Medical Bionics - Research Publications
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ItemThe Impact of Spatial Incongruence on an Auditory-Visual Illusion(PUBLIC LIBRARY SCIENCE, 2009-07-31)BACKGROUND: The sound-induced flash illusion is an auditory-visual illusion--when a single flash is presented along with two or more beeps, observers report seeing two or more flashes. Previous research has shown that the illusion gradually disappears as the temporal delay between auditory and visual stimuli increases, suggesting that the illusion is consistent with existing temporal rules of neural activation in the superior colliculus to multisensory stimuli. However little is known about the effect of spatial incongruence, and whether the illusion follows the corresponding spatial rule. If the illusion occurs less strongly when auditory and visual stimuli are separated, then integrative processes supporting the illusion must be strongly dependant on spatial congruence. In this case, the illusion would be consistent with both the spatial and temporal rules describing response properties of multisensory neurons in the superior colliculus. METHODOLOGY/PRINCIPAL FINDINGS: The main aim of this study was to investigate the importance of spatial congruence in the flash-beep illusion. Selected combinations of one to four short flashes and zero to four short 3.5 KHz tones were presented. Observers were asked to count the number of flashes they saw. After replication of the basic illusion using centrally-presented stimuli, the auditory and visual components of the illusion stimuli were presented either both 10 degrees to the left or right of fixation (spatially congruent) or on opposite (spatially incongruent) sides, for a total separation of 20 degrees. CONCLUSIONS/SIGNIFICANCE: The sound-induced flash fission illusion was successfully replicated. However, when the sources of the auditory and visual stimuli were spatially separated, perception of the illusion was unaffected, suggesting that the "spatial rule" does not extend to describing behavioural responses in this illusion. We also find no evidence for an associated "fusion" illusion reportedly occurring when multiple flashes are accompanied by a single beep.
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ItemThe Association of HMGB1 Gene with the Prognosis of HCC (Retracted Article)(PUBLIC LIBRARY SCIENCE, 2014-02-19)High-mobility group box 1 protein (HMGB1) is an evolutionarily ancient and critical regulator of cell death and survival. HMGB1 is a chromatin-associated nuclear protein molecule that triggers extracellular damage. The expression of HMGB1 has been reported in many types of cancers, but the role of HMGB1 in hepato cellular carcinoma (HCC) is unknown.The aim of this study was to analyze the roles of HMGB1 in HCC progression using HCC clinical samples. We also investigated the clinical outcomes of HCC samples with a special focus on HMBG1 expression. In an immunohistochemical study conducted on 208 cases of HCC, HMGB1 had high expression in 134 cases(64.4%).The HMGB1 expression level did not correlate with any clinicopathological parameters, except alpha fetoprotein (AFP) (p = 0.041) and CLIP stage (p = 0.007). However, survival analysis showed that the group with HMBG1 overexpression had a significantly shorter overall survival time than the group with a down-regulated expression of HMBG1 (HR = 0.568, CI (0.398, 0.811), p = 0.002). Multivariate analysis showed that HMGB1 expression was a significant and independent prognostic parameter (HR = 0.562, CI (0.388, 0.815), p = 0.002) for HCC patients. The ability of proliferation, migration and invasion of HCC cells was suppressed with the disruption of endogenous HMGB1 using small interfering RNAs. On the other hand, the ability of proliferation, migration and invasion of HCC cells was strengthened when the expression endogenous HMGB1 was enhanced using HMGB1 DNA. HMGB1 expression may be a novel and independent predictor for the prognosis of HCC patients. The overexpression of HMGB1 in HCC could be a novel, effective, and supplementary biomarker for HCC, since it plays a vital role in the progression of HCC.
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ItemAcross-frequency combination of interaural time difference in bilateral cochlear implant listeners.(Frontiers Media SA, 2014)The current study examined how cochlear implant (CI) listeners combine temporally interleaved envelope-ITD information across two sites of stimulation. When two cochlear sites jointly transmit ITD information, one possibility is that CI listeners can extract the most reliable ITD cues available. As a result, ITD sensitivity would be sustained or enhanced compared to single-site stimulation. Alternatively, mutual interference across multiple sites of ITD stimulation could worsen dual-site performance compared to listening to the better of two electrode pairs. Two experiments used direct stimulation to examine how CI users can integrate ITDs across two pairs of electrodes. Experiment 1 tested ITD discrimination for two stimulation sites using 100-Hz sinusoidally modulated 1000-pps-carrier pulse trains. Experiment 2 used the same stimuli ramped with 100 ms windows, as a control condition with minimized onset cues. For all stimuli, performance improved monotonically with increasing modulation depth. Results show that when CI listeners are stimulated with electrode pairs at two cochlear sites, sensitivity to ITDs was similar to that seen when only the electrode pair with better sensitivity was activated. None of the listeners showed a decrement in performance from the worse electrode pair. This could be achieved either by listening to the better electrode pair or by truly integrating the information across cochlear sites.
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ItemTemporal Processing in the Auditory System(SPRINGER, 2013-02)Central auditory processing in humans was investigated by comparing the perceptual effects of temporal parameters of electrical stimulation in auditory midbrain implant (AMI) and cochlear implant (CI) users. Four experiments were conducted to measure the following: effect of interpulse intervals on detection thresholds and loudness; temporal modulation transfer functions (TMTFs); effect of duration on detection thresholds; and forward masking decay. The CI data were consistent with a phenomenological model that based detection or loudness decisions on the output of a sliding temporal integration window, the input to which was the hypothetical auditory nerve response to each stimulus pulse. To predict the AMI data, the model required changes to both the neural response input (i.e., midbrain activity to AMI stimuli, compared to auditory nerve activity to CI stimuli) and the shape of the integration window. AMI data were consistent with a neural response that decreased more steeply compared to CI stimulation as the pulse rate increased or interpulse interval decreased. For one AMI subject, the data were consistent with a significant adaptation of the neural response for rates above 200 Hz. The AMI model required an integration window that was significantly wider (i.e., decreased temporal resolution) than that for CI data, the latter being well fit using the same integration window shape as derived from normal-hearing data. These models provide a useful way to conceptualize how stimulation of central auditory structures differs from stimulation of the auditory nerve and to better understand why AMI users have difficulty processing temporal cues important for speech understanding.
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ItemNo Preview AvailableneuroBi: A Highly Configurable Neurostimulator for a Retinal Prosthesis and Other Applications(IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC, 2015)To evaluate the efficacy of a suprachoroidal retinal prosthesis, a highly configurable external neurostimulator is required. In order to meet functional and safety specifications, it was necessary to develop a custom device. A system is presented which can deliver charge-balanced, constant-current biphasic pulses, with widely adjustable parameters, to arbitrary configurations of output electrodes. This system is shown to be effective in eliciting visual percepts in a patient with approximately 20 years of light perception vision only due to retinitis pigmentosa, using an electrode array implanted in the suprachoroidal space of the eye. The flexibility of the system also makes it suitable for use in a number of other emerging clinical neurostimulation applications, including epileptic seizure suppression and closed-loop deep brain stimulation. Clinical trial registration number NCT01603576 (www.clinicaltrials.gov).
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ItemNo Preview AvailableDirecting Human Induced Pluripotent Stem Cells into a Neurosensory Lineage for Auditory Neuron Replacement(MARY ANN LIEBERT, INC, 2014-08)Emerging therapies for sensorineural hearing loss include replacing damaged auditory neurons (ANs) using stem cells. Ultimately, it is important that these replacement cells can be patient-matched to avoid immunorejection. As human induced pluripotent stem cells (hiPSCs) can be obtained directly from the patient, they offer an opportunity to generate patient-matched neurons for transplantation. Here, we used an established neural induction protocol to differentiate two hiPSC lines (iPS1 and iPS2) and one human embryonic stem cell line (hESC; H9) toward a neurosensory lineage in vitro. Immunocytochemistry and qRT-PCR were used to analyze the expression of key markers involved in AN development at defined time points of differentiation. The hiPSC- and hESC-derived neurosensory progenitors expressed the dorsal hindbrain marker (PAX7), otic placodal marker (PAX2), proneurosensory marker (SOX2), ganglion neuronal markers (NEUROD1, BRN3A, ISLET1, ßIII-tubulin, Neurofilament kDa 160), and sensory AN markers (GATA3 and VGLUT1) over the time course examined. The hiPSC- and hESC-derived neurosensory progenitors had the highest expression levels of the sensory neural markers at 35 days in vitro. Furthermore, the neurons generated from this assay were found to be electrically active. While all cell lines analyzed produced functional neurosensory-like progenitors, variabilities in the levels of marker expression were observed between hiPSC lines and within samples of the same cell line, when compared with the hESC controls. Overall, these findings indicate that this neural assay was capable of differentiating hiPSCs toward a neurosensory lineage but emphasize the need for improving the consistency in the differentiation of hiPSCs into the required lineages.
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ItemCan ECAP Measures Be Used for Totally Objective Programming of Cochlear Implants?(SPRINGER, 2013-12)An experiment was conducted with eight cochlear implant subjects to investigate the feasibility of using electrically evoked compound action potential (ECAP) measures other than ECAP thresholds to predict the way that behavioral thresholds change with rate of stimulation, and hence, whether they can be used without combination with behavioral measures to determine program stimulus levels for cochlear implants. Loudness models indicate that two peripheral neural response characteristics contribute to the slope of the threshold versus rate function: the way that neural activity to each stimulus pulse decreases as rate increases and the slope of the neural response versus stimulus current function. ECAP measures related to these two characteristics were measured: the way that ECAP amplitude decreases with stimulus rate and the ECAP amplitude growth function, respectively. A loudness model (incorporating temporal integration and the two neural response characteristics) and regression analyses were used to evaluate whether the ECAP measures could predict the average slope of the behavioral threshold versus current function and whether individual variation in the measures could predict individual variation in the slope of the threshold function. The average change of behavioral threshold with increasing rate was well predicted by the model when using the average ECAP data. However, the individual variations in the slope of the thresholds versus rate functions were not well predicted by individual variations in ECAP data. It was concluded that these ECAP measures are not useful for fully objective programming, possibly because they do not accurately reflect the neural response characteristics assumed by the model, or are measured at current levels much higher than threshold currents.
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ItemNeural Responses in Parietal and Occipital Areas in Response to Visual Events Are Modulated by Prior Multisensory Stimuli(PUBLIC LIBRARY SCIENCE, 2013-12-31)The effect of multi-modal vs uni-modal prior stimuli on the subsequent processing of a simple flash stimulus was studied in the context of the audio-visual 'flash-beep' illusion, in which the number of flashes a person sees is influenced by accompanying beep stimuli. EEG recordings were made while combinations of simple visual and audio-visual stimuli were presented. The experiments found that the electric field strength related to a flash stimulus was stronger when it was preceded by a multi-modal flash/beep stimulus, compared to when it was preceded by another uni-modal flash stimulus. This difference was found to be significant in two distinct timeframes--an early timeframe, from 130-160 ms, and a late timeframe, from 300-320 ms. Source localisation analysis found that the increased activity in the early interval was localised to an area centred on the inferior and superior parietal lobes, whereas the later increase was associated with stronger activity in an area centred on primary and secondary visual cortex, in the occipital lobe. The results suggest that processing of a visual stimulus can be affected by the presence of an immediately prior multisensory event. Relatively long-lasting interactions generated by the initial auditory and visual stimuli altered the processing of a subsequent visual stimulus.
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ItemEvidence for Enhanced Multisensory Facilitation with Stimulus Relevance: An Electrophysiological Investigation(PUBLIC LIBRARY SCIENCE, 2013-01-23)Currently debate exists relating to the interplay between multisensory processes and bottom-up and top-down influences. However, few studies have looked at neural responses to newly paired audiovisual stimuli that differ in their prescribed relevance. For such newly associated audiovisual stimuli, optimal facilitation of motor actions was observed only when both components of the audiovisual stimuli were targets. Relevant auditory stimuli were found to significantly increase the amplitudes of the event-related potentials at the occipital pole during the first 100 ms post-stimulus onset, though this early integration was not predictive of multisensory facilitation. Activity related to multisensory behavioral facilitation was observed approximately 166 ms post-stimulus, at left central and occipital sites. Furthermore, optimal multisensory facilitation was found to be associated with a latency shift of induced oscillations in the beta range (14-30 Hz) at right hemisphere parietal scalp regions. These findings demonstrate the importance of stimulus relevance to multisensory processing by providing the first evidence that the neural processes underlying multisensory integration are modulated by the relevance of the stimuli being combined. We also provide evidence that such facilitation may be mediated by changes in neural synchronization in occipital and centro-parietal neural populations at early and late stages of neural processing that coincided with stimulus selection, and the preparation and initiation of motor action.
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ItemThe Categorisation of Non-Categorical Colours: A Novel Paradigm in Colour Perception(PUBLIC LIBRARY SCIENCE, 2013-03-25)In this paper, we investigate a new paradigm for studying the development of the colour 'signal' by having observers discriminate and categorize the same set of controlled and calibrated cardinal coloured stimuli. Notably, in both tasks, each observer was free to decide whether two pairs of colors were the same or belonged to the same category. The use of the same stimulus set for both tasks provides, we argue, an incremental behavioural measure of colour processing from detection through discrimination to categorisation. The measured data spaces are different for the two tasks, and furthermore the categorisation data is unique to each observer. In addition, we develop a model which assumes that the principal difference between the tasks is the degree of similarity between the stimuli which has different constraints for the categorisation task compared to the discrimination task. This approach not only makes sense of the current (and associated) data but links the processes of discrimination and categorisation in a novel way and, by implication, expands upon the previous research linking categorisation to other tasks not limited to colour perception.