Cortical visual mapping following ocular gene augmentation therapy for achromatopsia

The ability of the adult human brain to develop function following correction of congenital deafferentation is controversial. Specifically, cases of recovery from congenital visual deficits are rare. CNGA3-achromatopsia is a congenital hereditary disease caused by cone-photoreceptor dysfunction, leading to impaired acuity, photoaversion, and complete color blindness. Essentially, these patients have rod-driven vision only, seeing the world in blurry shades of grey. We use the uniqueness of this rare disease, in which the cone-photoreceptors and afferent fibers are preserved but do not function, as a model to study cortical visual plasticity. We had the opportunity to study two CNGA3-achromatopsia adults (one female) before and after ocular gene augmentation therapy. Alongside behavioral visual tests, we used novel fMRI based measurements to assess participants’ early-visual population receptive-field sizes and color regions. Behaviorally, minor improvements were observed including reduction in photoaversion, marginal improvement in acuity and a new ability to detect red color. No improvement was observed in color arrangement tests. Cortically, pre-treatment, patients’ population receptive-field sizes of early-visual areas were untypically large, but decreased following treatment specifically in the treated eye. We suggest this demonstrates cortical ability to encode new input, even at adulthood. On the other hand, no activation of color specific cortical regions was demonstrated in these patients neither before nor up to one year post-treatment. The source of this deficiency might be attributed either to insufficient recovery of cone function at the retinal level or to challenges the adult cortex faces when computing new cone-derived input to achieve color perception.