Thalamic Functional Connectivity Gradients in Children with Temporal Lobe Epilepsy

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Abstract Submission 

Xiyu Feng¹, Hua Xie², Rory Piper^1,3, Freya Prentice¹, Priyanka Illapani², Lauren Reppert², Seok-Jun Hong⁴, Mohamad Koubeissi⁵, Torsten Baldeweg¹, Leigh Sepeta²

¹UCL Great Ormond Street Institute of Child Health, London, United Kingdom, ²Children’s National Hospital, Washington, D.C., USA, ³Great Ormond Street Hospital, London, United Kingdom, ⁴Sungkyunkwan University, Seoul, South Korea, ⁵The George Washington University Medical Faculty Associates, Washington, D.C., USA

Xiyu Feng  
UCL Great Ormond Street Institute of Child Health
London, United Kingdom

Hua Xie  
Children’s National Hospital
Washington, D.C., USA

Rory Piper  
UCL Great Ormond Street Institute of Child Health|Great Ormond Street Hospital
London, United Kingdom|London, United Kingdom

Freya Prentice  
UCL Great Ormond Street Institute of Child Health
London, United Kingdom

Priyanka Illapani  
Children’s National Hospital
Washington, D.C., USA

Lauren Reppert  
Children’s National Hospital
Washington, D.C., USA

Seok-Jun Hong  
Sungkyunkwan University
Seoul, South Korea

Mohamad Koubeissi  
The George Washington University Medical Faculty Associates
Washington, D.C., USA

Torsten Baldeweg  
UCL Great Ormond Street Institute of Child Health
London, United Kingdom

Leigh Sepeta  
Children’s National Hospital
Washington, D.C., USA

The thalamus can participate in spread of epileptic activity (Wu et al., 2023) and is a target for therapeutic neuromodulation (Piper et al., 2022). Thalamic functional connectivity alterations exist in adult patients with temporal lobe epilepsy (TLE) and may affect seizure freedom after surgery (He et al., 2017). Here we used data-driven 'connectopic mapping' (Haak et al., 2018) to investigate the spatial organization (gradients) of thalamic cortical and subcortical connections in pediatric TLE. We aimed to uncover the functional gradients within the thalamus and investigate differences in thalamus to whole brain connectivity between children with TLE and healthy controls.

64 children with TLE (5-18 years, left TLE n=51, right n=13) and 61 healthy controls (6-20 years) underwent language fMRI using a covert verb generation task at Great Ormond Street Hospital, London, UK. For children with right TLE, images were flipped so the seizure focus is the left hemisphere for all patients. fMRI data were preprocessed using fMRIprep software. 1) Connectopic mapping: We generated within-thalamus FC similarity matrices for each hemisphere and applied non-linear manifold learning to this matrix, yielding gradients for each side of the thalamus. We also created projection maps depicting changes in thalamic-to-whole brain connectivity along this gradient. 2) A SurfStat linear model (Worsley et al., 2009) assessed variations in projection maps related to disease status and duration, age and gender.

The primary thalamic gradient followed an anterior-to-posterior axis (Fig. 1) for both children with TLE and controls. In the cortex, there were no differences in the projection maps between patients and controls (FDR-corrected p>0.05). The anterior thalamus displayed greater connectivity with prefrontal and orbitofrontal cortices, as well as the basal ganglia. The mid-thalamic gradient zone was preferentially connected to the somatosensory cortex and anterior hippocampus. The posterior thalamus was more connected with the visual cortex and posterior hippocampus. However, in the subcortex, projection maps exhibited differences between patients and controls (FDR-corrected p<0.05). Compared to controls, patients showed stronger connectivity of the anterior thalamus to subcortical areas (Fig. 2), including the ventral striatum, subthalamic nuclei, substantia nigra as well as amygdala and hippocampus in both ipsi- and contralesional hemispheres. Duration of epilepsy was not correlated with projection map variations in patients (FDR-corrected p>0.05). Age and gender did not affect the cortical or subcortical projection maps for patients or controls (FDR-corrected p>0.05).

A primary anterior-to-posterior functional gradient was observed within the thalami in both children with TLE and their healthy peers, revealing a gradual shift of thalamic connectivity across the entire brain. While there were no group differences in connectivity between thalamus and cortical regions, there was heightened connectivity in children with TLE between the anterior thalamus and the basal ganglia, with a predominance for the ipsilesional side. It has been suggested that within the loop involving the limbic system and thalamus, the basal ganglia play a significant seizure modulating role (Bröer, 2020; He et al., 2019). Further investigations are needed to explore the clinical potential of connectopic mapping.

Neurodevelopmental/ Early Life (eg. ADHD, autism) ¹

fMRI Connectivity and Network Modeling ²

Subcortical Structures

BOLD fMRI

Development

Epilepsy

FUNCTIONAL MRI

Pediatric Disorders

Sub-Cortical

Thalamus