Compensatory Cross-Modal Plasticity Persists After Sight Restoration.

Area of Science:

• Neuroscience
• Ophthalmology
• Genetics

Background:

• Sensory deprivation causes cross-modal plasticity, where intact senses reorganize to occupy cortical space of the lost sense.
• Cross-modal plasticity's role in restoring a lost sense, like vision, is debated, with some viewing it as maladaptive and others as crucial for neuronal maintenance.
• The first retinal gene therapy (GT) for inherited blindness has renewed interest in understanding neuroplastic changes during vision restoration.

Purpose of the Study:

• To investigate neuroplastic changes in patients with inherited blindness undergoing gene therapy for vision restoration.
• To examine cross-modal plasticity, specifically auditory responses in the visual cortex, before and after GT in RPE65 patients.
• To assess the impact of cross-modal plasticity on the success of vision restoration.

Main Methods:

• Functional magnetic resonance imaging (fMRI), including task-based and resting-state (rsfMRI), was used to compare RPE65 patients with sighted controls.
• Auditory and visual stimuli were presented, and brain activity was recorded before and 3 years after GT in RPE65 patients.
• Connectivity between auditory and visual brain regions was analyzed using rsfMRI.

Main Results:

• RPE65 patients exhibited robust auditory responses in the occipital cortex, overlapping visual responses, which significantly increased 3 years post-GT.
• Sighted controls showed no evidence of auditory cross-modal plasticity.
• rsfMRI revealed enhanced connectivity between auditory and visual areas 3 years after GT in RPE65 patients, compared to baseline.

Conclusions:

• RPE65 patients demonstrate auditory cross-modal plasticity, with enhanced visual cortex responses to non-visual stimuli after vision restoration.
• Auditory cross-modal functions did not impede the success of vision restitution achieved through GT.
• It is hypothesized that restored visual neurons become more responsive and strengthen auditory-visual cortical connectivity to accommodate new visual signals.