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Published on: August 5, 2014
Altered thalamic connectivity patterns in pediatric temporal lobe epilepsy: A gradient mapping study
Xiyu Feng1, Hua Xie2, Rory J Piper1,3
1UCL Great Ormond Street Institute of Child Health, London, UK.
Insights
Pediatric temporal lobe epilepsy (TLE) shows altered thalamic connectivity, particularly to the basal ganglia and mesial temporal regions. These changes may predict seizure outcomes and suggest new therapeutic targets.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Epilepsy Research
Background:
- The thalamus plays a crucial role in seizure propagation and is a target for neuromodulation in epilepsy.
- Pediatric temporal lobe epilepsy (TLE) presents unique challenges due to diverse etiologies and impacts on brain maturation.
- Previous studies on thalamic connectivity changes in TLE have primarily focused on adults.
Purpose of the Study:
- To investigate whole-brain thalamic connectivity patterns in children with TLE using a novel gradient mapping technique.
- To compare thalamic connectivity gradients between pediatric TLE patients and healthy controls.
- To examine associations between thalamic connectivity gradients and clinical factors like seizure history, hippocampal sclerosis, and surgical outcomes.
Main Methods:
- Functional magnetic resonance imaging (fMRI) was performed on 62 children with TLE (ages 5-18) and 61 controls (ages 6-20) during a covert verb generation task.
- Thalamic connectivity gradients were computed to identify primary axes of variation.
- Statistical comparisons were made between groups, and correlations with clinical variables were analyzed.
Main Results:
- Two primary thalamic connectivity gradients were identified: an anterior-posterior axis (G1) and a superior-inferior axis (G2).
- Children with TLE exhibited increased thalamic connectivity to the bilateral basal ganglia and mesial temporal regions compared to controls.
- Increased anterior thalamic-basal ganglia connectivity correlated with a history of focal to bilateral tonic-clonic seizures (FBTCS).
- Hippocampal sclerosis was linked to reduced thalamo-hippocampal connectivity, with stronger ipsilateral connectivity predicting better surgical outcomes.
Conclusions:
- Pediatric TLE is characterized by distinct thalamic connectivity patterns, including heightened connections to the basal ganglia and mesial temporal regions.
- Findings suggest a potential inhibitory role of basal ganglia output in modulating thalamo-cortical seizure transmission.
- Thalamo-hippocampal connectivity may serve as a predictive marker for post-surgical seizure control in pediatric TLE.
Objective:
The thalamus participates in seizure propagation and is a target for neuromodulation in epilepsy. Although thalamic connectivity changes have been reported in adults with temporal lobe epilepsy (TLE), pediatric TLE is distinct, characterized by greater etiological diversity and impact on brain maturation. This study applied a novel gradient mapping technique to investigate whole-brain thalamic connectivity patterns in children with TLE.
Methods:
Sixty-two children with TLE (ages 5-18) and 61 controls (ages 6-20) underwent a covert verb generation task functional magnetic resonance imaging (fMRI). Thalamic connectivity gradients were computed to capture primary axes of variation and compared between groups. Associations between thalamic gradients and focal to bilateral tonic-clonic seizure (FBTCS) history, hippocampal sclerosis, and post-surgical seizure outcomes were examined.
Results:
Two primary thalamic connectivity gradients were identified across both groups. The first (G1) followed an anterior-posterior axis, with anterior thalamic regions connected to prefrontal cortices and basal ganglia, and posterior regions to somatosensory and visual cortices. The second (G2) spanned a superior-inferior axis, with superior thalamus connected to dorsal frontal and parietal cortices, and inferior regions to ventral areas such as the inferior temporal lobe. No differences were found in neocortical connectivity; however, subcortical alterations were observed. Both gradients showed increased thalamic connectivity to the bilateral basal ganglia and mesial temporal regions in TLE compared to controls. Increased anterior thalamic-basal ganglia connectivity along G1 was more pronounced in children with a FBTCS history. Hippocampal sclerosis was associated with reduced bilateral thalamo-hippocampal connectivity along both gradients, and along G2, stronger ipsilateral thalamo-hippocampal connectivity predicted better post-surgical seizure control.
Significance:
This study identified two key thalamic connectivity patterns in pediatric TLE, revealing heightened thalamic connectivity to mesial temporal regions and to the basal ganglia. Findings suggest an adaptive inhibitory basal ganglia output on thalamo-cortical seizure transmission and the potential predictive value of thalamo-hippocampal connectivity for surgical outcomes.
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