Stroke is a leading cause of serious long-term adult-onset disability in the United States, with 25% of stroke patients experiencing some type of visual field deficit. Stroke in the territory of the posterior cerebral artery (PCA) causes blindness in all or parts of the visual hemi-field contralateral to the lesion. This blind field begins to contract within the first 10 days following stroke with some patients continuing to improve out to 6 months. While about 50% of patients experience some degree of visual improvement, only 12.5% of patients experience complete recovery. The underlying mediators of recovery remain poorly understood due to the brain's multifaceted response to ischemic injury. We test the hypothesis that post-stroke recovery is associated with: 1) neurovascular repair and 2) experience-dependent induction of neuroplasticity. To test this hypothesis, the proposed project details a longitudinal study of changes in visual perception and neural activity in stroke patients at 1 week, 1 month, and 3 months after stroke in the territory of the PCA. Visual recovery will be quantified with a clinical neuro-ophthalmological test of perceptual vision and correlated with different measures of neural activity using functional magnetic resonance imaging (fMRI).
Aim 1 tests the hypothesis that spontaneous visual recovery at 1 month, but not additional spontaneous recovery at 3 months, is specifically due to normalization of the perilesional tissue's neurovascular response to visual stimuli. This normalization could reflect recovery of previously dysfunctional ischemia-resilient neurons and/or vascular repair. The neurovascular response will be quantified at each time point with fMRI by calculating the time to peak activation following presentation of a full-field visual stimulus.
Aim 2 tests the hypothesis that tuning curve widening in perilesional cortex differentially underlies spontaneous perceptual visual recovery at 1 month, while shifts in the preferred retinotopic focus of perilesional voxels differentially explains additional spontaneous visual recovery at 3 months. This hypothesis is consistent with a model of post-stroke neuroplasticity in the motor cortex in which there is an initial non-specific expansion of activation that later consolidates and regains specificity but for a different location. These changes in a perilesional voxel's activation profile will be quantified from fMRI runs in which the patient views a pseudo-random presentation of flickering checkerboard wedges in 12 non-overlapping locations. The degree to which each voxel responds to each wedge location will constitute that voxel's spatial location tuning curve. Understanding how the brain's response after stroke influences visual perception will inform neuroplasticity research, clinical targets for rehabilitation treatments, outcome measures for clinical trials, and best practices for conducting fMRI research in a patient population with altered neurovascular functioning.

Public Health Relevance

Stroke is a leading cause of serious long-term adult disability in the United States, with 25% of stroke patients experiencing some type of visual field impairment. The proposed project is a longitudinal study of patients with visual deficits secondary to stroke with the goal of determining how spontaneous recovery of visual perception can be explained by neural/vascular repair and induction of neuroplasticity. Understanding how the brain's response after stroke influences visual perception will inform neuroplasticity research, clinical targets for rehabilitation treatments, outcome measures for clinical trials, and best practices for conducting fMRI research in a stroke patient population.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30EY027988-01A1
Application #
9467882
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Agarwal, Neeraj
Project Start
2018-09-24
Project End
2022-09-23
Budget Start
2018-09-24
Budget End
2019-09-23
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Rochester
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627