Neural energy metabolism encodes directed communication across the human cortex
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Abstract
Complex cognition depends on directed communication between brain regions. Yet, resting functional MRI resolves only undirected associations, and inferring the direction of signalling has proven difficult across the whole brain. Because synaptic transmission is metabolically asymmetric, with the postsynaptic neuron bearing most of the energetic cost, regional energy demand carries a physical signature of the direction of communication. Here, we show that this signature organizes the human cortex into a reproducible directed hierarchy, in which sensory and attentional systems preferentially drive higher-order networks, while the default mode and control networks act as principal receivers. Critically, the inferred directionality is independently predicted by two cellular markers of neuronal energy demand, regional mitochondrial density and laminar cytoarchitecture, linking macroscale information flow to its cellular substrate. The directed architecture recapitulates the known feedforward and feedback organization of visual pathways and, using an average CMRGlc template, extends to functional MRI acquired without PET. By grounding communication direction in energy metabolism, Metabolic Connectivity Mapping bridges correlative and effective connectivity and offers a scalable, biologically interpretable framework for mapping directed communication across the human brain.
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BibTeX
@misc{belenya2026neural,
title = {{Neural energy metabolism encodes directed communication across the human cortex}},
author = {R. Belenya and S. Epp and A. Bose and A. Hechler and L. Fraticelli and M. Ashrafi and A. Ranft and I. Yakushev and K. Kurcyus and G. Castrillon and V. Riedl},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.28.728560},
url = {https://www.biorxiv.org/content/10.64898/2026.05.28.728560v3},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Neural energy metabolism encodes directed communication across the human cortex
AU - R. Belenya
AU - S. Epp
AU - A. Bose
AU - A. Hechler
AU - L. Fraticelli
AU - M. Ashrafi
AU - A. Ranft
AU - I. Yakushev
AU - K. Kurcyus
AU - G. Castrillon
AU - V. Riedl
PY - 2026
DA - 2026/05/28
PB - bioRxiv
DO - 10.64898/2026.05.28.728560
UR - https://www.biorxiv.org/content/10.64898/2026.05.28.728560v3
AB - Complex cognition depends on directed communication between brain regions. Yet, resting functional MRI resolves only undirected associations, and inferring the direction of signalling has proven difficult across the whole brain. Because synaptic transmission is metabolically asymmetric, with the postsynaptic neuron bearing most of the energetic cost, regional energy demand carries a physical signature of the direction of communication. Here, we show that this signature organizes the human cortex into a reproducible directed hierarchy, in which sensory and attentional systems preferentially drive higher-order networks, while the default mode and control networks act as principal receivers. Critically, the inferred directionality is independently predicted by two cellular markers of neuronal energy demand, regional mitochondrial density and laminar cytoarchitecture, linking macroscale information flow to its cellular substrate. The directed architecture recapitulates the known feedforward and feedback organization of visual pathways and, using an average CMRGlc template, extends to functional MRI acquired without PET. By grounding communication direction in energy metabolism, Metabolic Connectivity Mapping bridges correlative and effective connectivity and offers a scalable, biologically interpretable framework for mapping directed communication across the human brain.
ER -