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Title

Intrinsic Brain Activity: Concept, Techniques, Application

Date of Award

Spring 5-15-2012

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Neurosciences)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Brain function has traditionally been studied in terms of physiological responses to environmental demands. However, this view ignores the fact that much of the brain's energy is devoted to its intrinsic operations, which are not visible in event-related responses. Recent studies of spontaneous fluctuations in the functional magnetic resonance imaging (fMRI) blood oxygen level dependent (BOLD) signal have revealed an important manifestation of intrinsic neuronal activity that provides insight into the brain's functional organization. Far from being noise, spontaneous fluctuations are correlated within anatomically connected and functionally related regions of the brain. Using correlation analysis, multiple large-scale intrinsic networks have been characterized in this fashion. The first aim of this thesis is to further characterize the specificity of correlations in intrinsic neuronal activity. We pursued this aim by investigating the thalamocortical system, where the specificity of anatomical connections has been well-described. Based on the technique of partial correlation mapping, we find highly specific correlations that can be observed down to the limits of the spatial resolution of our fMRI acquisition. Next, we performed diffusion weighted imaging (DWI) and reconstructed thalamocortical white matter tracts to compare our functional results with structural data. Additionally, we reconstructed a 3-dimensional representation of 2-dimensional histological atlas of the human brain. The combination of these pieces of data allowed us to perform cross-validation of these emerging functional and structural neuroimaging techniques and "gold-standard" validation with histology. Based on these data, we conclude that, on a voxel-by-voxel level, correlations in intrinsic activity compare well with DWI reconstruction of anatomical connectivity and compare well with our "gold-standard".

In the second part of our thesis, we investigate the unique phenomenon of cross-network anticorrelations, specifically between the default mode network and a task-positive network predominantly consisting of the salience and dorsal attention networks. Because observed anticorrelations can be biased by regression the global brain signal, we first characterize the properties of the global signal, discuss the mathematical consequences of global signal regression, and then characterize the impact of this maneuver on observed anticorrelated networks. Based on an extensive set of analyses and supporting findings from the electrophysiology literature, we conclude that observed anticorrelations are likely the result of a physiologic cause as opposed to a mathematical bias.

Finally, we assess the feasibility of using intrinsic activity for clinical purposes. This consists of two pathways. First, we explore functional mapping with intrinsic activity as a potential aid for presurgical functional network localization in patients with brain tumors. In our case series, we find that sensorimotor network localization matches well with "gold-standard" intra-operative cortical stimulation mapping and potentially holds many advantages to traditional task-evoked fMRI mapping. In our second pursuit, we performed an extensive review of the literature on neuropsychiatric disorders and intrinsic activity to assess the feasibility of using this technique as a clinical biomarker of disease. Taken together, the results of this thesis further our understanding of the nature and specificity of intrinsic activity, its relation to structural anatomy using a combination of neuroimaging techniques, and highlight the potential clinical applications stemming from the brain's intrinsic operations.

Language

English (en)

Chair and Committee

Marcus E Raichle

Committee Members

Dennis Barbour, Abraham Snyder, Joseph Price, W Thomas Thach, David Van Essen

Comments

Permanent URL: https://doi.org/10.7936/K71834DG

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