2006 — 2008 |
Gold, Brian Timothy |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Neural Substrates of Component Lexical Semantic Processes
[unreadable] DESCRIPTION (provided by applicant): Extracting meaning from words (lexical semantics) is critical to normal language functioning. Lexical semantic impairment can result from a variety of causes including developmental abnormalities, stroke and degenerative diseases but may reflect damage to one or more component processes. Current language models have identified two qualitatively different components of the lexical semantic system: 1) An automatic component enables rapid access to semantics within milliseconds of lexical input; and 2) a controlled component evolves more slowly and guides strategic retrieval of semantic information not recovered automatically. In addition, some processes associated with these components are thought to depend upon the modality of incoming stimuli. The objective of the project is to identify the neural correlates of these behaviorally separable automatic and controlled components of the lexical semantic system, within and across visual and auditory modalities. In a preliminary study, we identified dissociable neural correlates of visually cued automatic and controlled lexical semantic processing in healthy volunteers using event-related fMRI and a primed lexical decision task. A series of similar studies are proposed to characterize more precisely the roles of several frontal and temporal lobe brain regions in components of the lexical semantic system. The design is novel in that automatic and controlled semantic priming conditions will be compared directly, using randomized designs identical to those used in behavioral research. There are three goals. The first goal is to characterize more precisely the role of a left frontal region in visually cued controlled retrieval of lexical semantic information. The second goal is to characterize more precisely the role of a left temporal region in visually cued automatic lexical semantic processing. The third goal is to identify neural regions involved in auditorily cued lexical semantics that overlap, and are dissociable from, those involved in visually cued lexical semantics. Identifying neural systems associated with component processes involved in extracting meaning from words is of central importance to understanding the structure and organization of the lexical semantic system and should aid diagnosis and rehabilitation of language disorders. [unreadable] [unreadable] [unreadable]
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2009 — 2013 |
Gold, Brian Timothy |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
The Effects of Bilingualism On Age-Related Cognitive and Neurobiological Declines
Program Director/Principal Investigator (Last, First, Middle): Executive control refers to a set of supervisory processes that enable humans to flexibly shape thoughts and behavior in order to accomplish internal goals. Normal human aging is associated with marked decline in executive control functions. However, recent evidence suggests that lifelong bilingualism may attenuate age-related declines of some executive control functions. These findings suggest that bilingualism may promote neuroplasticity and/or compensatory brain reserve. However, despite potentially large social and scientific implications, considerable knowledge gaps exist in this field. The present work will fill several of these gaps through a series of studies aimed to understand the influences of bilingualism on cognition and neurobiology in aging. Specific Aim 1 is to obtain more detailed information about the influence of lifelong bilingualism on high-level working memory processes. Specific Aims 2-4 use cutting-edge neuroimaging methods to understand the neurobiological bases of bilingual executive control advantages. These aims are to understand potential functional neuroanatomic (Aim 2), structural grey matter (Aim 3), and white matter microstructure (Aim 4) bases of bilingual performance advantages, by linking imaging patterns directly to behavioral performance. Specific Aim 5 is to determine which bilingual cognitive/neurobiological advantages correlate with degree of experience/practice with the second language. Given the projected increase in the aged population, it is important to understand how specific lifestyle factors may affect age-related cognitive and neurobiological declines. Results from the present proposal will provide a detailed description of how an accessible lifestyle variable can offset age- related cognitive declines through neurobiological plasticity and/or compensatory brain reserve. Finally, research relevant to understanding the consequences of bilingualism is an issue of fundamental importance in our increasingly multilingual society. PHS 398/2590 (Rev. 11/07) Page Continuation Format Page
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2017 — 2021 |
Gold, Brian Timothy |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Contributions of Alzheimer's Pathology and Cerebrovascular Factors to Cognitive Aging
Alzheimer's disease is associated with the accumulation of pathological markers [amyloid-beta (A?) and tau], brain atrophy and a progressive loss of memory functions. However, a significant proportion of individuals with AD pathology do not develop cognitive impairment, indicating contributions of other factors to clinical AD. Increasing evidence suggests that factors strongly linked with brain aging, such as cerebrovascular alterations and declines in executive function, contribute to clinical AD. This link is not straightforward though as the effects of AD pathology and vascular alterations can be moderated by cognitive reserve and brain resilience. Our recent results suggest that levels of A? and tau in cerebrospinal fluid (CSF) and cerebrovascular declines associated with white matter hyperintensities (WMHs) are differentially related to patterns of executive function in cognitively normal older adults. In addition, our results suggest that some of the patterns appear modifiable based on positive lifestyle variables. This proposal seeks to define the interplay between AD pathology, cerebrovascular-related alterations and cognitive reserve that distinguish normal brain aging from AD-like cognitive declines. We propose to study of 120 cognitively normal older adults using measures of CSF A?, p-tau and t- tau, neuroimaging measures including event-related fMRI, multiple structural imaging measures. Structural neuroimaging measures will include volumetric measures, FLAIR imaging for quantification of WMH volumes and diffusion tensor imaging for quantification of regionally distributed white matter abnormalities. A subset of participants will complete the same CSF and imaging measures approximately 3 years later. We aim to (1) dissociate effects of AD pathology and brain aging on functional compensation (2) identify the separate and synergistic effects of AD pathology and cerebrovascular markers on cognitive declines over time and (3) identify reserve factors that moderate relationships between vascular and AD pathology markers on cognition. We will test hypotheses that AD pathology and cerebrovascular factors synergistically interact to predict AD-like cognitive declines. We will also test the hypothesis that reserve factors will offset the effects of some of these pathological and vascular changes on cognitive functions, via mechanisms of brain maintenance or plastic functional brain reorganization of large-scale brain functional networks in some older adults.
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2020 |
Gold, Brian Timothy Van Eldik, Linda J [⬀] |
P30Activity Code Description: To support shared resources and facilities for categorical research by a number of investigators from different disciplines who provide a multidisciplinary approach to a joint research effort or from the same discipline who focus on a common research problem. The core grant is integrated with the center's component projects or program projects, though funded independently from them. This support, by providing more accessible resources, is expected to assure a greater productivity than from the separate projects and program projects. |
Uk-Adrc Neuroimaging Supplement: Late and Part
PROJECT SUMMARY/ABSTRACT ? OVERALL (Adapted from Abstract of parent grant, UK-ADC) This is a proposal for a University of Kentucky Alzheimer?s Disease Research Center (UK-ADRC) neuroimaging supplement. This purpose of the supplement is to provide neuroimaging data on the UK-ADRC?s deeply phenotyped clinical cohort to the NIH?s recently funded initiative, Standardized Centralized Alzheimer's and Related Dementias Neuroimaging (SCAN). In addition, a secondary purpose of this supplement is to identify neuroimaging correlates of two AD-mimics: limbic-predominant age-related TDP-43 encephalopathy (LATE) and primary age-related tauopathy (PART). The UK-ADRC is an experienced and collaborative ADRC originally funded in 1985. Our principal mission is to serve as the focal point for all AD-related activities at UK and this region of the United States, by providing an environment and core resources that catalyze innovative research, outreach, education, and clinical programs. Our signature resources include: 1) a cognitively normal group of ~500 subjects followed longitudinally, with all committed to brain autopsy upon death; 2) a strong program in clinical-neuropathological correlations and short postmortem interval autopsies; 3) an established program studying preclinical biomarkers of AD using neuroimaging and biofluids; 4) an integrated centralized database and innovative biostatistical expertise to characterize clinical and biological transitions; and 5) a successful and close partnership with the African-American community and increased participation of underrepresented individuals in our longitudinal cohort and ADRC-affiliated research studies and clinical trials. The overall scientific emphasis of the UK-ADRC continues to be on our interrelated themes: Transitions & Translation. Our well-characterized, longitudinal cohort and historically strong neuropathology program focused on normal aging, preclinical disease states and early cognitive transitions have been central to our success in defining early pathogenic mechanisms underlying the transitions from normal cognitive aging to impairment. The depth of expertise and collaborative nature of our investigators have also resulted in substantial progress on translation of that knowledge into new targets and novel therapeutic strategies. The UK-ADRC provides an infrastructure and environment that focuses on these integrated themes and advances AD research, education, outreach, and clinical programs through highly interactive and effective components: Administrative Core, Clinical Core, Data Management and Statistics Core, Neuropathology Core, Outreach and Recruitment Core, Biomarker Core, and Research Education Component. The UK-ADRC will make resources from these Cores available to support the success of this ADRC neuroimaging supplement.
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2021 |
Gold, Brian Timothy |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Identifying Associations Between Brain Iron, Neurocognitive Networks and Protective Factors
Identifying Associations between Brain Iron, Neurocognitive Networks and Protective Factors Alzheimer?s disease (AD) involves accumulation of pathological levels of amyloid-beta (A?) and phospho-tau proteins. However, a significant proportion of individuals with AD pathology do not have clinical AD, indicating contributions of other factors. Novel in-vivo measures are required to track other factors contributing to AD-related cognitive declines. Increasing evidence suggests that age-related accumulation of brain iron and its correlates contribute to the manifestation of memory declines. Our recent neuroimaging results suggest that high brain iron concentration, measured with in vivo quantitative susceptibility mapping (QSM), is associated poor connectivity within brain memory networks. This proposal seeks to identify associations between QSM-based iron concentration and neurocognitive changes toward a goal of improving AD biomarkers. We will also define the interplay between QSM-based iron signal, AD pathology, inflammatory markers on cognitive declines. Finally, we will test the possibility that brain iron accumulation may be slowed by an antioxidant rich diet. We propose to study 140 healthy older adults using neuroimaging measures including fMRI and QSM, measures of CSF and plasma A?, p-tau and t-tau and inflammatory markers. Additional structural neuroimaging measures will include regional volumes, FLAIR imaging for quantification of WMH volumes and diffusion tensor imaging for quantification of regionally distributed white matter connectivity. A subset of participants will be complete the same CSF and imaging measures approximately 3 years later. We aim to identify (1) effects of QSM-based iron signal on functional and structural brain networks supporting cognition; (2) associations between brain iron, inflammatory markers, AD pathology and cognitive declines and; (3) modifiers of brain iron or its effects on cognition. We will test hypotheses that high QSM-based brain iron is associated with low connectivity in memory circuits independently of AD pathology but may and synergistically interacts with AD over time. We will also test the hypothesis that reserve factors will offset the effects of brain iron on cognitive functions via mechanisms of brain maintenance or plastic functional brain reorganization of large-scale brain functional networks in some older adults.
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