Understanding changes in the brain and changes in cognition with healthy aging is useful for defining neural substrates of cognition. fMRI is a potentially useful technique for the early diagnosis neurodegenerative conditions such as AD and the development of therapies to ameliorate cognitive decline in both healthy aging and AD. Still, it is unclear how to compare activation data in individual subjects or groups of subjects that differ in cortical morphology. Thus, the research proposed will examine appropriate ways of comparing functional activation between younger and older subjects using a task of working memory (WM), a cognitive ability that depends critically on prefrontal function and declines with aging. The overall goals of this research proposal are to:
Specific Aim number 1: To investigate patterns of age-related regional cortical degeneration and morphological alteration using high resolution 3D MRI images and corticals surface-based morphological analyses in young and older adults.
Specific Aim number 2: To examine methods of combining structural and functional data in the study of age-related attenuation of (WM) with fMRI in young and older subjects performing the N-Back task of WM. To do this, structural data from Aim number 1 will be used to determine how age-related degeneration is related to functional activation.
Specific Aim number 3: To use structure/function methods developed in Aim number 1 and Aim number 2 and N-Back task variants to examine the contribution of inhibitory processes and speed of mental processing to the attenuation of WM with aging. It is expected that the proposed studies will demonstrate that correcting functional activation for regional tissue measurements is useful in the examination of neural changes with healthy aging. Additionally, it is expected that WM deficits in older subjects will be greatly due to decline in inhibitory processes and slower cognitive processing as opposed to a decline in WM storage (span) or updating abilities.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Postdoctoral Individual National Research Service Award (F32)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-IFCN-8 (01))
Program Officer
Wagster, Molly V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Massachusetts General Hospital
United States
Zip Code
Salat, D H; Tuch, D S; van der Kouwe, A J W et al. (2010) White matter pathology isolates the hippocampal formation in Alzheimer's disease. Neurobiol Aging 31:244-56
Salat, David H; Greve, Douglas N; Pacheco, Jennifer L et al. (2009) Regional white matter volume differences in nondemented aging and Alzheimer's disease. Neuroimage 44:1247-58
Knake, Susanne; Salat, David H; Halgren, Eric et al. (2009) Changes in white matter microstructure in patients with TLE and hippocampal sclerosis. Epileptic Disord 11:244-50
Andrews-Hanna, Jessica R; Snyder, Abraham Z; Vincent, Justin L et al. (2007) Disruption of large-scale brain systems in advanced aging. Neuron 56:924-35