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Cortical and Brainstem Contributions to Binocular Eye Movements

Award Number: R01EY034626
ORGANIZATION: NATIONAL EYE INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2023
PERIOD OF PERFORMANCE END DATE: 06/30/2027
AWARD TERMINATION DATE: 05/29/2025

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Cortical and Brainstem Contributions to Binocular Eye Movements - The proposal challenges Hering’s theories of unitary conjugate and vergence commands that guide research on the neural architecture of oculomotor systems and buttress strabismus intervention. In most oculomotor research one eye is recorded, assuming that both eyes are “yoked”, rotating together. Yet most eye movements acquire objects divorced from frontoparallel or midline trajectories, and their control is poorly understood. While some evidence suggests the eyes are controlled independently, the assumptions of yoked control nevertheless dominate oculomotor research. Consequently, neural oculomotor structures are characterized as issuing cyclopean eye rotation commands. Recent monocular pursuit data from our lab argue against yoked control of vergence movements, which continues to form the basis of almost all oculomotor control models. We propose a new alternative model architecture with two synergistic components. One is cognitive and cortical and it moves each eye slowly and separately. The other is reflexive and in the brainstem, and it moves the eyes rapidly and conjugately as a pair. Our project has the potential to initiate revision of strabismus assessment by questioning the validity of the critical AC/A ratio diagnostic, and potentially guide clinicians’ decisions regarding intervention. Aims assess: Aim 1. Does monocular viewing reveal hidden architecture of binocular eye movement coordination? Our preliminary data show that during midline pursuit an occluded eye rotates inappropriately for the target’s motion, often with conjugacy. This might be because the target is misperceived as displaced off the midline, or eye rotation drifts in a random direction due to misperception of target depth. Alternatively, retinal motion in the viewing eye triggers brainstem conjugate circuitry that adds conjugacy to the covered eye’s behavior as our model postulates. We test if conjugacy arises because of misperceptions or of conjugate circuitry activation. Aim 2. Do asymmetric eye movements reveal contributions of conjugate and independent systems? In our model, the output of the rapid conjugate system is combined with that of a system that rotates each eye slowly and independently. We will test predictions of the model concerning how inappropriate ocular intrusions with Müller alignment and curiously slow midline saccades occur, as well as how asymmetric eye movements acquire targets in 3D space. Aim 3. Is the independent system influenced by cognition while the conjugate system is not? In our data, monocular viewing of an object moving in depth often succeeds in driving vergence pursuit in the covered eye but fails completely to drive vergence saccades. Furthermore, in the dark, smooth vergence follows self-generated limb motion, but inappropriate, apparently reflexive conjugate saccades occur when looking between thumbs “aligned” at different depths. We will test if only the slow system or rapid one is influenced by cognition, and if they use endogenous signals to track targets.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $484,509 )
2026	2026	THE SMITH-KETTLEWELL EYE RESEARCH INSTITUTE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	001	4	7/22/2026	NON-COMPETING CONTINUATION	$484,509
2026	2025	THE SMITH-KETTLEWELL EYE RESEARCH INSTITUTE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	3	12/4/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $484,509

Issue Date FY: 2025 ( Subtotal = $484,509 )
2025	2025	THE SMITH-KETTLEWELL EYE RESEARCH INSTITUTE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	001	3	8/8/2025	NON-COMPETING CONTINUATION	$484,509
2025	2024	THE SMITH-KETTLEWELL EYE RESEARCH INSTITUTE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	2	5/29/2025	TERMINATION	$0
														Subtotal = $484,509

Issue Date FY: 2024 ( Subtotal = $516,634 )
2024	2024	THE SMITH-KETTLEWELL EYE RESEARCH INSTITUTE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	2	6/14/2024	NON-COMPETING CONTINUATION	$484,509
2024	2024	THE SMITH-KETTLEWELL EYE RESEARCH INSTITUTE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	001	2	7/24/2024	SUPPLEMENT FOR EXPANSION	$32,125
														Subtotal = $516,634

Issue Date FY: 2023 ( Subtotal = $532,358 )
2023	2023	SMITH-KETTLEWELL EYE RESEARCH INSTITUTE, THE	2318 FILLMORE ST	SAN FRANCISCO	CA	94115	SAN FRANCISCO	USA	Vision Research	000	1	7/21/2023	NEW	$532,358
														Subtotal = $532,358

Grand Total All Awards = $2,018,010

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Cortical and Brainstem Contributions to Binocular Eye Movements

Award Number: R01EY034626

ORGANIZATION: NATIONAL EYE INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2023

PERIOD OF PERFORMANCE END DATE: 06/30/2027

AWARD TERMINATION DATE: 05/29/2025

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