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Reconstructing the Brain’s Wiring Diagram Is No Monkey Business

  • Kelly Shen
    Correspondence
    Address correspondence to Kelly Shen, Ph.D., Rotman Research Institute, Baycrest, 3560 Bathurst St, Toronto, Ontario, M6A 2E1, Canada.
    Affiliations
    Rotman Research Institute, Baycrest, Toronto, Ontario, Canada
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      Mapping the human “connectome,” or the brain’s anatomical wiring diagram, has become a major endeavor in bettering our understanding of brain dysfunction in neuropsychiatric disorders (
      • Worbe Y.
      Neuroimaging signature of neuropsychiatric disorders.
      ). It not only affords us the ability to examine macroscale structural changes and their impact on functional dynamics, but also allows us to examine the influence that microscale disease mechanisms, such as genetic or cellular factors, have on macroscale network organization (
      • Scholtens L.H.
      • van den Heuvel M.P.
      Multimodal connectomics in psychiatry: Bridging scales from micro to macro.
      ). Structural connectivity is also used to inform generative models of neuropsychiatric disorders (
      • Bassett D.S.
      • Xia C.H.
      • Satterthwaite T.D.
      Understanding the emergence of neuropsychiatric disorders with network neuroscience.
      ). These models represent one of the most exciting avenues for the future of neuropsychiatry because they provide predictions of individual brain health trajectories, linking specific disruptions in brain structure to distributed effects across functional networks. Work to determine their potential to guide individualized treatment options—including drug interventions, brain stimulation, and cognitive behavioral therapies—is currently underway. In these applications, the predominant method for mapping the human connectome has been diffusion-weighted magnetic resonance imaging (dMRI) tractography. While significant advances continue to be made in dMRI sequence acquisition as well as fiber modeling and tracking, tractography as a noninvasive means of estimating anatomical connectivity still suffers from several methodological issues that require careful consideration.
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      Linked Article

      • Estimating Brain Connectivity With Diffusion-Weighted Magnetic Resonance Imaging: Promise and Peril
        Biological Psychiatry: Cognitive Neuroscience and NeuroimagingVol. 5Issue 9
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          Diffusion-weighted magnetic resonance imaging (dMRI) is a popular tool for noninvasively assessing properties of white matter in the brain. Among other uses, dMRI data can be used to produce estimates of anatomical connectivity on the basis of tractography. However, direct comparisons of anatomical connectivity as estimated through invasive neural tract-tracing experiments and dMRI-derived connectivity have shown only a moderate relationship in nonhuman primate (particularly macaque) studies. Tractography is plagued by known problems associated with resolution, crossing fibers, and curving fibers, among others.
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