Spontaneous HRV fluctuations are linked to functional changes in resting state brain activation in younger and older adults.

Postmortem human brain tissue is an important resource for brain research. Spatial transcriptomics is a novel technology that utilizes formalin-fixed, paraffin-embedded (FFPE) or cryosections, with the former having good cytoarchitecture but poor RNA quality and vice versa for frozen tissue. Sheep brains (n=16) were used to test various protocols that simulate the conditions around the preparation and dissemination of human postmortem FFPE and frozen brain tissue to optimize for future spatial transcriptomic work. FFPE and frozen tissues were investigated for RNA quality, while hematoxylin and eosin-stained cryosections were analyzed by quantifying tissue voids as a proxy for cytoarchitectural integrity. Postmortem interval reduced the RNA integrity number equivalent (RINe) of frozen tissue from 7.2 (24 hr) to 4.8 (168 hr). In FFPE tissue, the percentage of RNA fragments greater than 200 nucleotides (DV200) values ranged from 18.9% to 69.01%, with the highest values observed in samples fixed for less than 24 hr. Pretreatment with liquid nitrogen before -80°C storage resulted in the lowest voids (11.6%) in cryosections, but cryoprotectants had little effect. These findings provide researchers with guidelines for tissue preparation in spatial transcriptomics. However, freezing protocols require further refinement to approach the cytoarchitecture of FFPE tissue.

TriPat‑XFE: a triangle pattern‑based explainable feature engineering framework for EEG classification.

Brain tumors are among the most common causes of death in humans. Early and accurate detection of brain cancers is critical for effective treatment. Imaging techniques such as computed tomography, magnetic resonance imaging, X-rays, and ultrasound are used as a preliminary reference by illness experts. Different learning strategies have been employed in the field of health to diagnose diseases early, reduce the intensity of experts, and minimize diagnostic errors. Image processing studies in brain research have begun to provide successful findings in recent years, thanks to the developed of machine learning and deep learning models. In this study, as a novelty to the studies in the literature, a hybrid algorithm is proposed that features were extracted with pre-trained based CNN, classification was made with SVM based different kernels. As a result, the brain tumors were detected with 98% classification performance.

The present study provides case-study evidence aimed at advancing both empirical knowledge and theory development on the Pipeline-as-a-Service (PaaS) technological model as an enabling perspective for research infrastructures. The case-study is the Italian Research Infrastructure for brain research “EBRAINS-Italy”, funded by the NextGenerationEU and National Recovery and Resilience Plan (NRRP) in Italy. Adopting an inductive case-study research design, the study develops a novel approach to Service Catalogue architecture tailored to complex, data-intensive research environments and clinical and ethical implications. The Service Catalogue constitutes a core governance mechanism of research infrastructures, as it offers a structured and formal representation of available services, including their scope, interfaces, and operational characteristics. Building on these insights, the paper proposes an approach to Service Catalogue Management (SCM) that leverages an existing Service-as-a-Service (SaaS) implementation and outlines its evolution toward a Pipeline-as-a-Service (PaaS) model. Within this governance framework, the Research Infrastructure Manager (RIM) emerges as a key strategy.

Understanding functional brain development in neonates represents a critical frontier in neuroscience. Due to the high plasticity of the infant brain, early detection of functional abnormalities and timely interventions are essential to improving long-term neurodevelopmental outcomes. However, progress in this field has been limited by the constraints of conventional neuroimaging modalities. The emergence of functional near-infrared spectroscopy (fNIRS) has opened new avenues for neonatal brain research. This narrative review provides a comprehensive synthesis of recent advancements in fNIRS for neonatal brain monitoring. We aim to delineate the technical principles of fNIRS, critically evaluate its applications in developmental assessment and clinical care, and discuss its future translational potential. By consolidating this evidence, this review clarifies the unique value of fNIRS, addresses the need for a consolidated framework in this rapidly evolving field, and identifies key challenges to guide future research. As a non-invasive, portable, and motion-resilient optical imaging technique, fNIRS is particularly well-suited for bedside assessment and naturalistic observation of brain function. Relying on the principle of neurovascular coupling, fNIRS measures changes in cerebral oxygenation to detect neural activity, thereby providing novel insights into cognitive development, pathological processes, and therapeutic responses in neonates. With continuous advancements in technology and methodology, fNIRS applications in neonatology have expanded markedly, facilitating significant progress in areas such as sensory processing and clinical evaluation of brain injuries. This review provides a comprehensive analysis of recent developments in fNIRS for neonatal brain monitoring. It outlines the technique's foundational principles, technical characteristics, advantages and limitations, and explores its applications in developmental assessment, clinical surveillance, and disease diagnostics, while offering perspectives on its clinical utility and future directions.

BackgroundPlasma brain‐derived Tau (BD‐Tau) has been identified as a superior biomarker of Alzheimers Disease (AD)‐related neurodegeneration compared to plasma total tau, as it exclusively reflects central nervous system (CNS)‐derived Tau. BD‐Tau also shows potential in predicting clinical outcome following acute ischemic stroke and traumatic brain injury, as well as in Creutzfeldt‐Jakob disease prognosis. We developed and qualified a Lumipulse G assay for the quantification of BD‐Tau in plasma, serum, and cerebrospinal fluid (CSF).MethodThe assay was developed utilizing an ADx BD‐Tau monoclonal antibody (mAb) (code#RD‐129) in conjunction with an alkaline phosphatase‐conjugated Fab fragment derived from an ADx N‐terminal Tau recombinant mAb (code#RD‐073). Analytical performance parameters, including measuring range, intra‐ and inter‐assay precision, lower limit of quantification (LLOQ), parallelism, and lot‐to‐lot consistency, were evaluated. The assay performance was benchmarked against a commercial BD‐Tau SIMOA test (Quanterix, Cat N° 104797) using EDTA plasma from 30 AD patients (AD CSF biomarker profile characterized) from the Amsterdam Dementia Cohort and 30 healthy controls from the Dutch Brain Research Registry (Hersenonderzoek.nl).ResultThe assay demonstrated robust quantification of BD‐Tau in CSF, plasma, and serum with measured concentrations ranging from 3 to 20 pg/mL across 15 paired plasma and serum samples. Serum levels were ∼10% lower than plasma concentrations but showing strong correlation (Spearman r = 0.74; p = 0.002). Median intra‐ and inter‐assay CV% were below 10% across six independent runs with measurements done in duplicate, on calibrator, spiked buffer and plasma samples. The LLOQ was determined to be 0.78 pg/mL based on precision profile. Lot‐to‐lot variability was below 10%. Significant correlation with the BD‐Tau SIMOA assay was observed (Spearman r = 0.89; p < 0.0001), with superior discriminatory power for AD versus controls in a first exploratory assessment using the plasma samples (Xplorer assay AUC: 0.69 vs SIMOA assay AUC: 0.59).ConclusionThe BD‐Tau Xplorer kit provides accurate and reproducible quantification of BD‐Tau on an automated platform. Further validation in larger and more differentiated cohorts is warranted to evaluate its context of use and value as a potential marker for prognosis and monitoring disease progression, not only in AD but across neurological diseases.

The concept of the «soul» originates in ancient philosophy and mythology, yet retains indirect relevance in contemporary scientific discourse. Although modern science often treats it as an epiphenomenon or conceptual atavism, the soul remains foundational for key psychological constructs and is linguistically embedded in disciplines such as psychology, psychiatry, and neuropsychology. This duality reflects a broader disciplinary divergence: while philosophy continues to engage with the soul as a legitimate object of inquiry, psychology, psychiatry, and neuroscience explicitly exclude it from their conceptual frameworks. However, emerging trends in post non classical science and neo classical philosophy suggest a reconsideration of ancient insights in light of new empirical data. Advances in cognitive science and neuroscience have reignited interest in the relationship between brain processes and subjective experience. This has prompted a gradual shift away from the classical Cartesian understanding of the psyche toward novel conceptualizations grounded in: • behavioral neurobiology; • cognitive neuroscience; • integrative neurobiological approaches. These developments are increasingly engaging with pre scientific conceptions of the soul, reevaluating them through the lens of contemporary brain research. The present article traces the evolution of the soul concept across historical and disciplinary boundaries — from mythological origins and ancient philosophical systems to modern cognitive and neuroscientific paradigms. It demonstrates how contemporary neuroscience is fostering a renewed, evidence based dialogue with age old questions about the nature of subjective experience and consciousness, particularly through advances in human brain research.

BackgroundDementias Platform UK (DPUK) Data Portal is designed to facilitate access multi‐modal cohort datasets for dementias research. Data storage and analysis facilities are provided accessing >65 population and clinical cohorts (n = 3.7m), by >1,100 users in 44 countries. International cross‐platform collaborations are underway with the AD Workbench, Dementias Platform Australia (DPAU), and colleagues in South Korea (Korean Dementia Research Centre (KDRC), Korean Brain Research Institute (KBRI), Yonsei University).Central to these collaborative projects are data pre‐processing pipelines using standard modality‐specific data models, data discovery and access brokerage, governance‐flexible federation models, and access to electronic health records. All of these can represent significant barriers to global data sharing. Examples of how these issues have been addressed, with relative degrees of success, will be presented with exemplar scientific collaborative projects using standardised and federation model pipelines:Methods1. The impact of intergenerational transmission of trauma in dementia‐like neurodegeneration2. The relationship between stages of frailty and cognitive decline3. Childhood adversity and late‐life mental health and wellbeing4. Mental health trajectories during the COVID‐19 pandemicResultsProject 1: Wet‐lab and dry‐lab integrative approach we are investigating intergenerational transmission of trauma in dementia across murine and human models. Preliminary results show that a structure shared in both animal and human models is implicated, the habenula (DPUK and KBRI)Project 2: Federation model and standardised psychosocial measures (C‐Surv) assessing the associations between frailty stage and cognitive decline in ELSA UK and MAS (DPUK and DPAU)Project 3: Federation model and standardised biopsychosocial measures (C‐Surv) assessing prediction models of early adversity and later life mental health and wellbeing. Using ELSA UK and MAS datasets, preliminary models show that early adversity predicts later life poor mental health and wellbeing (DPUK and DPAU)Project 4: Using a federation model and harmonised psychosocial measures we apply a temporal trend analysis to multi‐site datasets (ELSA UK, ELSA Brazil, Brains for Dementia Research (BDR) and the AllOfUs study).ConclusionsUsing established curation, harmonisation and federation pipelines, DPUK are working with partners to collaborate on exemplar neurodegenerative disease‐focused projects which avoid data transfer.

Infrared neural stimulation (INS) represents an invasive technique for modulating brain activity in animals, particularly primates, which serve as effective models for human brain research. Noninvasive approaches, such as transcranial laser stimulation, are safer but have lower spatial and temporal resolution, primarily altering metabolic processes rather than directly stimulating specific neurons. Invasive techniques provide better resolution by targeting neurons with focused laser beams but require intricate surgeries that damage the meninges, limiting studies to short-term experiments conducted mostly on anesthetized animals. We present a minimally invasive approach for long-term, high-resolution laser INS that does not disrupt brain tissue integrity and minimizes the risk of inflammation. Laser radiation is delivered through contact between a flexible optical fiber and the outer surface of the dura mater, allowing for chronic experiments on non-anesthetized primates who maintain their cognitive functions and physical activities. This method has enabled us to conduct a multi-day INS experiment and collect statistically reliable data on neurophysiological responses in a cognitively intact primate subjected to targeted high-resolution INS. We analyzed electrocorticogram and evoked potentials in various cortical areas while applying infrared laser stimulation directed at a selected point on the primary visual cortex of a rhesus macaque. Results indicated that even low-intensity laser stimulation (below conscious perception thresholds) caused synchronous biopotential changes not only at the stimulation site but also in certain distant cortical regions, suggesting a more complex brain response mechanism to INS than merely the activation of stimulated neurons. We believe the presented method will significantly facilitate chronic INS studies, further contributing to fundamental and clinical outcomes.

Brain health in youth - what are we measuring? - A comprehensive review.

Understanding the brain’s intrinsic mechanisms that drive the emergence of consciousness from anesthesia remains a substantial and unresolved challenge in brain research. Here, we show in mice that, when the brain is forced into a minimal responsive state by an anesthetic, a rapid activation of EphB1 receptor occurs in the ventral posteromedial nucleus (VPM) of the thalamus and contributes to promote the emergence of consciousness by activating the VPM glutamatergic neuron (VPMGlu) → primary somatosensory cortex glutamatergic neuron pathway. The ephrinB-EphB1 receptor signaling excites VPMGlu neurons through phosphorylation of NR2B, a subunit of N-methyl-D-aspartate receptors (NMDARs), at tyrosine-1472 (Y1472) and disinhibits VPMGlu neurons through ubiquitin degradation of potassium-chloride co-transporter 2 (KCC2). The EphB1/NR2B Y1472 phosphorylation and EphB1/KCC2 ubiquitin degradation are two independent mechanisms in the process of emergence from anesthesia and occur independent of the molecular targets of anesthesia. The present study provides insights into understanding the molecular and neural circuit basis that allows the brain to emerge from anesthesia and regain consciousness.

As most persons spend most of their time indoors (>80% on most days), indoor air quality is potentially an important health concern, particularly in elderly populations at high risk for dementia. It is important to note that until recently, little attention has been given to indoor air quality and related standards; most regulatory thresholds remain limited to outdoor environments. Recognizing that the environments in which we live and work shape health, it is time to place indoor air quality at the center of brain health policy and research agendas, and to take intentional steps towards comprehensive in-home assessment.

MicroRNAs (miRNA) are small non-coding RNAs that are key negative regulators of gene expression. Their roles include shaping the gene expression landscape during and after brain development by defining and maintaining levels of proteins that generate the distinct morphological and functional properties of neurons and other brain cell types. HT22, N2A, and SH-SY5Y are common immortalized neuronal cell lines that offer simple, less expensive, and time-saving options for in vitro modelling to evaluate miRNA functions. The extent to which these lines reflect primary neurons remains, however, unclear. Here, we benchmarked the miRNA profiles of cultured mouse hippocampal neurons against Argonaute-loaded miRNAs in the adult mouse hippocampus and miRNA data from the hippocampus of control human donors. We then compared the miRNA expression landscape in HT22, N2A and SH-SY5Y against mouse hippocampal primary cell cultures. We profiled over 700 miRNAs across the lines and detected 310 miRNAs in all four cell types. This included detection of neuron-enriched miRNAs such as miR-124 and miR-128, although the cell lines typically displayed lower levels of these than in primary neurons and reference adult hippocampal tissue. The miRNA profile in the HT22 cell line showed the highest correlation to the mouse primary neuronal cultures. Together, this study provides a dataset on basal miRNA expression across commonly used cell lines for neuroscience research and evidence for both conserved and distinct profiles that should be used to inform decisions on cell lines for modelling brain and miRNA research.

Adversity and trauma are postulated to account for the rise of multiple psychiatric disorders long after the events have taken place. This is thought to be due to the permanent changes that occur in the nervous system due to oxidative stress arising from the event. A proposed mechanism this occurs is through trauma born epigenetic imprints and defects on the Hypothalamic-Pituitary-Adrenal Axis which in turn affect the lateral habenula structure. These changes and resultant effects produce an environment which increases the risk for a population to gain dementia. We hypothesise that due to the epigenetic nature of generational trauma transmission, the greater associated risk of acquiring dementia would be passed down to future generations. We would use murine models to experimentally look at how trauma infliction affects the neuroanatomy of prenatal mice and explore how biologically and socially their offspring behaves because of their parents' history (with our collaborators at the Korean Brain Research Institute). This would be through analysis of lateral habenula structure and methylation assay analysis compared to control murine samples. We would compare the finding with the human longitudinal cohorts who have suffered from events of extreme adversity and see how dementia frequency and outcomes are exacerbated compared to normal populations (which would be completed by creation of a composite score from available risk-related variables). Analysis of these datasets would help to corroborate the link between trauma and its ability to disrupt the normal development of the nervous system. It would also help establish whether those descending from parents who faced extreme adversity are more at risk to develop dementia causing conditions. The associations between the murine and human models would be realised by translating findings through common variables. The overarching outcome would be to investigate through what means and the extent to which generations that hail from backgrounds of trauma and adversity are more likely to develop dementia. This work will provide a rich source of information in generational studies of dementia and also make people affected by these conditions to be more proactive with reducing other dementia risk factors.

BackgroundDiabetes is a known risk factor for dementia. However, the effect of diabetes on cognitive functioning and brain morphology among non‐demented individuals, particularly in the rural Indian population is less explored. This study aims to examine the association between diabetes, cognitive performance and MRI brain structure among community dwelling middle‐aged and older adults from rural India.MethodThis cross‐sectional study utilized baseline clinical, biochemical, and cognitive data of participants aged ≥45 years (n = 3,983, mean age=58 years) without dementia from the Centre for Brain Research ‐ Srinivaspura Aging, NeuroSenescence, and COGnition (CBR‐SANSCOG) study cohort, an ongoing prospective cohort study in rural southern India. Diabetes was diagnosed based on clinical history and/or HbA1c ≥6.5%. Cognitive performance was assessed across multiple domains using the culturally adapted COGNITO (Computerized assessment of adult information processing) battery. A subset of these participants (n = 1,336) underwent 3T brain MRI (Siemmens Magnetom Prisma scanner), and voxel‐based morphometry (VBM) analysis was performed on the T1‐weighted images. Multivariate linear regression analyses were conducted separately for cognitive and neuroimaging outcomes, adjusting for age, sex, education, body mass index (BMI), tobacco use, alcohol use, hypertension, and depression.ResultIndividuals with diabetes exhibited significantly poorer cognitive performance in the attention domain, particularly in the visual attention and mean reaction time tasks (p < 0.05) compared to individuals without diabetes. Additionally, higher HbA1c levels in these individuals were associated with poorer attentional task performance. The VBM analysis revealed significantly reduced grey matter volumes in several regions among individuals with diabetes, including the bilateral cerebellum and right putamen (p < 0.05, FWE‐cluster corrected).ConclusionThis study demonstrates that diabetes is associated with both cognitive impairments in the attention domain alongside grey matter loss in the bilateral cerebellum and right putamen even before the onset of dementia, highlighting the potential adverse impact of diabetes on brain health in rural Indians. Further, worsening glycaemic control among individuals with diabetes was associated with poorer attention. Therefore, early diagnosis and prompt interventions for diabetes could be a scalable and cost‐effective strategy to reduce dementia risk in this population.

Traditional EEG preprocessing approaches generally reconstruct signals in contaminated channels using interpolation by averaging the signals in neighboring channels. This further reduces the spatial resolution of the EEG signals and raises challenges in localized brain activity analysis, especially in task-EEG. To overcome this limitation, we propose a power-sensitive channel rejection (PSCR) approach allowing EEG signals to be processed without sacrificing regional specificity. Our research focused on task-based EEG (64-channel) acquired at Wayne State University (WSU), where participants with subjective cognitive complaints were asked to perform a motion direction discrimination task. The current dataset includes 82 consensus-diagnosed, community-dwelling African Americans (ages 60-90 years, 50 normal cognition (NC) and 32 mild cognitive impairment (MCI)) recruited through WSU and Michigan Alzheimer's Disease Research Center. Each task trial is divided into the following time periods: Stimulus Onset, Go-indication to Motion-Stop, NoGo-indication to Motion-Stop, Button-Press period. Artifacts in EEG signals often appear as segments with abnormal and abrupt changes in amplitude in individual channels. This will be reflected as segments with exceptionally high-power levels in the current source density (CSD). To reduce the noise effect, signals from adjacent channels are often averaged to formulate a region-of-interest (ROI). For each task period, to preserve regional specificity in localized brain activity analysis, we propose a power sensitive channel rejection approach, where a threshold is set based on statistical analysis (with 95% of confidence) and all the channels with CSD power level exceeding the threshold are excluded when calculating the ROI signal. We compared event-related regional-level CSD before and after power-based channel rejection. It was observed that when the proposed PSCR approach is applied, the differences in localized ROI neural activity between NC and MCI become more distinct. For instance, during the NoGo period, MCI exhibited noticeably higher neural activity in the medial-central region, possibly compensating for weakened activity in other regions. The proposed PSCR approach minimizes the interference between the ROIs and helps distinguish the differences in neural activity between NC and MCI. Potentially, this approach may benefit a wide spectrum of EEG-based brain research. NSF-2032709/Li; NIH-1R21AG046637-01A1/Kavcic and NIH-1R01AG054484-01A1/Kavcic; NIH-P30AG072931/Paulson; NIH-P30AG024824/Yung.

Zebrafish (Danio rerio) have emerged as a pivotal model organism in translational neuroscience, neuropharmacology and CNS disorder research, leveraging their striking anatomical and physiological parallels to humans. With a brain architecture and functional pathways that are closely similar to those of humans, zebrafish enable critical insights into brain development, neuro-circuitry and disease mechanisms. Notably, zebrafish have a number of benefits over more conventional mammalian models like mice and rats, including their rapid development, optical transparency allowing for real-time imaging and capacity to perform high-throughput genetic and pharmacological screens inexpensively. The combination of vertebrate complexity and experimental tractability that zebrafish possesses renders them uniquely placed for large-scale investigations of brain function and disease. This review synthesizes recent advancements in utilizing zebrafish to model brain disorders such as depression, anxiety, psychoses, autism spectrum disorders, cognitive impairments and drug-induced neurobehavioural alterations. By integrating findings from genetic, pharmacological and behavioural studies, we underscore zebrafish's unique advantages, including genetic tractability, cost-efficiency, high-throughput screening capacity and conserved neuroendocrine and behavioural responses. These features facilitate the exploration of complex neuropsychological processes and drug-brain interactions, bridging gaps between molecular mechanisms and behavioural outcomes. Zebrafish models have proven instrumental in unravelling the neurobiological underpinnings of human psychiatric and neurological disorders, offering a versatile platform for studying gene-environment interactions, neurodevelopmental trajectories and pharmacological interventions. Their translational relevance is further enhanced by rapid developmental cycles, optical transparency during early stages and robust behavioural assays that capture nuanced phenotypes. This review highlights the transformative role of zebrafish in accelerating drug discovery, optimizing neuropharmacological screening and advancing personalized therapeutic strategies. By consolidating evidence from diverse studies, we highlight zebrafish's capacity to address fundamental questions in neuroscience while fostering innovative approaches to diagnose, treat and prevent brain disorders, ultimately driving progress towards precision medicine in neurology and psychiatry.

BackgroundThe brain's nerve fiber network is disturbed in neurodegeneration, but resolving fiber trajectories over large fields‐of‐view to study connectivity changes remains prohibitive. Current methods study small volumes (electron microscopy), have limited resolution (diffusion MRI), or need birefringence‐preserving sample preparation and cannot resolve crossings (polarization microscopy). Here we show that computational scattered light imaging (ComSLI) resolves neuronal trajectories, including degenerating hippocampal tracts, with micron resolution in any histology section independent of sample preparation.MethodsWe studied standard‐sized 5‐10μm formalin‐fixed paraffin‐embedded (FFPE) sections prepared using various protocols (cf. text/figures) and two whole‐brain sections (Figure 1 – FFPE, from the Jülich BigBrain, 20μm, silver‐stained, and Figure 2E ‐ celloidin‐embedded and myelin‐stained in 1904, from the Institute for Brain Research, Düsseldorf, Germany).Computational scattered light imaging (ComSLI) was performed in Stanford and Jülich. The setup (Figure 1A,B) includes a micron‐resolution low angle‐of‐acceptance camera‐adapter‐lens system and a rotating LED lightsource. Images were acquired at 5‐15o rotation steps (24‐72 images/sample), with 3‐9μm pixel size. Motorized stages enable tile‐scanning. SLIX software quantified orientations, MATLAB was used for orientation analysis, and MRtrix3 for creating orientation distribution functions and subsequent tractography.ResultComSLI produced a micron‐resolution whole‐brain fiber orientation map (Figure 1C). Figures 1D‐E show zoomed‐in fiber orientations in corpus callosum/fornix and corona radiata. Microscopic resolutions enabled generating fiber orientation distributions at multiple scales (Figure 1F), leading to microstructure‐informed whole‐brain tracts (Figure 1G‐H).ComSLI works for various sample preparation protocols (Figure 2). Consecutive human hippocampal sections with different stains (iron, microglia, tau, and amyloid) show identical orientations (Figure 2B,C), quantified after co‐registration in Figure 2D. Orientations were also derived from a 120‐year‐old human section (Figure 2E‐F), and were consistent at various sample preparation steps (Figure 2G).ComSLI can study neurodegenerating tracts, such as the hippocampal perforant pathway (Figure 3). A healthy hippocampus includes strong perforant pathway connections through the subiculum and CA1 subfields (Figure 3A‐F), which almost entirely disappear in a sclerotic hippocampus (Figure 3G‐L), and are severely compromised in Alzheimer's disease (Figure 3M‐R).ConclusionComSLI is a cost‐effective method to study intricate fiber networks at micron‐resolution in any histological tissue section, and can reveal subtle changes in neurodegeneration.

BackgroundPrevious studies have reported the association of white matter hyperintensities (WMH), an indicator of cerebrovascular change, with hippocampus. And some studies have also found that hippocampal atrophy (HA) is associated with poor cognitive functions. However, the region‐specific association of WMH with HA, especially in rural Indian population, remains unclear and unexplored.MethodWe analysed baseline MRI data of participants aged 45+ years (n = 1253) from the Centre for Brain Research – Srinivaspura Aging NeuroSenescence and COGnition (CBR‐SANSCOG) study, collected between January 2018 and September 2024. We excluded subjects with dementia assessed using Clinical Dementia Rating (CDR ≥1) and gross brain pathology on MRI. Composite cognitive score was computed by averaging normalized domain‐wise scores across visuospatial, attention, memory and language from culturally adapted computerized neurocognitive test battery (COGNITO, Computerized Assessment of Adult Information Processing). HA score was computed as the ratio of the sum of hippocampal and inferior lateral ventricle volumes to hippocampal volume, which was normalized for age and sex. Higher HA score indicates higher hippocampal atrophy. WMH volume across periventricular (pWMH), subcortical (sWMH), infratentorial (iWMH), and juxtacortical (jWMH) regions were computed using deep‐learning‐based Lesion Segmentation Toolbox. Generalized linear model (GLM) was used to investigate the association between WMH and HA, and cognitive performance, adjusting for age, sex, and education.ResultIn our study (56.53±8.98 years, 35% female), we found that higher HA was associated with poorer attention (β = ‐0.33, 95% CI [‐0.07, ‐0.60], p = 0.01) and composite cognitive score (‐0.18, [‐0.01, ‐0.34], p = 0.03). Further, we found that higher pWMH (0.01, [0.01, 0.02], p <0.001), sWMH (0.07, [0.03, 0.10], p <0.001), iWMH (0.38, [0.21, 0.54], p <0.001), and jWMH (0.03, [0.02, 0.04], p <0.001) volumes were associated with higher HA.ConclusionOur study found that region‐specific contribution of WMH volume towards hippocampus atrophy differs, wherein contribution of infratentorial WMH volume was comparatively higher than other regions. This study highlights the need of detailed assessment of occurrence of WMH in the MRI and provide cerebrovascular‐risk modifying interventions to potentially slow HA and preserve cognitive function in aging Indian population.