Browsing by Author "Fallon, James"
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- ItemAnti-inflammatory Effects of Abdominal Vagus Nerve Stimulation on Experimental Intestinal Inflammation(Frontiers, 2019-05) Payne, Sophie; Furness, John; Burns, Owen; Sedo, Alicia; Hyakumura, Tomoko; Shepherd, Robert; Fallon, JamesElectrical stimulation of the cervical vagus nerve is an emerging treatment for inflammatory bowel disease (IBD). However, cervical vagal nerve stimulation (VNS) can produce unwanted side effects. Here, we investigated whether stimulating the vagus nerve closer to the end organ has fewer off-target effects, while reducing intestinal inflammation. An electrode array was developed to stimulate and record vagal neural responses in rats. Acute VNS off-target experiment: The cervical and abdominal vagus nerves of anaesthetised rats (n=5) were acutely implanted with an electrode array, stimulation delivered (10 Hz; symmetric biphasic current pulse; 320 nC per phase) and changes to heart rate, respiration and blood pressure assessed. Chronic VNS efficacy experiment: The abdominal vagus nerve was chronically implanted with an electrode array. After 2 weeks, the intestine was inflamed with TNBS (2.5% 2,4,6-trinitrobenzene sulphonic acid), an established method for rodent models of IBD. Rats were randomly selected to receive therapeutic VNS (n=7; 10 Hz; symmetric biphasic current pulse; 320 nC per phase; 3 hours/day) or no stimulation (n=8) for 5 days. Stool quality, C-reactive protein in blood and histology of the inflamed intestine were assessed. VNS off-target experiment: 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. VNS efficacy experiment: During the implantation period, electrically-evoked neural response thresholds remained stable (one-way RM ANOVA: P>0.05), and were below stimulation levels. VNS rats, compared to unstimulated rats, had improved stool quality (two-way RM ANOVA: P<0.0001), no blood in faeces (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). 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.
- ItemAn Automated Psychoacoustic Testing Apparatus for Use in Cats(Elsevier, 2014-03) Benovitski, Yuri; Blamey, Peter; Rathbone, Graeme; Fallon, JamesAnimal behavioral studies make a significant contribution to hearing research and provide vital information which is not available from human subjects. Animal psychoacoustics is usually extremely time consuming and labor intensive; in addition, animals may become stressed, especially if restraints or negative reinforcers such as electric shocks are used. We present a novel behavioral experimental system that was developed to allow efficient animal training in response to acoustic stimuli. Cats were required to perform a relatively simple task of moving toward and away from the device depending on whether the members of a tone pair were different or the same in frequency (go/no-go task). The experimental setup proved to be effective, with all animals (N = 7) performing at above 90% correct on an easy task. Animals were trained within 2-4 weeks and then generated a total of 150-200 trials per day, distributed within approximately 8 self initiated sessions. Data collected using this system were stable over 1 week and repeatable over long test periods (14 weeks). Measured frequency discrimination thresholds from 3 animals at 3 different reference frequencies were comparable with previously published results. The main advantages of the system are: relatively simple setup; large amounts of data can be generated without the need of researcher supervision; multiple animals can be tested simultaneously without removal from home pens; and no electric shocks or restraints are required.
- ItemAn automated system for rapid evaluation of high-density electrode arrays in neural prostheses(Institute of Physics, 2011-06) John, Sam; Shivdasani, Mohit; Leuenberger, James; Fallon, James; Shepherd, Robert; Millard, Rodney; Rathbone, Graeme; Williams, ChrisThe success of high density electrode arrays for use in neural prostheses depends on efficient impedance monitoring and fault detection. Conventional methods of impedance testing and fault detection are time consuming and are not always suited for in-vivo assessment of high density electrode arrays. Additionally the ability to evaluate impedances and faults such as open and short circuits both, in-vitro and in-vivo are important to ensure safe and effective stimulation. In the present work we describe an automated system for the rapid evaluation of high density electrode arrays. The system uses a current pulse similar to that used to stimulate neural tissue and measures the voltage across the electrode in order to calculate the impedance. The switching of the system was validated by emulating a high density electrode array using light emitting diodes and a resistor- capacitor network. The system was tested in-vitro and in-vivo using a range of commercially available and in-house developed electrode arrays. The system accurately identified faults on an 84 electrode array in less than 20 seconds and reliably measured impedances up to 110 kn using a 200µA, 250 µs per phase current pulse. This system has direct application for screening high density electrode arrays in both a clinical and experimental setting.
- ItemA beamformer post-filter for cochlear implant noise reduction(Acoustical Society of America, 2013-04) Hersbach, Adam; Grayden, David; Fallon, James; McDermott, HughCochlear implant users have limited ability to understand speech in noisy conditions. Signal processing methods to address this issue that use multiple microphones typically use beamforming to perform noise reduction. However, the effectiveness of the beamformer is diminished as the number of interfering noises increases and the acoustic environment becomes more diffuse. A multimicrophone noise reduction algorithm that aims to address this issue is presented in this study. The algorithm uses spatial filtering to estimate the signal-to-noise ratio (SNR) and attenuates time-frequency elements that have poor SNR. The algorithm was evaluated by measuring intelligibility of speech embedded in 4-talker babble where the interfering talkers were spatially separated and changed location during the test. Twelve cochlear implant users took part in the evaluation, which demonstrated a significant mean improvement of 4.6 dB (standard error 0.4, P<0.001) in speech reception threshold compared to an adaptive beamformer. The results suggest that a substantial improvement in performance can be gained for cochlear implant users in noisy environments where the noise is spatially separated from the target speech.
- ItemBehavioral frequency discrimination ability of partially deafened cats using cochlear implants(Elsevier, 2014-09) Benovitski, Yuri; Blamey, Peter; Rathbone, Graeme; Fallon, JamesThe aim of this study was to determine the effects of cochlear implant (CI) use on behavioral frequency discrimination ability in partially deafened cats. We hypothesized that the additional information provided by the CI would allow subjects to perform better on a frequency discrimination task. Four cats with a high frequency hearing loss induced by ototoxic drugs were first trained on a go/no-go, positive reinforcement, frequency discrimination task and reached asymptotic performance (measured by d' - detection theory). Reference frequencies (1, 4, and 7 kHz) were systematically rotated (Block design) every 9-11 days to cover the hearing range of the cats while avoiding bias arising from the order of testing. Animals were then implanted with an intracochlear electrode array connected to a CI and speech processor. They then underwent 6 months of continuous performance measurement with the CI turned on, except for one month when the stimulator was turned off. Overall, subjects performed the frequency discrimination task significantly better with their CI turned on than in the CI-off condition (3-way ANOVA, p < 0.001). The analysis showed no dependence on subject (3-way ANOVA, subject × on-off condition, p > 0.5); however, the CI only significantly improved performance for two (1 and 7 kHz) of the three reference frequencies. In this study we were able to show, for the first time, that cats can utilize information provided by a CI in performing a behavioral frequency discrimination task.
- ItemChronic intracochlear electrical stimulation at high charge densities results in platinum dissolution but not neural loss or functional changes in vivo(IOP Publishing, 2019-01) Shepherd, Robert; Carter, Paul; Enke, Ya Lang; Wise, Andrew; Fallon, JamesOBJECTIVE: Although there are useful guidelines defining the boundary between damaging and non-damaging electrical stimulation they were derived from acute studies using large surface area electrodes in direct contact with cortical neurons. These parameters are a small subset of the parameters used by neural stimulators. More recently, histological examination of cochleae from patients that were long-term cochlear implant users have shown evidence of particulate platinum (Pt). The pathophysiological effect of Pt within the cochlea is unknown. We examined the response of the cochlea to stimulus levels beyond those regarded as safe, and to evaluate the pathophysiological response of the cochlea following chronic stimulation at charge densities designed to induce Pt corrosion. APPROACH: 19 guinea pigs were systemically deafened and implanted with a cochlear electrode array containing eight Pt electrodes of 0.05 0.075 or 0.2 mm2 area. Animals were electrically stimulated continuously for 28 days using charge balanced current pulses at charge densities of 400, 267 or 100 muC/cm2/phase. Electrically-evoked auditory brainstem responses (EABRs) were recorded to monitor neural function. On completion of stimulation electrodes were examined using scanning electron microscopy (SEM) and cochleae examined histology. Finally, analysis of Pt was measured using Energy Dispersive X-ray Spectroscopy (EDS) and inductively coupled plasma mass spectrometry (ICP-MS). MAIN RESULTS: Compared with unstimulated control electrodes and electrodes stimulated at 100 muC/cm2/phase, stimulation at 267 or 400 muC/cm2/phase resulted in significant Pt corrosion. Cochleae stimulated at these high charge densities contained particulate Pt. The extent of the foreign body response depended on the level of stimulation; cochleae stimulated at 267 or 400 muC/cm2/phase exhibited an extensive tissue response that included a focal region of necrosis close to the electrode. Despite chronic stimulation at high charge densities there was no loss of auditory neurons (ANs) in stimulated cochleae compared with their contralateral controls. Indeed, we report a statistically significant increase in AN density proximal to electrodes stimulated at 267 or 400 muC/cm2/phase. Finally, there was no evidence of a reduction in AN function associated with chronic stimulation at 100, 267 or 400 muC/cm2/phase as evidenced by stable EABR thresholds over the stimulation program. SIGNIFICANCE: Chronic electrical stimulation of Pt electrodes at 267 or 400 muC/cm2/phase evoked a vigorous tissue response and produced Pt corrosion products that were located close to the electrode. Despite these changes at the electrode/tissue interface there was no evidence of neural loss or a reduction in neural function.
- ItemCochlear implant use causes changes in the auditory cortex(2013) Irving, Sam; Irvine, Dexter; Shepherd, Robert; Fallon, JamesThe tuning of sites within the auditory cortex changes within the first three months of cochlear implant use.
- ItemCochlear implantation for chronic electrical stimulation in the mouse.(Elsevier, 2013-12) Irving, Samuel; Trotter, Matthew; Fallon, James; Millard, Rodney; Shepherd, Robert; Wise, AndrewThe mouse is becoming an increasingly attractive model for auditory research due to the number of genetic deafness models available. These genetic models offer the researcher an array of congenital causes of hearing impairment, and are therefore of high clinical relevance. To date, the use of mice in cochlear implant research has not been possible due to the lack of an intracochlear electrode array and stimulator small enough for murine use, coupled with the difficulty of the surgery in this species. Here, we present a fully-implantable intracochlear electrode stimulator assembly designed for chronic implantation in the mouse. We describe the surgical approach for implantation, as well as presenting the first functional data obtained from intracochlear electrical stimulation in the mouse.
- ItemCombined optogenetic and electrical stimulation of auditory neurons increases effective stimulation frequency—an in vitro study(IOP Publishing, 2020-01) Hart, William; Richardson, Rachael; Kameneva, Tatiana; Thompson, Alex; Wise, Andrew; Fallon, James; Stoddart, Paul; Needham, KarinaOBJECTIVE: The performance of neuroprostheses, including cochlear and retinal implants, is currently constrained by the spatial resolution of electrical stimulation. Optogenetics has improved the spatial control of neurons in vivo but lacks the fast-temporal dynamics required for auditory and retinal signalling. The objective of this study is to demonstrate that combining optical and electrical stimulation in vitro could address some of the limitations associated with each of the stimulus modes when used independently. APPROACH: The response of murine auditory neurons expressing ChR2-H134 to combined optical and electrical stimulation was characterised using whole cell patch clamp electrophysiology. MAIN RESULTS: Optogenetic costimulation produces a three-fold increase in peak firing rate compared to optical stimulation alone and allows spikes to be evoked by combined subthreshold optical and electrical inputs. Subthreshold optical depolarisation also facilitated spiking in auditory neurons for periods of up to 30 ms without evidence of wide-scale Na+ inactivation. Significance These findings may contribute to the development of spatially and temporally selective optogenetic-based neuroprosthetics and complement recent developments in "fast opsins".
- ItemCombining cell-based therapies and neural prostheses to promote neural survival(Springer, 2011-10) Wise, Andrew; Fallon, James; Neil, Alison; Pettingill, Lisa; Geaney, Marilyn; Skinner, Stephen; Shepherd, RobertCochlear implants provide partial restoration of hearing for profoundly deaf patients by electrically stimulating spiral ganglion neurons (SGNs); however, these neurons gradually degenerate following the onset of deafness. Although the exogenous application of neurotrophins (NTs) can prevent SGN loss, current techniques to administer NTs for long periods of time have limited clinical applicability. We have used encapsulated choroid plexus cells (NTCells; Living Cell Technologies, Auckland, New Zealand) to provide NTs in a clinically viable manner that can be combined with a cochlear implant. Neonatal catswere deafened and unilaterally implanted with NTCells and a cochlear implant. Animals received chronic electrical stimulation (ES) alone, NTs alone, or combined NTs and ES (ES + NT) for a period of as much as 8 months. The opposite ear served as a deafened unimplanted control. Chronic ES alone did not result in increased survival of SGNs or their peripheral processes. NT treatment alone resulted in greater SGN survival restricted to the upper basal cochlear region and an increased density of SGN peripheral processes. Importantly, chronic ES in combination with NTs provided significant SGN survival throughout a wider extent of the cochlea, in addition to an increased peripheral process density. Re-sprouting peripheral processes were observed in the scala media and scala tympani, raising the possibility of direct contact between peripheral processes and a cochlear implant electrode array. We conclude that cell-based therapy is clinically viable and effective in promoting SGN survival for extended durations of cochlear implant use. These findings have important implications for the safe delivery of therapeutic drugs to the cochlea.
- ItemConsequences of Deafness and Electrical Stimulation on Auditory Systems(Thieme Medical Publishers, 2014-06) Fallon, James; Ryugo, David; Shepherd, Robert
- ItemCortical activation following chronic passive implantation of a wide-field suprachoroidal retinal prosthesis(IOP Publishing, 2014-06) Villalobos, Joel; Fallon, James; Nayagam, David; Shivdasani, Mohit; Luu, Chi; Allen, Penelope; Shepherd, Robert; Williams, ChrisOBJECTIVE: The research goal is to develop a wide-field retinal stimulating array for prosthetic vision. This study aimed at evaluating the efficacy of a suprachoroidal electrode array in evoking visual cortex activity after long term implantation. APPROACH: A planar silicone based electrode array (8 mm × 19 mm) was implanted into the suprachoroidal space in cats (ntotal = 10). It consisted of 20 platinum stimulating electrodes (600 μm diameter) and a trans-scleral cable terminated in a subcutaneous connector. Three months after implantation (nchronic = 6), or immediately after implantation (nacute = 4), an electrophysiological study was performed. Electrode total impedance was measured from voltage transients using 500 μs, 1 mA pulses. Electrically evoked potentials (EEPs) and multi-unit activity were recorded from the visual cortex in response to monopolar retinal stimulation. Dynamic range and cortical activation spread were calculated from the multi-unit recordings. MAIN RESULTS: The mean electrode total impedance in vivo following 3 months was 12.5 ± 0.3 kΩ. EEPs were recorded for 98% of the electrodes. The median evoked potential threshold was 150 nC (charge density 53 μC cm(-2)). The lowest stimulation thresholds were found proximal to the area centralis. Mean thresholds from multiunit activity were lower for chronic (181 ± 14 nC) compared to acute (322 ± 20 nC) electrodes (P < 0.001), but there was no difference in dynamic range or cortical activation spread. SIGNIFICANCE: Suprachoroidal stimulation threshold was lower in chronic than acute implantation and was within safe charge limits for platinum. Electrode-tissue impedance following chronic implantation was higher, indicating the need for sufficient compliance voltage (e.g. 12.8 V for mean impedance, threshold and dynamic range). The wide-field suprachoroidal array reliably activated the retina after chronic implantation.
- ItemCreating virtual electrodes with two-dimensional current steering(IOP Publishing Ltd, 2018-02) Spencer, Thomas; Fallon, James; Shivdasani, MohitOBJECTIVE: Current steering techniques have shown promise in retinal prostheses as a way to increase the number of distinct percepts elicitable without increasing the number of implanted electrodes. Previously, it has been shown that 'virtual' electrodes can be created between simultaneously stimulated electrode pairs, producing unique cortical response patterns. This study investigated whether virtual electrodes could be created using two-dimensional current steering, and whether these virtual electrodes can produce cortical responses with predictable spatial characteristics. Approach: Normally-sighted eyes of seven adult anaesthetised cats were implanted with a 42-channel electrode array in the suprachoroidal space and multi-unit neural activity was recorded from the visual cortex. Stimuli were delivered to individual physical electrodes, or electrodes grouped into triangular, rectangular, and hexagonal arrangements. Varying proportions of charge were applied to each electrode in a group to "steer" current and create virtual electrodes. The centroids of cortical responses to stimulation of virtual electrodes were compared to those evoked by stimulation of single physical electrodes. Results: Responses to stimulation of groups of up to six electrodes with equal ratios of charge on each electrode resulted in cortical activation patterns that were similar to those elicited by the central physical electrode (Centroid's: RM ANOVA on Ranks, p>0.05; Neural Spread: Stats Test; p>0.05). We were also able to steer the centroid of activation towards the direction of any of the electrodes of the group by applying a greater charge to that electrode, but the movement in the centroid was not found to be significant. Significance: The results suggest that current steering is possible in two dimensions between up to at least six electrodes, indicating it may be possible to increase the number of percepts in patients without increasing the number of physical electrodes. Being able to reproduce spatial characteristics of responses to individual physical electrodes suggests that this technique could also be used to compensate for faulty electrodes.
- ItemDeep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activity(Elsevier, Inc., 2019-07) Sinclair, Nicholas; McDermott, Hugh; Fallon, James; Perera, Thushara; Brown, Peter; Bulluss, Kristian; Thevathasan, WesleyDeep brain stimulation is an established therapy for Parkinson's disease; however, its effectiveness is hindered by limited understanding of therapeutic mechanisms and the lack of a robust feedback signal for tailoring stimulation. We recently reported that subthalamic nucleus deep brain stimulation evokes a neural response resembling a decaying high-frequency (200-500Hz) oscillation that typically has a duration of at least 10ms and is localizable to the dorsal sub-region. As the morphology of this response suggests a propensity for the underlying neural circuitry to oscillate at a particular frequency, we have named it evoked resonant neural activity. Here, we determine whether this evoked activity is modulated by therapeutic stimulation - a critical attribute of a feedback signal. Furthermore, we investigated whether any related changes occurred in spontaneous local field potentials. Evoked and spontaneous neural activity was intraoperatively recorded from 19 subthalamic nuclei in patients with Parkinson's disease. Recordings were obtained before therapeutic stimulation and during 130Hz stimulation at increasing amplitudes (0.67-3.38mA), 'washout' of therapeutic effects, and non-therapeutic 20Hz stimulation. Therapeutic efficacy was assessed using clinical bradykinesia and rigidity scores. The frequency and amplitude of evoked resonant neural activity varied with the level of 130Hz stimulation (p<.001). This modulation coincided with improvement in bradykinesia and rigidity (p<.001), and correlated with spontaneous beta band suppression (p<.001). Evoked neural activity occupied a similar frequency band to spontaneous high-frequency oscillations (200-400Hz), both of which decreased to around twice the 130Hz stimulation rate. Non-therapeutic stimulation at 20Hz evoked, but did not modulate, resonant activity. These results indicate that therapeutic deep brain stimulation alters the frequency of evoked and spontaneous oscillations recorded in the subthalamic nucleus that are likely generated by loops within the cortico-basal ganglia-thalamo-cortical network. Evoked resonant neural activity therefore has potential as a tool for providing insight into brain network function and has key attributes of a dynamic feedback signal for optimizing therapy.
- ItemDifferential effects of vagus nerve stimulation strategies on glycemia and pancreatic secretions(Wiley Periodicals LLC, 2020-06) Payne, Sophie; Ward, Glenn; MacIsaac, Richard; Hyakumura, Tomoko; Fallon, James; Villalobos, JoelDespite advancements in pharmacotherapies, glycemia is poorly controlled in type 2 diabetic patients. As the vagus nerve regulates energy metabolism, here we evaluated the effect various electrical vagus nerve stimulation strategies have on glycemia and glucose-regulating hormones, as a first step to developing a novel therapy of type 2 diabetes. Sprague-Dawley rats were anesthetized, the abdominal (anterior) vagus nerve implanted, and various stimulation strategies applied to the nerve: (a) 15 Hz; (b) 4 kHz, or 40 kHz and; (c) a combination of 15 Hz and 40 kHz to directionally activate afferent or efferent vagal fibers. Following a glucose bolus (500 mg/kg, I.V.), stimulation strategies were applied (60 min) and serial blood samples taken. No stimulation was used as a crossover control sequence. Applying 15 Hz stimulation significantly increased glucose (+2.9 ± 0.2 mM·hr, p = .015) and glucagon (+17.1 ± 8.0 pg·hr/ml, p = .022), compared to no stimulation. Application of 4 kHz stimulation also significantly increased glucose levels (+1.5 ± 0.5 mM·hr, p = .049), while 40 kHz frequency stimulation resulted in no changes to glucose levels but did significantly lower glucagon (-12.3 ± 1.1 pg·hr/ml, p = .0009). Directional afferent stimulation increased glucose (+2.4 ± 1.5 mM·hr) and glucagon levels (+39.5 ± 15.0 pg·hr/ml). Despite hyperglycemia resulting when VNS, aVNS, and 4 kHz stimulation strategies were applied, the changes in insulin levels were not significant (p ≥ .05). In summary, vagus nerve stimulation modulates glycemia by effecting glucagon and insulin secretions, and high-frequency 40 kHz stimulation may have potential application for the treatment of type 2 diabetes.
- ItemEffect of current focusing on the sensitivity of inferior colliculus neurons to amplitude-modulated stimulation(American Physiological Society, 2016-06) George, Shefin; Shivdasani, Mohit; Fallon, JamesIn multichannel cochlear implants (CIs), current is delivered to specific electrodes along the cochlea in the form of amplitude-modulated pulse trains, to convey temporal and spectral cues. Our previous studies have shown that focused multipolar (FMP) and tripolar (TP) stimulation produce more restricted neural activation and reduced channel interactions in the inferior colliculus (IC) compared with traditional monopolar (MP) stimulation, suggesting that focusing of stimulation could produce better transmission of spectral information. The present study explored the capability of IC neurons to detect modulated CI stimulation with FMP and TP stimulation compared with MP stimulation. The study examined multiunit responses of IC neurons in acutely deafened guinea pigs by systematically varying the stimulation configuration, modulation depth, and stimulation level. Stimuli were sinusoidal amplitude-modulated pulse trains (carrier rate of 120 pulses/s). Modulation sensitivity was quantified by measuring modulation detection thresholds (MDTs), defined as the lowest modulation depth required to differentiate the response of a modulated stimulus from an unmodulated one. Whereas MP stimulation showed significantly lower MDTs than FMP and TP stimulation (P values <0.05) at stimulation
- ItemEffect of embedded optical fibres on the mechanical properties of cochlear electrode arrays(Elsevier Ltd., 2016-02) Carland, Emma; Stoddart, Paul; Cadusch, Peter; Fallon, James; Wade, ScottIncorporating optical fibres in cochlear electrode arrays has been proposed to provide sensors to help minimise insertion trauma and also for the delivery of light in optical nerve stimulation applications. However, embedding an optical fibre into an electrode array may change its stiffness properties, which can affect the level of trauma during insertion. This report uses measurements of buckling and deflection force to compare the stiffness properties of a range of cochlear electrode arrays (Nucleus straight array, rat array, cat array and guinea pig array) with custom arrays containing an embedded optical fibre. The cladding diameters of the optical fibres tested were 125 µm, 80 µm and 50 µm. The results show that the stiffness of the optical-fibre-embedded arrays is related to the diameter of the optical fibre. Comparison with wired arrays suggests optical fibres with a diameter of 50 µm could be embedded into an electrode array without significantly changing the stiffness properties of the array
- ItemEffects of age on the preservation of residual hearing with cochlear implants(2013) Wise, Andrew; Irving, Sam; Shepherd, Robert; Fallon, JamesChronic cochlear implant (CI) use results in a significant loss of residual acoustic hearing in some, but not all, animals. The loss occurs more rapidly in animals deafened as adults than those deafened as neonates.
- ItemEffects of chronic cochlear electrical stimulation after an extended period of profound deafness on primary auditory cortex organization in cats(John Wiley & Sons Inc, 2014-03) Fallon, James; Robert, Shepherd; Irvine, DexterExtended 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.
- ItemEffects of deafness and cochlear implant use on temporal response characteristics in cat primary auditory cortex.(Elsevier, 2014-09) Fallon, James; Shepherd, Robert; Nayagam, David; Wise, Andrew; Heffer, Leon; Landry, Thomas; Irvine, DexterWe have previously shown that neonatal deafness of 7-13 months duration leads to loss of cochleotopy in the primary auditory cortex (AI) that can be reversed by cochlear implant use. Here we describe the effects of a similar duration of deafness and cochlear implant use on temporal processing. Specifically, we compared the temporal resolution of neurons in AI of young adult normal-hearing cats that were acutely deafened and implanted immediately prior to recording with that in three groups of neonatally deafened cats. One group of neonatally deafened cats received no chronic stimulation. The other two groups received up to 8 months of either low- or high-rate (50 or 500 pulses per second per electrode, respectively) stimulation from a clinical cochlear implant, initiated at 10 weeks of age. Deafness of 7-13 months duration had no effect on the duration of post-onset response suppression, latency, latency jitter, or the stimulus repetition rate at which units responded maximally (best repetition rate), but resulted in a statistically significant reduction in the ability of units to respond to every stimulus in a train (maximum following rate). None of the temporal response characteristics of the low-rate group differed from those in acutely deafened controls. In contrast, high-rate stimulation had diverse effects: it resulted in decreased suppression duration, longer latency and greater jitter relative to all other groups, and an increase in best repetition rate and cut-off rate relative to acutely deafened controls. The minimal effects of moderate-duration deafness on temporal processing in the present study are in contrast to its previously-reported pronounced effects on cochleotopy. Much longer periods of deafness have been reported to result in significant changes in temporal processing, in accord with the fact that duration of deafness is a major factor influencing outcome in human cochlear implantees.