Microstate-based Neurofeedback in Attention Deficit Hyperactivity Disorder Population: A Randomized Controlled Crossover Trial

Neurofeedback (NFB) therapy based on spectral neuromarkers of Attention-Deficit/Hyperactivity Disorder (ADHD) has faced challenges regarding its efficacy and replicability. In this study, we investigate whether a microstate-based EEG marker, recently implicated in ADHD, could serve as a novel target for neurofeedback. Emerging research suggests that ADHD patients often exhibit an excess of microstate D, a state characterized by fronto-central cortical activity linked to attentional functions. This study aims to assess whether neurofeedback training can effectively modulate microstate D in adult ADHD patients, along with its short-term neurobehavioral correlates. We employed a within-subject, crossover design with 19 adults with ADHD, who participated in two counterbalanced neurofeedback sessions: one aimed at upregulating microstate D percent time coverage, and the other at downregulating it. While patients were able to volitionally increase microstate D during the upregulation session, no significant change was observed during the downregulation session. Direct comparison between the two sessions revealed that online control of microstate D was specific to the closed-loop feedback, rather than merely task engagement. No short-term effects of the neurofeedback sessions were observed. No moderate nor major adverse effects were reported. Despite lack of statistical power, this study provides controlled indicationfor the specificity and safety of neurofeedback training based on microstate D in adult ADHD patients. Although the short-term design did not yield clinical improvements, the findings demonstrate the feasibility of microstate-based neurofeedback protocols in a clinical population and offer valuable technical and methodological insights for designing futur studies.