Resting-state FMRI correlates of clinical response to stimulant treatments in children and adolescents with ADHD.

Introduction: Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental condition in which symptoms respond to several pharmacological treatments. However, little is known about the brain mechanism of action of those treatments and the heterogeneity of response across different patients. Objectives: To determine the resting-state fMRI correlates of treatment response to stimulants in ADHD children. Methods: We recruited 68 boys and girls (ages 7-17) with ADHD in an outpatient setting. Sociodemographic, neuropsychological, and clinical data and blood samples were collected from participants, who also underwent neuroimaging (resting-state fMRI scan). Neuroimaging data were preprocessed (including motion correction) and (fractional) amplitude of low-frequency fluctuations ((f)ALFF) metrics were extracted with CPAC v1.4.3 software. All data passed quality control assessments. Initial comparison between 38 patients treated with stimulants and 23 treatmentnaïve patients was done with AFNI 3dttest++. (f)ALFF were also compared in a subsample (n=8) of naïve subjects pre- vs. postacute treatment with methylphenidate, all of whom had good clinical responses. Results: Initial cross-sectional between-group comparisons of (f) ALFF yielded no statistically significant results. In the pre-post within-subject comparison, methylphenidate induced a significant increase of fALFF in a cluster in the right primary visual cortex (MNI coordinates 12,-78,12, corrected p<0.05). Conclusions: Our findings suggest a modulatory effect of intrinsic BOLD signal fluctuations in the primary visual cortex by methylphenidate treatment in a small sample of clinically-responsive ADHD children and adolescents. Our preliminary results illustrate the improved statistical power of within-subject analyses, and highlight the primary visual cortex as a potentially relevant locus in the pharmacodynamics of ADHD treatment. [ABSTRACT FROM AUTHOR]