High intensity aerobic exercise improves information processing and motor performance in individuals with Parkinson's disease.

Parkinson's disease (PD) adversely affects information processing and motor performance. The impact of aerobic exercise on modifying the deleterious effects of PD underlying information and motor control processes is not well established. The primary aim of this project was to determine the effects of an 8-week high intensity exercise intervention on information processing and movement execution in individuals with PD. A secondary aim sought to understand the effects of antiparkinsonian medication relative to exercise on motor control processes. Data were collected at baseline (on- and off-medication) and upon completion of the exercise intervention (off-medication). Information processing and motor execution were evaluated via simple and choice reaction time paradigms (SRT and CRT) performed on a mobile device. Neither exercise nor medication impacted information processing or movement execution under the SRT paradigm. However, under CRT, exercise improved movement execution and information processing: total time was significantly reduced from 814 to 747 ms (p < 0.001), reaction time improved from 543 to 502 ms (p < 0.001), movement time improved from 270 to 246 ms (p = 0.01), and movement velocity improved from 28 cm/sec to 30 cm/sec (p = 0.01). Improvements in total time and reaction time in the CRT paradigm persisted 4 and 8 weeks following exercise cessation. Antiparkinsonian medication improved motor execution, but not information processing. The improvement in information processing following aerobic exercise, but not levodopa administration, suggests high intensity exercise may be enhancing neural processing and non-motor pathways outside those impacted by medication. The persistence of symptom improvement despite exercise intervention cessation indicates exercise is a candidate for disease modification. Trial registration: The trial was first registered at ClinicalTrials.gov on 7/10/2012 under registration number NCT01636297.

Forced and Voluntary Aerobic Cycling Interventions Improve Walking Capacity in Individuals With Chronic Stroke.

OBJECTIVES: To determine the efficacy of high-intensity cycling to improve walking capacity in individuals with chronic stroke, identify variables that predict improvement in walking capacity, and quantify the relationship between the 6-minute walk test (6MWT) and cardiopulmonary exercise (CPX) test variables. DESIGN: Secondary analysis of data from 2 randomized controlled trials. SETTING: Research laboratory. PARTICIPANTS: Individuals with chronic stroke (N=43). INTERVENTIONS: Participants were randomized to 1 of the following time-matched interventions, occurring 3 times per week for 8 weeks: (1) forced aerobic exercise and upper extremity repetitive task practice (FE+RTP [n=16]), (2) voluntary aerobic exercise and upper extremity repetitive task practice (VE+RTP [n=14]), or (3) a non-aerobic control group (n=13). MAIN OUTCOME MEASURE: Change in walking capacity as measured by the 6MWT from baseline to the end of treatment (EOT). RESULTS: Significant increases were observed in distance traveled during the 6MWT at the EOT compared with baseline in the FE+RTP (P<.001) and VE+RTP (P<.001) groups, but not in the control group (P=.21). Among aerobic exercise participants, a multivariate regression analysis revealed that cycling cadence, power output, and baseline 6MWT distance were significant predictors of change in walking capacity. CONCLUSIONS: An 8-week aerobic cycling intervention prescribed at 60% to 80% of heart rate reserve and moderate to high cadence and resistance led to significant improvements in walking capacity in our cohort of individuals with chronic stroke. Individuals with low baseline walking capacity levels may benefit most from aerobic cycling to improve over ground locomotion. Although the 6MWT did not elicit a cardiorespiratory response comparable to the maximal exertion CPX test, the 6MWT can be considered a valid and clinically relevant submaximal test of cardiorespiratory function in individuals with chronic stroke.

Predictors of Improved Aerobic Capacity in Individuals With Chronic Stroke Participating in Cycling Interventions.

OBJECTIVE: To determine demographic and physiological factors that predict improvement in aerobic capacity among individuals with chronic stroke participating in cycling interventions. DESIGN: Secondary analysis of data from 2 randomized clinical trials. SETTING: Research laboratory. PARTICIPANTS: Individuals with chronic stroke (N=44). INTERVENTIONS: Participants were randomized to one of the following interventions: forced aerobic exercise and upper extremity repetitive task practice (FE+UERTP, n=16), voluntary aerobic exercise and upper extremity repetitive task practice (VE+UERTP, n=15), or a nonaerobic control group (control, n=13). All interventions were time-matched and occurred 3 times per week for 8 weeks. MAIN OUTCOME MEASURE: Aerobic capacity as measured by peak oxygen consumption per unit time (VO2peak) during maximal cardiopulmonary exercise stress testing. RESULTS: Significant improvements in VO2peak were observed from baseline to postintervention in the VE+UERTP group (P<.001). Considerable variability was observed among participants relating to postintervention change in VO2peak. Among aerobic exercise participants, a multivariate regression analysis revealed that cycling cadence, baseline VO2peak, and group allocation were significant predictors of change in VO2peak. CONCLUSIONS: High exercise rate (cycling cadence) appears to be an important variable in improving aerobic capacity and should be considered when prescribing aerobic exercise for individuals with chronic stroke. Those with low VO2peak at baseline may benefit the most from aerobic interventions as it relates to cardiorespiratory fitness. Further investigation is warranted to understand the precise role of other exercise and demographic variables in the prescription of aerobic exercise for this population and their effects on secondary stroke prevention and mortality.

Subthalamic neural entropy is a feature of freezing of gait in freely moving people with Parkinson's disease.

The goal of this study was to investigate subthalamic (STN) neural features of Freezers and Non-Freezers with Parkinson's disease (PD), while freely walking without freezing of gait (FOG) and during periods of FOG, which were better elicited during a novel turning and barrier gait task than during forward walking. METHODS: Synchronous STN local field potentials (LFPs), shank angular velocities, and ground reaction forces were measured in fourteen PD subjects (eight Freezers) off medication, OFF deep brain stimulation (DBS), using an investigative, implanted, sensing neurostimulator (Activa® PC+S, Medtronic, Inc.). Tasks included standing still, instrumented forward walking, stepping in place on dual forceplates, and instrumented walking through a turning and barrier course. RESULTS: During locomotion without FOG, Freezers showed lower beta (13-30Hz) power (P=0.036) and greater beta Sample Entropy (P=0.032), than Non-Freezers, as well as greater gait asymmetry and arrhythmicity (P<0.05 for both). No differences in alpha/beta power and/or entropy were evident at rest. During periods of FOG, Freezers showed greater alpha (8-12Hz) Sample Entropy (P<0.001) than during walking without FOG. CONCLUSIONS: A novel turning and barrier course was superior to FW in eliciting FOG. Greater unpredictability in subthalamic beta rhythms was evident during stepping without freezing episodes in Freezers compared to Non-Freezers, whereas greater unpredictability in alpha rhythms was evident in Freezers during FOG. Non-linear analysis of dynamic neural signals during gait in freely moving people with PD may yield greater insight into the pathophysiology of FOG; whether the increases in STN entropy are causative or compensatory remains to be determined. Some beta LFP power may be useful for rhythmic, symmetric gait and DBS parameters, which completely attenuate STN beta power may worsen rather than improve FOG.

Sixty-hertz stimulation improves bradykinesia and amplifies subthalamic low-frequency oscillations.

BACKGROUND: The objective of this study was to investigate the hypothesis that attenuation of subthalamic nucleus (STN) alpha-/beta-band oscillations is causal to improvement in bradykinesia. METHODS: STN local field potentials from a sensing neurostimulator (Activa® PC+S; Medtronic, Inc.) and kinematics from wearable sensors were recorded simultaneously during 60- and 140-Hz deep brain stimulation (DBS) in 9 freely moving PD subjects (15 STNs) performing repetitive wrist flexion-extension. Kinematics were recorded during 20-Hz DBS in a subgroup. RESULTS: Both 60- and 140-Hz DBS improved the angular velocity and frequency of movement (P = 0.002 and P = 0.029, respectively, for 60 Hz; P < 0.001 and P < 0.001, respectively, for 140 Hz), but 60-Hz DBS did not attenuate beta-band power (13-30 Hz). In fact, 60-Hz DBS amplified alpha/low-beta (11-15 Hz, P = 0.007) and attenuated high-beta power (19-27 Hz, P < 0.001), whereas 140-Hz DBS broadly attenuated beta power (15-30 Hz, P < 0.001). Only 60-Hz DBS improved the regularity of angular range (P = 0.046) and 20-Hz DBS did not worsen bradykinesia. There was no correlation between beta-power modulation and bradykinesia. CONCLUSIONS: These novel results obtained from freely moving PD subjects demonstrated that both 140- and 60-Hz DBS improved bradykinesia and attenuated high beta oscillations; however, 60-Hz DBS amplified a subband of alpha/low-beta oscillations, and DBS at a beta-band frequency did not worsen bradykinesia. Based on recent literature, we suggest that both 140- and 60-Hz DBS decouple the cortico-STN hyperdirect pathway, whereas 60-Hz DBS increases coupling within striato-STN circuitry. These results inform future algorithms for closed-loop DBS in PD. © 2016 International Parkinson and Movement Disorder Society.

Subthalamic beta oscillations are attenuated after withdrawal of chronic high frequency neurostimulation in Parkinson's disease.

Subthalamic nucleus (STN) local field potential (LFP) recordings demonstrate beta (13-30Hz) band oscillations in Parkinson's disease (PD) defined as elevations of spectral power. The amount of attenuation of beta band power on therapeutic levels of high frequency (HF) deep brain stimulation (DBS) and/or dopaminergic medication has been correlated with the degree of improvement in bradykinesia and rigidity from the therapy, which has led to the suggestion that elevated beta band power is a marker of PD motor disability. A fundamental question has not been answered: whether there is a prolonged attenuation of beta band power after withdrawal of chronic HF DBS and whether this is related to a lack of progression or even improvement in the underlying motor disability. Until now, in human PD subjects, STN LFP recordings were only attainable in the peri-operative period and after short periods of stimulation. For the first time, using an investigational, implanted sensing neurostimulator (Activa® PC+S, Medtronic, Inc.), STN LFPs and motor disability were recorded/assessed after withdrawal of chronic (6 and 12month) HF DBS in freely moving PD subjects. Beta band power was similar within 14s and 60min after stimulation was withdrawn, suggesting that "off therapy" experiments can be conducted almost immediately after stimulation is turned off. After withdrawal of 6 and 12months of STN DBS, beta band power was significantly lower (P<0.05 at 6 and 12months) and off therapy UPDRS scores were better (P<0.05 at 12months) compared to before DBS was started. The attenuation in beta band power was correlated with improvement in motor disability scores (P<0.05). These findings were supported by evidence of a gradual increase in beta band power in two unstimulated STNs after 24months and could not be explained by changes in lead impedance. This suggests that chronic HF DBS exerts long-term plasticity in the sensorimotor network, which may contribute to a lack of progression in underlying motor disability in PD.

Beta oscillations in freely moving Parkinson's subjects are attenuated during deep brain stimulation.

BACKGROUND: Investigations into the effect of deep brain stimulation (DBS) on subthalamic (STN) beta (13-30 Hz) oscillations have been performed in the perioperative period with the subject tethered to equipment. Using an embedded sensing neurostimulator, this study investigated whether beta power was similar in different resting postures and during forward walking in freely moving subjects with Parkinson's disease (PD) and whether STN DBS attenuated beta power in a voltage-dependent manner. METHODS: Subthalamic local field potentials were recorded from the DBS lead, using a sensing neurostimulator (Activa(®) PC+S, Medtronic, Inc., Food and Drug Administration- Investigational Device Exemption (IDE)-, institutional review board-approved) from 15 PD subjects (30 STNs) off medication during lying, sitting, and standing, during forward walking, and during randomized periods of 140 Hz DBS at 0 V, 1 V, and 2.5/3 V. Continuous video, limb angular velocity, and forearm electromyography recordings were synchronized with neural recordings. Data were parsed to avoid any movement or electrical artifact during resting states. RESULTS: Beta power was similar during lying, sitting, and standing (P = 0.077, n = 28) and during forward walking compared with the averaged resting state (P = 0.466, n = 24), although akinetic rigid PD subjects tended to exhibit decreased beta power when walking. Deep brain stimulation at 3 V and at 1 V attenuated beta power compared with 0 V (P < 0.003, n = 14), and this was voltage dependent (P < 0.001). CONCLUSIONS: Beta power was conserved during resting and forward walking states and was attenuated in a voltage-dependent manner during 140-Hz DBS. Phenotype may be an important consideration if this is used for closed-loop DBS.

An 8-week aerobic cycling intervention elicits improved gait velocity and biomechanics in persons with Parkinson's disease.

BACKGROUND: It is unknown if improvements in gait velocity following an aerobic cycling intervention are accompanied by improved gait biomechanics in individuals with Parkinson's disease (PD) or if gait abnormalities are exaggerated in response to increased velocity. Research question Can an 8-week aerobic cycling intervention elicit improvements in locomotor function in individuals with mild to moderate PD? METHODS: A secondary analysis of data from a randomized clinical trial was conducted in individuals with mild to moderate idiopathic PD (N = 28). Participants were randomized to an aerobic cycling intervention (PDex, N = 14) consisting of 24 sessions at a targeted aerobic intensity of 60-80% of heart rate reserve or to a no intervention control group (PDcontrol, N = 14). Change in comfortable walking speed in addition to gait kinematics, kinetics, and spatiotemporal variables using motion capture were obtained at baseline and end of treatment (EOT). RESULTS: The PDex group made significantly greater improvements in the primary outcome, change in comfortable gait velocity, from 0.86 ± 0.24 m/s at baseline to 1.00 ± 0.23 m/s at EOT compared to the PDcontrol group who declined from 0.91 ± 0.23 m/s at baseline to 0.80 ± 0.29 at EOT (P = 0.002). Improvements in gait velocity for the PDex group were accompanied by improvements in gait kinematics, kinetics, and spatiotemporal parameters, while the PDcontrol group demonstrated slight worsening in all gait parameters over the 8-week period. Significance The 8-week moderate- to high-intensity cycling intervention elicited significantly greater improvements in gait velocity compared to the PDcontrol group. Increased gait velocity was accompanied by normalization of gait biomechanics, rather than an exaggeration of existing gait deviations. Aerobic cycling may be a viable treatment approach to improve gait velocity and gait biomechanics in individuals with mild to moderate PD and may mitigate declines in mobility.

Components of a successful community-based exercise program for individuals with Parkinson's disease: Results from a participant survey.

OBJECTIVES: The aim of the project was to examine the personal beliefs, motivators, and barriers in people with Parkinson's disease (PwPD) relating to their participation in a year-round community-based cycling program, Pedaling for Parkinson's (PFP). DESIGN: Cross-sectional survey from a 12-month pragmatic study. SETTING: Five community-based PFP sites. MAIN OUTCOME MEASURES: A survey was designed to capture the attitudes and beliefs of those participating in a PFP program. Survey responses were rated on a 5-point Likert scale (1-5; higher number representing a more positive response) assessing the subdomains of Personal Beliefs and Knowledge, Health and Disability, Program, and Fitness Environment following a 12-month exercise observational period. RESULTS: A total of 40 PwPD completed the survey. Mean subdomain scores were as follows: 4.37 (0.41) for Personal Beliefs and Knowledge, 4.25 (0.65) for Health and Disability, 4.11 (0.53) for Program, and 4.35 (0.44) for Fitness Environment. There were no significant correlations between survey subdomains and demographic variables (age, years of education, years since diagnosis, years attending the PFP program, and disease severity) or subdomains and exercise behavior (cadence, attendance, and heart rate). CONCLUSIONS: Regardless of demographic variables and disease severity, PwPD who attended a PFP program enjoyed the class, felt that their PD symptoms benefited from exercise, and were motivated to exercise by their PD diagnosis. Factors such as location of the gym, cost, and transportation were important. With the growing body of PD literature supporting the role of exercise in potentially altering the disease trajectory, it is critical that communities adopt and implement exercise programs that meet the needs of PwPD and facilitate compliance.

High intensity aerobic exercise improves bimanual coordination of grasping forces in Parkinson's disease.

INTRODUCTION: Parkinson's disease (PD) disrupts the control and coordination of grasping forces, likely due to a disruption in basal ganglia circuitry and diminished activity within the supplementary motor area (SMA). High intensity aerobic exercise has been shown to enhance connectivity between basal ganglia nuclei and cortical areas, including the SMA. The aim of this project was to determine the effects of high intensity lower extremity exercise on motor control patterns underlying a manual dexterity task. METHODS: PD participants completed eight weeks of high intensity aerobic exercise under forced or voluntary exercise (FE or VE) modalities. Grasping forces for each limb were quantified during a functional bimanual dexterity task. Data were collected while OFF antiparkinsonian medication at baseline, end of treatment (EOT), and eight weeks after exercise cessation (EOT+8). RESULTS: Eight weeks of high intensity exercise improved MDS-UPDRS Motor III clinical ratings by more than 4 points (~15%) for the FE and VE groups. Time to complete the task decreased nearly 30% across both groups as well. The control and coordination of grasping forces, simultaneity of force initiation, and rate of grip and load force exhibited significant improvements following exercise. In general, improvements in biomechanical outcomes were sustained following exercise cessation. CONCLUSION: High intensity aerobic exercise, achieved via a forced or voluntary mode, improved PD symptoms and bimanual dexterity. Sustained improvement of upper extremity motor control following exercise cessation indicates high intensity exercise enhances CNS functioning and suggests exercise may be a candidate for altering PD progression.

Errors in cognitive performance trigger postural instability in Parkinson's disease.

BACKGROUND: Globally, postural stability and cognitive performance are intimately linked in Parkinson's disease (PD). However, a fundamental gap exists in understanding the precise relationship between a disruption in executive function and its impact on postural stability. OBJECTIVE: This project aimed to determine the precise effects of cognitive errors on postural stability under dual-task conditions in participants with PD and controls. METHODS: Twenty-eight individuals with PD and 27 healthy controls completed a series of postural stability tests under single- and dual-tasks. The dual-task required maintenance of balance while performing an audio number discrimination task. RESULTS: In general, postural stability in PD and control subjects was similar across single-task conditions. In controls, an error in the cognitive task during dual-task conditions did not impact measures of postural sway. In contrast, in PD, postural sway increased in epochs surrounding cognitive errors relative to epochs without errors. CONCLUSIONS: Postural task selection plays a critical role when testing for balance deficits in PD compared to healthy controls. Furthermore, time synchronized analysis of cognitive and balance data revealed the greatest episodes of postural instabilities occurred around cognitive errors. The measurement and evaluation of cognitive-motor linkages, relative to postural stability, could provide a patient-specific fingerprint of balance function and provide more sensitive measures for fall risk in PD.

Development and Validation of a Mobile Application to Detect Visual Dysfunction Following Mild Traumatic Brain Injury.

INTRODUCTION: Following mild traumatic brain injury, visual dysfunction is a common occurrence, yet the condition often goes undiagnosed. A mobile application was developed to measure aspects of visual acuity and oculomotor function. The aim of this project was to validate the newly developed suite of outcomes conducive for use in the field to detect visual dysfunction. MATERIALS AND METHODS: A custom mobile application was developed on an Apple iPad using iOS operating system software version 11.0 in Objective C to measure near point of convergence (NPC), distance visual acuity, reading fluency, and self-rated convergence insufficiency (CI). To determine construct validity, 50 healthy young adults were administered NPC and distance visual acuity assessments using the iPad and standard clinical approaches. A ruler measurement was obtained simultaneous to the iPad NPC measurement to determine measurement accuracy. All testing was administered by a licensed optometrist and the order of testing (iPad versus clinical) was randomized. RESULTS: The correlation coefficient between the iPad and clinical measurements of NPC was 0.893, while iPad and ruler measurement was 0.947. Modest accordance was found between iPad and wall chart measures assessing distance visual acuity. A ceiling effect was evident with use of a wall chart to determine distance visual acuity. Healthy young adults scored a mean (SD) of 13.0 (7.4) on the Convergence Insufficiency Symptom Survey. Reading fluency was highly variable with a mean (SD) of 291 (119) words per minute. CONCLUSIONS: iPad measures of NPC were highly correlated with clinical measures, while visual acuity measured with the iPad showed modest correlation. Nonetheless, the suite of visual assessments provide value as screening tools, and when used in combination with reading fluency assessment and self-reported CI may be effective in identifying visual dysfunction following mild traumatic brain injury.

Use of a Smartphone to Gather Parkinson's Disease Neurological Vital Signs during the COVID-19 Pandemic.

INTRODUCTION: To overcome travel restrictions during the COVID-19 pandemic, consumer-based technology was rapidly deployed to the smartphones of individuals with Parkinson's disease (PD) participating in a 12-month exercise trial. The aim of the project was to determine the feasibility of utilizing a combined synchronous and asynchronous self-administered smartphone application to characterize PD symptoms. METHODS: A synchronous video virtual visit was completed for the administration of virtual Movement Disorder Society-Unified Parkinson's Disease Rating Scale III (vMDS-UPDRS III). Participants asynchronously completed a mobile application consisting of a measure of upper extremity bradykinesia (Finger Tapping Test) and information processing. RESULTS: Twenty-three individuals completed the assessments. The mean vMDS-UPDRS III was 23.65 ± 8.56 points. On average, the number of taps was significantly greater for the less affected limb, 97.96 ± 17.77 taps, compared to the more affected, 89.33 ± 18.66 taps (p = 0.025) with a significantly greater number of freezing episodes for the more affected limb (p < 0.05). Correlation analyses indicated the number of errors and the number of freezing episodes were significantly related to clinical ratings of vMDS-UPDRS III bradykinesia (Rho = 0.44, p < 0.01; R = 0.43, p < 0.01, resp.) and finger tapping performance (Rho = 0.31, p = 0.03; Rho = 0.32, p = 0.03, resp.). Discussion. The objective characterization of bradykinesia, akinesia, and nonmotor function and their relationship with clinical disease metrics indicate smartphone technology provides a remote method of characterizing important aspects of PD performance. While theoretical and position papers have been published on the potential of telemedicine to aid in the management of PD, this report translates the theory into a viable reality.

A validated measure of rigidity in Parkinson's disease using alternating finger tapping on an engineered keyboard.

INTRODUCTION: Reliable and accurate measures of rigidity have remained elusive in remote assessments of Parkinson's disease (PD). This has severely limited the utility of telemedicine in the care and treatment of people with PD. It has also had a large negative impact on the scope of available outcomes, and on the costs, of multicenter clinical trials in PD. The goal of this study was to determine if quantitative measures from an engineered keyboard were sensitive and related to clinical measures of rigidity. METHODS: Sixteen participants with idiopathic PD, off antiparkinsonian medications, and eleven age-matched control participants performed a 30 second repetitive alternating finger tapping task on an engineered keyboard and were assessed with the Unified Parkinson's Disease Rating Scale - motor (UPDRS-III). RESULTS: The speed of the key release was significantly slower in the PD compared to control cohorts (p < 0.0001). In the PD cohort key release speed correlated with the lateralized upper extremity UPDRS III rigidity score (r = - 0.58, p < 0.0001), but not with the lateralized upper extremity tremor score (r = - 0.14, p = 0.43). CONCLUSIONS: This validated measure of rigidity complements our previous validation of temporal metrics of the repetitive alternating finger tapping task with the UPDRS III, bradykinesia and with the ability to quantify tremor, arrhythmicity and freezing episodes, and suggests that 30 seconds of alternating finger tapping on a portable engineered keyboard could transform the treatment of PD with telemedicine and the precision of multicenter clinical trials.

Military-Specific Normative Data for Cognitive and Motor Single- and Dual-Task Assessments for Use in Mild Traumatic Brain Injury Assessment.

INTRODUCTION: Military personnel and civilian athletes are both at risk for mild traumatic brain injury. However, these groups are unique in their training and typical daily activities. A fundamental gap in the evaluation of military personnel following mild traumatic brain injury is the lack of military-specific normative reference data. This project aimed to determine if a separate normative sample should be used for military personnel on their performance of the Cleveland Clinic Concussion application and a recently developed dual-task module. METHODS: Data were collected from healthy military personnel (n = 305) and civilians (n = 281) 18 to 30 years of age. Participants completed the following assessments: simple and choice reaction time, Trail Making tests A&B, processing speed test, single-task postural stability, single-task cognitive assessment, and dual-task assessment. RESULTS: Civilian participants outperformed military service members on all cognitive tasks under single- and dual-task conditions (P ≤ 0.04). The military group outperformed civilians on all postural stability tasks under single- and dual-task conditions (P ≤ 0.01). CONCLUSION: Differences in cognitive performance and postural stability measures may be influenced by demographic differences between military and civilian cohorts. Thus, military-specific normative datasets must be established to optimize clinical interpretation of Cleveland Clinic Concussion assessments.

Excessive postural sway and the risk of falls at different stages of Parkinson's disease.

Excessive postural sway may result in falls in Parkinson's disease (PD). We measured postural sway using the sensory organization test (SOT) of dynamic posturography in static (platform still) and dynamic (sway referenced platform) conditions with normal, no and inappropriate visual feedback in 102 subjects with PD, off medication. Twenty-five healthy subjects were used as age-matched controls. Eighteen very early stage PD subjects had never used dopaminergic medication. Postural sway was normal in those subjects in all conditions, but was abnormal in subjects with more advanced symptoms (UPDRS III > 20, P < 0.01). Postural sway increased with disease severity in all conditions except static, eyes closed (P < 0.0001). We developed the SOT Fall Severity Scale (SOTFSS) from the number of times postural sway was so large that the subject had to take a step (registered as a "fall") and showed that falls mainly occurred in dynamic conditions, and were correlated with disease severity (P < 0.0001). In dynamic conditions the SOTFSS was correlated with the retropulsion score from the UPDRS III (N = 102, P < 0.0001) and with the subjects' self-reported fall frequency from the UPDRS II (N = 62, SOT5: P = 0.0419, SOT6: P = 0.0034).

Quantitative lateralized measures of bradykinesia at different stages of Parkinson's disease: the role of the less affected side.

The onset of motor abnormalities in Parkinson's disease (PD) is usually unilateral. However, current therapeutic trials do not analyze separately the performance of the more affected (MA) and less affected (LA) limbs. From a cohort of 85 subjects at different stages of PD, we asked whether the relationship between bradykinesia and disease severity was similar on both limbs and if the MA side remained more bradykinetic than the LA side in advanced PD. MA and LA limb determination was made from the history of the side first affected. Twenty-one age-matched subjects were used as controls. The velocities of finger and arm movements on both sides were inversely correlated with disease severity (P < 0.03). The slope of the decline in wrist movement velocity was steeper on the LA side (P = 0.029). When the regression lines were extrapolated to the y-axis (UPDRS III = 0) the performance of the LA side was not different from that of controls (P = 0.954 and P = 0.829 for finger and arm movements, respectively), whereas that of the MA side was slower (P = 0.019 and P = 0.016), suggesting that at the theoretical state of no disease the LA side would reflect less or no contralateral nigral pathology. With increasing disease severity, there was less difference between MA and LA sides in both finger and arm bradykinesia (P < 0.004). These findings highlight the value of analyzing separately the MA and LA sides in subjects with PD, especially for clinical trials of potential disease modifying agents in early stages of disease.

Kinematic Metrics from a Wireless Stylus Quantify Tremor and Bradykinesia in Parkinson's Disease.

A fundamental challenge in the clinical care of Parkinson disease (PD) is the current dependence on subjective evaluations of tremor and bradykinesia. New technologies offer the ability to evaluate motor deficits using purely objective measures. The aim of this study was to develop and evaluate the efficacy of a wireless stylus (Cleveland Clinic Stylus) with an embedded motion sensor to quantitatively assess tremor and bradykinesia in patients with PD with subthalamic nucleus (STN) deep brain stimulation (DBS). Twenty-one subjects were tested in various on and off DBS conditions while holding the Cleveland Clinic Stylus while at rest, maintaining a postural hold, and during a movement task. Kinematic metrics were calculated from the motion sensor data, including 3D angular velocity and 3D acceleration data, and were compared between the on and off conditions. Generalized estimating equations (GEEs) were used to determine the relationship between kinematic metrics and MDS-Unified Parkinson's Disease Rating Scale Motor III (UPDRS-III) subscores. Kinematic metrics from the rest and postural tasks were significantly related to the UPDRS-III subscores of tremor (p < 0.001 for all metrics), and kinematic metrics from the movement task were significantly related to the UPDRS-III subscore of bradykinesia (p < 0.001 for 3/7 metrics). Kinematic metrics (7/9) showed a significant effect of stimulation setting (range: p < 0.03- < 0.0001) across the three tasks, indicating significant improvements from DBS in these measures. The Cleveland Clinic Stylus provided quantitative kinematic measures of tremor and bradykinesia severity and detected significant improvements in these measures from medication and DBS therapy. This low-cost, easy-to-use tool can provide objective measures that will improve clinical care of PD patients by providing a more reliable and objective evaluation of movement symptoms, disease progression, and effects of therapy in and outside the clinical setting.

A Mobile Device Dual-Task Paradigm for the Assessment of mTBI.

RESEARCH OBJECTIVE: Dual-task performance, in which individuals complete two or more activities simultaneously, is impaired following mild traumatic brain injury. The aim of this project was to develop a dual-task paradigm that may be conducive to military utilization in evaluating cognitive-motor function in a standardized and scalable manner by leveraging mobile device technology. METHODS: Fifty healthy young adult civilians (18-24 years) completed four balance stances and a number discrimination task under single- and dual-task conditions. Postural stability was quantified using data gathered from iPad's native accelerometer and gyroscope. Cognitive task difficulty was manipulated by presenting stimuli at 30, 60, or 90 per minute. Performance of cognitive and balance tasks was compared between single- and dual-task trials. RESULTS: Cognitive performance from single- to dual-task paradigms showed no significant main effect of balance condition or the interaction of condition by frequency. From single- to dual-task conditions, a significant difference in postural control was revealed in only one stance: tandem with eyes closed, in which a slight improvement in postural stability was observed under dual-task conditions. CONCLUSION: The optimal dual-task paradigm to evaluate cognitive-motor performance with minimal floor and ceiling effects consists of tandem stance with eyes closed while stimuli are presented at a rate of one per second.