Topological reorganization of brain functional networks in patients with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes

Abstract

Mitochondrial 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 topological organization of brain functional network in MELAS has not been explored. Here, 45 patients with MELAS (22 at acute stage, 23 at chronic stage) and 22 normal controls were studied using resting- state functional magnetic resonance imaging and graph theory analysis approaches. Topological properties of brain functional networks including global and nodal metrics, rich club organization and modularity were analyzed. At the global level, MELAS patients exhibited reduced clustering coefficient, normalized clustering coefficient, normalized characteristic path length and local network efficiency compared with the controls. At the nodal level, several nodes with abnormal degree centrality and nodal efficiency were detected in MELAS patients, and the distribution of these nodes was partly consistent with the stroke-like lesions. For rich club organization, rich club nodes were reorganized and the connections among them were decreased in MELAS patients. Modularity analysis revealed that MELAS patents had altered intra- or inter-modular connections in default mode network, fronto-parietal network, sensorimotor network, occipital network and cerebellum network. Notably, the patients at acute stage showed more obvious changes in these topological properties than the patients at chronic stage. These findings indicated that MELAS patients, particularly those at acute stage, exhibited topological reorganization of the whole-brain functional network. This study may help us to understand the neuropathological mechanisms of MELAS.

Keywords: Brain functional networks; Graph theory analysis; MELAS; Resting state.