Mesencephalic Locomotor Region and Presynaptic Inhibition during Anticipatory Postural Adjustments in People with Parkinson's Disease.

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have a loss of presynaptic inhibition (PSI) during anticipatory postural adjustments (APAs) for step initiation. The mesencephalic locomotor region (MLR) has connections to the reticulospinal tract that mediates inhibitory interneurons responsible for modulating PSI and APAs. Here, we hypothesized that MLR activity during step initiation would explain the loss of PSI during APAs for step initiation in FOG (freezers). Freezers (n = 34) were assessed in the ON-medication state. We assessed the beta of blood oxygenation level-dependent signal change of areas known to initiate and pace gait (e.g., MLR) during a functional magnetic resonance imaging protocol of an APA task. In addition, we assessed the PSI of the soleus muscle during APA for step initiation, and clinical (e.g., disease duration) and behavioral (e.g., FOG severity and APA amplitude for step initiation) variables. A linear multiple regression model showed that MLR activity (R2 = 0.32, p = 0.0006) and APA amplitude (R2 = 0.13, p = 0.0097) explained together 45% of the loss of PSI during step initiation in freezers. Decreased MLR activity during a simulated APA task is related to a higher loss of PSI during APA for step initiation. Deficits in central and spinal inhibitions during APA may be related to FOG pathophysiology.

Postural control of prolonged standing in people with Parkinson's disease.

People with Parkinson's disease (pwPD) have reduced adaptability to postural control during prolonged standing compared to neurologically healthy individuals (control). Objective. The study aimed to characterize postural changes during prolonged standing and their effect on postural control in pwPD compared to control. We recorded the body sway of the second lumbar vertebra of 23 pwPD and 23 control while they performed prolonged standing (15 min). The number and amplitude of the body sway patterns (shifts, fidgets, and drifts), the root mean square, velocity, and frequency of the body sway were analyzed. The number of shifts in the anterior-posterior (AP) and medial-lateral (ML) directions was greater for the pwPD than the control. In addition, the amplitudes of shifts in the AP direction and fidgets in the AP and ML directions were greater for the pwPD than the control. Our results show that: (1) A larger number of shifts of body sway suggest references positions are frequently changing; (2) Fidgets is a pumping mechanism and can be sensory-demand action to restore mechanoreceptors activity on the foot sole; and (3) No drift changes may suggest there is no slow migration of reference position. We conclude that pwPD exhibits different behavior than healthy ones during prolonged standing, suggesting that prolonged standing could distinguish individuals with Parkinson's disease.

Perturbation-based balance training leads to improved reactive postural responses in individuals with Parkinson's disease and freezing of gait.

Perturbation-based balance training (PBT) exposes individuals to a series of sudden upright balance perturbations to improve their reactive postural responses. In this study, we aimed to evaluate the effect of a short PBT program on body balance recovery following a perturbation in individuals with freezing of gait due to Parkinson's disease. Volunteers (mean age = 64 years, SD = 10.6) were pseudorandomly assigned either to a PBT (n = 9) or to a resistance training (RT, n = 10) group. PBT was implemented through balance perturbations varying in the kind, direction, side and magnitude of support base displacements. Both groups exercised with progressive difficulty/load activities twice a week for 4 weeks. Specific gains and generalization to dual-tasking and faster-than-trained support base displacements were evaluated 24 h after the end of the training, and retention was evaluated after 30 days of no training. Results showed that, compared with RT, PBT led to more stable postural responses in the 30-day retention evaluation, as indicated by decreased CoP displacement, velocity and time to direction reversal and reduced numbers of near-falls. We found no transfer either to a dual task or to a higher perturbation velocity. In conclusion, a training program based on diverse unpredictable balance perturbations improved the stability of reactive postural responses to those perturbations suffered during the training, without generalization to more challenging tasks.

Control of interjoint coordination in the performance of manual circular movements can explain lateral specialization.

Between-arm performance asymmetry can be seen in different arm movements requiring specific interjoint coordination to generate the desired hand trajectory. In the current investigation, we assessed between-arm asymmetry of shoulder-elbow coordination and its stability in the performance of circular movements. Participants were 16 healthy right-handed university students. The task consisted of performing cyclic circular movements with either the dominant right arm or the nondominant left arm at movement frequencies ranging from 40% of maximum to maximum frequency in steps of 15%. Kinematic analysis of shoulder and elbow motions was performed through an optoelectronic system in the three-dimensional space. Results showed that as movement frequency increased circularity of left arm movements diminished, taking an elliptical shape, becoming significantly different from the right arm at higher movement frequencies. Shoulder-elbow coordination was found to be asymmetric between the two arms across movement frequencies, with lower shoulder-elbow angle coefficients and higher relative phase for the left compared to the right arm. Results also revealed greater variability of left arm movements in all variables assessed, an outcome observed from low to high movement frequencies. From these findings, we propose that specialization of the left cerebral hemisphere for motor control resides in its higher capacity to generate appropriate and stable interjoint coordination leading to the planned hand trajectory.

Effect of freezing of gait and dopaminergic medication in the biomechanics of lower limbs in the gait of patients with Parkinson's disease compared to neurologically healthy.

INTRODUCTION: This study aims to evaluate the effects of medication, and the freezing of gait (FoG) on the kinematic and kinetic parameters of gait in people with Parkinson's disease (pwPD) compared to neurologically healthy. METHODS: Twenty-two people with a clinical diagnosis of idiopathic PD in ON and OFF medication (11 FoG), and 18 healthy participants (control) were selected from two open data sets. All participants walked on the floor on a 10-meter-long walkway. The joint kinematic and ground reaction forces (GRF) variables of gait and the clinical characteristics were compared: (1) PD with FoG (pwFoG) and PD without FoG (pwoFoG) in the ON condition and control; (2) PD with FoG and PD without FoG in the OFF condition and control; (3) Group (PD with FoG and PD without FoG) and Medication. RESULTS: (1) FoG mainly affects distal joints, such as the ankle and knee; (2) PD ON showed changes in the range of motion of both distal and proximal joints, which may explain the increase in step length and gait speed expected with the use of L-Dopa; and (3) the medication showed improvements in the kinematic and kinetic parameters of the gait of people with pwFoG and pwoFoG equally; (4) pwPD showed a smaller second peak of the vertical component of the GRF than the control. CONCLUSION: The presence of FoG mainly affects distal joints, such as the ankle and knee. PD presents a lower application of GRF during the impulse period than healthy people, causing lower gait performances.

A public data set of walking full-body kinematics and kinetics in individuals with Parkinson's disease.

Background: To our knowledge, there is no Parkinson's disease (PD) gait biomechanics data sets available to the public. Objective: This study aimed to create a public data set of 26 idiopathic individuals with PD who walked overground on ON and OFF medication. Materials and methods: Their upper extremity, trunk, lower extremity, and pelvis kinematics were measured using a three-dimensional motion-capture system (Raptor-4; Motion Analysis). The external forces were collected using force plates. The results include raw and processed kinematic and kinetic data in c3d and ASCII files in different file formats. In addition, a metadata file containing demographic, anthropometric, and clinical data is provided. The following clinical scales were employed: Unified Parkinson's disease rating scale motor aspects of experiences of daily living and motor score, Hoehn & Yahr, New Freezing of Gait Questionnaire, Montreal Cognitive Assessment, Mini Balance Evaluation Systems Tests, Fall Efficacy Scale-International-FES-I, Stroop test, and Trail Making Test A and B. Results: All data are available at Figshare (https://figshare.com/articles/dataset/A_dataset_of_overground_walking_full-body_kinematics_and_kinetics_in_individuals_with_Parkinson_s_disease/14896881). Conclusion: This is the first public data set containing a three-dimensional full-body gait analysis of individuals with PD under the ON and OFF medication. It is expected to contribute so that different research groups worldwide have access to reference data and a better understanding of the effects of medication on gait.

Cognitive and emotional factors influence specific domains of postural control in individuals with moderate-to-severe Parkinson's disease.

INTRODUCTION: Cognition and emotional state are domains that highly interfere with postural control in individuals with Parkinson's disease (PD). This study aims to find associations between executive function, anxiety, depression, and reactive and anticipatory postural control domains in individuals with moderate-to-severe Parkinson's disease. METHODS: In this study, 34 individuals with PD while on medication were thoroughly assessed for postural control in perturbed, quiet standing and stepping. We performed multiple linear stepwise regressions using postural variables as dependent and cognitive/emotional as independent variables. RESULTS: The results showed that cognitive flexibility explained 23 % of anticipatory postural adjustments (APA) duration, inhibitory control explained 42 % of instability on a malleable surface, anxiety explained 21 % of APA amplitude, and 38 % of reactive postural response amplitude. CONCLUSION: Our results highlight the impact of emotional and cognitive states on particular domains of postural control in individuals with PD while on medication. These results may have significant implications for future treatments, mainly considering the predictors for postural control domains, which were consistent with the assumption that impairments in affective and executive domains underlie posture. As we have shown that cognitive and emotional states influence postural control domains in individuals with PD, this should be taken into account in rehabilitation protocols.

Freezing of gait, gait initiation, and gait automaticity share a similar neural substrate in Parkinson's disease.

Individuals with Parkinson's disease (PD) and freezing of gait (FOG) have difficulty initiating and maintaining a healthy gait pattern; however, the relationship among FOG severity, gait initiation, and gait automaticity, in addition to the neural substrate of this relationship has not been investigated. This study investigated the association among FOG severity during turning (FOG-ratio), gait initiation (anticipatory postural adjustment [APA]), and gait automaticity (dual-task cost [DTC]), and the neural substrates of these associations. Thirty-four individuals with FOG of PD were assessed in the ON-medication state. FOG-ratio during a turning test, gait automaticity using DTC on stride length and gait speed, and APA during an event-related functional magnetic resonance imaging protocol to assess brain activity from the regions of interest (e.g., dorsolateral prefrontal cortex [DLPFC] and mesencephalic locomotor region [MLR]) were assessed in separated days. Results showed that FOG-ratio, APA amplitude, and DTC on stride length are negatively associated among them (P < 0.05). APA amplitude and DTC on stride length explained 59% of the FOG-ratio variance (P < 0.05). Although the activity of the right DLPFC and right MLR explained 55% of the FOG-ratio variance (P < 0.05) and 30% of the DTC on stride length variance (P ≤ 0.05), only the activity of the right MLR explained 23% of the APA amplitude (P < 0.05). FOG severity during turning, APA amplitude, and stride length automaticity are associated among them and share a similar locomotor substrate, as the MLR activity was a common brain region in explaining the variance of these variables.

Caffeine Increases Endurance Performance via Changes in Neural and Muscular Determinants of Performance Fatigability.

PURPOSE: In the present study, we tested the hypothesis that caffeine would increase endurance performance via attenuation of neural and muscular determinants of performance fatigability during high-intensity, whole-body exercise. METHODS: Ten healthy males cycled until exhaustion (89% ± 2% of V̇O2max) after the ingestion of caffeine or placebo. During another four visits, the same exercise was performed after either caffeine or placebo ingestion but with exercise discontinued after completing either 50% or 75% of the duration of placebo trial. An additional trial with caffeine ingestion was also performed with interruption at the placebo time to exhaustion (isotime). Performance fatigability was measured via changes in maximal voluntary contraction, whereas neural and muscular determinants of performance fatigability were quantified via preexercise to postexercise decrease in quadriceps voluntary activation (VA) and potentiated twitch force, respectively. RESULTS: Compared with the placebo, caffeine increased time to exhaustion (+14.4 ± 1.6%, P = 0.017, 314.4 ± 47.9 vs 354.9 ± 40.8 s). Caffeine did not change the rate of decline in maximal voluntary contraction (P = 0.209), but caffeine reduced the twitch force decline at isotime when stimulating at single twitch (-58.6 ± 22.4 vs -45.7 ± 21.9%, P = 0.014) and paired 10 Hz electrical stimuli (-37.3 ± 13.2 vs -28.2 ± 12.9%, P = 0.025), and reduced the amplitude of electromyography signal during cycling at isotime (P = 0.034). The decline in VA throughout the trial was lower (P = 0.004) with caffeine (-0.5 ± 4.2%) than with placebo (-5.8 ± 8.5%). Caffeine also maintained peripheral oxygen saturation at higher levels (95.0 ± 1.9%) than placebo (92.0 ± 6.2%, P = 0.016). CONCLUSIONS: Caffeine ingestion improves performance during high-intensity, whole-body exercise via attenuation of exercise-induced reduction in VA and contractile function.

Between-leg asymmetry in automatic postural responses to stance perturbations in people with Parkinson's disease.

BACKGROUND: People with Parkinson's disease (PwPD) showed impairments of balance control which can be aggravated by the presence of higher interlateral postural asymmetry caused by a distinct dopaminergic loss in the substantia nigra between cerebral hemispheres. RESEARCH QUESTION: We evaluate asymmetries between the more and the less affected leg in PwPD in responses to unanticipated stance perturbations. METHODS: Sixteen 16 PwPD participated in the experiment that consisted of recovering a stable upright stance, keeping the feet in place, in response to a perturbation caused by a sudden release of a load equivalent to 7 % of the participant's body mass. Anterior displacement and velocity of the center of pressure (CoP), the latency of gastrocnemius medialis muscle (GM) activation onset, rate of GM activation, and normalized magnitude of muscular activation were analyzed. RESULTS: Analysis revealed significantly rate (p = 0.04) and magnitude (p = 0.02) higher activation of GM in the less affected limb. No significant effects of the leg were found for GM activation latency or CoP-related variables. SIGNIFICANCE: There is a higher contribution of the less affected leg in automatic postural responses in PwPD.

Kinematics predictors of spatiotemporal parameters during gait differ by age in healthy individuals.

Joint biomechanics and spatiotemporal gait parameters change with age or disease and are used in treatment decision-making. RESEARCH QUESTION: To investigate whether kinematic predictors of spatiotemporal parameters during gait differ by age in healthy individuals. METHODS: We used an open dataset with the gait data of 114 young adults (M = 28.0 years, SD = 7.5) and 128 older adults (M = 67.5 years, SD = 3.8) walking at a comfortable self-selected speed. Linear regression models were developed to predict spatiotemporal parameters separately for each group using joint kinematics as independent variables. RESULTS: In young adults, knee flexion loading response and hip flexion/extension were the common predictors of gait speed; hip flexion and hip extension contributed to explaining the stride length; hip flexion contributed to explaining the cadence and stride time. In older adults, ankle plantarflexion, knee flexion loading response, and pelvic rotation were the common predictors of the gait speed; ankle plantarflexion and knee flexion loading response contributed to explaining the stride length; ankle plantarflexion loading response and ankle plantarflexion contributed to explain the cadence, stride width and stride time. SIGNIFICANCE: Our results suggest that the ability of joint kinematic variables to estimate spatiotemporal parameters during gait differs by age in healthy individuals. Particularly in older adults, ankle plantarflexion was the common predictor of the spatiotemporal parameters, suggesting the importance of the ankle for gait parameters in this age group. This provides insight for clinicians into the most effective evaluation and has been used by physical professionals in prescribing the most appropriate exercises to attenuate the effects produced by age-related neuromuscular changes.

A systematic review on the effectiveness of perturbation-based balance training in postural control and gait in Parkinson's disease.

BACKGROUND: Pharmacological and surgical interventions do not improve postural control and gait effectively in people with Parkinson's disease (PD). An innovative and promising therapeutic intervention is perturbation-based balance training (PBT). OBJECTIVE: To perform a systematic review to summarise the current evidence for PBT on postural control and gait in people with PD. Intervention studies including PBT, in isolation or associated with other physical interventions, were included. LITERATURE SURVEY: PubMed, SciELO, PEDro and Cochrane databases were searched between June 2000 and March 2020. METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and is registered in the PROSPERO database (CRD42020203961). The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation. Studies were assessed for methodological quality using the PEDro scale. Two of the authors reviewed the search results and selected studies using predefined selection criteria. No restrictions based on severity of PD, time since diagnosis or age were used. SYNTHESIS: Eleven studies were selected for final evaluation. Most outcomes were downgraded in quality of evidence, mainly because of publication bias and limitations. The most consistent results indicate that PBT can improve postural control and gait in people with PD, including a reduction in the number of falls and a decrease in the severity of PD. CONCLUSION: PBT may be a promising option for the treatment of people with PD, and an adjunct to conventional physiotherapeutic treatment. However, deficiencies in the methodological quality and quality of evidence of studies included in this review have limited the reliability of the conclusions. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020203961.

Gait and posture are correlated domains in Parkinson's disease.

Establishing a relationship between gait and posture in patients with Parkinson's disease (PD) is essential for PD treatment and rehabilitation. While previous studies have indicated that gait and posture are independent domains in PD, shared neuromechanisms related to gait and posture control and previous studies investigating the relationship between gait and posture parameters in stroke survivors and neurologically healthy older adults have shown a correlated domain. Thus, this study analyzed the relationship of gait and posture domains, primarily through gait temporal sub-phases (i.e., double support and stance phases) and step width. We analyzed the spatial-temporal gait parameters at the self-selected velocity and center of pressure (CoP) during quiet standing of 22 idiopathic PD participants under and without dopaminergic medication conditions. The association between quiet standing and gait variables was assessed through the Spearman test, controlled by age, disease duration, NFoG-Q, and levodopa dosage. In ON medication, CoP area showed a significant correlation with stance phase and total double support; and RMS ML CoP showed a significant correlation with stance phase, total double support, and step width. In OFF medication, CoP area, RMS AP CoP, RMS ML CoP, and ML CoP velocity significantly correlated with stance phase and total double support. By showing the relationship between gait and posture domains in PD, our study adds novel knowledge about the shared gait-posture control, which could collaborate with new approaches during mobility treatment and assessment.

Biomechanical aspects that precede freezing episode during gait in individuals with Parkinson's disease: A systematic review.

BACKGROUND: The freezing episode (FE) management during gait in Parkinson's disease is inefficient with current medications, neurosurgery, and physical interventions. Knowing the biomechanical change patients suffer preceding FE would be the ultimate goal to measure, predict, and prevent these events. OBJECTIVE: We performed a systematic review to summarize the kinematic, kinetic, electromyographic, and spatio-temporal characteristics of the events that precede the FE during gait in Parkinson's disease. LITERATURE SURVEY: Databases searched included PubMed, Embase, and Cochrane and between 2001 to August 2021. METHODOLOGY: The present study was a systematic review registered in the PROSPERO database (CRD42021255082). Three reviewers searched and selected studies with methodologies involving biomechanical changes and kinetic, kinematic, electromyography, and spatiotemporal changes before FE in a patient with Parkinson's disease. The relevant articles that show the events preceding FE in patients with PD were identified. We excluded studies that describe or compare methods or algorithms to detect FE. Studies may include participants with all PD severity, time of disease, and age. SYNTHESIS: We selected ten articles for final evaluation. The most consistent results indicate a dramatic reduction of movement excursions with (1) decrease in stride length; (2) decreased gait speed; (3) postural instability with the increased double support phase; (4) incoordination of anterior tibial and gastrocnemius; (5) larger amplitude in the EMG of biceps femoris; (6) decreased range of motion in the sagittal plane at the ankle and hip joints; and (7) anterior pelvic tilt. CONCLUSION: FE is characterized by complex motor patterns than normal gait and mismatched gains in the perception and execution of the ongoing movement.

Differential activation of the plantar flexor muscles in balance control across different feet orientations on the ground.

The ankle plantar flexor muscles act synergistically to control quiet and dynamic body balance. Previous research has shown that the medial (MG) and lateral (LG) gastrocnemii, and soleus (SOL) are differentially activated as a function of motor task requirements. In the present investigation, we evaluated modulation of the plantar flexors' activation from feet orientation on the ground in an upright stance and the ensuing reactive response to a perturbation. A single group of young participants (n = 24) was evaluated in a task requiring initial stabilization of body balance against a backward pulling load (5% or 10% of body weight) attached to their trunk, and then the balance was suddenly perturbed, releasing the load. Four feet orientations were compared: parallel (0°), outward orientation at 15° and 30°, and the preferred orientation (M = 10.5°). Results revealed a higher activation magnitude of SOL compared to MG-LG when sustaining quiet balance against the 10% load. In the generation of reactive responses, MG was characterized by earlier, steeper, and proportionally higher activation than LG-SOL. Feet orientation at 30° led to higher muscular activation than the other orientations, while the activation relationship across muscles was unaffected by feet orientation. Our results support the conclusion of task-specific differential modulation of the plantar flexor muscles for balance control.

The effects of levodopa in the spatiotemporal gait parameters are mediated by self-selected gait speed in Parkinson's disease.

In individuals with Parkinson's disease (PD), the medication induces different and inconsistent results in the spatiotemporal parameters of gait, making it difficult to understand its effects on gait. As spatiotemporal gait parameters have been reported to be affected by gait speed, it is essential to consider the gait speed when studying walking biomechanics to interpret the results better when comparing the gait pattern of different conditions. Since the medication alters the self-selected gait speed of individuals with PD, this study analysed whether the change in gait speed can explain the selective effects of l-DOPA on the spatiotemporal parameters of gait in individuals with PD. We analysed the spatiotemporal gait parameters at the self-selected speed of 22 individuals with PD under ON and OFF states of l-DOPA medication. Bayesian mediation analysis evaluated which gait variables were affected by the medication state and checked if those effects were mediated by speed changes induced by medication. The gait speed was significantly higher among ON compared with OFF medication. All the spatiotemporal parameters of the gait were mediated by speed, with proportions of mediation close to 1 (effect entirely explained by speed changes). Our results show that a change in gait speed better explains the changes in the spatiotemporal gait parameters than the ON-OFF phenomenon. As an implication for rehabilitation, our results suggest that it is possible to assess the effect of l-DOPA on improving motor symptoms related to gait disorders by measuring gait speed.