Metabolic demands of the posteromedial default mode network are shaped by dorsal attention and frontoparietal control networks

Although BOLD signal decreases in the default mode network (DMN) are commonly observed during attention-demanding tasks, their neurobiological underpinnings are not fully understood. Previous work has shown decreases but also increases in glucose metabolism that match with or dissociate from these BOLD signal decreases, respectively. To resolve this discrepancy, we analyzed functional PET/MRI data from 50 healthy subjects during the performance of the visuo-spatial processing game Tetris® and combined this with previously published data sets of working memory as well as visual and motor stimulation. Our findings show that the glucose metabolism of the posteromedial DMN is dependent on the metabolic demands of the correspondingly engaged task-positive brain networks. Specifically, the dorsal attention (involved in Tetris®) and frontoparietal networks (engaged during working memory) shape the glucose metabolism of the posteromedial DMN in opposing directions. External attention-demanding tasks lead to a downregulation of the posteromedial DMN with consistent decreases in the BOLD signal and glucose metabolism, whereas working memory is subject to metabolically expensive mechanisms of BOLD signal suppression. We suggest that the former finding is mediated by decreased glutamate signaling, while the latter results from active GABAergic inhibition, regulating the competition between self-generated and task-driven internal demands. The results demonstrate that the DMN relates to cognitive processing in a flexible manner and does not always act as a cohesive task-negative network in isolation. ### Competing Interest Statement This research was funded in whole, or in part, by the Austrian Science Fund (FWF) KLI 610, PI: A. Hahn. For the purpose of open access, the author has applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission. S. Klug is supported by the MDPhD Excellence Program of the Medical University of Vienna. A.R. and L.S. are supported by the European Research Council under the European Unions Horizon 2020 research and innovation program (ERC-STG-716065 to A.R). LC is supported by the Australian NHMRC (GN2001283). R. Lanzenberger received travel grants and/or conference speaker honoraria within the last three years from Bruker BioSpin MR and Heel, and has served as a consultant for Ono Pharmaceutical. He received investigator-initiated research funding from Siemens Healthcare regarding clinical research using PET/MRI. He is a shareholder of the start-up company BM Health GmbH since 2019. M. Hacker received consulting fees and/or honoraria from Bayer Healthcare BMS, Eli Lilly, EZAG, GE Healthcare, Ipsen, ITM, Janssen, Roche, and Siemens Healthineers. W. Wadsak declares to having received speaker honoraria from the GE Healthcare and research grants from Ipsen Pharma, Eckert-Ziegler AG, Scintomics, and ITG, and working as a part time employee of CBmed Ltd. (Center for Biomarker Research in Medicine, Graz, Austria). All other authors report no competing interests in relation to this study.