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A comprehensive characterization of cognitive performance, clinical symptoms, and cortical activity following mild traumatic brain injury (mTBI).
(Applied Neuropsychology: Adult, 2023-11-28) Coyle, Hannah L; Bailey, Neil W; Ponsford, Jennie; Hoy, Kate E
The objective of this study was to investigate clinical symptoms, cognitive performance and cortical activity following mild traumatic brain injury (mTBI).
The acoustic and perceptual cues affecting melody segregation for listeners with a cochlear implant
(Frontiers, 2013-10) Marozeau, Jeremy; Innes-Brown, Hamish; Blamey, Peter
Our ability to listen selectively to single sound sources in complex auditory environments is termed “auditory stream segregation.” This ability is affected by peripheral disorders such as hearing loss, as well as plasticity in central processing such as occurs with musical training. Brain plasticity induced by musical training can enhance the ability to segregate sound, leading to improvements in a variety of auditory abilities. The melody segregation ability of 12 cochlear-implant recipients was tested using a new method to determine the perceptual distance needed to segregate a simple 4-note melody from a background of interleaved random-pitch distractor notes. In experiment 1, participants rated the difficulty of segregating the melody from distracter notes. Four physical properties of the distracter notes were changed. In experiment 2, listeners were asked to rate the dissimilarity between melody patterns whose notes differed on the four physical properties simultaneously. Multidimensional scaling analysis transformed the dissimilarity ratings into perceptual distances. Regression between physical and perceptual cues then derived the minimal perceptual distance needed to segregate the melody. The most efficient streaming cue for CI users was loudness. For the normal hearing listeners without musical backgrounds, a greater difference on the perceptual dimension correlated to the temporal envelope is needed for stream segregation in CI users. No differences in streaming efficiency were found between the perceptual dimensions linked to the F0 and the spectral envelope. Combined with our previous results in normally-hearing musicians and non-musicians, the results show that differences in training as well as differences in peripheral auditory processing (hearing impairment and the use of a hearing device) influences the way that listeners use different acoustic cues for segregating interleaved musical streams.
Acoustic Speech Analytics Are Predictive of Cerebellar Dysfunction in Multiple Sclerosis
(Springer, 2020-06) Noffs, Gustavo; Boonstra, Frederique; Perera, Thushara; Kolbe, Scott; Stankovich, Jim; Butzkueven, Helmut; Evans, Andrew; Vogel, Adam; van der Walt, Anneke
Speech production relies on motor control and cognitive processing and is linked to cerebellar function. In diseases where the cerebellum is impaired, such as multiple sclerosis (MS), speech abnormalities are common and can be detected by instrumental assessments. However, the potential of speech assessments to be used to monitor cerebellar impairment in MS remains unexplored. The aim of this study is to build an objectively measured speech score that reflects cerebellar function, pathology and quality of life in MS. Eighty-five people with MS and 21 controls participated in the study. Speech was independently assessed through objective acoustic analysis and blind expert listener ratings. Cerebellar function and overall disease disability were measured through validated clinical scores; cerebellar pathology was assessed via magnetic resonance imaging, and validated questionnaires informed quality of life. Selected speech variables were entered in a regression model to predict cerebellar function. The resulting model was condensed into one composite speech score and tested for prediction of abnormal 9-hole peg test (9HPT), and for correlations with the remaining cerebellar scores, imaging measurements and self-assessed quality of life. Slow rate of syllable repetition and increased free speech pause percentage were the strongest predictors of cerebellar impairment, complemented by phonatory instability. Those variables formed the acoustic composite score that accounted for 54% of variation in cerebellar function, correlated with cerebellar white matter volume (r = 0.3, p = 0.017), quality of life (r = 0.5, p < 0.001) and predicted an abnormal 9HPT with 85% accuracy. An objective multi-feature speech metric was highly representative of motor cerebellar impairment in MS.
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.
Adenosine tri-phosphate induced photoreceptor death and retinal remodelling in rats
(Wiley Periodicals Inc, 2014-09) Vessey, Kirstan; Greferath, Ursula; Aplin, Felix; Jobling, Andrew; Phipps, Joanna; Ho, Tracy; De longh, Robbert; Fletcher, Erica
Many common causes of blindness involve the death of retinal photoreceptors, followed by progressive inner retinal cell remodeling. For an inducible model of retinal degeneration to be useful, it must recapitulate these changes. Intravitreal administration of adenosine triphosphate (ATP) has recently been found to induce acute photoreceptor death. The aim of this study was to characterize the chronic effects of ATP on retinal integrity. Five-week-old, dark agouti rats were administered 50 mM ATP into the vitreous of one eye and saline into the other. Vision was assessed using the electroretinogram and optokinetic response and retinal morphology investigated via histology. ATP caused significant loss of visual function within 1 day and loss of 50% of the photoreceptors within 1 week. At 3 months, 80% of photoreceptor nuclei were lost, and total photoreceptor loss occurred by 6 months. The degeneration and remodeling were similar to those found in heritable retinal dystrophies and age-related macular degeneration and included inner retinal neuronal loss, migration, and formation of new synapses; Müller cell gliosis, migration, and scarring; blood vessel loss; and retinal pigment epithelium migration. In addition, extreme degeneration and remodeling events, such as neuronal and glial migration outside the neural retina and proliferative changes in glial cells, were observed. These extreme changes were also observed in the 2-year-old P23H rhodopsin transgenic rat model of retinitis pigmentosa. This ATP-induced model of retinal degeneration may provide a valuable tool for developing pharmaceutical therapies or for testing electronic implants aimed at restoring vision.
Advanced treatment of acrylic fiber manufacturing wastewater with a combined microbubble-ozonation/ultraviolet irradiation process
(Royal Society of Chemistry, 2015-09-09) Zheng, Tianlong; Zhang, Tao; Wang, Qunhui; Tian, Yanli; Shi, Zhining; Smale, Nicholas; Xu, Banghua
Zheng, T., T. Zhang, Q. Wang, Y. Tian, Z. Shi, N. Smale & B. Xu (2015). Advanced treatment of acrylic fiber manufacturing wastewater with a combined microbubble-ozonation/ultraviolet irradiation process. RSC Advances 5(95): 77601-77609
Advances in implantable bionic devices for blindness: a review
(Wiley-Blackwell, 2016-03) Lewis, Philip; Ayton, Lauren; Guymer, Robyn; Lowery, Arthur; Blamey, Peter; Allen, Penelope; Luu, Chi; Rosenfeld, Jeffrey
Since the 1950s, vision researchers have been working towards the ambitious goal of restoring a functional level of vision to the blind via electrical stimulation of the visual pathways. Groups based in Australia, USA, Germany, France and Japan report progress in the translation of retinal visual prosthetics from the experimental to clinical domains, with two retinal visual prostheses having recently received regulatory approval for clinical use. Regulatory approval for cortical visual prostheses is yet to be obtained; however, several groups report plans to conduct clinical trials in the near future, building upon the seminal clinical studies of Brindley and Dobelle. In this review, we discuss the general principles of visual prostheses employing electrical stimulation of the visual pathways, focusing on the retina and visual cortex as the two most extensively studied stimulation sites. We also discuss the surgical and functional outcomes reported to date for retinal and cortical prostheses, concluding with a brief discussion of novel developments in this field and an outlook for the future.
An all-diamond, hermetic electrical feedthrough array for a retinal prosthesis
(Elsevier, 2014-01) Ganesan, Kumaravelu; Garrett, David; Ahnood, Arman; Shivdasani, Mohit; Tong, Wei; Turnley, Ann; Fox, Kate; Meffin, Hamish; Prawer, Steven
The interface between medical implants and the human nervous system is rapidly becoming more and more complex. This rise in complexity is driving the need for increasing numbers of densely packed electrical feedthroughs to carry signals to and from implanted devices. This is particularly crucial in the field of neural prosthesis where high resolution stimulating or recording arrays near peripheral nerves or in the brain could dramatically improve the performance of these devices. Here we describe a flexible strategy for implementing high density, high count arrays of hermetic electrical feedthroughs by forming conducting nitrogen doped nanocrystalline diamond channels within an insulating polycrystalline diamond substrate. A unique feature of these arrays is that the feedthroughs can themselves be used as stimulating electrodes for neural tissue. Our particular application is such a feedthrough, designed as a component of a retinal implant to restore vision to the blind. The hermeticity of the feedthroughs means that the array can also form part of an implantable capsule which can interface directly with internal electronic chips. The hermeticity of the array is demonstrated by helium leak tests and electrical and electrochemical characterisation of the feedthroughs is described. The nitrogen doped nanocrystalline diamond forming the electrical feedthroughs is shown to be non cyctotoxic. New fabrication strategies, such as the one described here, combined with the exceptional biostability of diamond can be exploited to generate a range of biomedical implants that last for the lifetime of the user without fear of degradation.
Alternate subthalamic nucleus deep brain stimulation parameters to manage motor symptoms of Parkinson’s disease: Systematic review and meta-analysis
(John Wiley & Sons, 2018-09) Conway, Zachary; Silburn, Peter; Thevathasan, Wesley; O'Maley, Karen; Naughton, Geraldine; Cole, Michael
ABSTRACT Background The use of alternate frequencies, amplitudes and pulse widths to manage motor symptoms in Parkinson's disease (PD) patients with subthalamic nucleus deep brain stimulation (STN-DBS) is of clinical interest, but currently lacks systematic evidence. Objective/Hypothesis Systematically review whether alternate STN-DBS settings influence the therapy's efficacy for managing PD motor symptoms. Methods Systematic searches identified studies that; involved bilateral STN-DBS PD patients; manipulated ≥1 STN-DBS parameter (e.g. amplitude); assessed ≥1 motor symptom (e.g. tremor); and contrasted the experimental and chronic stimulation settings. A Mantel-Haenszel random-effects meta-analysis compared the UPDRS-III sub-scores at low (60-Hz) and high frequencies (≥130 Hz). Inter-study heterogeneity was assessed with the Cohen's χ2 and I2 index, while the standard GRADE evidence assessment examined strength of evidence. Results The meta-analysis indicated a very low quality for the pooled evidence due to risks of bias, significant heterogeneity and imprecision. Separate analyses involving studies that attempted to maintain the total electrical energy derived by increasing amplitude at 60-Hz frequencies suggested that low-frequency STN-DBS reduced UPDRS-III sub-scores by 5.8 points (95% CI=1.5-10.2; Z=2.6; P=0.009) compared to frequencies ≥130 Hz. This alternate stimulation strategy may be beneficial for those with severe axial symptoms post STN-DBS, however, benefits may only be short-term. Conclusion(s) The meta-analysis reported a very low quality of evidence for the efficacy of low-frequency STN-DBS for managing PD motor symptoms. Furthermore, it highlighted that lower amplitudes lead to the re-emergence of motor symptoms and further research is needed to understand the potential benefits of alternate STN-DBS parameters for PD patients. This article is protected by copyright. All rights reserved.
An Ambulatory Tremor Score for Parkinson’s Disease
(IOS Press, 2016-08) Braybrook, Michelle; O'Connor, Sam; Churchward, Philip; Perera, Thushara; Farzanehfar, Parisa; Horne, Malcolm
BACKGROUND: While tremor in Parkinson's Disease (PD) can be characterised in the consulting room, its relationship to treatment and fluctuations can be clinically helpful. OBJECTIVE: To develop an ambulatory assessment of tremor of PD. METHODS: Accelerometry data was collected using the Parkinson's KinetiGraph System (PKG, Global Kinetics). An algorithm was developed, which could successfully distinguish been subjects with a resting or postural tremor that involved the wrist whose frequency was greater than 3 Hz. Percent of time that tremor was present (PTT) between 09 : 00 and 18 : 00 was calculated. RESULTS: This algorithm was applied to 85 people with PD who had been assessed clinically for the presence and nature of tremor. The Sensitivity and Selectivity of a PTT >/=0.8% was 92.5% and 92.9% in identifying tremor, providing that the tremor was not a fine kinetic and postural tremor or was not in the upper limb. A PTT >1% provide high likely hood of the presence of clinical meaningful tremor. These cut-offs were retested on a second cohort (n = 87) with a similar outcome. The Sensitivity and Selectivity of the combined group was 88.7% and 89.5% respectively. Using the PTT, 50% of 22 newly diagnosed patients had a PTT >1.0%.The PKG's simultaneous bradykinesia scores was used to find a threshold for the emergence of tremor. Tremor produced artefactual increase in the PKG's dyskinesia score in 1% of this sample. CONCLUSIONS: We propose this as a means of assessing the presence of tremor and its relationship to bradykinesia.
Anatomical targeting for electrode localization in subthalamic nucleus deep brain stimulation: A comparative study.
(Journal of NeuroImaging, 2023-06-08) Tonroe, Thomas; McDermott, Hugh; Pearce, Patrick; Acevedo, Nicola; Thevathasan, Wesley; Xu, San San; Bulluss, Kristian; Perera, Thushara
In deep brain stimulation (DBS), accurate electrode placement is essential for optimizing patient outcomes. Localizing electrodes enables insight into therapeutic outcomes and development of metrics for use in clinical trials. Methods of defining anatomical targets have been described with varying accuracy and objectivity. To assess variability in anatomical targeting, we compare four methods of defining an appropriate target for DBS of the subthalamic nucleus for Parkinson's disease.
Anti-apoptotic gene Bcl2 is required for stapes development and hearing
(Macmillan Publishers Limited, 2012-08-09) Carpinelli, Marina; Wise, Andrew; Arhatari, Benedicta; Bouillet, Phillipe; Manji, Shehnaaz; Manning, Michael; Cooray, Anne; Burt, Rachel
In this paper we describe novel and specific roles for the apoptotic regulators Bcl2 and Bim in hearing and stapes development. Bcl2 is anti-apoptotic while Bim is pro-apoptotic. Characterization of the auditory systems of mice deficient for these molecules revealed that Bcl2 / mice suffered severe hearing loss. This was conductive in nature and did not affect sensory cells of the inner ear, with cochlear hair cells and neurons present and functional. Bcl2 / mice were found to have a malformed, often monocrural, porous stapes (the small stirrup-shaped bone of the middle ear), but a normally shaped malleus and incus. The deformed stapes was discontinuous with the incus and sometimes fused to the temporal bones. The defect was completely rescued in Bcl2 / Bim / mice and partially rescued in Bcl2 / Bimþ/ mice, which displayed high-frequency hearing loss and thickening of the stapes anterior crus. The Bcl2 / defect arose in utero before or during the cartilage stage of stapes development. These results implicate Bcl2 and Bim in regulating survival of second pharyngeal arch or neural crest cells that give rise to the stapes during embryonic development.
Anti-inflammatory Effects of Abdominal Vagus Nerve Stimulation on Experimental Intestinal Inflammation
(Frontiers, 2019-05) Payne, Sophie; Furness, John; Burns, Owen; Sedo, Alicia; Hyakumura, Tomoko; Shepherd, Robert; Fallon, James
Electrical stimulation of the cervical vagus nerve is an emerging treatment for inflammatory bowel disease (IBD). However, cervical vagal nerve stimulation (VNS) can produce unwanted side effects. Here, we investigated whether stimulating the vagus nerve closer to the end organ has fewer off-target effects, while reducing intestinal inflammation. An electrode array was developed to stimulate and record vagal neural responses in rats. Acute VNS off-target experiment: The cervical and abdominal vagus nerves of anaesthetised rats (n=5) were acutely implanted with an electrode array, stimulation delivered (10 Hz; symmetric biphasic current pulse; 320 nC per phase) and changes to heart rate, respiration and blood pressure assessed. Chronic VNS efficacy experiment: The abdominal vagus nerve was chronically implanted with an electrode array. After 2 weeks, the intestine was inflamed with TNBS (2.5% 2,4,6-trinitrobenzene sulphonic acid), an established method for rodent models of IBD. Rats were randomly selected to receive therapeutic VNS (n=7; 10 Hz; symmetric biphasic current pulse; 320 nC per phase; 3 hours/day) or no stimulation (n=8) for 5 days. Stool quality, C-reactive protein in blood and histology of the inflamed intestine were assessed. VNS off-target experiment: Abdominal VNS had no effect (two-way RM-ANOVA: P>0.05) on cardiac, respiratory and blood pressure parameters. However, during cervical VNS heart rate decreased by 31 ± 9 beats/minute (P>0.05), respiration was inhibited and blood pressure decreased. VNS efficacy experiment: During the implantation period, electrically-evoked neural response thresholds remained stable (one-way RM ANOVA: P>0.05), and were below stimulation levels. VNS rats, compared to unstimulated rats, had improved stool quality (two-way RM ANOVA: P<0.0001), no blood in faeces (P<0.0001), reduced plasma C-reactive protein (two-way RM ANOVA: P<0.05) and a reduction in resident inflammatory cell populations within the intestine (Kruskal-Wallis: P<0.05). Abdominal VNS did not evoke off-target effects, is an effective treatment of TNBS-induced inflammation, and may be an effective treatment of IBD in humans.
The Appearance of Phosphenes Elicited Using a Suprachoroidal Retinal Prosthesis
(iOVS, 2016-09) Sinclair, Nicholas; Shivdasani, Mohit; Perera, Thushara; Gillespie, Lisa; McDermott, Hugh; Ayton, Lauren; Blamey, Peter
Purpose: Phosphenes are the fundamental building blocks for presenting meaningful visual information to the visually impaired using a bionic eye device. The aim of this study was to characterize the size, shape, and location of phosphenes elicited using a suprachoroidal retinal prosthesis. Methods: Three patients with profound vision loss due to retinitis pigmentosa were implanted with a suprachoroidal electrode array, which was used to deliver charge-balanced biphasic constant-current pulses at various rates, amplitudes, and durations to produce phosphenes. Tasks assessing phosphene appearance, location, overlap, and the patients' ability to recognize phosphenes were performed using a custom psychophysics setup. Results: Phosphenes were reliably elicited in all three patients, with marked differences in the reported appearances between patients and between electrodes. Phosphene shapes ranged from simple blobs to complex forms with multiple components in both space and time. Phosphene locations within the visual field generally corresponded to the retinotopic position of the stimulating electrodes. Overlap between phosphenes elicited from adjacent electrodes was observed with one patient, which reduced with increasing electrode separation. In a randomized recognition task, two patients correctly identified the electrode being stimulated for 57.2% and 23% of trials, respectively. Conclusions: Phosphenes of varying complexity were successfully elicited in all three patients, indicating that the suprachoroidal space is an efficacious site for electrically stimulating the retina. The recognition scores obtained with two patients suggest that a suprachoroidal implant can elicit phosphenes containing unique information. This information may be useful when combining phosphenes into more complex and meaningful images that provide functional vision.
Applications of Phenomenological Loudness Models to Cochlear Implants
(Frontiers, 2021-01) McKay, Colette
Cochlear implants electrically stimulate surviving auditory neurons in the cochlea to provide severely or profoundly deaf people with access to hearing. Signal processing strategies derive frequency-specific information from the acoustic signal and code amplitude changes in frequency bands onto amplitude changes of current pulses emitted by the tonotopically arranged intracochlear electrodes. This article first describes how parameters of the electrical stimulation influence the loudness evoked and then summarizes two different phenomenological models developed by McKay and colleagues that have been used to explain psychophysical effects of stimulus parameters on loudness, detection, and modulation detection. The Temporal Model is applied to single-electrode stimuli and integrates cochlear neural excitation using a central temporal integration window analogous to that used in models of normal hearing. Perceptual decisions are made using decision criteria applied to the output of the integrator. By fitting the model parameters to a variety of psychophysical data, inferences can be made about how electrical stimulus parameters influence neural excitation in the cochlea. The Detailed Model is applied to multi-electrode stimuli, and includes effects of electrode interaction at a cochlear level and a transform between integrated excitation and specific loudness. The Practical Method of loudness estimation is a simplification of the Detailed Model and can be used to estimate the relative loudness of any multi-electrode pulsatile stimuli without the need to model excitation at the cochlear level. Clinical applications of these models to novel sound processing strategies are described.
Are long stimulus pulse durations the answer to improving spatial resolution in retinal prostheses?
(Annals of Translational Medicine, 2016-11) Petoe, Matthew; Shivdasani, Mohit
Retinal prostheses can provide artificial vision to patients with degenerate retinae by electrically stimulating the remaining inner retinal neurons. The evoked perception is generally adequate for light localization, but of limited spatial resolution owing to the indiscriminate activation of multiple retinal cell types, leading to distortions in the perceived image. Here we present a perspective on a recent work by Weitz and colleagues who demonstrate a focal confinement of retinal ganglion cell (RGC) activation when using extended pulse durations in the stimulation waveform. Using real-time calcium imaging, they provide evidence that long pulse durations selectively stimulate inner retinal neurons, whilst avoiding unwanted axonal activations. The application of this stimulation technique may provide enhanced spatial resolution for retinal prosthesis users. These experiments provide a robust analysis of the effects of increasing pulse duration and introduce the potential for alternative stimulation paradigms in retinal prostheses.
ASK1 inhibition: a therapeutic strategy with multi-system benefits
(Springer, 2020-02) Ogier, Jacqueline; Nayagam, Bryony; Lockhart, Paul
p38 mitogen-activated protein kinases (P38alpha and beta) and c-Jun N-terminal kinases (JNK1, 2, and 3) are key mediators of the cellular stress response. However, prolonged P38 and JNK signalling is associated with damaging inflammatory responses, reactive oxygen species-induced cell death, and fibrosis in multiple tissues, such as the kidney, liver, central nervous system, and cardiopulmonary systems. These responses are associated with many human diseases, including arthritis, dementia, and multiple organ dysfunctions. Attempts to prevent P38- and JNK-mediated disease using small molecule inhibitors of P38 or JNK have generally been unsuccessful. However, apoptosis signal-regulating kinase 1 (ASK1), an upstream regulator of P38 and JNK, has emerged as an alternative drug target for limiting P38- and JNK-mediated disease. Within this review, we compile the evidence that ASK1 mediates damaging cellular responses via prolonged P38 or JNK activation. We discuss the potential benefits of ASK1 inhibition as a therapeutic and summarise the studies that have tested the effects of ASK1 inhibition in cell and animal disease models, in addition to human clinical trials for a variety of disorders.
Assessing hearing by measuring heartbeat: The effect of sound level
(PLoS One, 2019-03) Shoushtarian, Mehrnaz; Weder, Stefan; Innes-Brown, Hamish; McKay, Colette
Functional near-infrared spectroscopy (fNIRS) is a non-invasive brain imaging technique that measures changes in oxygenated and de-oxygenated hemoglobin concentration and can provide a measure of brain activity. In addition to neural activity, fNIRS signals contain components that can be used to extract physiological information such as cardiac measures. Previous studies have shown changes in cardiac activity in response to different sounds. This study investigated whether cardiac responses collected using fNIRS differ for different loudness of sounds. fNIRS data were collected from 28 normal hearing participants. Cardiac response measures evoked by broadband, amplitude-modulated sounds were extracted for four sound intensities ranging from near-threshold to comfortably loud levels (15, 40, 65 and 90 dB Sound Pressure Level (SPL)). Following onset of the noise stimulus, heart rate initially decreased for sounds of 15 and 40 dB SPL, reaching a significantly lower rate at 15 dB SPL. For sounds at 65 and 90 dB SPL, increases in heart rate were seen. To quantify the timing of significant changes, inter-beat intervals were assessed. For sounds at 40 dB SPL, an immediate significant change in the first two inter-beat intervals following sound onset was found. At other levels, the most significant change appeared later (beats 3 to 5 following sound onset). In conclusion, changes in heart rate were associated with the level of sound with a clear difference in response to near-threshold sounds compared to comfortably loud sounds. These findings may be used alone or in conjunction with other measures such as fNIRS brain activity for evaluation of hearing ability.
At-Home Blood Pressure Measurements Provide Better Assessments of Orthostatic Hypotension in Parkinson's Disease.
(Journal of Personalized Medicine, 2023-08-28) Fernando, Chathurini V; Osborn, Sarah; Horne, Malcolm
Orthostatic hypotension (OH) is common in Parkinson's Disease (PD). It is intermittent, exacerbated by stressors including meals, medications, and dehydration, and frequently is unrecognized. Although intermittent, assessment is usually by a single "in clinic" BP measurement. This study examines whether 10 home measurements are more sensitive in detecting OH than a single "in clinic" measurement. Participants (44 people with PD and 16 controls) were instructed to measure lying and standing BP at home. BP was measured on five consecutive days upon waking and before bedtime. Symptoms were also assessed using the Movement Disorder Society United Parkinson's Disease Rating Scale and the Non-Motor Questionnaire. While a postural drop in systolic BP (≥20 mmHg) was recorded "in clinic" in thirteen of the forty-four PD participants, a postural drop was found in at least one of the ten home measurements in twenty-eight of the forty-four participants. Morning hypertension and variability in lying systolic BP was more common in these subjects than in those without a postural drop or the controls. A greater number of measurements of lying and standing BP are more likely to reveal orthostatic hypotension, variation in systolic BP, and hypertension than a single office measurement in people with PD.
Atoh1 gene therapy in the cochlea for hair cell regeneration
(Informa Pic, 2015-03-04) Richardson, Rachael; Atkinson, Patrick
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.

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