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This article is the author's final published version in Science Advances, Volume 8, Issue 45, November 2022, Page number eabn2293.

The published version is available at Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.


Network control theory is increasingly used to profile the brain's energy landscape via simulations of neural dynamics. This approach estimates the control energy required to simulate the activation of brain circuits based on structural connectome measured using diffusion magnetic resonance imaging, thereby quantifying those circuits' energetic efficiency. The biological basis of control energy, however, remains unknown, hampering its further application. To fill this gap, investigating temporal lobe epilepsy as a lesion model, we show that patients require higher control energy to activate the limbic network than healthy volunteers, especially ipsilateral to the seizure focus. The energetic imbalance between ipsilateral and contralateral temporolimbic regions is tracked by asymmetric patterns of glucose metabolism measured using positron emission tomography, which, in turn, may be selectively explained by asymmetric gray matter loss as evidenced in the hippocampus. Our investigation provides the first theoretical framework unifying gray matter integrity, metabolism, and energetic generation of neural dynamics.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

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