Biomedical subjects

John W Morley

Publications and source records attributed to John W Morley.

8 recordsLinked to original sources

PubMed2005

Evaluation of extraocular electrodes for a retinal prosthesis using evoked potentials in cat visual cortex.

OBJECTIVE: To assess the efficacy of a device using extraocular electrodes as a retinal prosthesis by evaluating the responses evoked in the visual cortex to electrical stimulation. METHODS: In anaesthetised cats, a lateral orbital dissection and ipsilateral parietal craniotomy was performed. Two extraocular retinal prosthesis (ERP) disc electrodes were sutured to the sclera on the lateral and superior aspects of the globe. Retinal stimulation was performed with charge-balanced constant-current pulses. Potentials evoked in the visual cortex were measured with a ball electrode placed on the lateral gyrus after removal of the dura. RESULTS: Stable attachment of the ERP electrodes to the globe was achieved with scleral sutures. Visual cortex responses were recorded with the electrodes in bipolar and monopolar configurations. The evoked response consisted of an early component with a peak around 8 ms, and a late component with a peak after 50 ms. Thresholds for evoking a response occurred at current intensities as low as 500 microA. Through extrapolation from evoked response amplitude data, thresholds as low as 300 microA were calculated. Cathodal monopolar stimulation demonstrated lower thresholds than anodal stimulation for evoking cortical responses. CONCLUSIONS: The ERP electrodes can be easily attached to the globe and are effective in electrically stimulating the retina, evoking responses in the primary visual cortex. Threshold charge-density was within safe limits for neural stimulation.

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PubMed2005

Feasibility of extraocular stimulation for a retinal prosthesis.

BACKGROUND: We present a new approach to developing a retinal prosthesis for blind patients based on extraocular stimulation of the eye with disc electrodes. METHODS: Experiments to assess the feasibility of using extraocular stimulation in a retinal prosthesis were carried out in anaesthetised adult cats (n=6). A craniotomy and lateral orbital dissection were performed. Ball or disc electrodes were placed on the posterior scleral surface of the eye after incision of the periorbita. Cortical potentials evoked by electrical stimulation with these electrodes were recorded at the primary visual cortex. The viability of adapting the Nucleus 24 auditory brainstem implant (ABI) as an extraocular retinal prosthesis was also investigated. RESULTS: Electrodes placed on the exterior of the eye could reliably evoke visual cortex responses for a variety of configurations. Threshold currents for eliciting an evoked response were lower than 100 microA with single pulses. Strength-duration curves and cortical activation maps were obtained for different stimulus paradigms. It was possible to excite the retina to evoke a cortical response using the electrodes and stimulus capabilities in a standard Nucleus 24 ABI. INTERPRETATION: It is possible to electrically stimulate the retina with electrodes placed in an extraocular location. Threshold currents required to elicit a response were low, and comparable to epiretinal implants. Prototype electrodes, and a potential implant, were found to be effective at retinal stimulation.

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PubMed2005

Stimulation of the retina with a multielectrode extraocular visual prosthesis.

BACKGROUND: An extraocular approach to developing a retinal prosthesis for blind patients using electrodes placed on the outer surface of the eye is suggested. Experiments were carried out to determine the feasibility of this approach, and evaluate electrode configurations and parameters for stimulation. METHODS: In anaesthetized cats, a 21-electrode extraocular retinal prosthesis (ERP) array was sutured to the sclera over the lateral surface of the eye. Electrically evoked potentials (EEP) were recorded at the visual cortex bilaterally in response to retinal stimulation with the electrode array. Bipolar stimulation of the ERP array electrodes in horizontal and vertical configurations and at different interelectrode separations was investigated with biphasic constant-current pulses. RESULTS: Electrical stimulation of the lateral retina with an ERP elicited EEP that were higher in the ipsilateral visual cortex. The threshold for bipolar retinal stimulation was 500 microA. EEP amplitude increased with increases in stimulus pulse duration and current intensity. Retinal stimulation was slightly more effective with electrodes in a vertical as opposed to horizontal orientation. A larger interelectrode separation resulted in a higher EEP amplitude. CONCLUSIONS: Retinal stimulation with a prototype ERP array is demonstrated. The thresholds for retinal excitation are below safe charge-density limits for chronic neural stimulation. Ipsilateral localization of the EEP suggests that localized retinal stimulation is occurring. An ERP is a new approach to retinal prosthesis research, and might lead to the development of a low-resolution visual prosthesis for blind patients.

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PubMed2004

Long-term depression is reduced in cerebellar Purkinje cells of dystrophin-deficient mdx mice.

The mdx (muscular dystrophy X-linked) mouse is a model for human Duchenne muscular dystrophy (DMD) and is characterized by the absence of the cytoskeletal protein dystrophin. Using a cerebellar slice preparation, we show that postsynaptically mediated long-term depression (LTD) is significantly reduced in mdx Purkinje cells, while presynaptically mediated paired-pulse facilitation (PPF) is normal. This disruption of LTD could contribute to the cognitive deficit in boys with Duchenne muscular dystrophy.

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PubMed2004

A patch-clamp investigation of membrane currents in a novel mammalian retinal ganglion cell line.

We characterised membrane currents in undifferentiated RGC-5 cells, a cell line used in in vitro models of apoptosis and glaucoma. The cells were inexcitable, with no voltage-dependent Na(+) currents or action potentials. Some novel currents were observed including basal Cl(-) currents, inwardly rectifiying K(+) currents and Gd(3+) insensitive stretch-activated currents. Our results highlight the differences between the electrophysiological properties of undifferentiated RGC-5 cells and retinal ganglion cells.

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PubMed2004

Surface stimulation of the brain with a prototype array for a visual cortex prosthesis.

We are developing a neural prosthesis to electrically stimulate the visual cortex to restore basic visual perceptions to blind patients. The effects on cortical excitation of different stimulus configurations using a prototype electrode array are presented. Cats underwent a bilateral craniotomy to expose the cortex. An array for brain stimulation was placed on the surface of the right hemisphere. Cortical stimulation was undertaken in a variety of configurations while measuring the evoked responses that propagated through transcallosal pathways, at a homologous region on the contralateral hemisphere. Cortical excitation elicited by stimulation with a particular paradigm could be assessed by measuring the spatial spread and amplitudes of evoked responses in the contralateral hemisphere. Results from this transcallosal model have allowed us to examine the spatial and amplitude effects of cortical stimulation with our prototype electrode array and will aid in developing a neuroprosthesis for blind patients.

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PubMed2004

An in-vivo paradigm for the evaluation of stimulating electrodes for use with a visual prosthesis.

BACKGROUND: Electrical stimulation of the visual cortex with surface electrodes is able to elicit basic visual perceptions in blind patients. The development of a visual prosthesis for the blind will require an in-vivo model for the optimization of cortical neurostimulation with multielectrode arrays. METHODS: In anaesthetized cats a bilateral craniotomy was performed and the dura was removed to expose the cerebral cortex. A prototype stimulating electrode array was placed on a gyrus in one hemisphere, and the transcallosal evoked response (TER) to cortical stimulation by this electrode array was recorded at a homologous region in the contralateral hemisphere. RESULTS: The stimulating electrode array elicited TER of short latency (6.9 ms) in the contralateral hemisphere. Bipolar stimulation of adjacent electrodes on the array evoked similar TER regardless of the polarity of stimulation. Electrodes spread apart on the array caused higher amplitude TER than electrodes placed close together. Multielectrode stimulation evoked lower amplitude TER than bipolar stimulation. CONCLUSIONS: This transcallosal model of cortical neurostimulation is a useful method to evaluate electrode arrays and stimulation techniques in the development of a visual prosthesis.

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PubMed2003

Altered inhibitory input to Purkinje cells of dystrophin-deficient mice.

We investigated evoked EPSPs and spontaneous IPSPs in cerebellar slices from dystrophin-deficient mdx mice. In the presence of the GABA(A) antagonist bicuculline the increase in EPSP amplitude was less in mdx Purkinje cells compared to control, and the amplitude of miniature IPSCs in mdx cells was also significantly less than in controls. This reduced inhibitory input is most likely due to the reported reduction in the size of GABA(A) channel clusters.

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