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Aims: The electroencephalography (EEG) microstates are indicative of fundamental information processing mechanisms, which are severely damaged in patients with prolonged disorders of consciousness (pDoC). We aimed to improve the topographic analysis of EEG microstates and explore indicators available for diagnosis and prognosis prediction of patients with pDoC, which were still lacking. Methods: We conducted EEG recordings on 59 patients with pDoC and 32 healthy controls. We refined the microstate method to accurately estimate topographical differences, and then classify and forecast the prognosis of patients with pDoC. An independent dataset was used to validate the conclusion. Results: Through optimized topographic analysis, the global explained variance (GEV) of microstate E increased significantly in groups with reduced levels of consciousness. However, its ability to classify the VS/UWS group was poor. In addition, the optimized GEV of microstate E exhibited a statistically significant decrease in the good prognosis group as opposed to the group with a poor prognosis. Furthermore, the optimized GEV of microstate E strongly predicted a patient's prognosis. Conclusion: This technique harmonizes with the existing microstate analysis and exhibits precise and comprehensive differences in microstate topography between groups. Furthermore, this method has significant potential for evaluating the clinical prognosis of pDoC patients. [ABSTRACT FROM AUTHOR]

A shared neuropathological hallmark in amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is nuclear clearance and cytoplasmic aggregation of TARDBP/TDP-43 (TAR DNA binding protein). We previously showed that the ability of TARDBP to repress nonconserved cryptic exons was impaired in brains of patients with ALS and FTD, suggesting that its nuclear depletion contributes to neurodegeneration. However, the critical pathways impacted by the failure to repress cryptic exons that may contribute to neurodegeneration remain undefined. Here, we report that transcriptome analysis of TARDBP-deficient neurons revealed downregulation of ATG7, a critical gene required for macroautophagy/autophagy. Mouse and Drosophila models lacking TARDBP/TBPH in motor neurons exhibiting age-dependent neurodegeneration and motor deficits showed reduction of ATG7 and accumulation of SQSTM1/p62 inclusions. Importantly, genetic upregulation of the autophagy pathway improved motor function and survival in TBPH-deficient flies. Together with our observation that ATG7 is reduced in ALS-FTD brain tissues, these findings identify the autophagy pathway as one key effector of nuclear depletion of TARDBP that contributes to neurodegeneration. We thus suggest that the autophagy pathway is a therapeutic target for ALS-FTD and other disorders exhibiting TARDBP pathology. Abbreviations: ALS: amyotrophic lateral sclerosis; ANOVA: analysis of variance; ChAT: choline acetyltransferase; CTSD: cathepsin D; FTD: frontotemporal dementia; LAMP1: lysosomal associated membrane protein 1; NMJ: neuromuscular junction; RBFOX3/NeuN: RNA binding fox-1 homolog 3; SQSTM1: sequestosome 1; TARDBP/TDP-43: TAR DNA binding protein 43. [ABSTRACT FROM AUTHOR]