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Oct 15Thu
  1. Cephalalgia41

    Alterations in the interstitial microenvironment across headache phases and clinical phenotypes in migraine: A multimodal diffusion MRI study.

    Multimodal diffusion MRI found no overall differences between migraine participants and healthy controls, but chronic migraine with medication-overuse headache showed reduced extracellular volume fraction and increased intracellular volume fraction versus controls, in the corpus callosum, anterior thalamic radiation, cingulum and optic radiations. Similar alterations appeared during headache. The findings suggest interstitial microenvironment changes tied to headache phase and disease burden rather than a stable trait.

  2. Nature77

    A microexon regulatory code reveals autism-linked genetic variation.

    An expanded map of neuronal microexons, built from extensive transcriptome profiling, adds hundreds of new microexons, including subtype-specific ones and others that trigger nonsense-mediated mRNA decay. A machine-learning sequence code predicts neuronally spliced microexons and identifies regulatory elements around them. Applied to autism, the code pinpoints rare splicing-altering variants, mostly in idiopathic individuals, that associate with autism status and converge on synaptic and other autism-linked genes.

    Why it matters: It links autism-associated genetic variation to a splicing code for neuronal microexons.

  3. Nature73

    Targeted stimulation of motor cortex ensembles drives learned movements.

    Stimulating about 20 layer 2/3 motor cortex neurons whose activity precedes movement onset triggered lever-press-like movements in task-engaged mice and reproduced the learned population activity pattern. Trial-by-trial variability in the evoked activity and movements was predicted by the initial state of M1 before stimulation. Stimulating movement-following neurons, or stimulating in disengaged mice, failed, supporting a causal, active role for M1 in generating learned movements.

    Why it matters: It provides causal evidence that small defined M1 ensembles drive learned movements.

  5. biorxiv.org61

    A microbiota-driven neuroepithelial feed-forward circuit drives gastroesophageal junction tumorigenesis

    Bile acid remodeling enriches the oral commensal Prevotella melaninogenica at the gastroesophageal junction, where bacterial succinate activates vagal sensory neurons and SUCNR1-expressing tuft cells. Tuft cells release 15-d-PGJ2 to sensitize sensory neurons, while neuronal CGRP drives expansion and tuft-cell differentiation of neuro-responsive epithelial progenitors through RAMP1, forming a self-reinforcing microbiota-neuron-epithelium circuit that promotes dysplastic progression. Genetic or pharmacological disruption of the circuit, including with the approved CGRP antagonist rimegepant, suppresses tumor development.

  6. statnews.com48

    Compass Pathways CEO: Psychedelics company will ‘go slow before we go fast’

    Compass Pathways CEO Kabir Nath said the company will take a cautious approach to launching COMP360, its synthetic psilocybin therapy for treatment-resistant depression, saying bad early patient or provider experiences could harm the broader sector. Compass plans to complete a rolling FDA submission this quarter and aims to launch early next year, expecting a REMS and investing in provider training. In Phase 3 trials, roughly a quarter of patients responded after a single dose, rising to about 40% after a second dose three weeks later.

  7. biorxiv.org54

    Transcriptomic and phenotypic characterization of Alzheimer's disease risk genes in neurons and astrocytes highlights shared and cell type specific cellular mechanisms

    Knockouts of roughly 250 candidate Alzheimer's disease genes in iPSC-derived iNeurons and iAstrocytes show highly cell-type-specific effects that converge on shared pathways. Disease-linked expression programs from postmortem patient samples responded to the knockouts, and phenotypic analyses profiled each gene. The screen identified CCDC6 roles in cell cycle and activation state in iAstrocytes and C2orf49 regulation of endoplasmic reticulum stress responses in iNeurons.

  8. nature.com81

    A microexon regulatory code reveals autism-linked genetic variation

    An expanded map of neuronal microexons and a machine learning model of microexon splicing reveal rare human genetic variation predicted to converge on a subset of microexons in genes linked to nervous system biology and neurodevelopmental disorders. Analysing 4,790 bulk RNA-seq samples and 47,380 single nuclei from human cortex, the authors detected 1,514 previously unannotated microexons, 292 of them differentially spliced between neural and non-neural cells. The work points to non-coding variants as a possible contributor to the roughly 85% of autism cases with no identified genetic cause.

    Why it matters: It offers a mechanistic explanation for much of the unexplained genetic aetiology of autism through non-coding microexon variation.

  9. nature.com71

    Targeted stimulation of motor cortex ensembles drives learned movements

    Optogenetic stimulation of motor-cortex neuron ensembles generated learned neural patterns and movements, showing that precisely timed activity in the primary motor cortex can produce skilled motor output. The work demonstrates an active role for primary motor cortex in skilled motor control rather than passive relay of elsewhere-generated commands.

    Why it matters: Causal evidence that timed motor-cortex ensemble activity alone can produce learned movements.

  10. nature.com63

    Elp1 is required for myeloid differentiation and brain repopulation

    A primary cultured haematopoietic stem and progenitor cell platform was used to analyse the molecular mechanisms of brain myeloid differentiation, and identified the elongation factor ELP1 as an important regulator of this process. ELP1 was shown to be required for myeloid differentiation and brain repopulation, pointing to a new molecular control point in the development of brain myeloid cells.

Oct 14Wed
  1. Cell76

    PTPRS mediates invasion of tetanus neurotoxin into the central nervous system.

    The receptor protein tyrosine phosphatase sigma (PTPRS) is the host receptor that carries tetanus neurotoxin into the central nervous system. Pull-down, mass spectrometry and a luciferase-based in vivo transport assay identified PTPRS as the retrograde transport receptor; global or motoneuron-specific PTPRS knockout abolished TeNT entry into the CNS in mice, and a PTPRS-binding-deficient TeNT mutant caused botulism-like flaccid paralysis. The finding exposes a targetable pathway for post-entry intervention and for drug delivery into the CNS.

    Why it matters: Identifies the long-sought host receptor mediating tetanus neurotoxin entry into the CNS.

  2. Cell75

    A high-dimensional population code in the bat motor cortex during natural dexterous flight.

    Motor cortex in freely flying bats uses a high-dimensional, sparse population code rather than wingbeat-dominated activity. Neurons showed mixed selectivity for flight kinematics and millisecond-scale entrainment to wingbeat phase, with successive wingbeats occupying distinct neural states despite bats executing accurate flights via precise individual wingbeat adjustments. This challenges prevailing views of motor cortical dynamics derived from constrained paradigms.

    Why it matters: It overturns expectations that motor cortex during rhythmic movement is dominated by the movement cycle.

  3. JAMA51

    Clinicopathologic Evaluation of Amyloid Clearance in Alzheimer Disease.

    Extensive amyloid clearance after aducanumab tracked with less downstream Alzheimer pathology in a clinicopathologic case report of a man in his 50s with mild cognitive impairment carrying the p.R47H TREM2 variant, who received 30 doses (cumulative 280 mg/kg) over 4.5 years. At autopsy four years after his final dose, brain regions with low residual amyloid, preferentially at gyral crests, showed less tau and slower longitudinal atrophy on MRI (β = -0.50; P < .001), while regions of high amyloid in sulcal depths had tau levels similar to those of untreated controls.

  4. Nat Biotechnol52

    Engrafting human cortical organoids.

    Xenocortication, a transplantation approach described by Kaganovsky and colleagues, integrates human cortical organoids into the mouse brain by grafting human induced pluripotent stem cell-derived cortical organoids into the cortical cavity of neonatal immunodeficient 'apallial' mice, in which most of the neocortex and hippocampus had been genetically depleted. Magnetic resonance imaging showed the grafts grew approximately 4.7-fold between 2 and 3 months after transplantation and accounted for nearly 92% of the combined cortical tissue volume. The approach addresses limited intracranial space and interactions with existing neural circuits that restrict organoid growth and integration after transplantation into rodents.

    Why it matters: Reports a transplantation method that markedly improves growth and integration of human cortical organoids in mice.

  5. nature.com46

    Can GLP-1s heal the brain? Obesity drugs get a makeover for addiction and depression

    Eli Lilly presented the first clinical results of brenipatide, a GLP-1 and GIP mimic related to tirzepatide, for alcohol use disorder at the Psych Congress in New Orleans; its half-life is 9–12 days versus 5–7 days for approved GLP-1 drugs. Kariya Pharmaceuticals shared early clinical results of the GLP-1 compound KP405 for Parkinson's disease, and Baseline Therapeutics plans phase III trials of BT-001 for alcohol use disorder starting in early 2027. Academic trials, including a 2025 semaglutide study in alcohol use disorder, have shown reduced craving and heavy drinking, encouraging industry interest in GLP-1 therapies for addiction and other brain disorders.

  6. jamanetwork.com77

    The 2026 Albert Lasker Basic Medical Research Award

    Emmanuel Mignot and Masashi Yanagisawa, winners of the 2026 Albert Lasker Basic Medical Research Award, identified the brain peptide orexin and established its role in sleep regulation. Their work linked orexin deficiency to narcolepsy. The Perspective traces how the discovery advanced understanding of the sleep disorder.

    Why it matters: Lasker Award honors the discovery of orexin and its link to narcolepsy.

Oct 13Tue
  1. biorxiv.org53

    Benchmarked sequencing methods reveal hidden mosaic variation in the human brain

    Benchmarking four duplex sequencing methods against bulk and single-neuron genome sequencing in matched human brain tissue showed that mosaic variant recovery is strongly method-dependent, with limited caller-level concordance. The new RIVER tool integrates read-level evidence, expanding cross-method-supported candidates by roughly two orders of magnitude; orthogonal sequencing at ~10,000x validated about half of tested RIVER-rescued candidates. Recovered variants resolved broadly distributed and regionally restricted clones and traced lineage among individual neurons.

    Why it matters: A benchmarked method that expands usable mosaic variant markers changes how brain lineage and mosaicism can be studied.

  2. nature.com57

    Human–artificial intelligence collaboration for comanaging epilepsy in real time

    A moderated large language model-based chat interface let epilepsy monitoring patients converse with their electroencephalography monitoring in real time via smartphone. In the small study, patient feedback reduced seizure-detector false alarms by about 80% without clinician input. This points to human-AI collaboration as a way to improve seizure detection accuracy in ambulatory monitoring.

  3. Sci Adv61

    MIMAS: An open-source microlens-array miniature microscope for accessible large-field cortical imaging in freely behaving mice.

    An open-source head-mounted fluorescence microscope using a 4 × 5 microlens array as its sole imaging element achieves cellular-resolution imaging over an approximately 4 × 4.5 mm2 field of view at 2.31 g. In freely behaving mice, it captured calcium signals from thousands of layer 2/3 neurons across multiple dorsal cortical regions, plus wide-field vascular imaging with vessel caliber-dependent hemodynamic responses to isoflurane. It offers labs a low-complexity route to large-scale cortical imaging.

    Why it matters: Open-source single-array optics put cellular-resolution wide-field cortical imaging within reach of ordinary labs.

  4. biopharmadive.com47

    Parkinson’s cell therapy developer files to go public

    Aspen Neuroscience, founded in 2018, has filed registration documents to list on the Nasdaq under ticker "ASPE" and would be the first Parkinson's-focused cell therapy developer to go public in the U.S. Its lead therapy sasineprocel, or ANPD001, reprograms a patient's own cells into dopamine-producing neurons and is entering late-stage testing after an early-stage trial. Aspen has raised about $347 million, posted a $62 million net loss in 2025 and nearly $37 million in the first six months of this year, and warned of substantial doubt about its ability to continue as a going concern without substantial additional capital.

  5. nature.com69

    Engrafting human cortical organoids

    Kaganovsky and colleagues, writing in Nature, describe xenocortication, a method for integrating human cortical organoids into the mouse brain. They transplanted human iPSC-derived cortical organoids into the cortical cavity of neonatal immunodeficient apallial mice, in which most of the neocortex and hippocampus had been genetically depleted. MRI showed the grafts grew approximately 4.7-fold between 2 and 3 months after transplantation and made up nearly 92% of the combined cortical tissue volume.

    Why it matters: The graft growth data show a new route to larger, better integrated human brain organoid models in rodents.

Oct 12Mon
  1. Mult Scler41

    Autologous haematopoietic stem cell transplantation affects paramagnetic rim lesions in multiple sclerosis.

    Autologous haematopoietic stem cell transplantation was associated with a reduction in paramagnetic rim lesions, a marker of chronic inflammation that disease-modifying therapies barely affect. In 30 transplanted people with multiple sclerosis, PRL count decreased in 40% of PRL-positive cases scanned before and after AHSCT and in 57% of those scanned after only, with no new PRL appearing. Annualised PRL disappearance rates were -0.36 and -0.43, suggesting an effect on central nervous system microglia/macrophages.

  2. Alzheimers Dement42

    The effects of improved access to diabetes medications on risk of Alzheimer's disease and related dementias.

    A dynamic microsimulation using 10 years of data on Americans aged 51 and older with diabetes estimates that increased utilization of GLP1s and SGLT2s by people with diabetes and HbA1c > 7 could avert 76,000-201,000 cases of Alzheimer's disease and related dementias over 10 years. Risk reduction is largest for Black and Hispanic individuals and those with HbA1c > 8, pointing to access and adherence for high-risk groups as the target with the largest benefit.

  3. doi.org50

    Vagal sensing of altered gut microbiota links to externalizing behaviors

    Sirtuin 3 (Sirt3) deficiency in mice produces externalizing, mood-related behaviors together with altered gut microbiome composition, elevated plasma choline, reduced GABA in the nucleus of the solitary tract, and changed expression of synaptic plasticity-related genes in the amygdala and BNST. Subdiaphragmatic vagotomy reversed these measures, making vagotomized Sirt3-knockout mice similar to wild-type mice. The work places the vagus nerve as the conduit linking host genetics, gut microbiota, and behavior.

    Why it matters: It identifies vagal signaling as the mechanistic link between a host gene, gut microbiota, and behavior.

Oct 11Sun
  1. Lancet40

    Migraine.

    Migraine is a chronic neurovascular disorder marked by recurrent moderate-to-severe head pain with disabling symptoms including aura, nausea, vomiting, phonophobia and photophobia. Its pathogenesis involves genetic and epigenetic factors across complex neurosensory and neurovascular networks. Decades of research have driven mechanism-based therapies that are transforming clinical practice and improving patients' lives.

    Why it matters: Reviews migraine pathogenesis and the mechanism-based therapies now changing clinical practice.

  2. biorxiv.org62

    Spatiotemporal AI modeling of gene regulation and variant effects in the developing human brain

    Seal, an interpretable AI transfer learning framework, models gene expression and variant effects with spatiotemporal resolution across 26 brain regions, 30 cell types, and seven developmental stages of the human brain. Applied to GWAS, it identifies cell types and developmental windows relevant to six neuropsychiatric conditions, and in Simons Simplex Collection autism whole genome data it uncovers a significant burden of de novo regulatory variants in transient fetal excitatory neurons.

    Why it matters: It links disease-associated variants to specific cell types and developmental windows in the developing brain.

  3. biorxiv.org61

    Cellular and molecular census of the pleiotropic disease locus Negr1 in zebrafish

    A knock-in reporter at the zebrafish Negr1 locus, combined with single-cell transcriptomics, whole-brain registration and single-neuron projection mapping, maps where this pleiotropic disease locus acts. Negr1 expression is graded across neuronal classes of brain and retina, radial glia, astrocyte-like cells and, most consistently, oligodendrocyte progenitor cells, with projection mapping suggesting three conserved hubs: olfactory bulb projection neurons, tectal periventricular projection neurons and cerebellar eurydendroid cells. The results support dose perturbation of a broadly expressed gene as the source of Negr1 pleiotropy across BMI, major depression, schizophrenia, autism-spectrum conditions and anorexia.

    Why it matters: It gives a cell-type atlas for a locus tied to BMI, depression, schizophrenia, autism and anorexia, informing which cells each trait may arise from.

  4. medicalxpress.com63

    Physical activity weakens link between genetic risk and depression severity, long-term data suggest

    Researchers at the University of Texas at San Antonio analyzed data from 23,517 adults in the NIH All of Us Research Program, combining depression polygenic risk scores, electronic health records and long-term Fitbit measurements averaging about 1.6 years per participant. Published in Nature Mental Health, the study found greater physical activity was associated with lower depression severity, with a stronger association among those with higher genetic vulnerability. The team aims to use such findings to develop personalized exercise recommendations for depression prevention and management.

    Why it matters: Long-term wearable data show physical activity buffers genetic risk of depression severity, informing precision-medicine approaches.

Oct 10Sat
  1. Sci Adv77

    Insights into temporal and spatial dynamics of short association fiber formation in the human fetal brain.

    In utero diffusion MRI and histology reconstruct short association fiber development in 243 fetuses, showing SAFs emerge before sulcal folding as flat, loosely arranged pathways along the subplate-white matter interface and later reorganize into U-shaped bundles. Maturation follows a sensorimotor-to-association gradient with nonlinear, bundle-specific trajectories, subplate changes preceding axonal coherence gains and early myelination. The work maps how the brain's local wiring forms prenatally and the origins of individual variability.

    Why it matters: It supplies the first in utero timeline of short association fiber formation across 243 fetuses.

Oct 9Fri
  1. biorxiv.org50

    Fine-tuning genomic models on rare splicing events identifies a novel biomarker of TDP-43 pathology

    Fine-tuned OpenSpliceAI, a specialized splice site prediction model, outperformed a splicing head on AlphaGenome's frozen backbone for detecting TDP-43 cryptic exons, though fine-tuning all AlphaGenome weights enabled generalization to held-out data. Genome-wide application of fine-tuned OpenSpliceAI identified new cryptic splicing events in CLDN11 and ARHGAP23, validated in FTLD-TDP brain tissue. The CLDN11 cryptic exon is predicted to generate a neoepitope that could serve as an oligodendrocyte-specific biomarker of TDP-43 pathology.

  2. Nature75

    A split attractor design for rapidly writing a navigational goal.

    Disinhibition acts as a gate that rapidly writes a heading measurement into a recurrent memory circuit in the fly navigation centre. Whole-cell recordings and modelling show that h∆K and PFG neurons form a ring attractor whose persistent bump activity depends on recurrent excitation, with inhibition decoupling h∆K from PFG during turns and rest. Inhibitory input onto h∆K rises during turns and is suppressed during odour and goal-directed runs, matching the model.

    Why it matters: It identifies a synaptic mechanism for rapid switching of attractor-based working memory circuits.

  3. Sci Adv54

    Rod photoreceptors have a dual dependency on both aerobic glycolysis and OXPHOS and diverge metabolically from other retinal neurons.

    Rod photoreceptors drive aerobic glycolysis in the retina and need both glycolysis and oxidative phosphorylation to maintain ATP, while inner retinal neurons (RBPMS-positive ganglion and calretinin-positive amacrine cells) rely on oxidative phosphorylation. Two-photon fluorescence lifetime imaging of biosensors with pharmacological protocols also showed rods can metabolize lactate, and a retinitis pigmentosa mutation increased lactate production in rods with otherwise subtle metabolic changes.

  4. medicalxpress.com51

    Common herbal sleep aid shows signs of addictive potential

    University of Connecticut researchers led by Steven Kinsey and Olivia Vanegas found that cannabinol (CBN), a cannabis-derived ingredient in over-the-counter sleep products, produced tolerance and withdrawal signs in mice given the compound twice daily for three days. Mice trained to recognize THC's effects responded identically to CBN, and CBN also weakened immune defense during a simulated bacterial challenge at non-psychoactive anti-inflammatory doses. The study appears in the November 2026 issue of Drug and Alcohol Dependence, and the authors say human research on dosing and long-term effects is still needed.

  5. JAMA74

    Nicotinamide Riboside for Patients With Early-Stage Parkinson Disease: The NOPARK Randomized Clinical Trial.

    Nicotinamide riboside, 500 mg twice daily for 52 weeks, did not improve clinical outcomes in early Parkinson disease and was worse than placebo. In the phase 3 NOPARK trial of 393 patients, the MDS-UPDRS parts I-III score worsened by 2.72 points with nicotinamide riboside relative to placebo (P = .02), and nonmotor symptom burden worsened more on treatment (NMSS difference 4.22 points, P = .009). The findings do not support nicotinamide riboside as a disease-modifying treatment.

    Why it matters: Phase 3 trial shows a proposed disease-modifying therapy for Parkinson disease was ineffective and worse than placebo.

Oct 8Thu
  1. nature.com53

    Editorial Expression of Concern: Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring

    Nature has issued an Editorial Expression of Concern on the 2017 paper by Sangdoo Kim, Hyunju Kim and colleagues, "Maternal gut bacteria promote neurodevelopmental abnormalities in mouse offspring," first published online on 13 September 2017. The notice is signed by the journal's editors, with correspondence directed to Gloria B. Choi of MIT or Jun R. Huh, now at Harvard Medical School and Brigham and Women's Hospital.

  2. biorxiv.org45

    Sex-dependent DNA methylation in amyotrophic lateral sclerosis

    A blood-based epigenome-wide association meta-analysis of 8,946 individuals (5,129 males, 3,817 females) from Project MinE and an Australian cohort identified seven sex-dependent ALS-associated differentially methylated positions at P < 9 × 10-8, mapping to KCNQ1, ADPRH, HLA-F, GHRLOS, IRF5, RAD51B and one intergenic region. Sex-stratified case-control analyses alone found no genome-wide significant sex differences; the interaction model did, with the strongest signal at KCNQ1 (P = 3.1 × 10-9). Six of the seven positions survived a four-stratum sensitivity analysis and none appeared in previous conventional ALS methylation analyses, pointing to a distinct sex-conditional component of the ALS blood methylome.

  3. doi.org60

    Intrinsic circadian organization of the spinal cord and dorsal root ganglia

    The spinal dorsal horn and dorsal root ganglia (DRGs) harbor tissue-autonomous circadian clocks, shown by sustained PER2 oscillations in real-time bioluminescence imaging. RNA sequencing across a 52-hour time course identified 626 rhythmic genes in DRGs (3.6% of expressed genes), arranged in discrete phase clusters enriched for transport, neuronal structure, and proteostasis. The work establishes peripheral sensory tissues as intrinsively circadian and maps their temporal molecular organization.

  4. nature.com40

    Nobel prizes 2026: brain switches, ‘ghost’ particle hunter, and ‘the chemistry of life’

    The 2026 Nobel Prizes in science honoured work on a brain 'switch' that controls neurons with light in medicine, the detection of cosmic neutrinos in physics, and the emergence of 'handed' organic molecules in chemistry. The medicine award was described as overdue. Nature's podcast of 7 October 2026 also covered research on the ancient human gut microbiome tracing early human journeys.

Oct 7Wed
  1. nature.com68

    A split attractor design for rapidly writing a navigational goal

    A recurrent h∆K–PFG neural circuit produces persistent heading memories using slow excitation, fast inhibition and a disinhibitory gate. Disinhibition acts as the switch that controls functional coupling of the network, allowing rapid transitions between measurement and memory states. The work identifies a circuit mechanism for writing a navigational goal quickly.

    Why it matters: It explains a neural circuit mechanism for rapidly storing a navigational goal.

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