Use of Virtual Reality Working Memory Task and Functional Near-Infrared Spectroscopy to Assess Brain Hemodynamic Responses to Methylphenidate in ADHD Children.

Virtual reality (VR) neuropsychological tests have emerged as a method to explore drug effects in real-life contexts in attention deficit hyperactivity disorder (ADHD) children. Functional near-infrared spectroscopy (fNIRS) is a useful tool to measure brain activity during VR tasks in ADHD children with motor restlessness. The present study aimed to explore the acute effects of methylphenidate (MPH) on behavioral performance and brain activity during a VR-based working memory task simulating real-life classroom settings in ADHD children. In total, 23 children with ADHD performed a VR n-back task before and 2 h after MPH administration concurrent with measurements of oxygenated hemoglobin signal changes with fNIRS. Altogether, 12 healthy control (HC) subjects participated in the same task but did not receive MPH treatment. Reaction time (RT) was shortened after MPH treatment in the 1-back condition, but changes in brain activation were not observed. In the 2-back condition, activation of the left dorsolateral prefrontal cortex (DLPFC) and bilateral medial prefrontal cortex (mPFC) was decreased alongside behavioral changes such as shorter RT, lower RT variability, and higher accuracy after MPH administration. Bilateral mPFC activation in the 2-back condition inversely correlated with task accuracy in the pre-MPH condition; this inverse correlation was not observed after MPH administration. In ADHD children, deactivation of the default mode network mediated by mPFC reduced during high working memory load, which was restored through MPH treatment. Our results suggest that the combination of VR classroom tasks and fNIRS examination makes it easy to assess drug effects on brain activity in ADHD children in settings simulating real-life.