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J Neurosci. 2016 Jun 22;36(25):6758-70. doi: 10.1523/JNEUROSCI.0493-16.2016.

Using Diffusion Tractography to Predict Cortical Connection Strength and Distance: A Quantitative Comparison with Tracers in the Monkey.

Author information

1
Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110.
2
Oxford Centre for Functional MRI of the Brain, University of Oxford, Oxford, United Kingdom OX3 9DU.
3
Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital, Hvidovre, Denmark 2650, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kongens Lyngby, Denmark 2800, and.
4
Stem-cell and Brain Research Institute, Bron, France 69500.
5
Department of Neuroscience, Washington University School of Medicine, St. Louis, Missouri 63110, vanessen@wustl.edu.

Abstract

Tractography based on diffusion MRI offers the promise of characterizing many aspects of long-distance connectivity in the brain, but requires quantitative validation to assess its strengths and limitations. Here, we evaluate tractography's ability to estimate the presence and strength of connections between areas of macaque neocortex by comparing its results with published data from retrograde tracer injections. Probabilistic tractography was performed on high-quality postmortem diffusion imaging scans from two Old World monkey brains. Tractography connection weights were estimated using a fractional scaling method based on normalized streamline density. We found a correlation between log-transformed tractography and tracer connection weights of r = 0.59, twice that reported in a recent study on the macaque. Using a novel method to estimate interareal connection lengths from tractography streamlines, we regressed out the distance dependence of connection strength and found that the correlation between tractography and tracers remains positive, albeit substantially reduced. Altogether, these observations provide a valuable, data-driven perspective on both the strengths and limitations of tractography for analyzing interareal corticocortical connectivity in nonhuman primates and a framework for assessing future tractography methodological refinements objectively.

SIGNIFICANCE STATEMENT:

Tractography based on diffusion MRI has great potential for a variety of applications, including estimation of comprehensive maps of neural connections in the brain ("connectomes"). Here, we describe methods to assess quantitatively tractography's performance in detecting interareal cortical connections and estimating connection strength by comparing it against published results using neuroanatomical tracers. We found the correlation of tractography's estimated connection strengths versus tracer to be twice that of a previous study. Using a novel method for calculating interareal cortical distances, we show that tractography-based estimates of connection strength have useful predictive power beyond just interareal separation. By freely sharing these methods and datasets, we provide a valuable resource for future studies in cortical connectomics.

KEYWORDS:

cerebral cortex; connectivity; diffusion tractography; macaque; neuroanatomy; retrograde tracing

PMID:
27335406
PMCID:
PMC4916250
DOI:
10.1523/JNEUROSCI.0493-16.2016
[Indexed for MEDLINE]
Free PMC Article

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