# Microstructural profiles of the human superficial white matter and their associations to cortical geometry and connectivity

## TL;DR

This study introduces a new method to analyze the brain's superficial white matter using 3D histology and 7T MRI, revealing its complex structure and links to cortical features.

## Contribution

A novel computational framework for studying superficial white matter using 3D histology and 7T MRI is developed and shared.

## Key findings

- The first 2 mm of superficial white matter shows high structural complexity.
- SWM microstructural gradients correlate with cortical curvature and functional connectivity.
- The method bridges histology and MRI to study SWM organization in vivo.

## Abstract

The superficial white matter (SWM), immediately beneath the cortical mantle, is thought to play a major role in cortico-cortical connectivity as well as large-scale brain function. Yet, this compartment remains rarely studied due to its complex organization. Our objectives were to develop and disseminate a robust computational framework to study SWM organization based on 3D histology and high-field 7T MRI. Using data from the BigBrain and Ahead 3D histology initiatives, we first interrogated variations in cell staining intensities across different cortical regions and different SWM depths. These findings were then translated to in vivo 7T quantitative myelin-sensitive MRI, including T1 relaxometry (T1 map) and magnetization transfer saturation (MTsat). As indicated by the statistical moments of the SWM intensity profiles, the first 2 mm below the cortico-subcortical boundary were characterized by high structural complexity. We quantified SWM microstructural variation using a nonlinear dimensionality reduction method and examined the relationship of the resulting microstructural gradients with indices of cortical geometry, as well as structural and functional connectivity. Our results showed correlations between SWM microstructural gradients, as well as curvature and cortico-cortical functional connectivity. Our study provides novel insights into the organization of SWM in the human brain and underscores the potential of SWM mapping to advance fundamental and applied neuroscience research.

The complex organization of the brain's superficial white matter is a challenge for studying its contribution to cortico-cortical connectivity and large-scale brain function. This study reports a novel computational approach based on 3D histology and 7-Tesla MRI, showing associations between superficial white matter microstructure and diverse cortical properties.