Intra-striatal dopaminergic inter-subject covariance in social drinkers and non-treatment-seeking alcohol use disorder participants.

One of the neurobiological correlates of alcohol use disorder (AUD) is the disruption of striatal dopaminergic function. Although regional differences in dopamine (DA) tone/function have been well studied, interregional relationships (represented as inter-subject covariance) have not been investigated and may offer a novel avenue for understanding DA tone. Positron emission tomography (PET) data with [C]raclopride in 22 social drinking controls and 17 AUD participants were used to generate group-level striatal covariance (partial Pearson correlation) networks, which were compared edgewise as well as on global network metrics and community structure.

Exploring dysfunctional barrier phenotypes associated with glaucoma using a human pluripotent stem cell-based model of the neurovascular unit.

Glaucoma is a neurodegenerative disease that results in the degeneration of retinal ganglion cells (RGCs) and subsequent loss of vision. While RGCs are the primary cell type affected in glaucoma, neighboring cell types selectively modulate RGCs to maintain overall homeostasis. Among these neighboring cell types, astrocytes, microvascular endothelial cells (MVECs), and pericytes coordinate with neurons to form the neurovascular unit that provides a physical barrier to limit the passage of toxic materials from the blood into neural tissue.

TYK2 regulates tau levels, phosphorylation and aggregation in a tauopathy mouse model.

Alzheimer's disease is one of at least 26 diseases characterized by tau-positive accumulation in neurons, glia or both. However, it is still unclear what modifications cause soluble tau to transform into insoluble aggregates. We previously performed genetic screens that identified tyrosine kinase 2 (TYK2) as a candidate regulator of tau levels.

The long-term effects of limbic non-convulsive status epilepticus in peri-adolescent rats.

To optimize the clinical approach to non-convulsive status epilepticus (NCSE), it is essential to gain insight into its long-term effects on cognition and behaviors. Here, we investigated limbic NCSE-induced hippocampal injury and behavioral deficits in peri-adolescent rats. NCSE was induced in P43 Sprague Dawleyrats with intrahippocampal subconvulsive doses of kainic acid (NCSE group, n = 14) under continuous epidural cortical electroencephalography (EEG).

Human Corneal Rim Perfusion Culture.

Human anterior segment perfusion cultures are frequently used for trabecular meshwork research. However, this model requires the use of whole eye globes which are expensive. Here, we describe a method using human corneal rims as an alternative to anterior segments for perfusion culture.

Acquisition of neurodegenerative features in isogenic OPTN(E50K) human stem cell-derived retinal ganglion cells associated with autophagy disruption and mTORC1 signaling reduction.

The ability to derive retinal ganglion cells (RGCs) from human pluripotent stem cells (hPSCs) has led to numerous advances in the field of retinal research, with great potential for the use of hPSC-derived RGCs for studies of human retinal development, in vitro disease modeling, drug discovery, as well as their potential use for cell replacement therapeutics. Of all these possibilities, the use of hPSC-derived RGCs as a human-relevant platform for in vitro disease modeling has received the greatest attention, due to the translational relevance as well as the immediacy with which results may be obtained compared to more complex applications like cell replacement. While several studies to date have focused upon the use of hPSC-derived RGCs with genetic variants associated with glaucoma or other optic neuropathies, many of these have largely described cellular phenotypes with only limited advancement into exploring dysfunctional cellular pathways as a consequence of the disease-associated gene variants.

CalTrig: A GUI-based Machine Learning Approach for Decoding Neuronal Calcium Transients in Freely Moving Rodents.

Advances in imaging using miniature microscopes have enabled researchers to study single-neuron activity in freely-moving animals. Tools such as MiniAN and CalmAn have been developed to convert isual signals umerical data, collectively referred to as CalV2N. However, substantial challenges remain in analyzing the large datasets generated by CalV2N, particularly in integrating data streams, evaluating CalV2N output quality, and reliably and efficiently identifying transients.

Trem2-deficiency aggravates and accelerates age-related myelin degeneration.

Aging is the greatest known risk factor for most neurodegenerative diseases. Myelin degeneration is an early pathological indicator of these diseases and a normal part of aging; albeit, to a lesser extent. Despite this, little is known about the contribution of age-related myelin degeneration on neurodegenerative disease.

High Diagnostic Yield and Clinical Utility of Next-Generation Sequencing in Children with Epilepsy and Neurodevelopmental Delays: A Retrospective Study.

Advances in genetics led to the identification of hundreds of epilepsy-related genes, some of which are treatable with etiology-specific interventions. However, the diagnostic yield of next-generation sequencing (NGS) in unexplained epilepsy is highly variable (10-50%). We sought to determine the diagnostic yield and clinical utility of NGS in children with unexplained epilepsy that is accompanied by neurodevelopmental delays and/or is medically intractable.

Coupled pulsatile vascular and paravascular fluid dynamics in the human brain.

Background: Cardiac pulsation propels blood through the cerebrovascular network to maintain cerebral homeostasis. The cerebrovascular network is uniquely surrounded by paravascular cerebrospinal fluid (pCSF), which plays a crucial role in waste removal, and its flow is suspected to be driven by arterial pulsations. Despite its importance, the relationship between vascular and paravascular fluid dynamics throughout the cardiac cycle remains poorly understood in humans.

Fluid biomarkers in the context of amyloid-targeting disease-modifying treatments in Alzheimer's disease.

Clinical management and therapeutics development for Alzheimer's disease (AD) have entered a new era, with recent approvals of monoclonal antibody therapies targeting the underlying pathophysiology of the disease and modifying its trajectory. Imaging and fluid biomarkers are becoming increasingly important in the clinical development of AD therapeutics. This review focuses on the evidence of fluid biomarkers from recent amyloid-β-targeting clinical trials, summarizing biomarker data across 12 trials.

Effect of depression treatment on health behaviors and cardiovascular risk factors in primary care patients with depression and elevated cardiovascular risk: data from the eIMPACT trial.

Background: Depression is an independent risk factor for cardiovascular disease (CVD), but it is unknown if successful depression treatment reduces CVD risk.

Methods: Using eIMPACT trial data, we examined the effect of modernized collaborative care for depression on indicators of CVD risk. A total of 216 primary care patients with depression and elevated CVD risk were randomized to 12 months of the eIMPACT intervention (internet cognitive-behavioral therapy [CBT], telephonic CBT, and select antidepressant medications) or usual primary care.

Characterization, enrichment, and computational modeling of cross-linked actin networks in trabecular meshwork cells.

Purpose: Cross-linked actin networks (CLANs) are prevalent in the glaucomatous trabecular meshwork (TM), yet their role in ocular hypertension remains unclear. We used a human TM cell line that spontaneously forms fluorescently-labeled CLANs (GTM3L) to explore the origin of CLANs, developed techniques to increase CLAN incidence in GMT3L cells, and computationally studied the biomechanical properties of CLAN-containing cells.

Methods: GTM3L cells were fluorescently sorted for viral copy number analysis.

Multiparametric MRI Scoring System of the Pancreas for the Diagnosis of Chronic Pancreatitis.

Background: Ductal features alone may not offer high diagnostic sensitivity or most accurate disease severity of chronic pancreatitis (CP).

Purpose: Diagnose CP based on multiparametric MRI and MRCP features.

Study Type: Prospective.

Sex-dependent, lateralized engagement of anterior insular cortex inputs to the dorsolateral striatum in binge alcohol drinking.

How does alcohol consumption alter synaptic transmission across time, and do these alcohol-induced neuroadaptations occur similarly in both male and female mice? Previously we identified that anterior insular cortex (AIC) projections to the dorsolateral striatum (DLS) are uniquely sensitive to alcohol-induced neuroadaptations in male, but not female mice, and play a role in governing binge alcohol consumption in male mice (Haggerty et al., 2022). Here, by using high-resolution behavior data paired with in-vivo fiber photometry, we show how similar levels of alcohol intake are achieved via different behavioral strategies across sexes, and how inter-drinking session thirst states predict future alcohol intakes in females, but not males.

Neural processing of sweet taste in reward regions is reduced following bariatric surgery.

Objective: Bariatric surgery reduces sweet-liking, but mechanisms remain unclear. We examined related brain responses.

Methods: A total of 24 nondiabetic bariatric surgery and 21 control participants with normal weight to overweight were recruited for an observational controlled cohort study.

Cryo-EM structures of cotton wool plaques' amyloid β and of tau filaments in dominantly inherited Alzheimer disease.

Cotton wool plaques (CWPs) have been described as features of the neuropathologic phenotype of dominantly inherited Alzheimer disease (DIAD) caused by some missense and deletion mutations in the presenilin 1 (PSEN1) gene. CWPs are round, eosinophilic amyloid-β (Aβ) plaques that lack an amyloid core and are recognizable, but not fluorescent, in Thioflavin S (ThS) preparations. Amino-terminally truncated and post-translationally modified Aβ peptide species are the main component of CWPs.

Inkjet-Printed, Flexible Organic Electrochemical Transistors for High-Performance Electrocorticography Recordings.

Organic electrochemical transistors (OECTs) have emerged as powerful tools for biosignal amplification, including electrocorticography (ECoG). However, their widespread application has been limited by the complexities associated with existing fabrication techniques, restricting accessibility and scalability. Here, we introduce a novel all-planar, all-printed high-performance OECT device that significantly enhances the accuracy and sensitivity of ECoG recordings.

Greater ventral striatal functional connectivity in cigarette smokers relative to non-smokers across a spectrum of alcohol consumption.

Cigarette smoking is associated with elevated risk of disease and mortality and contributes to heavy healthcare-related economic burdens. The nucleus accumbens is implicated in numerous reward-related behaviors, including reinforcement learning and incentive salience. The established functional connectivity of the accumbens includes regions associated with motivation, valuation, and affective processing.