Medical Bionics - Research Publications

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    Plug-and-play microphones for recording speech and voice with smart devices
    Noffs, G ; Cobler-Lichter, M ; Perera, T ; Kolbe, SC ; Butzkueven, H ; Boonstra, FMC ; van der Walt, A ; Vogel, AP (KARGER, 2023-11-16)
    INTRODUCTION Smart devices are widely available and capable of quickly recording and uploading speech segments for health-related analysis. The switch from laboratory recordings with professional-grade microphone set ups to remote, smart device-based recordings offers immense potential for the scalability of voice assessment. Yet, a growing body of literature points to a wide heterogeneity among acoustic metrics for their robustness to variation in recording devices. The addition of consumer-grade plug-and-play microphones has been proposed as a possible solution. Our aim was to assess if the addition of consumer-grade plug-and-play microphones increase the acoustic measurement agreement between ultra-portable devices and a reference microphone. METHODS Speech was simultaneously recorded by a reference high-quality microphone commonly used in research, and by two configurations with plug-and-play microphones. Twelve speech-acoustic features were calculated using recordings from each microphone to determine the agreement intervals in measurements between microphones. Agreement intervals were then compared to expected deviations in speech in various neurological conditions. Each microphone's response to speech and to silence were characterized through acoustic analysis to explore possible reasons for differences in acoustic measurements between microphones. The statistical differentiation of two groups, neurotypical and people with Multiple Sclerosis, using metrics from each tested microphone was compared to that of the reference microphone. RESULTS The two consumer-grade plug-and-play microphones favoured high frequencies (mean centre of gravity difference ≥ +175.3Hz) and recorded more noise (mean difference in signal-to-noise ≤ -4.2dB) when compared to the reference microphone. Between consumer-grade microphones, differences in relative noise were closely related to distance between the microphone and the speaker's mouth. Agreement intervals between the reference and consumer-grade microphones remained under disease-expected deviations only for fundamental frequency (f0, agreement interval ≤0.06Hz), f0 instability (f0 CoV, agreement interval ≤0.05%) and for tracking of second formant movement (agreement interval ≤1.4Hz/millisecond). Agreement between microphones was poor for other metrics, particularly for fine timing metrics (mean pause length and pause length variability for various tasks). The statistical difference between the two groups of speakers was smaller with the plug-and-play than with the reference microphone. CONCLUSION Measurement of f0 and F2 slope were robust to variation in recording equipment while other acoustic metrics were not. Thus, the tested plug-and-play microphones should not be used interchangeably with professional-grade microphones for speech analysis. Plug-and-play microphones may assist in equipment standardization within speech studies, including remote or self-recording, possibly with small loss in accuracy and statistical power as observed in this study.
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    Spread of activation and interaction between channels with multi-channel optogenetic stimulation in the mouse cochlea
    Azees, AA ; Thompson, AC ; Thomas, R ; Zhou, J ; Ruther, P ; Wise, AK ; Ajay, EA ; Garrett, DJ ; Quigley, A ; Fallon, JB ; Richardson, RT (ELSEVIER, 2023-12)
    For individuals with severe to profound hearing loss resulting from irreversibly damaged hair cells, cochlear implants can be used to restore hearing by delivering electrical stimulation directly to the spiral ganglion neurons. However, current spread lowers the spatial resolution of neural activation. Since light can be easily confined, optogenetics is a technique that has the potential to improve the precision of neural activation, whereby visible light is used to stimulate neurons that are modified with light-sensitive opsins. This study compares the spread of neural activity across the inferior colliculus of the auditory midbrain during electrical and optical stimulation in the cochlea of acutely deafened mice with opsin-modified spiral ganglion neurons (H134R variant of the channelrhodopsin-2). Monopolar electrical stimulation was delivered via each of four 0.2 mm wide platinum electrode rings at 0.6 mm centre-to-centre spacing, whereas 453 nm wavelength light was delivered via each of five 0.22 × 0.27 mm micro-light emitting diodes (LEDs) at 0.52 mm centre-to-centre spacing. Channel interactions were also quantified by threshold changes during simultaneous stimulation by pairs of electrodes or micro-LEDs at different distances between the electrodes (0.6, 1.2 and 1.8 mm) or micro-LEDs (0.52, 1.04, 1.56 and 2.08 mm). The spread of activation resulting from single channel optical stimulation was approximately half that of monopolar electrical stimulation as measured at two levels of discrimination above threshold (p<0.001), whereas there was no significant difference between optical stimulation in opsin-modified deafened mice and pure tone acoustic stimulation in normal-hearing mice. During simultaneous micro-LED stimulation, there were minimal channel interactions for all micro-LED spacings tested. For neighbouring micro-LEDs/electrodes, the relative influence on threshold was 13-fold less for optical stimulation compared electrical stimulation (p<0.05). The outcomes of this study show that the higher spatial precision of optogenetic stimulation results in reduced channel interaction compared to electrical stimulation, which could increase the number of independent channels in a cochlear implant. Increased spatial resolution and the ability to activate more than one channel simultaneously could lead to better speech perception in cochlear implant recipients.
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    Timing is Everything: Stochastic Optogenetic Stimulation Reduces Adaptation in Retinal Ganglion Cells.
    Kwan, WC ; Brunton, EK ; Begeng, JM ; Richardson, RT ; Ibbotson, MR ; Tong, W (IEEE, 2023-07)
    Optogenetics gives us unprecedented power to investigate brain connectivity. The ability to activate neural circuits with single cell resolution and its ease of application has provided a wealth of knowledge in brain function. More recently, optogenetics has shown tremendous utility in prosthetics applications, including vision restoration for patients with retinitis pigmentosa. One of the disadvantages of optogenetics, however, is its poor temporal bandwidth, i.e. the cell's inability to fire at a rate that matches the optical stimulation rate at high frequencies (>30 Hz). This research proposes a new strategy to overcome the temporal limits of optogenetic stimulation. Using whole-cell current clamp recordings in mouse retinal ganglion cells expressing channelrhodopsin-2 (H134R variant), we observed that randomizing inter-pulse intervals can significantly increase a retinal ganglion cell's temporal response to high frequency stimulation.Clinical Relevance- A significant disadvantage of optogenetic stimulation is its poor temporal dynamics which prohibit its widespread use in retinal prosthetics. We have shown that randomizing the interval between stimulation pulses reduces adaptation in retinal ganglion cells. This stimulation strategy may contribute to new levels of functional restoration in therapeutics which incorporate optogenetics.
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    Clinical outcomes of deep brain stimulation for obsessive-compulsive disorder: Insight as a predictor of symptom changes
    Acevedo, N ; Rossell, S ; Castle, D ; Groves, C ; Cook, M ; Mcneill, P ; Olver, J ; Meyer, D ; Perera, T ; Bosanac, P (WILEY, 2024-02)
    AIM: Deep brain stimulation (DBS) is a safe and effective treatment option for people with refractory obsessive-compulsive disorder (OCD). Yet our understanding of predictors of response and prognostic factors remains rudimentary, and long-term comprehensive follow-ups are lacking. We aim to investigate the efficacy of DBS therapy for OCD patients, and predictors of clinical response. METHODS: Eight OCD participants underwent DBS stimulation of the nucleus accumbens (NAc) in an open-label longitudinal trial, duration of follow-up varied between 9 months and 7 years. Post-operative care involved comprehensive fine tuning of stimulation parameters and adjunct multidisciplinary therapy. RESULTS: Six participants achieved clinical response (35% improvement in obsessions and compulsions on the Yale Brown Obsessive Compulsive Scale (YBOCS)) within 6-9 weeks, response was maintained at last follow up. On average, the YBOCS improved by 45% at last follow up. Mixed linear modeling elucidated directionality of symptom changes: insight into symptoms strongly predicted (P = 0.008) changes in symptom severity during DBS therapy, likely driven by initial changes in depression and anxiety. Precise localization of DBS leads demonstrated that responders most often had their leads (and active contacts) placed dorsal compared to non-responders, relative to the Nac. CONCLUSION: The clinical efficacy of DBS for OCD is demonstrated, and mediators of changes in symptoms are proposed. The symptom improvements within this cohort should be seen within the context of the adjunct psychological and biopsychosocial care that implemented a shared decision-making approach, with flexible iterative DBS programming. Further research should explore the utility of insight as a clinical correlate of response. The trial was prospectively registered with the ANZCTR (ACTRN12612001142820).
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    Anatomical targeting for electrode localization in subthalamic nucleus deep brain stimulation: A comparative study
    Tonroe, T ; McDermott, H ; Pearce, P ; Acevedo, N ; Thevathasan, W ; Xu, SS ; Bulluss, K ; Perera, T (WILEY, 2023-09)
    BACKGROUND AND PURPOSE: In deep brain stimulation (DBS), accurate electrode placement is essential for optimizing patient outcomes. Localizing electrodes enables insight into therapeutic outcomes and development of metrics for use in clinical trials. Methods of defining anatomical targets have been described with varying accuracy and objectivity. To assess variability in anatomical targeting, we compare four methods of defining an appropriate target for DBS of the subthalamic nucleus for Parkinson's disease. METHODS: The methods compared are direct visualization, red nucleus-based indirect targeting, mid-commissural point-based indirect targeting, and automated template-based targeting. This study assessed 226 hemispheres in 113 DBS recipients (39 females, 73 males, 62.2 ± 7.7 years). We utilized the electrode placement error (the Euclidean distance between the defined target and closest DBS electrode) as a metric for comparative analysis. Pairwise differences in electrode placement error across the four methods were compared using the Kruskal-Wallis H-test and Wilcoxon signed-rank tests. RESULTS: Interquartile ranges of the differences in electrode placement error spanned 1.18-1.56 mm. A Kruskal-Wallis H-test reported a statistically significant difference in the median of at least two groups (H(5) = 41.052, p < .001). Wilcoxon signed-rank tests reported statistically significant difference in two comparisons: direct visualization versus red nucleus-based indirect, and direct visualization versus automated template-based methods (T < 9215, p < .001). CONCLUSIONS: All methods were similarly discordant in their relative accuracy, despite having significant technical differences in their application. The differing protocols and technical aspects of each method, however, have the implication that one may be more practical depending on the clinical or research application at hand.
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    Flexible neural recording electrodes based on reduced graphene oxide interfaces
    Dong, M ; Chen, P ; Zhou, K ; Liu, M ; Thomas, S ; Coleman, HA ; Li, D ; Fallon, JB ; Majumder, M ; Parkington, HC ; Forsythe, JS (ELSEVIER SCIENCE SA, 2023-12-15)
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    Experienced Meditators Show Multifaceted Attention-Related Differences in Neural Activity
    Bailey, NW ; Baell, O ; Payne, JE ; Humble, G ; Geddes, H ; Cahill, I ; Hill, AT ; Chung, SW ; Emonson, M ; Murphy, OW ; Fitzgerald, PB (Springer, 2023-11-01)
    Objectives: Mindfulness meditation (MM) is suggested to improve attention. Research has explored this using the “attentional-blink” (AB) task, where stimuli are rapidly presented, and a second target stimulus (T2) is often missed if presented ~300 ms after an initial target stimulus (T1). Previous research has shown improved task accuracy during the AB task and altered neural activity following an intensive 3-month MM retreat. We tested whether these results replicated in a community sample of typical meditators. Method: Thirty-one mindfulness meditators and 30 non-meditators completed an AB task while electroencephalography (EEG) was recorded. Between-group comparisons were made for task accuracy, event-related potential activity (posterior-N2 and P3b), theta and alpha oscillatory phase synchronisation to stimuli presentation, and alpha-power. The primary aim was to examine effects within the time windows reported in previous research. Additional exploratory aims assessed effects across broader time windows. Results: No differences were detected in task accuracy or neural activity within our primary hypotheses. However, exploratory analyses showed posterior-N2 and theta phase synchronisation (where the phase of theta oscillations were synchronised to stimuli onset) effects indicating meditators showed a priority towards attending to T2 stimuli (p < 0.01). Meditators also showed more alpha-phase synchronisation, and lower alpha-power (with smaller amplitudes of activity in the alpha frequency) when processing T2 stimuli (p < 0.025). Conclusions: Our results showed multiple differences in neural activity that suggested enhanced attention in meditators. The neural activity patterns in meditators aligned with theoretical perspectives on activity associated with enhanced cognitive performance. These include enhanced alpha “gating” mechanisms (where alpha activity acts as a filter between sensory and higher order neural processes), increased oscillatory synchronisation to stimuli, and more equal allocation of neural activity across stimuli. However, meditators did not show higher task accuracy, nor were the effects consistent with our primary hypotheses or previous research. Preregistration: This study was not preregistered.
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    Developing the supraparticle technology for round window-mediated drug administration into the cochlea
    Gunewardene, N ; Ma, Y ; Lam, P ; Wagstaff, S ; Cortez-Jugo, C ; Hu, Y ; Caruso, F ; Richardsona, RT ; Wise, AK (ELSEVIER, 2023-09)
    The semi-permeable round window membrane (RWM) is the gateway to the cochlea. Although the RWM is considered a minimally invasive and clinically accepted route for localised drug delivery to the cochlea, overcoming this barrier is challenging, hindering development of effective therapies for hearing loss. Neurotrophin 3 (NT3) is an emerging treatment option for hearing loss, but its therapeutic effect relies on sustained delivery across the RWM into the cochlea. Silica supraparticles (SPs) are drug delivery carriers capable of providing long-term NT3 delivery, when injected directly into the guinea pig cochlea. However, for clinical translation, a RWM delivery approach is desirable. Here, we aimed to test approaches to improve the longevity and biodistribution of NT3 inside the cochlea after RWM implantation of SPs in guinea pigs and cats. Three approaches were tested (i) coating the SPs to slow drug release (ii) improving the retention of SPs on the RWM using a clinically approved gel formulation and (iii) permeabilising the RWM with hyaluronic acid. A radioactive tracer (iodine 125: 125I) tagged to NT3 (125I NT3) was loaded into the SPs to characterise drug pharmacokinetics in vitro and in vivo. The neurotrophin-loaded SPs were coated using a chitosan and alginate layer-by-layer coating strategy, named as '(Chi/Alg)SPs', to promote long term drug release. The guinea pigs were implanted with 5× 125I NT3 loaded (Chi/Alg) SPs on the RWM, while cats were implanted with 30× (Chi/Alg) SPs. A cohort of animals were also implanted with SPs (controls). We found that the NT3 loaded (Chi/Alg)SPs exhibited a more linear release profile compared to NT3 loaded SPs alone. The 125I NT3 loaded (Chi/Alg)SPs in fibrin sealant had efficient drug loading (~5 μg of NT3 loaded per SP that weights ~50 μg) and elution capacities (~49% over one month) in vitro. Compared to the SPs in fibrin sealant, the (Chi/Alg)SPs in fibrin sealant had a significantly slower 125I NT3 drug release profile over the first 7 days in vitro (~12% for (Chi/Alg) SPs in fibrin sealant vs ~43% for SPs in fibrin sealant). One-month post-implantation of (Chi/Alg) SPs, gamma count measurements revealed an average of 0.3 μg NT3 remained in the guinea pig cochlea, while for the cat, 1.3 μg remained. Histological analysis of cochlear tissue revealed presence of a 125I NT3 signal localised in the basilar membrane of the lower basal turn in some cochleae after 4 weeks in guinea pigs and 8 weeks in cats. Comparatively, and in contrast to the in vitro release data, implantation of the SPs presented better NT3 retention and distribution inside the cochlea in both the guinea pigs and cats. No significant difference in drug entry was observed upon acute treatment of the RWM with hyaluronic acid. Collectively, our findings indicate that SPs and (Chi/Alg)SPs can facilitate drug transfer across the RWM, with detectable levels inside the cat cochlea even after 8 weeks with the intracochlear approach. This is the first study to examine neurotrophin pharmacokinetics in the cochlea for such an extended period of times in these two animal species. Whilst promising, we note that outcomes between animals were variable, and opposing results were found between in vitro and in vivo release studies. These findings have important clinical ramifications, emphasising the need to understand the physical properties and mechanics of this complex barrier in parallel with the development of therapies for hearing loss.
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    Hybrid optogenetic and electrical stimulation for greater spatial resolution and temporal fidelity of cochlear activation
    Thompson, AC ; Wise, AK ; Hart, WL ; Needham, K ; Fallon, JB ; Gunewardene, N ; Stoddart, PR ; Richardson, RT (IOP PUBLISHING LTD, 2020-10)
    OBJECTIVE: Compared to electrical stimulation, optogenetic stimulation has the potential to improve the spatial precision of neural activation in neuroprostheses, but it requires intense light and has relatively poor temporal kinetics. We tested the effect of hybrid stimulation, which is the combination of subthreshold optical and electrical stimuli, on spectral and temporal fidelity in the cochlea by recording multiunit activity in the inferior colliculus of channelrhodopsin (H134R variant) transgenic mice. APPROACH: Pulsed light or biphasic electrical pulses were delivered to cochlear spiral ganglion neurons of acutely deafened mice, either as individual stimuli or as hybrid stimuli for which the timing of the electrical pulse had a varied delay relative to the start of the optical pulse. Response thresholds, spread of activation and entrainment data were obtained from multi-unit recordings from the auditory midbrain. MAIN RESULTS: Facilitation occurred when subthreshold electrical stimuli were applied at the end of, or up to 3.75 ms after subthreshold optical pulses. The spread of activation resulting from hybrid stimulation was significantly narrower than electrical-only and optical-only stimulation (p < 0.01), measured at equivalent suprathreshold levels of loudness that are relevant to cochlear implant users. Furthermore, temporal fidelity, measured as maximum following rates to 300 ms pulse trains bursts up to 240 Hz, was 2.4-fold greater than optical-only stimulation (p < 0.05). SIGNIFICANCE: By significantly improving spectral resolution of electrical- and optical-only stimulation and the temporal fidelity of optical-only stimulation, hybrid stimulation has the potential to increase the number of perceptually independent stimulating channels in a cochlear implant.
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    The effects of aging and musicianship on the use of auditory streaming cues
    Sauve, SA ; Marozeau, J ; Zendel, BR ; Fu, Q-J (PUBLIC LIBRARY SCIENCE, 2022-09-22)
    Auditory stream segregation, or separating sounds into their respective sources and tracking them over time, is a fundamental auditory ability. Previous research has separately explored the impacts of aging and musicianship on the ability to separate and follow auditory streams. The current study evaluated the simultaneous effects of age and musicianship on auditory streaming induced by three physical features: intensity, spectral envelope and temporal envelope. In the first study, older and younger musicians and non-musicians with normal hearing identified deviants in a four-note melody interleaved with distractors that were more or less similar to the melody in terms of intensity, spectral envelope and temporal envelope. In the second study, older and younger musicians and non-musicians participated in a dissimilarity rating paradigm with pairs of melodies that differed along the same three features. Results suggested that auditory streaming skills are maintained in older adults but that older adults rely on intensity more than younger adults while musicianship is associated with increased sensitivity to spectral and temporal envelope, acoustic features that are typically less effective for stream segregation, particularly in older adults.