White matter hyperintensities among older adults are associated with futile increase in frontal activation and functional connectivity during spatial search
Samuel N. Lockhart, Imaging of Dementia and Aging Lab, University of California Davis, Davis, CA, United States of America; Department of Neurology, University of California Davis, Davis, CA, United States of America; Neuroscience Graduate Group, University of California Davis, Davis, CA, United States of America.
Steven J. Luck, Neuroscience Graduate Group, University of California Davis, Davis, CA, United States of America; Department of Psychology, University of California Davis, Davis, CA, United States of America; Center for Mind and Brain, University of California Davis, Davis, CA, United States of America.
Joy Geng, Neuroscience Graduate Group, University of California Davis, Davis, CA, United States of America; Department of Psychology, University of California Davis, Davis, CA, United States of America; Center for Mind and Brain, University of California Davis, Davis, CA, United States of America.
Laurel Beckett, Department of Neurology, University of California Davis, Davis, CA, United States of America; Division of Biostatistics, University of California Davis, Davis, CA, United States of America.
Elizabeth A. Disbrow, Neuroscience Graduate Group, University of California Davis, Davis, CA, United States of America; Department of Neurology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, United States of America.
Owen Carmichael, Imaging of Dementia and Aging Lab, University of California Davis, Davis, CA, United States of America; Department of Neurology, University of California Davis, Davis, CA, United States of America; Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, United States of America.
Charles DeCarli, Imaging of Dementia and Aging Lab, University of California Davis, Davis, CA, United States of America; Department of Neurology, University of California Davis, Davis, CA, United States of America; Neuroscience Graduate Group, University of California Davis, Davis, CA, United States of America; Department of Psychology, University of California Davis, Davis, CA, United States of America.
Abstract
The mechanisms by which aging and other processes can affect the structure and function of brain networks are important to understanding normal age-related cognitive decline. Advancing age is known to be associated with various disease processes, including clinically asymptomatic vascular and inflammation processes that contribute to white matter structural alteration and potential injury. The effects of these processes on the function of distributed cognitive networks, however, are poorly understood. We hypothesized that the extent of magnetic resonance imaging white matter hyperintensities would be associated with visual attentional control in healthy aging, measured using a functional magnetic resonance imaging search task. We assessed cognitively healthy older adults with search tasks indexing processing speed and attentional control. Expanding upon previous research, older adults demonstrate activation across a frontal-parietal attentional control network. Further, greater white matter hyperintensity volume was associated with increased activation of a frontal network node independent of chronological age. Also consistent with previous research, greater white matter hyperintensity volume was associated with anatomically specific reductions in functional magnetic resonance imaging functional connectivity during search among attentional control regions. White matter hyperintensities may lead to subtle attentional network dysfunction, potentially through impaired frontal-parietal and frontal interhemispheric connectivity, suggesting that clinically silent white matter biomarkers of vascular and inflammatory injury can contribute to differences in search performance and brain function in aging, and likely contribute to advanced age-related impairments in cognitive control.
