Our long-term goal is to improve the efficacy of treatment eyelid motility disorders through basic and clinical understanding of blink control systems. Dopaminergic neurotransmission deficits are an etiologic factor in at least some age-linked motility defects.
Specific Aim 1 evaluates the role that dopamine plays in the neural control of blinking in a subhuman primate. We will examine eyelid kinematics, main sequence relationships, and sensory- motor interactions in models of dopamine depletion. Findings should define the role that dopamine plays in the normal control of blinkmetrics and excitability. Second, data from the current project period support the hypothesis that blepharospasm results from an interaction orf corneal irritation and/or weakness of eyelid closure with compromised adaptive regulation of blinking.
Specific Aim 2 tests the notion that blepharospasm results from a two stage process. In this model, a requirement to adapt to a peripheral insult by increasing blink gain must be coupled with a loss of inhibitory control over the adaptive process. We will examine dynamic, longitudinal changes in adaptive regulation of blink in an alert monkey model in which blinking is compromised monocularly with botulinum toxin and dopaminergic transmission is impaired via neurotoxin. To further describe blepharospasm and address the hypothesis that adaptive systems may contribute to disease, we will continue and extend correlative behavioral/physiological studies in patients with both blepharospasm and Bell's palsy-induced blepharospasm, a new class of blepharospasm that we identified in the current grant period. Finally, in the adaptive control of blinking, the central control system must compare differences between the intended and actual blink in order to make appropriate adjustments in motor output. We propose that somatosensory information provides the feedback required for adaptive control of blink motor system output. Feedback as to blink efficacy is matched to a copy of the motor command and the command adjusted so that intended and actual eyelid movements match.
In Specific Aim 3, we use a primate model in studies designed to determine whether elimination of trigeminal sensory feedback comprises the ability to execute the adaptive changes in blink that are required by unilateral orbicularis oculi paresis. Taken together, the studies proposed in this application will characterize key aspects of blink adaptive control systems and clarify their adaptive, and potentially maladaptive, roles in disorders of eyelid motility.
|Baker, Robert S; Radmanesh, Shardan M; Abell, Karen M (2002) The effect of apomorphine on blink kinematics in subhuman primates with and without facial nerve palsy. Invest Ophthalmol Vis Sci 43:2933-8|
|Abell, K M; Cowen, D E; Baker, R S et al. (1999) Eyelid kinematics following blepharoplasty. Ophthal Plast Reconstr Surg 15:236-42|
|Abell, K M; Baker, R S; Cowen, D E et al. (1998) Efficacy of gold weight implants in facial nerve palsy: quantitative alterations in blinking. Vision Res 38:3019-23|
|Sun, W S; Baker, R S; Chuke, J C et al. (1997) Age-related changes in human blinks. Passive and active changes in eyelid kinematics. Invest Ophthalmol Vis Sci 38:92-9|
|Baker, R S; Sun, W S; Hasan, S A et al. (1997) Maladaptive neural compensatory mechanisms in Bell's palsy-induced blepharospasm. Neurology 49:223-9|
|Hasan, S A; Baker, R S; Sun, W S et al. (1997) The role of blink adaptation in the pathophysiology of benign essential blepharospasm. Arch Ophthalmol 115:631-6|
|Huffman, M D; Baker, R S; Stava, M W et al. (1996) Kinematic analysis of eyelid movements in patients recovering from unilateral facial nerve palsy. Neurology 46:1079-85|
|Porter, J D; Baker, R S (1996) Muscles of a different 'color': the unusual properties of the extraocular muscles may predispose or protect them in neurogenic and myogenic disease. Neurology 46:30-7|
|Porter, J D; Baker, R S; Ragusa, R J et al. (1995) Extraocular muscles: basic and clinical aspects of structure and function. Surv Ophthalmol 39:451-84|
|Stava, M W; Huffman, M D; Baker, R S et al. (1994) Conjugacy of spontaneous blinks in man: eyelid kinematics exhibit bilateral symmetry. Invest Ophthalmol Vis Sci 35:3966-71|
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