Medical Bionics - Research Publications
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ItemIntensity Discrimination and Speech Recognition of Cochlear Implant Users(SPRINGER, 2018-10)The relation between speech recognition and within-channel or across-channel (i.e., spectral tilt) intensity discrimination was measured in nine CI users (11 ears). Within-channel intensity difference limens (IDLs) were measured at four electrode locations across the electrode array. Spectral tilt difference limens were measured with (XIDL-J) and without (XIDL) level jitter. Only three subjects could perform the XIDL-J task with the amount of jitter required to limit use of within-channel cues. XIDLs (normalized to %DR) were correlated with speech recognition (r = 0.67, P = 0.019) and were highly correlated with IDLs. XIDLs were on average nearly 3 times larger than IDLs and did not vary consistently with the spatial separation of the two component electrodes. The overall pattern of results was consistent with a common underlying subject-dependent limitation in the two difference limen tasks, hypothesized to be perceptual variance (how the perception of a sound differs on different presentations), which may also underlie the correlation of XIDLs with speech recognition. Evidence that spectral tilt discrimination is more important for speech recognition than within-channel intensity discrimination was not unequivocally shown in this study. However, the results tended to support this proposition, with XIDLs more correlated with speech performance than IDLs, and the ratio XIDL/IDL also being correlated with speech recognition. If supported by further research, the importance of perceptual variance as a limiting factor in speech understanding for CI users has important implications for efforts to improve outcomes for those with poor speech recognition.
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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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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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ItemTargeting the LOX/hypoxia axis reverses many of the features that make pancreatic cancer deadly: inhibition of LOX abrogates metastasis and enhances drug efficacy(WILEY, 2015-08)Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related mortality. Despite significant advances made in the treatment of other cancers, current chemotherapies offer little survival benefit in this disease. Pancreaticoduodenectomy offers patients the possibility of a cure, but most will die of recurrent or metastatic disease. Hence, preventing metastatic disease in these patients would be of significant benefit. Using principal component analysis (PCA), we identified a LOX/hypoxia signature associated with poor patient survival in resectable patients. We found that LOX expression is upregulated in metastatic tumors from Pdx1-Cre Kras(G12D/+) Trp53(R172H/+) (KPC) mice and that inhibition of LOX in these mice suppressed metastasis. Mechanistically, LOX inhibition suppressed both migration and invasion of KPC cells. LOX inhibition also synergized with gemcitabine to kill tumors and significantly prolonged tumor-free survival in KPC mice with early-stage tumors. This was associated with stromal alterations, including increased vasculature and decreased fibrillar collagen, and increased infiltration of macrophages and neutrophils into tumors. Therefore, LOX inhibition is able to reverse many of the features that make PDAC inherently refractory to conventional therapies and targeting LOX could improve outcome in surgically resectable disease.
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ItemPerceptual Spaces Induced by Cochlear Implant All-Polar Stimulation Mode(SAGE PUBLICATIONS INC, 2016-09-07)It has been argued that a main limitation of the cochlear implant is the spread of current induced by each electrode, which activates an inappropriately large range of sensory neurons. To reduce this spread, an alternative stimulation mode, the all-polar mode, was tested with five participants. It was designed to activate all the electrodes simultaneously with appropriate current levels and polarities to recruit narrower regions of auditory nerves at specific intracochlear electrode positions (denoted all-polar electrodes). In this study, the all-polar mode was compared with the current commercial stimulation mode: the monopolar mode. The participants were asked to judge the sound dissimilarity between pairs of two-electrode pulse-train stimuli that differed in the electrode positions and were presented in either monopolar or all-polar mode with pulses on the two electrodes presented either sequentially or simultaneously. The dissimilarity ratings were analyzed using a multidimensional scaling technique and three-dimensional stimulus perceptual spaces were produced. For all the conditions (mode and simultaneity), the first perceptual dimension was highly correlated with the position of the most apical activated electrode of the electrical stimulation and the second dimension with the position of the most basal electrode. In both sequential and simultaneous conditions, the monopolar and all-polar stimuli were significantly separated by a third dimension, which may indicate that all-polar stimuli have a perceptual quality that differs from monopolar stimuli. Overall, the results suggest that both modes might successfully represent spectral information in a sound processing strategy.
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ItemEffect of Pulse Rate and Polarity on the Sensitivity of Auditory Brainstem and Cochlear Implant Users to Electrical Stimulation(SPRINGER, 2015-10)To further understand the response of the human brainstem to electrical stimulation, a series of experiments compared the effect of pulse rate and polarity on detection thresholds between auditory brainstem implant (ABI) and cochlear implant (CI) patients. Experiment 1 showed that for 400-ms pulse trains, ABI users' thresholds dropped by about 2 dB as pulse rate was increased from 71 to 500 pps, but only by an average of 0.6 dB as rate was increased further to 3500 pps. This latter decrease was much smaller than the 7.7-dB observed for CI users. A similar result was obtained for pulse trains with a 40-ms duration. Furthermore, experiment 2 showed that the threshold difference between 500- and 3500-pps pulse trains remained much smaller for ABI than for CI users, even for durations as short as 2 ms, indicating the effect of a fast-acting mechanism. Experiment 3 showed that ABI users' thresholds were lower for alternating-polarity than for fixed-polarity pulse trains, and that this difference was greater at 3500 pps than at 500 pps, consistent with the effect of pulse rate on ABI users' thresholds being influenced by charge interactions between successive biphasic pulses. Experiment 4 compared thresholds and loudness between trains of asymmetric pulses of opposite polarity, in monopolar mode, and showed that in both cases less current was needed when the anodic, rather than the cathodic, current was concentrated into a short time interval. This finding is similar to that previously observed for CI users and is consistent with ABI users being more sensitive to anodic than cathodic current. We argue that our results constrain potential explanations for the differences in the perception of electrical stimulation by CI and ABI users, and have potential implications for future ABI stimulation strategies.
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ItemComment on: Short pulse width widens the therapeutic window of subthalamic neurostimulation(WILEY-BLACKWELL, 2015-10)
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ItemCortical Processing Related to Intensity of a Modulated Noise Stimulus-a Functional Near-Infrared Study(SPRINGER, 2018-06)Sound intensity is a key feature of auditory signals. A profound understanding of cortical processing of this feature is therefore highly desirable. This study investigates whether cortical functional near-infrared spectroscopy (fNIRS) signals reflect sound intensity changes and where on the brain cortex maximal intensity-dependent activations are located. The fNIRS technique is particularly suitable for this kind of hearing study, as it runs silently. Twenty-three normal hearing subjects were included and actively participated in a counterbalanced block design task. Four intensity levels of a modulated noise stimulus with long-term spectrum and modulation characteristics similar to speech were applied, evenly spaced from 15 to 90 dB SPL. Signals from auditory processing cortical fields were derived from a montage of 16 optodes on each side of the head. Results showed that fNIRS responses originating from auditory processing areas are highly dependent on sound intensity level: higher stimulation levels led to higher concentration changes. Caudal and rostral channels showed different waveform morphologies, reflecting specific cortical signal processing of the stimulus. Channels overlying the supramarginal and caudal superior temporal gyrus evoked a phasic response, whereas channels over Broca's area showed a broad tonic pattern. This data set can serve as a foundation for future auditory fNIRS research to develop the technique as a hearing assessment tool in the normal hearing and hearing-impaired populations.
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ItemAssessing hearing by measuring heartbeat: The effect of sound level(PUBLIC LIBRARY SCIENCE, 2019-02-28)Functional near-infrared spectroscopy (fNIRS) is a non-invasive brain imaging technique that measures changes in oxygenated and de-oxygenated hemoglobin concentration and can provide a measure of brain activity. In addition to neural activity, fNIRS signals contain components that can be used to extract physiological information such as cardiac measures. Previous studies have shown changes in cardiac activity in response to different sounds. This study investigated whether cardiac responses collected using fNIRS differ for different loudness of sounds. fNIRS data were collected from 28 normal hearing participants. Cardiac response measures evoked by broadband, amplitude-modulated sounds were extracted for four sound intensities ranging from near-threshold to comfortably loud levels (15, 40, 65 and 90 dB Sound Pressure Level (SPL)). Following onset of the noise stimulus, heart rate initially decreased for sounds of 15 and 40 dB SPL, reaching a significantly lower rate at 15 dB SPL. For sounds at 65 and 90 dB SPL, increases in heart rate were seen. To quantify the timing of significant changes, inter-beat intervals were assessed. For sounds at 40 dB SPL, an immediate significant change in the first two inter-beat intervals following sound onset was found. At other levels, the most significant change appeared later (beats 3 to 5 following sound onset). In conclusion, changes in heart rate were associated with the level of sound with a clear difference in response to near-threshold sounds compared to comfortably loud sounds. These findings may be used alone or in conjunction with other measures such as fNIRS brain activity for evaluation of hearing ability.
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ItemTemporal Coding of Voice Pitch Contours in Mandarin Tones(FRONTIERS MEDIA SA, 2018-07-24)Accurate perception of time-variant pitch is important for speech recognition, particularly for tonal languages with different lexical tones such as Mandarin, in which different tones convey different semantic information. Previous studies reported that the auditory nerve and cochlear nucleus can encode different pitches through phase-locked neural activities. However, little is known about how the inferior colliculus (IC) encodes the time-variant periodicity pitch of natural speech. In this study, the Mandarin syllable /ba/ pronounced with four lexical tones (flat, rising, falling then rising and falling) were used as stimuli. Local field potentials (LFPs) and single neuron activity were simultaneously recorded from 90 sites within contralateral IC of six urethane-anesthetized and decerebrate guinea pigs in response to the four stimuli. Analysis of the temporal information of LFPs showed that 93% of the LFPs exhibited robust encoding of periodicity pitch. Pitch strength of LFPs derived from the autocorrelogram was significantly (p < 0.001) stronger for rising tones than flat and falling tones. Pitch strength are also significantly increased (p < 0.05) with the characteristic frequency (CF). On the other hand, only 47% (42 or 90) of single neuron activities were significantly synchronized to the fundamental frequency of the stimulus suggesting that the temporal spiking pattern of single IC neuron could encode the time variant periodicity pitch of speech robustly. The difference between the number of LFPs and single neurons that encode the time-variant F0 voice pitch supports the notion of a transition at the level of IC from direct temporal coding in the spike trains of individual neurons to other form of neural representation.