Recent developments demonstrate that the brain carries out its functions through a number of large-scale functional sub-systems, or networks. One of the most studied brain networks is the default mode network (DMN); however, the internal structure of the DMN, and how it carries out its functions, still remains elusive. The topography of the DMN has been mapped using four different imaging techniques: through reductions in the blood flow of DMN regions during task engagement using 15O-PET; as the hypermetabolic regions at rest using FDG-PET; as the task-based deactivation using BOLD-fMRI; and through functional connectivity in resting-state fMRI. The task-based blood-flow reductions observed in 15O-PET studies, and task-based deactivations observed using BOLD-fMRI, seem to be reflective of the same neurophysiological processes, since BOLD signal is highly confounded by blood flow. It has also been postulated that resting-state functional connectivity and hypermetabolism in DMN regions reflect the same neurophysiological process; thus concluding that the resting-state functional connectivity is the measurement of the brain?s baseline, intrinsic, or resting-state activities. However, recent evidence has put such possibility under question by indicating that resting-state functional connectivity networks are active during anesthesia, sleep, and even task-performance. Such findings raise a critical, but as of yet unanswered, question: what is the role of such overlapping networks in DMN regions? We hypothesize that functional connectivity in the DMN regions is representative of a lower level process, which provides the underlying infrastructure for the higher-level network that carries out the actual function. Both functional connectivity and task-based deactivation in the DMN regions have been reported to be disrupted with normal aging, the pre-clinical stage of Alzheimer?s disease, mild cognitive impairment and Alzheimer?s disease. However, since the assumption in the field is that the DMN?s functional connectivity and task-based deactivation are representative of the same underlying neurophysiological process, there has been no study, to our knowledge, investigating the cascade of the events in which functional connectivity or negative BOLD response get disrupted. Disentangling the cascade of events in the AD is crucial for understanding the disease initiation, progress, and treatment. Our preliminary evidence in this project demonstrates that imposing alteration in the task-based deactivation network does not have any effect on the functional connectivity of the same regions. The current proposal will use asymptomatic stage of Alzheimer?s disease to test whether disruption in the underlying functional connectivity results in any change to the task-based deactivations in the DMN, which is an evidence for hierarchical structure.

Public Health Relevance

Both functional connectivity and task-based deactivation in default mode network have been reported to be disrupted in Alzheimer?s disease. We will provide novel evidence that the disruption of DMN?s functional connectivity will cause disruption in the task-based deactivation networks, but not the other way around.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Clinical Neuroscience and Neurodegeneration Study Section (CNN)
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Wise, Bradley C
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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