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FMRI hemodynamic response function (HRF) as a novel marker of brain function: applications for understanding obsessive-compulsive disorder pathology and treatment response

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Abstract

The hemodynamic response function (HRF) represents the transfer function linking neural activity with the functional MRI (fMRI) signal, modeling neurovascular coupling. Since HRF is influenced by non-neural factors, to date it has largely been considered as a confound or has been ignored in many analyses. However, underlying biophysics suggests that the HRF may contain meaningful correlates of neural activity, which might be unavailable through conventional fMRI metrics. Here, we estimated the HRF by performing deconvolution on resting-state fMRI data from a longitudinal sample of 25 healthy controls scanned twice and 44 adults with obsessive-compulsive disorder (OCD) before and after 4-weeks of intensive cognitive-behavioral therapy (CBT). HRF response height, time-to-peak and full-width at half-maximum (FWHM) in OCD were abnormal before treatment and normalized after treatment in regions including the caudate. Pre-treatment HRF predicted treatment outcome (OCD symptom reduction) with 86.4% accuracy, using machine learning. Pre-treatment HRF response height in the caudate head and time-to-peak in the caudate tail were top-predictors of treatment response. Time-to-peak in the caudate tail, a region not typically identified in OCD studies using conventional fMRI activation or connectivity measures, may carry novel importance. Additionally, pre-treatment response height in caudate head predicted post-treatment OCD severity (R = -0.48, P = 0.001), and was associated with treatment-related OCD severity changes (R = -0.44, P = 0.0028), underscoring its relevance. With HRF being a reliable marker sensitive to brain function, OCD pathology, and intervention-related changes, these results could guide future studies towards novel discoveries not possible through conventional fMRI approaches like standard BOLD activation or connectivity.

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Acknowledgements

We acknowledge Michelle Massi and Natalie Abrahami for their role in providing cognitive-behavioral therapy treatment for the participants with obsessive-compulsive disorder in this study.

Funding

This study was supported by US National Institutes of Mental Health (NIMH) grant R01 MH085900 (to Drs. Feusner and O’Neill).

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Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA, 90095, USA

    D. Rangaprakash, Reza Tadayonnejad, Joseph O’Neill & Jamie D. Feusner

  2. Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School and Harvard-MIT Health Sciences and Technology, Cambridge, MA, 02129, USA

    D. Rangaprakash

  3. Division of the Humanities and Social Sciences, California Institute of Technology, Pasadena, CA, 91125, USA

    Reza Tadayonnejad

  4. AU MRI Research Center, Department of Electrical and Computer Engineering, Auburn University, Auburn, AL, 36849, USA

    Gopikrishna Deshpande

  5. Department of Psychological Sciences, Auburn University, Auburn, AL, 36849, USA

    Gopikrishna Deshpande

  6. Alabama Advanced Imaging Consortium, Auburn University and University of Alabama Birmingham, Auburn, AL, USA

    Gopikrishna Deshpande

  7. Center for Health Ecology and Equity Research, Auburn University, Auburn, AL, USA

    Gopikrishna Deshpande

  8. Center for Neuroscience, Auburn University, Auburn, AL, USA

    Gopikrishna Deshpande

  9. School of Psychology, Capital Normal University, Beijing, China

    Gopikrishna Deshpande

  10. Key Laboratory for Learning and Cognition, Capital Normal University, Beijing, China

    Gopikrishna Deshpande

  11. Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, India

    Gopikrishna Deshpande

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  1. D. Rangaprakash
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  2. Reza Tadayonnejad
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  3. Gopikrishna Deshpande
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  4. Joseph O’Neill
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  5. Jamie D. Feusner
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Corresponding author

Correspondence to Jamie D. Feusner.

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Conflict of interest

All the authors (D.R., R.T., G.D, J.O., J.D.F.) declare no conflicts of interest.

Ethical approval

All procedures involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. UCLA institutional review board (IRB) approved the study procedures.

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Written informed consent was obtained from all individual participants included in the study.

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Rangaprakash, D., Tadayonnejad, R., Deshpande, G. et al. FMRI hemodynamic response function (HRF) as a novel marker of brain function: applications for understanding obsessive-compulsive disorder pathology and treatment response. Brain Imaging and Behavior 15, 1622–1640 (2021). https://doi.org/10.1007/s11682-020-00358-8

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