Auditory sensitivity may require dynamically unstable spike generators: evidence from a model of electrical stimulation.
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ABSTRACT:
SUBMITTER: O'Gorman DE
PROVIDER: S-EPMC2997813 | biostudies-other | 2010 Nov
REPOSITORIES: biostudies-other
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Project description:Background: The human auditory nerve contains 30,000 nerve fibers (NFs) that relay complex speech information to the brain with spectacular acuity. How speech is coded and influenced by various conditions is not known. It is also uncertain whether human nerve signaling involves exclusive proteins and gene manifestations compared with that of other species. Such information is difficult to determine due to the vulnerable, "esoteric," and encapsulated human ear surrounded by the hardest bone in the body. We collected human inner ear material for nanoscale visualization combining transmission electron microscopy (TEM), super-resolution structured illumination microscopy (SR-SIM), and RNA-scope analysis for the first time. Our aim was to gain information about the molecular instruments in human auditory nerve processing and deviations, and ways to perform electric modeling of prosthetic devices. Material and Methods: Human tissue was collected during trans-cochlear procedures to remove petro-clival meningioma after ethical permission. Cochlear neurons were processed for electron microscopy, confocal microscopy (CM), SR-SIM, and high-sensitive in situ hybridization for labeling single mRNA transcripts to detect ion channel and transporter proteins associated with nerve signal initiation and conductance. Results: Transport proteins and RNA transcripts were localized at the subcellular level. Hemi-nodal proteins were identified beneath the inner hair cells (IHCs). Voltage-gated ion channels (VGICs) were expressed in the spiral ganglion (SG) and axonal initial segments (AISs). Nodes of Ranvier (NR) expressed Nav1.6 proteins, and encoding genes critical for inter-cellular coupling were disclosed. Discussion: Our results suggest that initial spike generators are located beneath the IHCs in humans. The first NRs appear at different places. Additional spike generators and transcellular communication may boost, sharpen, and synchronize afferent signals by cell clusters at different frequency bands. These instruments may be essential for the filtering of complex sounds and may be challenged by various pathological conditions.
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Project description:Recent retinal studies have directed more attention to sophisticated stimulation strategies based on high-frequency (>1.0 kHz) electrical stimulation (HFS). In these studies, each retinal ganglion cell (RGC) type demonstrated a characteristic stimulus-strength-dependent response to HFS, offering the intriguing possibility of focally targeting retinal neurons to provide useful visual information by retinal prosthetics. Ionic mechanisms are known to affect the responses of electrogenic cells during electrical stimulation. However, how these mechanisms affect RGC responses is not well understood at present, particularly when applying HFS. Here, we investigate this issue via an in silico model of the RGC. We calibrate and validate the model using an in vitro retinal preparation. An RGC model based on accurate biophysics and realistic representation of cell morphology, was used to investigate how RGCs respond to HFS. The model was able to closely replicate the stimulus-strength-dependent suppression of RGC action potentials observed experimentally. Our results suggest that spike inhibition during HFS is due to local membrane hyperpolarization caused by outward membrane currents near the stimulus electrode. In addition, the extent of HFS-induced inhibition can be largely altered by the intrinsic properties of the inward sodium current. Finally, stimulus-strength-dependent suppression can be modulated by a wide range of stimulation frequencies, under generalized electrode placement conditions. In vitro experiments verified the computational modeling data. This modeling and experimental approach can be extended to further our understanding on the effects of novel stimulus strategies by simulating RGC stimulus-response profiles over a wider range of stimulation frequencies and electrode locations than have previously been explored.
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Project description:Benign epilepsy with centrotemporal spikes (BECTS) is a common form of childhood epilepsy linked to diverse cognitive abnormalities. The electroencephalogram of patients shows focal interictal epileptic spikes, particularly during non-rapid eye movement (NonREM) sleep. Spike formation involves thalamocortical networks, which also contribute to the generation of sleep slow oscillations (SOs) and spindles. Motivated by evidence that SO-spindle activity can be controlled through closed-loop auditory stimulation, here, we show in seven patients that auditory stimulation also reduces spike rates in BECTS. Stimulation during NonREM sleep decreases spike rates, with most robust reductions when tones are presented 1.5 to 3.5 s after spikes. Stimulation further reduces the amplitude of spikes closely following tones. Sleep spindles are negatively correlated with spike rates, suggesting that tone-evoked spindle activity mediates the spike suppression. We hypothesize spindle-related refractoriness in thalamocortical circuits as a potential mechanism. Our results open an avenue for the non-pharmacological treatment of BECTS.
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Project description:Dysphagia is common in neurological disease. However, our understanding of swallowing and its central nervous control is limited. Sensory information plays a vital role in the initiation of the swallowing reflex and is often reduced in stroke patients. We hypothesized that the sensitivity threshold of the anterior faucial pillar could be facilitated by either electrical stimulation (ES) or taste and smell information. The sensitivity threshold was measured by ES in the anterior faucial pillar region. The measurement was repeated 5 min after baseline. Thirty minutes after baseline, the participants underwent a test for taste and smell. Immediately after the test, the ES was repeated. Thirty healthy volunteers with a mean age of 27 ± 5.1 participated in the trial. Mean sensitivity threshold at baseline was 1.9 ± 0.59 mA. The values 5 min after baseline (1.74 ± 0.56 mA, p = 0.027) and 30 min after baseline (1.67 ± 0.58 mA, p = 0.011) were significantly lower compared to the baseline, but there was no difference between the latter (p = 0.321). After 5 min, a potentially facilitating effect was found on oral sensitivity by ES of the faucial pillar area. Thirty minutes later, this effect was still present.Trial registration Clinicaltrials.gov, NCT03240965. Registered 7th August 2017- https://clinicaltrials.gov/ct2/show/NCT03240965 .
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Project description:ObjectiveThe objective of this analysis was to evaluate the effectiveness of deep brain stimulation (DBS) and vagus nerve stimulation (VNS) for the treatment of drug-resistant epilepsy in adults and children.Data sourcesA literature search was performed using MEDLINE, EMBASE, the Cochrane Library, and the Centre for Reviews and Dissemination database, for studies published from January 2007 until December 2012.Review methodsSystematic reviews, meta-analyses, randomized controlled trials (RCTs), and observational studies (in the absence of RCTs) of adults or children were included. DBS studies were included if they specified that the anterior nucleus of thalamus was the area of the brain stimulated. Outcomes of interest were seizure frequency, health resource utilization, and safety. A cost analysis was also performed.ResultsThe search identified 6 studies that assessed changes in seizure frequency after electrical stimulation: 1 RCT on DBS in adults, 4 RCTs on VNS in adults, and 1 RCT on VNS in children. The studies of DBS and VNS in adults found significantly improved rates of seizure frequency, but the study of VNS in children did not find a significant difference in seizure frequency between the high and low stimulation groups. Significant reductions in hospitalizations and emergency department visits were found for adults and children who received VNS. No studies addressed the use of health resources for patients undergoing DBS. Five studies reported on adverse events, which ranged from serious to transient for both procedures in adults and were mostly transient in the 1 study of VNS in children.LimitationsWe found no evidence on DBS in children or on health care use related to DBS. The measurement of seizure frequency is self-reported and is therefore subject to bias and issues of compliance.ConclusionsBased on evidence of low to moderate quality, both DBS and VNS seemed to reduce seizure frequency in adults. In children, VNS did not appear to be as effective at reducing seizure frequency, but children had significantly fewer hospitalizations and ED visits after VNS implantation. Despite the considerable risks associated with these invasive procedures, long-term adverse events appear to be limited.Plain language summaryElectrical stimulation of specific areas of the brain is a procedure used to control epileptic seizures when more conventional treatments are not working. Most adults and children with epilepsy are able to control their seizures with medication, but for some patients, drugs are not effective and surgery to remove the part of the brain where the seizures start is not an appropriate option. This study looked at the research available on the effectiveness, safety, and cost of two types of electrical stimulation devices currently licensed for treatment of epilepsy for adults and children in Canada: vagus nerve stimulation (VNS) and deep brain stimulation (DBS). Both approaches appear to be effective at reducing the frequency of seizures in adults. However, the evidence on DBS is limited to a single study with adults; we found no studies of DBS with children. Studies on VNS showed that both adults and children had fewer hospitalizations and emergency department visits after the procedure. Both procedures carry serious risks, but several longer-term studies have found that adverse events appear to be limited. The cost of VNS, including the process of assessing whether or not patients are good candidates for the procedure, is estimated to be about $40,000 per person (and higher for DBS because the device is more expensive and the operating time is longer). Of the 70,000 people in Ontario with epilepsy, about 1,400 (300 children and 1,110 adults) may be candidates for VNS to reduce their seizures.
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