Resting-state brain intrinsic connectivity changes in children & adolescents with attention-deficit/hyperactivity disorder treated with stimulant medications

Résumé

Neuroimaging research seeks to identify biomarkers to improve the diagnosis, prognosis, and treatment of attention-deficit/hyperactivity disorder (ADHD), although clinical translation of findings remains distant. Resting-state functional magnetic resonance imaging (R-fMRI) is a technique increasingly used to characterize ‘functional connectivity’ in the brain. Despite mixed results to date and multiple methodological challenges, dominant hypotheses implicate hyperconnectivity across brain networks, which could be the target of pharmacological treatments. We describe the experience and results of the Clínica Universidad de Navarra Metilfenidato (CUNMET) pilot study, based in Spain. CUNMET tested the feasibility of identifying R-fMRI markers of clinical response in children with ADHD undergoing naturalistical pharmacological treatments. We analyzed cross-sectional data from 56 patients with ADHD (18 treated with methylphenidate, 18 treated with lisdexamfetamine, and 20 treatment-naive patients). Standard preprocessing and statistical analyses with attention to control for head motion and correction for multiple comparisons were performed. The only results that survived correction were noted in contrasts of children who responded clinically to lisdexamfetamine after long-term treatment versus treatment-naive patients. In these children, we observed stronger negative correlations (anticorrelations) across nodes in six networks, which is consistent with higher across-network functional segregation in patients treated with lisdexamfetamine, i.e., less inter-network interference than in treatment-naive patients. We also take note of the lessons learned, which could be helpful to those pursuing clinically relevant multidisciplinary research in ADHD en route to eventual personalized medicine.