Abstract

Rat auditory cortex was subjected to 0.1 mA anodal direct current in seven 10-min sessions on alternate days. Based on the well-known auditory cortex control of olivocochlear regulation through corticofugal projections, auditory brainstem responses (ABRs) were recorded as an indirect test of the effectiveness and reversibility of the multisession protocol of epidural stimulation. Increases of 20–30 dB ABR auditory thresholds shown after epidural stimulation reverted back to control levels 10 min after a single session. However, increases in thresholds revert 4 days after multisession stimulation. Less changes in wave amplitudes and threshold shifts were shown in ABR recorded contralaterally to the electrically stimulated side of the brain. To assess tissue effects of epidural electric stimulation on the brain cortex, well characterized functional anatomical markers of glial cells (GFAP/astrocytes and Iba1/microglial cells) and neurons (c-Fos) were analyzed in alternate serial sections by quantitative immunocytochemistry. Restricted astroglial and microglial reactivity was observed within the cytoarchitectural limits of the auditory cortex. However, interstitial GFAP overstaining was also observed in the ventricular surface and around blood vessels, thus supporting a potential global electrolytic stimulation of the brain. These results correlate with extensive changes in the distribution of c-Fos immunoreactive neurons among layers along sensory cortices after multisession stimulation. Quantitative immunocytochemical analysis supported this idea by showing a significant increase in the number of positive neurons in supragranular layers and a decrease in layer 6 with no quantitative changes detected in layer 5. Our data indicate that epidural stimulation of the auditory cortex induces a reversible decrease in hearing sensitivity due to local, restricted epidural stimulation. A global plastic response of the sensory cortices, also reported here, may be related to electrolytic effects of electric currents.

Highlights

  • Invasive techniques, such as epidural electric stimulation (EES), have been recently used to treat brain diseases (Nahas et al, 2010; Balossier et al, 2013; Levy et al, 2016; Williams et al, 2016)

  • After qualitative analysis of a single session stimulation in group 3 (n = 4), the auditory brainstem responses (ABRs) thresholds in the hemisphere ipsilateral to the EES showed an increase of approximately 20 dB; they recovered completely 10 min later (Figure 3)

  • Wave 2 average amplitude significantly decreases in ABRs after multisession protocol in response to clicks of 20–50 dB in the ipsilateral side to EES and 20–40 dB in the contralateral (Figures 4, 5)

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Summary

Introduction

Invasive techniques, such as epidural electric stimulation (EES), have been recently used to treat brain diseases (Nahas et al, 2010; Balossier et al, 2013; Levy et al, 2016; Williams et al, 2016). Electric stimulation of the brain has been effective in neuro-otological diseases such as auditory hallucinations (Koops et al, 2015), tinnitus (Zeng et al, 2015), aphasia (Cherney, 2011, 2016; Cherney et al, 2012), and auditory agnosia (Bestelmeyer et al, 2018) Among these clinical applications, electrostimulation currently stands out for its effectiveness in treating a wide range of central hearing disorders. The brain cortex can adjust and improve cochlear outputs after sound stimulation in real time In mustached bats, such corticofugal modulation was masterfully demonstrated by Xiao and Suga (2002), by CM recordings, through shifts in frequency tuning after electrical stimulation of the AC. Previous results from our laboratory have shown that restricted ablation of the rat AC significantly increases auditory thresholds (hearing suppression) analyzed by ABRs (Lamas et al, 2013)

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