Bionics Institute

East Melbourne, Australia

Bionics Institute

East Melbourne, Australia
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Peterson A.J.,Leibniz Institute for Neurobiology | Irvine D.R.F.,Monash University | Irvine D.R.F.,Bionics Institute | Heil P.,Leibniz Institute for Neurobiology | Heil P.,Center for Behavioral Brain science
Journal of Neuroscience | Year: 2014

In mammalian auditory systems, the spiking characteristics of each primary afferent (type I auditory-nerve fiber; ANF) are mainly determined by a single ribbon synapse in a single receptor cell (inner hair cell; IHC).ANFspike trains therefore provide a window into the operation of these synapses and cells. It was demonstrated previously (Heil et al., 2007) that the distribution of interspike intervals (ISIs) of cat ANFs during spontaneous activity can be modeled as resulting from refractoriness operating on a non-Poisson stochastic point process of excitation (transmitter release events from the IHC). Here,weinvestigate nonrenewal properties of these cat-ANF spontaneous spike trains, manifest as negative serial ISI correlations and reduced spike-count variability over short timescales.Apreviously discussed excitatory process, the constrained failure of events from a homogeneous Poisson point process, can account for these properties, but does not offer a parsimonious explanation for certain trends in the data. We then investigate a three-parameter model of vesicle-pool depletion and replenishment and find that it accounts for all experimental observations, including the ISI distributions, with only the release probability varying between spike trains. The maximum number of units (single vesicles or groups of simultaneously released vesicles) in the readily releasable pool and their replenishment time constant can be assumed to be constant (∼4 and 13.5 ms, respectively). We suggest that the organization of the IHC ribbon synapses not only enables sustained release of neurotransmitter but also imposes temporal regularity on the release process, particularly when operating at high rates. © 2014 the authors.

Gilson M.,RIKEN | Gilson M.,University of Melbourne | Fukai T.,RIKEN | Burkitt A.N.,University of Melbourne | Burkitt A.N.,Bionics Institute
PLoS Computational Biology | Year: 2012

Spike-timing-dependent plasticity (STDP) has been observed in many brain areas such as sensory cortices, where it is hypothesized to structure synaptic connections between neurons. Previous studies have demonstrated how STDP can capture spiking information at short timescales using specific input configurations, such as coincident spiking, spike patterns and oscillatory spike trains. However, the corresponding computation in the case of arbitrary input signals is still unclear. This paper provides an overarching picture of the algorithm inherent to STDP, tying together many previous results for commonly used models of pairwise STDP. For a single neuron with plastic excitatory synapses, we show how STDP performs a spectral analysis on the temporal cross-correlograms between its afferent spike trains. The postsynaptic responses and STDP learning window determine kernel functions that specify how the neuron "sees" the input correlations. We thus denote this unsupervised learning scheme as 'kernel spectral component analysis' (kSCA). In particular, the whole input correlation structure must be considered since all plastic synapses compete with each other. We find that kSCA is enhanced when weight-dependent STDP induces gradual synaptic competition. For a spiking neuron with a "linear" response and pairwise STDP alone, we find that kSCA resembles principal component analysis (PCA). However, plain STDP does not isolate correlation sources in general, e.g., when they are mixed among the input spike trains. In other words, it does not perform independent component analysis (ICA). Tuning the neuron to a single correlation source can be achieved when STDP is paired with a homeostatic mechanism that reinforces the competition between synaptic inputs. Our results suggest that neuronal networks equipped with STDP can process signals encoded in the transient spiking activity at the timescales of tens of milliseconds for usual STDP. © 2012 Gilson et al.

Wise A.K.,Bionics Institute | Wise A.K.,University of Melbourne | Gillespie L.N.,Bionics Institute | Gillespie L.N.,University of Melbourne
Journal of Neural Engineering | Year: 2012

Bionic devices electrically activate neural populations to partially restore lost function. Of fundamental importance is the functional integrity of the targeted neurons. However, in many conditions the ongoing pathology can lead to continued neural degeneration and death that may compromise the effectiveness of the device and limit future strategies to improve performance. The use of drugs that can prevent nerve cell degeneration and promote their regeneration may improve clinical outcomes. In this paper we focus on strategies of delivering neuroprotective drugs to the auditory system in a way that is safe and clinically relevant for use in combination with a cochlear implant. The aim of this approach is to prevent neural degeneration and promote nerve regrowth in order to improve outcomes for cochlear implant recipients using techniques that can be translated to the clinic. © 2012 IOP Publishing Ltd.

Badawy R.A.B.,St Vincents Hospital | Badawy R.A.B.,University of Melbourne | Lai A.,Bionics Institute | Vogrin S.J.,St Vincents Hospital | And 3 more authors.
Neurology | Year: 2013

In the past, the cortex has for the most part been considered to be the site of seizure origin in the different forms of epilepsy. Findings from histopathologic, electrophysiologic, and brain imaging studies now provide ample evidence demonstrating that like normal cerebral function, epileptic seizures involve widespread network interactions between cortical and subcortical structures. These studies show that different forms of generalized and focal epileptiform discharges and seizures engage various subcortical structures in varying ways. This interaction has been the subject of many reviews and is not the focus of the current work. The aim of this review is to examine the evidence suggesting the possibility for some of the subcortical structures to initiate seizures independently and the clinical implications of this. © 2013 American Academy of Neurology.

Richardson R.T.,Bionics Institute | Atkinson P.J.,Stanford University
Expert Opinion on Biological Therapy | Year: 2015

Introduction: The sensory epithelium of the cochlea is a complex structure containing hair cells, supporting cells and auditory nerve endings, all of which degenerate after hearing loss in mammals. Biological approaches are being considered to preserve and restore the sensory epithelium after hearing loss. Of particular note is the ectopic expression of the Atoh1 gene, which has been shown to convert residual supporting cells into hair cells with restoration of function in some cases.Areas covered: In this review, hair cell development, spontaneous regeneration and hair cell regeneration mediated by Atoh1 gene therapy in the cochlea are discussed.Expert opinion: Gene therapy can be safely delivered locally to the inner ear and can be targeted to the sensory epithelium of the cochlea. Expression of the Atoh1 gene in supporting cells results in their transformation into cells with the appearance and function of immature hair cells but with the resulting loss of the original supporting cell. While the feasibility of Atoh1 gene therapy in the cochlea is largely dependent on the severity of the hearing loss, hearing restoration can be achieved in some situations. With further advances in Atoh1 gene therapy, hearing loss may not be as permanent as once thought. © 2014 Informa UK, Ltd.

Tan J.,Bionics Institute | Tan J.,University of Melbourne | Wang Y.,University of Melbourne | Yip X.,Bionics Institute | And 4 more authors.
Advanced Materials | Year: 2012

Neurotrophin-BDNF can be effectively encapsulated in nanoporous poly(L-glutamic acid) particles prepared via mesoporous silica templating. The loaded BDNF can be released in a sustained manner with retained biological activity. Animal experiments demonstrate the released BDNF can efficiently rescue the auditory neurons (as indicated by the arrows) in the cochlea of guinea pigs with sensorineural hearing loss. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Francart T.,Catholic University of Leuven | Francart T.,Bionics Institute | McDermott H.J.,Bionics Institute | McDermott H.J.,University of Melbourne
Ear and Hearing | Year: 2013

The addition of acoustic stimulation to electric stimulation via a cochlear implant has been shown to be advantageous for speech perception in noise, sound quality, music perception, and sound source localization. However, the signal processing and fitting procedures of current cochlear implants and hearing aids were developed independently, precluding several potential advantages of bimodal stimulation, such as improved sound source localization and binaural unmasking of speech in noise. While there is a large and increasing population of implantees who use a hearing aid, there are currently no generally accepted fitting methods for this configuration. It is not practical to fit current commercial devices to achieve optimal binaural loudness balance or optimal binaural cue transmission for arbitrary signals and levels. There are several promising experimental signal processing systems specifically designed for bimodal stimulation. In this article, basic psychophysical studies with electric acoustic stimulation are reviewed, along with the current state of the art in fitting, and experimental signal processing techniques for electric acoustic stimulation. Copyright © 2013 by Lippincott Williams & Wilkins.

Badawy R.A.B.,St Vincents Hospital | Badawy R.A.B.,University of Melbourne | Vogrin S.J.,St Vincents Hospital | Lai A.,Bionics Institute | And 2 more authors.
Epilepsia | Year: 2013

Purpose To investigate whether using transcranial magnetic stimulation (TMS) to derive if measures of cortical excitability changes can distinguish between various adolescent/adult-onset generalized epilepsy syndromes at different phases of the disorder. Methods One hundred thirty-seven patients with adolescent/adult-onset generalized epilepsy divided into juvenile myoclonic epilepsy, juvenile absence epilepsy, and generalized epilepsy with tonic-clonic seizures only were studied. The cohorts were further divided into drug naive-new onset, refractory, and seizure-free groups. Motor threshold (MT) and paired pulse TMS at short (2, 5, 10, 15 msec) and long (100-300 msec) interstimulus intervals (ISIs) were measured. Results were compared to those of 20 controls. Key Findings In the drug-naive cohorts MT was reduced (p < 0.05) and cortical excitability increased at 2 and 5 msec and 150, 250, and 300 msec ISIs (p < 0.01) in juvenile myoclonic epilepsy compared to other generalized epilepsy groups and controls. Cortical excitability increased to a lesser degree in other generalized epilepsy syndromes compared to controls, but those two syndromes were not distinguishable from one another. The changes in paired pulse TMS were more prominent in the groups with refractory seizures and very small in the groups who were seizure free. Significance There are syndrome specific changes in cortical excitability associated with generalized epilepsy. These changes are also dependent on seizure control with medication. Juvenile myoclonic epilepsy has a higher cortical excitability profile compared to other adolescent/adult-onset generalized epilepsy syndromes and can be clearly distinguished from them during all phases. © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Badawy R.A.B.,St Vincents Hospital | Badawy R.A.B.,University of Melbourne | Vogrin S.J.,St Vincents Hospital | Lai A.,Bionics Institute | And 2 more authors.
Epilepsia | Year: 2013

Purpose Transcranial magnetic stimulation (TMS) was used to characterize measurable changes of cortical excitability in patients who were undergoing medical and surgical management of temporal lobe epilepsy (TLE) to investigate whether these alterations depended on timing of achieving seizure control throughout the course of illness and method of management. Methods Eighty-five patients with TLE divided into (1) drug naive-new onset, (2) early medically refractor, and (3) late medically refractory, (4) early seizure-free on antiepileptic drugs, and (5) late seizure-free on antiepileptic drugs, (6) postoperative refractory, and (7) postoperative seizure-free groups were studied. Motor threshold (MT) and paired-pulse TMS at short (2, 5, 10, and 15 msec) and long (100-300 msec) interstimulus intervals (ISIs) were measured. Results were compared to those of 20 controls. Key Findings A significant interhemispheric difference was observed early at onset prior to starting medication, with higher cortical excitability in the hemisphere ipsilateral to the seizure focus, whereas the unaffected hemisphere was normal. After that, cortical excitability was higher in both hemispheres in the refractory groups (medical and postoperative) compared to the seizure-free and drug-naive groups (p < 0.05). This effect was most prominent at the long ISIs. Significance Changes in cortical excitability seen in patients with TLE are influenced by the course of the disease. The alterations that occur due to epilepsy are closely related to course of illness and degree/timing of seizure control. Successful management leads to resolution of this cortical hyperexcitability in a similar fashion regardless of method: medication (intact generator, but modulated by drugs) or surgery (generator removed). © Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Villalobos J.,Bionics Institute
Investigative ophthalmology & visual science | Year: 2013

The safety of chronic implantation of a retinal prosthesis in the suprachoroidal space has not been established. This study aimed to determine the safety of a wide-field suprachoroidal electrode array following chronic implantation using histopathologic techniques and electroretinography. A platinum electrode array in a wide silicone substrate was implanted unilaterally in the suprachoroidal space in adult cats (n = 7). The lead and connector were tunneled out of the orbit and positioned subcutaneously. Postsurgical recovery was assessed using fundus photography and electroretinography (ERG). Following 3 months of passive implantation, the animals were terminated and the eyes assessed for the pathologic response to implantation. The implant was mechanically stable in the suprachoroidal space during the course of the study. The implanted eye showed a transient increase in ERG response amplitude at 2 weeks, which returned to normal by 3 months. Pigmentary changes were observed at the distal end of the implant, near the optic disc. Histopathologic assessment revealed a largely intact retina and a thin fibrous capsule around the suprachoroidal implant cavity. The foreign body response was minimal, with sporadic presence of macrophages and no active inflammation. All implanted eyes were negative for bacterial or fungal infections. A midgrade granuloma and thick fibrous buildup surrounded the extraocular cable. Scleral closure was maintained in six of seven eyes. There were no staphylomas or choroidal incarceration. A wide-field retinal prosthesis was stable and well tolerated during long-term suprachoroidal implantation in a cat model. The surgical approach was reproducible and overall safe.

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