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.

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.

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.

Preserved flexibility of dynamic postural control in individuals with Parkinson's disease.

BACKGROUND: Continuous oscillation of the support base requires anticipatory and reactive postural adjustments to maintain a stable balance. In this context, postural control flexibility or the ability to adjust balance mechanisms following the requirements of the environment is needed to counterbalance the predictable, continuous perturbation of body balance. Considering the inflexibility of postural responses in individuals with Parkinson's disease (PD), maintaining stability in the support base's continuous oscillations may be challenging. Varying the frequency of platform oscillation is an exciting approach to assess the interactions between reactive and anticipatory adjustments. RESEARCH QUESTION: This study aimed to analyze postural responses of individuals with PD on an oscillatory support base across different frequencies. METHODS: Thirty participants with moderate PD diagnosis (M = 64.47 years, SD = 8.59; Hoehn and Yahr scale 3) and fifteen healthy age-matched controls (M = 65.8 years, SD = 4.2) were tested. Subjects maintained a dynamic balance on a platform oscillating in sinusoidal translations. Four oscillation frequencies were evaluated in different trials that ranged from 0.2 to 0.8 Hz in steps of 0.2 Hz. RESULTS: Analysis showed similar performance between PD and healthy participants, with modulation of amplitudes of head displacement, center of pressure, center of mass and feet-head coordination to platform oscillation frequency. DISCUSSION: Our findings suggest a preserved ability of individuals with PD to dynamically control body balance on a support base with predictable oscillatory translations.

Age-Related Changes in Presynaptic Inhibition During Gait Initiation.

Age-related changes in presynaptic inhibition (PSI) have not been observed during gait initiation, which requires anticipatory postural adjustment (APA). As APA is centrally modulated and is impaired in older compared to young adults, here we aimed to study the presynaptic control and co-contraction levels in the ankle muscles during gait initiation in older compared to young adults. Fifteen older (age range 65-80 years) and 15 young adults (age range 19-30 years) performed a gait initiation task on a force platform under 3 conditions: (i) without electrical stimulation; (ii) test Hoffman reflex (H-reflex); and (iii) conditioned H-reflex. H-reflexes were evoked on the soleus muscle when the APA amplitude exceeded 10%-20% of the average baseline mediolateral force. Participants also performed quiet stance as a control task. Results showed that both age groups presented similar PSI levels during quiet stance (p = .941), while in the gait initiation older adults presented higher PSI levels, longer duration, and lower amplitude of APA than young adults (p < .05). Older adults presented higher co-contraction ratio in both tasks than young adults (p < .05). Correlations between the PSI levels and the APA amplitude (r = -0.61, p = .008), and between the PSI levels and the co-contraction ratio during gait initiation (r = -0.64, p = .005) were found for older adults only. APA amplitude explained 49% of the variance of the PSI levels (p = .003). Our findings suggest that older compared to young adults have increased presynaptic control to compensate for the decreased supraspinal modulation on impaired APAs during gait initiation.

Is freezing of gait correlated with postural control in patients with moderate-to-severe Parkinson's disease?

Freezing of gait (FoG) is one of the main reasons for movement initiation disorders and abnormal coupling of posture and gait in Parkinson's disease (PD). Patients with FoG have poor postural control when compared to patients without FoG. However, the nature of the interrelationship between FoG and domains of postural control remains unknown. The aim of this study was to estimate the association between different domains of postural control and severity of FoG in patients with moderate-to-severe PD. Thirty patients with idiopathic PD with FoG (age range 45-80 years, Hoehn & Yahr stages 3 and 4) participated in the study. We evaluated objective (FoG-ratio during turning task) and subjective (New Freezing of Gait Questionnaire, NFoG-Q) measures of FoG severity, reactive postural adjustments in response to an external perturbation, first step anticipatory adjustment for step initiation and quiet standing stability. In the multiple regression analysis, step initiation was the strongest significant correlation of the NFoG-Q score explaining 23% of the variance of the assessment. For the objective FoG measure, mediolateral CoP amplitude in quiet standing and mediolateral CoP amplitude in step initiation explained 39% of the variance of the FoG-ratio. As main conclusions, this study identified the association between objective and subjective measure for FoG severity and postural control domains. The results support conducting step initiation training during rehabilitation of individuals with FoG.

A Randomized, Controlled Trial of Exercise for Parkinsonian Individuals With Freezing of Gait.

BACKGROUND: Exercises with motor complexity induce neuroplasticity in individuals with Parkinson's disease (PD), but its effects on freezing of gait are unknown. The objective of this study was to verify if adapted resistance training with instability - exercises with motor complexity will be more effective than traditional motor rehabilitation - exercises without motor complexity in improving freezing-of-gait severity, outcomes linked to freezing of gait, and brain function. METHODS: Freezers were randomized either to the adapted resistance training with instability group (n = 17) or to the active control group (traditional motor rehabilitation, n = 15). Both training groups performed exercises 3 times a week for 12 weeks. The primary outcome was the New Freezing of Gait Questionnaire. Secondary outcomes were freezing of gait ratio (turning task), cognitive inhibition (Stroop-III test), motor signs (Unified Parkinson's Disease Rating Scale part-III [UPDRS-III]), quality of life (PD Questionnaire 39), anticipatory postural adjustment (leg-lifting task) and brain activation during a functional magnetic resonance imaging protocol of simulated anticipatory postural adjustment task. Outcomes were evaluated before and after interventions. RESULTS: Only adapted resistance training with instability improved all the outcomes (P < 0.05). Adapted resistance training with instability was more effective than traditional motor rehabilitation (in improving freezing-of-gait ratio, motor signs, quality of life, anticipatory postural adjustment amplitude, and brain activation; P < 0.05). Our results are clinically relevant because improvement in the New Freezing of Gait Questionnaire (-4.4 points) and UPDRS-III (-7.4 points) scores exceeded the minimally detectable change (traditional motor rehabilitation group data) and the moderate clinically important difference suggested for PD, respectively. The changes in mesencephalic locomotor region activation and in anticipatory postural adjustment amplitude explained the changes in New Freezing of Gait Questionnaire scores and in freezing-of-gait ratio following adapted resistance training with instability, respectively. CONCLUSIONS: Adapted resistance training with instability is able to cause significant clinical improvement and brain plasticity in freezers. © 2020 International Parkinson and Movement Disorder Society.

Loss of presynaptic inhibition for step initiation in parkinsonian individuals with freezing of gait.

KEY POINTS: Individuals with freezing of gait (FoG) due to Parkinson's disease (PD) have small and long anticipatory postural adjustments (APAs) associated with delayed step initiation. Individuals with FoG ('freezers') may require functional reorganization of spinal mechanisms to perform APAs due to supraspinal dysfunction. As presynaptic inhibition (PSI) is centrally modulated to allow execution of supraspinal motor commands, it may be deficient in freezers during APAs. We show that freezers presented PSI in quiet stance (control task), but they presented loss of PSI (i.e. higher ratio of the conditioned H-reflex relative to the test H-reflex) during APAs before step initiation (functional task), whereas non-freezers and healthy control individuals presented PSI in both the tasks. The loss of PSI in freezers was associated with both small APA amplitudes and FoG severity. We hypothesize that loss of PSI during APAs for step initiation in freezers may be due to FoG. ABSTRACT: Freezing of gait (FoG) in Parkinson's disease involves deficient anticipatory postural adjustments (APAs), resulting in a cessation of step initiation due to supraspinal dysfunction. Individuals with FoG ('freezers') may require functional reorganization of spinal mechanisms to perform APAs. As presynaptic inhibition (PSI) is centrally modulated to allow execution of supraspinal motor commands, here we hypothesized a loss of PSI in freezers during APA for step initiation, which would be associated with FoG severity. Seventy individuals [27 freezers, 22 non-freezers, and 21 age-matched healthy controls (HC)] performed a 'GO'-commanded step initiation task on a force platform under three conditions: (1) without electrical stimulation, (2) test Hoffman reflex (H-reflex) and (3) conditioned H-reflex. They also performed a control task (quiet stance). In the step initiation task, the H-reflexes were evoked on the soleus muscle when the amplitude of the APA exceeded 10-20% of the mean baseline mediolateral force. PSI was quantified by the ratio of the conditioned H-reflex relative to the test H-reflex in both the tasks. Objective assessment of FoG severity (FoG-ratio) was performed. Freezers presented lower PSI levels during quiet stance than non-freezers and HC (P < 0.05). During step initiation, freezers presented loss of PSI and lower APA amplitudes than non-freezers and HC (P < 0.05). Significant correlations were only found for freezers between loss of PSI and FoG-ratio (r = 0.59, P = 0.0005) and loss of PSI and APA amplitude (r = -0.35, P < 0.036). Our findings suggest that loss of PSI for step initiation in freezers may be due to FoG.

Young and older adults adapt automatic postural responses equivalently to repetitive perturbations but are unable to use predictive cueing to optimize recovery of balance stability.

Processing of contextual cues has been proposed to modulate the generation of automatic postural responses to unanticipated balance perturbations. In this investigation, we compared young and older individuals in responses to sudden rotations of the support base inducing either planti- or dorsiflexion of the ankles. Assessment was made in conditions resulting from the combination of visual directional cueing of the forthcoming platform rotation, and block versus random sequences of platform rotation directions. Results showed that, for both rotation directions, the block sequence led to reduced magnitude of activation of distal agonist muscles and direction-specific modulation of ground reaction forces to recover body balance. Visual directional cueing, conversely, failed to modulate either muscular responses or forces applied to the support base through the feet for balance recovery. Effects were similar between ages, suggesting that aging does not increase the influence of cognition on the generation of automatic postural responses, and that adaptation to repeated postural perturbations over trials is preserved in healthy older individuals.

Effects of spinal cord stimulation on postural control in Parkinson's disease patients with freezing of gait.

Freezing of gait (FoG) in Parkinson's disease (PD) is an incapacitating transient phenomenon, followed by continuous postural disorders. Spinal cord stimulation (SCS) is a promising intervention for FoG in patients with PD, however, its effects on distinct domains of postural control is not well known. The aim of this study is to assess the effects of SCS on FoG and distinct domains of postural control. Four patients with FoG were implanted with SCS systems in the upper thoracic spine. Anticipatory postural adjustment (APA), reactive postural responses, gait and FoG were biomechanically assessed. In general, the results showed that SCS improved FoG and APA. However, SCS failed to improve reactive postural responses. SCS seems to influence cortical motor circuits, involving the supplementary motor area. On the other hand, reactive posture control to external perturbation that mainly relies on neuronal circuitries involving the brainstem and spinal cord, is less influenced by SCS.

Measuring cortical motor hemodynamics during assisted stepping - An fNIRS feasibility study of using a walker.

Walkers are commonly prescribed worldwide to individuals unable to walk independently. Walker usage leads to improved postural control and voluntary movement during step. In the present study, we aimed to provide a concept-proof on the feasibility of an event-related protocol integrating the analyses of biomechanical variables of step initiation and functional near-infrared spectroscopy (fNIRS) to measure activation of the supplementary motor area (SMA) while using a walker. Healthy young participants were tested while stepping with versus without the use of the walker. Behavioral analysis showed that anticipatory postural adjustments (APA) decreased when supporting the body weight on the walker. Delta (without-with) of activation magnitude of the muscle tibialis anterior was positively correlated to the delta of deoxyhemoglobin concentration changes in the SMA. The novelty of this study is the development of a protocol to assess brain function together with biomechanical analysis during the use of a walker. The method sheds light to the potential utility of combining fNIRS and biomechanical assessment during assistive step initiation, which can represent a new opportunity to study populations with mobility deficits.

An fMRI-compatible force measurement system for the evaluation of the neural correlates of step initiation.

Knowledge of brain correlates of postural control is limited by the technical difficulties in performing controlled experiments with currently available neuroimaging methods. Here we present a system that allows the measurement of anticipatory postural adjustment of human legs to be synchronized with the acquisition of functional magnetic resonance imaging data. The device is composed of Magnetic Resonance Imaging (MRI) compatible force sensors able to measure the level of force applied by both feet. We tested the device in a group of healthy young subjects and a group of elderly subjects with Parkinson's disease using an event-related functional MRI (fMRI) experiment design. In both groups the postural behavior inside the magnetic resonance was correlated to the behavior during gait initiation outside the scanner. The system did not produce noticeable imaging artifacts in the data. Healthy young people showed brain activation patterns coherent with movement planning. Parkinson's disease patients demonstrated an altered pattern of activation within the motor circuitry. We concluded that this force measurement system is able to index both normal and abnormal preparation for gait initiation within an fMRI experiment.

Precueing time but not direction of postural perturbation induces early muscular activation: comparison between young and elderly individuals.

In this study, we evaluated the effect of precueing characteristics of an impending perturbation to upright stance on reactive responses of distal leg muscles. Young and older individuals were compared in a task of recovering stable upright stance following rotation of the supporting platform to induce anterior or posterior body sway. Directions of the supporting platform rotation were randomized across trials. Immediately before postural perturbation participants were cued about direction and/or time of platform rotation, or performed the task under directional and temporal uncertainty of the impending perturbation. Results showed that precueing time of perturbation led to earlier muscular activation onset, while precueing perturbation direction did not modulate either latency or magnitude of muscular activation. Those effects were similar between age groups. Our findings suggest that awareness of the perturbation time favored shorter response latencies in both the young and older individuals.

Aging increases flexibility of postural reactive responses based on constraints imposed by a manual task.

This study compared the effect of stability constraints imposed by a manual task on the adaptation of postural responses between 16 healthy elderly (mean age = 71.56 years, SD = 7.38) and 16 healthy young (mean age = 22.94 years, SD = 4.82) individuals. Postural stability was perturbed through unexpected release of a load attached to the participant's trunk while performing two versions of a voluntary task: holding a tray with a cylinder placed with its flat side down (low constraint) or with its rolling round side down (high constraint). Low and high constraint tasks were performed in alternate blocks of trials. Results showed that young participants adapted muscular activation and kinematics of postural responses in association with previous experience with the first block of manual task constraint, whereas the elderly modulated postural responses based on the current manual constraint. This study provides evidence for flexibility of postural strategies in the elderly to deal with constraints imposed by a manual task.

Resistance strength training's effects on late components of postural responses in the elderly.

The effect of resistance strength training on different phases of reactive postural responses to upright-stance perturbation was assessed in elderly women. Perturbation to body balance was produced by fast arm movements aiming at lifting different loads in either certain or uncertain contexts. Results from center-of-pressure analysis showed that lifting a light load under uncertainty led to more body sway than under certainty. Resistance strength training led to short periods of body sway in the compensation phase and to decreased variability in the stabilization phase of postural responses. These results suggest that neuromuscular adaptation from resistance strength training benefits late phases of postural responses to perturbation of body balance in the elderly.