Abstract
Multi-modal neuroimaging projects such as the Human Connectome Project (HCP) and UK Biobank are advancing our understanding of human brain architecture, function, connectivity, and their variability across individuals using high-quality non-invasive data from many subjects. Such efforts depend upon the accuracy of non-invasive brain imaging measures. However, ‘ground truth’ validation of connectivity using invasive tracers is not feasible in humans. Studies using nonhuman primates (NHPs) enable comparisons between invasive and non-invasive measures, including exploration of how “functional connectivity” from fMRI and “tractographic connectivity” from diffusion MRI compare with long-distance connections measured using tract tracing. Our NonHuman Primate Neuroimaging & Neuroanatomy Project (NHP_NNP) is an international effort (6 laboratories in 5 countries) to: (i) acquire and analyze high-quality multi-modal brain imaging data of macaque and marmoset monkeys using protocols and methods adapted from the HCP; (ii) acquire quantitative invasive tract-tracing data for cortical and subcortical projections to cortical areas; and (iii) map the distributions of different brain cell types with immunocytochemical stains to better define brain areal boundaries. We are acquiring high-resolution structural, functional, and diffusion MRI data together with behavioral measures from over 100 individual macaques and marmosets in order to generate non-invasive measures of brain architecture such as myelin and cortical thickness maps, as well as functional and diffusion tractography-based connectomes. We are using classical and next-generation anatomical tracers to generate quantitative connectivity maps based on brain-wide counting of labeled cortical and subcortical neurons, providing ground truth measures of connectivity. Advanced statistical modeling techniques address the consistency of both kinds of data across individuals, allowing comparison of tracer-based and non-invasive MRI-based connectivity measures. We aim to develop improved cortical and subcortical areal atlases by combining histological and imaging methods. Finally, we are collecting genetic and sociality-associated behavioral data in all animals in an effort to understand how genetic variation shapes the connectome and behavior.
Highlights
For over a century, neuroscientists investigated nonhuman primates (NHP) as a meso-scale model for understanding the anatomy, physiology and pathology of the human brain
Mapping ‘dense’ connectivity to a surface-based atlas The Van Essen and Kennedy labs have developed a ‘parcellationfree’ mapping of tracers to a cortical surface-based atlas (OHBM 2019 abstracts; Hou et al, in prep). This ‘contours-to-atlas’ surface mapping of tract tracing data serves three broad aims: firstly, to enable highresolution analyses that preserve fine-grained detail on data mapped to an atlas surface, allowing comparisons with other tracer injection results as well as data from other modalities, and secondly, to facilitate re-parcellation of connectivity data according to alternative delineations of cortical areas and their boundaries
How unique is the human brain, and how does it differ from other primates? While the mouse has become the most widely used model organism in neuroscience, there is increasing appreciation of the critical importance of NHP studies owing to their closer evolutionary proximity to humans
Summary
Neuroscientists investigated nonhuman primates (NHP) as a meso-scale model for understanding the anatomy, physiology and pathology of the human brain. The project’s goals include (i) implementing a high resolution HCP-style data acquisition and analysis approach in 100 macaques and marmosets; (ii) developing a comprehensive quantitative invasive tract tracing database accurately mapped onto MRI-based volumes and surfaces; (iii) comparing imaging-based functional and structural connectivity measures to “ground-truth” anatomical tract tracers; (iv) analyzing cytoarchitecture quantitatively via immunohistologically-defined cell types to map brain areas; (v) studying over 100 macaques and marmosets, to compare individual variability in social behavior, genetics and brain organization; and (vi) studying some macaque animals using a unique ultra-high resolution 10.5T scanner at UMinn Achieving these objectives will entail validation of non-invasive multi-modal imaging methods and establishing combined neuroimaging and neuroanatomy atlases.
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