Neurovascular Uncoupling In Schizophrenia: A Bimodal Meta-Analysis of Brain Perfusion and Glucose Metabolism

The use ofmodern neuroimaging approaches has demonstrated resting-state regional cerebralblood flow (rCBF) to be tightly coupled to resting cerebral glucose metabolism(rCMRglu) in healthy brains. In schizophrenia, several lines of evidence point towardsaberrant neurovascular coupling, especially in the prefrontal regions. To investigatethis, we used Signed Differential Mapping to undertake a voxel-based bimodal metaanalysisexamining the relationship between rCBF and rCMRglu in schizophrenia, asmeasured by Arterial Spin Labeling (ASL) and 18Flurodeoxyglucose Positron EmissionTomography (FDG-PET) respectively. We used 19 studies comprised of data from 557patients and 584 controls. Our results suggest that several key regions implicated in thepathophysiology of schizophrenia such as the frontoinsular cortex, dorsal ACC,putamen, and temporal pole show conjoint metabolic and perfusion abnormalities inpatients. In contrast, discordance between metabolism and perfusion were seen insuperior frontal gyrus and cerebellum, indicating that factors contributing toneurovascular uncoupling (e.g. inflammation, mitochondrial dysfunction, oxidativestress) are likely operates at these loci. Hybrid ASL-PET studies focusing on theseregions could confirm our proposition.