Faculty Bibliography

Extensive neuroimaging research in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) has identified brain atrophy as a disease phenotype. While it is also related to a complex genetic architecture, the transition from genetic risk factors to brain vulnerabilities remains unclear. Using a population-based approach, we examined the associations between epilepsy-related polygenic risk for HS (PRS-HS) and brain structure in healthy developing children, assessed their relation to brain network architecture, and evaluated its correspondence with case-control findings in TLE-HS diagnosed patients relative to healthy individuals We used genome-wide genotyping and structural T1-weighted magnetic resonance imaging (MRI) of 3,826 neurotypical children from the Adolescent Brain Cognitive Development (ABCD) study. Surface-based linear models related PRS-HS to cortical thickness measures, and subsequently contextualized findings with structural and functional network architecture based on epicentre mapping approaches. Imaging-genetic associations were then correlated to atrophy and disease epicentres in 785 patients with TLE-HS relative to 1,512 healthy controls aggregated across multiple sites. Higher PRS-HS was associated with decreases in cortical thickness across temporo-parietal as well as fronto-central regions of neurotypical children. These imaging-genetic effects were anchored to the connectivity profiles of distinct functional and structural epicentres. Compared with disease-related alterations from a separate epilepsy cohort, regional and network correlates of PRS-HS strongly mirrored cortical atrophy and disease epicentres observed in patients with TLE-HS, and highly replicable across different studies. Findings were consistent when using statistical models controlling for spatial autocorrelations and robust to variations in analytic methods. Capitalizing on recent imaging-genetic initiatives, our study provides novel insights into the genetic underpinnings of structural alterations in TLE-HS, revealing common morphological and network pathways between genetic vulnerability and disease mechanisms. These signatures offer a foundation for early risk stratification and personalized interventions targeting genetic profiles in epilepsy.

The Global Navigation Satellite System (GNSS) is commonly used for outdoor positioning. However, its effectiveness diminishes in urban canyons and indoor environments attributed to signal blockage. This study aims to explore the potential of GNSS signals penetrating indoor spaces through windows and to enhance indoor positioning with Three-Dimensional Mapping-Aided (3DMA) GNSS, a concept generally applied outdoors. The research employs a 3D model of a corridor with manually labeled window locations to predict satellite visibility within indoor areas. The study integrates Pedestrian Dead Reckoning (PDR) with an indoor Shadow-matching (I-SM) technique, utilizing an Extended Kalman Filter (EKF) to improve positioning accuracy. One of the findings indicates that the proposed method significantly enhances positioning performance and its availability, achieving a root mean square error (RMSE) that is 2 m better than using PDR alone or single epoch I-SM. The study concludes that integrating GNSS with I-SM technique and PDR can optimize an indoor positioning solution and highlights the potential for improved navigation solutions in complex urban environments.

BACKGROUND:Individuals with sensory processing disorders (SPDs) face challenges in wayfinding due to heightened sensitivity to environmental stimuli like noise and lighting. Although sensory maps have aided SPD individuals by aligning navigational routes with sensory needs, standardized protocols for creating these maps are lacking, with current methods largely qualitative. OBJECTIVE:This study aimed to establish a standardized, quantitative protocol for sensory map creation, evaluating sound, brightness, and crowding density in a healthcare setting to enhance map precision and support future automation. METHODS:Sensory data were collected from the 1st and 17th floors of a large urban ambulatory care center in New York City. A qualitative spatial audit was initially conducted, followed by quantitative measurements of sound (decibels), brightness (lux), and crowding density at designated nodes. Using Python, we developed Voronoi diagrams to visualize intensity distributions across floorplans, applying statistical methods to ensure data accuracy and consistency. RESULTS:Qualitative assessments identified high-stimulus areas, particularly in the main lobby and elevator zones, which aligned closely with quantitative findings. Brightness peaked in central, naturally lit areas, while noise levels were highest near heating, ventilation, and air conditioning (HVAC) systems and entry points. The quantitative method enabled a more nuanced representation, enhancing map detail and reliability. CONCLUSIONS:The developed quantitative protocol offers a robust framework for sensory mapping, improving accessibility for individuals with SPDs in complex spaces. This approach holds potential for automation, addressing current reproducibility limitations and advancing inclusive design in public and healthcare settings.

The ability to quickly learn and generalize is one of the brain's most impressive feats and recreating it remains a major challenge for modern artificial intelligence research. One of the most mysterious one-shot learning abilities displayed by humans is one-shot perceptual learning, whereby a single viewing experience drastically alters visual perception in a long-lasting manner. Where in the brain one-shot perceptual learning occurs and what mechanisms support it remain enigmatic. Combining psychophysics, 7 T fMRI, and intracranial recordings, we identify the high-level visual cortex as the most likely neural substrate wherein neural plasticity supports one-shot perceptual learning. We further develop a deep neural network model incorporating top-down feedback into a vision transformer, which recapitulates and predicts human behavior. The prior knowledge learnt by this model is highly similar to the neural code in the human high-level visual cortex. These results reveal the neurocomputational mechanisms underlying one-shot perceptual learning in humans.

OBJECTIVES/UNASSIGNED:To investigate the relationship between short and long sleep duration and subjective cognitive decline (SCD) in a diverse cohort of cognitively normal mid- to older-age adults. METHODS/UNASSIGNED:We conducted a cross-sectional analysis of the 2022 Behavioral Risk Factor Surveillance System (BRFSS) data, including 63,948 adults aged 40-70. SCD was assessed using BRFSS survey queries. Multivariable logistic regression models examined the association between sleep duration ( < 7, 7, ≥8 hours) and SCD, adjusting for age, sex, race/ethnicity, education, and history of depression. RESULTS/UNASSIGNED:Both short and long sleep durations were associated with higher odds of SCD. The association between short sleep and SCD was strongest among individuals in their 40s at the start of midlife. Findings were consistent across all ages for non-Hispanic Whites (NHW) and for Hispanics/Latinos in their 50s and 70s. Black/African American (B/AA) adults exhibited a stronger relationship between both short and long sleep duration and SCD as they aged from midlife into their 80s, compared to NHWs. CONCLUSIONS/UNASSIGNED:Short sleep duration is more strongly associated with subjective cognitive decline in midlife, particularly among B/AA adults. Addressing sleep disparities may help mitigate the risk of SCD.

INTRODUCTION/BACKGROUND:There has been a surge in attention to ethical controversies associated with organ donation in the USA. The Neurocritical Care Society (NCS) Ethics Committee sought to understand member experiences and attitudes related to organ donation in the USA. METHODS:We designed a survey of members who practice in the USA and have interacted with an organ procurement organization (OPO)/potential donor. The survey was disseminated by NCS from 1 June 2025 to 1 September 2025. Free-text responses were reviewed to identify themes. RESULTS:Of 2204 NCS members in the USA, there were 71 respondents who completed the survey and 37 respondents who provided free-text comments. Experiences and attitudes varied, but 59% of respondents indicated that they generally think that communication between the OPO and patient surrogates about donation after brain death/death by neurologic criteria seems appropriate, and 34% indicated that they generally think that communication between the OPO and patient surrogates regarding donation after cardiac death/death by circulatory-respiratory criteria (DCD) seems appropriate. Themes included (1) the need to improve education for the treatment team about organ donation; (2) blurred boundaries between patient care and care directed toward organ donation; (3) misalignment between OPOs and treatment team priorities; (4) loss of trust between patient surrogates and the treatment team based on interactions with OPOs; (5) suboptimal timing of communication between OPOs and patient surrogates; (6) concerns regarding a potential lack of transparency, empathy, and cultural sensitivity in communication between OPOs and patient surrogates; (7) opportunities for improvement in preoperative care before donation and palliation after extubation for DCD; and (8) changes in willingness to donate organs based on interactions with OPOs. CONCLUSIONS:Although the results from this survey reflect the experience and attitudes of a small percentage of NCS members in the USA, they indicate that there are opportunities for improvement in organ donation processes. Survey results will guide the NCS Ethics Committee in supporting members navigating ethical controversies related to organ donation.

Neurodegeneration, along with amyloid and tau, define the AT(N) framework of Alzheimer's disease that has shaped the development of diagnostics and therapeutics. Yet, biomarker development for neurodegeneration has lagged behind that for amyloid and tau, with limited definition of its heterogeneous microstructural aspects that may each serve as critical measures. In this issue of the JCI, Gong et al. leveraged diffusion MRI to derive a unique measure of axonal injury or axonal density index (ADI). Through cross-sectional and longitudinal analyses, they demonstrated that the ADI has superior performance in detecting, tracking, and predicting clinical impairment compared with prior diffusion MRI methods to evaluate axonal health and standard biomarkers of amyloid and tau. As such, the ADI measure may serve as an important expansion of the neurodegeneration biomarker repertoire.

OBJECTIVE:NF2-related schwannomatosis (NF2-SWN) is an autosomal dominant genetic disorder characterized by the development of schwannomas, meningiomas, and spinal ependymomas. Treatment with bevacizumab, a monoclonal antibody against VEGF, has been shown to result in decreased vestibular schwannoma size and hearing improvement in ~50% of NF2-SWN patients. It is unknown whether the same degree of benefit is seen in younger patients compared with older patients. The objective of this study is to determine the association between age and bevacizumab treatment outcomes in NF2-SWN. STUDY DESIGN/METHODS:Retrospective cohort study. SETTING/METHODS:Tertiary referral center. PATIENTS/METHODS:Thirty-seven patients with NF2-SWN. INTERVENTIONS/METHODS:Bevacizumab. MAIN OUTCOME MEASURES/METHODS:Change in tumor size of 20% or more. RESULTS:This study includes 37 patients with NF2-SWN who were treated with bevacizumab at our institution between 2014 and 2024. They were divided into 2 groups: 22 adults over the age of 25 (26 to 71 y) and 15 adolescent and young adult (AYA) patients under the age of 25 (12 to 24 y). The median treatment duration was 2.1 years. A significantly higher proportion of AYA schwannomas (37.5%, n=9) exhibited radiographic tumor progression during the treatment period compared with those of the older patient group (11.9%, n=5) (P=0.026), despite similar pre-treatment growth rates. There was no significant difference in the proportion of older and younger patients with hearing decline, improvement, or stability (P>0.05). CONCLUSIONS:AYA patients were significantly more likely to exhibit progression of tumor growth during bevacizumab treatment compared with older patients, though no significant differences were detected in hearing outcomes.