Diagnostic information was collected twice and augmented with magnetic resonance imaging (MRI) scanning at follow-up. We used resting state functional connectivity (RSFC) of the executive control network to investigate whether improved prefrontal top-down control was related to a developmental decrease in ADHD symptoms. In addition, we tested whether non-cortical RSFC, i.e., cerebellar and striatal RSFC, was aberrant in persistent and/or remittent ADHD compared to controls. Higher connectivity within frontal regions (anterior cingulate cortex) of the executive control network was related to decreases in ADHD symptoms. This association was driven by change in hyperactive/impulsive symptoms and not by change in inattention. Participants with remitting ADHD showed stronger RSFC than controls within this network, while persistent ADHD cases exhibited RSFC strengths intermediate to remittent ADHD cases and controls. Cerebellar and subcortical RSFC did not differ between participants with ADHD and controls. In line with the neurodevelopmental theory, symptom recovery in ADHD was related to stronger integration of prefrontal regions in the executive control network. The pattern of RSFC strength across remittent ADHD, persistent ADHD, and healthy controls potentially reflects the presence of compensatory neural mechanisms that aid symptomatic remission.