T033 Right prefrontal rTMS for the treatment of ADHD: Electrophysiological correlates and prognostic biomarkers

Abstract

Background Reduced excitability of the right prefrontal cortex (rPFC) has been implicated in attention deficit/hyperactivity disorder (ADHD). Despite its high prevalence, chronic treatments for ADHD are not tolerable by many patients. Modulation of the rPFC with rTMS may become a novel treatment alternative. Methods Drug-free adults with ADHD (n = 53) received 15 daily sessions of high-frequency repetitive TMS directed to the rPFC, using either deep (H-6r, dTMS), standard (Figure-8, 8TMS), or sham coils. Standard ADHD questionnaires were administered, and EEG recordings were taken before, during, and after the first and the last days of treatment. In addition, EEG was recorded during a Stop Signal task (SST), following single TMS pulses over the rPFC, and during the treatment session itself. Additional comparison group of healthy subjects (n = 41) was recorded under the same conditions, but did not undergo the chronic rTMS treatment. Results At baseline, amplitudes of TMS evoked potential (TEP) and the SST’s N200 and P300 components, were significantly lower in subjects with ADHD than those of healthy controls. Moreover, the TEP and SST amplitudes correlated with ADHD symptoms and with the behavioral inhibition measures. Following treatment, improvement in ADHD total symptoms was only evident in the dTMS group. Moreover, TEP was enhanced following the first treatment session with either 8TMS or dTMS, but long-term cumulative enhancement was evident only in the dTMS group. Finally, specific EEG bands recorded at rest and during the first treatment session were highly correlated with dTMS outcomes; yielding a prognostic marker that explains 90% of variance in therapeutic outcome. Discussion These findings suggest that 3 weeks high frequency dTMS treatment can serve as a novel treatment for ADHD in adults, possibly by enhancing excitability of the rPFC. Furthermore, electrophysiological activity elicited during the first treatment session can serve as a high quality prognostic marker. This predictor may promote superior treatment response rates under proper selection of patients and is a first step towards the development of personalized dTMS treatment.