Retinal prostheses can provide artificial vision to patients with degenerate retinae by electrically stimulating the remaining inner retinal neurons. The evoked perception is generally adequate for light localization, but of limited spatial resolution owing to the indiscriminate activation of multiple retinal cell types, leading to distortions in the perceived image. Here we present a perspective on a recent work by Weitz and colleagues who demonstrate a focal confinement of retinal ganglion cell (RGC) activation when using extended pulse durations in the stimulation waveform. Using real-time calcium imaging, they provide evidence that long pulse durations selectively stimulate inner retinal neurons, whilst avoiding unwanted axonal activations. The application of this stimulation technique may provide enhanced spatial resolution for retinal prosthesis users. These experiments provide a robust analysis of the effects of increasing pulse duration and introduce the potential for alternative stimulation paradigms in retinal prostheses.

BACKGROUND: Tremor is a debilitating symptom of Multiple Sclerosis (MS). Little is known about its pathophysiology and treatments are limited. Clinical trials investigating new interventions often rely on subjective clinical rating scales to provide supporting evidence of efficacy. NEW METHOD: We present a novel instrument (TREMBAL) which uses electromagnetic motion capture technology to quantify MS tremor. We aim to validate TREMBAL by comparison to clinical ratings using regression modelling with 310 samples of tremor captured from 13 MS participants who performed five different hand exercises during several follow-up visits. Minimum detectable change (MDC) and test-retest reliability were calculated and comparisons were made between MS tremor and data from 12 healthy volunteers. RESULTS: Velocity of the index finger was most congruent with clinical observation. Regression modelling combining different features, sensor configurations, and labelling exercises did not improve results. TREMBAL MDC was 84% of its initial measurement compared to 91% for the clinical rating. Intra-class correlations for test-retest reliability were 0.781 for TREMBAL and 0.703 for clinical ratings. Tremor was lower (p =  0.002) in healthy subjects. COMPARISON WITH EXISTING METHODS: Subjective scales have low sensitivity, suffer from ceiling effects, and mitigation against inter-rater variability is challenging. Inertial sensors are ubiquitous, however, their output is nonlinearly related to tremor frequency, compensation is required for gravitational artefacts, and their raw data cannot be intuitively comprehended. CONCLUSIONS: TREMBAL, compared with clinical ratings, gave measures in agreement with clinical observation, had marginally lower MDC, and similar test-retest reliability.

IMPORTANCE: Multiple sclerosis produces neurological impairments that are variable in duration, severity and quality. Speech is frequently impaired, resulting in decreased communication skills and quality of life. Advancements in technology now makes it possible to use quantitative acoustic assessment of speech as biomarkers of disease progression. OBSERVATIONS: Four domains of speech have been identified: articulation (slow articulation and imprecise consonants), voice (pitch and loudness instability), respiration (decreased phonatory time and expiratory pressure) and prosody (longer and frequent pauses, deficient loudness control). Studies also explored I) predictive models for diagnosis of MS and of ataxia using speech variables, II) the relationship of dysarthria with cognition and III) very few studies correlated neuroimaging with dysarthria. We could not identify longitudinal studies of speech or dysarthria in Multiple Sclerosis. CONCLUSION AND RELEVANCE: Refinement of objective measures of speech has enhanced our understanding of Multiple Sclerosis-related deficits in cross-sectional analysis while both integrative and longitudinal studies are identified as major gaps. This review highlights the potential for using quantitative acoustic assessments as clinical endpoints for diagnosing, monitoring progression and treatment in disease modifying trials.

Patients with intractable tremor not alleviated by pharmaceutical therapies can be successfully treated using Deep Brain Stimulation of subcortical areas such as the Subthalamic Nucleus (STN). Current DBS devices produce constant-current or constant-voltage biphasic pulse trains and offer a range of pulse rate and pulse duration options as well as different current or voltage levels. The clinical method of setting the parameters by observation is non-ideal, firstly because of the number of possible parameter combinations, and a current lack of knowledge of how the parameters interact with each other, and secondly because subjective clinical observation is prone to observer error and bias. In this study, we aimed to develop an objective method of recording the severity of tremor and to use it to explore the effect on tremor of stimulus parameters. Six patients with Essential Tremor who had been fitted with a DBS device in the Posterior Subthalamic Area (PSA) participated in the study. Tremor was measured by position sensors attached to the arms and wrists while the patient was holding both arms stretched out in front of them and when performing a finger-nose pointing task. Clinical rating of tremor was also performed. Results of the experiments showed that the optimal stimulus parameters were subject specific and the effects of each parameter were non-monotonic, often with a very specific range providing therapeutic benefit (for example, Fig. 1). The objective measures were more sensitive than clinical judgement and show that an objective fitting method could improve benefits in individual patients.

OBJECTIVE: Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. APPROACH: We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. MAIN RESULTS: In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as 'partial-FMP' stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). SIGNIFICANCE: The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode position. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance.

Deep Brain Stimulation (DBS) is rapidly emerging as a safe and effective treatment option for mitigating the effects of tremor. Despite the relative success of DBS for treating tremor, a common and typically unquantified adverse effect of treatment is dysarthria (slurred speech). Current assessment protocols are driven by the qualitative judgements of treating clinicians and lack the sensitivity and objectivity required to make reliable decisions about treatment optimisation. Therefore we aimed to pilot a speech evaluation procedure that would form the basis of an objective clinical DBS optimisation tool for use in patients with tremor. Six patients diagnosed with essential tremor receiving treatment via deep brain stimulation of the posterior sub-thalamic nucleus were recruited. Electrical stimulation parameters (i.e., pulse rate, pulse duration, and current amplitude) were systematically adjusted and speech samples recorded to identify the patient-specific settings required for optimal therapeutic benefit (reduced tremor) with minimal adverse effects (dysarthria). Altered speech production between stimulation parameters was quantified via acoustic analysis. Measures of timing (e.g., speech rate), intonation (e.g., pitch variation) and quality (e.g., noise-to-harmonics ratio) reflected increasing/decreasing levels of dysarthria (see associated figure). Via this protocol we aim to understand the inter-relationship between the effects of the parameters as well as to develop a real-time objective system for surgeons to optimise these parameters for each patient. A secondary outcome is to increase our understanding of how electrical parameter settings are related to movement and speech, and how the optimal parameters are related to the nature of the individual’s pathology.

OBJECTIVE: One strategy to improve the effectiveness of prosthetic vision devices is to process incoming images to ensure that key information can be perceived by the user. This paper presents the first comprehensive results of vision function testing for a suprachoroidal retinal prosthetic device utilizing of 20 stimulating electrodes. Further, we investigate whether using image filtering can improve results on a light localization task for implanted participants compared to minimal vision processing. No controlled implanted participant studies have yet investigated whether vision processing methods that are not task-specific can lead to improved results. APPROACH: Three participants with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal retinal prosthesis. All three completed multiple trials of a light localization test, and one participant completed multiple trials of acuity tests. The visual representations used were: Lanczos2 (a high quality Nyquist bandlimited downsampling filter); minimal vision processing (MVP); wide view regional averaging filtering (WV); scrambled; and, system off. MAIN RESULTS: Using Lanczos2, all three participants successfully completed a light localization task and obtained a significantly higher percentage of correct responses than using MVP ([Formula: see text]) or with system off ([Formula: see text]). Further, in a preliminary result using Lanczos2, one participant successfully completed grating acuity and Landolt C tasks, and showed significantly better performance ([Formula: see text]) compared to WV, scrambled and system off on the grating acuity task. SIGNIFICANCE: Participants successfully completed vision tasks using a 20 electrode suprachoroidal retinal prosthesis. Vision processing with a Nyquist bandlimited image filter has shown an advantage for a light localization task. This result suggests that this and targeted, more advanced vision processing schemes may become important components of retinal prostheses to enhance performance. ClinicalTrials.gov Identifier: NCT01503576.

BACKGROUND: The ability to separate two interleaved melodies is an important factor in music appreciation. This ability is greatly reduced in people with hearing impairment, contributing to difficulties in music appreciation. The aim of this study was to assess whether visual cues, musical training or musical context could have an effect on this ability, and potentially improve music appreciation for the hearing impaired. METHODS: Musicians (N = 18) and non-musicians (N = 19) were asked to rate the difficulty of segregating a four-note repeating melody from interleaved random distracter notes. Visual cues were provided on half the blocks, and two musical contexts were tested, with the overlap between melody and distracter notes either gradually increasing or decreasing. CONCLUSIONS: Visual cues, musical training, and musical context all affected the difficulty of extracting the melody from a background of interleaved random distracter notes. Visual cues were effective in reducing the difficulty of segregating the melody from distracter notes, even in individuals with no musical training. These results are consistent with theories that indicate an important role for central (top-down) processes in auditory streaming mechanisms, and suggest that visual cues may help the hearing-impaired enjoy music.