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Browsing by Author "Sinclair, Nicholas"

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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.
Deep brain stimulation for Parkinson's disease modulates high-frequency evoked and spontaneous neural activity
(Elsevier, Inc., 2019-07) Sinclair, Nicholas; McDermott, Hugh; Fallon, James; Perera, Thushara; Brown, Peter; Bulluss, Kristian; Thevathasan, Wesley
Deep brain stimulation is an established therapy for Parkinson's disease; however, its effectiveness is hindered by limited understanding of therapeutic mechanisms and the lack of a robust feedback signal for tailoring stimulation. We recently reported that subthalamic nucleus deep brain stimulation evokes a neural response resembling a decaying high-frequency (200-500Hz) oscillation that typically has a duration of at least 10ms and is localizable to the dorsal sub-region. As the morphology of this response suggests a propensity for the underlying neural circuitry to oscillate at a particular frequency, we have named it evoked resonant neural activity. Here, we determine whether this evoked activity is modulated by therapeutic stimulation - a critical attribute of a feedback signal. Furthermore, we investigated whether any related changes occurred in spontaneous local field potentials. Evoked and spontaneous neural activity was intraoperatively recorded from 19 subthalamic nuclei in patients with Parkinson's disease. Recordings were obtained before therapeutic stimulation and during 130Hz stimulation at increasing amplitudes (0.67-3.38mA), 'washout' of therapeutic effects, and non-therapeutic 20Hz stimulation. Therapeutic efficacy was assessed using clinical bradykinesia and rigidity scores. The frequency and amplitude of evoked resonant neural activity varied with the level of 130Hz stimulation (p<.001). This modulation coincided with improvement in bradykinesia and rigidity (p<.001), and correlated with spontaneous beta band suppression (p<.001). Evoked neural activity occupied a similar frequency band to spontaneous high-frequency oscillations (200-400Hz), both of which decreased to around twice the 130Hz stimulation rate. Non-therapeutic stimulation at 20Hz evoked, but did not modulate, resonant activity. These results indicate that therapeutic deep brain stimulation alters the frequency of evoked and spontaneous oscillations recorded in the subthalamic nucleus that are likely generated by loops within the cortico-basal ganglia-thalamo-cortical network. Evoked resonant neural activity therefore has potential as a tool for providing insight into brain network function and has key attributes of a dynamic feedback signal for optimizing therapy.
Determining the Contribution of Retinotopic Discrimination to Localization Performance With a Suprachoroidal Retinal Prosthesis
(IOVS, 2017-06) Petoe, Matthew; McCarthy, Chris; Shivdasani, Mohit; Sinclair, Nicholas; Scott, Adele; Ayton, Lauren; Barnes, Nick; Bionic Vision Australia Consortium
Purpose: With a retinal prosthesis connected to a head-mounted camera, subjects can perform low vision tasks using a combination of electrode discrimination and head-directed localization. The objective of the present study was to investigate the contribution of retinotopic electrode discrimination (perception corresponding to the arrangement of the implanted electrodes with respect to their position beneath the retina) to visual performance for three recipients of a 24-channel suprachoroidal retinal implant. Proficiency in retinotopic discrimination may allow good performance with smaller head movements, and identification of this ability would be useful for targeted rehabilitation. Methods: Three participants with retinitis pigmentosa performed localization and grating acuity assessments using a suprachoroidal retinal prosthesis. We compared retinotopic and nonretinotopic electrode mapping and hypothesized that participants with measurable acuity in a normal retinotopic condition would be negatively impacted by the nonretinotopic condition. We also expected that participants without measurable acuity would preferentially use head movement over retinotopic information. Results: Only one participant was able to complete the grating acuity task. In the localization task, this participant exhibited significantly greater head movements and significantly lower localization scores when using the nonretinotopic electrode mapping. There was no significant difference in localization performance or head movement for the remaining two subjects when comparing retinotopic to nonretinotopic electrode mapping. Conclusions: Successful discrimination of retinotopic information is possible with a suprachoroidal retinal prosthesis. Head movement behavior during a localization task can be modified using a nonretinotopic mapping. Behavioral comparisons using retinotopic and nonretinotopic electrode mapping may be able to highlight deficiencies in retinotopic discrimination, with a view to address these deficiencies in a rehabilitation environment. (ClinicalTrials.gov number, NCT01603576).
Factors Affecting Perceptual Thresholds in a Suprachoroidal Retinal Prosthesis
(The Association for Research in Vision and Ophthalmology Inc, 2014-10) Shivdasani, Mohit; Sinclair, Nicholas; Dimitrov, Peter; Varsamidis, Mary; Ayton, Lauren; Luu, Chi; Perera, Thushara; McDermott, Hugh; Blamey, Peter
PURPOSE: The suprachoroidal location for a retinal prosthesis provides advantages over other locations in terms of a simplified surgical procedure and a potentially more stable electrode-neural interface. The aim of this study was to assess the factors affecting perceptual thresholds, and to optimize stimulus parameters to achieve the lowest thresholds in patients implanted with a suprachoroidal retinal prosthesis. METHODS: Three patients with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal array. Perceptual thresholds measured on individual electrodes were analyzed as a function of stimulus (return configuration, pulse polarity, pulse width, interphase gap, and rate), electrode (area and number of ganged electrodes), and clinical (retinal thickness and electrode-retina distance) parameters. RESULTS: A total of 92.8% of 904 measurements made up to 680 days post implantation yielded thresholds (range, 44-436 nanocoulombs [nC]) below the safe charge limit. Thresholds were found to vary between individuals and to depend significantly on electrode-retina distance, negligibly on retinal thickness, and not on electrode area or the number of ganged electrodes. Lowest thresholds were achieved when using a monopolar return, anodic-first polarity, short pulse widths (100 μs) combined with long interphase gaps (500 μs), and high stimulation rates (≥400 pulses per second [pps]). CONCLUSIONS: With suprachoroidal stimulation, anodic-first pulses with a monopolar return are most efficacious. To enable high rates, an appropriate combination of pulse width and interphase gap must be chosen to ensure low thresholds and electrode voltages. Electrode-retina distance needs to be monitored carefully owing to its influence on thresholds. These results inform implantable stimulator specifications for a suprachoroidal retinal prosthesis. (ClinicalTrials.gov number, NCT01603576.).
Feedback control for deep brain stimulation for motor disorders
(IET, 2020-07) McDermott, Hugh; Sinclair, Nicholas
Deep brain stimulation (DBS) is an effective treatment for many people living with Parkinson’s disease (PD). Although the primary treatment for PD is based on medications, disease progression eventually leads to inadequate symptom control. DBS provides benefits by alleviating motor dysfunctions such as muscle rigidity and tremor. DBS devices deliver electric pulse trains into specific brain regions via implanted electrodes. Existing DBS systems usually provide continuous stimulation with constant settings of parameters such as the amount of charge delivered per pulse. However, PD is characterised by fluctuations in the severity and frequency of impairments. DBS would be improved if stimulation settings were adjusted automatically in response to each patient’s ever-changing needs. This requires a device incorporating sensing of signals that estimate the severity of motor impairment linked to an adaptive control algorithm that optimises therapeutic stimulation. Several types of signals are candidates for this function. Spontaneous local field potentials recorded by the DBS electrodes have shown promise in some experimental studies of adaptive DBS. More recently, DBS-evoked potentials have been reported. In particular, evoked resonant neural activity has properties including a larger amplitude than spontaneous potentials, suggesting it may be a suitable feedback signal to control adaptive DBS.
Identification of Characters and Localization of Images Using Direct Multiple-Electrode Stimulation With a Suprachoroidal Retinal Prosthesis
(IOVS, 2017-08) Shivdasani, Mohit; Sinclair, Nicholas; Gillespie, Lisa; Petoe, Matthew; Titchener, Samuel; Fallon, James; Perera, Thushara; Pardinas-Diaz, Darien; Barnes, Nick; Blamey, Peter; Bionic Vision Australia Consortium
Purpose: Retinal prostheses provide vision to blind patients by eliciting phosphenes through electrical stimulation. This study explored whether character identification and image localization could be achieved through direct multiple-electrode stimulation with a suprachoroidal retinal prosthesis. Methods: Two of three retinitis pigmentosa patients implanted with a suprachoroidal electrode array were tested on three psychophysical tasks. Electrode patterns were stimulated to elicit perception of simple characters, following which percept localization was tested using either static or dynamic images. Eye tracking was used to assess the association between accuracy and eye movements. Results: In the character identification task, accuracy ranged from 2.7% to 93.3%, depending on the patient and character. In the static image localization task, accuracy decreased from near perfect to <20% with decreasing contrast (patient 1). Patient 2 scored up to 70% at 100% contrast. In the dynamic image localization task, patient 1 recognized the trajectory of the image up to speeds of 64 deg/s, whereas patient 2 scored just above chance. The degree of eye movement in both patients was related to accuracy and, to some extent, stimulus direction. Conclusions: The ability to identify characters and localize percepts demonstrates the capacity of the suprachoroidal device to provide meaningful information to blind patients. The variation in scores across all tasks highlights the importance of using spatial cues from phosphenes, which becomes more difficult at low contrast. The use of spatial information from multiple electrodes and eye-movement compensation is expected to improve performance outcomes during real-world prosthesis use in a camera-based system. (ClinicalTrials.gov number, NCT01603576.).
neuroBi: A Highly Configurable Neurostimulator for a Retinal Prosthesis and Other Applications
(IEEE, 2015-07) Slater, Kyle; Sinclair, Nicholas; Nelson, Timothy; Blamey, Peter; McDermott, Hugh
To evaluate the efficacy of a suprachoroidal retinal prosthesis, a highly configurable external neurostimulator is required. In order to meet functional and safety specifications, it was necessary to develop a custom device. A system is presented which can deliver charge-balanced, constant-current biphasic pulses, with widely adjustable parameters, to arbitrary configurations of output electrodes. This system is shown to be effective in eliciting visual percepts in a patient with approximately 20 years of light perception vision only due to retinitis pigmentosa, using an electrode array implanted in the suprachoroidal space of the eye. The flexibility of the system also makes it suitable for use in a number of other emerging clinical neurostimulation applications, including epileptic seizure suppression and closed-loop deep brain stimulation. Clinical trial registration number NCT01603576 (www.clinicaltrials.gov).
Objective evaluation of bradykinesia in Parkinson’s disease using an inexpensive marker-less motion tracking system
(IOP Publishing, 2019-01) Lee, Wee Lih; Sinclair, Nicholas; Jones, Mary; Tan, Joy; Proud, Elizabeth; Peppard, Richard; McDermott, Hugh; Perera, Thushara
OBJECTIVE: Quantification of bradykinesia (slowness of movement) is crucial for the treatment and monitoring of Parkinson's disease. Subjective observational techniques are the de-facto 'gold standard', but such clinical rating scales suffer from poor sensitivity and inter-rater variability. Although various technologies have been developed for assessing bradykinesia in recent years, most still require considerable expertise and effort to operate. Here we present a novel method to utilize an inexpensive off-the-shelf hand-tracker (Leap Motion) to quantify bradykinesia. Approach: Eight participants with Parkinson's disease receiving benefit from deep brain stimulation were recruited for the study. Participants were assessed "on" and "off" stimulation, with the "on" condition repeated to evaluate reliability. Participants performed wrist pronation/supination, hand open/close, and finger-tapping tasks during each condition. Tasks were simultaneously captured by our software and rated by three clinicians. A linear regression model was developed to predict clinical scores and its performance was assessed with leave-one-out cross validation. Main Results: Aggregate bradykinesia scores predicted by our method were in strong agreement (R = 0.86) with clinical scores. The model was able to differentiate therapeutic states and comparison between the test-retest conditions yielded no significant difference (p = 0.50). Significance: These findings demonstrate that our method can objectively quantify bradykinesia in agreement with clinical observation and provide reliable measurements over time. The hardware is readily accessible, requiring only a modest computer and our software to perform assessments, thus making it suitable for both clinic- and home-based symptom tracking.
Objective evaluation of bradykinesia in Parkinson’s disease using an inexpensive marker-less motion tracking system
(IOP Publishing Ltd, 2019-01) Lih, Wee-Lih; Sinclair, Nicholas; Jones, Mary; Tan, Joy; Proud, Elizabeth; Peppard, Richard; McDermott, Hugh; Perera, Thushara
OBJECTIVE: Quantification of bradykinesia (slowness of movement) is crucial for the treatment and monitoring of Parkinson's disease. Subjective observational techniques are the de-facto 'gold standard', but such clinical rating scales suffer from poor sensitivity and inter-rater variability. Although various technologies have been developed for assessing bradykinesia in recent years, most still require considerable expertise and effort to operate. Here we present a novel method to utilize an inexpensive off-the-shelf hand-tracker (Leap Motion) to quantify bradykinesia. Approach: Eight participants with Parkinson's disease receiving benefit from deep brain stimulation were recruited for the study. Participants were assessed "on" and "off" stimulation, with the "on" condition repeated to evaluate reliability. Participants performed wrist pronation/supination, hand open/close, and finger-tapping tasks during each condition. Tasks were simultaneously captured by our software and rated by three clinicians. A linear regression model was developed to predict clinical scores and its performance was assessed with leave-one-out cross validation. Main Results: Aggregate bradykinesia scores predicted by our method were in strong agreement (R = 0.86) with clinical scores. The model was able to differentiate therapeutic states and comparison between the test-retest conditions yielded no significant difference (p = 0.50). Significance: These findings demonstrate that our method can objectively quantify bradykinesia in agreement with clinical observation and provide reliable measurements over time. The hardware is readily accessible, requiring only a modest computer and our software to perform assessments, thus making it suitable for both clinic- and home-based symptom tracking. .
On the neural basis of deep brain stimulation evoked resonant activity
(IOP Publishing, 2019-08) Sinclair, Nicholas; Fallon, James; Bulluss, Kristian; Thevathasan, Wesley; McDermott, Hugh
Objective: Deep brain stimulation can be a remarkably effective treatment for Parkinson’s disease and other conditions; however, an electrophysiological feedback signal is needed to improve surgical accuracy and for optimising therapy according to patient needs. Evoked responses may provide such a signal, although it is crucial to determine that recorded potentials are of neural origin and not a consequence of stimulation artefacts. Here, we use several in vitro and in vivo methods to establish the neural basis of resonant deep brain stimulation evoked activity. Approach: Recordings were obtained from deep brain stimulation electrodes in saline, in feline brain regions not expected to produce resonant neural responses, and in fourteen subthalamic nuclei in people with Parkinson’s disease following stimulation with 60 μs per phase biphasic current pulses with different polarities. Main results: Electrodes in saline did not exhibit stimulation artefacts beyond 1 ms. Changing the pulse polarity reversed the stimulation artefact. Electrodes in feline brain elicited early latency activity (<5ms); however, the activity did not resemble a decaying oscillation. Electrodes in human subthalamic nuclei evoked resonant neural activity that was not reversed by changing the pulse polarity. The latency of resonant peaks from stimuli with opposing polarities differed by about the expected amount and were strongly correlated (ρ = 0.998, p < 0.001). Resonant peak amplitudes were also strongly correlated (ρ = 0.945, p < 0.001). Significance: The absence of resonant activity in recordings from electrodes in saline and feline brain, in addition to findings that resonant activity occurs in the subthalamic nucleus but not neighbouring white matter regions, demonstrates that such activity is not an artefact of the stimulation and recording system. Furthermore, non-reversal of resonant activity with changing pulse polarity in human subthalamic nuclei indicates that it is independent from stimulation artefact. Thus, these methods provide strong evidence of the neural basis of deep brain stimulation evoked resonant activity.
A palm-worn device to quantify rigidity in Parkinson’s disease
(Elsevier B.V., 2019-02) Perera, Thushara; Lee, Wee-Lih; Jones, Mary; Tan, Joy; Proud, Elizabeth; Begg, Angus; Sinclair, Nicholas; Peppard, Richard; McDermott, Hugh
BACKGROUND: Parkinsonian rigidity is identified on clinical examination as resistance to passive movement. Measurement of rigidity commonly relies on ordinal rating scales (MDS-UPDRS), however instrumented objective measures may provide greater mechanistic insight. NEW METHOD: We present a palm-worn instrument to objectively quantify rigidity on a continuous scale. The device employs a miniature motor to flex the third digit of the hand about the metacarpophalangeal joint whilst transducers record flexion/extension forces. We aim to determine congruence with the MDS-UPDRS, investigate sensitivity to the impact of deep brain stimulation (DBS) and contralateral movement, and make comparisons with healthy individuals. Eight participants with Parkinson's disease underwent evaluation during conditions: on and off DBS, and with and without contralateral limb movement to activate rigidity. During each DBS condition, wash-in/out effects were tracked using both our instrument and two blinded clinical raters. Sixteen healthy volunteers (age-matched/young) served as controls. RESULTS: Rigidity measured using our instrument had moderate agreement with the MDS-UPDRS and showed differences between therapeutic state, activation conditions, and disease/healthy cohorts. Rigidity gradually worsened over a one-hour period after DBS cessation, but improved more rapidly with DBS resumption. COMPARISON WITH EXISTING METHODS: Previous attempts to quantify rigidity include manual approaches where a clinician is required to manipulate limbs while sensors passively gather information, or large automated instruments to move the wrist or elbow. CONCLUSION: Given its ability to track changes in rigidity due to therapeutic intervention, our technique could have applications where continuous measurement is required or where a suitably qualified rater is absent.
Subthalamic Nucleus Deep Brain Stimulation Evokes Resonant Neural Activity
(Wiley Periodicals, Inc., 2018-05) Sinclair, Nicholas; McDermott, Hugh; Bulluss, Kristian; Fallon, James; Perera, Thushara; Xu, San San; Brown, Peter; Thevathasan, Wesley
Deep brain stimulation (DBS) is a rapidly expanding treatment for neurological and psychiatric conditions; however, a target-specific biomarker is required to optimize therapy. Here, we show that DBS evokes a large-amplitude resonant neural response focally in the subthalamic nucleus. This response is greatest in the dorsal region (the clinically optimal stimulation target for Parkinson disease), coincides with improved clinical performance, is chronically recordable, and is present under general anesthesia. These features make it a readily utilizable electrophysiological signal that could potentially be used for guiding electrode implantation surgery and tailoring DBS therapy to improve patient outcomes.
Tailoring Subthalamic Nucleus Deep Brain Stimulation for Parkinson's Disease Using Evoked Resonant Neural Activity
(Frontiers in Human Neuroscience, 2020-02) Thevathasan, Wesley; Sinclair, Nicholas; Bulluss, Kristian; McDermott, Hugh
Towards guided and automated programming of subthalamic area stimulation in Parkinson’s disease
(Brain Communications, 2022-01-13) San San, Xu; Sinclair, Nicholas; Bullus, Kristian; Perera, Thushara; Lee, Wee-lih; McDermott, Hugh; Thevathasan, Wesley
Selecting the ideal contact to apply subthalamic nucleus deep brain stimulation in Parkinson’s disease can be an arduous process, with outcomes highly dependent on clinician expertise. This study aims to assess whether neuronal signals recorded intraoperatively in awake patients, and the anatomical location of contacts, can assist programming. In a cohort of 14 patients with Parkinson’s disease, implanted with subthalamic nucleus deep brain stimulation, the four contacts on each lead in the 28 hemispheres were ranked according to proximity to a nominated ideal anatomical location and power of the following neuronal signals: evoked resonant neural activity, beta oscillations and high-frequency oscillations. We assessed how these rankings predicted, on each lead: (i) the motor benefit from deep brain stimulation applied through each contact and (ii) the ‘ideal’ contact to apply deep brain stimulation. The ranking of contacts according to each factor predicted motor benefit from subthalamic nucleus deep brain stimulation, as follows: evoked resonant neural activity; r2 = 0.50, Akaike information criterion 1039.9, beta; r2 = 0.50, Akaike information criterion 1041.6, high-frequency oscillations; r2 = 0.44, Akaike information criterion 1057.2 and anatomy; r2 = 0.49, Akaike information criterion 1048.0. Combining evoked resonant neural activity, beta and high-frequency oscillations ranking data yielded the strongest predictive model (r2 = 0.61, Akaike information criterion 1021.5). The ‘ideal’ contact (yielding maximal benefit) was ranked first according to each factor in the following proportion of hemispheres; evoked resonant neural activity 18/28, beta 17/28, anatomy 16/28, high-frequency oscillations 7/28. Across hemispheres, the maximal available deep brain stimulation benefit did not differ from that yielded by contacts chosen by clinicians for chronic therapy or contacts ranked first according to evoked resonant neural activity. Evoked resonant neural activity, beta oscillations and anatomy similarly predicted how motor benefit from subthalamic nucleus deep brain stimulation varied across contacts on each lead. This could assist programming by providing a probability ranking of contacts akin to a ‘monopolar survey’. However, these factors identified the ‘ideal’ contact in only a proportion of hemispheres. More advanced signal processing and anatomical techniques may be needed for the full automation of contact selection.
Vision function testing for a suprachoroidal retinal prosthesis: effects of image filtering
(IOP Publishing, 2016-04) Barnes, Nick; Scott, Adele; Lieby, Paulette; Petoe, Matthew; McCarthy, Chris; Stacey, Ashley; Ayton, Lauren; Sinclair, Nicholas; Shivdasani, Mohit; Lovell, Nigel; McDermott, Hugh; Walker, Janine; BVA Consortium
OBJECTIVE: One strategy to improve the effectiveness of prosthetic vision devices is to process incoming images to ensure that key information can be perceived by the user. This paper presents the first comprehensive results of vision function testing for a suprachoroidal retinal prosthetic device utilizing of 20 stimulating electrodes. Further, we investigate whether using image filtering can improve results on a light localization task for implanted participants compared to minimal vision processing. No controlled implanted participant studies have yet investigated whether vision processing methods that are not task-specific can lead to improved results. APPROACH: Three participants with profound vision loss from retinitis pigmentosa were implanted with a suprachoroidal retinal prosthesis. All three completed multiple trials of a light localization test, and one participant completed multiple trials of acuity tests. The visual representations used were: Lanczos2 (a high quality Nyquist bandlimited downsampling filter); minimal vision processing (MVP); wide view regional averaging filtering (WV); scrambled; and, system off. MAIN RESULTS: Using Lanczos2, all three participants successfully completed a light localization task and obtained a significantly higher percentage of correct responses than using MVP ([Formula: see text]) or with system off ([Formula: see text]). Further, in a preliminary result using Lanczos2, one participant successfully completed grating acuity and Landolt C tasks, and showed significantly better performance ([Formula: see text]) compared to WV, scrambled and system off on the grating acuity task. SIGNIFICANCE: Participants successfully completed vision tasks using a 20 electrode suprachoroidal retinal prosthesis. Vision processing with a Nyquist bandlimited image filter has shown an advantage for a light localization task. This result suggests that this and targeted, more advanced vision processing schemes may become important components of retinal prostheses to enhance performance. ClinicalTrials.gov Identifier: NCT01503576.

Browsing by Author "Sinclair, Nicholas"

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