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.

The impact of comorbidities and COVID-19 on the evolution of community onset sepsis.

Sepsis is a disease with high mortality and morbidity despite advances in diagnostic procedures and therapeutic strategies. The aim of this study was to evaluate the profile and outcomes of community-onset sepsis. This retrospective, multicenter study included five 24-h health care units and was conducted from January 2018 to December 2021. Patients were diagnosed with sepsis or septic shock according to the Sepsis 3.0 criterion. A total of 2630 patients diagnosed as having sepsis (68.4%, 1800) or septic shock (31.6%, 830) in the 24-h health care unit were included; 43.76% of the patients were admitted to the intensive care unit, 12.2% died, 4.1% had sepsis and 30% had septic shock. The comorbidities that were independent predictors of septic shock were chronic kidney disease on dialysis (CKD-d), bone marrow transplantation and neoplasia. CKD and neoplasia were also independent predictors of mortality, with ORs of 2.00 (CI 1.10-3.68) p = 0.023 and 1.74 (CI 1.319-2.298) p = < 0.0001, respectively. Mortality according to the focus of primary infection was as follows: pulmonary 40.1%; COVID-19 35.7%; abdominal 8.1% and urinary 6.2%. Mortality due to the COVID-19 outbreak had an OR of 4.94 (CI 3.08-8.13) p ≤ 0.0001. Even though community-onset sepsis can be potentially fatal, this study revealed that some comorbidities lead to an increased risk of septic shock (d-CKD and neoplasia) and mortality. COVID-19 infection as the primary focus was an independent predictor of mortality in patients with sepsis when compared to other foci.

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.

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.

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.

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.

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.

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.

The Adapted Resistance Training with Instability Randomized Controlled Trial for Gait Automaticity.

BACKGROUND: Deficits in the cerebellar locomotor region (CLR) have been associated with loss of gait automaticity in individuals with freezing of gait in Parkinson's disease (freezers); however, exercise interventions that restore gait automaticity in freezers are lacking. We evaluated the effects of the adapted resistance training with instability ([ARTI] complex exercises) compared with traditional motor rehabilitation (without complex exercises) on gait automaticity and attentional set-shifting. We also verified associations between gait automaticity change and CLR activation change previously published. METHODS: Freezers were randomized either to the experimental group (ARTI, 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. Gait automaticity (dual-task and dual-task cost [DTC] on gait speed and stride length), single-task gait speed and stride length, attentional set-shifting (time between Trail Making Test parts B and A), and CLR activation during a functional magnetic resonance imaging protocol of simulated step initiation task were evaluated before and after interventions. RESULTS: Both training groups improved gait parameters in single task (P < 0.05), but ARTI was more effective than traditional motor rehabilitation in improving DTC on gait speed, DTC on stride length, dual-task stride length, and CLR activation (P < 0.05). Changes in CLR activation were associated with changes in DTC on stride length (r = 0.68, P = 0.002) following ARTI. Only ARTI improved attentional set-shifting at posttraining (P < 0.05). CONCLUSIONS: ARTI restores gait automaticity and improves attentional set-shifting in freezers attributed to the usage of exercises with high motor complexity. © 2020 International Parkinson and Movement Disorder Society.

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.

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.