Browsing by Author "Peppard, Richard"

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    Balance control systems in Parkinson’s disease and the impact of pedunculopontine area stimulation
    (Brain, 2018-08) Perera, Thushara; Tan, Joy; Cole, Michael; Yohanandan, Shivanthan; Silberstein, Paul; Cook, Raymond; Peppard, Richard; Aziz, Tipu; Coyne, Terry; Brown, Peter; Silburn, Peter; Thevathasan, Wesley
    Impaired balance is a major contributor to falls and diminished quality of life in Parkinson's disease, yet the pathophysiology is poorly understood. Here, we assessed if patients with Parkinson's disease and severe clinical balance impairment have deficits in the intermittent and continuous control systems proposed to maintain upright stance, and furthermore, whether such deficits are potentially reversible, with the experimental therapy of pedunculopontine nucleus deep brain stimulation. Two subject groups were assessed: (i) 13 patients with Parkinson's disease and severe clinical balance impairment, implanted with pedunculopontine nucleus deep brain stimulators; and (ii) 13 healthy control subjects. Patients were assessed in the OFF medication state and blinded to two conditions; off and on pedunculopontine nucleus stimulation. Postural sway data (deviations in centre of pressure) were collected during quiet stance using posturography. Intermittent control of sway was assessed by calculating the frequency of intermittent switching behaviour (discontinuities), derived using a wavelet-based transformation of the sway time series. Continuous control of sway was assessed with a proportional-integral-derivative (PID) controller model using ballistic reaction time as a measure of feedback delay. Clinical balance impairment was assessed using the 'pull test' to rate postural reflexes and by rating attempts to arise from sitting to standing. Patients with Parkinson's disease demonstrated reduced intermittent switching of postural sway compared with healthy controls. Patients also had abnormal feedback gains in postural sway according to the PID model. Pedunculopontine nucleus stimulation improved intermittent switching of postural sway, feedback gains in the PID model and clinical balance impairment. Clinical balance impairment correlated with intermittent switching of postural sway (rho = - 0.705, P < 0.001) and feedback gains in the PID model (rho = 0.619, P = 0.011). These results suggest that dysfunctional intermittent and continuous control systems may contribute to the pathophysiology of clinical balance impairment in Parkinson's disease. Clinical balance impairment and their related control system deficits are potentially reversible, as demonstrated by their improvement with pedunculopontine nucleus deep brain stimulation.
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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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    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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    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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    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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    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.
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    Potential for optimising Deep Brain stimulation through tremor quantification
    (2013) Perera, Thushara; McKay, Colette; Peppard, Richard; McDermott, Hugh; Vogel, Adam
    Deep Brain Stimulation (DBS) can be used to minimise tremor when pharmaceutical therapies fail •DBS devices emit a bi-phasic pulse train with variable: » Amplitude » Pulse Duration » Frequency •These parameters are set based on clinical observation of tremor and side-effects