2003 — 2007 |
Disbrow, Elizabeth A |
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. |
Linking Functional Imaging, Neurophysiology &Anatomy @ University of California Davis
[unreadable] DESCRIPTION (provided by applicant): [unreadable] Brain imaging methods such as functional magnetic resonance imaging (fMRI), magnetic source imaging (MSI) and diffusion tensor imaging (DTI) are rapidly evolving as essential tools for assaying normal and abnormal brain function. The overall goal of this research is to enhance our understanding of the relationship between the signals measured using these imaging techniques and the underlying neural activity. We propose to conduct a series of experiments in anesthetized macaque monkeys to examine the correlation between functional brain imaging signals, specifically the BOLD signals of fMRI, the modeled current sources of MSI, and the imaging of white-matter tracts with DTI, with "gold standard" single and multi-unit electrophysiological recordings, and neuroanatomical tracing techniques. The specific aims are 1) To measure the stimulus evoked changes in magnitude, location and timing of functional brain imaging signals and relate them to changes in underlying neural activity, 2) To correlate non-invasive anatomic connectivity measures derived from tractography of DTI with connectivity derived using neuroanatomical techniques, and 3) To compare measures of functional connectivity based on the covariance of fMRI and MSI time-series with anatomic connectivity derived from DTI and neuroanatomic studies. These experiments represent a unique collaborative effort to combine several techniques in the same animal to generate a better understanding of the ability of modem imaging techniques to track changes in the nervous system under varying stimulus conditions and to uncover the circuitry necessary for complex sensory abilities. Our efforts are among the first to bridge the gap between imaging, neurophysiology and anatomy, an essential step in relating the wealth of electrophysiological recording data from macaque monkeys to the human cortex, and in understanding complex functions such as the sensory integration necessary for cognitive processes like object recognition and language. [unreadable] [unreadable]
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2004 |
Disbrow, Elizabeth A |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Linking Functional Imaging, Neurophysiology and Anatomy @ University of California Davis
functional magnetic resonance imaging; neurophysiology; neuroanatomy; Primates; animal colony; bioimaging /biomedical imaging; clinical research;
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2006 — 2008 |
Disbrow, Elizabeth A |
P51Activity Code Description: To support centers which include a multidisciplinary and multi-categorical core research program using primate animals and to maintain a large and varied primate colony which is available to affiliated, collaborative, and visiting investigators for basic and applied biomedical research and training. |
Linking Functional Imaging, Nuerophysiology &Anatomy @ University of California Davis |
1 |
2009 — 2010 |
Disbrow, Elizabeth A |
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. |
Neural Substrates of Switching in Parkinson's Disease @ University of California At Davis
The focus of the proposed work is to determine the underlying neural substrates of task switching deficits in Parkinson's disease (PD) and to link these dysfunctions with behavioral impairments in everyday life. Although PD was initially considered a motor disorder, deficits in cognitive function contribute significantly to the hallmark signs of PD. However, there is a lack of consensus regarding the pathophysiology of these deficits primarily because of the diversity of tasks previously studied and the challenge of separating the cognitive aspects, such as task switching, from motor execution. Task switching is the ability to make a change in the plan (switching from one response option to another, e.g. pressing one button vs. another) and switching can be externally generated, based on environmental stimuli, or internally or self-generated. We have chosen to study motor planning, specifically switching, because it is a critical part of normal motor behavior and is intimately intertwined with the motor deficits associated with PD. Our HYPOTHESIS is that the planning of these aspects of switching behavior relies on separate basal ganglia (BG)-thalamocortical circuits that are differentially affected by PD. SPECIFIC AIM 1 is to test the prediction that PD-related behavioral deficits in internally generated and externally cued switching are correlated with individual BG-thalamocortical circuits that are differentially affected by PD. SPECIFIC AIM 2 is to determine if parkinsonian switching deficits and related abnormalities in BG-thalamocortical activity are correlated with the hallmark signs of PD such as bradykinesia, as well as impairments in daily activities including verbal fluency and gait initiation. We have designed a behavioral task that will allow us to dissociate not only motor planning from execution, but also internally vs. externally generated switching. We will measure patterns of cortical activation and synchronization with functional magnetic resonance imaging and magnetoencephalography, respectively, to obtain complimentary anatomic and physiologic views of switching dysfunctions in PD. Further, we propose to provide a link between the abnormal brain activity of PD and difficulties in everyday life. SIGNIFICANCE: While cognitive abilities are an integral part of normal motor behavior, our developing appreciation of cognitive dysfunction in PD has not yet been incorporated into standard clinical practice. Cognitive symptoms differ among parkinsonian patients, change over the course of the disease, and may be differentially affected by dopamine replacement, yet the treatment across patients is similar. Our results can be used to inform target-specific drug development, direct tailored cognitive neuro-rehabilitation, and evaluate emerging PD treatment options. 2.
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