Electrical Stimulation publications

In all commercial cochlear implant (CI) devices, the electric stimulation is performed with a rectangular pulse that generally has two phases of opposite polarity. To date, developing new stimulation strategies has relied on the efficacy of this shape. Here, we investigate the potential of a novel stimulation paradigm that uses biophysically-inspired electrical ramped pulses. Using electrically-evoked auditory brainstem response (eABR) recordings in mice, we found that less charge, but higher current level amplitude, is needed to evoke responses with ramped shapes that are similar in amplitude to responses obtained with rectangular shapes. The most charge-efficient pulse shape had a rising ramp over both phases, supporting findings from previous in vitro studies. This was also true for longer phase durations. Our study presents the first physiological data on CI-stimulation with ramped pulse shapes. By reducing charge consumption ramped pulses have the potential to produce more battery-efficient CIs and may open new perspectives for designing other efficient neural implants in the future.

Age-related hearing loss (ARHL) is associated with weakened inhibition in the central auditory nervous system including the cochlear nucleus. One of the main inhibitory neurons of the cochlear nucleus is the D-stellate neuron, which provides extensive glycinergic inhibition within the local neural network. It remains unclear how physiological activities of D-stellate neurons change during ARHL and what are the underlying mechanisms. Using in vitro whole-cell patch clamp technique, we studied the intrinsic membrane properties of D-stellate neurons, the changes of their firing properties, and the underlying mechanisms in CBA/CaJ mice at the ages of 3–4 months (young), 17–19 months (middle age), and 27–33 months (aged). We found that the intrinsic membrane properties of D-stellate neurons were unchanged among these three age groups. However, these neurons showed decreased firing rate with age in response to sustained auditory nerve stimulation. Further investigation showed that auditory nerve-evoked excitatory postsynaptic currents (EPSCs) were significantly reduced in strength with age. These findings suggest that D-stellate neurons receive weakened synaptic inputs from the auditory nerve and decreased sound driven activity with age, which are expected to reduce the overall inhibition and enhance the central gain in the cochlear nucleus during ARHL.

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.

Hearing impairment is the most common sensory deficit. It is frequently caused by the expression of an allele carrying a single dominant missense mutation. Herein, we show that a single intracochlear injection of an artificial microRNA carried in a viral vector can slow progression of hearing loss for up to 35 weeks in the Beethoven mouse, a murine model of non-syndromic human deafness caused by a dominant gain-of-function mutation in Tmc1 (transmembrane channel-like 1). This outcome is noteworthy because it demonstrates the feasibility of RNA-interference-mediated suppression of an endogenous deafness-causing allele to slow progression of hearing loss. Given that most autosomal-dominant non-syndromic hearing loss in humans is caused by this mechanism of action, microRNA-based therapeutics might be broadly applicable as a therapy for this type of deafness.

We proposed a piezoelectric artificial basilar membrane (ABM) composed of a microelectromechanical system cantilever array. The ABM mimics the tonotopy of the cochlea: frequency selectivity and mechanoelectric transduction. The fabricated ABM exhibits a clear tonotopy in an audible frequency range (2.92–12.6 kHz). Also, an animal model was used to verify the characteristics of the ABM as a front end for potential cochlear implant applications. For this, a signal processor was used to convert the piezoelectric output from the ABM to an electrical stimulus for auditory neurons. The electrical stimulus for auditory neurons was delivered through an implanted intra-cochlear electrode array. The amplitude of the electrical stimulus was modulated in the range of 0.15 to 3.5 V with incoming sound pressure levels (SPL) of 70.1 to 94.8 dB SPL. The electrical stimulus was used to elicit an electrically evoked auditory brainstem response (EABR) from deafened guinea pigs. EABRs were successfully measured and their magnitude increased upon application of acoustic stimuli from 75 to 95 dB SPL. The frequency selectivity of the ABM was estimated by measuring the magnitude of EABRs while applying sound pressure at the resonance and off-resonance frequencies of the corresponding cantilever of the selected channel. In this study, we demonstrated a novel piezoelectric ABM and verified its characteristics by measuring EABRs.