FUNCTIONAL CONNECTIVITY IN THE BRAIN: A NEW APPROACH

Washington University, Saint Louis MO

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Abstract

DESCRIPTION (provided by applicant): Oxygen levels within the human brain fluctuate without any apparent external driver. Unexpectedly, these intrinsic fluctuations are correlated among distant regions, forming resting state networks. These networks appear to be relevant to brain function. Resting state data can provide evidence for functional connections between brain regions. Aspects of behavioral performance can be predicted by the ongoing level of slow correlated BOLD fluctuations. Finally, multiple neurological and psychiatric disorders including autism and schizophrenia are associated with abnormalities in resting state networks. Despite their potential importance for understanding normal and disordered cognition, resting state networks remain a poorly understood phenomenon in human cognitive neuroscience. We seek to better understand the origin and significance of correlated oxygen fluctuations by characterizing them at high spatial and temporal resolution and identifying the electrophysiological signals associated with them both at rest and during task performance. We will use oxygen polarography in a novel way. Guided initially by resting state fMRI scans, we will insert multiple platinum microelectrodes into a macaque brain to verify and characterize correlated fluctuations in oxygen concentration. We will record simultaneous electrophysiological signals from these electrodes and ask what portion of the electrophysiological spectrum (slow cortical potentials, local field potentials, multi-unit activit) is associated with task-driven and/or with resting-state correlated oxygen fluctuations. To accomplish this, we will exploit the advantages of polarography over fMRI, including co- localized and simultaneous oxygen and electrical signals, higher spatial and temporal resolution, resistance to movement artifacts, and ease of use in awake behaving animals. Our overall aim is to determine the transfer function mapping electrophysiology signals onto oxygen fluctuations, and whether this transfer function is network-specific, depends on the cortical layer being recorded from, or reflects the ongoing behavioral state of the animal (e.g., task-engaged, sleeping and under anesthesia). The clinical significance of this work is that it will lead to improved use of fMRI information for the diagnosis, prognosis and etiology of brain disorders. The scientific significance, at a high level, is that it will inform our understanding of large-scae brain architecture and cognitive processing.