Phonemic fluency and brain connectivity in age-related macular degeneration: a pilot study.

Abstract

Age-related macular degeneration (AMD), the leading cause of blindness in developed nations, has been associated with poor performance on tests of phonemic fluency. This pilot study sought to (1) characterize the relationship between phonemic fluency and resting-state functional brain connectivity in AMD patients and (2) determine whether regional connections associated with phonemic fluency in AMD patients were similarly linked to phonemic fluency in healthy participants. Behavior-based connectivity analysis was applied to resting-state, functional magnetic resonance imaging data from seven patients (mean age=79.9±7.5 years) with bilateral AMD who completed fluency tasks prior to imaging. Phonemic fluency was inversely related to the strength of functional connectivity (FC) among six pairs of brain regions, representing eight nodes: left opercular portion of inferior frontal gyrus (which includes Broca's area), left superior temporal gyrus (which includes part of Wernicke's area), inferior parietal lobe (bilaterally), right superior parietal lobe, right supramarginal gyrus, right supplementary motor area, and right precentral gyrus. The FC of these reference links was not related to phonemic fluency among 32 healthy individuals (16 younger adults, mean age=23.5±4.6 years and 16 older adults, mean age=68.3±3.4 years). Compared with healthy individuals, AMD patients exhibited higher mean connectivity within the reference links and within the default mode network, possibly reflecting compensatory changes to support performance in the setting of reduced vision. These findings are consistent with the hypothesis that phonemic fluency deficits in AMD reflect underlying brain changes that develop in the context of AMD.

Department

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Citation

Published Version (Please cite this version)

10.1089/brain.2014.0277

Publication Info

Whitson, Heather E, Ying-Hui Chou, Guy G Potter, Michele T Diaz, Nan-Kuei Chen, Eleonora M Lad, Micah A Johnson, Scott W Cousins, et al. (2015). Phonemic fluency and brain connectivity in age-related macular degeneration: a pilot study. Brain connectivity, 5(2). pp. 126–135. 10.1089/brain.2014.0277 Retrieved from https://hdl.handle.net/10161/27509.

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Scholars@Duke

Whitson

Heather Elizabeth Whitson

Professor of Medicine

Dr. Whitson's research is focused on improving care options and resilience for people with multiple chronic conditions.  In particular, she has interest and expertise related to the link between age-related changes in the eye and brain (e.g., How does late-life vision loss impact the aging brain or cognitive outcomes?  Is Alzheimer's disease associated with distinctive changes in the retina, and could such changes help diagnose Alzheimer's disease early in its course?).  Dr. Whitson leads a collaborative Alzheimer's Disease initiative that brings together investigators from Duke University and the University of North Carolina (UNC) at Chapel Hill, with a bold vision to transform dementia research and care across Eastern North Carolina. Dr. Whitson is also interested in improving health services to better meet the needs of medically complex patients.  Within the Duke Aging Center, she leads research efforts aimed at promoting resilience to late-life stressors (e.g., surgery, sensory loss, infection).  She has developed a novel rehabilitation model for people with co-existing vision and cognitive deficits, and she is part of a inter-disciplinary team seeking to improve peri-operative outcomes for frail or at-risk seniors who must undergo surgery.  As a co-leader of a national resilience collaborative, she seeks to better understand the biological and psychological factors that determine how well we "bounce back" after health stressors.  

Potter

Guy Glenn Potter

Associate Professor in Psychiatry and Behavioral Sciences
Cousins

Scott William Cousins

Robert Machemer, M.D. Distinguished Professor of Ophthalmology

Scott W. Cousins, M.D. is currently the Robert Machemer, M.D. Professor of Ophthalmology and Immunology, Vice Chair for Research, and Director of the Duke Center for Macular Diseases at Duke Eye Center. As Vice Chair, he oversees all basic science research as well as the Ophthalmology Site-Based Research Group, which administrates clinical research for Duke Eye Center. Dr. Cousins is also Medical Director of Hospital-Based Imaging and Procedures for Duke Eye Center.

Dr. Cousins is a retina-trained ophthalmologist who specializes in the diagnosis and treatment of macular diseases, especially age-related macular degeneration (AMD), diabetic retinopathy, and retinal vascular diseases. Dr. Cousins is active in both clinical and laboratory research. In his clinical practice, Dr. Cousins is involved in many trials and innovative therapies for the treatment of macular diseases, especially AMD and diabetic retinopathy. He has served as site PI for numerous phase1-3 clinical trials in AMD, diabetic retinopathy, and other retinal disorders. He has served as a consultant or member of data safety monitoring committees (DSMC) for numerous pharmaceutical and biotechnology startup companies.

In his scientific laboratory, Dr. Cousins pursues both NIH-funded and industry-funded research in various areas of dry and wet AMD. In particular, he is studying the role of circulating bone marrow-derived progenitors (stem cells) in contributing to wet AMD. His laboratory is attempting to develop treatments for dry macular degeneration and improving vision in eyes with wet macular degeneration. His program is also developing blood tests and new imaging technologies for the identification of patients who are at high risk for progressing into complications.

Dr. Cousins has published over 100 peer-reviewed manuscripts, book chapters, and other publications addressing topics of research or clinical care of retinal disease, especially AMD. In 2006, Dr. Cousins was awarded the prestigious Alcon Research Foundation Clinician Scientist Award. In 2008, the National Institutes of Health invited Dr. Cousins to join the National Advisory Eye Council. Dr. Cousins is also a member of the American Academy of Ophthalmology, the American Society of Retina Specialists, the Retina Society, the Association for Research in Vision and Ophthalmology, the American Association of Immunologists, and the American Medical Association.

In 2010, Dr. Cousins was named one of the “Top 34 Ophthalmologists in the United States” by Becker’s ASC Review, a leading source of business and legal news for ambulatory surgery centers. They cited his leadership of the Duke Center for Macular Diseases and his ongoing research in macular degeneration as reasons for the honor.

Madden

David Joseph Madden

Professor in Psychiatry and Behavioral Sciences

My research focuses primarily on the cognitive neuroscience of aging: the investigation of age-related changes in perception, attention, and memory, using both behavioral measures and neuroimaging techniques, including positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and diffusion tensor imaging (DTI).

The behavioral measures have focused on reaction time, with the goal of distinguishing age-related changes in specific cognitive abilities from more general effects arising from a slowing in elementary perceptual processes. The cognitive abilities of interest include selective attention as measured in visual search tasks, semantic and episodic memory retrieval, and executive control processes.

The behavioral measures are necessary to define the cognitive abilities of interest, and the neuroimaging techniques help define the functional neuroanatomy of those abilities. The PET and fMRI measures provide information regarding neural activity during cognitive performance. DTI is a recently developed technique that images the structural integrity of white matter. The white matter tracts of the brain provide critical pathways linking the gray matter regions, and thus this work will complement the studies using PET and fMRI that focus on gray matter activation.

A current focus of the research program is the functional connectivity among regions, not only during cognitive task performance but also during rest. These latter measures, referred to as intrinsic functional connectivity, are beginning to show promise as an index of overall brain functional efficiency, which can be assessed without the implementation of a specific cognitive task. From DTI, information can be obtained regarding how anatomical connectivity constrains intrinsic functional connectivity. It will be important to determine the relative influence of white matter pathway integrity, intrinsic functional connectivity, and task-related functional connectivity, as mediators of age-related differences in behavioral measures of cognitive performance.

Ultimately, the research program can help link age-related changes in cognitive performance to changes in the structure and function of specific neural systems. The results also have implications for clinical translation, in terms of the identification of neural biomarkers for the diagnosis of neural pathology and targeting rehabilitation procedures.


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