Neural Markers of Methylphenidate Response in Children With Attention Deficit Hyperactivity Disorder

BACKGROUND: Despite widespread use of stimulants to treat ADHD, individual responses vary considerably and few predictors of response have been identified. The identification of reliable and clinically feasible biomarkers would facilitate a precision medicine approach to pharmacological treatment of ADHD. We test the hypothesis that two electroencephalography (EEG) based neural signatures of ADHD, resting aperiodic slope exponent and novelty P3 amplitude, are markers of methylphenidate response in children. We hypothesize that positive response to methylphenidate treatment will be associated with greater abnormality of both neural markers. METHODS: Twenty-nine 7-11 year-old children with ADHD and a history of methylphenidate treatment, and 30 controls completed resting EEG and visual oddball event related potential (ERP) paradigms. ADHD participants were characterized as methylphenidate responders (n = 16) or non-responders (n = 13) using the clinical global improvement (CGI-I) scale during blinded retrospective interview. All participants abstained from prescribed medications for at least 48 hours prior to the EEG. RESULTS: As expected, methylphenidate responders (CGI-I rating < 3) demonstrated attenuated P3 amplitude relative to controls. Unexpectedly, methylphenidate non-responders showed atypically flat aperiodic spectral slope relative to controls, while responders did not differ on this measure. CONCLUSION: ADHD symptoms associated with atypical patterns of intrinsic neural activity may be less responsive to methylphenidate. In contrast, ADHD symptoms associated with abnormal frontal-striatal neural network excitation may be correctable with methylphenidate. Altogether, EEG is a feasible and promising candidate methodology for identifying biomarkers of stimulant response.