Dynamic reconfiguration and transition of whole-brain networks in patients with MELAS revealed by a hidden Markov model.

Objectives: Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) is a rare maternally inherited disease. The neuropathologic mechanisms and neural network alterations underlying stroke-like episodes (SLEs), a recurrent paroxysmal clinical event, remain unclear. The hidden Markov model (HMM) can detect profound alterations in neural activities across the whole-brain network. Materials and methods: We initially collected data from a prospective cohort from 2019 to 2024. The confirmed diagnosis of MELAS was conducted through genetic testing or a muscle biopsy. Healthy control volunteers were recruited from the local community. By utilizing the HMM, we evaluated the temporal characteristics and transitions of HMM states and the specific community pattern of transitions and activation maps of the whole brain for subjects. Results: Thirty-six MELAS patients at the acute stage (MELAS-acute group) and 30 healthy controls (HC group) were included in this study. Based on HMM, fractional occupancies in states 5 and 6 for MELAS were significantly decreased ( Conclusion: This study suggests dynamic reconfiguration of HMM states, special transition modules, and multiple transition pathways in MELAS, providing novel insights into the neural network mechanisms underlying MELAS.