Research Themes

 

Neuroimaging Markers of Preclinical Dementia States

We are contributing to the identification of neuroimaging markers of preclinical Alzheimer’s disease (AD) and related disorders. For example, in a series of studies, we identified subtle DTI-based white matter (WM) microstructural alterations in limbic tracts in normal adults at high risk for AD. In an early study of its kind, we further showed that diffusion properties in some of these WM limbic tracts are linked with markers of AD pathology measured in cerebrospinal fluid (CSF). We are also actively involved in multi-center consortia devoted to identifying neuroimaging biomarkers of cerebral small vessel disease (cSVD). For example, through our interactions with MarkVCID consortium colleagues, we have recently found that a new imaging method, diffusion-prepared arterial spin labeling (DP-ASL), holds promise as a measure of early cSVD as it appears to index physiological dysfunction in blood-brain barrier clearance of toxic substances such as amyloid-beta.

 

 

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Brain Aging and Executive Function

We are also contributing to our understanding about some of the neurobiological bases of age-related cognitive declines, such as WM changes and brain iron accumulation. In a series of studies, we have found evidence suggesting that poor WM microstructure is associated with aberrant functional brain activation and poor executive performance in older adults. We have further explored functional connectivity patterns linked with high executive performance and how some of these patterns are negatively affected by age-related brain iron accumulation. 

 

 

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Positive Modifiers of Cognitive Function in Older Adults

We take an active interest in identifying positive lifestyle variables may mitigate age-related cognitive declines. We have been particularly interested in aerobic fitness and bilingualism as potential modifiers as they do not require high education or socioeconomic status. We have found evidence that aerobic fitness in older adults is positively associated with WM microstructure in tracts connecting frontal regions. In addition, we have found that superior aerobic fitness is associated with higher blood flow to the default mode brain network, even in older adults with less than optimal heart functioning. Our work on bilingualism suggests that older adults who speak two languages on a regular basis show differences in executive performance and brain function than their monolingual peers.

 

 

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Dissociating Executive Functions in Prefrontal Cortex

My early work was conducted with younger adults and explored the possibility of a rostro-caudal gradient within prefrontal cortex (PFC). Specifically, this work explored whether rostral PFC regions are preferential for control processes requiring internally generated/maintained task sets. We also explored the neurocognitive interface between conflict signaling and working memory. Previous work suggested that the anterior cingulate cortex (ACC) detects conflict, and then triggers the dorsolateral prefrontal cortex (DLPFC) to regulate that conflict. Our findings in this area have suggested that the ACC-DLPFC loop appears to have strong interplay with the working memory system, enabling it to maintain stimulus-response conflict signals within working memory to guide subsequent behavioral adjustment consistent with internal goals.

 

 

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