A Multimodal Investigation of Thalamic Nuclei in Children with Temporal Lobe Epilepsy
Poster No:
262
Submission Type:
Abstract Submission
Authors:
Xiyu Feng1, Rory Piper1, Freya Prentice1, Maria Eriksson1, Jonathan Clayden1, Torsten Baldeweg1
Institutions:
1UCL Great Ormond Street Institute of Child Health, London, UK
First Author:
Co-Author(s):
Introduction:
The thalamus is classically implicated as a key propagation point for epileptic activity. Functional and structural rearrangements may mediate the large-scale spread of such activity (Larivière et al., 2020). The thalamus consists of several subnuclei, which are differentially affected by epilepsy pathologies (Tung et al., 2022, 2023), recruited during seizures (Wu et al., 2023), and serve as targets for neuromodulation (Piper et al., 2022). However, comprehensive investigations of how epilepsy reconfigures functional networks and volumetry of thalamic nuclei in TLE remain to be conducted. This study pursued a multimodal characterization of thalamic nuclei alterations in children with TLE, assessing both volumetric and functional connectivity changes. We hypothesized that (1) volume reductions in thalamic subnuclei are co-localized with functional connectivity abnormalities in children with TLE compared to controls, and (2) distinct thalamic subnuclei involvement corresponds to network rearrangements linked to TLE phenotypes and seizure outcomes.
Methods:
We retrospectively analyzed structural and functional MRI data from 86 children with unilateral TLE (ages 6–19) and 72 controls (ages 6–20). Of the 42 patients with documented seizure outcomes at least one year after surgery, outcomes were categorized as seizure-free (equivalent to Engel 1A) or not seizure-free. For four thalamic nuclei groups (anterior, lateral, medial, posterior/pulvinar) in each hemisphere, we extracted two measures: 1) Volumes using the THOMAS pipeline (Su et al., 2019); 2) fMRI-connectivity-based hubness, which indicates whether a brain region is highly connected to or isolated from other parts of the brain (Royer et al., 2022). Age- and sex-adjusted measures were compared between groups using t-tests. Multiple comparisons were corrected using the false discovery rate (FDR).
Results:
Children with TLE exhibited volume reductions in thalamic nuclei ipsilateral to the seizure focus compared to controls (all p < 0.05, Cohen's d = 0.37–0.67; Figure 1). Particularly, the pulvinar nuclei exhibited significant atrophy co-occurring with reduced functional hubness (all p < 0.05, Cohen's d = 0.67, 0.46). Subgroup analyses revealed more severe ipsilateral thalamic atrophy in patients with hippocampal sclerosis compared to those without this etiology (all p < 0.05, partial η² = 0.06–0.09). Altered functional hubness of the bilateral anterior thalamic nuclei was associated with a history of focal-to-bilateral tonic-clonic seizures (p < 0.05, partial η² = 0.10). Furthermore, asymmetry in atrophy and hubness between ipsilateral and contralateral sides differentiated seizure-free from not seizure-free patients after resection: Patients who were not seizure-free exhibited greater atrophy and hubness reductions in the ipsilateral thalamus (all p < 0.05, partial η² = 0.096, 0.092; Figure 2).
·Figure 1. Summary of Volume and Functional-connectivity-based Hubness Changes in the Thalamus of Children with TLE.
·Figure 2. Asymmetry Patterns of Thalamic Volume and Functional-Connectivity-Based Hubness in Seizure-Free and Not Seizure-Free Patients After Surgery.
Conclusions:
This study offers a detailed analysis of thalamic alterations in children with TLE, identifying atrophy in the seizure-onset hemisphere and abnormal functional connectivity affecting both hemispheres. Notably, the co-localized atrophy and reduced connectivity in the pulvinar suggest a pronounced disruption in response to temporal seizures. The pulvinar, with its earlier and more prominent involvement compared to the anterior nuclei during temporal-onset seizures (Wu et al., 2023), has been recently increasingly noted in TLE research, such as pulvinar stimulation for seizure modulation (Wong et al., 2023). Previous findings have proposed that a thalamic functional network associated with seizure recurrence may already be established presurgically in adults with TLE (He et al., 2017). Expanding on this, our study demonstrates the link between thalamic alterations and post-surgical seizure outcomes in pediatric TLE, emphasizing the value of volume and functional connectivity as joint imaging biomarkers of brain network reorganization underpinning disease severity.
Disorders of the Nervous System:
Neurodevelopmental/ Early Life (eg. ADHD, autism) 1
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 2
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Subcortical Structures
Novel Imaging Acquisition Methods:
Anatomical MRI
BOLD fMRI
Keywords:
Epilepsy
FUNCTIONAL MRI
PEDIATRIC
STRUCTURAL MRI
Thalamus
1|2Indicates the priority used for review
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Provide references using APA citation style.
Larivière, S. (2020). Network-based atrophy modeling in the common epilepsies: A worldwide ENIGMA study. Science Advances, 6(47), eabc6457.
Piper, R. J. (2022). Towards network-guided neuromodulation for epilepsy. Brain: A Journal of Neurology, awac234.
Royer, J. (2022). Epilepsy and brain network hubs. Epilepsia, 63(3), 537–550.
Su, J. H. (2019). Thalamus Optimized Multi Atlas Segmentation (THOMAS): Fast, fully automated segmentation of thalamic nuclei from structural MRI. NeuroImage, 194, 272–282.
Tung, H. (2022). Characterization of Hippocampal-Thalamic-Cortical Morphometric Reorganization in Temporal Lobe Epilepsy. Frontiers in Neurology, 12.
Tung, H. (2023). Morphological and metabolic asymmetries of the thalamic subregions in temporal lobe epilepsy predict cognitive functions. Scientific Reports, 13(1), 22611.
Wong, G. M. (2023). Stimulation of the pulvinar nucleus of the thalamus in epilepsy: A systematic review and individual patient data (IPD) analysis. Clinical Neurology and Neurosurgery, 235, 108041.
Wu, T. Q. (2023). Multisite thalamic recordings to characterize seizure propagation in the human brain. Brain, 146(7), 2792–2802.