The long-term objective of our research is to better understand the mechanisms underlying both normal and abnormal ocular motor and vestibular function in Huntington's Disease (HD). Our recent research has shown that patients with HD have selective deficits in generating """"""""volitional"""""""" saccades (e.g. antisaccades and predictive saccades) as well as defects in suppression of unwanted reflexive saccades in response to novel stimuli.
The first aim of the present proposal is to develop more subtle ways of testing and quantifying the higher level control of saccadic and also pursuit eye movements. A new saccade paradigm will be tested that measures the amplitude and latency of saccades while making sequences of saccades to a series of seen or remembered targets. We will also compare the gain and timing of smooth pursuit movements to stimuli that produce a more reflexive response (sudden movement of a full field stimulus) with stimuli that produce a more volitional response (tracking of a small target moving on a visually rich background). We expect HD patients to show deficits in more volitional pursuit.
The second aim i s to evaluate further postural and vestibular control in patients with HD. Using moving platform posturography, we will measure postural control in patients with HD and compare the results with measurement of their vestibulo-ocular reflex. We will test the hypothesis that the ataxia of HD patients is related to a disorder of central processing of vestibular information. All of our testing results will be correlated with results of tests of neurological and psychological function and MRI studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center (P50)
Project #
5P50NS016375-15
Application #
3738271
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
15
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Wu, Dan; Faria, Andreia V; Younes, Laurent et al. (2017) Mapping the order and pattern of brain structural MRI changes using change-point analysis in premanifest Huntington's disease. Hum Brain Mapp 38:5035-5050
Faria, Andreia V; Ratnanather, J Tilak; Tward, Daniel J et al. (2016) Linking white matter and deep gray matter alterations in premanifest Huntington disease. Neuroimage Clin 11:450-460
Krause, Amanda; Mitchell, Claire; Essop, Fahmida et al. (2015) Junctophilin 3 (JPH3) expansion mutations causing Huntington disease like 2 (HDL2) are common in South African patients with African ancestry and a Huntington disease phenotype. Am J Med Genet B Neuropsychiatr Genet 168:573-85
Younes, Laurent; Ratnanather, J Tilak; Brown, Timothy et al. (2014) Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis. Hum Brain Mapp 35:792-809
Ross, Christopher A; Pantelyat, Alex; Kogan, Jane et al. (2014) Determinants of functional disability in Huntington's disease: role of cognitive and motor dysfunction. Mov Disord 29:1351-8
Hua, Jun; Unschuld, Paul G; Margolis, Russell L et al. (2014) Elevated arteriolar cerebral blood volume in prodromal Huntington's disease. Mov Disord 29:396-401
Unschuld, Paul G; Liu, Xinyang; Shanahan, Megan et al. (2013) Prefrontal executive function associated coupling relates to Huntington's disease stage. Cortex 49:2661-73
Biglan, K M; Dorsey, E R; Evans, R V V et al. (2012) Plasma 8-hydroxy-2'-deoxyguanosine Levels in Huntington Disease and Healthy Controls Treated with Coenzyme Q10. J Huntingtons Dis 1:65-9
Unschuld, Paul G; Joel, Suresh E; Liu, Xinyang et al. (2012) Impaired cortico-striatal functional connectivity in prodromal Huntington's Disease. Neurosci Lett 514:204-9
Unschuld, Paul G; Joel, Suresh E; Pekar, James J et al. (2012) Depressive symptoms in prodromal Huntington's Disease correlate with Stroop-interference related functional connectivity in the ventromedial prefrontal cortex. Psychiatry Res 203:166-74

Showing the most recent 10 out of 26 publications