The goal of this project is to create noninvasive methodology to image the connectional neuroanatomy of the human brain using diffusion MRI. Two recent developments make this possible. First, we have shown in macaque that every region of the cerebral cortex reliably gives rise to a predictable number of fiber tracts connecting it with unique sets of neuronal subpopulations distributed within cortical and subcortical regions. Second, we have shown, also in macaque, that novel forms of high angular resolution diffusion spectrum MRI (DSI) have the unique capacity to define connectional neuroanatomy non-invasively. The goal of the present project is to define, for the first time, the connectional neuroanatomy of the monkey brain non-invasively, and to build a bridge from the macaque brain to the human brain in order to accomplish a previously impossible goal - the determination of connectional neuroanatomy in the human brain. To achieve this goal, three steps are necessary. First, we will validate diffusion MRI in macaque by comparison to the gold standard of isotope tract tracer injections, the tracer injections and MRI to be performed in the same animals. The technical parameters that optimally and most accurately replicate the findings of the tract tracer studies will be determined, and potential sources of MRI error quantified and minimized. Second, post-mortem human brains will be imaged to achieve the highest possible resolution of these human brains, with the aim of replicating the mandatory principles of organization of the white matter pathways identified as defining the connections of the monkey brain. Next, the brains of living human subjects will be imaged, to attempt to replicate the findings in the post- mortem specimens, in order to establish the limitations of the methodology in vivo. To convey this technology into the broader imaging arena, we will investigate the hypothesis that structural and functional connectivity are correlated by comparing the results with those of resting state connectivity in the living human brain.

Public Health Relevance

The goal of this study is to develop and validate scientific methods for the study of the wiring and connections of the human brain. We will first use MRI and conventional tract tracing techniques in the monkey brain to optimize our MRI methods, and we will then study brains of people who are deceased, and also the brains of healthy human volunteers, to identify how these neural circuits are organized in the human. These studies have potential to provide new and valuable information about the human nervous system. This information is essential for understanding normal development;developmental disorders such as autism;neurological illnesses such as Alzheimer disease, multiple sclerosis, and traumatic brain injury;and psychiatric diseases such as schizophrenia.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neurotechnology Study Section (NT)
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Freund, Michelle
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Massachusetts General Hospital
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Takahashi, Emi; Dai, Guangping; Rosen, Glenn D et al. (2011) Developing neocortex organization and connectivity in cats revealed by direct correlation of diffusion tractography and histology. Cereb Cortex 21:200-11
Takahashi, Emi; Dai, Guangping; Wang, Ruopeng et al. (2010) Development of cerebral fiber pathways in cats revealed by diffusion spectrum imaging. Neuroimage 49:1231-40
Sosnovik, David E; Wang, Ruopeng; Dai, Guangping et al. (2009) Diffusion MR tractography of the heart. J Cardiovasc Magn Reson 11:47
Reese, Timothy G; Benner, Thomas; Wang, Ruopeng et al. (2009) Halving imaging time of whole brain diffusion spectrum imaging and diffusion tractography using simultaneous image refocusing in EPI. J Magn Reson Imaging 29:517-22
Gilbert, Richard J; Gaige, Terry A; Wang, Ruopeng et al. (2008) Resolving the three-dimensional myoarchitecture of bovine esophageal wall with diffusion spectrum imaging and tractography. Cell Tissue Res 332:461-8
Wedeen, V J; Wang, R P; Schmahmann, J D et al. (2008) Diffusion spectrum magnetic resonance imaging (DSI) tractography of crossing fibers. Neuroimage 41:1267-77
Jonasson, Lisa; Bresson, Xavier; Thiran, Jean-Philippe et al. (2007) Representing diffusion MRI in 5-D simplifies regularization and segmentation of white matter tracts. IEEE Trans Med Imaging 26:1547-54
Weng, Jun-Cheng; Chen, Jyh-Horng; Yang, Pai-Feng et al. (2007) Functional mapping of rat barrel activation following whisker stimulation using activity-induced manganese-dependent contrast. Neuroimage 36:1179-88
Gilbert, Richard J; Napadow, Vitaly J; Gaige, Terry A et al. (2007) Anatomical basis of lingual hydrostatic deformation. J Exp Biol 210:4069-82
Schmahmann, Jeremy D; Pandya, Deepak N; Wang, Ruopeng et al. (2007) Association fibre pathways of the brain: parallel observations from diffusion spectrum imaging and autoradiography. Brain 130:630-53

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