Neurophysiological findings in Attention Deficit Hyperactivity Disorder, a Pandora’s box with therapeutic implications

Aim: Growing evidence suggests that Attention Deficit Hyperactivity Disorder (ADHD) may not be a single entity with a universal remedy, but rather a group of conditions resulting from interactive bio-psycho-social factors and requiring specifically targeted interventions. ADHD research, including neurophysiology, faces inconsistent findings due to heterogeneity. This variety might indicate different physiopathogenic mechanisms. This study aimed to identify dysfunctional mechanisms behind ADHD symptoms and test if targeting these dysfunctions can improve clinical outcomes. Methods: 230 children with ADHD diagnosis studied with hypothesis-related variables from electroencephalogram (EEG) visual inspection and quantitative z-scored power, coherence and ratios, and from event-related brain potentials (ERPs) z-sored P50, N100, N200, P300 latencies amplitudes and ratios. Parametric and non-parametric classifications were conducted on neurophysiological findings to identify clusters and design neuropsychologically-based recommended treatments (NBRTx). Treatment response evaluated thrgbrough ADHD scores comparing NBRTx with guidelines recommended treatment (GBRTx). Treatment selected by agreement between each child’s physician and the parents, both parties thoroughly informed. Results: Six clusters of neurophysiological findings were identified, each characterized by a combination of EEG/ERP abnormalities hypothetically related to distinct dysfunctional mechanisms. Cluster (C) findings, hypothetical dysfunction, and treatment recommendations: C1: Longer P300 latencies, hypodopaminergia: methylphenidate. C2: Centrotemporal spiles, hyperexcitable network: carbamazepine. C3: Bisynchronous spike-waves complexes, thalamocortical involvement: valproic. C4: Altered psychosis-related variables: risperidone. C5: Altered migraine-related variables: valproic. C6: Abnormal maturational interhemispheric rate: tailored psychotherapy. At 3 months, ADHD scores decreased with methylphenidate (MPH) only in C1. In other clusters children under NBRTx had good responses, those under GBRTx did not, and were switched to NBRTx with significant improvement at 6 months. Conclusions: Six different neurophysiological mechanisms responding to targeted interventions were identified by neurophysiological signatures. A personalized medicine approach guided by physiopathogenic mechanisms may be necessary when facing multifactorial, heterogeneous disorders such as ADHD.