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.

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.

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.

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.

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.

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.