Postsurgical Changes in the Central Autonomic Network Impact Cardiorespiratory Function in Epilepsy
Poster No:
1453
Submission Type:
Abstract Submission
Authors:
Haatef Pourmotabbed1, Derek Doss1, William Nobis2, Dario Englot2, Victoria Morgan2, Catie Chang1
Institutions:
1Vanderbilt University, Nashville, TN, 2Vanderbilt University Medical Center, Nashville, TN
First Author:
Co-Author(s):
Introduction:
Patients with temporal lobe epilepsy (TLE) experience abnormal breathing patterns and cardiac autonomic function even during the interictal period (between seizures), which have been linked to higher risk for sudden unexpected death in epilepsy (SUDEP) (Sainju et al., 2023; Sivathamboo et al., 2021). Furthermore, prior studies have shown that TLE patients exhibit impairments of structural morphology and interictal functional connectivity (FC) in neuroregulatory arousal and autonomic circuits that extend beyond the temporal lobe (Allen et al., 2019; Englot et al., 2020). However, it is unknown how these chronic brain network impairments directly contribute to cardiorespiratory dysfunction. The purpose of this study was to relate FC disruptions of the central autonomic network in TLE to interictal cardiorespiratory deficits. We also examined how brain network changes following epilepsy surgical treatment can impact cardiorespiratory function.
Methods:
This study included simultaneous fMRI, respiratory, and photoplethysmography (PPG) data collected from 72 unilateral TLE patients and 105 controls. 35 of the TLE patients also had fMRI scans collected one year after surgery (26 selective amygdalohippocampectomy, 8 anterior temporal lobe resection, and 1 laser ablation of the amygdala and hippocampus). The breathing rate (BR) and low- and high-frequency heart rate variability (LF/HF-HRV) were estimated from the respiratory and PPG data and averaged over the entire scan duration. Mean fMRI signals were extracted for 70 extratemporal autonomic regions from the Brainnetome atlas (Fan et al., 2016) and for 18 neuroregulatory centers in the brainstem, basal forebrain, extended amygdala, and hypothalamus (Edlow et al., 2024; Neudorfer et al., 2020; Zaborszky et al., 2008). The Pearson correlation was then used to compute the average FC strength of each region within the autonomic subnetwork.
The presurgical FC, BR, and HRV were compared between patients and controls (t-tests), and Spearman correlation tests were used to identify brain regions whose presurgical FC in the patients was significantly associated with the BR and HRV. We then computed the pre-to-postsurgical difference in the total FC strength of the identified regions and related the change in FC to the pre-to-postsurgical difference in the BR and HRV (Spearman correlation). All statistical analyses were performed while controlling for age and sex, and statistical significance was assessed at p < 0.05 (FDR corrected).
The presurgical FC, BR, and HRV were compared between patients and controls (t-tests), and Spearman correlation tests were used to identify brain regions whose presurgical FC in the patients was significantly associated with the BR and HRV. We then computed the pre-to-postsurgical difference in the total FC strength of the identified regions and related the change in FC to the pre-to-postsurgical difference in the BR and HRV (Spearman correlation). All statistical analyses were performed while controlling for age and sex, and statistical significance was assessed at p < 0.05 (FDR corrected).
Results:
The FC strength of 78 out of 88 autonomic regions was significantly reduced in TLE compared to controls (mean t-value = -3.5; Fig. 1). Additionally, the TLE patients had a higher BR and a lower LF-HRV relative to controls. Decreased FC of the insula, cingulate gyrus, medial prefrontal cortex, orbitofrontal cortex, thalamus, basal ganglia, pedunculopontine tegmentum nucleus, and nucleus basalis of Meynert was significantly associated with a higher BR in the TLE patients (36 regions; mean rho = -0.35), and decreased FC of the insula, cingulate gyrus, orbitofrontal cortex, thalamus, basal ganglia, median raphe, parabrachial nuclear complex, and extended amygdala was significantly associated with a lower LF-HRV (44 regions; mean rho = 0.31). Pre-to-postsurgical alterations in the total FC strength of these regions had a significant positive correlation with pre-to-postsurgical changes in LF-HRV (rho = 0.49; Fig. 2) and a non-significant negative correlation with changes in BR (rho = -0.2).
Conclusions:
Overall, our results indicate that TLE patients have widespread FC disruptions in neuroregulatory regions outside of the temporal lobe and that impaired neural communication in these regions may contribute to interictal cardiorespiratory abnormalities. Our findings also suggest that postsurgical alterations in the FC may influence cardiac autonomic function. Therefore, therapeutic targeting of brain networks in TLE may help reduce the risk of severe cardiorespiratory dysfunction and SUDEP.
Modeling and Analysis Methods:
Connectivity (eg. functional, effective, structural)
fMRI Connectivity and Network Modeling 1
Task-Independent and Resting-State Analysis 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
Brainstem
Computational Neuroscience
Epilepsy
FUNCTIONAL MRI
Other - Functional connectivity; resting-state; autonomic nervous system; cardiac and respiratory function
1|2Indicates the priority used for review
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Provide references using APA citation style.
Edlow, B. L. et al. (2024). Multimodal MRI reveals brainstem connections that sustain wakefulness in human consciousness. Sci Transl Med, 16(745), eadj4303.
Englot, D. J. et al. (2020). Impaired vigilance networks in temporal lobe epilepsy: Mechanisms and clinical implications. Epilepsia, 61(2), 189-202.
Fan, L. et al. (2016). The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture. Cereb Cortex, 26(8), 3508-3526.
Neudorfer, C. et al. (2020). A high-resolution in vivo magnetic resonance imaging atlas of the human hypothalamic region. Sci Data, 7(1), 305.
Sainju, R. K. et al. (2023). Interictal respiratory variability predicts severity of hypoxemia after generalized convulsive seizures. Epilepsia, 64(9), 2373-2384.
Sivathamboo, S. et al. (2021). Association of Short-term Heart Rate Variability and Sudden Unexpected Death in Epilepsy. Neurology, 97(24), e2357-e2367.
Zaborszky, L. et al. (2008). Stereotaxic probabilistic maps of the magnocellular cell groups in human basal forebrain. Neuroimage, 42(3), 1127-1141.