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            null (Ed.)Research has found that the vividness of conscious experience is related to brain dynamics. Despite both being anaesthetics, propofol and ketamine produce different subjective states: we explore the different effects of these two anaesthetics on the structure of dynamic attractors reconstructed from electrophysiological activity recorded from cerebral cortex of two macaques. We used two methods: the first embeds the recordings in a continuous high-dimensional manifold on which we use topological data analysis to infer the presence of higher-order dynamics. The second reconstruction, an ordinal partition network embedding, allows us to create a discrete state-transition network, which is amenable to information-theoretic analysis and contains rich information about state-transition dynamics. We find that the awake condition generally had the ‘richest’ structure, visiting the most states, the presence of pronounced higher-order structures, and the least deterministic dynamics. By contrast, the propofol condition had the most dissimilar dynamics, transitioning to a more impoverished, constrained, low-structure regime. The ketamine condition, interestingly, seemed to combine aspects of both: while it was generally less complex than the awake condition, it remained well above propofol in almost all measures. These results provide deeper and more comprehensive insights than what is typically gained by using point-measures of complexity.more » « less
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            He, Bing; Wu, Ruiming; Sangani, Neel; Pugalenthi, Pradeep_Varathan; Patania, Alice; Risacher, Shannon_L; Nho, Kwangsik; Apostolova, Liana_G; Shen, Li; Saykin, Andrew_J; et al (, Alzheimer's & Dementia)Abstract INTRODUCTIONAlzheimer's disease (AD) initiates years prior to symptoms, underscoring the importance of early detection. While amyloid accumulation starts early, individuals with substantial amyloid burden may remain cognitively normal, implying that amyloid alone is not sufficient for early risk assessment. METHODSGiven the genetic susceptibility of AD, a multi‐factorial pseudotime approach was proposed to integrate amyloid imaging and genotype data for estimating a risk score. Validation involved association with cognitive decline and survival analysis across risk‐stratified groups, focusing on patients with mild cognitive impairment (MCI). RESULTSOur risk score outperformed amyloid composite standardized uptake value ratio in correlation with cognitive scores. MCI subjects with lower pseudotime risk score showed substantial delayed onset of AD and slower cognitive decline. Moreover, pseudotime risk score demonstrated strong capability in risk stratification within traditionally defined subgroups such as early MCI, apolipoprotein E (APOE) ε4+ MCI,APOEε4– MCI, and amyloid+ MCI. DISCUSSIONOur risk score holds great potential to improve the precision of early risk assessment. HighlightsAccurate early risk assessment is critical for the success of clinical trials.A new risk score was built from integrating amyloid imaging and genetic data.Our risk score demonstrated improved capability in early risk stratification.more » « less
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