Network-specific metabolic cost of functional connectivity in the human brain
- 1Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria
Abstract
Despite decades of extensive research, the complex architecture underlying human brain signaling remains incompletely understood. Previous work investigating the relationship between brain glucose metabolism and functional connectivity (FC) employed whole-brain analysis, without accounting for network interactions, dependencies or hierarchies. Here, we assess network-specific differences in the relationship between FC and metabolic demand, using [18F]FDG PET/MR data from three independent datasets. The metabolic cost of FC, i.e., the change in glucose demand associated with corresponding changes in FC, was modeled at rest, during cognitive task performance and in Alzheimer's disease (AD). Our findings reveal network-specific differences in metabolic cost, with the default mode (DM), somatomotor (SM) and fronto-temporal networks accounting for highest, intermediate and lowest metabolic demands, respectively. Similarly, time-resolved variability of FC demonstrated highest costs for states with DM network involvement and lowest for SM network participation. This relationship was reversed in participants with AD, who exhibited decreased demands in the DM network and increased costs in the SM network. Cognitive performance consistently revealed cost reductions in the DM and SM networks, as well as increases in task relevant networks. Together, these results highlight the flexibility of functional network architecture associated with cognitive demands and neuropathology, and shed light on the complex interplay between glucose metabolism and network interactions.
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BibTeX
@misc{tuchler2026networkspecific,
title = {{Network-specific metabolic cost of functional connectivity in the human brain}},
author = {S. M. Tüchler and P. Falb and C. Milz and M. Murgas and M. B. Reed and S. Graf and G. Schlosser and C. Schmidt and A. Mayerweg and S. Klug and I. Pörnbacher and L. Artmeier and A. Harouak and A. Sahl and M. Grohmann and L. Nics and G. M. Godbersen and S. Rasul and D. Rujescu and M. Hacker and R. Lanzenberger and A. Hahn and For the Alzheimer's Disease Neuroimaging Initiative},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.09.750304},
url = {https://www.biorxiv.org/content/10.64898/2026.09.09.750304v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Network-specific metabolic cost of functional connectivity in the human brain
AU - S. M. Tüchler
AU - P. Falb
AU - C. Milz
AU - M. Murgas
AU - M. B. Reed
AU - S. Graf
AU - G. Schlosser
AU - C. Schmidt
AU - A. Mayerweg
AU - S. Klug
AU - I. Pörnbacher
AU - L. Artmeier
AU - A. Harouak
AU - A. Sahl
AU - M. Grohmann
AU - L. Nics
AU - G. M. Godbersen
AU - S. Rasul
AU - D. Rujescu
AU - M. Hacker
AU - R. Lanzenberger
AU - A. Hahn
AU - For the Alzheimer's Disease Neuroimaging Initiative
PY - 2026
DA - 2026/09/09
PB - bioRxiv
DO - 10.64898/2026.09.09.750304
UR - https://www.biorxiv.org/content/10.64898/2026.09.09.750304v1
AB - Despite decades of extensive research, the complex architecture underlying human brain signaling remains incompletely understood. Previous work investigating the relationship between brain glucose metabolism and functional connectivity (FC) employed whole-brain analysis, without accounting for network interactions, dependencies or hierarchies. Here, we assess network-specific differences in the relationship between FC and metabolic demand, using [18F]FDG PET/MR data from three independent datasets. The metabolic cost of FC, i.e., the change in glucose demand associated with corresponding changes in FC, was modeled at rest, during cognitive task performance and in Alzheimer's disease (AD). Our findings reveal network-specific differences in metabolic cost, with the default mode (DM), somatomotor (SM) and fronto-temporal networks accounting for highest, intermediate and lowest metabolic demands, respectively. Similarly, time-resolved variability of FC demonstrated highest costs for states with DM network involvement and lowest for SM network participation. This relationship was reversed in participants with AD, who exhibited decreased demands in the DM network and increased costs in the SM network. Cognitive performance consistently revealed cost reductions in the DM and SM networks, as well as increases in task relevant networks. Together, these results highlight the flexibility of functional network architecture associated with cognitive demands and neuropathology, and shed light on the complex interplay between glucose metabolism and network interactions.
ER -