Matt is the Scientific Program Manager for the Mobilize and Restore Centers at Stanford University. He is interested in developing digital health tools that optimize human mobility and performance. His previous research has focused on cross-sectional, longitudinal, translational, and feasibility studies in people with Parkinson’s disease, people with multiple sclerosis, and firefighters. These studies included evaluating objective biomarkers of disease or performance, optimizing and evaluating novel treatments and interventions, developing real-time closed-loop algorithms, and clinical trials. He helps run the various scientific outreach and training programs of the Mobilize and Restore Centers.
Research Engineer, Bioengineering
PhD, University of Illinois at Urbana-Champaign, Neuroscience (2016)
MS, University of Illinois at Urbana-Champaign, Mechanical Engineering (2016)
BS/BA, University of San Diego, Mechanical Engineering (2007)
- Kinematic adaptive deep brain stimulation for gait impairment and freezing of gait in Parkinson's disease. Brain stimulation 2023
The Sequence Effect Worsens Over Time in Parkinson's Disease and Responds to Open and Closed-Loop Subthalamic Nucleus Deep Brain Stimulation.
Journal of Parkinson's disease
The sequence effect is the progressive deterioration in speech, limb movement, and gait that leads to an inability to communicate, manipulate objects, or walk without freezing of gait. Many studies have demonstrated a lack of improvement of the sequence effect from dopaminergic medication, however few studies have studied the metric over time or investigated the effect of open-loop deep brain stimulation in people with Parkinson's disease (PD).To investigate whether the sequence effect worsens over time and/or is improved on clinical (open-loop) deep brain stimulation (DBS).Twenty-one people with PD with bilateral subthalamic nucleus (STN) DBS performed thirty seconds of instrumented repetitive wrist flexion extension and the MDS-UPDRS III off therapy, prior to activation of DBS and every six months for up to three years. A sub-cohort of ten people performed the task during randomized presentations of different intensities of STN DBS.The sequence effect was highly correlated with the overall MDS-UPDRS III score and the bradykinesia sub-score and worsened over three years. Increasing intensities of STN open-loop DBS improved the sequence effect and one subject demonstrated improvement on both open-loop and closed-loop DBS.Sequence effect in limb bradykinesia worsened over time off therapy due to disease progression but improved on open-loop DBS. These results demonstrate that DBS is a useful treatment of the debilitating effects of the sequence effect in limb bradykinesia and upon further investigation closed-loop DBS may offer added improvement.
View details for DOI 10.3233/JPD-223368
View details for PubMedID 37125563
Bradykinesia and its progression are related to inter-hemispheric beta coherence.
Annals of neurology
OBJECTIVE: Bradykinesia is the major cardinal motor sign of Parkinson's disease (PD), but its neural underpinnings are unclear. The goal of this study was to examine whether changes in bradykinesia following long-term subthalamic nucleus (STN) deep brain stimulation (DBS) are linked to local STN beta (13-30 Hz) dynamics or a wider bilateral network dysfunction.METHODS: Twenty-one individuals with Parkinson's disease implanted with sensing neurostimulators (Activa PC+S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to six months for an average of three years. At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (>60 minutes) before completing a repetitive wrist-flexion extension task, a validated quantitative assessment of bradykinesia, while local field potentials were recorded. Local STN beta dynamics were investigated via beta power and burst duration, while interhemispheric beta synchrony was assessed with STN-STN beta coherence.RESULTS: Higher interhemispheric STN beta coherence, but not contralateral beta power or burst duration, was significantly associated with worse bradykinesia. Bradykinesia worsened off therapy over time. Interhemispheric STN-STN beta coherence also increased over time, whereas beta power and burst duration remained stable. The observed change in bradykinesia was related to the change in interhemispheric beta coherence, with greater increases in synchrony associated with further worsening of bradykinesia.INTERPRETATION: Together, these findings implicate interhemispheric beta synchrony as a neural correlate of the progression of bradykinesia following chronic STN DBS. This could imply the existence of a pathological bilateral network contributing to bradykinesia in PD. This article is protected by copyright. All rights reserved.
View details for DOI 10.1002/ana.26605
View details for PubMedID 36641645
Quantitative Digitography Measures Motor Symptoms and Disease Progression in Parkinson's Disease.
Journal of Parkinson's disease
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
Proceedings of the Ninth Annual Deep Brain Stimulation Think Tank: Advances in Cutting Edge Technologies, Artificial Intelligence, Neuromodulation, Neuroethics, Pain, Interventional Psychiatry, Epilepsy, and Traumatic Brain Injury.
Frontiers in human neuroscience
2022; 16: 813387
DBS Think Tank IX was held on August 25-27, 2021 in Orlando FL with US based participants largely in person and overseas participants joining by video conferencing technology. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging deep brain stimulation (DBS) technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank IX speakers was that DBS expanded in its scope and has been applied to multiple brain disorders in an effort to modulate neural circuitry. After collectively sharing our experiences, it was estimated that globally more than 230,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. As such, this year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia and Australia; cutting-edge technologies, neuroethics, interventional psychiatry, adaptive DBS, neuromodulation for pain, network neuromodulation for epilepsy and neuromodulation for traumatic brain injury.
View details for DOI 10.3389/fnhum.2022.813387
View details for PubMedID 35308605
Concurrent stimulation and sensing in bi-directional brain interfaces: a multi-site translational experience.
Journal of neural engineering
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 1) active instead of passive recharge, 2) sense-channel blanking in the amplifier, 3) high-pass filter settings, 4) tissue-electrode impedance mismatch management, 5) time-frequency trade-offs in the classifier, 6) 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.
View details for DOI 10.1088/1741-2552/ac59a3
View details for PubMedID 35234664
Can People with Parkinson's Disease Self-Trigger Gait Initiation? A Comparison of Cueing Strategies
JOURNAL OF PARKINSONS DISEASE
2022; 12 (2): 607-619
An external cue can markedly improve gait initiation in people with Parkinson's disease (PD) and is often used to overcome freezing of gait (FOG). It is unknown if the effects of external cueing are comparable if the imperative stimulus is triggered by the person receiving the cue (self-triggered) or an external source.Two experiments were conducted to compare the effects of self- versus externally triggered cueing on anticipatory postural adjustments (APAs) during gait initiation in people with PD.In experiment 1, 10 individuals with PD and FOG initiated gait without a cue or in response to a stimulus triggered by the experimenter or by the participant. Experiment 2 compared self- versus externally triggered cueing across three groups: healthy young adults (n = 16), healthy older adults (n = 11), and a group with PD (n = 10).Experiment 1: Externally triggered cues significantly increased APA magnitudes compared to uncued stepping, but not when the same cue was self-triggered. Experiment 2: APAs were not significantly improved with a self-triggered cue compared to un-cued stepping in both the PD and healthy older adult groups, but the young adults showed a significant facilitation of APA magnitude.The effectiveness of an external cue on gait initiation in people with PD and older adults is critically dependent upon whether the source of the trigger is endogenous (self-produced) or exogenous (externally-generated). These results may explain why cueing interventions that rely upon self-triggering of the stimulus are often ineffective in people with PD.
View details for DOI 10.3233/JPD-212732
View details for Web of Science ID 000759160900012
View details for PubMedID 34806616
Lack of progression of beta dynamics after long-term subthalamic neurostimulation.
Annals of clinical and translational neurology
OBJECTIVE: To investigate the progression of neural and motor features of Parkinson's disease in a longitudinal study, after washout of medication and bilateral subthalamic nucleus deep brain stimulation (STN DBS).METHODS: Participants with clinically established Parkinson's disease underwent bilateral implantation of DBS leads (18 participants, 13 male) within the STN using standard functional frameless stereotactic technique and multi-pass microelectrode recording. Both DBS leads were connected to an implanted investigative sensing neurostimulator (Activa PC+S, Medtronic, PLC). Resting state STN local field potentials (LFPs) were recorded and motor disability, (the Movement Disorder Society-Unified Parkinson's Disease Rating Scale - motor subscale, MDS-UPDRS III) was assessed off therapy at initial programming, and after 6months, 1year, and yearly out to 5years of treatment. The primary endpoint was measured at 3years. At each visit, medication had been held for over 12/24h and DBS was turned off for at least 60min, by which time LFP spectra reached a steady state.RESULTS: After 3years of chronic DBS, there were no increases in STN beta band dynamics (p=0.98) but there were increases in alpha band dynamics (p=0.0027, 25 STNs). Similar results were observed in a smaller cohort out to 5years. There was no increase in the MDS-UPDRS III score.INTERPRETATION: These findings provide evidence that the beta oscillopathy does not substantially progress following combined STN DBS plus medication in moderate to advanced Parkinson's disease.
View details for DOI 10.1002/acn3.51463
View details for PubMedID 34636182
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
2021; 2021: 959-962
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
Differential Effects of Pathological Beta Burst Dynamics Between Parkinson's Disease Phenotypes Across Different Movements.
Frontiers in neuroscience
2021; 15: 733203
Background: Resting state beta band (13-30 Hz) oscillations represent pathological neural activity in Parkinson's disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb, and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states. Methods: Subthalamic (STN) and local field potentials (LFPs) were recorded from a sensing neurostimulator (Activa PC + S, Medtronic PLC.) in fourteen PD participants (six tremor-dominant and eight akinetic-rigid) off medication/off STN DBS during 30 s of repetitive alternating finger tapping, wrist-flexion extension, stepping in place, and free walking. Beta power peaks and beta burst dynamics were identified by custom algorithms and were compared among movement tasks and between tremor-dominant and akinetic-rigid groups. Results: Beta power peaks were evident during fine, limb, and axial movements in 98% of movement trials; the peak frequencies were similar during each type of movement. Burst power and duration were significantly larger in the high beta band, but not in the low beta band, in the akinetic-rigid group compared to the tremor-dominant group. Conclusion: The conservation of beta peak frequency during different activity states supports the feasibility of patient-specific closed loop DBS algorithms driven by the dynamics of the same beta band during different activities. Akinetic-rigid participants had greater power and longer burst durations in the high beta band than tremor-dominant participants during movement, which may relate to the difference in underlying pathophysiology between phenotypes.
View details for DOI 10.3389/fnins.2021.733203
View details for PubMedID 34858125
- Ramp Rate Evaluation and Configuration for Safe and Tolerable Closed-Loop Deep Brain Stimulation 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 2020; 14
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
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
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
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
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
REM sleep without atonia is associated with increased rigidity in patients with mild to moderate Parkinson's disease.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology
OBJECTIVE: Increased muscle activity during rapid eye movement (REM) sleep (i.e. REM sleep without atonia) is common in people with Parkinson's disease (PD). This study tested the hypotheses that people with PD and REM sleep without atonia (RSWA) would present with more severe and symmetric rigidity compared to individuals with PD without RSWA and age-matched controls.METHODS: Sixty-one individuals participated in this study (41 PD, 20 controls). An overnight sleep study was used to classify participants with PD as having either elevated (PD-RSWA+) or normal muscle activity (PD-RSWA-) during REM sleep. Quantitative measures of rigidity were obtained using a robotic manipulandum that passively pronated and supinated the forearm.RESULTS: Quantitative measures of forearm rigidity were significantly higher in the PD-RSWA+ group compared to the control group. Rigidity was significantly more asymmetric between limbs in the PD-RSWA- group compared with controls, while there was no significant difference in symmetry between the control and PD-RSWA+ groups.CONCLUSION: In people with mild to moderate PD, RSWA is associated with an increased and more symmetric presentation of upper limb rigidity.SIGNIFICANCE: Dysfunction of brainstem systems that control muscle tone during REM sleep may contribute to increased rigidity during wakefulness in people with PD.
View details for DOI 10.1016/j.clinph.2020.04.017
View details for PubMedID 32451296
- Neural Closed loop deep brain stimulation for freezing of Gait. Brain stimulation 2020
Demonstration of Kinematic-Based Closed-loop Deep Brain Stimulation for Mitigating Freezing of Gait in People with Parkinson's Disease
IEEE. 2020: 3612–16
View details for Web of Science ID 000621592203233
A Closed-loop Deep Brain Stimulation Approach for Mitigating Burst Durations in People with Parkinson's Disease
IEEE. 2020: 3617–20
View details for Web of Science ID 000621592203234
Modulation of anticipatory postural adjustments using a powered ankle orthosis in people with Parkinson's disease and freezing of gait.
Gait & posture
2019; 72: 188–94
BACKGROUND: Freezing of gait (FOG) during gait initiation in people with Parkinson's disease (PD) may be related to a diminished ability to generate anticipatory postural adjustments (APAs). Externally applied perturbations that mimic the desired motion of the body during an APA have been demonstrated to shorten and amplify APAs; however, no portable device has been tested. In this study, a portable powered ankle-foot orthosis (PPAFO) testbed was utilized to investigate the effect of mechanical assistance, provided at the ankle joint, on the APAs during gait initiation.RESEARCH QUESTION: Does mechanical assistance provided at the ankle joint improve APAs during gait initiation in people with PD and FOG?METHODS: Thirteen participants with PD and FOG initiated gait across five test conditions: two self-initiated (uncued) conditions in walking shoes [Baseline-Shoes], and the PPAFO in unpowered passive mode [Baseline-PPAFOPassive]; three "go" cued conditions that included an acoustic tone with the PPAFO in unpowered passive mode [Acoustic+PPAFOPassive], the mechanical assistance from the PPAFO [PPAFOActive], and the acoustic tone paired with mechanical assistance [Acoustic+PPAFOActive]. A warning-cue preceded the imperative "go" cue for all the cued trials. Peak amplitudes and timings of the vertical ground reaction forces (GRFs) and center of pressure (COP) shifts from onset to toe-off were compared across conditions.RESULTS: Mechanical assistance significantly increased the peak amplitudes of the GRFs and COP shifts, reduced APA variability, and decreased the time to toe-off relative to the passive conditions.SIGNIFICANCE: These findings demonstrate the potential utility of mechanical assistance at the ankle joint (with or without an acoustic cue) as a method to generate more consistent, shortened, and amplified APAs in people with PD and FOG.
View details for DOI 10.1016/j.gaitpost.2019.05.002
View details for PubMedID 31226601
A Neuromechanical Model of Reduced Dorsiflexor Torque During the Anticipatory Postural Adjustments of Gait Initiation
IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING
2018; 26 (11): 2210–16
Anticipatory postural adjustments (APAs) precede gait initiation and function to accelerate the center of mass forward and towards the initial stance leg. Impairments in APA generation, such as those seen in people with Parkinson's disease (PD), can impact the quality of the first step. An initial burst of activity in the dorsiflexor muscle (tibialis anterior) of the stepping leg is an important contributor to the posterior excursion of the center of pressure that accelerates the center of mass forward during an APA. Tibialis anterior activation can be diminished or absent in people with PD; however, the neuromechanical consequence of this diminished dorsiflexor torque on APA generation is not fully understood. Computational models of gait initiation that include components of the neuromuscular system may provide additional insight. In this paper, an inverted pendulum model of the body generated from healthy young adult data was used to simulate reduced dorsiflexor torque during an APA for gait initiation. Forward body lean angle and center of pressure were assessed over various settings of decreased dorsiflexor torque and compared to experimental data from a person with PD. Results from the model demonstrate that reducing the peak dorsiflexor torque by as little as 8-Nm may alter forward body lean and the center of pressure excursion from their nominal trajectories. These results can help inform how much torque is needed from an external device to effectively modulate APAs for gait initiation, as well as provide insight into compensation strategies for reduced dorsiflexor torque in pathology.
View details for DOI 10.1109/TNSRE.2018.2874991
View details for Web of Science ID 000451250400013
View details for PubMedID 30307872