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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ItemAssociation between hemorrhagic transformation after endovascular therapy and poststroke seizures(WILEY, 2018-02)OBJECTIVE: Endovascular therapy has recently become standard therapy for select patients with acute ischemic stroke. Infarcted brain tissue may undergo hemorrhagic transformation (HT) after endovascular therapy. We investigated the association between HT and occurrence of poststroke seizures in patients treated with endovascular therapy. METHODS: Consecutive patients treated with endovascular therapy for acute anterior circulation ischemic stroke were included. HT was assessed with computed tomography/magnetic resonance imaging (CT/MRI) at 24 h after stroke onset. Patients were followed for up to 2 years for seizure occurrence. RESULTS: A total of 205 (57.1% male) patients were analyzed. Median age was 69 years (interquartile range [IQR] 57-78). Among patients with HT, 17.9% (10/56) developed poststroke seizures compared with 4.0% (6/149) among those without HT (hazard ratio [HR] 5.52; 95% confidence interval [CI] 2.00-15.22; P = .001). The association remained significant after adjustment for cortical involvement, baseline National Institutes of Health Stroke Scale score, age and use of intravenous tissue plasminogen activator and clot retrieval (HR 4.85; 95% CI 1.60-14.76; P = .005). In patients who developed seizures within the follow-up period, median time to first seizure was 111 days (IQR 28-369) in patients with HT and 36 days (IQR 0.5-183) in patients without HT. SIGNIFICANCE: A patient who develops HT following endovascular therapy for acute ischemic stroke had a nearly 5 times higher rate of developing poststroke seizures within 2 years. HT may be used as an imaging biomarker for poststroke seizures.
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ItemNeural Electrodes Based on 3D Organic Electroactive Microfibers(WILEY-V C H VERLAG GMBH, 2018-03-21)Abstract Neural electrodes used for in vivo biomedical applications (e.g., prostheses, bionic implants) result in glial invasion, leading to the formation of a nonexcitable scar that increases the distance between neurons and electrode and increases the resistance to current flow. The result is progressive deterioration in the performance of stimulation or recording of neural activity and inevitable device failure. Also, electrodes with a 2D surface have a limited proximity to neurons. In the present study, a macroporous and fibrous 3D neural electrode is developed using poly‐L‐lactic acid fibrous membranes imbued with electroactive properties via a coating of the conductive polymer poly(3,4‐ethylenedioxythiophene) (PEDOT), using vapor phase polymerization. The electrical properties of the PEDOT‐coated substrates are studied using sheet resistance and impedance. PEDOT electrode biocompatibility is assessed through in vitro assays using patch‐clamp electrophysiology and calcium imaging of isolated and cultured rat hippocampal neurons. PEDOT fibers support robust normal functional development of neurons, including synaptic networking and communication. Stimulation and recording of activity in brain slices and from the surface of the brain using 3D‐PEDOT fibrous electrodes are indistinguishable from recordings using conventional glass or platinum electrodes. In vivo studies reveal minimal reactive gliosis in response to electrode implantation.
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ItemHeterogeneity of Purkinje cell simple spike-complex spike interactions: zebrin- and non-zebrin-related variations(WILEY, 2017-08-01)KEY POINTS: Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spikes. Although they are generated by distinct mechanisms, interactions between the two spike types exist. Zebrin staining produces alternating positive and negative stripes of PCs across most of the cerebellar cortex. Thus, here we compared simple spike-complex spike interactions both within and across zebrin populations. Simple spike activity undergoes a complex modulation preceding and following a complex spike. The amplitudes of the pre- and post-complex spike modulation phases were correlated across PCs. On average, the modulation was larger for PCs in zebrin positive regions. Correlations between aspects of the complex spike waveform and simple spike activity were found, some of which varied between zebrin positive and negative PCs. The implications of the results are discussed with regard to hypotheses that complex spikes are triggered by rises in simple spike activity for either motor learning or homeostatic functions. ABSTRACT: Purkinje cells (PCs) generate two types of action potentials, called simple and complex spikes (SSs and CSs). We first investigated the CS-associated modulation of SS activity and its relationship to the zebrin status of the PC. The modulation pattern consisted of a pre-CS rise in SS activity, and then, following the CS, a pause, a rebound, and finally a late inhibition of SS activity for both zebrin positive (Z+) and negative (Z-) cells, though the amplitudes of the phases were larger in Z+ cells. Moreover, the amplitudes of the pre-CS rise with the late inhibitory phase of the modulation were correlated across PCs. In contrast, correlations between modulation phases across CSs of individual PCs were generally weak. Next, the relationship between CS spikelets and SS activity was investigated. The number of spikelets/CS correlated with the average SS firing rate only for Z+ cells. In contrast, correlations across CSs between spikelet numbers and the amplitudes of the SS modulation phases were generally weak. Division of spikelets into likely axonally propagated and non-propagated groups (based on their interspikelet interval) showed that the correlation of spikelet number with SS firing rate primarily reflected a relationship with non-propagated spikelets. In sum, the results show both zebrin-related and non-zebrin-related physiological heterogeneity in SS-CS interactions among PCs, which suggests that the cerebellar cortex is more functionally diverse than is assumed by standard theories of cerebellar function.
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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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ItemAuditory Stream Segregation and Selective Attention for Cochlear Implant Listeners: Evidence From Behavioral Measures and Event-Related Potentials(FRONTIERS MEDIA SA, 2018-08-21)The role of the spatial separation between the stimulating electrodes (electrode separation) in sequential stream segregation was explored in cochlear implant (CI) listeners using a deviant detection task. Twelve CI listeners were instructed to attend to a series of target sounds in the presence of interleaved distractor sounds. A deviant was randomly introduced in the target stream either at the beginning, middle or end of each trial. The listeners were asked to detect sequences that contained a deviant and to report its location within the trial. The perceptual segregation of the streams should, therefore, improve deviant detection performance. The electrode range for the distractor sounds was varied, resulting in different amounts of overlap between the target and the distractor streams. For the largest electrode separation condition, event-related potentials (ERPs) were recorded under active and passive listening conditions. The listeners were asked to perform the behavioral task for the active listening condition and encouraged to watch a muted movie for the passive listening condition. Deviant detection performance improved with increasing electrode separation between the streams, suggesting that larger electrode differences facilitate the segregation of the streams. Deviant detection performance was best for deviants happening late in the sequence, indicating that a segregated percept builds up over time. The analysis of the ERP waveforms revealed that auditory selective attention modulates the ERP responses in CI listeners. Specifically, the responses to the target stream were, overall, larger in the active relative to the passive listening condition. Conversely, the ERP responses to the distractor stream were not affected by selective attention. However, no significant correlation was observed between the behavioral performance and the amount of attentional modulation. Overall, the findings from the present study suggest that CI listeners can use electrode separation to perceptually group sequential sounds. Moreover, selective attention can be deployed on the resulting auditory objects, as reflected by the attentional modulation of the ERPs at the group level.
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ItemBalance control systems in Parkinson's disease and the impact of pedunculopontine area stimulation(OXFORD UNIV PRESS, 2018-10)Impaired balance is a major contributor to falls and diminished quality of life in Parkinson's disease, yet the pathophysiology is poorly understood. Here, we assessed if patients with Parkinson's disease and severe clinical balance impairment have deficits in the intermittent and continuous control systems proposed to maintain upright stance, and furthermore, whether such deficits are potentially reversible, with the experimental therapy of pedunculopontine nucleus deep brain stimulation. Two subject groups were assessed: (i) 13 patients with Parkinson's disease and severe clinical balance impairment, implanted with pedunculopontine nucleus deep brain stimulators; and (ii) 13 healthy control subjects. Patients were assessed in the OFF medication state and blinded to two conditions; off and on pedunculopontine nucleus stimulation. Postural sway data (deviations in centre of pressure) were collected during quiet stance using posturography. Intermittent control of sway was assessed by calculating the frequency of intermittent switching behaviour (discontinuities), derived using a wavelet-based transformation of the sway time series. Continuous control of sway was assessed with a proportional-integral-derivative (PID) controller model using ballistic reaction time as a measure of feedback delay. Clinical balance impairment was assessed using the 'pull test' to rate postural reflexes and by rating attempts to arise from sitting to standing. Patients with Parkinson's disease demonstrated reduced intermittent switching of postural sway compared with healthy controls. Patients also had abnormal feedback gains in postural sway according to the PID model. Pedunculopontine nucleus stimulation improved intermittent switching of postural sway, feedback gains in the PID model and clinical balance impairment. Clinical balance impairment correlated with intermittent switching of postural sway (rho = - 0.705, P < 0.001) and feedback gains in the PID model (rho = 0.619, P = 0.011). These results suggest that dysfunctional intermittent and continuous control systems may contribute to the pathophysiology of clinical balance impairment in Parkinson's disease. Clinical balance impairment and their related control system deficits are potentially reversible, as demonstrated by their improvement with pedunculopontine nucleus deep brain stimulation.
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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.