Abstracts

Impaired Functional Connectivity of the Central Autonomic Network Relates to Interictal Cardiorespiratory Dysfunction in Epilepsy

Abstract number : 2.31
Submission category : 5. Neuro Imaging / 5B. Functional Imaging
Year : 2024
Submission ID : 1212
Source : www.aesnet.org
Presentation date : 12/8/2024 12:00:00 AM
Published date :

Authors :
Presenting Author: Haatef Pourmotabbed, MS – Vanderbilt University

Derek Doss, BE – Vanderbilt University
William Nobis, MD, PhD – Vanderbilt University Medical Center
Victoria Morgan, PhD – Vanderbilt University Medical Center
Dario Englot, MD, PhD – Vanderbilt University Medical Center
Catie Chang, PhD – Vanderbilt University

Rationale: Patients with temporal lobe epilepsy (TLE) experience interictal deficits of cardiorespiratory and autonomic function, which have been linked to increased risk for sudden unexpected death in epilepsy (SUDEP)1,2. Prior studies have also shown that TLE patients at high risk for SUDEP present with structural, cellular, and functional connectivity (FC) abnormalities in central autonomic regions3. However, it is not clear how these chronic brain impairments directly impact cardiorespiratory function. The purpose of this study was to investigate FC disruptions of the central autonomic network in TLE and to relate the FC to interictal cardiorespiratory dysfunction.

Methods: This study included simultaneous fMRI, respiratory, and photoplethysmography (PPG) data collected from 69 unilateral TLE patients (40.2 ± 13.0 years; 33 females; 30 left and 39 right TLE) and 105 controls (36.7 ± 12.8 years; 56 females). Measures of breathing rate (BR) and low- and high-frequency heart rate variability (LF/HF-HRV) were derived from the respiratory and PPG data. Mean fMRI signals were extracted for central autonomic regions of the Brainnetome atlas4 and for neuroregulatory arousal and autonomic centers in the brainstem5, basal forebrain6, and bed nucleus of the stria terminalis7. The average FC (Pearson correlation) of each brain region in the autonomic subnetwork was computed, compared between patients and controls (two-sample t-test), and related to the BR and HRV of the patients (Spearman’s rho). All statistical tests were performed with age and sex covariates.

Results: The average FC of 93 out of the 116 autonomic regions was significantly reduced in TLE compared to controls (mean t = -2.98; p < 0.05, false discovery rate [FDR]-corrected), and the patients had an increased BR and decreased LF-HRV (pFDR < 0.01) (Fig. 1). Decreased FC of the mesial temporal lobe, insula, cingulate gyrus, thalamus, medial/orbitofrontal cortex, fusiform gyrus, basal ganglia, and basal forebrain was associated with higher BR in the patients (43 regions; mean rho = -0.34; pFDR < 0.05), and decreased FC of the cingulate gyrus, thalamus, orbitofrontal cortex, and basal ganglia was associated with lower LF-HRV (8 regions; mean rho = 0.38, pFDR < 0.05) (Fig. 2).

Conclusions: We showed that the FC of a widespread network of autonomic and arousal regions was altered in TLE, which agrees with the findings of previous studies3,8. Our results indicate that the impaired FC of the central autonomic network contributes to interictal deficits of respiration and cardiac autonomic function, potentially acting as a neural mechanism underlying elevated risk for SUDEP. Mapping of these autonomic network impairments may help identify therapeutic targets to reduce the risk of severe cardiorespiratory dysfunction and SUDEP.

Funding: This work was supported by NIH grants T32 EB021937 and R01 NS112252, NS110130, and NS108445.

Neuro Imaging