Brainmarker-I differentially predicts remission to various attention- deficit/hyperactivity disorder treatments: A Discovery, Transfer, and Blinded Validation Study

Helena Voetterl*, Guido van Wingen, Giorgia Michelini, Kristi R Griffiths, Evian Gordon, Roger DeBeus, Mayuresh S Korgaonkar, Sandra K Loo, Donna Palmer, Rien Breteler, Damiaan Denys, L Eugene Arnold, Paul du Jour, Rosalinde van Ruth, Jeanine Jansen, Hanneke van Dijk, Martijn Arns

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


Background: Attention-deficit/hyperactivity disorder is characterized by neurobiological heterogeneity, possibly explaining why not all patients benefit from a given treatment. As a means to select the right treatment (stratification), biomarkers may aid in personalizing treatment prescription, thereby increasing remission rates. Methods: The biomarker in this study was developed in a heterogeneous clinical sample (N = 4249) and first applied to two large transfer datasets, a priori stratifying young males (<18 years) with a higher individual alpha peak frequency (iAPF) to methylphenidate (N = 336) and those with a lower iAPF to multimodal neurofeedback complemented with sleep coaching (N = 136). Blinded, out-of-sample validations were conducted in two independent samples. In addition, the association between iAPF and response to guanfacine and atomoxetine was explored. Results: Retrospective stratification in the transfer datasets resulted in a predicted gain in normalized remission of 17% to 30%. Blinded out-of-sample validations for methylphenidate (n = 41) and multimodal neurofeedback (n = 71) corroborated these findings, yielding a predicted gain in stratified normalized remission of 36% and 29%, respectively. Conclusions: This study introduces a clinically interpretable and actionable biomarker based on the iAPF assessed during resting-state electroencephalography. Our findings suggest that acknowledging neurobiological heterogeneity can inform stratification of patients to their individual best treatment and enhance remission rates.

Original languageEnglish
Pages (from-to)52-60
Number of pages9
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number1
Early online date28 Feb 2022
Publication statusPublished - Jan 2023


  • ADHD
  • Biomarker
  • EEG
  • Stratified psychiatry

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