Lack of evidence for predictive utility from resting state fMRI data for individual exposure-based cognitive behavioral therapy outcomes: A machine learning study in two large multi-site samples in anxiety disorders.

Journal: NeuroImage
PMID: 38796977

Abstract

Data-based predictions of individual Cognitive Behavioral Therapy (CBT) treatment response are a fundamental step towards precision medicine. Past studies demonstrated only moderate prediction accuracy (i.e. ability to discriminate between responders and non-responders of a given treatment) when using clinical routine data such as demographic and questionnaire data, while neuroimaging data achieved superior prediction accuracy. However, these studies may be considerably biased due to very limited sample sizes and bias-prone methodology. Adequately powered and cross-validated samples are a prerequisite to evaluate predictive performance and to identify the most promising predictors. We therefore analyzed resting state functional magnet resonance imaging (rs-fMRI) data from two large clinical trials to test whether functional neuroimaging data continues to provide good prediction accuracy in much larger samples. Data came from two distinct German multicenter studies on exposure-based CBT for anxiety disorders, the Protect-AD and SpiderVR studies. We separately and independently preprocessed baseline rs-fMRI data from n = 220 patients (Protect-AD) and n = 190 patients (SpiderVR) and extracted a variety of features, including ROI-to-ROI and edge-functional connectivity, sliding-windows, and graph measures. Including these features in sophisticated machine learning pipelines, we found that predictions of individual outcomes never significantly differed from chance level, even when conducting a range of exploratory post-hoc analyses. Moreover, resting state data never provided prediction accuracy beyond the sociodemographic and clinical data. The analyses were independent of each other in terms of selecting methods to process resting state data for prediction input as well as in the used parameters of the machine learning pipelines, corroborating the external validity of the results. These similar findings in two independent studies, analyzed separately, urge caution regarding the interpretation of promising prediction results based on neuroimaging data from small samples and emphasizes that some of the prediction accuracies from previous studies may result from overestimation due to homogeneous data and weak cross-validation schemes. The promise of resting-state neuroimaging data to play an important role in the prediction of CBT treatment outcomes in patients with anxiety disorders remains yet to be delivered.

Authors

  • Kevin Hilbert
  • Joscha Böhnlein
    Institute for Translational Psychiatry, University of Münster, Germany. Electronic address: joscha.boehnlein@uni-muenster.de.
  • Charlotte Meinke
    Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Alice V Chavanne
    Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Till Langhammer
    Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany.
  • Lara Stumpe
    Institute for Translational Psychiatry, University of Münster, Germany.
  • Nils Winter
    Institute for Translational Psychiatry, University of Münster, Germany.
  • Ramona Leenings
    Institute for Translational Psychiatry, University of Münster, Münster, Germany.
  • Dirk Adolph
    Mental Health Research and Treatment Center, Faculty of Psychology, Ruhr-Universität Bochum, Bochum, Germany.
  • Volker Arolt
    Department of Psychiatry, University of Muenster, Muenster, Germany.
  • Sophie Bischoff
    Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Jan C Cwik
    Department of Clinical Psychology and Psychotherapy, Faculty of Human Sciences, Universität zu Köln, Germany.
  • Jürgen Deckert
    Center for Mental Health, Department of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Würzburg, Germany.
  • Katharina Domschke
    Department of Psychiatry and Psychotherapy, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Thomas Fydrich
    Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany; Zentrum für Psychotherapie, Humboldt-Universität zu Berlin, Berlin, Germany. Electronic address: fydrich@hu-berlin.de.
  • Bettina Gathmann
    Institute of Medical Psychology and Systems Neuroscience, University of Münster, Germany.
  • Alfons O Hamm
    Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany.
  • Ingmar Heinig
    Institute of Clinical Psychology & Psychotherapy, Technische Universität Dresden, Dresden, Germany.
  • Martin J Herrmann
    Department of Psychiatry, Psychosomatics, and Psychotherapy, Center for Mental Health, University Hospital of Würzburg, Germany.
  • Maike Hollandt
    Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany.
  • Jürgen Hoyer
    Institute of Clinical Psychology & Psychotherapy, Technische Universität Dresden, Dresden, Germany.
  • Markus Junghöfer
    Institute for Biomagnetism and Biosignalanalysis, University of Münster, Germany.
  • Tilo Kircher
    Department of Psychiatry, University of Marburg, Marburg, Germany.
  • Katja Koelkebeck
    LVR-University-Hospital Essen, Department of Psychiatry and Psychotherapy, University of Duisburg-Essen, Essen, Germany.
  • Martin Lotze
    Functional Imaging Unit. Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
  • Jürgen Margraf
    Mental Health Research and Treatment Center, Faculty of Psychology, Ruhr-Universität Bochum, Bochum, Germany.
  • Jennifer L M Mumm
    Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Peter Neudeck
    Protect-AD Study Site Cologne, Cologne, Germany; Institut für Klinische Psychologie und Psychotherapie, TU Chemnitz, Germany.
  • Paul Pauli
    Department of Psychology, University of Würzburg, Würzburg, Germany.
  • Andre Pittig
    Translational Psychotherapy, Institute of Psychology, University of Göttingen, Germany.
  • Jens Plag
    Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany; Department of Psychiatry, Psychotherapy and Psychosomatics, Alexianer Krankenhaus Hedwigshoehe, St. Hedwig Kliniken, Berlin, Germany.
  • Jan Richter
    Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany; Department of Experimental Psychopathology, University of Hildesheim, Hildesheim, Germany.
  • Isabelle C Ridderbusch
    Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
  • Winfried Rief
    Department of Clinical Psychology and Psychotherapy, Faculty of Psychology & Center for Mind, Brain and Behavior - CMBB, Philipps-University of Marburg, Marburg, Germany.
  • Silvia Schneider
    Faculty of Psychology, Clinical Child and Adolescent Psychology, Mental Health Research and Treatment Center, Ruhr-Universität Bochum, Bochum, Germany.
  • Hanna Schwarzmeier
    Department of Psychiatry, Psychosomatics, and Psychotherapy, Center for Mental Health, University Hospital of Würzburg, Germany.
  • Fabian R Seeger
    Department of Psychiatry, Psychosomatics, and Psychotherapy, Center for Mental Health, University Hospital of Würzburg, Germany.
  • Niklas Siminski
    Department of Psychiatry, Psychosomatics, and Psychotherapy, Center for Mental Health, University Hospital of Würzburg, Germany.
  • Benjamin Straube
    Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
  • Thomas Straube
    Institute for Translational Psychiatry, University of Münster, Germany.
  • Andreas Ströhle
    Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Hans-Ulrich Wittchen
  • Adrian Wroblewski
    Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
  • Yunbo Yang
    Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany.
  • Kati Roesmann
    Institute of Clinical Psychology and Psychotherapy, University of Siegen, Germany.
  • Elisabeth J Leehr
    Institute for Translational Psychiatry, University of Münster, Germany.
  • Udo Dannlowski
    Department of Psychiatry and Psychotherapy, University of Münster, Germany.
  • Ulrike Lueken
    Department of Psychology, Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Chemnitzer Straße 46, 01187, Dresden, Germany, ulrike.lueken@tu-dresden.de.

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