Abstract

Retinal degeneration (rd) is one of the leading causes of blindness in the modern world today. Various strategies including electrical stimulation are being researched for the restoration of partial or complete vision. Previous studies have demonstrated that the effectiveness of electrical stimulation in somatosensory, frontal and visual cortices is dependent on stimulation parameters including stimulation frequency and brain states. The aim of the study is to investigate the effect of applying a prolonged electrical stimulation on the eye of rd mice with various stimulation frequencies, in awake and anesthetized brain states. We recorded spontaneous electrocorticogram (ECoG) neural activity in prefrontal cortex and primary visual cortex in a mouse model of retinitis pigmentosa (RP) after prolonged (5-day) transcorneal electrical stimulation (pTES) at various frequencies (2, 10, and 20 Hz). We evaluated the absolute power and coherence of spontaneous ECoG neural activities in contralateral primary visual cortex (contra Vcx) and contralateral pre-frontal cortex (contra PFx). Under the awake state, the absolute power of theta, alpha and beta oscillations in contra Vcx, at 10 Hz stimulation, was higher than in the sham group. Under the anesthetized state, the absolute power of medium-, high-, and ultra-high gamma oscillations in the contra PFx, at 2 Hz stimulation, was higher than in the sham group. We also observed that the ultra-high gamma band coherence in contra Vcx-contra PFx was higher than in the sham group, with both 10 and 20 Hz stimulation frequencies. Our results showed that pTES modulates rd brain oscillations in a frequency and brain state-dependent manner. These findings suggest that non-invasive electrical stimulation of retina changes patterns of neural oscillations in the brain circuitry. This also provides a starting point for investigating the sustained effect of electrical stimulation of the retina to brain activities.

Highlights

  • Electrical stimulation has a long history of clinical applications, ranging from the use of live organisms to deliver electric current to tissues for pain therapy, to the more recent wide usage of implantable devices in clinical settings (Takeda et al, 2017; Capogrosso et al, 2018)

  • The present study addresses the following research question; Will the prolonged electrical stimulation of the retina influence brain activity on a local and global scale, i.e., in the primary visual cortex and non-visual area, respectively? To this end, we recorded resting or spontaneous electrocorticogram (ECoG) activity arising in neurons of the pre-frontal cortex and primary visual cortex in response to transcorneal electrical stimulation (TES)

  • All other oscillatory bands showed non-significant changes (p > 0.025) in spontaneous absolute power across all stimulation groups after TES compared to sham group (Figure 6A and Table 1A)

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Summary

Introduction

Electrical stimulation has a long history of clinical applications, ranging from the use of live organisms to deliver electric current to tissues for pain therapy, to the more recent wide usage of implantable devices in clinical settings (Takeda et al, 2017; Capogrosso et al, 2018). TES in Retinal Degeneration Mice and repetitive transcranial magnetic stimulation (rTMS) have been severally demonstrated to cause neuromodulatory effects which induce long lasting changes in the brain. Both techniques have been shown to change cortical excitability that persists even after the end of the stimulation period (Wagner et al, 2009; Bailey et al, 2016). The resultant effects of these stimulation paradigms are often dependent on the frequency of stimulation which could either increase or decrease cortical excitability (López-Alonso et al, 2014). It reported an increase in alpha and beta oscillations during and following stimulation and a wide spread activation of brain regions was observed following stimulation (Mangia et al, 2014)

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