Allen Institute for Brain Science

Disentangling the Effects of Craniotomy and Traumatic Brain Injury in Experimental Models: A Narrative Review

Many widely used open-head models of traumatic brain injury (TBI) require craniotomy before injury, while sham-operated animals undergo surgery without impact and serve as controls. However, sham surgery itself may alter physiological, molecular, and behavioral parameters, compli...

Mechanistic versus descriptive interpretation of brain activity pattern reconstruction

The geometric eigenmodes, derived from the shape of the cortical surface, have been suggested as a better model for explaining brain function due to their high accuracy in reconstructing patterns of both spontaneous and stimulus-evoked brain activity patterns captured by function...

Exploring transcriptomic and genomic latent variable correction approaches in differential expression analysis

Abstract Background Differential expression analysis is a central tool for studying the biological processes altered in human diseases via transcriptomic signatures. However, transcriptomic datasets are systematically confounded by latent variables from two distinct sources: unme...

Plasma and cerebrospinal fluid proteomics reveal distinct patterns of senescence and neuropathology in aging rhesus macaques

Aging is the primary risk factor for neurodegenerative disease, yet the protein signatures that distinguish physiological brain aging from pathological decline remain incompletely defined in translational models. Using the targeted NULISAseq proteomic platform, we profiled cerebr...

AI-based characterization of Alzheimer’s disease phenotypes from population-scale single-cell data

The complexity of Alzheimer’s disease (AD) manifests in diverse clinical phenotypes, including cognitive impairment and neuropsychiatric symptoms. However, the etiology of these phenotypes remains elusive. To address this, the PsychAD project generated a population-level single-n...

Single-nucleus transcriptome-wide association study of human brain disorders

Abstract Common brain disorders impose a substantial health burden, but localizing their genetic risk in the brain remains challenging 1 . Although genome-wide association studies have identified numerous loci associated with neuropsychiatric and neurodegenerative disorders, many...

Personalized single-cell transcriptomics reveals molecular diversity in Alzheimer’s disease

Alzheimer’s disease (AD) is highly heterogeneous and driven by diverse molecular and cellular mechanisms. Functional genomics investigates these mechanisms from genetic variants to gene expression and regulation. We performed personalized functional genomics analysis on populatio...

Efficient differential expression analysis of large-scale single-cell transcriptomics data using Dreamlet

Abstract Advances in single-cell and -nucleus transcriptomics have enabled generation of increasingly large-scale datasets from hundreds of subjects and millions of cells. These studies promise to give unprecedented insight into the cell type specific biology of human disease. Ye...

Single-nucleus atlas of cell-type specific genetic regulation in the human brain

Abstract Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of th...

Lifespan single-cell transcriptomic atlas of the human prefrontal cortex

The human brain undergoes profound changes from early development through late adulthood, shaping cognition, behaviour and vulnerability to disease1,2. Understanding how these changes are organized within specific brain regions and cell types is essential for interpreting normal...

Single-cell atlas of transcriptomic vulnerability across brain disorders

Abstract Neurodegenerative and neuropsychiatric diseases impose a considerable societal and public health burden. However, our understanding of the molecular mechanisms underlying these highly complex conditions remains limited 1,2 . Here, to gain deeper insights into the aetiolo...

Blood proteomics of menopause map to brain aging and dementia risk

Abstract Menopause is a hallmark process in biological aging that has been implicated in later neurodegenerative risk, but the pathways underlying this connection remain unclear. Here we used blood proteomics data from several cohorts to identify biological changes associated wit...

Real-time, cross-modal genotype mapping of free-moving Drosophila larvae via simultaneous mechano-electrophysiological recording

Drosophila larvae provide a powerful model for interrogating genes associated with human muscle and neurological disorders; however, existing genotyping and phenotyping approaches remain low-throughput and often rely on destructive, invasive, or toxic procedures. Here, we present...

International variation in neuropsychological test use practices: Implications for test adaptation and fair assessment

Neuropsychological test selection varies substantially across countries and languages, yet which instruments clinicians use internationally remains poorly documented. Using a survey of International Neuropsychological Society members (INSConnect, 2023), we examined instrument end...

Blended Care in the mCIMT-BiT Pirate Group in Children with Unilateral Cerebral Palsy: A Feasibility Study

Aims Intensive upper limb rehabilitation is essential for children with unilateral cerebral palsy (uCP). Home-based training may extend practice opportunities and reduce logistical barriers. This study examined the feasibility of a blended care approach in the mCIMT-BiT Pirate gr...

Microglial PGRN downregulation contributes to phagocytosis-mediated retinal microvascular endothelial cell damage in early experimental diabetes

Diabetic retinopathy (DR), a major cause of vision loss, involves retinal microvascular dysfunction. While microglial phagocytosis of endothelial cells has been reported to contribute to diabetic retinal damage, the endogenous mechanisms driving microglial hyperphagocytosis in ea...

Factors associated with variability in recovery after mild traumatic brain injury among adults referred to outpatient concussion clinics

BACKGROUND: To understand factors associated with symptom and disability recovery trajectories among adults referred to outpatient clinics after mild traumatic brain injury. METHODS: Adults (n = 110; mean age 39 years, 36% men), were assessed at clinic intake (baseline mean 6.5 w...

Neocortical long-range inhibition promotes cortical synchrony and sleep

Abstract Sleep and wakefulness are associated with distinct cortical patterns of rhythmic activity 1 . During low-arousal states such as slow-wave sleep, synchronous low-frequency rhythms dominate activity across widespread cortical regions. Although inhibitory neurons are increa...

ERK-dependent hyperexcitability of BLA neurons projecting to dCA3 underlies social dysfunction in a male mouse model of fragile X syndrome

Background Social dysfunction is a core symptom of autism spectrum disorder (ASD), including fragile X syndrome (FXS), but its underlying neural circuits and molecular mechanisms remain poorly understood. Previous studies have implicated the amygdala and hippocampus in social beh...

Hyperactive lateral hypothalamic GABAergic neurons drive abnormal aggression in neuroligin-3 R451C knock-in mice

Aggressive behaviors represent a common and clinically challenging comorbidity in individuals with autism spectrum disorder (ASD), yet the underlying neural mechanisms remain poorly understood. This study aimed to investigate the circuit-level pathology driving elevated aggressio...