Transcorneal Electrical Stimulation Induces Long-Lasting Enhancement of Brain Functional and Directional Connectivity in Retinal Degeneration Mice

To investigate neuromodulation of functional and directional connectivity features in both visual and non-visual brain cortices after short-term and long-term retinal electrical stimulation in retinal degeneration mice. We performed spontaneous electrocorticography (ECoG) in retinal degeneration (rd) mice following prolonged transcorneal electrical stimulation (pTES) at varying currents (400, 500 and 600 μA) and different time points (transient or day 1 post-stimulation, 1-week post-stimulation and 2-weeks post-stimulation). We also set up a sham control group of rd mice which did not receive any electrical stimulation. Subsequently we analyzed alterations in cross-frequency coupling (CFC), coherence and directional connectivity of the primary visual cortex and the prefrontal cortex. It was observed that the sham control group did not display any significant changes in brain connectivity across all stages of electrical stimulation. For the stimulated groups, we observed that transient electrical stimulation of the retina did not significantly alter brain coherence and connectivity. However, for 1-week post-stimulation, we identified enhanced increase in theta-gamma CFC. Meanwhile, enhanced coherence and directional connectivity appeared predominantly in theta, alpha and beta oscillations. These alterations occurred in both visual and non-visual brain regions and were dependent on the current amplitude of stimulation. Interestingly, 2-weeks post-stimulation demonstrated long-lasting enhancement in network coherence and connectivity patterns at the level of cross-oscillatory interaction, functional connectivity and directional inter-regional communication between the primary visual cortex and prefrontal cortex. Application of electrical stimulation to the retina evidently neuromodulates brain coherence and connectivity of visual and non-visual cortices in retinal degeneration mice and the observed alterations are largely maintained. pTES holds strong possibility of modulating higher cortical functions including pathways of cognition, awareness, emotion and memory.