Tools for integrating brain microstructure with functional dynamics in human and non-human primates

PROJECT SUMMARY Understanding how macroscopic brain function emerges from microstructure is essential for understanding disease mechanisms and neuropharmacological interventions. Despite progress in collecting mesoscale cyto-, chemo-, and myeloarchitecture data under the NIH BRAIN Initiative, the lack of tools to reconstruct and link these microstructure maps to brain dynamics hinders advancement. This proposal aims to develop novel tools to enable researchers to test hypotheses linking brain structure and function in silico. We have developed a tool, called BrainBuilder, to reconstruct 3D mesoscale microstructural atlases of the human and macaque cortex. In the proposed work (Aim 1) we will extend this tool to reconstruct the subcortex and thereby create complete chemo-, myelo- and cytoarchitectural mesoscale atlases that span the entire cerebrum for the macaque and human. To make these and other brain imaging data easily accessible we will (Aim 2) enhance a software toolbox called Neuromaps for multi-scale, multi-modal and cross-species brain imaging analysis. Neuromaps facilitates representation and transformation of brain annotations between standard reference spaces. We will integrate existing macaque brain imaging data into Neuromaps, streamline interspecies brain mapping, and add molecularly-enriched functional network analysis. This will allow researchers to link microstructural features to BOLD signals and understand molecular contributions to brain dynamics. Finally, we will (Aim 3) extend mechanistic brain simulation tools to incorporate microstructural feature maps. We will enhance an open toolbox for neural mass modeling (NMM) simulations, by integrating user-provided microstructural maps, such as the ones we have created. This will enable the simulation of neuronal dynamics with more accurate representations of brain structure. We will validate these models against empirical data, focusing on their ability to reproduce functional dynamics based on chemoarchitectonic maps. This project will therefore greatly ease the integration of microstructural data into models of whole-brain function. These advancements will facilitate the exploration of the biological parameters and mechanisms underpinning brain function. They will enable researchers to link microstructural information with brain dynamics, promote reproducible science, and accelerate the translation of basic and clinical research from model organisms to humans.