Project Details
Description
PROJECT SUMMARY
To understand complex neural pathways and networks and their remarkable ability to generate human
behaviors, it is critical to precisely map brain connectomics in vivo. We propose to make significant advances in
such brain mapping by founding the Center for Mesoscale Connectomics (CMC). We will first map the mesoscale
connections between the frontal and parietal cortices. These connections likely subserve higher-order functions
such as attention, decision-making, prospection, and executive control. One key, underappreciated feature of
cortical connectivity is its specific variations within a given brain region, further supporting the critical need for
descriptions of connectivity at a finer scale. Unfortunately, there has traditionally been a major gap in our pursuit
of creating a human brain “wiring diagram” at high spatial resolution, especially since the gold standard for
mesoscale brain connectivity, anatomical tract-tracing, cannot be performed in humans. Moreover, techniques
that can be applied to humans, such as diffusion MRI tractography, may not recapitulate anatomical connectivity
at this scale. Due to this gap, we are lacking an accurate wiring diagram of the human brain that can only
be obtained through a multi-modal, cross-species, multi-scale approach. Here, we propose to combine advanced
anatomical tract-tracing (Aim 1), polarization-sensitive optical coherence tomography (PS-OCT) (Aim 2), and
ultra-high field diffusion tractography (Aim 3) to create such accurate wiring diagrams of human and macaque
brains while bridging spatial resolutions and species.
Importantly, we will computationally bridge species, methods, and spatial scales via state-of-the art registration
and joint (multimodal) modeling of fiber orientations. Subsequently, the remarkable amount of information
available in each dataset will be further enhanced using optimized tractography methods.
At the end of the proposed funding period, we expect to have complete maps of the mesoscale organization of
fronto-parietal connections. We will be poised to apply our multimodal, cross-species methods brain-wide,
including both cortical and subcortical circuits. Importantly, the foundation will be laid for computing noninvasive,
in vivo, accurate, mesoscale connectivity maps of whole human brains through dMRI tractography, which will
allow researchers to link brain connectivity with cognition, behavior, and disease.
Status | Active |
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Effective start/end date | 9/15/23 → 8/31/24 |
Funding
- National Institute of Neurological Disorders and Stroke: $3,905,717.00
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