All Publications


  • Kinematic adaptive deep brain stimulation for gait impairment and freezing of gait in Parkinson's disease. Brain stimulation Melbourne, J. A., Kehnemouyi, Y. M., O'Day, J. J., Wilkins, K. B., Gala, A. S., Petrucci, M. N., Lambert, E. F., Dorris, H., Diep, C., Herron, J. A., Bronte-Stewart, H. M. 2023

    View details for DOI 10.1016/j.brs.2023.07.003

    View details for PubMedID 37429355

  • Quantitative Digitography Measures Motor Symptoms and Disease Progression in Parkinson's Disease. Journal of Parkinson's disease Wilkins, K. B., Petrucci, M. N., Kehnemouyi, Y., Velisar, A., Han, K., Orthlieb, G., Trager, M. H., O'Day, J. J., Aditham, S., Bronte-Stewart, H. 2022

    Abstract

    BACKGROUND: Assessment of motor signs in Parkinson's disease (PD) requires an in-person examination. However, 50% of people with PD do not have access to a neurologist. Wearable sensors can provide remote measures of some motor signs but require continuous monitoring for several days. A major unmet need is reliable metrics of all cardinal motor signs, including rigidity, from a simple short active task that can be performed remotely or in the clinic.OBJECTIVE: Investigate whether thirty seconds of repetitive alternating finger tapping (RAFT) on a portable quantitative digitography (QDG) device, which measures amplitude and timing, produces reliable metrics of all cardinal motor signs in PD.METHODS: Ninety-six individuals with PD and forty-two healthy controls performed a thirty-second QDG-RAFT task and clinical motor assessment. Eighteen individuals were followed longitudinally with repeated assessments for an average of three years and up to six years.RESULTS: QDG-RAFT metrics showed differences between PD and controls and provided correlated metrics for total motor disability (MDS-UPDRS III) and for rigidity, bradykinesia, tremor, gait impairment, and freezing of gait (FOG). Additionally, QDG-RAFT tracked disease progression over several years off therapy and showed differences between akinetic-rigid and tremor-dominant phenotypes, as well as people with and without FOG.CONCLUSIONS: QDG is a reliable technology, which could be used in the clinic or remotely. This could improve access to care, allow complex remote disease management based on data received in real time, and accurate monitoring of disease progression over time in PD. QDG-RAFT also provides the comprehensive motor metrics needed for therapeutic trials.

    View details for DOI 10.3233/JPD-223264

    View details for PubMedID 35694934

  • OpenSense: An open-source toolbox for inertial-measurement-unit-based measurement of lower extremity kinematics over long durations. Journal of neuroengineering and rehabilitation Al Borno, M., O'Day, J., Ibarra, V., Dunne, J., Seth, A., Habib, A., Ong, C., Hicks, J., Uhlrich, S., Delp, S. 2022; 19 (1): 22

    Abstract

    BACKGROUND: The ability to measure joint kinematics in natural environments over long durations using inertial measurement units (IMUs) could enable at-home monitoring and personalized treatment of neurological and musculoskeletal disorders. However, drift, or the accumulation of error over time, inhibits the accurate measurement of movement over long durations. We sought to develop an open-source workflow to estimate lower extremity joint kinematics from IMU data that was accurate and capable of assessing and mitigating drift.METHODS: We computed IMU-based estimates of kinematics using sensor fusion and an inverse kinematics approach with a constrained biomechanical model. We measured kinematics for 11 subjects as they performed two 10-min trials: walking and a repeated sequence of varied lower-extremity movements. To validate the approach, we compared the joint angles computed with IMU orientations to the joint angles computed from optical motion capture using root mean square (RMS) difference and Pearson correlations, and estimated drift using a linear regression on each subject's RMS differences over time.RESULTS: IMU-based kinematic estimates agreed with optical motion capture; median RMS differences over all subjects and all minutes were between 3 and 6 degrees for all joint angles except hip rotation and correlation coefficients were moderate to strong (r=0.60-0.87). We observed minimal drift in the RMS differences over 10min; the average slopes of the linear fits to these data were near zero (- 0.14-0.17deg/min).CONCLUSIONS: Our workflow produced joint kinematics consistent with those estimated by optical motion capture, and could mitigate kinematic drift even in the trials of continuous walking without rest, which may obviate the need for explicit sensor recalibration (e.g. sitting or standing still for a few seconds or zero-velocity updates) used in current drift-mitigation approaches when studying similar activities. This could enable long-duration measurements, bringing the field one step closer to estimating kinematics in natural environments.

    View details for DOI 10.1186/s12984-022-01001-x

    View details for PubMedID 35184727

  • Assessing inertial measurement unit locations for freezing of gait detection and patient preference. Journal of neuroengineering and rehabilitation O'Day, J., Lee, M., Seagers, K., Hoffman, S., Jih-Schiff, A., Kidzinski, L., Delp, S., Bronte-Stewart, H. 2022; 19 (1): 20

    Abstract

    BACKGROUND: Freezing of gait, a common symptom of Parkinson's disease, presents as sporadic episodes in which an individual's feet suddenly feel stuck to the ground. Inertial measurement units (IMUs) promise to enable at-home monitoring and personalization of therapy, but there is a lack of consensus on the number and location of IMUs for detecting freezing of gait. The purpose of this study was to assess IMU sets in the context of both freezing of gait detection performance and patient preference.METHODS: Sixteen people with Parkinson's disease were surveyed about sensor preferences. Raw IMU data from seven people with Parkinson's disease, wearing up to eleven sensors, were used to train convolutional neural networks to detect freezing of gait. Models trained with data from different sensor sets were assessed for technical performance; a best technical set and minimal IMU set were identified. Clinical utility was assessed by comparing model- and human-rater-determined percent time freezing and number of freezing events.RESULTS: The best technical set consisted of three IMUs (lumbar and both ankles, AUROC=0.83), all of which were rated highly wearable. The minimal IMU set consisted of a single ankle IMU (AUROC=0.80). Correlations between these models and human raters were good to excellent for percent time freezing (ICC=0.93, 0.89) and number of freezing events (ICC=0.95, 0.86) for the best technical set and minimal IMU set, respectively.CONCLUSIONS: Several IMU sets consisting of three IMUs or fewer were highly rated for both technical performance and wearability, and more IMUs did not necessarily perform better in FOG detection. We openly share our data and software to further the development and adoption of a general, open-source model that uses raw signals and a standard sensor set for at-home monitoring of freezing of gait.

    View details for DOI 10.1186/s12984-022-00992-x

    View details for PubMedID 35152881

  • Ramp Rate Evaluation and Configuration for Safe and Tolerable Closed-Loop Deep Brain Stimulation. International IEEE/EMBS Conference on Neural Engineering : [proceedings]. International IEEE EMBS Conference on Neural Engineering Petrucci, M. N., Wilkins, K. B., Orthlieb, G. C., Kehnemouyi, Y. M., O'Day, J. J., Herron, J. A., Bronte-Stewart, H. M. 2021; 2021: 959-962

    Abstract

    Closed-loop deep brain stimulation is a novel form of therapy that has shown benefit in preliminary studies and may be clinically available in the near future. Initial closed-loop studies have primarily focused on responding to sensed biomarkers with adjustments to stimulation amplitude, which is often perceptible to study participants depending on the slew or "ramp" rate of the amplitude changes. These subjective responses to stimulation ramping can result in transient side effects, illustrating that ramp rate is a unique safety parameter for closed-loop neural systems. This presents a challenge to the future of closed-loop neuromodulation systems: depending on the goal of the control policy, clinicians will need to balance ramp rates to avoid side effects and keep the stimulation therapeutic by responding in time to affect neural dynamics. In this paper, we demonstrate the results of an initial investigation into methodology for finding safe and tolerable ramp rates in four people with Parkinson's disease (PD). Results suggest that optimal ramp rates were found more accurately during varying stimulation when compared to simply toggling between maximal and minimal intensity levels. Additionally, switching frequency instantaneously was tolerable at therapeutic levels of stimulation. Future work should focus on including optimization techniques to find ramp rates.

    View details for DOI 10.1109/ner49283.2021.9441336

    View details for PubMedID 35574294

    View details for PubMedCentralID PMC9097241

  • Gait Parameters Measured from Wearable Sensors Reliably Detect Freezing of Gait in a Stepping in Place Task. Sensors (Basel, Switzerland) Diep, C., O'Day, J., Kehnemouyi, Y., Burnett, G., Bronte-Stewart, H. 2021; 21 (8)

    Abstract

    Freezing of gait (FOG), a debilitating symptom of Parkinson's disease (PD), can be safely studied using the stepping in place (SIP) task. However, clinical, visual identification of FOG during SIP is subjective and time consuming, and automatic FOG detection during SIP currently requires measuring the center of pressure on dual force plates. This study examines whether FOG elicited during SIP in 10 individuals with PD could be reliably detected using kinematic data measured from wearable inertial measurement unit sensors (IMUs). A general, logistic regression model (area under the curve = 0.81) determined that three gait parameters together were overall the most robust predictors of FOG during SIP: arrhythmicity, swing time coefficient of variation, and swing angular range. Participant-specific models revealed varying sets of gait parameters that best predicted FOG for each participant, highlighting variable FOG behaviors, and demonstrated equal or better performance for 6 out of the 10 participants, suggesting the opportunity for model personalization. The results of this study demonstrated that gait parameters measured from wearable IMUs reliably detected FOG during SIP, and the general and participant-specific gait parameters allude to variable FOG behaviors that could inform more personalized approaches for treatment of FOG and gait impairment in PD.

    View details for DOI 10.3390/s21082661

    View details for PubMedID 33920070

  • Ramp Rate Evaluation and Configuration for Safe and Tolerable Closed-Loop Deep Brain Stimulation Petrucci, M. N., Wilkins, K. B., Orthlieb, G. C., Kehnemouyi, Y. M., O'Day, J. J., Herron, J. A., Bronte-Stewart, H. M., IEEE IEEE. 2021: 959-962
  • Perspective: Evolution of Control Variables and Policies for Closed-Loop Deep Brain Stimulation for Parkinson's Disease Using Bidirectional Deep-Brain-Computer Interfaces. Frontiers in human neuroscience Bronte-Stewart, H. M., Petrucci, M. N., O'Day, J. J., Afzal, M. F., Parker, J. E., Kehnemouyi, Y. M., Wilkins, K. B., Orthlieb, G. C., Hoffman, S. L. 2020; 14: 353

    Abstract

    A deep brain stimulation system capable of closed-loop neuromodulation is a type of bidirectional deep brain-computer interface (dBCI), in which neural signals are recorded, decoded, and then used as the input commands for neuromodulation at the same site in the brain. The challenge in assuring successful implementation of bidirectional dBCIs in Parkinson's disease (PD) is to discover and decode stable, robust and reliable neural inputs that can be tracked during stimulation, and to optimize neurostimulation patterns and parameters (control policies) for motor behaviors at the brain interface, which are customized to the individual. In this perspective, we will outline the work done in our lab regarding the evolution of the discovery of neural and behavioral control variables relevant to PD, the development of a novel personalized dual-threshold control policy relevant to the individual's therapeutic window and the application of these to investigations of closed-loop STN DBS driven by neural or kinematic inputs, using the first generation of bidirectional dBCIs.

    View details for DOI 10.3389/fnhum.2020.00353

    View details for PubMedID 33061899

    View details for PubMedCentralID PMC7489234

  • A Closed-loop Deep Brain Stimulation Approach for Mitigating Burst Durations in People with Parkinson's Disease. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference Petrucci, M. N., Anderson, R. W., O'Day, J. J., Kehnemouyi, Y. M., Herron, J. A., Bronte-Stewart, H. M. 2020; 2020: 3617–20

    Abstract

    Increased beta band synchrony has been demonstrated to be a biomarker of Parkinson's disease (PD). This abnormal synchrony can often be prolonged in long bursts of beta activity, which may interfere with normal sensorimotor processing. Previous closed loop deep brain stimulation (DBS) algorithms used averaged beta power to drive neurostimulation, which were indiscriminate to physiological (short) versus pathological (long) beta burst durations. We present a closed-loop DBS algorithm using beta burst duration as the control signal. Benchtop validation results demonstrate the feasibility of the algorithm in real-time by responding to pre-recorded STN data from a PD participant. These results provide the basis for future improved closed-loop algorithms focused on burst durations for in mitigating symptoms of PD.

    View details for DOI 10.1109/EMBC44109.2020.9176196

    View details for PubMedID 33018785

  • Demonstration of Kinematic-Based Closed-loop Deep Brain Stimulation for Mitigating Freezing of Gait in People with Parkinson's Disease. Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference O'Day, J. J., Kehnemouyi, Y. M., Petrucci, M. N., Anderson, R. W., Herron, J. A., Bronte-Stewart, H. M. 2020; 2020: 3612–16

    Abstract

    Impaired gait in Parkinson's disease is marked by slow, arrhythmic stepping, and often includes freezing of gait episodes where alternating stepping halts completely. Wearable inertial sensors offer a way to detect these gait changes and novel deep brain stimulation (DBS) systems can respond with clinical therapy in a real-time, closed-loop fashion. In this paper, we present two novel closed-loop DBS algorithms, one using gait arrhythmicity and one using a logistic-regression model of freezing of gait detection as control signals. Benchtop validation results demonstrate the feasibility of running these algorithms in conjunction with a closed-loop DBS system by responding to real-time human subject kinematic data and pre-recorded data from leg-worn inertial sensors from a participant with Parkinson's disease. We also present a novel control policy algorithm that changes neurostimulator frequency in response to the kinematic inputs. These results provide a foundation for further development, iteration, and testing in a clinical trial for the first closed-loop DBS algorithms using kinematic signals to therapeutically improve and understand the pathophysiological mechanisms of gait impairment in Parkinson's disease.

    View details for DOI 10.1109/EMBC44109.2020.9176638

    View details for PubMedID 33018784

  • Neural Closed loop deep brain stimulation for freezing of Gait. Brain stimulation Petrucci, M. N., Neuville, R. S., Afzal, M. F., Velisar, A. n., Anidi, C. M., Anderson, R. W., Parker, J. E., O'Day, J. J., Wilkins, K. B., Bronte-Stewart, H. M. 2020

    View details for DOI 10.1016/j.brs.2020.06.018

    View details for PubMedID 32634599

  • The turning and barrier course reveals gait parameters for detecting freezing of gait and measuring the efficacy of deep brain stimulation. PloS one O'Day, J. n., Syrkin-Nikolau, J. n., Anidi, C. n., Kidzinski, L. n., Delp, S. n., Bronte-Stewart, H. n. 2020; 15 (4): e0231984

    Abstract

    Freezing of gait (FOG) is a devastating motor symptom of Parkinson's disease that leads to falls, reduced mobility, and decreased quality of life. Reliably eliciting FOG has been difficult in the clinical setting, which has limited discovery of pathophysiology and/or documentation of the efficacy of treatments, such as different frequencies of subthalamic deep brain stimulation (STN DBS). In this study we validated an instrumented gait task, the turning and barrier course (TBC), with the international standard FOG questionnaire question 3 (FOG-Q3, r = 0.74, p < 0.001). The TBC is easily assembled and mimics real-life environments that elicit FOG. People with Parkinson's disease who experience FOG (freezers) spent more time freezing during the TBC compared to during forward walking (p = 0.007). Freezers also exhibited greater arrhythmicity during non-freezing gait when performing the TBC compared to forward walking (p = 0.006); this difference in gait arrhythmicity between tasks was not detected in non-freezers or controls. Freezers' non-freezing gait was more arrhythmic than that of non-freezers or controls during all walking tasks (p < 0.05). A logistic regression model determined that a combination of gait arrhythmicity, stride time, shank angular range, and asymmetry had the greatest probability of classifying a step as FOG (area under receiver operating characteristic curve = 0.754). Freezers' percent time freezing and non-freezing gait arrhythmicity decreased, and their shank angular velocity increased in the TBC during both 60 Hz and 140 Hz STN DBS (p < 0.05) to non-freezer values. The TBC is a standardized tool for eliciting FOG and demonstrating the efficacy of 60 Hz and 140 Hz STN DBS for gait impairment and FOG. The TBC revealed gait parameters that differentiated freezers from non-freezers and best predicted FOG; these may serve as relevant control variables for closed loop neurostimulation for FOG in Parkinson's disease.

    View details for DOI 10.1371/journal.pone.0231984

    View details for PubMedID 32348346

  • Demonstration of Kinematic-Based Closed-loop Deep Brain Stimulation for Mitigating Freezing of Gait in People with Parkinson's Disease O'Day, J. J., Kehnemouyi, Y. M., Petrucci, M. N., Anderson, R. W., Herron, J. A., Bronte-Stewart, H. M., IEEE IEEE. 2020: 3612–16
  • A Closed-loop Deep Brain Stimulation Approach for Mitigating Burst Durations in People with Parkinson's Disease Petrucci, M. N., Anderson, R. W., O'Day, J. J., Kehnemouyi, Y. M., Herron, J. A., Bronte-Stewart, H. M., IEEE IEEE. 2020: 3617–20
  • Neuromodulation targets pathological not physiological beta bursts during gait in Parkinson's disease NEUROBIOLOGY OF DISEASE Anidi, C., O'Day, J. J., Anderson, R. W., Afzal, M., Syrkin-Nikolau, J., Velisar, A., Bronte-Stewart, H. M. 2018; 120: 107–17
  • Neuromodulation targets pathological not physiological beta bursts during gait in Parkinson's disease. Neurobiology of disease Anidi, C. M., O'Day, J. J., Anderson, R. W., Afzal, M. F., Syrkin-Nikolau, J., Velisar, A., Bronte-Stewart, H. M. 2018

    Abstract

    Freezing of gait (FOG) is a devastating axial motor symptom in Parkinson's disease (PD) leading to falls, institutionalization, and even death. The response of FOG to dopaminergic medication and deep brain stimulation (DBS) is complex, variable, and yet to be optimized. Fundamental gaps in the knowledge of the underlying neurobiomechanical mechanisms of FOG render this symptom one of the unsolved challenges in the treatment of PD. Subcortical neural mechanisms of gait impairment and FOG in PD are largely unknown due to the challenge of accessing deep brain circuitry and measuring neural signals in real time in freely-moving subjects. Additionally, there is a lack of gait tasks that reliably elicit FOG. Since FOG is episodic, we hypothesized that dynamic features of subthalamic (STN) beta oscillations, or beta bursts, may contribute to the Freezer phenotype in PD during gait tasks that elicit FOG. We also investigated whether STN DBS at 60 Hz or 140 Hz affected beta burst dynamics and gait impairment differently in Freezers and Non-Freezers. Synchronized STN local field potentials, from an implanted, sensing neurostimulator (Activa PC + S, Medtronic, Inc.), and gait kinematics were recorded in 12 PD subjects, off-medication during forward walking and stepping-in-place tasks under the following randomly presented conditions: NO, 60 Hz, and 140 Hz DBS. Prolonged movement band beta burst durations differentiated Freezers from Non-Freezers, were a pathological neural feature of FOG and were shortened during DBS which improved gait. Normal gait parameters, accompanied by shorter bursts in Non-Freezers, were unchanged during DBS. The difference between the mean burst duration between hemispheres (STNs) of all individuals strongly correlated with the difference in stride time between their legs but there was no correlation between mean burst duration of each STN and stride time of the contralateral leg, suggesting an interaction between hemispheres influences gait. These results suggest that prolonged STN beta burst durations measured during gait is an important biomarker for FOG and that STN DBS modulated long not short burst durations, thereby acting to restore physiological sensorimotor information processing, while improving gait.

    View details for PubMedID 30196050

  • Sixty hertz subthalamic deep brain stimulation improves freezing of gait with less attenuation of beta band power than 140Hz stimulation Anidi, C., O'Day, J., Afzal, M., Syrkin-Nikolau, J., Velisar, A., Bronte-Stewart, H. LIPPINCOTT WILLIAMS & WILKINS. 2018
  • Coordinated Reset Vibrotactile Stimulation Shows Prolonged Improvement in Parkinson's Disease MOVEMENT DISORDERS Syrkin-Nikolau, J., Neuville, R., O'Day, J., Anidi, C., Koop, M., Martin, T., Tass, P. A., Bronte-Stewart, H. 2018; 33 (1): 179–80

    View details for PubMedID 29150859

    View details for PubMedCentralID PMC5836884