475 results match your criteria: "Wu Tsai Neurosciences Institute[Affiliation]"

Basic Science and Pathogenesis.

Alzheimers Dement

December 2024

Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA.

Background: Vascular dysfunction, blood-brain barrier (BBB) dysregulation, and neuroinflammation are thought to participate in Alzheimer`s disease (AD) pathogenesis, though the mechanism is poorly understood. Among pathways of interest, AD pathology appears to affect vascular endothelial growth factor-A (VEGFA) signaling in a bidirectional manner. Higher VEGF levels are thought to have a protective role and slow cognitive decline.

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Toward Alleviating the Stigma of Hearing Aids: A Review.

Audiol Res

December 2024

Starkey Hearing, Eden Prairie, MN 55344, USA.

Despite the significant advancements in hearing aid technology, their adoption rates remain low, with stigma continuing to be a major barrier for many. This review aims to assess the origins and current state of hearing aid stigma, as well as explore potential strategies for alleviating it. This review examines the societal perceptions, psychological impacts, and recent technological advancements that can influence hearing aid adoption and reduce stigma.

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Motor output results from the coordinated activity of neural circuits distributed across multiple brain regions that convey information to the spinal cord via descending motor pathways. Yet the organizational logic through which supraspinal systems target discrete components of spinal motor circuits remains unclear. Here, using viral transsynaptic tracing along with serial two-photon tomography, we have generated a whole-brain map of monosynaptic inputs to spinal V1 interneurons, a major inhibitory population involved in motor control.

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Organizing the continuous stream of visual input into categories like places or faces is important for everyday function and social interactions. However, it is unknown when neural representations of these and other visual categories emerge. Here, we used steady-state evoked potential electroencephalography to measure cortical responses in infants at 3-4 months, 4-6 months, 6-8 months, and 12-15 months, when they viewed controlled, gray-level images of faces, limbs, corridors, characters, and cars.

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Introduction: The availability of amyloid beta (Aβ) targeting therapies for Alzheimer's disease (AD) is increasing the demand for scalable biomarkers that are sensitive to early cerebral Aβ accumulation.

Methods: We evaluated fully-automated Lumipulse plasma Aβ/Aβ immunoassays for detecting cerebral Aβ in 457 clinically unimpaired (CU) and clinically impaired (CI) Stanford Alzheimer's Disease Research Center (Stanford ADRC) participants and 186 CU in the Stanford Aging and Memory Study (SAMS). Longitudinal change in ADRC plasma Aβ/Aβ and cognition and cross-sectional associations with SAMS memory and tau positron emission tomography (PET) were examined.

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The rich diversity of synapses facilitates the capacity of neural circuits to transmit, process and store information. Here, we used multiplex super-resolution proteometric imaging through array tomography to define features of single synapses in the adult mouse neocortex. We find that glutamatergic synapses cluster into subclasses that parallel the distinct biochemical and functional categories of receptor subunits: GluA1/4, GluA2/3 and GluN1/GluN2B.

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Human aging affects the ability to remember new experiences, in part, because of altered neural function during memory formation. One potential contributor to age-related memory decline is diminished neural selectivity -- i.e.

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Old age is associated with a decline in cognitive function and an increase in neurodegenerative disease risk. Brain ageing is complex and is accompanied by many cellular changes. Furthermore, the influence that aged cells have on neighbouring cells and how this contributes to tissue decline is unknown.

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The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated.

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As the field of neural organoids and assembloids rapidly expands, there is an emergent need for guidance and advice on designing, conducting and reporting experiments to increase the reproducibility and utility of these models. Here, our consortium- representing specialized laboratories from around the world- presents a framework for the experimental process that ranges from ensuring the quality and integrity of human pluripotent stem cells to characterizing and manipulating neural cells in vitro, and from transplantation techniques to considerations for modeling human development, evolution, and disease. As with all scientific endeavors, we advocate for rigorous experimental designs tailored to explicit scientific questions, and transparent methodologies and data sharing, to provide useful knowledge for both current research practices and for developing regulatory standards.

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Sensory Entrained TMS (seTMS) enhances motor cortex excitability.

bioRxiv

November 2024

Department of Psychiatry and Behavioral Sciences, Stanford University Medical Center, 401 Quarry Road, Stanford, CA, 94305, USA.

Transcranial magnetic stimulation (TMS) applied to the motor cortex has revolutionized the study of motor physiology in humans. Despite this, TMS-evoked electrophysiological responses show significant variability, due in part to inconsistencies between TMS pulse timing and ongoing brain oscillations. Variable responses to TMS limit mechanistic insights and clinical efficacy, necessitating the development of methods to precisely coordinate the timing of TMS pulses to the phase of relevant oscillatory activity.

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Synthetic receptors that mediate antigen-dependent cell responses are transforming therapeutics, drug discovery and basic research. However, established technologies such as chimeric antigen receptors can only detect immobilized antigens, have limited output scope and lack built-in drug control. Here we engineer synthetic G-protein-coupled receptors (GPCRs) that are capable of driving a wide range of native or non-native cellular processes in response to a user-defined antigen.

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Article Synopsis
  • The study focuses on how rats can adapt their decision-making based on context, which is vital for navigating complex environments.
  • Researchers created a new task to analyze this context-dependent behavior and discovered that different neural strategies can be used by rats to accomplish the same task.
  • Results showed significant variability in how individual rats performed the task, revealing insights into the neural mechanisms underlying flexible decision-making and suggesting that these findings could apply to both biological and artificial systems.
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The inner ear organs responsible for hearing (cochlea) and balance (vestibular system) are susceptible to oxidative stress due to the high metabolic demands of their sensorineural cells. Oxidative stress-induced damage to these cells can cause hearing loss or vestibular dysfunction, yet the precise mechanisms remain unclear due to the limitations of animal models and challenges of obtaining living human inner ear tissue. Therefore, we developed an in vitro oxidative stress model of the pre-natal human inner ear using otic progenitor cells (OPCs) derived from human-induced pluripotent stem cells (hiPSCs).

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Small molecule modulation of p75 engages the autophagy-lysosomal pathway and reduces huntingtin aggregates in cellular and mouse models of Huntington's disease.

Neurotherapeutics

November 2024

Department of Neurology & Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA; Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.

Huntington's disease (HD) is a neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene encoding a mutant huntingtin (mHtt) protein. mHtt aggregates within neurons causing degeneration primarily in the striatum. There is currently a need for disease-modifying treatments for HD.

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The Consortium for Clarity in ADRD Research Through Imaging (CLARiTI).

Alzheimers Dement

November 2024

Department of Medicine, University of Wisconsin School of Medicine and Public Health, Health Sciences Learning Center, Madison, Wisconsin, USA.

The presence of multiple pathologies is the largest predictor of dementia. A major gap in the field is the in vivo detection of mixed pathologies and their antecedents. The Alzheimer's Disease Research Centers (ADRCs) are uniquely positioned to address this gap.

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Article Synopsis
  • Olfactory dysfunction may signal early stages of Alzheimer's disease (AD), prompting research into the piriform cortex using tau PET-MR imaging.
  • A study of 94 older adults revealed increased tau uptake in the piriform cortex correlating with disease severity, particularly in those with Alzheimer’s compared to amyloid-negative controls.
  • The results indicate heightened tau levels in AD and mild cognitive impairment, connecting greater piriform uptake with poorer memory performance, while no significant changes were observed in cognitively unimpaired Parkinson's disease.
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An integrated transcriptomic cell atlas of human neural organoids.

Nature

November 2024

Department of Biosystems Science and Engineering, ETH Zürich, Basel, Switzerland.

Human neural organoids, generated from pluripotent stem cells in vitro, are useful tools to study human brain development, evolution and disease. However, it is unclear which parts of the human brain are covered by existing protocols, and it has been difficult to quantitatively assess organoid variation and fidelity. Here we integrate 36 single-cell transcriptomic datasets spanning 26 protocols into one integrated human neural organoid cell atlas totalling more than 1.

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In music ensemble performance, perception-action coupling enables the processing of auditory feedback from oneself and other players. However, improvised actions may affect this coupling differently from predetermined actions. This study used two-person EEG to examine how pianists responded to altered pitch feedback to their own or their partner's actions while they alternated scores or improvised melodies.

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Dynamic interactions between large-scale brain networks underpin human cognitive processes, but their electrophysiological mechanisms remain elusive. The triple network model, encompassing the salience network (SN), default mode network (DMN), and frontoparietal network (FPN), provides a framework for understanding these interactions. We analyzed intracranial electroencephalography (EEG) recordings from 177 participants across four diverse episodic memory experiments, each involving encoding as well as recall phases.

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The ability to control movement and learn new motor skills is one of the fundamental functions of the brain. The basal ganglia (BG) and the cerebellum (CB) are two key brain regions involved in controlling movement, and neuronal plasticity within these two regions is crucial for acquiring new motor skills. However, how these regions interact to produce a cohesive unified motor output remains elusive.

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A β-hydroxybutyrate shunt pathway generates anti-obesity ketone metabolites.

Cell

November 2024

Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA; Sarafan ChEM-H, Stanford University, Stanford, CA, USA; Stanford Diabetes Research Center, Stanford University, Stanford, CA, USA; Wu Tsai Human Performance Alliance, Stanford University, Stanford, CA, USA; The Phil & Penny Knight Initiative for Brain Resilience at the Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. Electronic address:

β-Hydroxybutyrate (BHB) is an abundant ketone body. To date, all known pathways of BHB metabolism involve the interconversion of BHB and primary energy intermediates. Here, we identify a previously undescribed BHB secondary metabolic pathway via CNDP2-dependent enzymatic conjugation of BHB and free amino acids.

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