David Eidelberg, MD Seminar #2

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-specific networks can also be used to measure rates of progression in natural history studies and to assess responses to symptomatic treatment or to potential disease modifying agents. 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, reproducible treatment-induced networks have been reported for established interventions such as deep brain stimulation (DBS) and novel therapeutic strategies such as subthalamic gene therapy and oral nicotinamide riboside (NR), and as a potential imaging marker of the placebo response. Indeed, changes in the expression of these networks with treatment have been found to correlate consistently with clinical outcome. Together, the data suggest a role for functional brain networks as treatment biomarkers in clinical trials for PD and other brain disorders.