Browsing by Author "Thompson, Alexander"

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    Challenges for the application of optical stimulation in the cochlea for the study and treatment of hearing loss
    (Taylor and Francis, 2017-02) Richardson, Rachael; Thompson, Alexander; Wise, Andrew; Needham, Karina
    INTRODUCTION: Electrical stimulation has long been the most effective strategy for evoking neural activity from bionic devices and has been used with great success in the cochlear implant to allow deaf people to hear speech and sound. Despite its success, the spread of electrical current stimulates a broad region of neural tissue meaning that contemporary devices have limited precision. Optical stimulation as an alternative has attracted much recent interest for its capacity to provide highly focused stimuli, and therefore, potentially improved sensory perception. Given its specificity of activation, optical stimulation may also provide a useful tool in the study of fundamental neuroanatomy and neurophysiological processes. Areas covered: This review examines the advances in optical stimulation - infrared, nanoparticle-enhanced, and optogenetic-based - and its application in the inner ear for the restoration of auditory function following hearing loss. Expert opinion: Initial outcomes suggest that optogenetic-based approaches hold the greatest potential and viability amongst optical techniques for application in the cochlea. The future success of this approach will be governed by advances in the targeted delivery of opsins to auditory neurons, improvements in channel kinetics, development of optical arrays, and innovation of opsins that activate within the optimal near-infrared therapeutic window.
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    Infrared neural stimulation fails to evoke neural activity in the deaf guinea pig cochlea.
    (Elsevier, 2015-03) Thompson, Alexander; Fallon, James; Wise, Andrew; Wade, Scott
    At present there is some debate as to the processes by which infrared neural stimulation (INS) activates neurons in the cochlea, as the lasers used for INS can potentially generate a range of secondary stimuli e.g. an acoustic stimulus is produced when the light is absorbed by water. To clarify whether INS in the cochlea requires functioning hair cells and to explore the potential relevance to cochlear implants, experiments using INS were performed in the cochleae of both normal hearing and profoundly deaf guinea pigs. A response to laser stimulation was readily evoked in normal hearing cochlea. However, no response was evoked in any profoundly deaf cochleae, for either acute or chronic deafening, contrary to previous work where a response was observed after acute deafening with ototoxic drugs. A neural response to electrical stimulation was readily evoked in all cochleae after deafening. The absence of a response from optical stimuli in profoundly deaf cochleae suggests that the response from INS in the cochlea is hair cell mediated.
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    Optical stimulation of neural tissue
    (IET, 2020-07) Rachael, Richardson; Ibbotson, Michael; Thompson, Alexander; Wise, Andrew; Fallon, James
    Electrical stimulation has been used for decades in devices such as pacemakers, cochlear implants and more recently for deep brain and retinal stimulation and electroceutical treatment of disease. However, current spread from the electrodes limits the precision of neural activation, leading to a low quality therapeutic outcome or undesired side-effects. Alternative methods of neural stimulation such as optical stimulation offer the potential to deliver higher spatial resolution of neural activation. Direct optical stimulation is possible with infrared light, while visible light can be used to activate neurons if the neural tissue is genetically modified with a light sensitive ion channel. Experimentally, both methods have resulted in highly precise stimulation with little spread of activation at least in the cochlea, each with advantages and disadvantages. Infrared neural stimulation does not require modification of the neural tissue, but has very high power requirements. Optogenetics can achieve precision of activation with lower power, but only in conjunction with targeted insertion of a light sensitive ion channel into the nervous system via gene therapy. This review will examine the advantages and limitations of optical stimulation of neural tissue, using the cochlea as an exemplary model and recent developments for retinal and deep brain stimulation.
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    Thermal damage threshold of neurons during infrared stimulation
    (Biomedical Optics Express, 2020-04) Brown, William; Needham, Karina; Begeng, James; Thompson, Alexander; Nayagam, Bryony; Kameneva, Tatiana; Stoddart, Paul
    In infrared neural stimulation (INS), laser-evoked thermal transients are used to generate small depolarising currents in neurons. The laser exposure poses a moderate risk of thermal damage to the target neuron. Indeed, exogenous methods of neural stimulation often place the target neurons under stressful non-physiological conditions, which can hinder ordinary neuronal function and hasten cell death. Therefore, quantifying the exposure-dependent probability of neuronal damage is essential for identifying safe operating limits of INS and other interventions for therapeutic and prosthetic use. Using patch-clamp recordings in isolated spiral ganglion neurons, we describe a method for determining the dose-dependent damage probabilities of individual neurons in response to both acute and cumulative infrared exposure parameters based on changes in injection current. The results identify a local thermal damage threshold at approximately 60 °C, which is in keeping with previous literature and supports the claim that damage during INS is a purely thermal phenomenon. In principle this method can be applied to any potentially injurious stimuli, allowing for the calculation of a wide range of dose-dependent neural damage probabilities. Unlike histological analyses, the technique is well-suited to quantifying gradual neuronal damage, and critical threshold behaviour is not required.