Browsing by Author "Rathbone, Graeme"
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- ItemAcute Cochlear Nucleus Compression Alters Tuning Properties of Inferior Colliculus Neurons(Karger Publishers, 2009) Crea, Katherine; Shivdasani, Mohit; Argent, Rebecca; Mauger, Stefan; Rathbone, Graeme; O'Leary, Stephen; Paolini, AntonioAuditory brainstem implants (ABI) have been used in neurofibromatosis type 2 (NF2) patients in an attempt to restore hearing sensation, with limited clinical success. Factors associated with poor clinical outcomes for NF2 ABI patients include larger tumour size, longer duration of hearing loss, and brainstem distortion and/or deformation caused by tumours that compress the brainstem. The present study investigated changes in tuning properties of inferior colliculus (IC) neurons following compression of the contralateral cochlear nucleus (CN). The left CN in adult rats (n = 8) was exposed and a 32-channel acute recording probe inserted along the tonotopic gradient of the right IC. In 4 animals, an ethylene vinyl acetate bead was applied to the exposed CN. Three recordings were made corresponding to T(1) = 0 min (before compression), T(2) = 45 min (during compression) and T(3) = 225 min (following bead removal/recovery). Recordings consisted of a response area protocol using pure tones of various frequencies and intensities (1-44 kHz; 10-70 dB SPL) to determine the characteristic frequency for each probe site. Compression of the CN led to sharpened tuning curves, decreased spike rate, and increased threshold and characteristic frequency in the IC. Reversal of compression enabled these variables, excluding threshold, to recover to baseline. NF2 patients may have poorer ABI performance due to damage to the physical structure of the CN, resulting in alterations to the tonotopic organisation of the auditory pathway which may complicate ABI implantation and activation.
- 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.
- 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.
- ItemAn in vivo investigation of first spike latencies in the inferior colliculus in response to multichannel penetrating auditory brainstem implant stimulation(IOP Publishing Ltd, 2010-05-04) Mauger, Stefan; Shivdasani, Mohit; Rathbone, Graeme; Argent, Rebecca; Paolini, AntonioThe cochlear nucleus (CN) is the first auditory processing site within the brain and the target location of the auditory brainstem implant (ABI), which provides speech perception to patients who cannot benefit from a cochlear implant (CI). Although there is variance between ABI recipient speech performance outcomes, performance is typically low compared to CI recipients. Temporal aspects of neural firing such as first spike latency (FSL) are thought to code for many speech features; however, no studies have investigated FSL from CN stimulation. Consequently, ABIs currently do not incorporate CN-specific temporal information. We therefore systematically investigated inferior colliculus (IC) neuron’s FSL response to frequency-specific electrical stimulation of the CN in rats. The range of FSLs from electrical stimulation of many neurons indicates that both monosynaptic and polysynaptic pathways were activated, suggesting initial activation of multiple CN neuron types. Electrical FSLs for a single neuron did not change irrespective of the CN frequency region stimulated, indicating highly segregated projections from the CN to the IC. These results present the first evidence of temporal responses to frequency-specific CN electrical stimulation. Understanding the auditory system’s temporal response to electrical stimulation will help in future ABI designs and stimulation strategies.
- ItemAn in vivo investigation of inferior colliculus single neuron responses to cochlear nucleus pulse train stimulation.(American Physiological Society, 2012) Mauger, Stefan; Shivdasani, Mohit; Rathbone, Graeme; Paolini, AntonioThe auditory brain stem implant (ABI) is being used clinically to restore hearing to patients unable to benefit from a cochlear implant (CI). Speech perception outcomes for ABI users are typically poor compared with most CI users. The ABI is implanted either on the surface of or penetrating through the cochlear nucleus in the auditory brain stem and uses stimulation strategies developed for auditory nerve stimulation with a CI. Although the stimulus rate may affect speech perception outcomes with current stimulation strategies, no studies have systematically investigated the effect of stimulus rate electrophysiologically or clinically. We therefore investigated rate response properties and temporal response properties of single inferior colliculus (IC) neurons from penetrating ABI stimulation using stimulus rates ranging from 100 to 1,600 pulses/s in the rat. We found that the stimulus rate affected the proportion of response types, thresholds, and dynamic ranges of IC activation. The stimulus rate was also found to affect the temporal properties of IC responses, with higher rates providing more temporally similar responses to acoustic stimulation. Suppression of neural firing and inhibition in IC neurons was also found, with response properties varying with the stimulus rate. This study demonstrated that changes in the ABI stimulus rate results in significant differences in IC neuron response properties. Due to electrophysiological differences, the stimulus rate may also change perceptual properties. We suggest that clinical evaluation of the ABI stimulus rate should be performed.
- ItemInferior colliculus responses to dual‐site intralamina stimulation in the ventral cochlear nucleus(John Wiley and Sons, 2010) Shivdasani, Mohit; Mauger, Stefan; Argent, Rebecca; Rathbone, Graeme; Paolini, AntonioA major limitation of the present auditory brainstem implant (ABI) is its inability to access the tonotopic organization of the ventral cochlear nucleus (VCN). A previous study by our group indicated that stimulation of single sites within a given VCN frequency region did not always elicit frequency-specific responses within the central nucleus of the inferior colliculus (CIC) and, in some cases, did not elicit a response at all. In this study, we hypothesized that sequential stimulation (with a short inter-pulse delay of 320 μs) of two VCN sites in similar frequency regions would enhance responsiveness in CIC neurons. Multiunit neural recordings in response to pure tones were obtained at 58 VCN and 164 CIC sites in anesthetized rats. Of the 58 VCN sites, 39 pairs of sites with similar characteristic frequencies were chosen for electrical stimulation. Each member of a VCN pair was electrically stimulated individually, followed by sequential stimulation of the pair, while recording CIC responses. On average, CIC sites were found to respond to dual-site VCN stimulation with significantly lower thresholds, wider dynamic ranges, a greater extent of activation with increasing current levels, and a higher degree of frequency specificity compared to single-site stimulation. While these effects were positive for the most part, in some cases dual-site stimulation resulted in increased CIC thresholds and decreased dynamic ranges, extent of activation, and frequency specificity. The results suggest that multi-site stimulation within VCN isofrequency laminae using penetrating electrodes could significantly improve ABI stimulation strategies and implant performance.
- ItemInferior Colliculus Responses to Multichannel Microstimulation of the Ventral Cochlear Nucleus: Implications for Auditory Brainstem Implants(American Physiological Society, 2008) Shivdasani, Mohit; Mauger, Stefan; Rathbone, Graeme; Paolini, AntonioMultichannel techniques were used to assess the frequency specificity of activation in the central nucleus of the inferior colliculus (CIC) produced by electrical stimulation of localized regions within the ventral cochlear nucleus (VCN). Data were recorded in response to pure tones from 141 and 193 multiunit clusters in the rat VCN and the CIC, respectively. Of 141 VCN sites, 126 were individually stimulated while recording responses in the CIC. A variety of CIC response types were seen with an increase in both electrical and acoustic stimulation levels. The majority of sites exhibited monotonic rate level types acoustically while spike rate saturation was achieved predominantly with electrical stimulation. In 20.6% of the 364 characteristic frequency aligned VCN-CIC pairs, the CIC sites did not respond to stimulation. In 26% of the 193 CIC sites, a high correlation was observed between acoustic tuning and electrical tuning obtained through VCN stimulation. A high degree of frequency specificity was found in 58% of the 118 lowest threshold VCN-CIC pairs. This was dependent on electrode placement within the VCN as a higher degree of frequency specificity was achieved with stimulation of medial, central and postero-lateral VCN regions than more antero-lateral regions. Broadness of acoustic tuning in the CIC played a role in frequency-specific activation. Narrowly tuned CIC sites showed the lowest degree of frequency specificity upon stimulation of the antero-lateral VCN regions. This data provides significant implications for Auditory Brainstem Implant electrode placement, current localization, power requirements and facilitation of information transfer to higher brain centers.
- ItemNeural synchrony in ventral cochlear nucleus neuron populations is not mediated by intrinsic processes but is stimulus induced: implications for auditory brainstem implants(IOP Publishing Ltd, 2009) Shivdasani, Mohit; Mauger, Stefan; Rathbone, Graeme; Paolini, AntonioThe aim of this investigation was to elucidate if neural synchrony forms part of the spike time-based theory for coding of sound information in the ventral cochlear nucleus (VCN) of the auditory brainstem. Previous research attempts to quantify the degree of neural synchrony at higher levels of the central auditory system have indicated that synchronized firing of neurons during presentation of an acoustic stimulus could play an important role in coding complex sound features. However, it is unknown whether this synchrony could in fact arise from the VCN as it is the first station in the central auditory pathway. Cross-correlation analysis was conducted on 499 pairs of multiunit clusters recorded in the urethane-anesthetized rat VCN in response to pure tones and combinations of two tones to determine the presence of neural synchrony. The shift predictor correlogram was used as a measure for determining the synchrony owing to the effects of the stimulus. Without subtraction of the shift predictor, over 65% of the pairs of multiunit clusters exhibited significant correlation in neural firing when the frequencies of the tones presented matched their characteristic frequencies (CFs). In addition, this stimulus-evoked neural synchrony was dependent on the physical distance between electrode sites, and the CF difference between multiunit clusters as the number of correlated pairs dropped significantly for electrode sites greater than 800 microm apart and for multiunit cluster pairs with a CF difference greater than 0.5 octaves. However, subtraction of the shift predictor correlograms from the raw correlograms resulted in no remaining correlation between all VCN pairs. These results suggest that while neural synchrony may be a feature of sound coding in the VCN, it is stimulus induced and not due to intrinsic neural interactions within the nucleus. These data provide important implications for stimulation strategies for the auditory brainstem implant, which is used to provide functional hearing to the profoundly deaf through electrical stimulation of the VCN.
- ItemRing and peg electrodes for minimally-Invasive and long-term sub-scalp EEG recordings(Elsevier, Ltd., 2017-06) Benovitski, Yuri; Lai, Alan; McGowan, Ceara; Burns, Owen; Maxim, Vanessa; Nayagam, David; Millard, Rodney; Rathbone, Graeme; le Chevoir, M.A.; Williams, R.A.; Grayden, David; May, C.N.; Murphy, M.; D'Souza, Wendyl; Cook, Mark; Williams, ChrisOBJECTIVE: Minimally-invasive approaches are needed for long-term reliable Electroencephalography (EEG) recordings to assist with epilepsy diagnosis, investigation and more naturalistic monitoring. This study compared three methods for long-term implantation of sub-scalp EEG electrodes. METHODS: Three types of electrodes (disk, ring, and peg) were fabricated from biocompatible materials and implanted under the scalp in five ambulatory ewes for 3months. Disk electrodes were inserted into sub-pericranial pockets. Ring electrodes were tunneled under the scalp. Peg electrodes were inserted into the skull, close to the dura. EEG was continuously monitored wirelessly. High resolution CT imaging, histopathology, and impedance measurements were used to assess the status of the electrodes at the end of the study. RESULTS: EEG amplitude was larger in the peg compared with the disk and ring electrodes (p<0.05). Similarly, chewing artifacts were lower in the peg electrodes (p<0.05). Electrode impedance increased after long-term implantation particularly for those within the bone (p<0.01). Micro-CT scans indicated that all electrodes stayed within the sub-scalp layers. All pegs remained within the burr holes as implanted with no evidence of extrusion. Eight of 10 disks partially eroded into the bone by 1.0mm from the surface of the skull. The ring arrays remained within the sub-scalp layers close to implantation site. Histology revealed that the electrodes were encapsulated in a thin fibrous tissue adjacent to the pericranium. Overlying this was a loose connective layer and scalp. Erosion into the bone occurred under the rim of the sub-pericranial disk electrodes. CONCLUSIONS: The results indicate that the peg electrodes provided high quality EEG, mechanical stability, and lower chewing artifact. Whereas, ring electrode arrays tunneled under the scalp enable minimal surgical techniques to be used for implantation and removal.
- ItemSpatiotemporal interactions in the visual cortex following paired electrical stimulation of the retina(The Association for Research in Vision and Ophthalmology Inc., 2014-11) Cicione, Rosemary; Fallon, James; Rathbone, Graeme; Williams, Chris; Shivdasani, MohitPURPOSE: Retinal prostheses use spatiotemporal patterns of electrical stimulation across multiple electrodes to provide visual percepts to blind patients. It is generally assumed that percepts produced by individual electrodes are independent of one another, which may not be the case. In this study, we aimed to quantify interactions between pairs of electrical stimuli delivered to the retina. METHODS: Normally sighted cats were implanted with a suprachoroidal electrode array. The retina was stimulated with a paired-pulse paradigm that consisted of a conditioning stimulus followed by a test stimulus, while recording multiunit activity in the visual cortex. Conditioning current, and spatial and temporal separation between the conditioning and test stimuli were varied. Cortical interactions were quantified by changes in multiunit activity elicited by stimulation with the paired-pulse paradigm, compared to stimulation of the test stimulus alone (control). RESULTS: Interactions varied as a function of conditioning current and temporal separation between the two stimulating pulses. Cortical activity increased compared to the control condition at an interstimulus delay of 1.025 ms and was significantly suppressed for delays between 20 and 90 ms, returning to near control levels for longer delays. The level of interactions increased when the conditioning current was increased. Interactions were found to be similar for electrode separations up to 3 mm. CONCLUSIONS: Interactions between sequential stimulation of pairs of electrodes in a suprachoroidal retinal prosthesis occur for delays up to 100 ms and electrode separations of several millimeters. Knowledge of these spatiotemporal interactions is essential for developing effective patterns of stimulation for retinal prostheses.
- ItemSuprachoroidal electrical stimulation: Effects of stimulus pulse parameters on visual cortical responses(IOPscience, 2013-10) John, Sam; Shivdasani, Mohit; Williams, Chris; Morley, John; Shepherd, Robert; Rathbone, Graeme; Fallon, JamesObjective. Neural responses to biphasic constant current pulses depend on stimulus pulse parameters such as polarity, duration, amplitude and interphase gap. The objective of this study was to systematically evaluate and optimize stimulus pulse parameters for a suprachoroidal retinal prosthesis. Approach. Normally sighted cats were acutely implanted with platinum electrode arrays in the suprachoroidal space. Monopolar stimulation comprised of monophasic and biphasic constant current pulses with varying polarity, pulse duration and interphase gap. Multiunit responses to electrical stimulation were recorded in the visual cortex. Main results. Anodal stimulation elicited cortical responses with shorter latencies and required lower charge per phase than cathodal stimulation. Clinically relevant retinal stimulation required relatively larger charge per phase compared with other neural prostheses. Increasing the interphase gap of biphasic pulses reduced the threshold of activation; however, the benefits of using an interphase gap need to be considered in light of the pulse duration and polarity used and other stimulation constraints. Based on our results, anodal first biphasic pulses between 300–1200 µs are recommended for suprachoroidal retinal stimulation. Significance. These results provide insights into the efficacy of different pulse parameters for suprachoroidal retinal stimulation and have implications for the design of safe and clinically relevant stimulators for retinal prostheses.
- ItemVisual cortex responses to suprachoroidal electrical stimulation of the retina: effects of electrode return configuration(IOP Publishing Ltd, 2012) Cicione, Rosemary; Shivdasani, Mohit; Fallon, James; Luu, Chi; Allen, Penny; Rathbone, Graeme; Shepherd, Robert; Williams, ChrisA clinically effective retinal prosthesis must evoke localized phosphenes in a retinotopic manner in response to stimulation of each of the retinal electrodes, evoke brightness cues over a wide dynamic range and function within safe stimulus limits. The effects of varying return configuration for retinal stimulation are currently unknown. To investigate this, we implanted a flexible, 7x12 electrode array into the suprachoroidal space of normally-sighted, anesthetized cats. Multi-unit activity in the primary visual cortex was recorded in response to electrical stimulation using various return configurations: monopolar vitreous (MPV), common ground (CG), hexagonal (HX), monopolar remote (MPR) and bipolar (BP_N). MPV stimulation was found to be the most charge efficient and was most likely to induce cortical activity within safe charge limits. HX and CG stimulation were found to exhibit greater retinal selectivity compared to the MPV return at the expense of lower cortical yield and higher P50 charge levels, while cortical selectivity was unaffected by choice of return. Responses using MPR and widely spaced BP_N configurations were similar to those using the MPV return. These results suggest that choice of return configuration for a retinal prosthesis will be balanced between resolution and stimulation within safe charge limits.