Medical Bionics - Research Publications
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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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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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ItemGaze Compensation as a Technique for Improving Hand-Eye Coordination in Prosthetic Vision(ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-01)PURPOSE: Shifting the region-of-interest within the input image to compensate for gaze shifts ("gaze compensation") may improve hand-eye coordination in visual prostheses that incorporate an external camera. The present study investigated the effects of eye movement on hand-eye coordination under simulated prosthetic vision (SPV), and measured the coordination benefits of gaze compensation. METHODS: Seven healthy-sighted subjects performed a target localization-pointing task under SPV. Three conditions were tested, modeling: retinally stabilized phosphenes (uncompensated); gaze compensation; and no phosphene movement (center-fixed). The error in pointing was quantified for each condition. RESULTS: Gaze compensation yielded a significantly smaller pointing error than the uncompensated condition for six of seven subjects, and a similar or smaller pointing error than the center-fixed condition for all subjects (two-way ANOVA, P < 0.05). Pointing error eccentricity and gaze eccentricity were moderately correlated in the uncompensated condition (azimuth: R2 = 0.47; elevation: R2 = 0.51) but not in the gaze-compensated condition (azimuth: R2 = 0.01; elevation: R2 = 0.00). Increased variability in gaze at the time of pointing was correlated with greater reduction in pointing error in the center-fixed condition compared with the uncompensated condition (R2 = 0.64). CONCLUSIONS: Eccentric eye position impedes hand-eye coordination in SPV. While limiting eye eccentricity in uncompensated viewing can reduce errors, gaze compensation is effective in improving coordination for subjects unable to maintain fixation. TRANSLATIONAL RELEVANCE: The results highlight the present necessity for suppressing eye movement and support the use of gaze compensation to improve hand-eye coordination and localization performance in prosthetic vision.
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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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ItemAn objective in vivo diagnostic method for inflammatory bowel disease(ROYAL SOC, 2018-03)Inflammatory damage to the bowel, as occurs in inflammatory bowel disease (IBD), is debilitating to patients. In both patients and animal experimental models, histological analyses of biopsies and endoscopic examinations are used to evaluate the disease state. However, such measurements often have delays and are invasive, while endoscopy is not quantitatively objective. Therefore, a real-time quantitative method to assess compromised mucosal barrier function is advantageous. We investigated the correlation of in vivo changes in electrical transmural impedance with histological measures of inflammation. Four platinum (Pt) ball electrodes were placed in the lumen of the rat small intestine, with a return electrode under the skin. Electrodes placed within the non-inflamed intestine generated stable impedances during the 3 h testing period. Following an intraluminal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), an established animal model of IBD, impedances in the inflamed region significantly decreased relative to a region not exposed to TNBS (p < 0.05). Changes in intestinal transmural impedance were correlated (p < 0.05) with histologically assessed damage to the mucosa and increases in neutrophil, eosinophil and T-cell populations at 3 h compared with tissue from control regions. This quantitative, real-time assay may have application in the diagnosis and clinical management of IBD.
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ItemSubthalamic nucleus deep brain stimulation evokes resonant neural activity(WILEY, 2018-05)Deep brain stimulation (DBS) is a rapidly expanding treatment for neurological and psychiatric conditions; however, a target-specific biomarker is required to optimize therapy. Here, we show that DBS evokes a large-amplitude resonant neural response focally in the subthalamic nucleus. This response is greatest in the dorsal region (the clinically optimal stimulation target for Parkinson disease), coincides with improved clinical performance, is chronically recordable, and is present under general anesthesia. These features make it a readily utilizable electrophysiological signal that could potentially be used for guiding electrode implantation surgery and tailoring DBS therapy to improve patient outcomes. Ann Neurol 2018;83:1027-1031.