This application proposes studies that build upon our findings in the previous grant period on the role of aging, dry eye and blink adaptation in the development of the eyelid dystonia, benign essential blepharospasm (BEB). These studies explained important features that characterize BEB: (1) disease onset typically occurs after age 50; (2) trigeminal reflex blinks are hyperexcitable; (3) dry eye frequently precedes disease onset; and (4) repetitive bursts of eyelid muscle contractions create involuntary spasms of lid closure. We found that aging significantly increased trigeminal reflex blink excitability after age 60 in humans. This increased excitability pointed to reductions in trigeminal inhibition with aging as a contributing factor in the development of BEB. In humans, we demonstrated that the blink adaptations in response to dry eye included increased trigeminal reflex blink excitability and the generation of multiple blinks to a single trigeminal stimulus, blink oscillations. Because shortening the interval between the occurrences of the blink oscillations of dry eye would create the spasms of lid closure present in BEB, disturbing the blink adaptations to dry eye might generate BEB. We confirmed this hypothesis by creating a rodent model of blepharospasm. Thus, our previous work revealed that a disturbance in blink adaptation, motor learning, was a critical component of the origin of BEB. The primary goals of this application are to characterize the two error signals that initiate and modulate blink adaptation and to determine the role of the cerebellum in the origin and maintenance of BEB. We propose to: (1) determine what blink adaptations a single error signal engenders in humans; (2) establish the neural changes in the cerebellum and trigeminal complex initiated by these error signals in rodents; and (3) characterize the role of the cerebellum in initiating and maintaining BEB using our animal model. The data from these experiments may establish the neural underpinnings of and point toward new treatments.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY007391-17
Application #
6786788
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Hunter, Chyren
Project Start
1987-09-30
Project End
2006-02-28
Budget Start
2004-02-29
Budget End
2005-02-28
Support Year
17
Fiscal Year
2004
Total Cost
$376,250
Indirect Cost
Name
State University New York Stony Brook
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Kaminer, Jaime; Thakur, Pratibha; Evinger, Craig (2015) Effects of subthalamic deep brain stimulation on blink abnormalities of 6-OHDA lesioned rats. J Neurophysiol 113:3038-46
Evinger, Craig (2015) Benign Essential Blepharospasm is a Disorder of Neuroplasticity: Lessons From Animal Models. J Neuroophthalmol 35:374-9
Kaminer, Jaime; Thakur, Pratibha; Evinger, Craig (2014) Frequency matters: beta-band subthalamic nucleus deep-brain stimulation induces Parkinsonian-like blink abnormalities in normal rats. Eur J Neurosci 40:3237-42
Ryan, Michael; Kaminer, Jaime; Enmore, Patricia et al. (2014) Trigeminal high-frequency stimulation produces short- and long-term modification of reflex blink gain. J Neurophysiol 111:888-95
Evinger, Craig (2013) Animal models for investigating benign essential blepharospasm. Curr Neuropharmacol 11:53-8
Powers, Alice S; Basso, Michele A; Evinger, Craig (2013) Blinks slow memory-guided saccades. J Neurophysiol 109:734-41
Dolgonos, Sarah; Ayyala, Haripriya; Evinger, Craig (2011) Light-induced trigeminal sensitization without central visual pathways: another mechanism for photophobia. Invest Ophthalmol Vis Sci 52:7852-8
Kaminer, Jaime; Powers, Alice S; Horn, Kyle G et al. (2011) Characterizing the spontaneous blink generator: an animal model. J Neurosci 31:11256-67
Schade Powers, Alice; Coburn-Litvak, Pamela; Evinger, Craig (2010) Conditioned eyelid movement is not a blink. J Neurophysiol 103:641-7
Lepora, N F; Porrill, J; Yeo, C H et al. (2009) Recruitment in retractor bulbi muscle during eyeblink conditioning: EMG analysis and common-drive model. J Neurophysiol 102:2498-513

Showing the most recent 10 out of 46 publications