Adaptive deep brain stimulation (aDBS) is a promising new technology with increasing use in experimental trials to treat a diverse array of indications such as movement disorders (Parkinson’s ...disease, essential tremor), psychiatric disorders (depression, OCD), chronic pain and epilepsy. In many aDBS trials, a neural biomarker of interest is compared with a predefined threshold and stimulation amplitude is adjusted accordingly. Across indications and implant locations, potential biomarkers are greatly influenced by sleep. Successful chronic embedded adaptive detectors must incorporate a strategy to account for sleep, to avoid unwanted or unexpected algorithm behavior. Here, we show a dual algorithm design with two independent detectors, one used to track sleep state (wake/sleep) and the other used to track parkinsonian motor state (medication-induced fluctuations). Across six hemispheres (four patients) and 47 days, our detector successfully transitioned to sleep mode while patients were sleeping, and resumed motor state tracking when patients were awake. Designing “sleep aware” aDBS algorithms may prove crucial for deployment of clinically effective fully embedded aDBS algorithms.
Gait is a core motor function and is impaired in numerous neurological diseases, including Parkinson's disease (PD). Treatment changes in PD are frequently driven by gait assessments in the clinic, ...commonly rated as part of the Movement Disorder Society (MDS) Unified PD Rating Scale (UPDRS) assessment (item 3.10). We proposed and evaluated a novel approach for estimating severity of gait impairment in Parkinson's disease using a computer vision-based methodology. The system we developed can be used to obtain an estimate for a rating to catch potential errors, or to gain an initial rating in the absence of a trained clinician-for example, during remote home assessments. Videos (n=729) were collected as part of routine MDS-UPDRS gait assessments of Parkinson's patients, and a deep learning library was used to extract body key-point coordinates for each frame. Data were recorded at five clinical sites using commercially available mobile phones or tablets, and had an associated severity rating from a trained clinician. Six features were calculated from time-series signals of the extracted key-points. These features characterized key aspects of the movement including speed (step frequency, estimated using a novel Gamma-Poisson Bayesian model), arm swing, postural control and smoothness (or roughness) of movement. An ordinal random forest classification model (with one class for each of the possible ratings) was trained and evaluated using 10-fold cross validation. Step frequency point estimates from the Bayesian model were highly correlated with manually labelled step frequencies of 606 video clips showing patients walking towards or away from the camera (Pearson's r=0.80, p<0.001). Our classifier achieved a balanced accuracy of 50% (chance = 25%). Estimated UPDRS ratings were within one of the clinicians' ratings in 95% of cases. There was a significant correlation between clinician labels and model estimates (Spearman's ρ=0.52, p<0.001). We show how the interpretability of the feature values could be used by clinicians to support their decision-making and provide insight into the model's objective UPDRS rating estimation. The severity of gait impairment in Parkinson's disease can be estimated using a single patient video, recorded using a consumer mobile device and within standard clinical settings; i.e., videos were recorded in various hospital hallways and offices rather than gait laboratories. This approach can support clinicians during routine assessments by providing an objective rating (or second opinion), and has the potential to be used for remote home assessments, which would allow for more frequent monitoring.
Advances in therapeutic neuromodulation devices have enabled concurrent stimulation and electrophysiology in the central nervous system. However, stimulation artifacts often obscure the sensed ...underlying neural activity. Here, we develop a method, termed Period-based Artifact Reconstruction and Removal Method (PARRM), to remove stimulation artifacts from neural recordings by leveraging the exact period of stimulation to construct and subtract a high-fidelity template of the artifact. Benchtop saline experiments, computational simulations, five unique in vivo paradigms across animal and human studies, and an obscured movement biomarker are used for validation. Performance is found to exceed that of state-of-the-art filters in recovering complex signals without introducing contamination. PARRM has several advantages: (1) it is superior in signal recovery; (2) it is easily adaptable to several neurostimulation paradigms; and (3) it has low complexity for future on-device implementation. Real-time artifact removal via PARRM will enable unbiased exploration and detection of neural biomarkers to enhance efficacy of closed-loop therapies.
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•PARRM removes artifacts that obscure neural activity in neuromodulation recordings•PARRM is effective with both low- and high-sampling-rate recordings•PARRM is adaptable to several neurostimulation paradigms•The low complexity of PARRM makes it suitable for future on-device implementation
Electrophysiological recordings concurrent with electrical stimulation of the brain and spinal cord are often corrupted by stimulation artifact. The removal of stimulation artifact is a necessary step toward identifying neural biomarkers that can be consistently used to titrate neuromodulation therapies or discover the underlying disease neuropathology. Thus, we developed a Period-based Artifact Reconstruction and Removal Method (PARRM) to provide a solution to removing such artifacts from low- and high-sample-rate recordings. PARRM is adaptive to changes in artifact shape, is robust to aliasing, and has low computational overhead readily implementable for use in real time. Our method aims to enable the investigation, and eventual development, of closed-loop neuromodulation therapies.
Dastin-van Rijn and Provenza et al. developed the Period-based Artifact Reconstruction and Removal Method (PARRM) to remove stimulation artifacts from electrophysiological recordings. PARRM is superior to comparable methods, adaptable to several neurostimulation paradigms, and of low complexity for future on-device implementation. These features make PARRM effective for identifying neural biomarkers for closed-loop therapies.
Neural recordings using invasive devices in humans can elucidate the circuits underlying brain disorders, but have so far been limited to short recordings from externalized brain leads in a hospital ...setting or from implanted sensing devices that provide only intermittent, brief streaming of time series data. Here, we report the use of an implantable two-way neural interface for wireless, multichannel streaming of field potentials in five individuals with Parkinson's disease (PD) for up to 15 months after implantation. Bilateral four-channel motor cortex and basal ganglia field potentials streamed at home for over 2,600 h were paired with behavioral data from wearable monitors for the neural decoding of states of inadequate or excessive movement. We validated individual-specific neurophysiological biomarkers during normal daily activities and used those patterns for adaptive deep brain stimulation (DBS). This technological approach may be widely applicable to brain disorders treatable by invasive neuromodulation.
Dystonia is a disabling movement disorder characterized by excessive muscle contraction for which the underlying pathophysiology is incompletely understood and treatment interventions limited in ...efficacy. Here we utilize a novel, sensing-enabled, deep brain stimulator device, implanted in a patient with cervical dystonia, to record local field potentials from chronically implanted electrodes in the sensorimotor cortex and subthalamic nuclei bilaterally. This rechargeable device was able to record large volumes of neural data at home, in the naturalistic environment, during unconstrained activity. We confirmed the presence of theta (3–7 Hz) oscillatory activity, which was coherent throughout the cortico-subthalamic circuit and specifically suppressed by high-frequency stimulation. Stimulation also reduced the duration, rate and height of theta bursts. These findings motivated a proof-of-principle trial of a new form of adaptive deep brain stimulation - triggered by theta-burst activity recorded from the motor cortex. This facilitated increased peak stimulation amplitudes without induction of dyskinesias and demonstrated improved blinded clinical ratings compared to continuous DBS, despite reduced total electrical energy delivered. These results further strengthen the pathophysiological role of low frequency (theta) oscillations in dystonia and demonstrate the potential for novel adaptive stimulation strategies linked to cortico-basal theta bursts.
. To provide a design analysis and guidance framework for the implementation of concurrent stimulation and sensing during adaptive deep brain stimulation (aDBS) with particular emphasis on artifact ...mitigations.
. We defined a general architecture of feedback-enabled devices, identified key components in the signal chain which might result in unwanted artifacts and proposed methods that might ultimately enable improved aDBS therapies. We gathered data from research subjects chronically-implanted with an investigational aDBS system, Summit RC + S, to characterize and explore artifact mitigations arising from concurrent stimulation and sensing. We then used a prototype investigational implantable device, DyNeuMo, and a bench-setup that accounts for tissue-electrode properties, to confirm our observations and verify mitigations. The strategies to reduce transient stimulation artifacts and improve performance during aDBS were confirmed in a chronic implant using updated configuration settings.
We derived and validated a 'checklist' of configuration settings to improve system performance and areas for future device improvement. Key considerations for the configuration include (a) active instead of passive recharge, (b) sense-channel blanking in the amplifier, (c) high-pass filter settings, (d) tissue-electrode impedance mismatch management, (e) time-frequency trade-offs in the classifier, (f) algorithm blanking and transition rate limits. Without proper channel configuration, the aDBS algorithm was susceptible to limit-cycles of oscillating stimulation independent of physiological state. By applying the checklist, we could optimize each block's performance characteristics within the overall system. With system-level optimization, a 'fast' aDBS prototype algorithm was demonstrated to be feasible without reentrant loops, and with noise performance suitable for subcortical brain circuits.
. We present a framework to study sources and propose mitigations of artifacts in devices that provide chronic aDBS. This work highlights the trade-offs in performance as novel sensing devices translate to the clinic. Finding the appropriate balance of constraints is imperative for successful translation of aDBS therapies.
Institutional Review Board and Investigational Device Exemption numbers: NCT02649166/IRB201501021 (University of Florida), NCT04043403/IRB52548 (Stanford University), NCT03582891/IRB1824454 (University of California San Francisco). IDE #180 097.
We estimate that 208,000 deep brain stimulation (DBS) devices have been implanted to address neurological and neuropsychiatric disorders worldwide. DBS Think Tank presenters pooled data and ...determined that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. The DBS Think Tank was founded in 2012 providing a space where clinicians, engineers, researchers from industry and academia discuss current and emerging DBS technologies and logistical and ethical issues facing the field. The emphasis is on cutting edge research and collaboration aimed to advance the DBS field. The Eighth Annual DBS Think Tank was held virtually on September 1 and 2, 2020 (Zoom Video Communications) due to restrictions related to the COVID-19 pandemic. The meeting focused on advances in: (1) optogenetics as a tool for comprehending neurobiology of diseases and on optogenetically-inspired DBS, (2) cutting edge of emerging DBS technologies, (3) ethical issues affecting DBS research and access to care, (4) neuromodulatory approaches for depression, (5) advancing novel hardware, software and imaging methodologies, (6) use of neurophysiological signals in adaptive neurostimulation, and (7) use of more advanced technologies to improve DBS clinical outcomes. There were 178 attendees who participated in a DBS Think Tank survey, which revealed the expansion of DBS into several indications such as obesity, post-traumatic stress disorder, addiction and Alzheimer's disease. This proceedings summarizes the advances discussed at the Eighth Annual DBS Think Tank.
The ability to arise from a sitting to a standing position is often impaired in Parkinson's disease (PD). This impairment is associated with an increased risk of falling, and higher risk of dementia. ...We propose a novel approach to estimate Movement Disorder Society Unified PD Rating Scale (MDS-UPDRS) ratings for “item 3.9” (arising from chair) using a computer vision-based method, whereby we use clinically informed reasoning to engineer a small number of informative features from high dimensional markerless pose estimation data.
We analysed 447 videos collected via the KELVIN-PD™ platform, recorded in clinical settings at multiple sites, using commercially available mobile smart devices. Each video showed an examination for item 3.9 of the MDS-UPDRS and had an associated severity rating from a trained clinician on the 5-point scale (0, 1, 2, 3 or 4).
The deep learning library OpenPose was used to extract pose estimation key points from each frame of the videos, resulting in time-series signals for each key point. From these signals, features were extracted which capture relevant characteristics of the movement; velocity variation, smoothness, whether the patient used their hands to push themselves up, how stooped the patient was while sitting and how upright the patient was when fully standing. These features were used to train an ordinal classification system (with one class for each of the possible ratings on the UPDRS), based on a series of random forest classifiers.
The UPDRS ratings estimated by this system, using leave-one-out cross validation, corresponded exactly to the ratings made by clinicians in 79% of videos, and were within one of those made by clinicians in 100% of cases. The system was able to distinguish normal from Parkinsonian movement with a sensitivity of 62.8% and a specificity of 90.3%. Analysis of misclassified examples highlighted the potential of the system to detect potentially mislabelled data.
We show that our computer-vision based method can accurately quantify PD patients’ ability to perform the arising from chair action. As far as we are aware this is the first study estimating scores for item 3.9 of the MDS-UPDRS from singular monocular video. This approach can help prevent human error by identifying unusual clinician ratings, and provides promise for such a system being used routinely for clinical assessments, either locally or remotely, with potential for use as stratification and outcome measures in clinical trials.
•The ability to arise from a chair, often impaired in Parkinson’s disease, is commonly assessed subjectively by clinicians.•A novel approach, using 2D pose estimation and machine learning, can robustly estimate disease severity using only videos.•The system is a good candidate for routine in office use or for remote home assessment of patients.
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