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Maturation of auditory brainstem projections and calyces in the congenitally deaf (dn/dn) mouse
(John Wiley and Sons, 2007-11-27) Youssoufian, Monique; Couchman, Kiri; Shivdasani, Mohit; Paolini, Antonio G.; Walmsley, Bruce
he deaf dn/dn mouse is a valuable model of human congenital deafness. In this study we used the lipophylic dye DiA to trace auditory nerve and cochlear nucleus projections in the dn/dn mouse. In both normal and deaf mice, the ipsilateral projections from the anteroventral cochlear nucleus (AVCN) to the lateral superior olive (LSO), and the contralateral projections from the AVCN to the medial nucleus of the trapezoid body (MNTB) were intact. With age, there was a noted increase in the fenestration of the endbulb and calyx of Held, and this morphological maturation was also observed in the deaf mice, although there was a significant difference in total endbulb volume at P20 between normal and deaf mice. However, total calyceal volume was not significantly different between normal and deaf mice. There was electrophysiological evidence of in vivo spontaneous ventral cochlear nucleus activity in normal and deaf animals, indicating that this activity may be responsible for the appropriate connectivity in the deaf mice. Our results indicate that congenital deafness caused by the dn/dn mutation does not result in aberrant projections between the AVCN and the ipsilateral MNTB and contralateral LSO but can cause abnormalities in endbulb size.
Inferior 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, Antonio
Multichannel 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.
Neural 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, Antonio
The 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.
Acute 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, Antonio
Auditory 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.
Promoting neurite outgrowth from spiral ganglion neuron explants using polypyrrole/BDNF-coated electrodes
(Wiley Periodicals, 2009-10) Evans, Alison; Thompson, Brianna; Wallace, Gordon; Millard, Rodney; O'Leary, Stephen; Clark, Graeme; Shepherd, Robert; Richardson, Rachael
Release of neurotrophin-3 (NT3) and brain-derived neurotrophic factor (BDNF) from hair cells in the cochlea is essential for the survival of spiral ganglion neurons (SGNs). Loss of hair cells associated with a sensorineural hearing loss therefore results in degeneration of SGNs, potentially reducing the performance of a cochlear implant. Exogenous replacement of either or both neurotrophins protects SGNs from degeneration after deafness. We previously incorporated NT3 into the conducting polymer polypyrrole (Ppy) synthesized with para-toluene sulfonate (pTS) to investigate whether Ppy/pTS/NT3-coated cochlear implant electrodes could provide both neurotrophic support and electrical stimulation for SGNs. Enhanced and controlled release of NT3 was achieved when Ppy/pTS/NT3-coated electrodes were subjected to electrical stimulation. Here we describe the release dynamics and biological properties of Ppy/pTS with incorporated BDNF. Release studies demonstrated slow passive diffusion of BDNF from Ppy/pTS/BDNF, with electrical stimulation significantly enhancing BDNF release over seven days. A three-day SGN explant assay found neurite outgrowth from explants was 12.3-fold greater when polymers contained BDNF (p<0.001), although electrical stimulation did not increase neurite outgrowth further. The versatility of Ppy to store and release neurotrophins, conduct electrical charge and act as a substrate for nerve-electrode interactions is discussed for specialized applications such as cochlear implants.
Audiovisual integration in noise by children and adults
(Elsevier,, 2010) Barutchu, Ayla; Danaher, Jaclyn; Crewther, Sheila; Innes-Brown, Hamish; Shivdasani, Mohit; Paolini, Antonio
The aim of this study was to investigate the development of multisensory facilitation in primary school age children under conditions of auditory noise. Motor reaction times and accuracy were recorded from 8-year-olds, 10-year-olds and adults during an auditory, a visual, and an audiovisual detection task. Auditory signal-to-noise ratios (SNRs) of 30, 22, 12 and 9 dB across the different age groups were compared. Multisensory facilitation was greater in adults than in children, though performance for all age-groups was affected by the presence of background noise. It is posited that changes in multisensory facilitation with increased auditory noise may be due to changes in attention bias.
Evaluation of stimulus parameters and electrode geometry for an effective suprachoroidal retinal prosthesis
(IOP Publishing Ltd, 2010) Shivdasani, Mohit; Luu, Chi; Cicione, Rosemary; Fallon, James; Allen, Penny; Leuenberger, James; Suaning, Gregg; Lovell, Nigel; Shepherd, Robert; Williams, Chris
Several approaches have been proposed for placement of retinal prostheses; epiretinal, sub-retinal, and suprachoroidal. We aimed to systematically evaluate the effectiveness of varying a range of stimulus parameters and electrode geometry for a suprachoroidal electrode array, using cortical evoked responses to monopolar electrical stimulation in cats. Our results indicate that charge thresholds were not dependent on electrode size, pulse widths or position of the return electrode tested, but were dependent on the number of sites stimulated in parallel. Further, we found that the combination of monopolar stimulation with large diameter electrodes, wide pulse widths and parallel stimulation minimized the voltage requirements for stimulation. These results provide useful insights for the design specifications of a low voltage suprachoroidal stimulator.
Inferior 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, Antonio
A 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.
An 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, Antonio
The 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.
Effects of prismatic adaptation on spatial gradients in neglect: a comparison of visual and auditory target detection with central attentional load
(Elsevier, 2010-07) Eramudugolla, Ranmalee; Boyce, Angela; Irvine, Dexter; Mattingley, Jason
Prismatic adaptation is increasingly recognised as an effective procedure for rehabilitating symptoms of spatial neglect – producing relatively long-lasting improvements on a variety of spatial attention tasks. The mechanisms by which the aftereffects of adaptation change neglect patients’ performance on these tasks remain controversial. It is not clear, for example, whether adaptation directly influences the pathological ipsilesional attention bias that underlies neglect, or whether it simply changes exploratory motor behaviour. Also, while there is considerable evidence for prism effects on neglect symptoms in the visual, proprioceptive and tactile systems, few studies have examined the generalization of aftereffects to sensory systems that are not directly involved in the adaptation procedure itself. Here we used visual and auditory versions of a target detection task with central attentional load. Under these conditions, patients with spatial neglect demonstrated a spatial gradient in their ability to detect peripheral visual or auditory targets. The effect of prism adaptation on the patients’ pathological attention gradient on these two tasks was compared. The findings have implications for understanding the level at which prism adaptation may be acting on neglect symptoms.
Vitamin D-deficient diet rescues hearing loss in Klotho mice
(Elsevier, 2010-12-08) Carpinelli, Marina; Wise, Andrew; Burt, Rachel
Klotho-deficient mice exhibit a premature aging syndrome, a feature of which is mild hearing loss. In the present study, the hearing phenotype of Klotho mice was characterized to better determine how well this phenotype resembles presbycusis in humans. It was demonstrated that Klotho animals have auditory-evoked brainstem response (ABR) threshold shifts of 14e18 dB in response to pure tone stimuli of 4, 8, 16 and 32 kHz, and similarly, in response to clicks; however, cochlear histology and spiral ganglion neuron density appeared normal in these mice. It was further demonstrated that a vitamin D-deficient diet normalizes serum calcitriol (1,25(OH)2D3) levels and prevents hearing loss in Klotho mice. It is concluded that hearing loss in Klotho mice is caused by elevated renal 1a-hydroxylase expression and consequent excessive production of calcitriol. These findings implicate the vitamin D metabolic pathway in hearing loss and pose questions as to the mechanism by which elevated calcitriol levels mediate such hearing loss.
The relationship between multisensory integration and IQ in children
(American Psychological Association, 2010-12-13) Barutchu, Ayla; Crewther, Sheila; Fifer, Joanne; Shivdasani, Mohit; Innes-Brown, Hamish; Toohey, Sarah; Danaher, Jaclyn; Paolini, Antonio
It is well accepted that multisensory integration has a facilitative effect on perceptual and motor processes, evolutionarily enhancing the chance of survival of many species, including humans. Yet, there is a limited understanding of the relationship between multisensory processes, environmental noise and children’s cognitive abilities. Thus, this study investigated the relationship between multisensory integration, auditory background noise and the general intellectual abilities of school age children (N = 88, M age = 9 years, 7 months) using a simple audiovisual detection paradigm. We provide evidence that children with enhanced multisensory integration in quiet and noisy conditions are likely to score above average on the full-scale Wechsler Intelligence Scale for Children (WISC-IV). Conversely, ~ 45% of tested children, with relatively low verbal and non-verbal intellectual abilities, showed reduced multisensory integration in either quiet or noise. Interestingly, ~ 20% of children showed improved multisensory integration abilities in the presence of auditory background noise. The findings of the present study suggest that stable and consistent multisensory integration in quiet and noisy environments is associated with the development of optimal general intellectual abilities. Further theoretical implications are discussed.
Biocompatibility of Immobilized Aligned Carbon Nanotubes
(Wiley, 2011) Nayagam, David; Williams, Richard; Chen, Jun; Magee, Kylie; Irwin, Jennifer; Tan, Justin; Innis, Peter; Leung, Ronald; Finch, Sue; Williams, Chris; Clark, Graeme; Wallace, Gordon
In vivo host responses to an electrode-like array of aligned carbon nanotubes (ACNTs) embedded within a biopolymer sheet are reported. This biocompatibility study assesses the suitability of immobilized carbon nanotubes for bionic devices. Inflammatory responses and foreign-body histiocytic reactions are not substantially elevated when compared to negative controls following 12 weeks implantation. A fibrous capsule isolates the implanted ACNTs from the surrounding muscle tissue. Filamentous nanotube fragments are engulfed by macrophages, and globular debris is incorporated into the fibrous capsule with no further reaction. Scattered leukocytes are observed, adherent to the ACNT surface. These data indicate that there is a minimal local foreign-body response to immobilized ACNTs, that detached fragments are phagocytosed into an inert material, and that ACNTs do not attract high levels of surface fouling. Collectively, these results suggest that immobilized nanotube structures should be considered for further investigation as bionic components.
A data-driven framework for neural field modeling
(Elsevier Ltd., 2011-02) Freestone, Dean; Aram, Parham; Dewar, Michael; Scerri, Kenneth; Grayden, David; Kadirkamanathan, Visakan
This paper presents a framework for creating neural field models from electrophysiological data. The Wilson and Cowan or Amari style neural field equations are used to form a parametric model, where the parameters are estimated from data. To illustrate the estimation framework, data is generated using the neural field equations incorporating modeled sensors enabling a comparison between the estimated and true parameters. To facilitate state and parameter estimation, we introduce a method to reduce the continuum neural field model using a basis function decomposition to form a finite-dimensional state-space model. Spatial frequency analysis methods are introduced that systematically specify the basis function configuration required to capture the dominant characteristics of the neural field. The estimation procedure consists of a two-stage iterative algorithm incorporating the unscented Rauch–Tung–Striebel smoother for state estimation and a least squares algorithm for parameter estimation. The results show that it is theoretically possible to reconstruct the neural field and estimate intracortical connectivity structure and synaptic dynamics with the proposed framework.
An improved cochlear implant electrode array for use in experimental studies
(Elevier, 2011-03) Shepherd, Robert; Verhoeven, Kristien; Xu, Jin; Risi, Frank; Fallon, James; Wise, Andrew
Experimental studies play an important role in establishing the safety and efficacy of cochlear implants and they continue to provide insight into a new generation of electrode arrays and stimulation strategies. One drawback has been the limited depth of insertion of an electrode array in experimental animals. We compared the insertion depth and trauma associated with the insertion of Cochlear Ltd's Hybrid-L (HL) array with a standard 8 ring array in cat cochleae. Both arrays were inserted into cadaver cochleae and an X-ray recorded their anatomical location. The implanted cochlea was serially sectioned and photographed at 300 mum intervals for evidence of electrode insertion trauma. Subsequently two cats were chronically implanted with HL arrays and electrically-evoked potentials recorded over a three month period. Mean insertion depth for the HL arrays was 334.8 degrees (SD = 21 degrees ; n = 4) versus 175.5 degrees (SD = 6 degrees ; n = 2) for the standard array. This relates to approximately 10.5 mm and 6 mm respectively. A similar insertion depth was measured in a chronically implanted animal with an HL array. Histology from each cadaver cochleae showed that the electrode array was always located in the scala tympani; there was no evidence of electrode insertion trauma to the basilar membrane, the osseous spiral lamina or the spiral ligament. Finally, evoked potential data from the chronically implanted animals exhibited significantly lower thresholds compared with animals implanted with a standard 8 ring array, with electrical thresholds remaining stable over a three-month observation period. Cochlear Ltd's HL electrode array can be safely inserted approximately 50% of the length of the cat scala tympani, placing the tip of the array close to the 4 kHz place. This insertion depth is considerably greater than is routinely achieved using a standard 8-ring electrode array ( approximately 12 kHz place). The HL array evokes low thresholds that remain stable over three months of implantation. This electrode array has potential application in a broad area of cochlear implant related research.
Enhanced auditory neuron survival following cell- based BDNF treatment in the deaf guinea pig
(PLOS, 2011-04-05) Pettingill, Lisa; Wise, Andrew; Geaney, Marilyn; Shepherd, Robert
Exogenous neurotrophin delivery to the deaf cochlea can prevent deafness-induced auditory neuron degeneration, however, we have previously reported that these survival effects are rapidly lost if the treatment stops. In addition, there are concerns that current experimental techniques are not safe enough to be used clinically. Therefore, for such treatments to be clinically transferable, methods of neurotrophin treatment that are safe, biocompatible and can support long-term auditory neuron survival are necessary. Cell transplantation and gene transfer, combined with encapsulation technologies, have the potential to address these issues. This study investigated the survival-promoting effects of encapsulated BDNF over-expressing Schwann cells on auditory neurons in the deaf guinea pig. In comparison to control (empty) capsules, there was significantly greater auditory neuron survival following the cell-based BDNF treatment. Concurrent use of a cochlear implant is expected to result in even greater auditory neuron survival, and provide a clinically relevant method to support auditory neuron survival that may lead to improved speech perception and language outcomes for cochlear implant patients.
An 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, Chris
The 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.
A technical comparison of digital frequency-lowering techniques available in two current hearing aids
(PLoS ONE, 2011-07) McDermott, Hugh
Background: Recently two major manufacturers of hearing aids introduced two distinct frequency-lowering techniques that were designed to compensate in part for the perceptual effects of high-frequency hearing impairments. The Widex ‘‘Audibility Extender’’ is a linear frequency transposition scheme, whereas the Phonak ‘‘SoundRecover’’ scheme employs nonlinear frequency compression. Although these schemes process sound signals in very different ways, studies investigating their use by both adults and children with hearing impairment have reported significant perceptual benefits. However, the modifications that these innovative schemes apply to sound signals have not previously been described or compared in detail. Methods: The main aim of the present study was to analyze these schemes’technical performance by measuring outputs from each type of hearing aid with the frequency-lowering functions enabled and disabled. The input signals included sinusoids, flute sounds, and speech material. Spectral analyses were carried out on the output signals produced by the hearing aids in each condition. Conclusions: The results of the analyses confirmed that each scheme was effective at lowering certain high-frequency acoustic signals, although both techniques also distorted some signals. Most importantly, the application of either frequency-lowering scheme would be expected to improve the audibility of many sounds having salient high-frequency components. Nevertheless, considerably different perceptual effects would be expected from these schemes, even when each hearing aid is fitted in accordance with the same audiometric configuration of hearing impairment. In general, these findings reinforce the need for appropriate selection and fitting of sound-processing schemes in modern hearing aids to suit the characteristics and preferences of individual listeners.
The effect of deafness duration on neurotrophin gene therapy for spiral ganglion neuron protection
(Elsevier, 2011-08) Wise, Andrew; Tu, Tian; Atkinson, Patrick; Flynn, Brianna; Sgro, Beatrice; Hume, Cliff; O'Leary, Stephen; Shepherd, Robert; Richardson, Rachael
A cochlear implant can restore hearing function by electrically exciting spiral ganglion neurons (SGNs) in the deaf cochlea. However, following deafness SGNs undergo progressive degeneration ultimately leading to their death. One significant cause of SGN degeneration is the loss of neurotrophic support that is normally provided by cells within the organ of Corti (OC). The administration of exogenous neurotrophins (NTs) can protect SGNs from degeneration but the effects are short-lived once the source of NTs has been exhausted. NT gene therapy, whereby cells within the cochlea are transfected with genes enabling them to produce NTs, is one strategy for providing a cellular source of NTs that may provide long-term support for SGNs. As the SGNs normally innervate sensory cells within the OC, targeting residual OC cells for gene therapy in the deaf cochlea may provide a source of NTs for SGN protection and targeted regrowth of their peripheral fibers. However, the continual degeneration of the OC over extended periods of deafness may deplete the cellular targets for NT gene therapy and hence limit the effectiveness of this method in preventing SGN loss. This study examined the effects of deafness duration on the efficacy of NT gene therapy in preventing SGN loss in guinea pigs that were systemically deafened with aminoglycosides. Adenoviral vectors containing green fluorescent protein (GFP) with or without genes for Brain Derived Neurotrophic Factor (BDNF) and Neurotrophin-3 (NT3) were injected into the scala media (SM) compartment of cochleae that had been deafened for one, four or eight weeks prior to the viral injection. The results showed that viral transfection of cells within the SM was still possible even after severe degeneration of the OC. Supporting cells (pillar and Deiters' cells), cells within the stria vascularis, the spiral ligament, endosteal cells lining the scala compartments and interdental cells in the spiral limbus were transfected. However, the level of transfection was remarkably lower following longer durations of deafness. There was a significant increase in SGN survival in the entire basal turn for cochleae that received NT gene therapy compared to the untreated contralateral control cochleae for the one week deaf group. In the four week deaf group significant SGN survival was observed in the lower basal turn only. There was no increase in SGN survival for the eight week deaf group in any cochlear region. These findings indicated that the efficacy of NT gene therapy diminished with increasing durations of deafness leading to reduced benefits in terms of SGN protection. Clinically, there remains a window of opportunity in which NT gene therapy can provide ongoing trophic support for SGNs.
Susceptibility to the flash-beep illusion is increased in children compared to adults
(Wiley, 2011-09) Innes-Brown, Hamish; Baratchu, Ayla; Shivdasani, Mohit; Crewther, David; Grayden, David; Paolini, Antonio
Audio-visual integration was studied in children aged 8-17 (N=30) and adults (N=22) using the “flash-beep illusion” paradigm, where the presentation of two beeps causes a single flash to be perceived as two flashes (fission illusion), and a single beep causes two flashes to be perceived as one flash (fusion illusion). Children reported significantly more fission illusions than adults, indicating that auditory and visual information was integrated more often, and less selectivity than in adults. Within either group, illusion reports did not correlate with either age or motor coordination measures. The current results show that the form of multisensory integration indexed by the illusion is slow to mature in normally-developing children.

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