Background/Objectives: Cognitive control capacity (CCC) describes the maximum volume of information an individual can reliably process per unit time, a key cognitive factor of multitasking performance. While sustained high-load multitasking is known to induce cumulative cognitive impairment, it remains untested whether CCC is associated with vulnerability to this decline across subjective, behavioral, and neural levels. This study systematically characterized how individual differences in CCC relate to multitasking processing ability and examined whether a higher CCC is associated with smaller cognitive fatigue during extended operations. Methods: CCC was assessed in 313 college students via the adaptive MFTA_A paradigm. Participants scoring in the upper and lower 27% of the CCC distribution formed the high-CCC group (n = 42, 3.65 ± 0.33 bps) and the low-CCC group (n = 41, 2.04 ± 0.28 bps). All participants completed a 1 h multitasking information-processing test comprising tracking, instrument monitoring, and listening subtasks. Alertness was measured with the Psychomotor Vigilance Task before and after the test, subjective workload was rated across four Visual Analogue Scale dimensions, and continuous task-state EEG was recorded to analyze spectral power and microstate dynamics. Results: Relative to low-CCC participants, the high-CCC group showed smaller post-test alertness declines, consistently higher multitasking scores across all blocks, and sustained higher theta/alpha ratios and parietal beta power throughout the task. High-CCC participants also exhibited descriptively stronger activation of microstate C and a late rebound pattern in microstate D transitions, while the low-CCC group showed early stabilization of D-state dynamics without compensatory adjustment. Subjective workload ratings rose equivalently across time in both groups, with no significant between-group differences. Conclusions: CCC is strongly associated with multitasking efficiency. Higher CCC is associated with larger information-processing capacity and better sustained performance during high-load work. This association may be supported by more efficient neural resource allocation and more robust cognitive control network engagement, with exploratory evidence of adaptive brain network reorganization under fatigue. CCC is associated with both immediate multitasking performance and alertness maintenance capacity during prolonged operations.
Objectives: Microvascular injury after traumatic brain injury (TBI) is the basis for the occurrence of neurological dysfunction. This study aims to dynamically observe cerebrovascular hemodynamics using TCCD to evaluate the stability of the microcirculatory network before and after TBI. Methods: In this study, a moderate TBI model in rats was established, comprising a sham group and TBI groups at days 1 (1 d), 3 d, 5 d, 7 d, 10 d, 14 d, 21 d, and 35 d (n = 5), and each group underwent TCCD and pathological examinations. Examinations were conducted to acquire hemodynamic parameters for every subgroup. Importantly, vessel density (VDnorm), number of endpoints (NEPnorm), and average vessel diameter (AVDnorm) of the injured-side brain tissue to calculate the Microcirculation Structural Score (MSS) were quantified and normalized from histological brain sections, while intracranial vessel hemodynamic indicators including PI, were obtained by TCCD. We analyzed correlations between microcirculation parameters and vessel hemodynamic parameters to validate whether the PI reflects microcirculatory alterations after TBI. Results: This study found that 1–3 days post-TBI was the peak period of vascular injury. From 5 to 14 days, microvascular density and intracranial large vessel blood flow parameters recovered before the microcirculatory structure. From 21 to 35 days, microvessels continued to remodel, with AVDnorm negatively correlated with PI of middle cerebral artery cortical branches (MCAcb-PI) (r = −0.626, p < 0.001). Then, a weighted PI (PIindex) was constructed, which was positively correlated with the microcirculatory injury MSS (r = 0.592, p < 0.001). Conclusions: PIindex can quantitatively assess microcirculatory injury and vascular structural remodeling. TCCD serves as a simple and feasible novel tool to monitor microcirculatory changes after TBI.
Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder where early molecular disruptions precede overt pathology and neuronal loss. To identify transcriptional events that bias neurons toward degeneration or resilience, we reanalyzed two single-nucleus RNA-sequencing datasets originally generated to investigate glial responses in an established AD murine model. Methods: Using a neuron-centric analytical framework, excitatory neuronal cells were selected for downstream bioinformatics involving unsupervised clustering, trajectory inference, and functional analyses. Results: This approach revealed neuronal heterogeneity and enabled reconstruction of inferred transcriptional trajectories in a discovery dataset. Three distinct neuronal states along an inferred continuum from stability to degeneration were identified: a homeostatic state, a transitional stress-adaptive state, and an AD-associated state. The transitional state was positioned near a trajectory bifurcation point, indicating divergence toward either partial resilience or an AD-like trajectory. Differential gene expression and pathway analyses revealed RNA-processing dysregulation in the transitional state, suggesting that early alterations in RNA metabolism may play a key role in biasing neurons toward pathological progression. The homeostatic and transitional neuronal states were independently validated, whereas the AD-associated state was not, potentially reflecting differences in brain-region sampling, sequencing strategies, and/or the transient nature of the disease-associated state. Conclusions: This study identified distinct neuronal transcriptional states and inferred trajectories associated with AD-related vulnerability, highlighting RNA-processing dysfunction as a candidate mechanistic contributor of neuronal fate divergence in AD progression. This work provides a foundation for future studies to define cell-type-specific RNA dysregulation in relevant animal models and human postmortem brain tissues to determine whether early RNA-metabolic imbalance and upstream signaling drivers can serve as mechanistic biomarkers or therapeutic intervention points in AD.
Background/Objectives: Cortical development in children and adolescents shows marked regional heterogeneity, but whether age-related trajectory properties are organized consistently along an externally defined sensorimotor–association (S–A) axis across morphometric phenotypes remains unclear. This study aimed to characterize relative net change, trajectory nonlinearity, and timing centroids across cortical phenotypes and determine how these properties relate to the sensorimotor–association (S–A) axis. Methods: This cross-sectional study included structural MRI data from 936 screened clinical participants aged 6–18 years. Normative age trajectories were modeled for 68 Desikan–Killiany cortical regions using cortical thickness (CT), surface area (SA), cortical volume (CV), and Morphometric INverse Divergence (MIND)-derived nodal degree. Scanner was included as a fixed effect in the model. Relative change (RC), nonlinearity index (NLI), and timing centroid (TC) were extracted from sex-averaged conditional median trajectories within the 6–15-year analysis window. Associations with the S–A axis were tested using Spearman correlations and 10,000 hemisphere-preserving spatial spin permutations, with a two-sided per-test p < 0.05 criterion. Participant-level bootstrap resampling quantified estimation uncertainty. Results: In fitted trajectories, CT, CV, and MIND nodal degree showed net decreases in most cortical regions, whereas SA showed predominantly net increases. Regional distributions of NLI and TC also differed across phenotypes. Of 12 predefined S–A association tests, seven met the two-sided Spin criterion. Toward the association-cortex end, TC increased for CT, CV, and MIND nodal degree, RC increased for SA and MIND nodal degree, and NLI increased for SA but decreased for MIND nodal degree. Conclusions: Cortical age-related trajectories show phenotype- and property-specific spatial associations with the external S–A axis. Concordant gradients of relative net change can coexist with opposite gradients of trajectory nonlinearity, indicating that a common cortical hierarchy is expressed through different age-related properties across cortical phenotypes.
Objective: To compare the clinical characteristics, treatment timelines, and short-term outcomes of patients with acute ischemic stroke (AIS) who developed stroke at extremely high altitude or in lowland areas and received intravenous thrombolysis, and to investigate factors associated with failure to achieve the recommended door-to-needle time (DNT). Methods: This two-center retrospective cohort study included consecutive patients with AIS treated with intravenous alteplase between January 2019 and February 2026 at Xizang Autonomous Region People’s Hospital and West China Hospital, Sichuan University. Demographic and clinical data, laboratory findings, onset-to-door time, DNT, onset-to-needle time, and in-hospital outcomes were collected. Binary logistic regression was used to identify factors associated with DNT > 60 min. Results: Among 348 patients, 170 were in the high-altitude group and 178 in the lowland group. High-altitude patients were younger, had higher rates of smoking and alcohol consumption, lower oxygen saturation, and higher red blood cell counts and hemoglobin levels (all p < 0.001). DNT was significantly longer at high altitude (p < 0.001). No significant differences were found in discharge NIHSS scores, early neurological improvement, favorable functional outcome, hemorrhagic transformation, or in-hospital mortality (all p > 0.05), although the study was underpowered to detect clinically meaningful differences in hemorrhagic transformation and in-hospital mortality. High-altitude setting remained independently associated with DNT > 60 min after adjustment (aOR, 5.381; 95% CI, 3.068–9.438; p < 0.001), reflecting a composite of altitude-related and center-specific factors. Conclusions: This study provides real-world clinical evidence on intravenous alteplase thrombolysis for patients with AIS at high altitude and helps address the limited efficacy and safety data available for high-altitude populations in previous thrombolysis studies. The comparable short-term neurological outcomes suggest that thrombolysis is feasible in this setting, although the limited statistical power for secondary safety outcomes warrants confirmation in larger studies. The longer DNT observed at the high-altitude center likely reflects both altitude-related and center-specific operational factors, and further research is needed to clarify their relative contributions. These findings may provide a clinical basis for assessing the applicability of reperfusion strategies in the unique high-altitude environment.
