Transcranial magnetic stimulation in non-human primates: A systematic review.

Transcranial magnetic stimulation (TMS) is widely employed as a tool to investigate and treat brain diseases. However, little is known about the direct effects of TMS on the brain. Non-human primates (NHPs) are a valuable translational model to investigate how TMS affects brain circuits given their neurophysiological similarity with humans and their capacity to perform complex tasks that approach human behavior. This systematic review aimed to identify studies using TMS in NHPs as well as to assess their methodological quality through a modified reference checklist. The results show high heterogeneity and superficiality in the studies regarding the report of the TMS parameters, which have not improved over the years. This checklist can be used for future TMS studies with NHPs to ensure transparency and critical appraisal. The use of the checklist would improve methodological soundness and interpretation of the studies, facilitating the translation of the findings to humans. The review also discusses how advancements in the field can elucidate the effects of TMS in the brain.

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.

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.

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.

Frontal Hemodynamic Response During Step Initiation Under Cognitive Conflict in Older and Young Healthy People.

Gait initiation is a daily challenge even for healthy individuals as it requires the timely coupling between the automatic anticipatory postural adjustment (APA) and the voluntary step according to the context. Modulation of this motor event has been thought to involve higher level brain control, including cognitive inhibitory circuitries. Despite the known participation of the supplementary motor area (SMA) in the modulation of some parameters of APA, the participation of areas controlling inhibition during gait initiation still needs to be investigated. In this study, the hemodynamic responses of the SMA and dorsolateral prefrontal cortex (DLPFC) were assessed using functional near-infrared spectroscopy (fNIRS) during a gait initiation task under cognitive conflict to select the foot to step (congruent [CON] and incongruent [INC] conditions). The older group (OG) showed worse inhibitory control than the young group (YG) along with more impairments in APA parameters. OG also had a lower amplitude of hemodynamic responses in both areas than YG in the INC. The INC increased the correlation between SMA and DLPFC only in the YG. Aging seems to impair the interaction between the hemodynamic responses of SMA and DLPFC, which influences APA performance in gait initiation under cognitive conflict.

Brain networks associated with anticipatory postural adjustments in Parkinson's disease patients with freezing of gait.

Specific impairments of anticipatory postural adjustment (APA) during step initiation have been reported in patients with Parkinson's disease (PD) and freezing of gait (FoG). Although APA disruption has been associated with FoG, there is scarce knowledge about its neural correlates. We sought to better understand the neural networks involved with APA in patients with FoG by assessing the level of hemodynamic response of specific brain regions and the functional connectivity during the leg lifting task. In the current investigation, APAs of patients with PD, with and without (nFoG) freezing were assessed during a leg lifting task in an event-related, functional magnetic resonance imaging (er-fMRI) protocol. Results identified a high hemodynamic response in the right anterior insula (AI) and supplementary motor area (SMA) in the FoG group when an APA was required. The nFoG had stronger connectivity between the right and left insulae than the FoG group. The strength of this connectivity was negatively correlated with the severity of FoG. Both groups showed different brain network organizations comprising the SMA and the bilateral AI. The SMA was found to be a hub in patients with FoG when an APA was required for the task. Our findings suggest that both groups used compensatory mechanism comprising the insulae during APA. Neither group used the entire network comprised of the insulae and SMA to accomplish the task. The FoG group relied more on SMA as a hub than as part of a broader network to exchange information during the APA.

Spinal Cord Stimulation for Freezing of Gait: From Bench to Bedside.

Spinal cord stimulation (SCS) has been used for the treatment of chronic pain for nearly five decades. With a high degree of efficacy and a low incidence of adverse events, it is now considered to be a suitable therapeutic alternative in most guidelines. Experimental studies suggest that SCS may also be used as a therapy for motor and gait dysfunction in parkinsonian states. The most common and disabling gait dysfunction in patients with Parkinson's disease (PD) is freezing of gait (FoG). We review the evolution of SCS for gait disorders from bench to bedside and discuss potential mechanisms of action, neural substrates, and clinical outcomes.

Short-term resistance training with instability reduces impairment in V wave and H reflex in individuals with Parkinson's disease.

This study had two objectives: 1) to compare the effects of 3 wk of resistance training (RT) and resistance training with instability (RTI) on evoked reflex responses at rest and during maximal voluntary isometric contraction (MVIC) of individuals with Parkinson's disease (PD) and 2) to determine the effectiveness of RT and RTI in moving values of evoked reflex responses of individuals with PD toward values of age-matched healthy control subjects (HCs) (z-score analysis). Ten individuals in the RT group and 10 in the RTI group performed resistance exercises twice a week for 3 wk, but only the RTI group included unstable devices. The HC group (n = 10) were assessed at pretest only. Evoked reflex responses at rest (H reflex and M wave) and during MVIC [supramaximal M-wave amplitude (Msup) and supramaximal V-wave amplitude (Vsup)] of the plantar flexors were assessed before and after the experimental protocol. From pretraining to posttraining, only RTI increased ratio of maximal H-reflex amplitude to maximal M-wave amplitude at rest (Hmax/Mmax), Msup, Vsup/Msup, and peak torque of the plantar flexors (P < 0.05). At posttraining, RTI was more effective than RT in increasing resting Hmax and Vsup and in moving these values to those observed in HCs (P < 0.05). We conclude that short-term RTI is more effective than short-term RT in modulating H-reflex excitability and in increasing efferent neural drive, approaching average values of HCs. Thus short-term RTI may cause positive changes at the spinal and supraspinal levels in individuals with PD. NEW & NOTEWORTHY Maximal H-reflex amplitude (Hmax) at rest and efferent neural drive [i.e., supramaximal V-wave amplitude (Vsup)] to skeletal muscles during maximal contraction are impaired in individuals with Parkinson's disease. Short-term resistance training with instability was more effective than short-term resistance training alone in increasing Hmax and Vsup of individuals with Parkinson's disease, reaching the average values of healthy control subjects.

Balance and fear of falling in subjects with Parkinson's disease is improved after exercises with motor complexity.

Resistance training with instability (RTI) uses exercises with high motor complexity that impose high postural control and cognitive demands that may be important for improving postural instability and fear of falling in subjects with Parkinson's disease (PD). Here, we hypothesized that: 1) RTI will be more effective than resistance training (RT) in improving balance (Balance Evaluation Systems Test [BESTest] and overall stability index [Biodex Balance System®]) and fear of falling (Falls Efficacy Scale-International [FES-I] score) of subjects with Parkinson's disease (PD); and 2) changes in BESTest and FES-I after RTI will be associated with changes in cognitive function (Montreal Cognitive Assessment [MoCA] score - previously published) induced by RTI. Thirty-nine subjects with moderate PD were randomly assigned to a nonexercising control, RT, and RTI groups. While RT and RTI groups performed progressive RT twice a week for 12 weeks, the RTI group added progressive unstable devices to increase motor complexity of the resistance exercises. There were significant group × time interactions for BESTest, overall stability index, and FES-I scores (P < 0.05). Only RTI improved BESTest, overall stability index and FES-I scores, and RTI was more effective than RT in improving biomechanical constraints and stability in gait (BESTest sections) at post-training (P < 0.05). There were strong correlations between relative changes in BESTest and MoCA (r = 0.72, P = 0.005), and FES-I and MoCA (r = -0.75, P = 0.003) after RTI. Due to the increased motor complexity in RTI, RTI is recommended for improving balance and fear of falling, which are associated with improvement in cognitive function of PD.

Keeping your balance while balancing a cylinder: interaction between postural and voluntary goals.

The present study investigated whether postural responses are influenced by the stability constraint of a voluntary, manual task. We also examined how task constraint and first experience (the condition with which the participants started the experiment) influence the kinematic strategies used to simultaneously accomplish a postural response and a voluntary task. Twelve healthy, older adults were perturbed during standing, while holding a tray with a cylinder placed with the flat side down (low constraint, LC) or with the rolling, round side down (high constraint, HC). Central set changed according to the task constraint, as shown by a higher magnitude of both the gastrocnemius and tibialis anterior muscle activation bursts in the HC than in the LC condition. This increase in muscle activation was not reflected, however, in changes in the center of pressure or center of mass displacement. Task constraint influenced the peak shoulder flexion for the voluntary tray task but not the peak hip flexion for the postural task. In contrast, first experience influenced the peak hip flexion but not the peak shoulder flexion. These results suggest an interaction between two separate control mechanisms for automatic postural responses and voluntary stabilization tasks.

The interaction of postural and voluntary strategies for stability in Parkinson's disease.

This study assessed the effects of stability constraints of a voluntary task on postural responses to an external perturbation in subjects with Parkinson's disease (PD) and healthy elderly participants. Eleven PD subjects and twelve control subjects were perturbed with backward surface translations while standing and performing two versions of a voluntary task: holding a tray with a cylinder placed with the flat side down [low constraint (LC)] or with the rolling, round side down [high constraint (HC)]. Participants performed alternating blocks of LC and HC trials. PD participants accomplished the voluntary task as well as control subjects, showing slower tray velocity in the HC condition compared with the LC condition. However, the latency of postural responses was longer in the HC condition only for control subjects. Control subjects presented different patterns of hip-shoulder coordination as a function of task constraint, whereas PD subjects had a relatively invariant pattern. Initiating the experiment with the HC task led to 1) decreased postural stability in PD subjects only and 2) reduced peak hip flexion in control subjects only. These results suggest that PD impairs the capacity to adapt postural responses to constraints imposed by a voluntary task.