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Category: neuroscience – Page 52

Bayesian probabilistic density mapping of the decussating dentato-rubro-thalamic tract to predict clinical tremor improvement in MRgFUS

OBJECTIVE Magnetic resonance–guided focused ultrasound (MRgFUS) is increasingly recognized as an effective treatment option for patients with medication-refractory essential tremor (ET). Indirect coordinates of the ventral intermediate nucleus of the thalamus, as well as the dentato-rubro-thalamic tract (DRTT) originating from the ipsilateral dentate nucleus, known as the “nondecussating DRTT” (nd-DRTT), are commonly used as targets for sonication. Anatomically, the DRTT originating from the contralateral dentate nucleus, referred to as the “decussating DRTT” (d-DRTT), constitutes the predominant component of the two fiber populations. However, the d-DRTT is rarely visualized using conventional diffusion tensor imaging (DTI) because of the technical challenges associated with resolving crossing fiber orientations. Probabilistic tractography enables the differentiation of crossing fibers, thus allowing for visualization of both the d-DRTT and nd-DRTT. Authors of this study aimed to evaluate whether the d-DRTT delineated by probabilistic tractography represents an anatomical target more important than indirect coordinates or the nd-DRTT. METHODS Consecutive patients with medically refractory ET who underwent unilateral MRgFUS thalamotomy at a single institution between May 2022 and August 2024 were analyzed. Tremor severity was assessed using the Clinical Rating Scale for Tremor Part B, and the percentage improvement at 3 months after treatment was calculated as an indicator of functional recovery. Probabilistic tractography of the DRTT was performed post hoc using preoperative diffusion MRI and Bayesian modeling (BedpostX) and probabilistic tracking (ProbtrackX). The distances between the sonicated lesion as detected on postoperative MRI and each of the following were compared: indirect coordinates, nd-DRTT, and d-DRTT. Subgroup analysis was performed on patients with a peak lesion temperature ≥ 55°C. Pearson correlation was used to assess the relationships between distance metrics and clinical outcomes. RESULTS Probabilistic tractography successfully visualized the d-DRTT in all 28 patients included in the study. The d-DRTT was more lateral than both the indirect coordinate and the nd-DRTT (p < 0.01 for both), with a nonsignificant tendency for a more anterior position relative to the nd-DRTT (p = 0.054). Among the patients with a peak lesion temperature ≥ 55°C, the distance between the sonicated lesion and the d-DRTT showed a strong correlation with clinical outcomes, whereas that between the lesion and nd-DRTT showed a moderate correlation; the indirect coordinates showed no significant correlation. CONCLUSIONS Probabilistic tractography successfully visualized the d-DRTT, and its location appears to capture the “tremor-relevant” neural pathway more accurately than either the indirect coordinate or the nd-DRTT.

Abstract: Proposing a no-nonsense strategy for the treatment of dominant neurodevelopmental disorders:

Xiaochang Zhang & team introduce exon annotation for nonsense-mediated mRNA (EANMD) and report on alternatively spliced exons in the brain that trigger mRNA decay, noting modulation of such exons in disease-causal genes can potentially treat neurodevelopmental disorders.

Address correspondence to: Xiaochang Zhang, University of Chicago, Cummings Life Science Center 507A, 920 E. 58th St., Chicago, Illinois 60,637, USA. Phone: 773.834.5369; Email: [email protected].

New 3D device harnesses living brain cells for computing

Princeton researchers have combined brain cells and advanced electronics into a single 3D device that can be programmed to recognize patterns using computational techniques. Past attempts at using brain cells to do computation have relied on 2D cultures grown in a petri dish or 3D clusters that are probed and monitored from outside. The Princeton device takes a different approach, working from the inside out.

Using advanced fabrication techniques, the team created a 3D mesh made of microscopic metal wires and electrodes supported by a thin epoxy coating. Because the coating is so thin, it has just the right amount of flexibility to interface with the soft neurons that grow around it. The team used the mesh as a scaffold to culture tens of thousands of neurons into a vast 3D network that can be used to do computation.

The study was published in Nature Electronics on Apr. 23.

Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein

Online now: Tsang et al. identify the T-type calcium channel Cav3.1 as a neuronal leucine sensor in hypothalamic POMC neurons. Leucine directly binds Cav3.1, lowering its activation threshold. Loss of Cav3.1 in POMC neurons abolishes high-protein diet-induced appetite suppression, while pharmacological activation promotes weight loss and potentiates the effects of anorectic agents.

Tau Blood Test Detects Alzheimer’s Disease Risk Years Before Brain Changes

New research suggests that plasma phosphorylated tau 217 (pTau217) can detect Alzheimer’s disease pathology years before it appears on traditional PET scans. In longitudinal studies, elevated pTau217 levels accurately predicted future amyloid accumulation and cognitive decline in currently asymptomatic, healthy older adults. While not yet recommended for routine clinical screening, this biomarker offers a potential “clock” for estimating the onset of symptoms within a three to four year margin.

Participants who were amyloid-beta-negative and had very low pTau217 (below ~2.6% in this cohort) rarely became amyloid-beta-positive, suggesting this subgroup may be low risk and might not require amyloid-beta PET until pTau217 rises, the researchers said.

Higher baseline plasma %pTau217 also predicted tau accumulation in the brain — even when amyloid levels were still low, suggesting it captures very early disease processes.

In terms of cognition, across the full cohort, higher plasma pTau217 was associated with faster decline on a composite cognitive score. However, this relationship was largely driven by individuals who already had elevated amyloid; among amyloid-negative participants, pTau217 did not significantly predict cognitive decline over the follow-up period.

Multicentre gene therapy for OTOF-related deafness followed up to 2.5 years

A new international study co-led by investigators from Mass General Brigham and the Eye & ENT Hospital of Fudan University shows that a gene therapy for a rare form of genetic deafness successfully restored hearing in most participants, with results lasting up to 2.5 years. The results, the largest clinical trial of gene therapy for inherited hearing loss to date and the longest follow-up reported so far, are published in Nature. According to the authors, these latest findings reinforce earlier trials that show gene therapy can be used to treat some forms of inherited deafness, helping guide future research and care.

“It’s remarkable to see patients go from complete deafness to being able to hear,” said the study’s corresponding author, Zheng-Yi Chen, DPhil, the Ines and Fredrick Yeatts Chair in Otolaryngology and an associate scientist at Mass Eye and Ear, a member of the Mass General Brigham healthcare system. “For many patients, that also means the ability to develop and use speech.”

Genetic mutations account for up to 60% of hearing loss present at birth. In this study, researchers used a gene therapy they developed to treat autosomal recessive deafness 9 (DFNB9), caused by mutations in the OTOF gene. The OTOF gene provides the body with instructions to make a protein called otoferlin, which is essential for hearing function. Without it, hair cells in the inner ear cannot pass sound signals to the brain, causing severe-to-complete deafness at birth. OTOF mutations account for about 2 to 8 in every 100 cases.

Gene therapies are designed to add a working version of mutated genes that lead to disease. Since a single faulty gene causes DFNB9, it is well-suited for gene therapy research. The treatment is a single injection into the inner ear that uses a harmless virus (AAV) to deliver a working copy of the OTOF gene to the cells needed for hearing.

This latest trial enrolled 42 participants across eight sites in China, ranging in age from infants to adults (0.8 to 32.3 years). Each participant received one of three doses of a single gene therapy treatment: 36 in one ear and six in both ears. The research team then followed participants for up to 2.5 years, to see if treatment remained safe, affected their hearing and speech recognition. The researchers also sought to better understand why some participants may respond better than others.

“These multicenter trial results validate the effectiveness of our OTOF gene therapy,” said Yilai Shu, MD, PhD, a professor from Eye & ENT Hospital of Fudan University, who led the study. “The procedure can be broadly implemented in hospital settings, ensuring consistent delivery for a larger patient population.”

Abstract: Multicentre gene therapy for OTOF-related deafness followed up to 2.5 years https://www.nature.com/articles/s41586-026-10393-y.

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Just two doses of new nasal spray found to slow brain ageing and restore memory

Recently, a growing body of research suggests that the brain fog one experiences as they grow older is linked to a tide of inflammation deep within the brain’s memory centre. Scientists call this “neuroinflammaging” – thought to be the inevitable price of growing older.

But now, a new mice study suggests that this inflammation behind brain ageing and brain fog can actually be reversed with a simple nasal spray. This spray could reshape the future of therapies for conditions like Alzheimer’s disease, and may even change what is known about brain ageing itself, say researchers from Texas A&M University.

Immune molecule long tied to inflammation may benefit the aging brain

Inflammation in the brain is usually seen as harmful in the aging process—it’s thought to contribute to Alzheimer’s and dementia. But a new study in mice suggests that inflammation, led by an immune molecule called STING (stimulator of interferon genes), might have a role in protecting the aging brain. The findings also have implications for new experimental Alzheimer’s drugs that are designed to block STING.

For the study published in Cell Reports, scientists at Tufts University School of Medicine examined brain function, inflammation, and movement in genetically engineered to lack STING, compared with normal controls. They found that mice without STING had worse memory and movement problems, mimicking the senility and frailty seen in people with dementia and Alzheimer’s disease.

“Our data suggest that the that STING supports may actually be necessary for the brain to stay healthy and in balance during old age,” says Shruti Sharma, an assistant professor of immunology at Tufts University School of Medicine and the study’s senior author.

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