Interphase Gaps in Symmetric Biphasic Pulses Reduce the Therapeutic Window in Ventral Intermediate Nucleus of the Thalamus-Deep Brain Stimulation for Essential Tremor.

INTRODUCTION: Symmetric biphasic pulses enlarge the therapeutic window in thalamic deep brain stimulation in patients with essential tremor. Adding an interphase gap to these symmetric biphasic pulses may further affect the therapeutic window. MATERIALS AND METHODS: Nine patients (16 hemispheres) were included in this study. Biphasic pulses (anodic phase first) with interphase gaps of 0, 10, 20, 50, and 100 µs were tested, in random order. The outcome parameters were the therapeutic threshold (TT) and side-effect threshold (SET), and thus also the therapeutic window (TW). RESULTS: Increasing interphase gaps lowered both SET and TT (linear mixed-effects model; p < 0.001 and p < 0.001). Because SET decreased predominantly, increasing interphase gaps resulted in smaller TWs (linear mixed-effects model; p < 0.001). DISCUSSION AND CONCLUSIONS: Introducing an interphase gap in a symmetric biphasic pulse may lead to less selectivity in fiber or neuronal activation. Our findings show that, in the context of anode-first biphasic pulses, the use of zero-interphase gaps results in the largest TW. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT05177900.

Aligning Dentato-Rubro-Thalamic Tract and Subthalamic Nucleus Targets in a Patient with Comorbid Essential Tremor and Parkinson's Disease: Case Report.

Deep brain stimulation is an established treatment option for both essential tremor (ET) and Parkinson's disease (PD), although typically targeting different brain structures. Some patients are diagnosed with comorbid ET and PD. Selecting the optimal stimulation target in these patients is challenging. We present a patient with comorbid ET and PD in whom we used bilaterally a single parietal trajectory to align the dentato-rubro-thalamic tract and the subthalamic nucleus. Although parietal trajectories are challenging, we reached satisfactory outcomes for both conditions without complications. Single-electrode deep brain stimulation of the dentato-rubro-thalamic tract and the subthalamic nucleus through a parietal approach may represent a feasible treatment option in this patient group.

Transcutaneous electrical nerve inhibition using medium frequency alternating current.

Transcutaneous medium-frequency alternating electrical current is defined as an alternating current between 1 and 10 kHz and is capable of producing an instant, reversible block. This study aims to evaluate the efficacy of sensory perception and force production of the index and middle finger after transcutaneous medium-frequency alternating electrical current stimulation of the distal median nerve. A single-center prospective interventional cohort study was conducted in adult healthy volunteers at the Jessa Hospital, Hasselt, Belgium. Two different electrodes (PALS & 3M) were placed on the distal median nerve, which was located using a Sonosite X-Porte Ultrasound transducer, with the first electrode being placed on the skin at the level of the transverse carpal ligament and the second electrode 7 cm proximally to the first electrode. The tactile sensation was evaluated with Semmes-Weinstein monofilament test and sensation of pressure/pain was evaluated with an algometer. Peak force production was assessed with an electronic dynamometer. All measurements were performed at baseline and tMFAEC stimulation frequencies of 2 and 10 kHz in a randomized manner. Statistical analysis was performed with a one-way ANOVA with repeated measures test or a Friedman rank sum test, followed by the Wilcoxon signed rank test adjusted with Bonferroni correction. A p-value < 0.05 was considered statistically significant. From 9 to 13th of April 2021, 25 healthy volunteers were included in the Jessa Hospital, Hasselt, Belgium. A statistically significant reduction in tactile sensation during 2 kHz and 10 kHz stimulation compared to baseline was observed (2.89 ± 0.22 (PALS2); 3.35 ± 0.25 (3M2) and 2.14 ± 0.12 (PALS10); 2.38 ± 0.12 (3M10) versus - 1.75 ± 0.09 (baseline), p < 0.0001). 3M electrodes showed a tendency towards the elevation of pressure pain threshold compared to baseline. No significant difference in mean peak forces of the index and middle fingers after transcutaneous medium-frequency alternating electrical current stimulation with 2 and 10 kHz was found. This study demonstrates that transcutaneous medium-frequency alternating electrical current stimulation on the distal median nerve inhibits tactile sensory nerve activity in the index and middle finger when stimulation of 2 kHz and, to a lesser extent, 10 kHz was applied. A reduction of motor nerve activity was not observed but force production measurements may be prone to error.Trial registration: clinicaltrials.gov on 01/04/2021. NCT-Number: NCT04827173.

Objective assessment of spectral ripple discrimination in cochlear implant listeners using cortical evoked responses to an oddball paradigm.

Cochlear implants (CIs) can partially restore functional hearing in deaf individuals. However, multiple factors affect CI listener's speech perception, resulting in large performance differences. Non-speech based tests, such as spectral ripple discrimination, measure acoustic processing capabilities that are highly correlated with speech perception. Currently spectral ripple discrimination is measured using standard psychoacoustic methods, which require attentive listening and active response that can be difficult or even impossible in special patient populations. Here, a completely objective cortical evoked potential based method is developed and validated to assess spectral ripple discrimination in CI listeners. In 19 CI listeners, using an oddball paradigm, cortical evoked potential responses to standard and inverted spectrally rippled stimuli were measured. In the same subjects, psychoacoustic spectral ripple discrimination thresholds were also measured. A neural discrimination threshold was determined by systematically increasing the number of ripples per octave and determining the point at which there was no longer a significant difference between the evoked potential response to the standard and inverted stimuli. A correlation was found between the neural and the psychoacoustic discrimination thresholds (R2=0.60, p<0.01). This method can objectively assess CI spectral resolution performance, providing a potential tool for the evaluation and follow-up of CI listeners who have difficulty performing psychoacoustic tests, such as pediatric or new users.

Auditory mismatch negativity in cochlear implant users: a window to spectral discrimination.

A cochlear implant (CI) can partially restore hearing in patients with severe to profound sensorineural hearing loss. However, the large outcome variability in CI users prompts the need for more objective measures of speech perception performance. Electrophysiological metrics of CI performance may be an important tool for audiologists in the assessment of hearing rehabilitation. Utilizing electroencephalography (EEG), it may be possible to evaluate speech perception correlates such as spectral discrimination. The mismatch negativity (MMN) of 10 CI subjects was recorded for stimuli containing different spectral densities. The neural spectral discrimination threshold, estimated by the MMN responses, showed a significant correlation with the behavioral spectral discrimination threshold measured in each subject. Results suggest that the MMN can be potentially used to obtain an objective estimate of spectral discrimination abilities in CI users.

Cochlear implant artifact attenuation in late auditory evoked potentials: a single channel approach.

Recent evidence suggests that late auditory evoked potentials (LAEP) provide a useful objective metric of performance in cochlear implant (CI) subjects. However, the CI produces a large electrical artifact that contaminates LAEP recordings and confounds their interpretation. Independent component analysis (ICA) has been used in combination with multi-channel recordings to effectively remove the artifact. The applicability of the ICA approach is limited when only single channel data are needed or available, as is often the case in both clinical and research settings. Here we developed a single-channel, high sample rate (125 kHz), and high bandwidth (0-100 kHz) acquisition system to reduce the CI stimulation artifact. We identified two different artifacts in the recording: 1) a high frequency artifact reflecting the stimulation pulse rate, and 2) a direct current (DC, or pedestal) artifact that showed a non-linear time varying relationship to pulse amplitude. This relationship was well described by a bivariate polynomial. The high frequency artifact was completely attenuated by a 35 Hz low-pass filter for all subjects (n = 22). The DC artifact could be caused by an impedance mismatch. For 27% of subjects tested, no DC artifact was observed when electrode impedances were balanced to within 1 kΩ. For the remaining 73% of subjects, the pulse amplitude was used to estimate and then attenuate the DC artifact. Where measurements of pulse amplitude were not available (as with standard low sample rate systems), the DC artifact could be estimated from the stimulus envelope. The present artifact removal approach allows accurate measurement of LAEPs from CI subjects from single channel recordings, increasing their feasibility and utility as an accessible objective measure of CI function.

Rate and onset cues can improve cochlear implant synthetic vowel recognition in noise.

Understanding speech-in-noise is difficult for most cochlear implant (CI) users. Speech-in-noise segregation cues are well understood for acoustic hearing but not for electric hearing. This study investigated the effects of stimulation rate and onset delay on synthetic vowel-in-noise recognition in CI subjects. In experiment I, synthetic vowels were presented at 50, 145, or 795 pulse/s and noise at the same three rates, yielding nine combinations. Recognition improved significantly if the noise had a lower rate than the vowel, suggesting that listeners can use temporal gaps in the noise to detect a synthetic vowel. This hypothesis is supported by accurate prediction of synthetic vowel recognition using a temporal integration window model. Using lower rates a similar trend was observed in normal hearing subjects. Experiment II found that for CI subjects, a vowel onset delay improved performance if the noise had a lower or higher rate than the synthetic vowel. These results show that differing rates or onset times can improve synthetic vowel-in-noise recognition, indicating a need to develop speech processing strategies that encode or emphasize these cues.

Towards a closed-loop cochlear implant system: application of embedded monitoring of peripheral and central neural activity.

Although the cochlear implant (CI) is widely considered the most successful neural prosthesis, it is essentially an open-loop system that requires extensive initial fitting and frequent tuning to maintain a high, but not necessarily optimal, level of performance. Two developments in neuroscience and neuroengineering now make it feasible to design a closed-loop CI. One development is the recording and interpretation of evoked potentials (EPs) from the peripheral to the central nervous system. The other is the embedded hardware and software of a modern CI that allows recording of EPs. We review EPs that are pertinent to behavioral functions from simple signal detection and loudness growth to speech discrimination and recognition. We also describe signal processing algorithms used for electric artifact reduction and cancellation, critical to the recording of electric EPs. We then present a conceptual design for a closed-loop CI that utilizes in an innovative way the embedded implant receiver and stimulators to record short latency compound action potentials ( ~1 ms), auditory brainstem responses (1-10 ms) and mid-to-late cortical potentials (20-300 ms). We compare EPs recorded using the CI to EPs obtained using standard scalp electrodes recording techniques. Future applications and capabilities are discussed in terms of the development of a new generation of closed-loop CIs and other neural prostheses.

Oscillatory dipoles as a source of phase shifts in field potentials in the mammalian auditory brainstem.

A popular model of binaural processing, proposed by Jeffress (1948), states that external interaural time delays (ITDs) are compensated by internal axonal delays allowing ITD to be spatially represented by a population of coincidence detectors in the medial superior olive (MSO). Isolating single-neuron responses in MSO is difficult because of the presence of a strong extracellular field potential known as the neurophonic, so that few studies have tested Jeffress's key prediction. Phase delays in the nucleus laminaris neurophonic in owls have been observed and are consistent with a Jeffress-like model. Here, we recorded neurophonic responses in cat MSO to monaural tones at locations along its dendritic axis. Fourier analysis of the neurophonic was used to extract amplitude and phase at the stimulus frequency. Amplitude, as a function of depth, showed two peaks separated by a dip. A half-cycle phase shift was observed at depths close to the dip, over a wide frequency range. Current source density analysis for contralateral (ipsilateral) stimulation shows a current source close to the neurophonic amplitude peak and a sink a few hundred micrometers ventromedially (dorsolaterally). These results are consistent with a dipole configuration: contralateral (ipsilateral) excitation causes a current sink at the ventromedial (dorsolateral) dendrites and a source at the soma and dorsolateral (ventromedial) dendrites. Incorporating these results in a dipole model explains the phase and amplitude patterns observed. We conclude that the half-cycle phase shift is consistent with a current dipole, making it difficult to derive measurements of axonal delays from the neurophonic.

Comparison of bandwidths in the inferior colliculus and the auditory nerve. I. Measurement using a spectrally manipulated stimulus.

A defining feature of auditory systems across animal divisions is the ability to sort different frequency components of a sound into separate neural frequency channels. Narrowband filtering in the auditory periphery is of obvious advantage for the representation of sound spectrum and manifests itself pervasively in human psychophysical studies as the critical band. Peripheral filtering also alters coding of the temporal waveform, so that temporal responses in the auditory periphery reflect both the stimulus waveform and peripheral filtering. Temporal coding is essential for the measurement of the time delay between waveforms at the two ears-a critical component of sound localization. A number of human psychophysical studies have shown a wider effective critical bandwidth with binaural stimuli than with monaural stimuli, although other studies found no difference. Here we directly compare binaural and monaural bandwidths (BWs) in the anesthetized cat. We measure monaural BW in the auditory nerve (AN) and binaural BW in the inferior colliculus (IC) using spectrally manipulated broadband noise and response metrics that reflect spike timing. The stimulus was a pair of noise tokens that were interaurally in phase for all frequencies below a certain flip frequency (f(flip)) and that had an interaural phase difference of pi above f(flip). The response was measured as a function of f(flip) and, using a separate stimulus protocol, as a function of interaural correlation. We find that both AN and IC filter BW depend on characteristic frequency, but that there is no difference in mean BW between the AN and IC.