Chemoarchitectural signatures of subcortical shape alterations in generalized epilepsy.
Yao MengJinming XiaoSiqi YangJiao LiQiang XuQirui ZhangGuang Ming LuHuafu ChenZhiqiang ZhangWei LiaoPublished in: Communications biology (2024)
Genetic generalized epilepsies (GGE) exhibit widespread morphometric alterations in the subcortical structures. Subcortical structures are essential for understanding GGE pathophysiology, but their fine-grained morphological diversity has yet to be comprehensively investigated. Furthermore, the relationships between macroscale morphological disturbances and microscale molecular chemoarchitectures are unclear. High-resolution structural images were acquired from patients with GGE (n = 97) and sex- and age-matched healthy controls (HCs, n = 184). Individual measurements of surface shape features (thickness and surface area) of seven bilateral subcortical structures were quantified. The patients and HCs were then compared vertex-wise, and shape anomalies were co-located with brain neurotransmitter profiles. We found widespread morphological alterations in GGE and prominent disruptions in the thalamus, putamen, and hippocampus. Shape area dilations were observed in the bilateral ventral, medial, and right dorsal thalamus, as well as the bilateral lateral putamen. We found that the shape area deviation pattern was spatially correlated with the norepinephrine transporter and nicotinic acetylcholine (Ach) receptor (α 4 β 2 ) profiles, but a distinct association was seen in the muscarinic Ach receptor (M 1 ). The findings provided a comprehensive picture of subcortical morphological disruptions in GGE, and further characterized the associated molecular mechanisms. This information may increase our understanding of the pathophysiology of GGE.
Keyphrases
- white matter
- high resolution
- spinal cord
- end stage renal disease
- deep brain stimulation
- multiple sclerosis
- chronic kidney disease
- ejection fraction
- newly diagnosed
- optical coherence tomography
- case report
- healthcare
- air pollution
- deep learning
- mass spectrometry
- gene expression
- molecular dynamics
- dna methylation
- minimally invasive
- social media
- binding protein
- single molecule
- cerebral ischemia
- atomic force microscopy