AJNR. American journal of neuroradiology · 2026
Altered Connectome Gradient and Its Association with Gene Expression Profiles in Patients with MELAS.
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Wang Rong, Yu Qingyun, Sun Chong, Liu Xueling, Hu Bin, Yang Liqin, Geng Daoying, Lin Jie, Li Yuxin
Аннотация
BACKGROUND AND PURPOSE: Hierarchy is a fundamental principle of network organization in the human brain. Functional gradient introduces a new perspective in identifying hierarchy alterations by capturing major axes of functional connectivity in low-dimensional space. However, whether this gradient structure is disrupted in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) and how this disruption is modulated by the gene-expression profiles remain unknown.
MATERIALS AND METHODS: Thirty-one patients with MELAS at the acute stage (MELAS-acute) and 31 healthy controls underwent resting-state functional MR imaging. On the basis of whole-brain voxelwise functional connectivity patterns, functional gradient values were generated and group-averaged gradient values were further extracted and compared from the global-to-voxel level. In combination with the Allen Human Brain Atlas, we then assessed the spatial correlations between MELAS-related gradient alterations and gene-expression profiles.
RESULTS: Relative to the healthy controls, patients with MELAS-acute exhibited global alterations in the principal gradients, including reduced gradient range and gradient variation. In addition, patients showed lower gradient values in the default mode network but higher values in the ventral attention network and the sensorimotor network at the network and voxel levels. Furthermore, we established a link between MELAS-acute-related principal gradient and gene-expression profiles, with 2 gene sets mainly enriched in mitochondrion, neuron, glutamatergic synapse, and ATPase activity.
CONCLUSIONS: These results highlight the connectome gradient alterations in patients with MELAS at the acute stage and their linkage with gene-expression profiles, providing insight into the neurobiological basis of functional alterations during the acute stroke-like episodes stage in MELAS.
MATERIALS AND METHODS: Thirty-one patients with MELAS at the acute stage (MELAS-acute) and 31 healthy controls underwent resting-state functional MR imaging. On the basis of whole-brain voxelwise functional connectivity patterns, functional gradient values were generated and group-averaged gradient values were further extracted and compared from the global-to-voxel level. In combination with the Allen Human Brain Atlas, we then assessed the spatial correlations between MELAS-related gradient alterations and gene-expression profiles.
RESULTS: Relative to the healthy controls, patients with MELAS-acute exhibited global alterations in the principal gradients, including reduced gradient range and gradient variation. In addition, patients showed lower gradient values in the default mode network but higher values in the ventral attention network and the sensorimotor network at the network and voxel levels. Furthermore, we established a link between MELAS-acute-related principal gradient and gene-expression profiles, with 2 gene sets mainly enriched in mitochondrion, neuron, glutamatergic synapse, and ATPase activity.
CONCLUSIONS: These results highlight the connectome gradient alterations in patients with MELAS at the acute stage and their linkage with gene-expression profiles, providing insight into the neurobiological basis of functional alterations during the acute stroke-like episodes stage in MELAS.