Biology subjects

Karat, B. G.

Publications and source records attributed to Karat, B. G..

4 recordsLinked to original sources

bioRxiv2026

A surface-intrinsic framework for topology-preserving hippocampal alignment and precision morphometry

Accurate alignment of hippocampal anatomy across individuals remains challenging due to complex and highly variable folding patterns that are not well captured by conventional volumetric approaches. HippUnfold introduced a surface-based representation of the hippocampus, but key components--including coordinate estimation and inter-subject correspondence--were defined in the volumetric domain, making them susceptible to topological errors and interpolation artifacts. Here, we introduce a surface-intrinsic formulation of hippocampal unfolding in which geometry, intrinsic coordinates, and correspondence are defined directly on subject-specific surface manifolds. Intrinsic anterior-posterior and proximal-distal coordinates are computed by solving Laplace equations on the surface, and correspondence is established through surface-based resampling in unfolded space, replacing inverse volumetric warping. Relative to the original HippUnfold approach, this formulation improves test-retest consistency, subject identifiability, and mesh quality, while better preserving subject-specific gyral and sulcal morphology. Surface representations show reduced distortion between folded and unfolded spaces and eliminate misplaced or outlier vertices associated with volumetric warping. These improvements translate to enhanced sensitivity in a clinical application, improving lateralization of temporal lobe epilepsy. These results demonstrate that a surface-intrinsic formulation provides a principled and robust foundation for hippocampal unfolding, enabling topology-preserving alignment and more accurate characterization of inter-individual variability in health and disease.

neuroscience↗

bioRxiv2025

Hippocampal grey matter changes across scales in Alzheimer's Disease

Alzheimers disease (AD) is a progressive and debilitating neurodegenerative disease of the central nervous system, characterized by deterioration in cognitive function including extensive memory impairment. The hippocampus, a medial temporal lobe region, is a key orchestrator in the encoding and retrieval of memory and is believed to be one of the first regions to deteriorate in AD. In this work we examined hippocampal macrostructure (specifically gyrification and thickness) and microstructure in Alzheimers disease (AD) and mild cognitive impairment (MCI) relative to healthy aged controls in the Alzheimers Disease Neuroimaging Initiative (ADNI) dataset. We first utilized an iterative training paradigm to adapt an existing deep learning approach for capturing hippocampal topology to elderly individuals as well as individuals with potential hippocampal degeneration. Using this new model, we found notable decreases in both thickness and gyrification in AD and MCI across both the subfields and anterior-posterior axis. Using the diffusion tensor representation derived from diffusion MRI data, we found significant increases in the mean diffusivity across the extent of the hippocampus in AD and MCI, which may be related to a number of changes such as loss of neuronal cells, decreased fiber density, demyelination, and increased presence of CSF. Examining the primary direction of diffusion relative to canonical hippocampal axes, we found distinct diffusion orientation shifts in AD and MCI throughout the anterior-posterior extent of the subiculum and CA1. Specifically, we found a decrease in diffusion oriented tangentially, and an increase in diffusion oriented along the long-axis. This could potentially be related to the known degeneration of the perforant path, which is greatly affected in AD and is a largely tangential oriented pathway. The AD-related changes in diffusion orientations were found to not have significant spatial overlap with AD-related changes in mean diffusivity, suggesting that they may be capturing distinct spatially-localized disease processes. Finally, we showed that the macro- and microstructure of the hippocampus in AD changed less across age relative to MCI and controls. As well, the age-related hippocampal macrostructure changes in MCI appeared indistinguishable from healthy aging.

neuroscience↗

bioRxiv2024

The developing hippocampus: Microstructural evolution through childhood and adolescence

The hippocampus is a structure in the medial temporal lobe which serves multiple cognitive functions. While important, the development of the hippocampus in the formative period of childhood and adolescence has not been extensively investigated, with most contemporary research focusing on macrostructural measures of volume. Thus, there has been little research on the development of the micron-scale structures (i.e., microstructure) of the hippocampus, which engender its cognitive functions. The current study examined age-related changes of hippocampal microstructure using diffusion MRI data acquired with an ultra-strong gradient (300 mT/m) MRI scanner in a sample of children and adolescents (N=88; 8-19 years). Surface-based hippocampal modelling was combined with established microstructural approaches, such as Diffusion Tensor Imaging (DTI) and Neurite Orientation Dispersion Density Imaging (NODDI), and a more advanced gray matter diffusion model Soma And Neurite Density Imaging (SANDI). No significant changes in macrostructural measures (volume, gyrification, and thickness) were found between 8-19 years, while significant changes in microstructure measures related to neurites (from NODDI and SANDI), soma (from SANDI), and mean diffusivity (from DTI) were found. In particular, there was a significant increase across age in neurite MR signal fraction and a significant decrease in extracellular MR signal fraction and mean diffusivity across the hippocampal subfields and long-axis. A significant negative correlation between age and MR apparent soma radius was found in the subiculum and CA1 throughout the anterior and body of the hippocampus. Further surface-based analyses uncovered variability in age-related microstructural changes between the subfields and long-axis, which may reflect ostensible developmental differences along these two axes. Finally, correlation of hippocampal surfaces representing age-related changes of microstructure with maps derived from histology allowed for postulation of the potential underlying microstructure that diffusion changes across age may be capturing. Overall, distinct neurite and soma developmental profiles in the human hippocampus during late childhood and adolescence are reported for the first time.

neuroscience↗

bioRxiv2022

Investigating the in vivo Spatial Distribution of Hippocampal Microstructure and Macrostructure

The hippocampus is classically divided into mesoscopic subfields which contain varying microstructure that contribute to their unique functional roles. It has been challenging to characterize this microstructure with current MR based neuroimaging techniques. In this work, we used diffusion MRI and a novel surface-based approach in the hippocampus which revealed distinct microstructural distributions of neurite density and dispersion, T1w/T2w ratio as a proxy for myelin content, fractional anisotropy, and mean diffusivity. We used the Neurite Orientation Dispersion and Density Imaging (NODDI) model optimized for gray matter diffusivity to characterize neurite density and dispersion. We found that neurite dispersion was highest in the Cornu Ammonis (CA) 1 and subiculum subfields which likely captures the large heterogeneity of tangential and radial fibers, such as the Schaffer collaterals, perforant path, and pyramidal neurons. Neurite density and T1w/T2w were highest in the subiculum and CA3 and lowest in CA1, which may reflect known myeloarchitecture differences between these subfields. Using a simple logistic regression model, we showed that neurite density, dispersion, and T1w/T2w measures provided good separability across the subfields, suggesting that they may be sensitive to the known variability in subfield cyto- and myeloarchitecture. We report macrostructural measures of gyrification, thickness, and curvature that were in line with ex vivo descriptions of hippocampal anatomy. We employed a multivariate orthogonal projective non-negative matrix factorization (OPNNMF) approach to capture co-varying regions of macro- and microstructure across the hippocampus. The clusters were highly variable along the medial-lateral (proximal-distal) direction, likely reflecting known differences in morphology, cytoarchitectonic profiles, and connectivity. Finally, we show that by examining the main direction of diffusion relative to canonical hippocampal axes, we could identify regions with stereotyped microstructural orientations that may map onto specific fiber pathways, such as the Schaffer collaterals, perforant path, fimbria, and alveus. These results highlight the value of combining in vivo diffusion MRI with computational approaches for capturing hippocampal microstructure, which may provide useful features for understanding cognition and for diagnosis of disease states.

neuroscience↗