Static versus Functional PET: Making Sense of Metabolic Connectivity

Recently, Jamadar et al. (2021, Metabolic and hemodynamic resting-state connectivity of the human brain: a high-temporal resolution simultaneous BOLD-fMRI and FDG-fPET multimodality study. Cereb Cortex. 31(6), 2855-2867) compared the patterns of brain connectivity or covariance as obtained from 3 neuroimaging measures: 1) functional connectivity estimated from temporal correlations in the functional magnetic resonance imaging blood oxygen level-dependent signal, metabolic connectivity estimated, 2) from temporal correlations in 16-s frames of dynamic [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), which they designate as functional FDG-PET (fPET), and 3) from intersubject correlations in static FDG-PET images (sPET). Here, we discuss a number of fundamental issues raised by the Jamadar study. These include the choice of terminology, the interpretation of cross-modal findings, the issue of group- to single-subject level inferences, and the meaning of metabolic connectivity as a biomarker. We applaud the methodological approach taken by the authors, but wish to present an alternative perspective on their findings. In particular, we argue that sPET and fPET can both provide valuable information about brain connectivity. Certainly, resolving this conundrum calls for further experimental and theoretical efforts to advance the developing framework of PET-based brain connectivity indices.