- Publication Date:
- NSF-PAR ID:
- Journal Name:
- Scientific Reports
- Sponsoring Org:
- National Science Foundation
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Loss of consciousness, but not etiology, predicts better working memory performance years after concussionBackground: Patients with uncomplicated cases of concussion are thought to fully recover within several months as symptoms resolve. However, at the group level, undergraduates reporting a history of concussion (mean: 4.14 years post-injury) show lasting deficits in visual working memory performance. To clarify what predicts long-term visual working memory outcomes given heterogeneous performance across group members, we investigated factors surrounding the injury, including gender, number of mild traumatic brain injuries, time since mild traumatic brain injury (mTBI), loss of consciousness (LOC) (yes, no), and mTBI etiology (non-sport, team sport, high impact sport, and individual sport). We also collected low-density resting state electroencephalogram to test whether spectral power was correlated with performance. Aim: The purpose of this study was to identify predictors for poor visual working memory outcomes in current undergraduates with a history of concussion. Methods: Participants provided a brief history of their injury and symptoms. Participants also completed an experimental visual working memory task. Finally, low-density resting-state electroencephalogram was collected. Results: The key observation was that LOC at the time of injury predicted superior visual working memory years later. In contrast, visual working memory performance was not predicted by other factors, including etiology, high impact sports, or electroencephalogram spectralmore »
Type 2 diabetes mellitus accelerates brain aging and cognitive decline: Complementary findings from UK Biobank and meta-analysesBackground: Type 2 diabetes mellitus (T2DM) is known to be associated with neurobiological and cognitive deficits; however, their extent, overlap with aging effects, and the effectiveness of existing treatments in the context of the brain are currently unknown. Methods: We characterized neurocognitive effects independently associated with T2DM and age in a large cohort of human subjects from the UK Biobank with cross-sectional neuroimaging and cognitive data. We then proceeded to evaluate the extent of overlap between the effects related to T2DM and age by applying correlation measures to the separately characterized neurocognitive changes. Our findings were complemented by meta-analyses of published reports with cognitive or neuroimaging measures for T2DM and healthy controls (HCs). We also evaluated in a cohort of T2DM-diagnosed individuals using UK Biobank how disease chronicity and metformin treatment interact with the identified neurocognitive effects. Results: The UK Biobank dataset included cognitive and neuroimaging data (N = 20,314), including 1012 T2DM and 19,302 HCs, aged between 50 and 80 years. Duration of T2DM ranged from 0 to 31 years (mean 8.5 ± 6.1 years); 498 were treated with metformin alone, while 352 were unmedicated. Our meta-analysis evaluated 34 cognitive studies (N = 22,231) and 60 neuroimaging studies: 30more »
Designing Ụbụrụ: The Alpha Stage: Executive Function Rehabilitation Application for Mild Traumatic Brain InjuryỤbụrụ is an executive function computerized rehabilitation application specifically designed for mild Traumatic Brain Injury (mTBI) individuals. Ụbụrụ utilizes serious games to train cognitive flexibility, planning, and organization. This paper explores the rationale and components behind the alpha stage of the application’s development, and its first design iteration. Currently, individuals with a history of mTBI have limited rehabilitation options as a result of lack of knowledge in terms of available services, access, time, or financial and insurance constraints. Due to the invisible nature of mTBIs, perception of injury severity is diminished, individuals are not properly equipped with how to proceed forward with rehabilitation, and awareness of injury can be inadvertently compromised. The intention behind the Ụbụrụ application is to be a computerized cognitive rehabilitation alternative and additive when limitations such as time, finances, or insurance exist.
Single-cell RNA transcriptome analysis of CNS immune cells reveals CXCL16/CXCR6 as maintenance factors for tissue-resident T cells that drive synapse elimination
Emerging RNA viruses that target the central nervous system (CNS) lead to cognitive sequelae in survivors. Studies in humans and mice infected with West Nile virus (WNV), a re-emerging RNA virus associated with learning and memory deficits, revealed microglial-mediated synapse elimination within the hippocampus. Moreover, CNS-resident memory T (TRM) cells activate microglia, limiting synapse recovery and inducing spatial learning defects in WNV-recovered mice. The signals involved in T cell-microglia interactions are unknown.
Here, we examined immune cells within the murine WNV-recovered forebrain using single-cell RNA sequencing to identify putative ligand-receptor pairs involved in intercellular communication between T cells and microglia. Clustering and differential gene analyses were followed by protein validation and genetic and antibody-based approaches utilizing an established murine model of WNV recovery in which microglia and complement promote ongoing hippocampal synaptic loss.
Profiling of host transcriptome immune cells at 25 days post-infection in mice revealed a shift in forebrain homeostatic microglia to activated subpopulations with transcriptional signatures that have previously been observed in studies of neurodegenerative diseases. Importantly, CXCL16/CXCR6, a chemokine signaling pathway involved in TRM cell biology, was identified as critically regulating CXCR6 expressing CD8+TRM cell numbers within the WNV-recovered forebrain. We demonstrate that CXCL16 is highlymore »
We provide a comprehensive assessment of the role of CXCL16/CXCR6 as an interaction link between microglia and CD8+T cells that maintains forebrain TRM cells, microglial and astrocyte activation, and ongoing synapse elimination in virally recovered animals. We also show that therapeutic targeting of CXCL16 in mice during recovery may reduce CNS CD8+TRM cells.
Have you ever felt “groggy” after hitting your head? We are learning more about how important it is to protect your brain from injuries, such as concussion. Concussion is also called mild traumatic brain injury (mTBI). After an mTBI, most people think patients recover within a few weeks. We noticed that some college students who had had an mTBI were struggling to remember information for a few seconds. This ability is called working memory and we need it for most thinking jobs, like remembering the name of someone you just met, or what you wanted to get from the fridge. In our experiments, we tested different groups of students to see if they could remember things for 1 s, like the color of squares. Participants with a history of mTBI (on average, more than 4 years after injury) performed worse than students without a history of mTBI. The take-home message is that there can be lasting effects of mTBI, even years after it happens.