Medical Bionics - Research Publications
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ItemHuman cortical processing of interaural coherence(CELL PRESS, 2022-05-20)Sounds reach the ears as a mixture of energy generated by different sources. Listeners extract cues that distinguish different sources from one another, including how similar sounds arrive at the two ears, the interaural coherence (IAC). Here, we find listeners cannot reliably distinguish two completely interaurally coherent sounds from a single sound with reduced IAC. Pairs of sounds heard toward the front were readily confused with single sounds with high IAC, whereas those heard to the sides were confused with single sounds with low IAC. Sounds that hold supra-ethological spatial cues are perceived as more diffuse than can be accounted for by their IAC, and this is accounted for by a computational model comprising a restricted, and sound-frequency dependent, distribution of auditory-spatial detectors. We observed elevated cortical hemodynamic responses for sounds with low IAC, suggesting that the ambiguity elicited by sounds with low interaural similarity imposes elevated cortical load.
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ItemBlood glucose modulation and safety of efferent vagus nerve stimulation in a type 2 diabetic rat model(WILEY, 2022-04-01)Vagus nerve stimulation is emerging as a promising treatment for type 2 diabetes. Here, we evaluated the ability of stimulation of the vagus nerve to reduce glycemia in awake, freely moving metabolically compromised rats. A model of type 2 diabetes (n = 10) was induced using a high-fat diet and low doses of streptozotocin. Stimulation of the abdominal vagus nerve was achieved by pairing 15 Hz pulses on a distal pair of electrodes with high-frequency blocking stimulation (26 kHz, 4 mA) on a proximal pair of electrodes to preferentially produce efferent conducting activity (eVNS). Stimulation was well tolerated in awake, freely moving rats. During 1 h of eVNS, glycemia decreased in 90% of subjects (-1.25 ± 1.25 mM h, p = 0.017), and 2 dB above neural threshold was established as the most effective "dose" of eVNS (p = 0.009). Following 5 weeks of implantation, eVNS was still effective, resulting in significantly decreased glycemia (-1.7 ± 0.6 mM h, p = 0.003) during 1 h of eVNS. There were no overt changes in fascicle area or signs of histopathological damage observed in implanted vagal nerve tissue following chronic implantation and stimulation. Demonstration of the biocompatibility and safety of eVNS in awake, metabolically compromised animals is a critical first step to establishing this therapy for clinical use. With further development, eVNS could be a promising novel therapy for treating type 2 diabetes.
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ItemPlatinum dissolution and tissue response following long-term electrical stimulation at high charge densities(IOP PUBLISHING LTD, 2021-04-01)Objective. Established guidelines for safe levels of electrical stimulation for neural prostheses are based on a limited range of the stimulus parameters used clinically. Recent studies have reported particulate platinum (Pt) associated with long-term clinical use of these devices, highlighting the need for more carefully defined safety limits. We previously reported no adverse effects of Pt corrosion products in the cochleae of guinea pigs following 4 weeks of electrical stimulation using charge densities far greater than the published safe limits for cochlear implants. The present study examines the histopathological effects of Pt within the cochlea following continuous stimulation at a charge density well above the defined safe limits for periods up to 6 months.Approach. Six cats were bilaterally implanted with Pt electrode arrays and unilaterally stimulated using charge balanced current pulses at a charge density of 267μC cm-2phase-1using a tripolar electrode configuration. Electrochemical measurements were made throughout the implant duration and evoked potentials recorded at the outset and on completion of the stimulation program. Cochleae were examined histologically for particulate Pt, tissue response, and auditory nerve survival; electrodes were examined for surface corrosion; and cochlea, brain, kidney, and liver tissue analysed for trace levels of Pt.Main results. Chronic stimulation resulted in both a significant increase in tissue response and particulate Pt within the tissue capsule surrounding the electrode array compared with implanted, unstimulated control cochleae. Importantly, there was no stimulus-induced loss of auditory neurons (ANs) or increase in evoked potential thresholds. Stimulated electrodes were significantly more corroded compared with unstimulated electrodes. Trace analysis revealed Pt in both stimulated and control cochleae although significantly greater levels were detected within stimulated cochleae. There was no evidence of Pt in brain or liver; however, trace levels of Pt were recorded in the kidneys of two animals. Finally, increased charge storage capacity and charge injection limit reflected the more extensive electrode corrosion associated with stimulated electrodes.Significance. Long-term electrical stimulation of Pt electrodes at a charge density well above existing safety limits and nearly an order of magnitude higher than levels used clinically, does not adversely affect the AN population or reduce neural function, despite a stimulus-induced tissue response and the accumulation of Pt corrosion product. The mechanism resulting in Pt within the unstimulated cochlea is unclear, while the level of Pt observed systemically following stimulation at these very high charge densities does not appear to be of clinical significance.
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ItemPreclinical safety study of a fully implantable, sub-scalp ring electrode array for long-term EEG recordings(IOP Publishing Ltd, 2022-06-01)OBJECTIVE: Long-term electroencephalogram (EEG) recordings can aid diagnosis and management of various neurological conditions such as epilepsy. In this study we characterize the safety and stability of a clinical grade ring electrode arrays by analyzing EEG recordings, fluoroscopy, and computed tomography (CT) imaging with long-term implantation and histopathological tissue response. APPROACH: Seven animals were chronically implanted with EEG recording array consisting of four electrode contacts. Recordings were made bilaterally using a bipolar longitudinal montage. The array was connected to a fully implantable micro-processor controlled electronic device with two low-noise differential amplifiers and a transmitter-receiver coil. An external wearable was used to power, communicate with the implant via an inductive coil, and store the data. The sub-scalp electrode arrays were made using medical grade silicone and platinum. The electrode arrays were tunneled in the subgaleal cleavage plane between the periosteum and the overlying dermis. These were implanted for 3-7 months before euthanasia and histopathological assessment. EEG and impedance were recorded throughout the study. MAIN RESULTS: Impedance measurements remained low throughout the study for 11 of 12 channels over the recording period ranged from 3 to 5 months. There was also a steady amplitude of slow-wave EEG and chewing artifact (noise). The post-mortem CT and histopathology showed the electrodes remained in the subgaleal plane in 6 of 7 sheep. There was minimal inflammation with a thin fibrotic capsule that ranged from 4 to 101μm. There was a variable fibrosis in the subgaleal plane extending from 210 to 3617μm (S3-S7) due to surgical cleavage. One sheep had an inflammatory reaction due to electrode extrusion. The passive electrode array extraction force was around 1N. SIGNIFICANCE: Results show sub-scalp electrode placement was safe and stable for long term implantation. This is advantageous for diagnosis and management of neurological conditions where long-term, EEG monitoring is required.
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ItemReducing false discoveries in resting-state functional connectivity using short channel correction: an fNIRS study.(SPIE-Intl Soc Optical Eng, 2022-01)Significance: Functional near-infrared spectroscopy (fNIRS) is a neuroimaging tool that can measure resting-state functional connectivity; however, non-neuronal components present in fNIRS signals introduce false discoveries in connectivity, which can impact interpretation of functional networks. Aim: We investigated the effect of short channel correction on resting-state connectivity by removing non-neuronal signals from fNIRS long channel data. We hypothesized that false discoveries in connectivity can be reduced, hence improving the discriminability of functional networks of known, different connectivity strengths. Approach: A principal component analysis-based short channel correction technique was applied to resting-state data of 10 healthy adult subjects. Connectivity was analyzed using magnitude-squared coherence of channel pairs in connectivity groups of homologous and control brain regions, which are known to differ in connectivity. Results: By removing non-neuronal components using short channel correction, significant reduction of coherence was observed for oxy-hemoglobin concentration changes in frequency bands associated with resting-state connectivity that overlap with the Mayer wave frequencies. The results showed that short channel correction reduced spurious correlations in connectivity measures and improved the discriminability between homologous and control groups. Conclusions: Resting-state functional connectivity analysis with short channel correction performs better than without correction in its ability to distinguish functional networks with distinct connectivity characteristics.
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ItemTowards guided and automated programming of subthalamic area stimulation in Parkinson's disease(OXFORD UNIV PRESS, 2022-01-04)Selecting the ideal contact to apply subthalamic nucleus deep brain stimulation in Parkinson's disease can be an arduous process, with outcomes highly dependent on clinician expertise. This study aims to assess whether neuronal signals recorded intraoperatively in awake patients, and the anatomical location of contacts, can assist programming. In a cohort of 14 patients with Parkinson's disease, implanted with subthalamic nucleus deep brain stimulation, the four contacts on each lead in the 28 hemispheres were ranked according to proximity to a nominated ideal anatomical location and power of the following neuronal signals: evoked resonant neural activity, beta oscillations and high-frequency oscillations. We assessed how these rankings predicted, on each lead: (i) the motor benefit from deep brain stimulation applied through each contact and (ii) the 'ideal' contact to apply deep brain stimulation. The ranking of contacts according to each factor predicted motor benefit from subthalamic nucleus deep brain stimulation, as follows: evoked resonant neural activity; r 2 = 0.50, Akaike information criterion 1039.9, beta; r 2 = 0.50, Akaike information criterion 1041.6, high-frequency oscillations; r 2 = 0.44, Akaike information criterion 1057.2 and anatomy; r 2 = 0.49, Akaike information criterion 1048.0. Combining evoked resonant neural activity, beta and high-frequency oscillations ranking data yielded the strongest predictive model (r 2 = 0.61, Akaike information criterion 1021.5). The 'ideal' contact (yielding maximal benefit) was ranked first according to each factor in the following proportion of hemispheres; evoked resonant neural activity 18/28, beta 17/28, anatomy 16/28, high-frequency oscillations 7/28. Across hemispheres, the maximal available deep brain stimulation benefit did not differ from that yielded by contacts chosen by clinicians for chronic therapy or contacts ranked first according to evoked resonant neural activity. Evoked resonant neural activity, beta oscillations and anatomy similarly predicted how motor benefit from subthalamic nucleus deep brain stimulation varied across contacts on each lead. This could assist programming by providing a probability ranking of contacts akin to a 'monopolar survey'. However, these factors identified the 'ideal' contact in only a proportion of hemispheres. More advanced signal processing and anatomical techniques may be needed for the full automation of contact selection.
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ItemSpeech token detection and discrimination in individual infants using functional near-infrared spectroscopy(NATURE PORTFOLIO, 2021-12-14)Speech detection and discrimination ability are important measures of hearing ability that may inform crucial audiological intervention decisions for individuals with a hearing impairment. However, behavioral assessment of speech discrimination can be difficult and inaccurate in infants, prompting the need for an objective measure of speech detection and discrimination ability. In this study, the authors used functional near-infrared spectroscopy (fNIRS) as the objective measure. Twenty-three infants, 2 to 10 months of age participated, all of whom had passed newborn hearing screening or diagnostic audiology testing. They were presented with speech tokens at a comfortable listening level in a natural sleep state using a habituation/dishabituation paradigm. The authors hypothesized that fNIRS responses to speech token detection as well as speech token contrast discrimination could be measured in individual infants. The authors found significant fNIRS responses to speech detection in 87% of tested infants (false positive rate 0%), as well as to speech discrimination in 35% of tested infants (false positive rate 9%). The results show initial promise for the use of fNIRS as an objective clinical tool for measuring infant speech detection and discrimination ability; the authors highlight the further optimizations of test procedures and analysis techniques that would be required to improve accuracy and reliability to levels needed for clinical decision-making.
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ItemLow-frequency STN-DBS provides acute gait improvements in Parkinson's disease: a double-blinded randomised cross-over feasibility trial(BMC, 2021-08-10)BACKGROUND: Some people with Parkinson's disease (PD) report poorer dynamic postural stability following high-frequency deep brain stimulation of the subthalamic nucleus (STN-DBS), which may contribute to an increased falls risk. However, some studies have shown low-frequency (60 Hz) STN-DBS improves clinical measures of postural stability, potentially providing support for this treatment. This double-blind randomised crossover study aimed to investigate the effects of low-frequency STN-DBS compared to high-frequency stimulation on objective measures of gait rhythmicity in people with PD. METHODS: During high- and low-frequency STN-DBS and while off-medication, participants completed assessments of symptom severity and walking (e.g., Timed Up-and-Go). During comfortable walking, the harmonic ratio, an objective measures of gait rhythmicity, was derived from head- and trunk-mounted accelerometers to provide insight in dynamic postural stability. Lower harmonic ratios represent less rhythmic walking and have discriminated people with PD who experience falls. Linear mixed model analyses were performed on fourteen participants. RESULTS: Low-frequency STN-DBS significantly improved medial-lateral and vertical trunk rhythmicity compared to high-frequency. Improvements were independent of electrode location and total electrical energy delivered. No differences were noted between stimulation conditions for temporal gait measures, clinical mobility measures, motor symptom severity or the presence of gait retropulsion. CONCLUSIONS: This study provides evidence for the acute benefits of low-frequency stimulation for gait outcomes in STN-DBS PD patients, independent of electrode location. However, the perceived benefits of this therapy may be diminished for people who experienced significant tremor pre-operatively, as lower frequencies may cause these symptoms to re-emerge. TRIAL REGISTRATION: This study was prospectively registered with the Australian and New Zealand Clinical Trials Registry on 5 June 2018 (ACTRN12618000944235).
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ItemHow accurately are subthalamic nucleus electrodes implanted relative to the ideal stimulation location for Parkinson's disease?(PUBLIC LIBRARY SCIENCE, 2021-07-15)INTRODUCTION: The efficacy of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) depends on how closely electrodes are implanted relative to an individual's ideal stimulation location. Yet, previous studies have assessed how closely electrodes are implanted relative to the planned location, after homogenizing data to a reference. Thus here, we measured how accurately electrodes are implanted relative to an ideal, dorsal STN stimulation location, assessed on each individual's native imaging. This measure captures not only the technical error of stereotactic implantation but also constraints imposed by planning a suitable trajectory. METHODS: This cross-sectional study assessed 226 electrodes in 113 consecutive PD patients implanted with bilateral STN-DBS by experienced clinicians utilizing awake, microelectrode guided, surgery. The error (Euclidean distance) between the actual electrode trajectory versus a nominated ideal, dorsal STN stimulation location was determined in each hemisphere on native imaging and predictive factors sought. RESULTS: The median electrode location error was 1.62 mm (IQR = 1.23 mm). This error exceeded 3 mm in 28/226 electrodes (12.4%). Location error did not differ between hemispheres implanted first or second, suggesting brain shift was minimised. Location error did not differ between electrodes positioned with (48/226), or without, a preceding microelectrode trajectory shift (suggesting such shifts were beneficial). There was no relationship between location error and case order, arguing against a learning effect. DISCUSSION/CONCLUSION: The proximity of STN-DBS electrodes to a nominated ideal, dorsal STN, stimulation location is highly variable, even when implanted by experienced clinicians with brain shift minimized, and without evidence of a learning effect. Using this measure, we found that assessments on awake patients (microelectrode recordings and clinical examination) likely yielded beneficial intraoperative decisions to improve positioning. In many patients the error is likely to have reduced therapeutic efficacy. More accurate methods to implant STN-DBS electrodes relative to the ideal stimulation location are needed.
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ItemAnalysis methods for measuring passive auditory fNIRS responses generated by a block-design paradigm(SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS, 2021-04-01)Significance: Functional near-infrared spectroscopy (fNIRS) is an increasingly popular tool in auditory research, but the range of analysis procedures employed across studies may complicate the interpretation of data. Aim: We aim to assess the impact of different analysis procedures on the morphology, detection, and lateralization of auditory responses in fNIRS. Specifically, we determine whether averaging or generalized linear model (GLM)-based analysis generates different experimental conclusions when applied to a block-protocol design. The impact of parameter selection of GLMs on detecting auditory-evoked responses was also quantified. Approach: 17 listeners were exposed to three commonly employed auditory stimuli: noise, speech, and silence. A block design, comprising sounds of 5 s duration and 10 to 20 s silent intervals, was employed. Results: Both analysis procedures generated similar response morphologies and amplitude estimates, and both indicated that responses to speech were significantly greater than to noise or silence. Neither approach indicated a significant effect of brain hemisphere on responses to speech. Methods to correct for systemic hemodynamic responses using short channels improved detection at the individual level. Conclusions: Consistent with theoretical considerations, simulations, and other experimental domains, GLM and averaging analyses generate the same group-level experimental conclusions. We release this dataset publicly for use in future development and optimization of algorithms.