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Peer-reviewedCC BYFrontiers in network physiology

Investigating cardiorespiratory fitness, cerebral blood flow, and brain metabolism in epilepsy

  • Yun Lien1
  • Brandon S. Mitchell1
  • Jerzy P. Szaflarski2
  • Lawrence Ver Hoef2
  • Thomas W. Buford3
  • Adam M. Goodman1
  • William R. Willoughby4
  • Charity J. Morgan5
  • Anna Moyana2
  • Jennifer Pilkington2
  • Amy R. August6
  • Joshua T. Bennett6
1 more authors
  • Jane B. Allendorfer2
6 affiliations
  1. 1Department of Psychology, University of Alabama at Birmingham , , ,
  2. 2Department of Neurology, University of Alabama at Birmingham , , ,
  3. 3Department of Medicine, University of Alabama at Birmingham , , ,
  4. 4Department of Radiology, University of Alabama at Birmingham , , ,
  5. 5Department of Biostatistics, University of Alabama at Birmingham , , ,
  6. 6University of Alabama at Birmingham Center for Exercise Medicine , , ,
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Abstract

Introduction: Idiopathic generalized epilepsies (IGEs) are characterized by seizures that propagate through widespread thalamocortical networks including the anterior cingulate cortex (ACC). Poor cardiorespiratory fitness may exacerbate neurovascular and metabolic vulnerability including heightened susceptibility to sudden unexpected death in epilepsy. We aimed to examine cardiorespiratory fitness, regional cerebral blood flow (CBF), and metabolite concentrations in patients with IGEs (PwIGEs) and to determine the effect of seizure control status on these physiological and neurochemical measures.

Methods: Forty-six participants (31 PwIGEs, 15 healthy controls) underwent a graded exercise test to assess maximal oxygen uptake (VO2peak) as a measure of cardiorespiratory fitness and completed 3T MRI including multi-delayed pseudo-continuous arterial spin labeling (pCASL) to assess CBF and single-voxel spectroscopy (SVS) to assess ratios of N-acetylaspartate and glutamate/glutamine complex to total creatine (NAA/tCr and Glx/tCr, respectively) in the ACC and thalamus. Group differences and seizure control effects in PwIGEs were examined using analysis of covariance (ANCOVA).

Results: VO2peak, thalamic CBF, ACC NAA/tCr, and ACC Glx/tCr did not significantly differ between groups. PwIGEs exhibited higher ACC CBF (p = 0.039) and lower thalamic NAA/tCr (p = 0.012) than healthy controls. PwIGEs with active seizures showed significantly lower thalamic Glx/tCr compared to those who were seizure-free (p = 0.003).

Discussion: These findings suggest poor cardiorespiratory fitness is not epilepsy-specific and likely attributable to lifestyle and that region-specific alterations in perfusion and metabolic milieu in PwIGEs characterized by higher ACC CBF and lower thalamic NAA/tCr and Glx/tCr in those with active seizures. The multimodal neuroimaging approach provides convergent evidence of thalamocortical network dysregulation underlying IGE pathophysiology.

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Cite

BibTeXRIS
BibTeX
@article{lien2026investigating,
  title = {{Investigating cardiorespiratory fitness, cerebral blood flow, and brain metabolism in epilepsy}},
  author = {Yun Lien and Brandon S. Mitchell and Jerzy P. Szaflarski and Lawrence Ver Hoef and Thomas W. Buford and Adam M. Goodman and William R. Willoughby and Charity J. Morgan and Anna Moyana and Jennifer Pilkington and Amy R. August and Joshua T. Bennett and Jane B. Allendorfer},
  journal = {Frontiers in network physiology},
  year = {2026},
  month = oct,
  doi = {10.3389/fnetp.2026.1894335},
  url = {https://europepmc.org/article/PMC/PMC13727442},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Investigating cardiorespiratory fitness, cerebral blood flow, and brain metabolism in epilepsy
AU  - Yun Lien
AU  - Brandon S. Mitchell
AU  - Jerzy P. Szaflarski
AU  - Lawrence Ver Hoef
AU  - Thomas W. Buford
AU  - Adam M. Goodman
AU  - William R. Willoughby
AU  - Charity J. Morgan
AU  - Anna Moyana
AU  - Jennifer Pilkington
AU  - Amy R. August
AU  - Joshua T. Bennett
AU  - Jane B. Allendorfer
PY  - 2026
DA  - 2026/10/20
JO  - Frontiers in network physiology
DO  - 10.3389/fnetp.2026.1894335
UR  - https://europepmc.org/article/PMC/PMC13727442
AB  - Introduction: Idiopathic generalized epilepsies (IGEs) are characterized by seizures that propagate through widespread thalamocortical networks including the anterior cingulate cortex (ACC). Poor cardiorespiratory fitness may exacerbate neurovascular and metabolic vulnerability including heightened susceptibility to sudden unexpected death in epilepsy. We aimed to examine cardiorespiratory fitness, regional cerebral blood flow (CBF), and metabolite concentrations in patients with IGEs (PwIGEs) and to determine the effect of seizure control status on these physiological and neurochemical measures.  Methods: Forty-six participants (31 PwIGEs, 15 healthy controls) underwent a graded exercise test to assess maximal oxygen uptake (VO2peak) as a measure of cardiorespiratory fitness and completed 3T MRI including multi-delayed pseudo-continuous arterial spin labeling (pCASL) to assess CBF and single-voxel spectroscopy (SVS) to assess ratios of N-acetylaspartate and glutamate/glutamine complex to total creatine (NAA/tCr and Glx/tCr, respectively) in the ACC and thalamus. Group differences and seizure control effects in PwIGEs were examined using analysis of covariance (ANCOVA).  Results: VO2peak, thalamic CBF, ACC NAA/tCr, and ACC Glx/tCr did not significantly differ between groups. PwIGEs exhibited higher ACC CBF (p = 0.039) and lower thalamic NAA/tCr (p = 0.012) than healthy controls. PwIGEs with active seizures showed significantly lower thalamic Glx/tCr compared to those who were seizure-free (p = 0.003).  Discussion: These findings suggest poor cardiorespiratory fitness is not epilepsy-specific and likely attributable to lifestyle and that region-specific alterations in perfusion and metabolic milieu in PwIGEs characterized by higher ACC CBF and lower thalamic NAA/tCr and Glx/tCr in those with active seizures. The multimodal neuroimaging approach provides convergent evidence of thalamocortical network dysregulation underlying IGE pathophysiology.
SN  - 2674-0109
ER  -