Biology subjects

Yeh, F.-c.

Publications and source records attributed to Yeh, F.-c..

9 recordsLinked to original sources

bioRxiv2026

Cortical asymmetry and its developmental change have distinct relationships with brain connectivity

The two cerebral hemispheres specialize while remaining interconnected. Does greater structural asymmetry imply less connectivity, and does connectivity also relate to how asymmetry changes during development? We addressed these questions in three independent cohorts spanning birth to 22 years, measuring asymmetry as the magnitude of the left-right difference in association tract overlap across 74 homotopic cortical region pairs. The regional pattern of asymmetry was similar across cohorts. In all three cohorts, more asymmetric regions had lower connectional density to cortical and non-cortical targets. However, involvement of the corpus callosum, the major pathway connecting the hemispheres, showed no consistent inverse relationship with regional asymmetry across cohorts. Instead, callosal involvement conditioned the relationship between mean regional asymmetry and its age-related change. In the two older cohorts, greater mean asymmetry accompanied more positive age effects among regions with appreciable callosal overlap, whereas this relationship was weak or negative among regions with little callosal overlap (standardized interactions +0.42 and +0.56). The pattern replicated across the two cohorts at matched ages, and longitudinal region-mean estimates in the Adolescent Brain Cognitive Development cohort were similar in direction and magnitude. In the youngest cohort, regions converged toward the mean, narrowing the between-region spread by 12%, with no detected callosal moderation. More asymmetric regions have lower overall connectional density, whereas callosal involvement helps explain how regional asymmetry changes with age.

neuroscience↗

bioRxiv2026

Reproducibility of Diffusion, Shape, and Connectivity Metrics Across Scanners: Implications for Multi-Site Tractography

Multi-site diffusion MRI studies face scanner-induced variability that can obscure biological signal. Harmonization methods such as ComBat have been developed to address this, but have been evaluated primarily on diffusion scalar metrics. Whether scanner reproducibility differs across fundamentally distinct tract-derived representations has not been systematically compared. Here, we compared the reproducibility of three metric families (diffusion, shape, and connectivity) across 36 association tracts using the MASiVar dataset (5 subjects, 4 scanners, 27 sessions). We assessed intraclass correlation coefficients (ICC) and multivariate subject discrimination at baseline, under dimensionality reduction, and after ComBat harmonization. At baseline, shape metrics showed the highest reproducibility (median ICC 0.69), followed by connectivity (0.49) and diffusion (0.34). Shape and connectivity achieved comparable subject discrimination (both 1.75), significantly exceeding diffusion (1.23). ComBat harmonization improved all families but harmonized diffusion (0.58) remained below unharmonized shape (0.69), indicating that metric family selection remains consequential even after harmonization. Under low-dimensional representation, connectivity showed the largest gains (ICC 0.86, subject discrimination 3.0), exceeding other families at any dimensionality. Analysis of principal component loadings identified a small number of cortical regions per tract (median 6) that capture 95% of the reproducible connectivity signal, providing a per-tract reference for selecting the most informative regions in future multi-site studies. These findings indicate that the choice of which tract-derived metrics to analyze in multi-site studies deserves at least as much consideration as how to harmonize them.

neuroscience↗

bioRxiv2025

Cross-species brain circuitry from diffusion MRI tractography and mouse viral tracing

Understanding how brain networks support cognition requires knowing not only which regions are connected but the direction in which neuronal signals propagate. However, directed connectivity cannot be measured non-invasively in primates or humans, limiting systems-level inference. Here we integrate projection polarity from [~]1,200 mouse viral tracing experiments with species-specific diffusion MRI tractography to construct directed connectomes across mouse, marmoset, macaque, and human. Using a common cross-species atlas, we developed a path efficiency metric that balances projection strength against axonal length and applied shortest-path algorithms to quantify directional influence. This framework revealed conserved and divergent organization: the entorhinal-hippocampal projection was the most efficient in all species; humans showed strengthened anterior insula-superior temporal pathways; macaques exhibited peak inferior temporal outflows; and marmosets maintained disproportionately strong olfactory influence. These results provide a scalable and ethically feasible approach for modeling directed neuronal signaling across species.

neuroscience↗

bioRxiv2025

A common cross-species atlas of cortical gray matter

Translational neuroscience requires consistent anatomical frameworks to compare brain organization across species despite differences in size and specialization. Existing atlases are species-specific, limiting cross-species analyses. Here we developed a hierarchical common atlas delineating homologous cortical and subcortical gray matter regions across mouse, rat, marmoset, rhesus macaque, and human, built upon population-averaged minimal deformation templates and uniform tissue segmentation. The atlas was validated through cross-atlas Dice similarity against established human parcellations, cross-scale containment against species-specific atlases, cross-species geometric consistency of regional positioning, and comparison of independent mouse and marmoset invasive tracer connectivity, with a per-region homology confidence index quantifying the strength of each regional assignment. Cross-species tracer comparison revealed a structured gradient of correspondence, with sensorimotor connections showing strong conservation and association connections showing progressive divergence. This freely available atlas provides a unified coordinate system for comparative neuroscience, enabling quantitative evaluation of where cross-species correspondence holds and where species-specific divergence emerges.

neuroscience↗

bioRxiv2021

Multimodal Magnetic Resonance Histology and Light Sheet Imaging for Quantitative Neurogenetics of the Mouse

Paul Lauterbur closed his seminal paper on MRI with the statement that "zeugmatographic (imaging) techniques should find many useful applications in studies of the internal structures, states and composition of microscopic objects" [1]. Magnetic resonance microscopy was subsequently demonstrated in 1986 by three groups [2] [3] [4]. The application of MRI to the study of tissue structure, i.e. magnetic resonance histology (MRH) was suggested in 1993 [5]. MRH, while based on the same physical principals as MRI is something fundamentally different than the clinical exams which are typically limited to voxel dimensions of ~ 1 mm3. Preclinical imaging systems can acquire images with voxels ~ 1000 times smaller. The MR histology images presented here have been acquired at yet another factor of 1000 increase in spatial resolution. Figure S1 in the supplement shows a comparison of a state-of-the-art fractional anisotropy images of a C57 mouse brain in vivo @ 150 m resolution (voxel volume of 3.3 x10-3 mm3) with the atlas we have generated for this work at 15 m spatial resolution (voxel volume of 3.3 x 10-6 mm3). In previous work, we have demonstrated the utility of MR histology in neurogenetics at spatial/angular resolution of 45 m /46 angles [6]. At this spatial/angular resolution it is possible to map whole brain connectivity with high correspondence to retroviral tracers [7]. But the MRH derived connectomes can be derived in less than a day where the retroviral tracer studies require months/years [8]. The resolution index (angular samples/voxel volume) for this previous work was >500,000 [9]. Figure S2 shows a comparison between that previous work and the new atlas presented in this paper with a resolution index of 32 million. Light sheet microscopy (LSM) has undergone similar rapid evolution over the last 20 years. The invention of tissue clearing, advances in immunohistochemistry and development of selective plane illumination microscopy (SPIM) now make it possible to acquire whole mouse brain images at submicron spatial resolution with a vast array of cell specific markers [10] [11] [12] [13]. And these advantages can be realized in scan times of < 6hrs. The major limitation from these studies is the distortion in the tissue from dissection from the cranium, swelling from clearing and staining, and tissue damage from handling. We report here the merger of these two methods: O_LIMRH with the brain in the skull to provide accurate geometry, cytoarchitectural measures using scalar imaging metrics and whole brain connectivity at 15 m isotropic spatial resolution with super resolution track density images @ 5 m isotropic resolution; C_LIO_LIwhole brain multichannel LSM @ 1.8x1.8x4.0 m; C_LIO_LIa big image data infrastructure that enables label mapping from the atlas to the MR image, geometric correction to the light sheet data, label mapping to the light sheet volumes and quantitative extraction of regional cell density. These methods make it possible to generate a comprehensive collection of image derived phenotypes (IDP) of cells and circuits covering the whole mouse brain with throughput that can be scaled for quantitative neurogenetics. C_LI

neuroscience↗

bioRxiv2021

Fiber tractography bundle segmentation depends on scanner effects, acquisition, diffusion sensitization, and bundle segmentation workflow

When investigating connectivity and microstructure of white matter pathways of the brain using diffusion tractography bundle segmentation, it is important to understand potential confounds and sources of variation in the process. While cross-scanner and cross-protocol effects on diffusion microstructure measures are well described (in particular fractional anisotropy and mean diffusivity), it is unknown how potential sources of variation effect bundle segmentation results, which features of the bundle are most affected, where variability occurs, nor how these sources of variation depend upon the method used to reconstruct and segment bundles. In this study, we investigate six potential sources of variation, or confounds, for bundle segmentation: variation (1) across scan repeats, (2) across scanners, (3) across vendors (4) across acquisition resolution, (5) across diffusion schemes, and (6) across diffusion sensitization. We employ four different bundle segmentation workflows on two benchmark multi-subject cross-scanner and cross-protocol databases, and investigate reproducibility and biases in volume overlap, shape geometry features of fiber pathways, and microstructure features within the pathways. We find that the effects of acquisition protocol, in particular acquisition resolution, result in the lowest reproducibility of tractography and largest variation of features, followed by vendor-effects, scanner-effects, and finally diffusion scheme and b-value effects which had similar reproducibility as scan-rescan variation. However, confounds varied both across pathways and across segmentation workflows, with some bundle segmentation workflows more (or less) robust to sources of variation. Despite variability, bundle dissection is consistently able to recover the same location of pathways in the deep white matter, with variation at the gray matter/ white matter interface. Next, we show that differences due to the choice of bundle segmentation workflows are larger than any other studied confound, with low-to-moderate overlap of the same intended pathway when segmented using different methods. Finally, quantifying microstructure features within a pathway, we show that tractography adds variability over-and-above that which exists due to noise, scanner effects, and acquisition effects. Overall, these confounds need to be considered when harmonizing diffusion datasets, interpreting or combining data across sites, and when attempting to understand the successes and limitations of different methodologies in the design and development of new tractography or bundle segmentation methods.

neuroscience↗

bioRxiv2020

Redundancy Circuits of the Commissural Pathways in Human and Rhesus Macaque Brains

It has been hypothesized that the human brain has traded redundancy for efficiency, but the structural existence has not been identified to examine this claim. Here, we report three redundancy circuits of the commissural pathways in primate brains, namely the orbitofrontal, temporal, and occipital redundancy circuits of the anterior commissure and corpus callosum. Each redundancy circuit has two distinctly separated routes connecting a common pair of cortical regions. We mapped their trajectories in human and rhesus macaque brains using individual and population-averaged tractography. The dissection results confirmed the existence of these redundancy circuits connecting the orbitofrontal lobe, amygdala, and visual cortex. The volume analysis showed a significant reduction in the orbitofrontal and occipital redundancy circuits of the human brain, whereas the temporal redundancy circuit had a substantial organizational difference between the human and rhesus macaque. Our overall findings suggest that the human brain is more efficient in the commissural pathway, as shown by the significantly reduced volume of the anterior commissure which serves as the backup connections for the corpus callosum. This reduction of the redundancy circuit may explain why humans are more vulnerable to psychiatric brain disorders stemming from the corpus callosum compared to non-human primates. SignificanceWe report and describe the connection routes of three redundancy circuits of the commissural pathways in human and rhesus macaque brains and compare their volumes. Our tractography and dissection studies confirmed that the human brain has smaller redundancy circuits. This is the first time such redundancy circuits of the commissural pathways have been identified, and their differences quantified in human and rhesus macaque to verify the redundancy-efficiency tradeoff hypothesis. The findings provide new insight into the topological organization of the human brain and may help understand the circuit mechanism of brain disorders involving these pathways.

neuroscience↗

bioRxiv2020

In vivo Restricted-Diffusion Imaging (RDI) is sensitive to differences in axonal density in typical children and adults

BackgroundThe ability to dissociate axonal density in vivo from other microstructural properties of white matter is important for the diagnosis and treatment of neurologic disease, and new methods to do so are being developed. We investigated one such method-restricted diffusion imaging (RDI)-to see whether it can more accurately replicate histological axonal density patterns in the corpus callosum (CC) of adults and children compared to diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and generalized q-sampling imaging (GQI) methods. To do so, we compared known axonal density patterns defined by histology to to diffusion-weighted imaging (DWI) scans of 840 healthy 20- to 40-year-old adults, and, in a replication and extension, to DWI scans of 129 typically developing 7-month-old to 18-year-old children and adolescents. Contrast analyses were used to to compare pattern similarities between the in-vivo metric and previously-published histological density models. We found that RDI was effective at mapping axonal density of small (Cohens d= 2.60) and large fiber sizes (Cohens d= 2.84) in adults. The same pattern was observed in the developing sample (Cohens d= 3.09 and 3.78, respectively). Other metrics, notably NODDIs intracellular volume fraction (ICVF), were also sensitive to differences in axonal density across the longitudinal axis of the CC. In conclusion, the study showed that RDI is effective at measuring axonal density of small and large axons in adults and children, with both single- and multi-shell acquisition DWI data. Its effectiveness and availability to be used on standard as well as advanced DWI acquisitions makes it a promising method in clinical settings.

neuroscience↗

bioRxiv2020

Shape Analysis of the Human Association Pathways

Shape analysis has been widely used in digital image processing and computer vision, but they have not been utilized to compare the structural characteristics of the human association pathways. Here we used shape analysis to derive length, area, volume, and shape metrics from diffusion MRI tractography and utilized them to study the morphology of human association pathways. The reliability analysis showed that shape descriptors achieved moderate to good test-retest reliability. Further analysis on association pathways showed left dominance in the arcuate fasciculus, cingulum, uncinate fasciculus, frontal aslant tract, and right dominance in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus. The superior longitudinal fasciculus has a mixed lateralization profile with different metrics showing either left or right dominance. The analysis of between-subject variations shows that the overall layout of the association pathways does not variate a lot across subjects, as shown by low between-subject variation in length, span, diameter, and radius. In contrast, the area of the pathway innervation region has a considerable between-subject variation. A follow-up analysis is warranted to thoroughly investigate the nature of population variations and their structure-function correlation.

neuroscience↗