Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD

Anna Kaiser; Pascal M Aggensteiner; Hilario Blasco Fontecilla; Tomas Ros; Eric Acquaviva; Yohan Attal; Tobias Banaschewski; Sarah Baumeister; Elisa Bousquet; Aurore Bussalb; Marie Delhaye; Richard Delorme; Renate Drechsler; Allison Goujon; Alexander Häge; Louis Mayaud; Konstantin Mechler; Caroline Menache; Olivier Revol; Friederike Tagwerker; Susanne Walitza; Anna Maria Werling; Stéphanie Bioulac; Diane Purper-Ouakil; Daniel Brandeis

doi:10.3389/fpsyt.2023.1331004

Limited usefulness of neurocognitive functioning indices as predictive markers for treatment response to methylphenidate or neurofeedback@home in children and adolescents with ADHD

Front Psychiatry. 2024 Jan 12:14:1331004. doi: 10.3389/fpsyt.2023.1331004. eCollection 2023.

Authors

Anna Kaiser¹, Pascal M Aggensteiner¹, Hilario Blasco Fontecilla², Tomas Ros³, Eric Acquaviva⁴, Yohan Attal⁵, Tobias Banaschewski¹, Sarah Baumeister¹, Elisa Bousquet⁶, Aurore Bussalb⁷, Marie Delhaye⁸, Richard Delorme⁴, Renate Drechsler⁹, Allison Goujon⁶, Alexander Häge¹, Louis Mayaud⁷, Konstantin Mechler¹, Caroline Menache¹⁰, Olivier Revol¹¹, Friederike Tagwerker⁹, Susanne Walitza⁹, Anna Maria Werling⁹, Stéphanie Bioulac^{12

13}, Diane Purper-Ouakil^{6

14

15}, Daniel Brandeis^{1

9

16

17}

Affiliations

¹ Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim/Heidelberg University, Mannheim, Germany.
² UNIR Health Sciences School and Medical Center and UNIR-itei, CIBERSAM, Madrid, Spain.
³ Department of Neuroscience, Campus Biotech CISA-Université de Genève, Genève, Switzerland.
⁴ Child and Adolescent Psychiatry Department and Child Brain Institute, Robert Debré Hospital, Assistance Publique-Hôpitaux de Paris and Universite Paris Cite, Paris, France.
⁵ myBrain Technologies, Paris, France.
⁶ Unit of Child and Adolescent Psychiatry (MPEA1), CHU Montpellier-Saint Eloi Hospital, University of Montpellier, Montpellier, France.
⁷ Mensia Technologies, Paris, France.
⁸ Child and Adolescent Psychiatry, Erasme Academic Hospital, Université Libre de Bruxelles, Bruxelles, Belgium.
⁹ Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
¹⁰ Clinique des Grangettes, Chêne-Bougeries, Geneva, Switzerland.
¹¹ Unit of Child and Adolescent Psychiatry, Hospices civils de Lyon, Hôpital Femme Mère Enfant, Bron Cedex, France.
¹² SANPSY, USR 3413, CNRS, Bordeaux, France.
¹³ Clinique du Sommeil, CHU Pellegrin, Bordeaux Cedex, France.
¹⁴ Development and Trajectories, INSERM CESP U 1018 Psychiatry, Montpellier, France.
¹⁵ CESP, INSERM U 1018, Paul Brousse Hospital, Villejuif, France.
¹⁶ Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
¹⁷ Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.

Abstract

Introduction: Earlier studies exploring the value of executive functioning (EF) indices for assessing treatment effectiveness and predicting treatment response in attention-deficit/hyperactivity disorder (ADHD) mainly focused on pharmacological treatment options and revealed rather heterogeneous results. Envisioning the long-term goal of personalized treatment selection and intervention planning, this study comparing methylphenidate treatment (MPH) and a home-based neurofeedback intervention (NF@Home) aimed to expand previous findings by assessing objective as well as subjectively reported EF indices and by analyzing their value as treatment and predictive markers.

Methods: Children and adolescents (n = 146 in the per protocol sample) aged 7-13 years with a formal diagnosis of an inattentive or combined presentation of ADHD were examined. We explored the EF performance profile using the Conners Continuous Performance Task (CPT) and the BRIEF self-report questionnaire within our prospective, multicenter, randomized, reference drug-controlled NEWROFEED study with sites in five European countries (France, Spain, Switzerland, Germany, and Belgium). As primary outcome for treatment response, the clinician-rated ADHD Rating Scale-IV was used. Patients participating in this non-inferiority trial were randomized to either NF@home (34-40 sessions of TBR or SMR NF depending on the pre-assessed individual alpha peak frequency) or MPH treatment (ratio: 3:2). Within a mixed-effects model framework, analyses of change were calculated to explore the predictive value of neurocognitive indices for ADHD symptom-related treatment response.

Results: For a variety of neurocognitive indices, we found a significant pre-post change during treatment, mainly in the MPH group. However, the results of the current study reveal a rather limited prognostic value of neurocognitive indices for treatment response to either NF@Home or MPH treatment. Some significant effects emerged for parent-ratings only.

Discussion: Current findings indicate a potential value of self-report (BRIEF global score) and some objectively measured neurocognitive indices (CPT commission errors and hit reaction time variability) as treatment markers (of change) for MPH. However, we found a rather limited prognostic value with regard to predicting treatment response not (yet) allowing recommendation for clinical use. Baseline symptom severity was revealed as the most relevant predictor, replicating robust findings from previous studies.

Keywords: ADHD; executive functions; methylphenidate; neurocognitive functioning; neurofeedback; predictive marker; treatment marker.

Copyright © 2024 Kaiser, Aggensteiner, Blasco Fontecilla, Ros, Acquaviva, Attal, Banaschewski, Baumeister, Bousquet, Bussalb, Delhaye, Delorme, Drechsler, Goujon, Häge, Mayaud, Mechler, Menache, Revol, Tagwerker, Walitza, Werling, Bioulac, Purper-Ouakil and Brandeis.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. AB reports grants from EU H2020 SME research and innovation grant N°684,809 during the conduct of the study. HB is the recipient of a MINECO grant (2019–2021). In 2019, he was the recipient of a PHUH intensification grant. He also received funding from a clinical trial sponsored by Janssen (ESKETINSUI2002). LM reports grants from EC H2020 SME Biomarker and personal fees from Mensia Technologies during the conduct of the study. SW’s work was supported in the last years by the Swiss National Science Foundation (SNF), diff. EU FP7s, HSM Hochspezialisierte Medizin of the Kanton Zurich, Switzerland, Bfarm Germany, ZInEP, Hartmann Müller Stiftung, Olga Mayenfisch, Gertrud Thalmann, Vontobel, Unicentia, Erika Schwarz, Heuberg Fonds, National Government of Health (BAG), Gesundheitsförderung Schweiz and Horizon Europe. The funders were not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.