Estimation of Gait Parameters in Huntington's Disease Using Wearable Sensors in the Clinic and Free-living Conditions.

In Huntington's disease (HD), wearable inertial sensors could capture subtle changes in motor function. However, disease-specific validation of methods is necessary. This study presents an algorithm for walking bout and gait event detection in HD using a leg-worn accelerometer, validated only in the clinic and deployed in free-living conditions. Seventeen HD participants wore shank- and thigh-worn tri-axial accelerometers, and a wrist-worn device during two-minute walk tests in the clinic, with video reference data for validation. Thirteen participants wore one of the thigh-worn tri-axial accelerometers (AP: ActivPAL4) and the wrist-worn device for 7 days under free-living conditions, with proprietary AP data used as reference. Gait events were detected from shank and thigh acceleration using the Teager-Kaiser energy operator combined with unsupervised clustering. Estimated step count (SC) and temporal gait parameters were compared with reference data. In the clinic, low mean absolute percentage errors were observed for stride (shank/thigh: 0.6/0.9%) and stance (shank/thigh: 3.3/7.1%) times, and SC (shank/thigh: 3.1%). Similar errors were observed for proprietary AP SC (3.2%), with higher errors observed for the wrist-worn device (10.9%). At home, excellent agreement was observed between the proposed algorithm and AP software for SC and time spent walking (ICC [Formula: see text]). The wrist-worn device overestimated SC by 34.2%. The presented algorithm additionally allowed stride and stance time estimation, whose variability correlated significantly with clinical motor scores. The results demonstrate a new method for accurate estimation of HD gait parameters in the clinic and free-living conditions, using a single accelerometer worn on either the thigh or shank.

Language-Independent Acoustic Biomarkers for Quantifying Speech Impairment in Huntington's Disease.

PURPOSE: Changes in voice and speech are characteristic symptoms of Huntington's disease (HD). Objective methods for quantifying speech impairment that can be used across languages could facilitate assessment of disease progression and intervention strategies. The aim of this study was to analyze acoustic features to identify language-independent features that could be used to quantify speech dysfunction in English-, Spanish-, and Polish-speaking participants with HD. METHOD: Ninety participants with HD and 83 control participants performed sustained vowel, syllable repetition, and reading passage tasks recorded with previously validated methods using mobile devices. Language-independent features that differed between HD and controls were identified. Principal component analysis (PCA) and unsupervised clustering were applied to the language-independent features of the HD data set to identify subgroups within the HD data. RESULTS: Forty-six language-independent acoustic features that were significantly different between control participants and participants with HD were identified. Following dimensionality reduction using PCA, four speech clusters were identified in the HD data set. Unified Huntington's Disease Rating Scale (UHDRS) total motor score, total functional capacity, and composite UHDRS were significantly different for pairwise comparisons of subgroups. The percentage of HD participants with higher dysarthria score and disease stage also increased across clusters. CONCLUSION: The results support the application of acoustic features to objectively quantify speech impairment and disease severity in HD in multilanguage studies. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25447171.

Assessment of Fitbit Charge 4 for sleep stage and heart rate monitoring against polysomnography and during home monitoring in Huntington's disease.

STUDY OBJECTIVES: Wearable devices that monitor sleep stages and heart rate offer the potential for longitudinal sleep monitoring in patients with neurodegenerative diseases. Sleep quality reduces with disease progression in Huntington's disease (HD). However, the involuntary movements characteristic of HD may affect the accuracy of wrist-worn devices. This study compares sleep stage and heart rate data from the Fitbit Charge 4 (FB) against polysomnography (PSG) in participants with HD. METHODS: Ten participants with manifest HD wore an FB during overnight hospital-based PSG, and 9 of these participants continued to wear the FB for 7 nights at home. Sleep stages (30-second epochs) and minute-by-minute heart rate were extracted and compared against PSG data. RESULTS: FB-estimated total sleep and wake times and sleep stage times were in good agreement with PSG, with intraclass correlations of 0.79-0.96. However, poor agreement was observed for wake after sleep onset and the number of awakenings. FB detected waking with 68.6 ± 15.5% sensitivity and 93.7 ± 2.5% specificity, rapid eye movement sleep with high sensitivity and specificity (78.7 ± 31.9%, 95.6 ± 2.3%), and deep sleep with lower sensitivity but high specificity (56.4 ± 28.8%, 95.0 ± 4.8%). FB heart rate was strongly correlated with PSG, and the mean absolute error between FB and PSG heart rate data was 1.16 ± 0.42 beats/min. At home, longer sleep and shorter wake times were observed compared with hospital data, whereas percentage sleep stage times were consistent with hospital data. CONCLUSIONS: Results suggest the potential for long-term monitoring of sleep patterns using wrist-worn wearable devices as part of symptom management in HD. CITATION: Doheny EP, Renerts K, Braun A, et al. Assessment of Fitbit Charge 4 for sleep stage and heart rate monitoring against polysomnography and during home monitoring in Huntington's disease. J Clin Sleep Med. 2024;20(7):1163-1171.

On-Off and Proportional Closed-Loop Adaptive Deep Brain Stimulation Reduces Motor Symptoms in Freely Moving Hemiparkinsonian Rats.

OBJECTIVES: Closed-loop adaptive deep brain stimulation (aDBS) continuously adjusts stimulation parameters, with the potential to improve efficacy and reduce side effects of deep brain stimulation (DBS) for Parkinson's disease (PD). Rodent models can provide an effective platform for testing aDBS algorithms and establishing efficacy before clinical investigation. In this study, we compare two aDBS algorithms, on-off and proportional modulation of DBS amplitude, with conventional DBS in hemiparkinsonian rats. MATERIALS AND METHODS: DBS of the subthalamic nucleus (STN) was delivered wirelessly in freely moving male and female hemiparkinsonian (N = 7) and sham (N = 3) Wistar rats. On-off and proportional aDBS, based on STN local field potential beta power, were compared with conventional DBS and three control stimulation algorithms. Behavior was assessed during cylinder tests (CT) and stepping tests (ST). Successful model creation was confirmed via apomorphine-induced rotation test and Tyrosine Hydroxylase-immunocytochemistry. Electrode location was histologically confirmed. Data were analyzed using linear mixed models. RESULTS: Contralateral paw use in parkinsonian rats was reduced to 20% and 25% in CT and ST, respectively. Conventional, on-off, and proportional aDBS significantly improved motor function, restoring contralateral paw use to approximately 45% in both tests. No improvement in motor behavior was observed with either randomly applied on-off or low-amplitude continuous stimulation. Relative STN beta power was suppressed during DBS. Relative power in the alpha and gamma bands decreased and increased, respectively. Therapeutically effective adaptive DBS used approximately 40% less energy than did conventional DBS. CONCLUSIONS: Adaptive DBS, using both on-off and proportional control schemes, is as effective as conventional DBS in reducing motor symptoms of PD in parkinsonian rats. Both aDBS algorithms yield substantial reductions in stimulation power. These findings support using hemiparkinsonian rats as a viable model for testing aDBS based on beta power and provide a path to investigate more complex closed-loop algorithms in freely behaving animals.

Multivariable closed-loop control of deep brain stimulation for Parkinson's disease.

Objective. Closed-loop deep brain stimulation (DBS) methods for Parkinson's disease (PD) to-date modulate either stimulation amplitude or frequency to control a single biomarker. While good performance has been demonstrated for symptoms that are correlated with the chosen biomarker, suboptimal regulation can occur for uncorrelated symptoms or when the relationship between biomarker and symptom varies. Control of stimulation-induced side-effects is typically not considered.Approach.A multivariable control architecture is presented to selectively target suppression of either tremor or subthalamic nucleus beta band oscillations. DBS pulse amplitude and duration are modulated to maintain amplitude below a threshold and avoid stimulation of distal large diameter axons associated with stimulation-induced side effects. A supervisor selects between a bank of controllers which modulate DBS pulse amplitude to control rest tremor or beta activity depending on the level of muscle electromyographic (EMG) activity detected. A secondary controller limits pulse amplitude and modulates pulse duration to target smaller diameter axons lying close to the electrode. The control architecture was investigated in a computational model of the PD motor network which simulated the cortico-basal ganglia network, motoneuron pool, EMG and muscle force signals.Main results.Good control of both rest tremor and beta activity was observed with reduced power delivered when compared with conventional open loop stimulation, The supervisor avoided over- or under-stimulation which occurred when using a single controller tuned to one biomarker. When DBS amplitude was constrained, the secondary controller maintained the efficacy of stimulation by increasing pulse duration to compensate for reduced amplitude. Dual parameter control delivered effective control of the target biomarkers, with additional savings in the power delivered.Significance.Non-linear multivariable control can enable targeted suppression of motor symptoms for PD patients. Moreover, dual parameter control facilitates automatic regulation of the stimulation therapeutic dosage to prevent overstimulation, whilst providing additional power savings.

Effects of Contralateral Deep Brain Stimulation and Levodopa on Subthalamic Nucleus Oscillatory Activity and Phase-Amplitude Coupling.

BACKGROUND: The modulatory effects of medication and deep brain stimulation (DBS) on subthalamic nucleus (STN) neural activity in Parkinson's disease have been widely studied. However, effects on the contralateral side to the stimulated STN, in particular, changes in local field potential (LFP) oscillatory activity and phase-amplitude coupling (PAC), have not yet been reported. OBJECTIVE: The aim of this study was to examine changes in STN LFP activity across a range of frequency bands and STN PAC for different combinations of DBS and medication on/off on the side contralateral to the applied stimulation. MATERIALS AND METHODS: We examined STN LFPs that were recorded using externalized leads from eight parkinsonian patients during unilateral DBS from the side contralateral to the stimulation. LFP spectral power in alpha (5 to ∼13 Hz), low beta (13 to ∼20 Hz), high beta (20-30 Hz), and high gamma plus high-frequency oscillation (high gamma+HFO) (100-400 Hz) bands were estimated for different combinations of medication and unilateral stimulation (off/on). PAC between beta and high gamma+HFO in the STN LFPs was also investigated. The effect of the condition was examined using linear mixed models. RESULTS: PAC in the STN LFP was reduced by DBS when compared to the baseline condition (no medication and stimulation). Medication had no significant effect on PAC. Alpha power decreased with DBS, both alone and when combined with medication. Beta power decreased with DBS, medication, and DBS and medication combined. High gamma+HFO power increased during the application of contralateral DBS and was unaltered by medication. CONCLUSIONS: The results provide new insights into the effects of DBS and levodopa on STN LFP PAC and oscillatory activity on the side contralateral to stimulation. These may have important implications in understanding mechanisms underlying motor improvements with DBS, including changes on both contralateral and ipsilateral sides, while suggesting a possible role for contralateral sensing during unilateral DBS.

Prediction of low pulse oxygen saturation in COVID-19 using remote monitoring post hospital discharge.

BACKGROUND: Monitoring systems have been developed during the COVID-19 pandemic enabling clinicians to remotely monitor physiological measures including pulse oxygen saturation (SpO2), heart rate (HR), and breathlessness in patients after discharge from hospital. These data may be leveraged to understand how symptoms vary over time in COVID-19 patients. There is also potential to use remote monitoring systems to predict clinical deterioration allowing early identification of patients in need of intervention. METHODS: A remote monitoring system was used to monitor 209 patients diagnosed with COVID-19 in the period following hospital discharge. This system consisted of a patient-facing app paired with a Bluetooth-enabled pulse oximeter (measuring SpO2 and HR) linked to a secure portal where data were available for clinical review. Breathlessness score was entered manually to the app. Clinical teams were alerted automatically when SpO2 < 94 %. In this study, data recorded during the initial ten days of monitoring were retrospectively examined, and a random forest model was developed to predict SpO2 < 94 % on a given day using SpO2 and HR data from the two previous days and day of discharge. RESULTS: Over the 10-day monitoring period, mean SpO2 and HR increased significantly, while breathlessness decreased. The coefficient of variation in SpO2, HR and breathlessness also decreased over the monitoring period. The model predicted SpO2 alerts (SpO2 < 94 %) with a mean cross-validated. sensitivity of 66 ± 18.57 %, specificity of 88.31 ± 10.97 % and area under the receiver operating characteristic of 0.80 ± 0.11. Patient age and sex were not significantly associated with the occurrence of asymptomatic SpO2 alerts. CONCLUSION: Results indicate that SpO2 alerts (SpO2 < 94 %) on a given day can be predicted using SpO2 and heart rate data captured on the two preceding days via remote monitoring. The methods presented may help early identification of patients with COVID-19 at risk of clinical deterioration using remote monitoring.

Comparison of Acoustic Voice Features Derived From Mobile Devices and Studio Microphone Recordings.

OBJECTIVES/HYPOTHESIS: Improvements in mobile device technology offer new opportunities for remote monitoring of voice for home and clinical assessment. However, there is a need to establish equivalence between features derived from signals recorded from mobile devices and gold standard microphone-preamplifiers. In this study acoustic voice features from android smartphone, tablet, and microphone-preamplifier recordings were compared. METHODS: Data were recorded from 37 volunteers (20 female) with no history of speech disorder and six volunteers with Huntington's disease (HD) during sustained vowel (SV) phonation, reading passage (RP), and five syllable repetition (SR) tasks. The following features were estimated: fundamental frequency median and standard deviation (F0 and SD F0), harmonics-to-noise ratio (HNR), local jitter, relative average perturbation of jitter (RAP), five-point period perturbation quotient (PPQ5), difference of differences of amplitude and periods (DDA and DDP), shimmer, and amplitude perturbation quotients (APQ3, APQ5, and APQ11). RESULTS: Bland-Altman analysis revealed good agreement between microphone and mobile devices for fundamental frequency, jitter, RAP, PPQ5, and DDP during all tasks and a bias for HNR, shimmer and its variants (APQ3, APQ5, APQ11, and DDA). Significant differences were observed between devices for HNR, shimmer, and its variants for all tasks. High correlation was observed between devices for all features, except SD F0 for RP. Similar results were observed in the HD group for SV and SR task. Biological sex had a significant effect on F0 and HNR during all tests, and for jitter, RAP, PPQ5, DDP, and shimmer for RP and SR. No significant effect of age was observed. CONCLUSIONS: Mobile devices provided good agreement with state of the art, high-quality microphones during structured speech tasks for features derived from frequency components of the audio recordings. Caution should be taken when estimating HNR, shimmer and its variants from recordings made with mobile devices.

Computational Model of the Effect of Mitochondrial Dysfunction on Excitation-Contraction Coupling in Skeletal Muscle.

It has become well established that mitochondria not only regulate myoplasmic calcium in skeletal muscle, but also use that calcium to stimulate oxidative phosphorylation (OXPHOS). While experimental approaches have allowed for imaging of mitochondrial calcium and membrane potentials in isolated fibers, capturing the role of mitochondria and the impact of mitochondrial impairments on excitation-contraction coupling (ECC) remains difficult to explore in intact muscle. Computational models have been widely used to examine the structure and function of skeletal muscle contraction; however, models of ECC to date lack communication between the myoplasm and mitochondria for regulating calcium and ATP during sustained contractions. To address this, a mathematical model of mitochondrial calcium handling and OXPHOS was integrated into a physiological model of ECC incorporating action potential propagation, calcium handling between the sarcoplasmic reticulum (SR) and the myoplasm, and crossbridge cycling. The model was used to examine the protective role of mitochondria during repeated stimulation and the impact of mitochondrial dysfunction on ECC resulting from progressive OXPHOS inhibition. Pathological myoplasmic calcium accumulation occurred through distinct mechanisms in the model in the case of either electron transport chain, F1F0 ATP synthase, or adenine nucleotide transporter impairments. To investigate the effect of each impairment on force, a model of calcium-stimulated apoptosis was utilized to capture dysfunction-induced reductions in muscle mass, driving whole muscle force loss. The model presented in this study can be used to examine the role of mitochondria in the regulation of calcium, ATP, and force generation during voluntary contraction.

Age-related fatigability in knee extensors and knee flexors during dynamic fatiguing contractions.

This study investigated the effects of dynamic knee extension and flexion fatiguing task on torque and neuromuscular responses in young and older individuals. Eighteen young (8 males; 25.1 ± 3.2 years) and 17 older (8 males; 69.7 ± 3.7 years) volunteered. Following a maximal voluntary isometric contraction test, participants performed a fatiguing task involving 22 maximal isokinetic (concentric) knee extension and flexion contractions at 60°/s, while surface EMG was recorded simultaneously from the knee extensors (KE) and flexors (KF). Fatigue-induced relative torque reductions were similar between age groups for KE (peak torque decrease: 25.15% vs 26.81%); however, KF torque was less affected in older individuals (young vs older peak torque decrease: 27.6% vs 11.5%; p < 0.001) and this was associated with greater increase in hamstring EMG amplitude (p < 0.001) and hamstrings/quadriceps peak torque ratio (p < 0.01). Furthermore, KE was more fatigable than KF only among older individuals (peak torque decrease: 26.8% vs 11.5%; p < 0.001). These findings showed that the age-related fatigue induced by a dynamic task was greater for the KE, with greater age-related decline in KE compared to KF.

Methods for Lowering the Power Consumption of OS-Based Adaptive Deep Brain Stimulation Controllers.

The identification of a new generation of adaptive strategies for deep brain stimulation (DBS) will require the development of mixed hardware-software systems for testing and implementing such controllers clinically. Towards this aim, introducing an operating system (OS) that provides high-level features (multitasking, hardware abstraction, and dynamic operation) as the core element of adaptive deep brain stimulation (aDBS) controllers could expand the capabilities and development speed of new control strategies. However, such software frameworks also introduce substantial power consumption overhead that could render this solution unfeasible for implantable devices. To address this, in this work four techniques to reduce this overhead are proposed and evaluated: a tick-less idle operation mode, reduced and dynamic sampling, buffered read mode, and duty cycling. A dual threshold adaptive deep brain stimulation algorithm for suppressing pathological oscillatory neural activity was implemented along with the proposed energy saving techniques on an energy-efficient OS, YetiOS, running on a STM32L476RE microcontroller. The system was then tested using an emulation environment coupled to a mean field model of the parkinsonian basal ganglia to simulate local field potential (LFPs) which acted as a biomarker for the controller. The OS-based controller alone introduced a power consumption overhead of 10.03 mW for a sampling rate of 1 kHz. This was reduced to 12 µW by applying the proposed tick-less idle mode, dynamic sampling, buffered read and duty cycling techniques. The OS-based controller using the proposed methods can facilitate rapid and flexible testing and implementation of new control methods. Furthermore, the approach has the potential to become a central element in future implantable devices to enable energy-efficient implementation of a wide range of control algorithms across different neurological conditions and hardware platforms.

Cortical network effects of subthalamic deep brain stimulation in a thalamo-cortical microcircuit model.

Objective. High frequency deep brain stimulation (DBS) of the subthalamic nucleus (STN) suppresses excessive beta band (∼13-30 Hz) activity of the motor cortex in Parkinson's disease (PD). While the mechanisms of action of STN DBS are not well-understood, strong evidence supports a role for cortical network modulating effects elicited by antidromic activation of cortical axons via the hyperdirect pathway.Approach. A spiking model of the thalamo-cortical microcircuit was developed to examine modulation of cortical network activity by antidromic STN DBS, mediated by direct activation of deep pyramidal neurons (PNs) and subsequent indirect activation of other thalamo-cortical structures.Main results. Increasing synaptic coupling strength from cortical granular to superficial layers, from inhibitory neurons to deep PNs, and from thalamus reticular to relay cells, along with thalamocortical connection strength, accompanied by reduced coupling from cortical superficial to granular layers, from thalamus relay cells to reticular neurons, and corticothalamic connection strength, led to increased beta activity and neural synchrony, as observed in PD. High frequency DBS desynchronized correlated neural activity, resulting in clusters of both excited and inhibited deep cortical PNs. The emergence of additional frequency components in the local field potential (LFP), and increased power at subharmonics of the DBS frequency as observed in patients with dyskinesia during DBS, occurred under different stimulus amplitudes and frequencies. While high-frequency (>100 Hz) DBS suppressed the LFP beta power, low-frequency (<40 Hz) DBS increased beta power when more than 10% of PNs were activated, but reduced the total beta power at lower levels of neural activation.Significance. The results suggest a potential mechanism for experimentally observed alterations in cortical neural activity during DBS via the propagation of DBS stimuli throughout the cortical network, modulated by short-term synaptic plasticity, and the emergence of resonance due to interaction of DBS with existing M1 rhythms by engaging feedforward-feedback loops.

Effects of extracellular potassium on calcium handling and force generation in a model of excitation-contraction coupling in skeletal muscle.

It is well-established that extracellular potassium (Ko+) accumulation reduces muscle fiber excitability, however the effects of Ko+ on the excitation-contraction coupling (ECC) pathway are less understood. In vivo and in vitro studies following fatiguing stimulation protocols are limited in their ability to capture the effects of Ko+ on force production in combination with other simultaneously changing factors. To address this, a computational model of ECC for slow and fast twitch muscle is presented to explore the relative contributions of excitability-induced and metabolic-induced changes in force generation in response to increasing [Formula: see text] . The model incorporates mechanisms previously unexplored in modelling studies, including the effects of extracellular calcium on excitability, calcium-dependent inhibition of calcium release, ATP-dependent ionic pumping, and the contribution of ATP hydrolysis to intracellular phosphate accumulation rate. The model was able to capture the frequency-dependent biphasic Force- [Formula: see text] response observed experimentally. Force potentiation for moderately elevated [Formula: see text] was driven by increased action potential duration, myoplasmic calcium potentiation, and phosphate accumulation rate, while attenuation of force at higher [Formula: see text] was due to action potential failure resulting in reduced calcium release. These results suggest that altered calcium release and phosphate accumulation work together with elevated Ko+ to affect force during sustained contractions.

Analysis and Biophysics of Surface EMG for Physiotherapists and Kinesiologists: Toward a Common Language With Rehabilitation Engineers.

Recent decades have seen a move toward evidence-based medicine to inform the clinical decision-making process with reproducible findings from high-quality research studies. There is a need for objective, quantitative measurement tools to increase the reliability and reproducibility of studies evaluating the efficacy of healthcare interventions, particularly in the field of physical and rehabilitative medicine. Surface electromyography (sEMG) is a non-invasive measure of muscle activity that is widely used in research but is under-utilized as a clinical tool in rehabilitative medicine. Other types of electrophysiological signals (e.g., electrocardiography, electroencephalography, intramuscular EMG) are commonly recorded by healthcare practitioners, however, sEMG has yet to successfully transition to clinical practice. Surface EMG has clear clinical potential as an indicator of muscle activation, however reliable extraction of information requires knowledge of the appropriate methods for recording and analyzing sEMG and an understanding of the underlying biophysics. These concepts are generally not covered in sufficient depth in the standard curriculum for physiotherapists and kinesiologists to encourage a confident use of sEMG in clinical practice. In addition, the common perception of sEMG as a specialized topic means that the clinical potential of sEMG and the pathways to application in practice are often not apparent. The aim of this paper is to address barriers to the translation of sEMG by emphasizing its benefits as an objective clinical tool and by overcoming its perceived complexity. The many useful clinical applications of sEMG are highlighted and examples provided to illustrate how it can be implemented in practice. The paper outlines how fundamental biophysics and EMG signal processing concepts could be presented to a non-technical audience. An accompanying tutorial with sample data and code is provided which could be used as a tool for teaching or self-guided learning. The importance of observing sEMG in routine use in clinic is identified as an essential part of the effective communication of sEMG recording and signal analysis methods. Highlighting the advantages of sEMG as a clinical tool and reducing its perceived complexity could bridge the gap between theoretical knowledge and practical application and provide the impetus for the widespread use of sEMG in clinic.

Adaptive gait segmentation algorithm for walking bout detection using tri-axial accelerometers.

Gait analysis has many potential applications in understanding the activity profiles of individuals in their daily lives, particularly when studying the progression of recovery following injury, or motor deterioration in pathological conditions. One of the many challenges of conducting such analyses in the home environment is the correct and automatic identification of bouts of gait activity. To address this, a novel method for determining bouts of gait from accelerometer data recorded from the shank is presented. This method is fully automated and includes an adaptive thresholding approach which avoids the necessity for identifying subject-specific thresholds. The algorithm was tested on data recorded from 15 healthy subjects during self-selected slow, normal and fast walking speeds ranging from 0.48 ± 0.19 to 1.38 ± 0.33m/s and a single subject with PD walking at their normal walking speed (1.41 ± 0.08m/s) using accelerometers on the shanks. Intra-Class Correlation (ICC) confirmed high levels of agreement between bout onset/offset times and durations estimated using the algorithm, experimentally recorded stopwatch times and manual annotation for the healthy subjects (r=0.975, p <; 0.001; r=0.984, p<; 0.001) and moderate agreement for the PD subject (r=0.663, p<; 0.001). Mean absolute errors between accelerometer-derived and manually-annotated times were calculated, and ranged from 0.91 ± 0.05 s to 1.17 ± 2.26 s for bout onset detection, 0.80 ± 0.23 s to 2.41 ± 3.77 s for offset detection and 1.27 ± 0.13 s to 3.67 ± 4.59 s for bout durations.

Estimation of respiration rate and sleeping position using a wearable accelerometer.

Wearable inertial sensors offer the possibility to monitor sleeping position and respiration rate during sleep, enabling a comfortable and low-cost method to remotely monitor patients. Novel methods to estimate respiration rate and position during sleep using accelerometer data are presented, with algorithm performance examined for two sensor locations, and accelerometer-derived respiration rate compared across sleeping positions. Eleven participants (9 male; aged: 47.82±14.14 years; BMI 30.9±5.27 kg/m2; AHI 5.77±4.18) undergoing a scheduled clinical polysomnography (PSG) wore a tri-axial accelerometer on their chest and upper abdomen. PSG cannula flow and position data were used as benchmark data for respiration rate (breaths per minute, bpm) and position. Sleeping position was classified using logistic regression, with features derived from filtered acceleration and orientation. Accelerometer-derived respiration rate was estimated for 30 s epochs using an adaptive peak detection algorithm which combined filtered acceleration and orientation data to identify individual breaths. Sensor-derived and PSG respiration rates were then compared. Mean absolute error (MAE) in respiration rate did not vary between sensor locations (abdomen: 1.67±0.37 bpm; chest: 1.89±0.53 bpm; p=0.52), while reduced MAE was observed when participants lay on their side (1.58±0.54 bpm) compared to supine (2.43±0.95 bpm), p<0.01. MAE was less than 2 bpm for 83.6% of all 30 s windows across all subjects. The position classifier distinguished supine and left/right with a ROC AUC of 0.87, and between left and right with a ROC AUC of 0.94. The proposed methods may enable a low-cost solution for in-home, long term sleeping posture and respiration monitoring.

Quantitative clinical assessment of motor function during and following LSVT-BIG® therapy.

BACKGROUND: LSVT-BIG® is an intensively delivered, amplitude-oriented exercise therapy reported to improve mobility in individuals with Parkinson's disease (PD). However, questions remain surrounding the efficacy of LSVT-BIG® when compared with similar exercise therapies. Instrumented clinical tests using body-worn sensors can provide a means to objectively monitor patient progression with therapy by quantifying features of motor function, yet research exploring the feasibility of this approach has been limited to date. The aim of this study was to use accelerometer-instrumented clinical tests to quantify features of gait, balance and fine motor control in individuals with PD, in order to examine motor function during and following LSVT-BIG® therapy. METHODS: Twelve individuals with PD undergoing LSVT-BIG® therapy, eight non-exercising PD controls and 14 healthy controls were recruited to participate in the study. Functional mobility was examined using features derived from accelerometry recorded during five instrumented clinical tests: 10 m walk, Timed-Up-and-Go, Sit-to-Stand, quiet stance, and finger tapping. PD subjects undergoing therapy were assessed before, each week during, and up to 13 weeks following LSVT-BIG®. RESULTS: Accelerometry data captured significant improvements in 10 m walk and Timed-Up-and-Go times with LSVT-BIG® (p <  0.001), accompanied by increased stride length. Temporal features of the gait cycle were significantly lower following therapy, though no change was observed with measures of asymmetry or stride variance. The total number of Sit-to-Stand transitions significantly increased with LSVT-BIG® (p <  0.001), corresponding to a significant reduction of time spent in each phase of the Sit-to-Stand cycle. No change in measures related to postural or fine motor control was observed with LSVT-BIG®. PD subjects undergoing LSVT-BIG® showed significant improvements in 10 m walk (p <  0.001) and Timed-Up-and-Go times (p = 0.004) over a four-week period when compared to non-exercising PD controls, who showed no week-to-week improvement in any task examined. CONCLUSIONS: This study demonstrates the potential for wearable sensors to objectively quantify changes in motor function in response to therapeutic exercise interventions in PD. The observed improvements in accelerometer-derived features provide support for instrumenting gait and sit-to-stand tasks, and demonstrate a rescaling of the speed-amplitude relationship during gait in PD following LSVT-BIG®.

Self-Tuning Deep Brain Stimulation Controller for Suppression of Beta Oscillations: Analytical Derivation and Numerical Validation.

Closed-loop control strategies for deep brain stimulation (DBS) in Parkinson's disease offer the potential to provide more effective control of patient symptoms and fewer side effects than continuous stimulation, while reducing battery consumption. Most of the closed-loop methods proposed and tested to-date rely on controller parameters, such as controller gains, that remain constant over time. While the controller may operate effectively close to the operating point for which it is set, providing benefits when compared to conventional open-loop DBS, it may perform sub-optimally if the operating conditions evolve. Such changes may result from, for example, diurnal variation in symptoms, disease progression or changes in the properties of the electrode-tissue interface. In contrast, an adaptive or "self-tuning" control mechanism has the potential to accommodate slowly varying changes in system properties over a period of days, months, or years. Such an adaptive mechanism would automatically adjust the controller parameters to maintain the desired performance while limiting side effects, despite changes in the system operating point. In this paper, two neural modeling approaches are utilized to derive and test an adaptive control scheme for closed-loop DBS, whereby the gain of a feedback controller is continuously adjusted to sustain suppression of pathological beta-band oscillatory activity at a desired target level. First, the controller is derived based on a simplified firing-rate model of the reciprocally connected subthalamic nucleus (STN) and globus pallidus (GPe). Its efficacy is shown both when pathological oscillations are generated endogenously within the STN-GPe network and when they arise in response to exogenous cortical STN inputs. To account for more realistic biological features, the control scheme is then tested in a physiologically detailed model of the cortical basal ganglia network, comprised of individual conductance-based spiking neurons, and simulates the coupled DBS electric field and STN local field potential. Compared to proportional feedback methods without gain adaptation, the proposed adaptive controller was able to suppress beta-band oscillations with less power consumption, even as the properties of the controlled system evolve over time due to alterations in the target for beta suppression, beta fluctuations and variations in the electrode impedance.

Simulation of Closed-Loop Deep Brain Stimulation Control Schemes for Suppression of Pathological Beta Oscillations in Parkinson's Disease.

This study presents a computational model of closed-loop control of deep brain stimulation (DBS) for Parkinson's disease (PD) to investigate clinically viable control schemes for suppressing pathological beta-band activity. Closed-loop DBS for PD has shown promising results in preliminary clinical studies and offers the potential to achieve better control of patient symptoms and side effects with lower power consumption than conventional open-loop DBS. However, extensive testing of algorithms in patients is difficult. The model presented provides a means to explore a range of control algorithms in silico and optimize control parameters before preclinical testing. The model incorporates (i) the extracellular DBS electric field, (ii) antidromic and orthodromic activation of STN afferent fibers, (iii) the LFP detected at non-stimulating contacts on the DBS electrode and (iv) temporal variation of network beta-band activity within the thalamo-cortico-basal ganglia loop. The performance of on-off and dual-threshold controllers for suppressing beta-band activity by modulating the DBS amplitude were first verified, showing levels of beta suppression and reductions in power consumption comparable with previous clinical studies. Proportional (P) and proportional-integral (PI) closed-loop controllers for amplitude and frequency modulation were then investigated. A simple tuning rule was derived for selecting effective PI controller parameters to target long duration beta bursts while respecting clinical constraints that limit the rate of change of stimulation parameters. Of the controllers tested, PI controllers displayed superior performance for regulating network beta-band activity whilst accounting for clinical considerations. Proportional controllers resulted in undesirable rapid fluctuations of the DBS parameters which may exceed clinically tolerable rate limits. Overall, the PI controller for modulating DBS frequency performed best, reducing the mean error by 83% compared to DBS off and the mean power consumed to 25% of that utilized by open-loop DBS. The network model presented captures sufficient physiological detail to act as a surrogate for preclinical testing of closed-loop DBS algorithms using a clinically accessible biomarker, providing a first step for deriving and testing novel, clinically suitable closed-loop DBS controllers.