Biology subjects

Pierotich, L.

Publications and source records attributed to Pierotich, L..

3 recordsLinked to original sources

bioRxiv2026

A Mechanical Theory for the Formation of Short Association Fibers in the Brain

The development of neural connections in the brain results from a complex interplay between biological processes and mechanical forces. A key question in neuroscience is how physical forces and the mechanical properties of brain tissue influence the formation of structural connections. Here, we demonstrate that mechanical forces play an essential role in shaping the emergence of short-range connections, particularly U-shaped fibers that link neighboring regions of the cortex. Using a computational model that incorporates our "stress-dependent axon reorientation" hypothesis, we simulate how growing axons respond to the mechanical stress field generated by cortical folding. Our results suggest that axonal growth and reorientation may be strongly influenced by local mechanical cues, helping establish the organization of these short-range pathways. Supported by in vivo diffusion tensor imaging and histological observations, our findings provide a physical explanation for why these fibers predominantly adopt U-shaped trajectories, and why connections between gyri (ridges) are more prevalent than those between sulci (valleys) or spanning gyri and sulci. These results suggest that understanding the mechanics of brain folding is critical for fully explaining the formation of brain connectivity and its variations in health and disorder. Teaser: Mechanical forces during cortical folding guide the formation of short association fibers in the brain.

bioengineering↗

bioRxiv2025

Insights into Temporal and Spatial Dynamics of Short Association Fiber Formation in the Human Fetal Brain

Short association fibers (SAFs) form the local scaffold of cortical connectivity, supporting early functional specialization and marking sites of neurodevelopmental vulnerability. However, their development before birth remains largely unknown. Leveraging advanced fetal diffusion MRI and a histology-validated framework, we present the first in-utero reconstruction of SAF pathways in the human brain. We tracked their volumetric and microstructural developmental trajectories in 243 fetuses spanning a critical period when the brains connectome is rapidly forming. We found that SAFs emerge before sulcal folding, initially as flat, loosely arranged pathways along the subplate-white matter interface, and later reorganize into coherent U-shaped bundles. Their maturation followed a sensorimotor-to-association gradient, paralleling cortical development. Nonlinear, bundle-specific trajectories captured multiphasic maturation, with subplate dynamics preceding increases in axonal coherence and early myelination. By filling a missing link in lifespan brain connectivity, this study establishes a prenatal reference for cortical wiring and provides tools for investigating the origins of neurodevelopmental disorders.

neuroscience↗

bioRxiv2024

White matter tract crossing and bottleneck regions in the fetal brain

There is a growing interest in using diffusion MRI to study the white matter tracts and structural connectivity of the fetal brain. Recent progress in data acquisition and processing suggests that this imaging modality has a unique role in elucidating the normal and abnormal patterns of neurodevelopment in utero. However, there have been no efforts to quantify the prevalence of crossing tracts and bottleneck regions, important issues that have been extensively researched for adult brains. In this work, we determined the brain regions with crossing tracts and bottlenecks between 23 and 36 gestational weeks. We performed probabilistic tractography on 59 fetal brain scans and extracted a set of 51 distinct white tracts, which we grouped into 10 major tract bundle groups. We analyzed the results to determine the patterns of tract crossings and bottlenecks. Our results showed that 20-25% of the white matter voxels included two or three crossing tracts. Bottlenecks were more prevalent. Between 75-80% of the voxels were characterized as bottlenecks, with more than 40% of the voxels involving four or more tracts. The results of this study highlight the challenge of fetal brain tractography and structural connectivity assessment and call for innovative image acquisition and analysis methods to mitigate these problems.

neuroscience↗