Syngap1 promotes cognitive function through regulation of cortical sensorimotor dynamics.

Perception, a cognitive construct, emerges through sensorimotor integration (SMI). The genetic mechanisms that shape SMI required for perception are unknown. Here, we demonstrate in mice that expression of the autism/intellectual disability gene, Syngap1, in cortical excitatory neurons is required for the formation of somatomotor networks that promote SMI-mediated perception.

Enriched phenotypes in rare variant carriers suggest pathogenic mechanisms in rare disease patients.

Background: The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the presenting symptoms. Moreover, the same dysfunctional series of interrelated symptoms implicated in rare recessive diseases may also lead to milder and potentially preventable symptoms in carriers in the general population.

Dynamical constraints on neural population activity.

The manner in which neural activity unfolds over time is thought to be central to sensory, motor and cognitive functions in the brain. Network models have long posited that the brain's computations involve time courses of activity that are shaped by the underlying network. A prediction from this view is that the activity time courses should be difficult to violate.

Effects of HMG CoA reductase (HMGCR) deficiency on skeletal muscle development.

Pathogenic variants in HMGCR were recently linked to a limb-girdle muscular dystrophy (LGMD) phenotype. The protein product HMG CoA reductase (HMGCR) catalyzes a key component of the cholesterol synthesis pathway. The two other muscle diseases associated with HMGCR, statin-associated myopathy (SAM) and autoimmune anti-HMGCR myopathy, are not inherited in a Mendelian pattern.

Adaptive Approaches to Exercise Rehabilitation for Postural Tachycardia Syndrome and Related Autonomic Disorders.

Exercise is a well-documented, nonpharmacologic treatment for individuals with autonomic dysfunction and associated orthostatic intolerance, such as postural tachycardia syndrome and related disorders. Exercise has been shown to increase blood volume, reverse cardiovascular deconditioning, and improve quality of life. Current first-line standard of care treatment for autonomic dysfunction combines graded approaches to exercise with medications and lifestyle modifications.

Head and Neck Paraganglioma in Pacak-Zhuang Syndrome.

Head and neck paragangliomas (HNPGLs) are typically slow-growing, hormonally inactive tumors of parasympathetic paraganglia. Inactivation of prolyl-hydroxylase domain-containing 2 protein causing indirect gain-of-function of hypoxia-inducible factor-2α (HIF-2α), encoded by EPAS1, was recently shown to cause carotid body hyperplasia. We previously described a syndrome with multiple sympathetic paragangliomas caused by direct gain-of-function variants in EPAS1 (Pacak-Zhuang syndrome, PZS) and developed a corresponding mouse model.

Recent Advances in the Genetics of Ataxias: An Update on Novel Autosomal Dominant Repeat Expansions.

Purpose Of Review: Autosomal dominant cerebellar ataxias, also known as spinocerebellar ataxias (SCAs), are genetically and clinically diverse neurodegenerative disorders characterized by progressive cerebellar dysfunction. Despite advances in sequencing technologies, a large proportion of patients with SCA still lack a definitive genetic diagnosis. The advent of advanced bioinformatic tools and emerging genomics technologies, such as long-read sequencing, offers an unparalleled opportunity to close the diagnostic gap for hereditary ataxias.

Recommendations for mitochondria transfer and transplantation nomenclature and characterization.

Intercellular mitochondria transfer is an evolutionarily conserved process in which one cell delivers some of their mitochondria to another cell in the absence of cell division. This process has diverse functions depending on the cell types involved and physiological or disease context. Although mitochondria transfer was first shown to provide metabolic support to acceptor cells, recent studies have revealed diverse functions of mitochondria transfer, including, but not limited to, the maintenance of mitochondria quality of the donor cell and the regulation of tissue homeostasis and remodelling.

Association of plasma biomarkers of Alzheimer's pathology and neurodegeneration with gait performance in older adults.

Background: Declining gait performance is seen in aging individuals, due to neural and systemic factors. Plasma biomarkers provide an accessible way to assess evolving brain changes; non-specific neurodegeneration (NfL, GFAP) or evolving Alzheimer's disease (Aβ 42/40 ratio, P-Tau181).

Methods: In a population-based cohort of older adults, we evaluate the hypothesis that plasma biomarkers of neurodegeneration and Alzheimer's Disease pathology are associated with worse gait performance.

Incomplete remyelination via therapeutically enhanced oligodendrogenesis is sufficient to recover visual cortical function.

Myelin loss induces neural dysfunction and contributes to the pathophysiology of neurodegenerative diseases, injury conditions, and aging. Because remyelination is often incomplete, better understanding endogenous remyelination and developing remyelination therapies that restore neural function are clinical imperatives. Here, we use in vivo two-photon microscopy and electrophysiology to study the dynamics of endogenous and therapeutic-induced cortical remyelination and functional recovery after cuprizone-mediated demyelination in mice.

Ramping Dynamics in the Frontal Cortex Unfold Over Multiple Timescales During Motor Planning.

Plans are formulated and refined throughout the period leading up to their execution, ensuring that the appropriate behaviors are enacted at the appropriate times. While existing evidence suggests that memory circuits convey the passage of time through diverse neuronal responses, it remains unclear whether the neural circuits involved in planning exhibit analogous temporal dynamics. Using publicly available data, we analyzed how activity in the mouse frontal motor cortex evolves during motor planning.

Random noise promotes slow heterogeneous synaptic dynamics important for robust working memory computation.

Recurrent neural networks (RNNs) based on model neurons that communicate via continuous signals have been widely used to study how cortical neural circuits perform cognitive tasks. Training such networks to perform tasks that require information maintenance over a brief period (i.e.

Paramagnetic rim lesion formation is predicted by the initial gadolinium-enhancing lesion diameter.

Background: Paramagnetic rim lesions (PRLs) are a magnetic resonance imaging (MRI) marker of compartmentalized intraparenchymal inflammation.

Objectives: The primary objective was to investigate clinical, demographic, and MRI factors that may be predictive of the future formation of PRL.

Methods: This is a retrospective analysis of longitudinal data.

Neurovascular coupling: a review of spontaneous neocortical dynamics linking neuronal activity to hemodynamics and what we have learned from the rodent brain.

The brain is a complex neural network whose functional dynamics offer valuable insights into behavioral performance and health. Advances in fMRI have provided a unique window into studying human brain networks, providing us with a powerful tool for clinical research. Yet many questions about the underlying correlates between spontaneous fMRI and neural activity remain poorly understood, limiting the impact of this research.

Blood pressure targets, medication considerations and special concerns in elderly hypertension III: Focus on stroke and neurodegenerative disorders.

Controlling hypertension has become an important issue in the elderly population in whom neurological comorbidities are highly prevalent. Most of the large-scale trials focusing on hypertension management in older populations have excluded patients with comorbid neurological disorders. However, this population requires special considerations, as the benefits of antihypertensive agents are mostly uncertain and there is a higher risk of adverse events.

Prognostic Impact of 1-Year Changes in Creatinine- and Cystatin C-Based Estimated Glomerular Filtration Rate After Stroke on 5-Year Outcomes: Insights From the Third China National Stroke Registry.

Background: The impact of long-term renal function change on stroke outcomes remains unclear. This study used the CNSR-III (Third China National Stroke Registry) cohort to determine whether changes in estimated glomerular filtration rate based on creatinine and cystatin C (eGFR) during the first year post stroke were associated with 5-year stroke outcomes.

Methods And Results: We included 4270 patients with centrally tested serum creatinine and cystatin C at admission and 1 year post admission and evaluated 5-year follow-up data.

Elevated Cerebrospinal Fluid α-Synuclein Seeding Activity Predicts Central Lewy Body Diseases.

Background: Cerebrospinal fluid (CSF) α-synuclein seeding activity (SSA) via a seed amplification assay might predict central Lewy body diseases (LBD) in at-risk individuals.

Objective: The aim was to assess CSF SSA in a prospective, longitudinal study.

Methods: Participants self-reported risk factors were genetics, olfactory dysfunction, dream enactment behavior, orthostatic intolerance, or hypotension; individuals who had ≥3 confirmed risk factors underwent CSF sampling and were followed for up to 7.

Diagnosing Epilepsy with Normal Interictal EEG Using Dynamic Network Models.

Objective: Whereas a scalp electroencephalogram (EEG) is important for diagnosing epilepsy, a single routine EEG is limited in its diagnostic value. Only a small percentage of routine EEGs show interictal epileptiform discharges (IEDs) and overall misdiagnosis rates of epilepsy are 20% to 30%. We aim to demonstrate how network properties in EEG recordings can be used to improve the speed and accuracy differentiating epilepsy from mimics, such as functional seizures - even in the absence of IEDs.

Safety and Efficacy of Metformin for Idiopathic Intracranial Hypertension. A U.S-Based Real-World Data Retrospective Multicenter Cohort Study.

Introduction: Managing idiopathic intracranial hypertension (IIH) is challenging due to limited treatment options. This study evaluates metformin as a potential therapy for IIH, examining its impact on disease outcomes and safety.

Methods: We performed a retrospective cohort study using the TriNetX database, covering data from 2009 to August 2024.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

High-Field-Blinded Assessment of Portable Ultra-Low-Field Brain MRI for Multiple Sclerosis.

Background And Purpose: MRI is crucial for multiple sclerosis (MS), but the relative value of portable ultra-low field MRI (pULF-MRI), a technology that holds promise for extending access to MRI, is unknown. We assessed white matter lesion (WML) detection on pULF-MRI compared to high-field MRI (HF-MRI), focusing on blinded assessments, assessor self-training, and multiplanar acquisitions.

Methods: Fifty-five adults with MS underwent pULF-MRI following their HF-MRI.

The TRP Channels Serving as Chemical-to-Electrical Signal Converter.

Biology uses many signaling mechanisms. Among them, calcium and membrane potential are two prominent mediators for cellular signaling. TRPM4 and TRPM5, two calcium-activated monovalent cation-conducting ion channels, offer a direct linkage between these two signals.

General Kernel Machine Methods for Multi-Omics Integration and Genome-Wide Association Testing With Related Individuals.

Integrating multi-omics data may help researchers understand the genetic underpinnings of complex traits and diseases. However, the best ways to integrate multi-omics data and use them to address pressing scientific questions remain a challenge. One important and topical problem is how to assess the aggregate effect of multiple genomic data types (e.

Identifying cognitive test scores associated with early tau burden in Alzheimer's disease.

Introduction: This study aimed to identify cognitive tests that optimally relate to tau positron emission tomography (PET) signal in the inferior temporal cortex (ITC), a neocortical region associated with early tau accumulation in Alzheimer's disease (AD).

Methods: We analyzed cross-sectional data from the harvard aging brain study (HABS) (= 128) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study (= 393). We used elastic net regression to identify the most robust cognitive correlates of tau PET signal in the ITC.

Dense-core vesicles contain exosomes in secretory cells.

Dense-core vesicles (DCVs) are found in various types of cells, such as neurons, pancreatic β- cells, and chromaffin cells. These vesicles release transmitters, peptides, and hormones to regulate diverse functions, such as the stress response, immune response, behavior, and blood glucose levels. In traditional electron microscopy after chemical fixation, it is often reported that the dense cores occupy a portion of the vesicle toward the center and are surrounded by a clear halo.