The midbrain superior colliculus (SC) typically requires influence from ipsilateral visual cortex to play its critical role in generating visuomotor responses to contralateral cues. Thus, visual cortex lesions eliminate both normal visual feature processing and the visual functions of the ipsilateral SC. The result is a contralateral hemianopia. Although insights from animal models suggest amelioration of this deficit is possible through a number of interventions, none of these offers viable therapeutic options for human patients. However, using an animal model, we have recently demonstrated that a non-invasive rehabilitative training paradigm (using auditory-visual cues) can permanently reinstate vision in animals rendered hemianopic by unilateral removal of all contiguous areas of visual cortex. Unfortunately, we are largely ignorant of the neural changes that induce this reinstatement of vision. Nevertheless, our preliminary data do suggest that cross-modal training produces a functional reorganization in a cortico-SC circuit that involves specific regions of association cortex (i.e., the anterior ectosylvian sulcus, AES). These adaptive changes render SC neurons once again capable of visual responses and of supporting visual behavior in the absence of ipsilateral visual cortex ? presumably via compensatory inputs from AES. Our objective here is to use physiological and behavioral techniques to evaluate the physiological consequences of large visual cortex lesions on the neuronal properties in the AES and SC of hemianopic animals, and to determine how their properties are modified by cross-modal training so that vision is restored. Our overarching hypothesis is that cross-modal training, via Hebbian mechanisms, is able to amplify the normally subthreshold inputs to these regions from sources other than visual cortex. Understanding how the inherent plasticity of this circuit can be harnessed via non-surgical, behavioral training techniques to ameliorate hemineglect will help us understand the latent functional capabilities of this system, and provide invaluable insights to facilitate strategies for dealing with this debilitating condition in human patients.

Public Health Relevance

Hemianopia is a common consequence of stroke, seizure, and traumatic brain injury, and a condition that substantially degrades one?s quality of life. Our previous work shows that there is an effective non-invasive cross-modal training program that can ameliorate this condition, thereby restoring sight in the previously blind visual field. The present proposal will determine the changes in the brain through which this rehabilitation is produced, and in doing so lead to a better understanding of how visual functions are segregated in the brain, how other senses enhance the plasticity of this system, and how to develop more effective strategies for rehabilitating visual dysfunction.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Flanders, Martha C
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Wake Forest University Health Sciences
Anatomy/Cell Biology
Schools of Medicine
United States
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Cuppini, Cristiano; Stein, Barry E; Rowland, Benjamin A (2018) Development of the Mechanisms Governing Midbrain Multisensory Integration. J Neurosci 38:3453-3465
Bach, Eva C; Vaughan, John W; Stein, Barry E et al. (2017) Pulsed Stimuli Elicit More Robust Multisensory Enhancement than Expected. Front Integr Neurosci 11:40