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Functional Brain Networks to Evaluate Treatment Responses in Parkinson’s Disease

  • Current Perspectives
  • Published:
Neurotherapeutics

Abstract

Network analysis of functional brain scans acquired with [18F]-fluorodeoxyglucose positron emission tomography (FDG PET, to map cerebral glucose metabolism), or resting-state functional magnetic resonance imaging (rs-fMRI, to map blood oxygen level-dependent brain activity) has increasingly been used to identify and validate reproducible circuit abnormalities associated with neurodegenerative disorders such as Parkinson’s disease (PD). In addition to serving as imaging markers of the underlying disease process, these networks can be used singly or in combination as an adjunct to clinical diagnosis and as a screening tool for therapeutics trials. Disease networks can also be used to measure rates of progression in natural history studies and to assess treatment responses in individual subjects. Recent imaging studies in PD subjects scanned before and after treatment have revealed therapeutic effects beyond the modulation of established disease networks. Rather, other mechanisms of action may be at play, such as the induction of novel functional brain networks directly by treatment. To date, specific treatment-induced networks have been described in association with novel interventions for PD such as subthalamic adeno-associated virus glutamic acid decarboxylase (AAV2-GAD) gene therapy, as well as sham surgery or oral placebo under blinded conditions. Indeed, changes in the expression of these networks with treatment have been found to correlate consistently with clinical outcome. In aggregate, these attributes suggest a role for functional brain networks as biomarkers in future clinical trials.

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Data Availability

Data will be available from the corresponding author upon reasonable request.

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Acknowledgements

Aspects of this work were supported by the National Institute of Neurological Disorders and Stroke (NIH R01 NS105979 to D.E.) and The Michael J. Fox Foundation for Parkinson’s Research (MJFF-008252 to D.E.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Institute of Neurological Disorders and Stroke. The authors wish to thank Ms. Christine Edwards for manuscript preparation and editorial assistance.

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  1. Center for Neurosciences, The Feinstein Institutes for Medical Research, 350 Community Drive, Manhasset, NY, 11030, USA

    János A. Barbero, Prashin Unadkat, Yoon Young Choi & David Eidelberg

  2. Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, 11549, USA

    János A. Barbero & Prashin Unadkat

  3. Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, 11030, USA

    Prashin Unadkat

  4. Molecular Medicine and Neurology, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, 11549, USA

    David Eidelberg

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Barbero, J.A., Unadkat, P., Choi, Y.Y. et al. Functional Brain Networks to Evaluate Treatment Responses in Parkinson’s Disease. Neurotherapeutics 20, 1653–1668 (2023). https://doi.org/10.1007/s13311-023-01433-w

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