Abstract
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.
Highlights
The human brain is a dynamic organ that produces large scale coordinated electrophysiological activities in billions of neurons
It has been demonstrated that crossfrequency coupling (CFC) between the phases of low frequency oscillations (LFOs) and the amplitudes of high frequency oscillations (HFOs) play important roles in visualrelated activities (Spaak et al, 2012)
Two weeks after the start of the 7-days prolonged transcorneal electrical stimulation (pTES) (2-weeks poststimulation or post-stimulation stage 2), there was maintained elevated increase in theta-medium gamma phase amplitude coupling (PAC) of rd10 mice stimulated with 400 μA (P = 0.010), 500 μA (P = 0.011), and 600 μA (P = 0.011), respectively, compared with theta-medium gamma PAC at the pre-stimulation stage (Figures 2A,B)
Summary
The human brain is a dynamic organ that produces large scale coordinated electrophysiological activities in billions of neurons. Notwithstanding the area of occurrence, CFC often features an interaction where the phase of low frequency oscillations such as theta (5–10 Hz) or alpha (10–15 Hz) has been demonstrated to couple or modulate the amplitude of high frequency gamma oscillations (30–100 Hz) (Zhang et al, 2019). This phase amplitude coupling (PAC) of the associated brain rhythms has been severally proven to play important roles in higher cognitive functions of the brain including visual functions (Sokoliuk and VanRullen, 2012), working memory (Lega et al, 2014) and behavioral functions (Ohki et al, 2020) amongst others
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