Altered Dynamic Functional Connectivity in Patients With Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke‐Like Episodes (MELAS) at Acute and Chronic Stages: Shared and Specific Brain Connectivity Abnormalities

Abstract

BackgroundMitochondrial encephalomyopathy with lactic acidosis and stroke‐like episodes (MELAS) is a rare maternally inherited genetic disease; however, little is known about its underlying brain basis. Furthermore, the dynamic functional connectivity (dFC) of brain networks in MELAS has not been explored.PurposeTo investigate the abnormalities of dFC in patients with MELAS at the acute and chronic stages, and to determine the possible relations between dynamic connectivity alterations and volumes of stroke‐like lesions (SLLs).Study TypeProspective.SubjectsTwenty‐two MELAS patients at the acute stage, 23 MELAS patients at the chronic stage, and 22 healthy controls.Field Strength/SequenceSingle‐shot gradient‐recalled echo planar imaging (EPI) sequence at 3T.AssessmentDynamic FC states were estimated using the sliding window approach and k‐means clustering analyses. Combined with graph theory, the topological properties of the dFC network were also accessed.Statistical TestsPermutation test, Pearson correlation coefficient, and false discovery rate correction.ResultsWe identified four dFC states and found that MELAS patients (especially at the acute stage) spent more time in a state with weaker connectivity (state 1) and less time in states with stronger connectivity. In addition, volumes of acute SLLs were positively correlated with mean dwell time in state 1 (r = 0.539, P < 0.05) and negatively correlated with the number of transitions (r = −0.520, P < 0.05). Furthermore, MELAS patients at the acute stage exhibited significantly increased global efficiency (P < 0.01) and decreased local efficiency (P < 0.001) compared to the controls and the patients at the chronic stage. Patients at the chronic stage only showed significantly (P < 0.001) decreased local efficiency compared to the controls.Data ConclusionOur findings suggest similar and distinct dFC alterations in MELAS patents at the acute and chronic stages, providing novel insights for understanding the neuropathological mechanisms of MELAS.Level of Evidence 2Technical Efficacy Stage Stage 2J. MAGN. RESON. IMAGING 2021;53:427–436.

MRI Features of Stroke-Like Episodes in Mitochondrial Encephalomyopathy With Lactic Acidosis and Stroke-Like Episodes

“…Wang et al ( 51 ) reported that MELAS patients, particularly those at the acute stage, exhibited topological reorganization of the whole-brain functional network based on resting-state fMRI. They also found that MELAS patients spent more time in a state with weaker connectivity and less time in states with stronger connectivity, and patients at the acute stage exhibited that global efficiency was markedly increased while local efficiency was decreased, compared to the controls and the patients at the chronic period ( 52 ). Additionally, Rodan et al ( 53 ) demonstrated that MELAS patients' fMRI activation in response to visual cortex stimulus was significantly increased in primary visual striate cortex V1 and extrastriate regions V2 to V5 after L-arginine treatment with task fMRI.…”

Abnormal Dynamic Functional Connectivity in Patients With End-Stage Renal Disease

“…To decompose the preprocessed rs-fMRI data into different independent components (ICs), a spatial group ICA was performed using the Group ICA of fMRI Toolbox (GIFT, version 4.0b) 2 ( Calhoun et al, 2001 ). Although some studies selected a high-order ICA approach to obtain cortical and subcortical functional parcellations ( Kim et al, 2017 ; Fiorenzato et al, 2019 ; Wang et al, 2021 ), we applied a low-order model, given the fact that the ICs obtained from the lower-order model were more consistent with previous anatomical and functional segmentations ( Calhoun et al, 2008 ; Smith et al, 2009 ; Shi et al, 2018 ). Group ICA included the following steps: first, a two-step principal component analysis (subject-specific and group level) was used to decompose the data into 23 ICs.…”

Acupuncture Treatment Decreased Temporal Variability of Dynamic Functional Connectivity in Chronic Tinnitus

“…When the mental activity is unconstrained, dynamics are potentially even more prominent under the resting state. Evidences suggested that dynamic functional connectivity (DFC) supply us new information about abnormal FC on the brain of patients with various diseases (Demirtas et al, 2016;Guo et al, 2018;Wang et al, 2020;Chen et al, 2020a,b). However, the abnormal DFC and the neural activity change after acupuncture treatment were unclear in tinnitus patients.…”