Even though the blink reflex is a common clinical test, the detailed organization of the neural circuits that underlie blinking is uncertain. Establishing this neural circuitry is crucial for effectively interpreting the results of this common clinical test. This application proposes to investigate two clinically significant facets of blink reflex organization - the linkage of blinks with saccadic gaze shifts and the role of compensatory modification of the blink reflex in diseases like hemifacial spasm. Blinking and gaze continuously interact. For example, smooth pursuit eye movements suppress spontaneous blinking while large saccadic eye or head movements evoke a blink. Blinking also influences gaze. Stimuli that elicit reflex blinks also cause cocontraction of the extraocular muscles and modulate the activity of neck muscles. Disease states modify this reciprocal linkage. Patients with abnormally slow saccadic eye movements can make normal velocity saccades when they combine the saccade with a voluntary blink. Conversely, blinks induce saccadic oscillations in some patients. A major goal of this proposal is to ascertain the neural circuits linking blinking and gaze. This application proposes physiological and anatomical studies to identify and characterize neural circuits linking gaze and blinking in rodents. Using behavioral experiments and detailed organization of the linkage will be investigated in rodents and humans with known diseases. Uncontrollable blinking characterizes the human disease of hemifacial spasm. This disease arises from damage to the VIIth nerve that leads to facial muscle weakness. The usual treatment for such spasms is further weakening of the muscle with surgery or repeated injections of botulinum toxin A. It is possible, however, that the hyperexcitability of the blink reflex is an extreme attempt by the nervous system to compensate for the original muscle weakness. Thus, treatments that eliminate the spasms by weakening the muscle may actually increase the neural hyperexcitability that initiated the disorder. A major goal of this proposal is to determine whether muscle weakening induces or exacerbates hemifacial spasm in humans. These studies will use physiological and behavioral approaches to test this hypothesis in humans and rodents. If successful, these studies will be extended to ascertain if aiding lid closure is a more effective treatment for lid spasms than muscle weakening. The studies outlined in this proposal will significantly expand the value of the blink reflex as a clinical tool. Moreover, if the hypothesis concerning the causes of hemifacial spasm is correct, these investigations may be pivotal in developing improved treatments for this disease.
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