The brain is a patchwork of regions, each specialized for a different, often very specific function. For example, some brain regions process only visual information whereas others control motor actions. Although these regions are found in the same general location across individuals, their precise location varies considerably from one person to the next. This variability is especially marked for brain regions engaged in higher-order functions such as face recognition or language. What determines the function of a given patch of cortex? A deep-rooted assumption in neuroscience is that the connectivity of a given region to the rest of the brain determines that region's function. For example, primary visual cortex is a visual region because of its input from the retina via the optic radiations. However, it is unknown whether this tight relationship between connectivity and function holds beyond primary sensory and motor regions. Here, I will use a novel method I developed in my thesis work that combines functional MRI and connectivity patterns as measured noninvasively through diffusion-weighted imaging, to answer two fundamental questions about the human brain: 1) Does the pattern of connectivity to the rest of the brain predict functionally-specific fMRI responses voxel by voxel across the cortex in individual subjects? 2) Do these connectivity patterns develop early in childhood and determine the functional specialization acquired later? Aim 1 will identify the connectivity patterns that predict the spatial profile of responses to perceptual, linguistic, and cognitive tasks in each individual's brain, thus accounting for functional specialization and individual variability in adults.
Aim 2 will identify the connectivity patterns of 5 year olds that predict the functional organization of their brains two years later. As these children learn to rea, particular regions of their brains will develop specialized responses to visually-presented words. Here we ask whether the location of this specialized response is predicted by the pattern of connectivity several years earlier before they learn to read. The results of this study will characterize the relationship between structure and function in the adult human brain and will test the causal role of connectivity in shaping development of the functional specialization of the cortex. This work will provide insight into the physical mechanisms that determine neural specialization and plasticity, and in turn, individual differences in health and disease. By identifying the mechanisms underlying neural and behavioral individuality, this research will directly inform disorders of neurodevelopment as well as heterogeneity in the typical population.

Public Health Relevance

This proposal will test whether the anatomical connections between brain regions determine the location and selectivity of specialized functions in adults and children, and the results will have valuable insights into the developmental origins of healthy adult brain function. These results will also have practical relevance for clinical research, by providing a method to infer functional brain maps from structural images alone in individuals who cannot be functionally scanned, for example in pre-surgical mapping of low-functioning or comatose subjects, or in sleeping infants (enabling earlier diagnosis and intervention in neurodevelopmental disorders such as autism, ADHD, and dyslexia).

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1)
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Freund, Lisa S
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Massachusetts Institute of Technology
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United States
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Saygin, Z M; Kliemann, D; Iglesias, J E et al. (2017) High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas. Neuroimage 155:370-382
Saygin, Zeynep M; Osher, David E; Norton, Elizabeth S et al. (2016) Connectivity precedes function in the development of the visual word form area. Nat Neurosci 19:1250-5
Osher, David E; Saxe, Rebecca R; Koldewyn, Kami et al. (2016) Structural Connectivity Fingerprints Predict Cortical Selectivity for Multiple Visual Categories across Cortex. Cereb Cortex 26:1668-83