This is a 1st competitive renewal of our project ?Biophysical Basis of Resting State Connectivity by MRI?. Our goals are to determine whether inter-regional correlations in resting state fluctuations of MRI (rsfMRI) signals from the brain reliably measure functional connectivity (rsFC) between brain regions, and to establish how MRI data correlate with other metrics of connectivity. These goals are directly relevant for the validation and interpretation of human applications of rsfMRI. Studies performed to date have focused on mesoscopic scale networks (100m - 10mm) within a well defined functional region of primary somatosensory cortex (S1) in non-human primates, where we can measure spatial patterns of resting state correlations at high resolution and validate their interpretation with electrophysiological signals and anatomic tracers. In the next phase, we aim to expand these studies to further establish the origins and significance of rsFC measurements. Cerebral cortex exhibits a laminar structure, but the laminar distribution of rsFC is poorly understood. In addition, whether the strong inference that rsfMRI correlations directly represent and link functional connectivity extends beyond the fine-grained level of sub-regions in S1 to more macroscopic dimensions remains unexplored. Moreover, recent studies of apparent slow variations of rsfMRI correlations suggest that the resting state itself exhibits dynamic variations that may be of functional importance. We therefore propose three specific aims: [1] to identify the origins of rsFC by measuring the connectivity patterns of rsfMRI signals across and between cortical layers in sub-regions of S1, S2, thalamus and corresponding contralateral regions. We will acquire fMRI data at 9.4T using vibrotactile stimuli to identify functionally distinct candidate areas of activation in bilateral S1, S2, and thalamus, and measure resting state correlations between voxels within and across layers in these regions: [2] to measure the effects of selective deprivation of spinal, thalamic, cortical and inter-hemispheric inputs on rsfMRI and demonstrate their relationships to behavior: [3] to validate measurements of rsFC signals in normal and input-deprived conditions by direct comparisons with quantitative intracranial electrophysiology and histology. We will acquire rsfMRI and invasive multi-electrode measurements in the same animals to quantitatively compare different metrics of neural activity and anatomical connections. We will acquire fMRI data at 9.4T from monkey brain to study functionally distinct areas in SI, SII, and thalamus. We will use innovative mathematical analyses to quantify variations in resting state correlations across time and whether these patterns agree with slow variations in electrophysiological correlations. We will perform invasive multichannel microelectrode array measurements in the same animals so that we can quantitatively compare different metrics of neural activity and anatomical connections. We believe that the proposed studies have considerable importance for validating the neural basis of resting state functional connectivity measures, and have direct implications for human fMRI studies and their applications.

Public Health Relevance

Neuroscientists and clinicians currently use MRI to depict connectivity within neural circuits in the human brain by analyzing small signal ?uctuations that arise during acquisitions of long series of images while a subject is at rest. However, there have been very few studies that validate the interpretation of these signals and their biophysical origin has not been substantiated. The studies proposed would establish the relationships between these MRI metrics of connectivity and gold standard electrophysiological recordings of neural electrical activity and maps of anatomic connections from injected tracers in the brains of non-human primates.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Biomedical Imaging Technology Study Section (BMIT)
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Babcock, Debra J
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Vanderbilt University Medical Center
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Wang, Feng; Zu, Zhongliang; Wu, Ruiqi et al. (2018) MRI evaluation of regional and longitudinal changes in Z-spectra of injured spinal cord of monkeys. Magn Reson Med 79:1070-1082
Wu, Tung-Lin; Wang, Feng; Mishra, Arabinda et al. (2018) Resting-state functional connectivity in the rat cervical spinal cord at 9.4 T. Magn Reson Med 79:2773-2783
Shi, Zhaoyue; Wu, Ruiqi; Yang, Pai-Feng et al. (2017) High spatial correspondence at a columnar level between activation and resting state fMRI signals and local field potentials. Proc Natl Acad Sci U S A 114:5253-5258
Schilling, Kurt G; Gao, Yurui; Stepniewska, Iwona et al. (2017) The VALiDATe29 MRI Based Multi-Channel Atlas of the Squirrel Monkey Brain. Neuroinformatics 15:321-331
Chen, Li Min; Yang, Pai-Feng; Wang, Feng et al. (2017) Biophysical and neural basis of resting state functional connectivity: Evidence from non-human primates. Magn Reson Imaging 39:71-81
Wu, Tung-Lin; Mishra, Arabinda; Wang, Feng et al. (2016) Effects of isoflurane anesthesia on resting-state fMRI signals and functional connectivity within primary somatosensory cortex of monkeys. Brain Behav 6:e00591
Wilson 3rd, George H; Yang, Pai-Feng; Gore, John C et al. (2016) Correlated inter-regional variations in low frequency local field potentials and resting state BOLD signals within S1 cortex of monkeys. Hum Brain Mapp 37:2755-66
Gao, Yurui; Parvathaneni, Prasanna; Schilling, Kurt G et al. (2016) A 3D high resolution ex vivo white matter atlas of the common squirrel monkey (Saimiri sciureus) based on diffusion tensor imaging. Proc SPIE Int Soc Opt Eng 9784:
Ding, Zhaohua; Xu, Ran; Bailey, Stephen K et al. (2016) Visualizing functional pathways in the human brain using correlation tensors and magnetic resonance imaging. Magn Reson Imaging 34:8-17
Wu, Tung-Lin; Wang, Feng; Anderson, Adam W et al. (2016) Effects of anesthesia on resting state BOLD signals in white matter of non-human primates. Magn Reson Imaging 34:1235-1241

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