Medical Bionics - Research Publications

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    Neural Electrodes Based on 3D Organic Electroactive Microfibers
    Marroquin, JB ; Coleman, HA ; Tonta, MA ; Zhou, K ; Winther-Jensen, B ; Fallon, J ; Duffy, NW ; Yan, E ; Abdulwahid, AA ; Jasieniak, JJ ; Forsythe, JS ; Parkington, HC (Wiley, 2018-03-21)
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    Gaze Compensation as a Technique for Improving Hand-Eye Coordination in Prosthetic Vision
    Titchener, SA ; Shivdasani, MN ; Fallon, JB ; Petoe, MA (ASSOC RESEARCH VISION OPHTHALMOLOGY INC, 2018-01-01)
    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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    An objective in vivo diagnostic method for inflammatory bowel disease
    Payne, SC ; Shepherd, RK ; Sedo, A ; Fallon, JB ; Furness, JB (ROYAL SOC, 2018-03-01)
    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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    Subthalamic nucleus deep brain stimulation evokes resonant neural activity
    Sinclair, NC ; McDermott, HJ ; Bulluss, KJ ; Fallon, JB ; Perera, T ; Xu, SS ; Brown, P ; Thevathasan, W (WILEY, 2018-05-01)
    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.
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    Temporal Coding of Voice Pitch Contours in Mandarin Tones
    Peng, F ; Innes-Brown, H ; McKay, CM ; Fallon, JB ; Zhou, Y ; Wang, X ; Hu, N ; Hou, W (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.
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    Anti-inflammatory Effects of Abdominal Vagus Nerve Stimulation on Experimental Intestinal Inflammation
    Payne, SC ; Furness, JB ; Burns, O ; Sedo, A ; Flyakumurat, T ; Shepherd, RK ; Fallon, JB (FRONTIERS MEDIA SA, 2019-05-08)
    Electrical stimulation of the cervical vagus nerve is an emerging treatment for inflammatory bowel disease (IBD). However, side effects from cervical vagal nerve stimulation (VNS) are often reported by patients. Here we hypothesized that stimulating the vagus nerve closer to the end organ will have fewer off-target effects and will effectively reduce intestinal inflammation. Specifically, we aimed to: (i) compare off-target effects during abdominal and cervical VNS; (ii) verify that VNS levels were suprathreshold; and (iii) determine whether abdominal VNS reduces chemically-induced intestinal inflammation in rats. An electrode array was developed in-house to stimulate and record vagal neural responses. In a non-recovery experiment, stimulation-induced off-target effects were measured by implanting the cervical and abdominal vagus nerves of anaesthetized rats (n = 5) and recording changes to heart rate, respiration and blood pressure during stimulation (10 Hz; symmetric biphasic current pulse; 320 nC per phase). In a chronic experiment, the efficacy of VNS treatment was assessed by implanting an electrode array onto the abdominal vagus nerve and recording in vivo electrically-evoked neural responses during the implantation period. After 14 days, the intestine was inflamed with TNBS (2.5% 2,4,6-trinitrobenzene sulphonic acid) and rats received therapeutic VNS (n = 7; 10 Hz; 320 nC per phase; 3 h/day) or no stimulation (n = 8) for 4.5 days. Stool quality, plasma C-reactive protein and histology of the inflamed intestine were assessed. Data show that abdominal VNS had no effect (two-way RM-ANOVA: P ≥ 0.05) on cardiac, respiratory and blood pressure parameters. However, during cervical VNS heart rate decreased by 31 ± 9 beats/minute (P ≥ 0.05), respiration was inhibited and blood pressure decreased. Data addressing efficacy of VNS treatment show that electrically-evoked neural response thresholds remained stable (one-way RM ANOVA: P ≥ 0.05) and therapeutic stimulation remained above threshold. Chronically stimulated rats, compared to unstimulated rats, had improved stool quality (two-way RM ANOVA: P < 0.0001), no blood in feces (P < 0.0001), reduced plasma C-reactive protein (two-way RM ANOVA: P < 0.05) and a reduction in resident inflammatory cell populations within the intestine (Kruskal-Wallis: P < 0.05). In conclusion, abdominal VNS did not evoke off-target effects, is an effective treatment of TNBS-induced inflammation, and may be an effective treatment of IBD in humans.
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    Wireless induction coils embedded in diamond for power transfer in medical implants
    Sikder, MKU ; Fallon, J ; Shivdasani, MN ; Ganesan, K ; Seligman, P ; Garrett, DJ (SPRINGER, 2017-12-01)
    Wireless power and data transfer to medical implants is a research area where improvements in current state-of-the-art technologies are needed owing to the continuing efforts for miniaturization. At present, lithographical patterning of evaporated metals is widely used for miniature coil fabrication. This method produces coils that are limited to low micron or nanometer thicknesses leading to high impedance values and thus limiting their potential quality. In the present work we describe a novel technique, whereby trenches were milled into a diamond substrate and filled with silver active braze alloy, enabling the manufacture of small, high cross-section, low impedance microcoils capable of transferring up to 10 mW of power up to a distance of 6 mm. As a substitute for a metallic braze line used for hermetic sealing, a continuous metal loop when placed parallel and close to the coil surface reduced power transfer efficiency by 43%, but not significantly, when placed perpendicular to the microcoil surface. Encapsulation of the coil by growth of a further layer of diamond reduced the quality factor by an average of 38%, which can be largely avoided by prior oxygen plasma treatment. Furthermore, an accelerated ageing test after encapsulation showed that these coils are long lasting. Our results thus collectively highlight the feasibility of fabricating a high-cross section, biocompatible and long lasting miniaturized microcoil that could be used in either a neural recording or neuromuscular stimulation device.
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    A partial hearing animal model for chronic electro-acoustic stimulation
    Irving, S ; Wise, AK ; Millard, RE ; Shepherd, RK ; Fallon, JB (IOP PUBLISHING LTD, 2014-08-01)
    OBJECTIVE: Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. APPROACH: This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. MAIN RESULTS: Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. SIGNIFICANCE: This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual hearing following cochlear implantation. The ability to record CAPs via the CI has clinical direct relevance for obtaining objective measures of residual hearing.
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    Evaluation of focused multipolar stimulation for cochlear implants in long-term deafened cats
    George, SS ; Wise, AK ; Fallon, JB ; Shepherd, RK (IOP PUBLISHING LTD, 2015-06-01)
    OBJECTIVE: Focused multipolar (FMP) stimulation has been shown to produce restricted neural activation using intracochlear stimulation in animals with a normal population of spiral ganglion neurons (SGNs). However, in a clinical setting, the widespread loss of SGNs and peripheral fibres following deafness is expected to influence the effectiveness of FMP. APPROACH: We compared the efficacy of FMP stimulation to both monopolar (MP) and tripolar (TP) stimulation in long-term deafened cat cochleae (n = 8). Unlike our previous study, these cochleae contained <10% of the normal SGN population adjacent to the electrode array. We also evaluated the effect of electrode position on stimulation modes by using either modiolar facing or lateral wall facing half-band electrodes. The spread of neural activity across the inferior colliculus, a major nucleus within the central auditory pathway, was used as a measure of spatial selectivity. MAIN RESULTS: In cochleae with significant SGN degeneration, we observed that FMP and TP stimulation resulted in greater spatial selectivity than MP stimulation (p < 0.001). However, thresholds were significantly higher for FMP and TP stimulation compared to MP stimulation (p < 0.001). No difference between FMP and TP stimulation was found in any measures. The high threshold levels for FMP stimulation was significantly reduced without compromising spatial selectivity by varying the degree of current focusing (referred as 'partial-FMP' stimulation). Spatial selectivity of all stimulation modes was unaffected by the electrode position. Finally, spatial selectivity in long-term deafened cochleae was significantly less than that of cochleae with normal SGN population (George S S et al 2014 J. Neural Eng. 11 065003). SIGNIFICANCE: The present results indicate that the greater spatial selectivity of FMP and TP stimulation over MP stimulation is maintained in cochleae with significant neural degeneration and is not adversely affected by electrode position. The greater spatial selectivity of FMP and TP stimulation would be expected to result in improved clinical performance.
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    Effects of chronic cochlear electrical stimulation after an extended period of profound deafness on primary auditory cortex organization in cats
    Fallon, JB ; Shepherd, RK ; Irvine, DRF (WILEY, 2014-03-01)
    Extended periods of deafness have profound effects on central auditory system function and organization. Neonatal deafening results in loss of the normal cochleotopic organization of the primary auditory cortex (AI), but environmentally-derived intracochlear electrical stimulation, via a cochlear implant, initiated shortly after deafening, can prevent this loss. We investigated whether such stimulation initiated after an extended period of deafness can restore cochleotopy. In two groups of neonatally-deafened cats, a multi-channel intracochlear electrode array was implanted at 8 weeks of age. One group received only minimal stimulation, associated with brief recordings at 4-6-week intervals, over the following 6 months to check the efficacy of the implant. In the other group, this 6-month period was followed by 6 months of near-continuous intracochlear electrical stimulation from a modified clinical cochlear implant system. We recorded multi-unit clusters in the auditory cortex and used two different methods to define the region of interest in the putative AI. There was no evidence of cochleotopy in any of the minimally stimulated animals, confirming our earlier finding. In three of six chronically stimulated cats there was clear evidence of AI cochleotopy, and in a fourth cat in which the majority of penetrations were in the anterior auditory field there was clear evidence of cochleotopy in that field. The finding that chronic intracochlear electrical stimulation after an extended period of deafness is able to restore cochleotopy in some (but not all) cases has implications for the performance of patients implanted after an extended period of deafness.