In adulthood, stroke damage to the primary visual cortex (V1) causes a large, contralateral loss of conscious vision referred to as hemianopia or cortical blindness (CB). Although this condition affects up to million new cases each year in the US alone, there is a total lack of accepted vision restoration therapies ? in marked contrast with early-onset physical therapies prescribed to those with motor cortex damage. Two decades of work in chronic CB patients, whose deficits are deemed stable, permanent and thus amenable to scientific study, have generated one method consistently able to recover vision after long-standing V1 damage: gaze- contingent visual training to detect or discriminate stimuli in the blind field. Over the last 2 grant periods, we have taken clear leadership in the field, providing hope that an effective therapy for CB may finally be on the horizon. However, while characterizing training-induced recovery and its underlying mechanisms, we also found that recovery in chronic CB requires months of daily training and the vision restored is low-contrast, coarse, impaired by excessive internal processing noise and restricted to the blind field perimeter. Accumulating evidence suggests that these limitations may occur because chronic patients have lost a substantial portion of neurons that contribute to vision fundamentals not only in V1, but through retrograde degeneration, in the dorsal lateral geniculate nucleus (dLGN) and retina. Our new pilot data show subacute CB patients <6 months post-stroke to lack significant signs of degeneration, and more than half of subacutes tested retained visual discrimination abilities in their blind field, which disappeared by the start of the chronic period (6 months post-stroke). Moreover, when training was administered to subacutes, they recovered the same discrimination abilities as chronics, but much faster, and with recovery extending deeper into their blind field. These data form a strong premise for testing the hypothesis that substantial differences in plastic potential between subacute and chronic V1-stroke visual systems can be exploited to maximize visual restoration in CB, and that the extent of recovery attainable is limited by the amount of retrograde degeneration sustained. We now propose to:
(Aim 1) assess how visual performance relates to structural evidence of retrograde degeneration in the subacute period post-V1-stroke. We will then (Aim 2) assess the impact of subacute training on blind-field functions, the progression of retrograde degeneration and the continued potential for training-induced recovery in the chronic period. Finally, we will (Aim 3) contrast mechanistic substrates of perceptual learning in subacute & chronic CB. All in all, the work proposed is unique in the field, which it stands to advance significantly by generating entirely new knowledge and understanding of the change in visual plastic potential with time in the early period after permanent V1 damage in humans. This knowledge is important both neuro-scientifically, and for devising more effective treatment and realistic outcome expectations for this growing patient population.
The proposed work examines changes in plastic potential of the visual system with time from stroke affecting primary visual cortex. We will measure structural and mechanistic aspects of progressive degeneration along the early visual pathways, correlating them with changes in visual performance and responsiveness to visual restoration training in the blind field. This project will advance both scientific knowledge, as well as technical capability and clinical practices for restoring vision and quality of life for people suffering from cortical blindness.
|Cavanaugh, Matthew R; Huxlin, Krystel R (2017) Visual discrimination training improves Humphrey perimetry in chronic cortically induced blindness. Neurology 88:1856-1864|
|Cavanaugh, Matthew R; Barbot, Antoine; Carrasco, Marisa et al. (2017) Feature-based attention potentiates recovery of fine direction discrimination in cortically blind patients. Neuropsychologia :|