Novel lower-extremity dexterity assessment for Parkinson's disease: validation against measures of arm dexterity and general mobility.

PURPOSE: To establish criterion and construct validity of a novel, clinically feasible assessment of lower-extremity dexterity for PD patients. METHODS: Thirty-three PD patients performed a unilateral lower-extremity dexterity task "off" and "on" dopaminergic medications with each leg. The task involves iteratively tapping targets with the foot in a specified pattern, and the measured outcome is the time to complete the movement sequence, with longer times indicating worse performance. We correlated leg movement time with standard, validated measures of gait (comfortable and maximal walk speeds), general mobility (timed up and go), upper-extremity dexterity (9-Hole Pegboard), and elements of the Unified Parkinson Disease Rating Scale (MDS-UPDRS). RESULTS: We found significant relationships between lower extremity dexterity and each of these tasks "off" and "on" medications. Task performance also captures known features of PD, including dopamine-mediated improvement in performance and asymmetrical symptom presentation. CONCLUSIONS: This task provides a simple assessment of lower extremity function that correlates with validated measures of dexterity, gait, and mobility. It provides objective, continuous data, is inexpensive, requires little technical expertise/equipment, has a small physical footprint, and can be administered quickly. These features increase the feasibility of implementing this assessment tool in clinical settings.Implications for rehabilitationWe introduce a novel task that captures lower extremity dexterity in individuals with Parkinson's disease (PD).The task is validated against gold standard measures of upper extremity dexterity, gait, and general mobility.Performance on the task is sensitive to known features of PD, including dopamine-mediated improvements and asymmetrical symptom presentation.The task is easy to implement and provides higher quality data compared to other common clinical assessments (e.g., MDS-UPDRS).

Cortical and Subthalamic Nucleus Spectral Changes During Limb Movements in Parkinson's Disease Patients with and Without Dystonia.

BACKGROUND: Dystonia is an understudied motor feature of Parkinson's disease (PD). Although considerable efforts have focused on brain oscillations related to the cardinal symptoms of PD, whether dystonia is associated with specific electrophysiological features is unclear. OBJECTIVE: The objective of this study was to investigate subcortical and cortical field potentials at rest and during contralateral hand and foot movements in patients with PD with and without dystonia. METHODS: We examined the prevalence and distribution of dystonia in patients with PD undergoing deep brain stimulation surgery.  During surgery, we recorded intracranial electrophysiology from the motor cortex and directional electrodes in the subthalamic nucleus (STN) both at rest and during self-paced repetitive contralateral hand and foot movements. Wavelet transforms and mixed models characterized changes in spectral content in patients with and without dystonia. RESULTS: Dystonia was highly prevalent at enrollment (61%) and occurred most commonly in the foot. Regardless of dystonia status, cortical recordings display beta (13-30 Hz) desynchronization during movements versus rest, while STN signals show increased power in low frequencies (6.0 ± 3.3 and 4.2 ± 2.9 Hz peak frequencies for hand and foot movements, respectively). Patients with PD with dystonia during deep brain stimulation surgery displayed greater M1 beta power at rest and STN low-frequency power during movements versus those without dystonia. CONCLUSIONS: Spectral power in motor cortex and STN field potentials differs markedly during repetitive limb movements, with cortical beta desynchronization and subcortical low-frequency synchronization, especially in patients with PD with dystonia. Greater knowledge on field potential dynamics in human motor circuits can inform dystonia pathophysiology in PD and guide novel approaches to therapy. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Asymmetric walking on an incline affects aspects of positive mechanical work asymmetrically.

The purpose of this study was to determine the extent to which we could use a split-belt experimental paradigm to increase limb or joint work. Split-belt treadmill walking was combined with uphill walking at 0°, 5° and 10° in young, healthy individuals to assess whether we could specifically target increased force output between and within limbs. Thirteen healthy, young adults participated in this study. Participants performed walking trials with the left belt at 1.0 m/s and the right belt at 0.5 m/s. Repeated measures ANOVAs assessed the effects of speed of the treadmill belt and incline on total and joint specific positive extensor work as well as relative work. Mechanical work varied because of the speed and incline of the treadmill belt at the level of the total limb and across joints. Positive lower extremity relative joint work varied as a result of treadmill belt speed and treadmill incline. Positive mechanical work was greater on the limb that was on the faster treadmill belt, regardless of incline. Increases in relative knee but not hip joint work increased as incline increased. The current investigation shows that the nervous system can shift mechanical work production both between and within limbs to safely walk in a novel split-belt environment. This work extends previous research by demonstrating that researchers/clinicians can also use increasing treadmill incline (or some other means to add increased resistive forces) during split-belt treadmill walking to encourage increased mechanical output at particular limbs and/or joints which may have rehabilitation implications.

Effects of sensory manipulations on locomotor adaptation to split-belt treadmill walking in healthy younger and older adults.

Locomotor adaptation relies on processes of both the peripheral and central nervous systems that may be compromised with advanced age (e.g., proprioception, sensorimotor integration). Age-related changes to these processes may result in reduced rates of locomotor adaptation under normal conditions and should cause older adults to be disproportionately more affected by sensory manipulations during adaptation compared to younger adults. 17 younger and 10 older adults completed five separate 5-minute split-belt walking trials: three under normal sensory conditions, one with 30% bodyweight support (meant to reduce proprioceptive input), and one with goggles that constrained the visual field (meant to reduce visual input). We fit step length symmetry data from each participant in each trial with a single exponential function and used the time constant to quantify locomotor adaption rate. Group by trial ANOVAs were used to test the effects of age, condition, and their interaction on adaptation rates. Contrary to our hypothesis, we found no evidence that sensory manipulations disproportionately affected older compared to younger adults, at least in our relatively small sample. In fact, in both groups, adaptation rates remained unaffected across all trials, including both normal and sensory manipulated trials. Our results provide evidence that both younger and older adults were able to adequately reweight sources of sensory information based on environmental constraints, indicative of well-functioning neural processes of motor adaptation.

Dopamine-mediated improvements in dynamic balance control in Parkinson's disease.

BACKGROUND: Impaired dynamic balance control increases fall risk and contributes to immobility in individuals with Parkinson's disease (PD). It is unclear whether higher-level neural processes of the central nervous system contribute to impaired balance control. RESEARCH QUESTION: Are dopamine-mediated neural processes of the higher-level central nervous system important for dynamic balance control in PD? METHODS: 21 individuals with idiopathic PD performed step-threshold assessments before and after self-administered dopaminergic medication. Individuals withstood progressively larger postural perturbations, during which they were explicitly instructed to avoid stepping to recover balance. The perturbation magnitude which elicited stepping responses on four consecutive trials is referred to as the step-threshold. Dynamic balance control was quantified as the minimum margin of stability captured during the largest sub-threshold trial (i.e., the maximum amount of compensated postural instability during the task). We compared dynamic balance between off and on medication states and between individuals who exhibited motor adaptive behavior and those who did not. RESULTS: Dopaminergic medications significantly improved step-thresholds and allowed individuals to withstand greater amounts of instability without stepping, indicating dopamine-mediated improvement in dynamic balance control. Individuals who displayed behavioral evidence for higher-level neural processes (motor adaptation across repeated perturbations) displayed superior dynamic balance control versus those who did not. Anteroposterior ground reaction forces captured during perturbations suggest that individuals alter force profiles to avoid stepping at ∼200 ms after perturbation onset-a latency consistent with a transcortical process. SIGNIFICANCE: Combined, our results indicate that higher-level, dopamine-mediated neural processes are responsible for dynamic balance control in PD. We hypothesize that this process incorporates sensorimotor integration, motor response initiation/inhibition, and goal- and reward-driven behaviors. Interventions targeting these processes may improve dynamic postural control in individuals with PD.

Older but not younger adults rely on multijoint coordination to stabilize the swinging limb when performing a novel cued walking task.

Motor flexibility, the ability to employ multiple motor strategies to meet task demands, may facilitate ambulation in complex environments that constrain movements; loss of motor flexibility may impair mobility. The purpose of this study was to determine the effects of obesity (a specific model of mobility impairment) and advanced age on motor flexibility during a task that constrained foot placement while walking. Twenty-one community-dwelling obese (OB) and 25 normal weight (NW) older adults (46 total older adults-OA) and 10 younger adults (YA) walked normally on a treadmill (baseline) then walked while stepping on lighted cues projected onto the treadmill at locations corresponding to average foot placement during normal walking (cued). The uncontrolled manifold (UCM) analysis was used to partition total variance in a set of seven lower-limb segment angles into components that did ("bad" variance) and did not ("good" variance) affect step-to-step variance in the trajectory of the swing foot. Motor flexibility was operationalized as an increase (baseline to cued) in total variance with an increase in good variance that exceeded the change in bad variance. There was no significant group × walking task interaction for total and good variance for OB vs NW, but there was a strong and significant interaction effect for OA vs YA (p < 0.01; Cohen's d > 1.0). Whereas YA reduced both good and bad variance, OA increased good variance beyond the change in bad variance. In OA, these changes were associated with several functional measures of mobility. Cued walking may place greater demands on OA requiring greater reliance on motor flexibility, although otherwise healthy older obese adults may be able to compensate for functional and cognitive declines associated with obesity by increasing motor flexibility under such tasks. The extent to which motor flexibility is employed during novel or constrained tasks may be a biomarker of healthy aging and a target for (re)habilitation.

Walking Speed Reliably Measures Clinically Significant Changes in Gait by Directional Deep Brain Stimulation.

Introduction: Although deep brain stimulation (DBS) often improves levodopa-responsive gait symptoms, robust therapies for gait dysfunction from Parkinson's disease (PD) remain a major unmet need. Walking speed could represent a simple, integrated tool to assess DBS efficacy but is often not examined systematically or quantitatively during DBS programming. Here we investigate the reliability and functional significance of changes in gait by directional DBS in the subthalamic nucleus. Methods: Nineteen patients underwent unilateral subthalamic nucleus DBS surgery with an eight-contact directional lead (1-3-3-1 configuration) in the most severely affected hemisphere. They arrived off dopaminergic medications >12 h preoperatively and for device activation 1 month after surgery. We measured a comfortable walking speed using an instrumented walkway with DBS off and at each of 10 stimulation configurations (six directional contacts, two virtual rings, and two circular rings) at the midpoint of the therapeutic window. Repeated measures of ANOVA contrasted preoperative vs. maximum and minimum walking speeds across DBS configurations during device activation. Intraclass correlation coefficients examined walking speed reliability across the four trials within each DBS configuration. We also investigated whether changes in walking speed related to modification of step length vs. cadence with a one-sample t-test. Results: Mean comfortable walking speed improved significantly with DBS on vs. both DBS off and minimum speeds with DBS on (p < 0.001, respectively). Pairwise comparisons showed no significant difference between DBS off and minimum comfortable walking speed with DBS on (p = 1.000). Intraclass correlations were ≥0.949 within each condition. Changes in comfortable walk speed were conferred primarily by changes in step length (p < 0.004). Conclusion: Acute assessment of walking speed is a reliable, clinically meaningful measure of gait function during DBS activation. Directional and circular unilateral subthalamic DBS in appropriate configurations elicit acute and clinically significant improvements in gait dysfunction related to PD. Next-generation directional DBS technologies have significant potential to enhance gait by individually tailoring stimulation parameters to optimize efficacy.

The timing of locomotor propulsion in healthy adults walking at multiple speeds.

In computational models of human walking, both magnitude and timing of locomotor propulsion are important for mechanical and metabolic efficiency, suggesting that these are likely tightly controlled by the neuromuscular system. Studies of actual human walking have focused primarily on magnitude-related measures of propulsion, often ignoring its timing. The purpose of this study was to quantify the timing of onset and peak propulsion relative to contralateral heel strike (HS) in healthy, young adults walking at multiple speeds. Propulsion was quantified at the ground-level using the anterior component of the anteroposterior ground reaction force, the limb-level using individual limb power, and the joint-level using ankle power. Contrary to common computational models, most of our timing-related measures indicated that propulsion occurred after contralateral HS. Timing-related measures of propulsion also changed with walking speed - as speed increased, individuals initiated propulsion earlier in the support phase. Timing of locomotor propulsion is theoretically important for walking performance, especially metabolic efficiency, and could therefore provide important clinical information. This study provides a set of relatively simple metrics that can be used to quantify propulsion and benchmark data that can be used for future comparisons with individuals or populations with gait impairments.

Lower extremity joints and muscle groups in the human locomotor system alter mechanical functions to meet task demand.

To facilitate movement through mechanically complex environments, terrestrial animals have evolved locomotor systems capable of flexibly altering internal mechanics to meet external demands. They do this by shifting imposed workloads between joints/muscle groups (central mechanical flexibility) and/or by altering the function of individual joints/muscle groups (local mechanical flexibility). In human locomotion research, central mechanical flexibility is well established and regularly reported. Local mechanical flexibility at major lower extremity joints and muscle groups, however, has received relatively less attention. We used an emerging biomechanical analysis known as functional indexing to test the hypothesis that lower extremity joints and muscle groups within the human locomotor system alter their mechanical function to meet altered locomotor demands. Thirteen healthy adults walked across a range of speeds (0.8, 1.2, 1.6, 2.0 m s-1) and slopes (0 deg, +5 deg, +10 deg) to determine whether hip, knee and ankle joints and their extensors and flexors altered their mechanical function in response to increased speed and slope. As walking speed increased, the knee and its extensors altered their function to behave more like mechanical springs while the ankle and its extensors altered their function to behave more like motors. As slope increased, all three joints and their extensors decreased spring- and damper-like behavior and increased motor-like behavior. Our results indicate that humans - similarly to many other terrestrial animals - utilize local mechanical flexibility to meet the demands of the locomotor task at hand.

Altered joint kinetic strategies of healthy older adults and individuals with Parkinson's disease to walk at faster speeds.

Individuals with Parkinson's disease (PD) exhibit poorer walking performance compared to healthy, age-matched adults. Lower extremity joint kinetics may provide insight into this performance deficit but are currently lacking in the PD literature, especially across multiple speeds. The primary purpose of this study was to compare joint kinetics between individuals with PD and healthy older adults at both comfortable and maximal walking speeds. Secondarily, we quantified relationships between joint kinetics and walking speeds within each group. Biomechanical gait analyses were conducted for 13 individuals with PD and 12 age-matched controls during comfortable (CWS) and maximal (MWS) speed walking. Relative contributions to total positive work from the hip, knee, and ankle were compared across groups and speeds. Within each group, relationships between relative joint work and CWS and MWS were also quantified. Significant group by speed interactions indicated that healthy older adults increased hip and decreased ankle relative work at MWS compared to CWS whereas relative work at all joints in PD group remained stable across speeds. In the older group, positive relationships were observed between relative hip work and MWS. In the PD group, negative relationships were observed between relative hip work and CWS and MWS. Healthy older adults disproportionately increased mechanical contributions from the hip at MWS compared to CWS. Individuals with PD did not exhibit similar disproportionate scaling of joint kinetics across speed conditions. Inability to appropriately scale joint kinetics in PD may represent an inflexible neuromuscular system in PD, which may limit walking performance in this population.

The relationships between physical capacity and biomechanical plasticity in old adults during level and incline walking.

Old compared to young adults exhibit increased hip and decreased ankle mechanical output during walking - a phenomenon known as biomechanical plasticity. Previous comparison studies suggest that low compared to high capacity old adults exhibit larger magnitudes of this plasticity, however the precise relationship between capacity and plasticity magnitude remains unclear. The purpose of this study was to quantify the relationships between physical capacity and biomechanical plasticity magnitude during level and incline walking. Data were collected for 32 old adults walking over level and inclined (+10°) surfaces at self-selected, comfortable speeds. Physical capacity was measured using the Short-Form Health Survey Physical Component (SF-36 PC) and biomechanical plasticity was quantified by ratios of hip extensor to ankle plantarfexor peak torques, angular impulses, peak positive powers, and positive work (larger ratios indicate larger magnitudes of plasticity). SF-36 PC scores correlated positively with all four biomechanical plasticity ratios during level walking and three of the four ratios during incline walking. Some of the biomechanical plasticity ratios correlated positively with comfortable walking speeds and stride frequencies, indicating better walking performance with larger magnitudes of plasticity. Additionally, all four biomechanical plasticity ratios were larger during incline compared to level walking, suggesting the need for larger magnitudes of plasticity during the more difficult task. These results indicate that larger magnitudes of biomechanical plasticity afford functional benefits such as increased level and incline walking performance for old adults. Increased walking performance has the potential to increase quality of life in the growing population of old adults.

Comparison of ankle kinematics and ground reaction forces between prospectively injured and uninjured collegiate cross country runners.

Biomechanical comparative studies on running-related injuries have included either currently or retrospectively injured runners. The purpose of this study was to prospectively compare ankle joint and ground reaction force variables between collegiate runners who developed injuries during the cross country season and those who did not. Running gait analyses using a motion capture system and force platform were conducted on 19 collegiate runners prior to the start of their cross country season. Ten runners sustained running-related injuries and 9 remained healthy during the course of the season. Strike index, peak loading rate of the vertical ground reaction force, dorsiflexion range of motion (ROM), eversion ROM, peak eversion angle, peak eversion velocity, and eversion duration from the start of the season were compared between injury groups. Ankle eversion ROM and peak eversion velocity were greater in uninjured runners while peak eversion angle was greater in injured runners. Greater ankle eversion ROM and eversion velocity with lower peak eversion angle may be beneficial in reducing injury risk in collegiate runners. The current data may only be applicable to collegiate cross country runners with similar training and racing schedules and threshold magnitudes of ankle kinematic variables to predict injury risk are still unknown.

Ankle and knee kinetics between strike patterns at common training speeds in competitive male runners.

The purpose of this study was to investigate the interaction of foot strike and common speeds on sagittal plane ankle and knee joint kinetics in competitive rear foot strike (RFS) runners when running with a RFS pattern and an imposed forefoot strike (FFS) pattern. Sixteen competitive habitual male RFS runners ran at two different speeds (i.e. 8 and 6 min mile(-1)) using their habitual RFS and an imposed FFS pattern. A repeated measures analysis of variance was used to assess a potential interaction between strike pattern and speed for selected ground reaction force (GRF) variables and, sagittal plane ankle and knee kinematic and kinetic variables. No foot strike and speed interaction was observed for any of the kinetic variables. Habitual RFS yielded a greater loading rate of the vertical GRF, peak ankle dorsiflexor moment, peak knee extensor moment, peak knee eccentric extensor power, peak dorsiflexion and sagittal plane knee range of motion compared to imposed FFS. Imposed FFS yielded greater maximum vertical GRF, peak ankle plantarflexor moment, peak ankle eccentric plantarflexor power and sagittal plane ankle ROM compared to habitual RFS. Consistent with previous literature, imposed FFS in habitual RFS reduces eccentric knee extensor and ankle dorsiflexor involvement but produce greater eccentric ankle plantarflexor action compared to RFS. These acute differences between strike patterns were independent of running speeds equivalent to typical easy and hard training runs in competitive male runners. Current findings along with previous literature suggest differences in lower extremity kinetics between habitual RFS and imposed FFS running are consistent among a variety of runner populations.

Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women.

Theacrine is a purine alkaloid found primarily in the leaves of the Camellia Kucha plant and is now included within dietary supplements. To compare the effects of a theacrine-containing dietary supplement with caffeine and placebo on energy and mood, as well as objective measures of cognitive performance, heart rate, and blood pressure, 10 healthy men (20.8 ± 0.7 years) and 10 healthy women (22.2 ± 1.1 years) ingested the dietary supplement TheaTrim (Purus Labs; containing a branded form of theacrine (Teacrine™) and caffeine (150 mg)), caffeine only (150 mg), or a placebo on three different days, separated by approximately one week. Before, and for up to 4 h following, ingestion of the assigned condition, subjects completed a subjective assessment of energy and mood, as well as tests of cognitive performance (trail making test (TMT), digit symbol substitution test (DSST)), and reaction time. Heart rate and blood pressure were measured. No condition or interaction effects were noted for TMT, DSST, or reaction time, despite a trend for improvement in selected variables with both TheaTrim and caffeine treatment. Condition effects or trends were noted for subjective feelings, with values for attentive, alert, focused, and energetic higher for TheaTrim than for placebo and caffeine, while values for lethargic and groggy were lower for TheaTrim than for placebo and caffeine. Heart rate and blood pressure were largely unaffected by treatment. These data indicate that TheaTrim treatment does not result in a statistically significant improvement in cognitive performance but may favorably impact multiple subjective feelings related to energy and mood.