Bradykinesia and Its Progression Are Related to Interhemispheric Beta Coherence.

OBJECTIVE: Bradykinesia is the major cardinal motor sign of Parkinson 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 PD implanted with sensing neurostimulators (Activa® PC + S, Medtronic, PLC) in the STN participated in a longitudinal 'washout' therapy study every three to 6 months for an average of 3 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 At each visit, participants were withdrawn from medication (12/24/48 hours) and had DBS turned off (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. ANN NEUROL 2023;93:1029-1039.

Semi-automated approaches to optimize deep brain stimulation parameters in Parkinson's disease.

BACKGROUND: Deep brain stimulation (DBS) is a treatment option for Parkinson's disease patients when medication does not sufficiently manage their symptoms. DBS can be a highly effect therapy, but only after a time-consuming trial-and-error stimulation parameter adjustment process that is susceptible to clinician bias. This trial-and-error process will be further prolonged with the introduction of segmented electrodes that are now commercially available. New approaches to optimizing a patient's stimulation parameters, that can also handle the increasing complexity of new electrode and stimulator designs, is needed. METHODS: To improve DBS parameter programming, we explored two semi-automated optimization approaches: a Bayesian optimization (BayesOpt) algorithm to efficiently determine a patient's optimal stimulation parameter for minimizing rigidity, and a probit Gaussian process (pGP) to assess patient's preference. Quantified rigidity measurements were obtained using a robotic manipulandum in two participants over two visits. Rigidity was measured, in 5Hz increments, between 10-185Hz (total 30-36 frequencies) on the first visit and at eight BayesOpt algorithm-selected frequencies on the second visit. The participant was also asked their preference between the current and previous stimulation frequency. First, we compared the optimal frequency between visits with the participant's preferred frequency. Next, we evaluated the efficiency of the BayesOpt algorithm, comparing it to random and equal interval selection of frequency. RESULTS: The BayesOpt algorithm estimated the optimal frequency to be the highest tolerable frequency, matching the optimal frequency found during the first visit. However, the participants' pGP models indicate a preference at frequencies between 70-110 Hz. Here the stimulation frequency is lowest that achieves nearly maximal suppression of rigidity. BayesOpt was efficient, estimating the rigidity response curve to stimulation that was almost indistinguishable when compared to the longer brute force method. CONCLUSIONS: These results provide preliminary evidence of the feasibility to use BayesOpt for determining the optimal frequency, while pGP patient's preferences include more difficult to measure outcomes. Both novel approaches can shorten DBS programming and can be expanded to include multiple symptoms and parameters.

Six-Minute Walk Test Performance in Persons With Multiple Sclerosis While Using Passive or Powered Ankle-Foot Orthoses.

OBJECTIVE: To determine whether a powered ankle-foot orthosis (AFO) that provides dorsiflexor and plantar flexor assistance at the ankle can improve walking endurance of persons with multiple sclerosis (MS). DESIGN: Short-term intervention. SETTING: University research laboratory. PARTICIPANTS: Participants (N=16) with a neurologist-confirmed diagnosis of MS and daily use of a prescribed custom unilateral passive AFO. INTERVENTIONS: Three 6-minute walk tests (6MWTs), 1 per footwear condition: shoes (no AFO), prescribed passive AFO, and portable powered AFO (PPAFO). Assistive devices were worn on the impaired limb. MAIN OUTCOME MEASURES: Distance walked and metabolic cost of transport were recorded during each 6MWT and compared between footwear conditions. RESULTS: Each participant completed all three 6MWTs within the experimental design. PPAFO use resulted in a shorter 6MWT distance than did a passive AFO or shoe use. No differences were observed in metabolic cost of transport between footwear conditions. CONCLUSIONS: The current embodiment of this PPAFO did not improve endurance walking performance during the 6MWT in a sample of participants with gait impairment due to MS. Further research is required to determine whether expanded training or modified design of this powered orthosis can be effective in improving endurance walking performance in persons with gait impairment due to MS.

Impact of SCBA size and fatigue from different firefighting work cycles on firefighter gait.

Risk of slips, trips and falls in firefighters maybe influenced by the firefighter's equipment and duration of firefighting. This study examined the impact of a four self-contained breathing apparatus (SCBA) three SCBA of increasing size and a prototype design and three work cycles one bout (1B), two bouts with a five-minute break (2B) and two bouts back-to-back (BB) on gait in 30 firefighters. Five gait parameters (double support time, single support time, stride length, step width and stride velocity) were examined pre- and post-firefighting activity. The two largest SCBA resulted in longer double support times relative to the smallest SCBA. Multiple bouts of firefighting activity resulted in increased single and double support time and decreased stride length, step width and stride velocity. These results suggest that with larger SCBA or longer durations of activity, firefighters may adopt more conservative gait patterns to minimise fall risk. Practitioner Summary: The effects of four self-contained breathing apparatus (SCBA) and three work cycles on five gait parameters were examined pre- and post-firefighting activity. Both SCBA size and work cycle affected gait. The two largest SCBA resulted in longer double support times. Multiple bouts of activity resulted in more conservative gait patterns.

Physiological responses to simulated firefighter exercise protocols in varying environments.

For decades, research to quantify the effects of firefighting activities and personal protective equipment on physiology and biomechanics has been conducted in a variety of testing environments. It is unknown if these different environments provide similar information and comparable responses. A novel Firefighting Activities Station, which simulates four common fireground tasks, is presented for use with an environmental chamber in a controlled laboratory setting. Nineteen firefighters completed three different exercise protocols following common research practices. Simulated firefighting activities conducted in an environmental chamber or live-fire structures elicited similar physiological responses (max heart rate: 190.1 vs 188.0 bpm, core temperature response: 0.047°C/min vs 0.043°C/min) and accelerometry counts. However, the response to a treadmill protocol commonly used in laboratory settings resulted in significantly lower heart rate (178.4 vs 188.0 bpm), core temperature response (0.037°C/min vs 0.043°C/min) and physical activity counts compared with firefighting activities in the burn building. Practitioner Summary: We introduce a new approach for simulating realistic firefighting activities in a controlled laboratory environment for ergonomics assessment of fire service equipment and personnel. Physiological responses to this proposed protocol more closely replicate those from live-fire activities than a traditional treadmill protocol and are simple to replicate and standardise.

The Sequence Effect Worsens Over Time in Parkinson's Disease and Responds to Open and Closed-Loop Subthalamic Nucleus Deep Brain Stimulation.

BACKGROUND: 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). OBJECTIVE: To investigate whether the sequence effect worsens over time and/or is improved on clinical (open-loop) deep brain stimulation (DBS). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Can People with Parkinson's Disease Self-Trigger Gait Initiation? A Comparison of Cueing Strategies.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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). RESULTS: 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. CONCLUSION: 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.

Quantitative Digitography Measures Motor Symptoms and Disease Progression in 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.

Modulation of Beta Oscillations in the Pallidum During Externally Cued Gait.

Freezing of gait (FOG) is a particularly debilitating symptom of Parkinson's disease (PD) and is often refractory to treatment. A striking feature of FOG is that external sensory cues can be used to overcome freezing and improve gait. Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) and globus pallidus (GP) show that beta-band power modulates with gait phase. In the STN, beta-band oscillations are modulated by external cues, but it is unknown if this relationship holds in the globus pallidus (GP). Here we report LFP data recorded from the left GP, using a Medtronic PC + S device, in a 68-year-old man with PD and FOG during treadmill walking. A "stepping stone" task was used during which stepping was cued using visual targets of constant color or targets that unpredictably changed color, requiring a step length adjustment. Gait performance was quantified using measures of treadmill ground reaction forces and center of pressure and body kinematics from video monitoring. Beta-band power (12-30 Hz) and number of freezing episodes were measured. Cues which unpredictably changed color improved FOG more than conventional cues and were associated with greater modulation of beta-band power in phase with gait. This preliminary finding suggests that cueing-induced improvement of FOG may relate to beta-band modulation.

White matter microstructure in Parkinson's disease with and without elevated rapid eye movement sleep muscle tone.

People with Parkinson's disease who have elevated muscle activity during rapid eye movement sleep (REM sleep without atonia) typically have a worse motor and cognitive impairment compared with those with normal muscle atonia during rapid eye movement sleep. This study used tract-based spatial statistics to compare diffusion MRI measures of fractional anisotropy, radial, mean and axial diffusivity (measures of axonal microstructure based on the directionality of water diffusion) in white matter tracts between people with Parkinson's disease with and without rapid eye movement sleep without atonia and controls and their relationship to measures of motor and cognitive function. Thirty-eight individuals with mild-to-moderate Parkinson's disease and 21 matched control subjects underwent ultra-high field MRI (7 T), quantitative motor assessments of gait and bradykinesia and neuropsychological testing. The Parkinson's disease cohort was separated post hoc into those with and without elevated chin or leg muscle activity during rapid eye movement sleep based on polysomnography findings. Fractional anisotropy was significantly higher, and diffusivity significantly lower, in regions of the corpus callosum, projection and association white matter pathways in the Parkinson's group with normal rapid eye movement sleep muscle tone compared with controls, and in a subset of pathways relative to the Parkinson's disease group with rapid eye movement sleep without atonia. The Parkinson's disease group with elevated rapid eye movement sleep muscle tone showed significant impairments in the gait and upper arm speed compared with controls and significantly worse scores in specific cognitive domains (executive function, visuospatial memory) compared with the Parkinson's disease group with normal rapid eye movement sleep muscle tone. Regression analyses showed that gait speed and step length in the Parkinson's disease cohort were predicted by measures of fractional anisotropy of the anterior corona radiata, whereas elbow flexion velocity was predicted by fractional anisotropy of the superior corona radiata. Visuospatial memory task performance was predicted by the radial diffusivity of the posterior corona radiata. These findings show that people with mild-to-moderate severity of Parkinson's disease who have normal muscle tone during rapid eye movement sleep demonstrate compensatory-like adaptations in axonal microstructure that are associated with preserved motor and cognitive function, but these adaptations are reduced or absent in those with increased rapid eye movement sleep motor tone.

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.

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.

Ramp Rate Evaluation and Configuration for Safe and Tolerable Closed-Loop Deep Brain Stimulation.

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.

Differential Effects of Pathological Beta Burst Dynamics Between Parkinson's Disease Phenotypes Across Different Movements.

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.

REM Sleep Without Atonia and Gait Impairment in People with Mild-to-Moderate Parkinson's Disease.

BACKGROUND: Subtle gait deficits can be seen in people with idiopathic rapid eye movement (REM) sleep behavior disorder (RBD), a prodromal stage of Parkinson's disease (PD) and related alpha-synucleinopathies. It is unknown if the presence and level of REM sleep without atonia (RSWA, the electromyographic hallmark of RBD) is related to the severity of gait disturbances in people with PD. OBJECTIVE: We hypothesized that gait disturbances in people with mild-to-moderate PD would be greater in participants with RSWA compared to those without RSWA and matched controls, and that gait impairment would correlate with measures of RSWA. METHODS: Spatiotemporal characteristics of gait were obtained from 41 people with PD and 21 age-matched controls. Overnight sleep studies were used to quantify muscle activity during REM sleep and group participants with PD into those with RSWA (PD-RSWA+, n = 22) and normal REM sleep muscle tone (PD-RSWA-, n = 19). Gait characteristics were compared between groups and correlated to RSWA. RESULTS: The PD-RSWA+ group demonstrated significantly reduced gait speed and step lengths and increased stance and double support times compared to controls, and decreased speed and cadence and increased stride velocity variability compared to PD-RSWA- group. Larger RSWA scores were correlated with worse gait impairment in the PD group. CONCLUSION: The presence and level of muscle tone during REM sleep is associated with the severity of gait disturbances in PD. Pathophysiological processes contributing to disordered gait may occur earlier and/or progress more rapidly in people with PD and RBD.

Lack of progression of beta dynamics after long-term subthalamic neurostimulation.

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 6 months, 1 year, and yearly out to 5 years of treatment. The primary endpoint was measured at 3 years. At each visit, medication had been held for over 12/24 h and DBS was turned off for at least 60 min, by which time LFP spectra reached a steady state. RESULTS: After 3 years 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 5 years. 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.

Demonstration of Kinematic-Based Closed-loop Deep Brain Stimulation for Mitigating Freezing of Gait in People with Parkinson's Disease.

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.

A Closed-loop Deep Brain Stimulation Approach for Mitigating Burst Durations in People with Parkinson's Disease.

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.

Perspective: Evolution of Control Variables and Policies for Closed-Loop Deep Brain Stimulation for Parkinson's Disease Using Bidirectional Deep-Brain-Computer Interfaces.

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.

REM sleep without atonia is associated with increased rigidity in patients with mild to moderate Parkinson's disease.

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.

Modulation of anticipatory postural adjustments using a powered ankle orthosis in people with Parkinson's disease and freezing of gait.

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.