Browsing by Author "McDermott, Hugh"

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    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.
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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.
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    A beamformer post-filter for cochlear implant noise reduction
    (Acoustical Society of America, 2013-04) Hersbach, Adam; Grayden, David; Fallon, James; McDermott, Hugh
    Cochlear implant users have limited ability to understand speech in noisy conditions. Signal processing methods to address this issue that use multiple microphones typically use beamforming to perform noise reduction. However, the effectiveness of the beamformer is diminished as the number of interfering noises increases and the acoustic environment becomes more diffuse. A multimicrophone noise reduction algorithm that aims to address this issue is presented in this study. The algorithm uses spatial filtering to estimate the signal-to-noise ratio (SNR) and attenuates time-frequency elements that have poor SNR. The algorithm was evaluated by measuring intelligibility of speech embedded in 4-talker babble where the interfering talkers were spatially separated and changed location during the test. Twelve cochlear implant users took part in the evaluation, which demonstrated a significant mean improvement of 4.6 dB (standard error 0.4, P<0.001) in speech reception threshold compared to an adaptive beamformer. The results suggest that a substantial improvement in performance can be gained for cochlear implant users in noisy environments where the noise is spatially separated from the target speech.
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    Clinical Outcomes for Adult Cochlear Implant Recipients Experiencing Loss of Usable Acoustic Hearing in the Implanted Ear
    (Wolters Kluwer Health, Inc, 2015-05) Plant, Kerrie; van Hoesel, Richard; McDermott, Hugh; Dawson, Pamela; Cowan, Robert
    OBJECTIVES: The first aim of the study was to quantify the change in clinical performance after cochlear implantation for adults who had pre-operative levels of acoustic hearing in each ear of greater than or equal to 46% phoneme score on an open-set monosyllabic word test, and who subsequently experienced loss of useable acoustic hearing in the implanted ear. Pre- and postoperative spatial hearing abilities were assessed, because a clinical consideration for candidates with bilateral acoustic hearing is the potential for post-operative reduction in spatial hearing ability. Second, it was of interest to examine whether preoperative localization ability, as an indicator of access to interaural timing and level cues preoperatively, might be correlated with post-operative change in spatial hearing abilities. DESIGN: Clinical performance measures in the binaural condition were obtained preoperatively and at 12 months postoperatively in 19 postlinguistically hearing-impaired adult subjects. Preoperative localization ability was investigated as a potential correlate with post-operative change in spatial hearing abilities. RESULTS: Significant postoperative group mean improvement in speech perception was observed on measures of open-set monosyllabic word perception in quiet and on an adaptive sentence test presented in coincident 4-talker babble. Observed benefit was greater for a lower presentation level of 55 dB SPL as compared with a conversational speech level of 65 dB SPL. Self-reported ratings of benefit also improved for all questionnaires administered. Objective assessment of localization ability revealed poorer localization postoperatively, although subjective ratings of post-operative change in localization ability in real-world environments were more variable. Postoperative spatial release from masking was not different to that measured preoperatively for the configuration where the side of the head with the hearing aid was advantaged, but improved postoperatively for the configuration that advantaged the implanted side. Preoperative binaural localization ability was not correlated with postoperative spatial hearing abilities. CONCLUSIONS: The findings from this study support cochlear implantation for candidates with pre-operative levels of binaural acoustic hearing within the range examined within the present study. This includes subjects with preoperative open-set monosyllabic word scores ranging from 11 to 62% in the implanted ear, and from 16 to 75% on the contralateral side. Post-operative improvement would be expected for those subjects on a range of clinical measures, even when acoustic hearing was lost in the implanted ear after implantation.
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    Clinical validation of a precision electromagnetic tremor measurement system in participants receiving deep brain stimulation for essential tremor
    (IOP Publishing, 2016-08) Perera, Thushara; Yohanandan, Shivanthan; Thevathasan, Wesley; Jones, Mary; Peppard, Richard; Evans, Andrew; Tan, Joy; McKay, Colette; McDermott, Hugh
    Tremor is characterized commonly through subjective clinical rating scales. Accelerometer-based techniques for objective tremor measurement have been developed in the past, yet these measures are usually presented as an unintuitive dimensionless index without measurement units. Here we have developed a tool (TREMBAL) to provide quantifiable and objective measures of tremor severity using electromagnetic motion tracking. We aimed to compare TREMBAL's objective measures with clinical tremor ratings and determine the test-retest reliability of our technique. Eight participants with ET receiving deep brain stimulation (DBS) therapy were consented. Tremor was simultaneously recorded using TREMBAL and video during DBS adjustment. After each adjustment, participants performed a hands-outstretched task (for postural tremor) and a finger-nose task (for kinetic tremor). Video recordings were de-identified, randomized, and shown to a panel of movement disorder specialists to obtain their ratings. Regression analysis and Pearson's correlations were used to determine agreement between datasets. Subsets of the trial were repeated to assess test-retest reliability. Tremor amplitude and velocity measures were in close agreement with mean clinical ratings (r > 0.90) for both postural and kinetic tremors. Test-retest reliability for both translational and rotational components of tremor showed intra-class correlations >0.80. TREMBAL assessments showed that tremor gradually improved with increasing DBS therapy-this was also supported by clinical observation. TREMBAL measurements are a sensitive, objective and reliable assessment of tremor severity. This tool may have application in clinical trials and in aiding automated optimization of deep brain stimulation.
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    Comment on: Short pulse width widens the therapeutic window of subthalamic neurostimulation
    (John Wiley and Sons, 2015-09-11) McDermott, Hugh; McKay, Colette
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    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.
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    The effect of presentation level and stimulation rate on speech perception and modulation detection for cochlear implant users.
    (Acoustical Society of America, 2017-06) Brochier, Tim; McDermott, Hugh; McKay, Colette
    In order to improve speech understanding for cochlear implant users, it is important to maximize the transmission of temporal information. The combined effects of stimulation rate and presentation level on temporal information transfer and speech understanding remain unclear. The present study systematically varied presentation level (60, 50, and 40 dBA) and stimulation rate [500 and 2400 pulses per second per electrode (pps)] in order to observe how the effect of rate on speech understanding changes for different presentation levels. Speech recognition in quiet and noise, and acoustic amplitude modulation detection thresholds (AMDTs) were measured with acoustic stimuli presented to speech processors via direct audio input (DAI). With the 500 pps processor, results showed significantly better performance for consonant-vowel nucleus-consonant words in quiet, and a reduced effect of noise on sentence recognition. However, no rate or level effect was found for AMDTs, perhaps partly because of amplitude compression in the sound processor. AMDTs were found to be strongly correlated with the effect of noise on sentence perception at low levels. These results indicate that AMDTs, at least when measured with the CP910 Freedom speech processor via DAI, explain between-subject variance of speech understanding, but do not explain within-subject variance for different rates and levels.
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    Encoding speech in cochlear implants using simultaneous amplitude and rate modulation
    (Acoustical Society of America, 2018-10) Brochier, Tim; McKay, Colette; McDermott, Hugh
    To improve speech perception for cochlear implant (CI) users, it is essential to improve the transmission of temporal envelopes. The most common speech processors deliver temporal envelopes via the CI using fixed-rate amplitude modulated (AM) pulse trains. Psychophysical studies suggest that rate modulation (RM) and AM are perceived by a shared temporal integration mechanism, but the potential for them to constructively combine to encode temporal envelopes has yet to be explored. In this experiment, a speech processing strategy called amplitude and rate temporal modulation was developed to encode speech temporal envelopes with simultaneous AM and RM. The strategy was tested for perception of clean speech at 60 and 40 dBA, and 60 dBA speech in noise (+10 dB SNR). The amount of RM was varied and the amount of AM was held constant to determine whether the addition of RM could enhance the perception of temporal envelopes and improve speech understanding. At the lowest RM amount, speech scores were poorest for all speech conditions. For 60 dBA clean speech and speech in noise, speech scores were significantly better at the highest RM amounts, suggesting that RM combined with AM can be used to enhance perception of temporal envelopes.
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    Evaluating machine learning algorithms estimating tremor severity ratings on the Bain-Findley scale
    (IOP Publishing, 2016-11) Yohanandan, Shivanthan; Jones, Mary; Peppard, Richard; Tan, Joy; McDermott, Hugh; Perera, Thushara
    Tremor is a debilitating symptom of some movement disorders. Effective treatment, such as deep brain stimulation (DBS), is contingent upon frequent clinical assessments using instruments such as the Bain–Findley tremor rating scale (BTRS). Many patients, however, do not have access to frequent clinical assessments. Wearable devices have been developed to provide patients with access to frequent objective assessments outside the clinic via telemedicine. Nevertheless, the information they report is not in the form of BTRS ratings. One way to transform this information into BTRS ratings is through linear regression models (LRMs). Another, potentially more accurate method is through machine learning classifiers (MLCs). This study aims to compare MLCs and LRMs, and identify the most accurate model that can transform objective tremor information into tremor severity ratings on the BTRS. Nine participants with upper limb tremor had their DBS stimulation amplitude varied while they performed clinical upper-extremity exercises. Tremor features were acquired using the tremor biomechanics analysis laboratory (TREMBAL). Movement disorder specialists rated tremor severity on the BTRS from video recordings. Seven MLCs and 6 LRMs transformed TREMBAL features into tremor severity ratings on the BTRS using the specialists’ ratings as training data. The weighted Cohen’s kappa ( w) defined the models’ rating accuracy. This study shows that the Random Forest MLC was the most accurate model ( w = 0.81) at transforming tremor information into BTRS ratings, thereby improving the clinical interpretation of tremor information obtained from wearable devices.
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    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.).
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    Factors Predicting Postoperative Unilateral and Bilateral Speech Recognition in Adult Cochlear Implant Recipients with Acoustic Hearing
    (Wolters Kluwer Health, Inc., 2015-10) Plant, Kerrie; McDermott, Hugh; van Hoesel, Richard; Dawson, Pamela; Cowan, Robert
    OBJECTIVES: The first objective was to examine factors that could be predictive of postoperative unilateral (cochlear implant alone) speech recognition ability in a group of subjects with greater degrees of preoperative acoustic hearing than has been previously examined. Second, the study aimed to identify factors predictive of speech recognition in the best-aided, bilateral listening condition. DESIGN: Participants were 65 postlinguistically hearing-impaired adults with preoperative phoneme in quiet scores of greater than or equal to 46% in one or both ears. Preoperative demographic and audiometric factors were assessed as predictors of 12-month postoperative unilateral and bilateral monosyllabic word scores in quiet and of bilateral speech reception threshold (SRT) in babble. RESULTS: The predictive regression model accounted for 34.1% of the variance in unilateral word recognition scores in quiet. Factors that predicted better scores included: a shorter duration of severe to profound hearing loss in the implanted ear; and poorer pure-tone-averaged thresholds in the contralateral ear. Predictive regression models of postimplantation bilateral function accounted for 36.0% of the variance for word scores in quiet, and 30.9% of the variance for SRT in noise. A shorter duration of severe to profound hearing loss in the implanted ear, a lower age at the time of implantation, and better contralateral hearing thresholds were associated with higher bilateral word recognition in quiet and SRT in noise. CONCLUSIONS: In this group of cochlear implant recipients with preoperative acoustic hearing, a shorter duration of severe to profound hearing loss in the implanted ear was shown to be predictive of better unilateral and bilateral outcomes. However, further research is warranted to better understand the impact of that factor in a larger number of subjects with long-term hearing impairment of greater than 30 years. Better contralateral hearing was associated with poorer unilateral word scores with the implanted ear alone, but better absolute bilateral speech recognition. As a result, it is clear that different models would need to be developed to predict unilateral and bilateral postimplantation scores.
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    The feasibility of using acoustic markers of speech for optimizing patient outcomes during randomized amplitude variation in deep brain stimulation: a proof of principle methods study
    (Frontiers Media S.A., 2015-07-14) Vogel, Adam; McDermott, Hugh; Perera, Thushara; Jones, Mary; Peppard, Richard; McKay, Colette
    Background: Deep brain stimulation (DBS) is an effective treatment for reducing symptoms of tremor. A common and typically subjectively determined adverse effect of DBS is dysarthria. Current assessment protocols are driven by the qualitative judgments of treating clinicians and lack the sensitivity and objectivity required to optimize patient outcomes where multiple stimulation parameters are trialed. Objective: To examine the effect of DBS on speech in patients receiving stimulation to the posterior sub-thalamic area (PSA) via randomized manipulation of amplitude parameters. Methods: Six patients diagnosed with tremor receiving treatment via DBS of the PSA were assessed in a double-blinded, within-subjects experimental protocol. Amplitude (i.e., voltage or current) was randomly adjusted across 10 settings, while speech samples (e.g., sustained vowel, counting to 10) were recorded to identify the patient-specific settings required for optimal therapeutic benefit (reduced tremor) with minimal adverse effects (altered speech). Speech production between stimulation parameters was quantified using acoustic analysis. Results: Speech changed as a response to DBS but those changes were not uniform across patients nor were they generally in line with changes in amplitude with the exception of reduced vocal control and increased mean silence length in two patients. Speech outcomes did not correlate with changes in tremor. Conclusion: Intra-individual changes in speech were detected as a response to modified amplitude; however, no clear pattern was observed across patients as a group. The use of objective acoustic measures allows for quantification of speech changes during DBS optimization protocols, even when those changes are subtle and potentially difficult to detect perceptually.
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    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.
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    Influence of contralateral acoustic hearing on adult bimodal outcomes after cochlear implantation
    (Taylor & Francis Online, 2016-08) Plant, Kerrie; van Hoesel, Richard; McDermott, Hugh; Cowan, Robert
    OBJECTIVE: To examine post-implantation benefit and time taken to acclimate to the cochlear implant for adult candidates with more hearing in the contralateral non-implanted ear than has been previously considered within local candidacy guidelines. DESIGN: Prospective, within-subject experimental design. STUDY SAMPLE: Forty postlingual hearing-impaired adult subjects with a contralateral ear word score in quiet ranging from 27% to 100% (median 67%). RESULTS: Post-implantation improvement of 2.4 dB and 4.0 dB was observed on a sentence in coincident babble test at presentation levels of 65 and 55 dB SPL respectively, and a 2.1 dB benefit in spatial release from masking (SRM) advantage observed when the noise location favoured the implanted side. Significant post-operative group mean change of between 2.1 and 3.0 was observed on the sub-scales of the speech, spatial, and qualities (SSQ) questionnaire. Degree of post-implantation speech reception threshold (SRT) benefit on the coincident babble test and on perception of soft speech and sounds in the environment was greater for subjects with less contralateral hearing. The degree of contralateral acoustic hearing did not affect time taken to acclimate to the device. CONCLUSIONS: The findings from this study support cochlear implantation for candidates with substantial acoustic hearing in the contralateral ear, and provide guidance regarding post-implantation expectations.
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    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).
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    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.
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    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. .
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    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.
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    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.