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

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.