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.
Reference Articles
Gold BT, Powell DK, Andersen AH, Smith CD (2010). Alterations in multiple measures of white matter integrity in normal women at high risk for Alzheimer's disease. Neuroimage 52:1487-1494.
Gold BT, Zhu Z, Brown CA, Andersen AH, LaDu MJ, Tai L, Jicha GA, Kryscio RJ, Estus S, Nelson PT, Scheff SW, Abner E, Schmitt FA, Van Eldik LJ, & Smith CD (2014). White matter integrity is associated with CSF markers of AD in normal adults. Neurobiology of Aging 35, 2263-2271.
Lu H, Kashani AH, Arfanakis K, Caprihan A, DeCarli C, Gold BT, Maillard P, Satizabal CL, Stables L, Wang DJJ, Corriveau RA, Singh H, Smith EE, Fischl B, van der Kouwe A, Schwab K, Helmer KG & Greenberg SM; MarkVCID Consortium (2021) MarkVCID Cerebral small vessel consortium: II Neuroimaging protocols. Alzheimer's & Dementia 17: 716-725.
Gold BT, Shao X, Sudduth TL, Jicha GA, Wilcock DM, Seago ER, & Wang DJJ (2021). Water exchange rate across the blood-brain barrier is associated with CSF amyloid-β 42 in healthy older adults. Alzheimer's & Dementia (doi: 10.1002/alz.12357).
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.
Reference Articles
Gold BT, Powell DK, Xuan L, Jicha GA, & Smith CD (2010). Age-related slowing of task switching is associated with decreased integrity of frontoparietal white matter. Neurobiology of Aging 31: 512-522.
Zhu Z, Johnson NF, Kim C, Gold BT (2015). Reduced frontal cortex efficiency is associated with lower white matter integrity in aging. Cerebral Cortex 25, 138-146.
Brown CA, Schmitt FA, Smith CD & Gold BT (2019). Distinct Patterns of Default Mode and Executive Control Network Circuitry Contribute to Present and Future Executive Function in Older Adults. Neuroimage 195: 320-332.
Zachariou V, Bauer CE, Seago ER, Raslau FD, Powell DK, & Gold BT (2020). Cortical iron disrupts functional connectivity networks supporting working memory performance in older adults. Neuroimage 223. doi: 10.1016/j.neuroimage.2020.117309.
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.
Reference Articles
Johnson NF, Kim C, Clasey J, Bailey A, & Gold BT (2012). Cardiorespiratory Fitness is Positively Correlated with Cerebral White Matter Integrity in Healthy Seniors. Neuroimage 59: 1514-1523.
Johnson NF, Gold BT, Bailey AL, Clasey JL, Hakun JG, White M, Long D, Powell DK (2015). Cardiorespiratory Fitness Modifies the Relationship between Myocardial Function and Cerebral Blood Flow in Older Adults. Neuroimage 131: 126-132.
Gold BT, Kim C, Johnson NF, Kryscio RJ, & Smith CD (2013). Lifelong bilingualism maintains neural efficiency for cognitive control in aging. The Journal of Neuroscience 33: 387-396. PMCID: PMC3710134.
Stern Y, Chételat G, Habeck C, Arenaza-Urquijo E, Vemuri P, Estanga A, Bartres-Faz D, Cantillon M, Clouston S, Elman J, Gold BT, et al. (2019). Mechanisms Underlying Resilience in Ageing. Nature Reviews Neuroscience 20: 246.
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.
Reference Articles
Gold BT, Balota DA, Jones SJ, Powell DK, Smith CD, & Andersen AH (2006). Dissociation of automatic and strategic lexical-semantics: Functional magnetic resonance imaging evidence for differing roles of multiple frontotemporal regions. The Journal of Neuroscience 26: 6523-6532.
Kim C, Johnson NF, Cilles SE, & Gold BT (2011). Common and distinct mechanisms of cognitive flexibility in prefrontal cortex. The Journal of Neuroscience 31: 4771-4779. PMCID: PMC3086290
Kim C, Cilles SE, Johnson NF, & Gold BT (2012). Domain general and domain preferential brain regions associated with different types of task switching: A meta-analysis. Human Brain Mapping 33: 130-142. PMCID: PMC3421461