All Publications

  • 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


    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


    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

  • 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., Syrkin-Nikolau, J., Anidi, C., Kidzinski, L., Delp, S., Bronte-Stewart, H. 2020; 15 (4): e0231984


    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

  • 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


    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

  • Neural Closed loop deep brain stimulation for freezing of Gait. Brain stimulation Petrucci, M. N., Neuville, R. S., Afzal, M. F., Velisar, A., 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

  • 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


    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