Factors impacting performance on the 6-minute walk test by people with late-onset Pompe disease.

INTRODUCTION/AIMS: Pompe disease is a progressive myopathy that combines motor, respiratory, and cardiac impairments. The 6-min walk test is the gold standard for assessing disease severity at the motor level. The objective of this study was to better determine the parameters that influence the total distance covered in patients with Pompe disease. METHODS: We performed a retrospective review of 15 patients with late-onset Pompe disease who were followed regularly at a single referral center. Logistic regression was used to investigate the links between motor, respiratory and cardiac variables and 6-min walk test performance. RESULTS: When considering baseline clinical and demographic variables, a seven-step backward elimination regression analysis yielded a model with two predictors (age and the use of an assistive device) that explained 85.5% of the variance. When considering the cardiorespiratory variables monitored during gait, a three-step backward elimination regression analysis showed that two predictors (heart rate recovery and the baseline partial pressure of carbon dioxide) explained 42.2% of the variance. DISCUSSION: Our results highlighted the importance of respiratory and cardiac adaptation during exercise (along with motor ability) during the 6-min walk test in patients with Pompe disease. Further studies of larger cohorts are necessary to validate the model, which might enable investigators to determine whether intra-individual fluctuations in 6-min walk test performance are related to physiological parameters and/or to other variables such as the patient's level of motivation during the test.

A new paradigm to study the influence of attentional load on cortical activity for motor preparation of step initiation.

Motor programme for gait initiation can vary as a function of attentional resources. The objective of the present study was to determine whether alertness, orientation and executive control can modulate cortical activation during step initiation. The attention network test (ANT) was used to control the influence of different attentional components on kinetic characteristics of step initiation and the associated cortical activity. Thirty healthy adults performed ANT combined with step initiation. The step execution time (SET) and anticipatory postural adjustments (APAs) were recorded. Movement-related cortical potentials (MRCPs) and event-related spectral perturbations (ERSPs) after response emission were analysed according to the presence or absence of cueing or conflict resolution. Step reaction time and thus SET were significantly shorter with cueing, whereas APA duration and SET were longer during conflict resolution. Moreover, alertness was related to a higher rate of anticipated responses, and conflicting situations were associated with a greater amount of multiple APAs. Attentional load did not affect MRCPs but ERSPs: trials with a cue showed earlier posterior alpha and beta desynchronisations before APA onset. Furthermore, we found earlier, more pronounced and longer alpha- and beta-band desynchronisations over the sensorimotor cortex for trials with incongruent flankers. Our results showed that attention has an impact on step initiation. A specific pattern of response-locked ERSPs seems to mirror behavioural effects of attentional load on step initiation. This new paradigm combining ANT and step initiation is, therefore, promising to investigate the interaction between attention and gait initiation in pathological populations.

The plurality of mechanisms of gait initiation disorders in Parkinson's disease: Relationships with motor, cognitive and limbic functions.

BACKGROUND: Deficient postural adaptation and freezing lead to gait initiation abnormalities in Parkinson's disease. Gait initiation is characterized by longer motor preparation, which is a marker of increased risk of falling, and by abnormal postural adjustments. Better understanding the nature of these motor preparation disturbances will enable us to adapt rehabilitation and reduce falls. RESEARCH QUESTION: Our objective was to describe the different components (in the motor, cognitive and limbic domains) of gait initiation parameters in Parkinson's disease. METHODS: Forty-four patients with Parkinson's disease performed repeated step initiations under high attentional load with decision-making. The proportions of multiple anticipatory postural adjustments and anticipatory postural adjustment errors, markers of abnormal motor preparation, were measured. A logistic regression analysis studied the relationships between step initiation perturbations and the demographic, motor, cognitive, and neuropsychiatric characteristics of the patients. RESULTS: Multiple anticipatory postural adjustments and anticipatory postural adjustments errors lengthened step execution time. Motor severity explained the multiple anticipatory postural adjustments, suggesting a pathological role. Attentional performance explained anticipatory postural adjustments errors. Demographic and neuropsychiatric characteristics didn't contribute significantly to the abnormal anticipatory postural adjustments. SIGNIFICANCE: Motor disability contributes to the delay in step execution in Parkinson's disease through multiple anticipatory postural adjustments, highlighting the need to target motor preparation improvement in rehabilitation.

The contribution of executive control dysfunction to freezing of gait in Parkinson's disease.

OBJECTIVE: An executive dysfunction is supposed to contribute to freezing of gait (FoG) in Parkinson's disease. We aimed to investigate at a behavioral and cortical levels whether an attentional load (particularly, a conflicting situation) can specifically impact preparation and execution phases of step initiation in parkinsonian patients with FoG. METHODS: Fifteen patients with FoG, 16 without and 15 controls performed an adapted version of the Attention Network Test, with step initiation as response instead of the standard manual keypress. Kinetic and kinematic features of gait initiation as well as high-resolution electroencephalography were recorded during the task. RESULTS: Patients with FoG presented an impaired executive control. Step execution time was longer in parkinsonian patients. However, the executive control effect on step execution time was not different between all groups. Compared to patients, controls showed a shorter step initiation-locked alpha desynchronization, and an earlier, more intense and shorter beta desynchronization over the sensorimotor cortex. Even though controls were faster, the induced alpha and beta activity associated with the effect of executive control didn't differ between patients and controls. CONCLUSIONS: Tasks of conflict resolution lead to a comparable alteration of step initiation and its underlying brain activity in all groups. Links between executive control, gait initiation and FoG seem more complex than expected. SIGNIFICANCE: This study questions the cognitive hypothesis in the pathophysiology of freezing of gait. Executive dysfunction is associated with FoG but is not the main causal mechanism since the interaction between attention and motor preparation didn't provoke FoG.

Multi-approach comparative study of EEG patterns associated with the most common forms of dementia.

Electroencephalography's (EEG) sensitivity in discriminating dementia syndromes remains unclear. This study aimed to investigate EEG markers in patients with major cognitive disorders. The studied population included 4 groups of patients: Alzheimer's disease with associated vascular lesions, Alzheimer's disease without vascular lesions (AD-V), Lewy body disease and vascular dementia (VaD); and completed by a control group composed by cognitively unimpaired patients. EEGs were analysed quantitatively using spectral analysis, functional connectivity and micro-states. By comparison to the controls, expected slowing and alterations of functional connectivity were detected in patients with dementia. Among these patients, an overall increase in power in the alpha band was observed in the VaD group, mainly when compared to the 2 AD groups, while the Alzheimer's disease without vascular lesions group exhibited increased power in the beta-2 band and higher functional connectivity in the same frequency band. Micro-state analyses revealed differences in temporal dynamics for the VaD group. A number of EEG modifications reported as markers of some syndromes were found, but others were not reproduced.

EEG-based functional connectivity and executive control in patients with Parkinson's disease and freezing of gait.

OBJECTIVE: To explore changes over time in the network specificities underpinning a visual attentional task in patients with Parkinson's disease and freezing of gait (the PD + FoG group), patients with Parkinson's disease but no FoG (PD-FoG), and healthy controls (HCs). METHODS: High-resolution electroencephalography (EEG) data were acquired for 15 PD + FoG patients, 14 PD-FoG patients, and 18 HCs performing the Attention Network Test. After source localization, functional connectivity was assessed and compared by applying the dynamic phase-locking value method. RESULTS: The PD + FoG patients showed an impairment in executive control. Furthermore, the PD + FoG patients showed abnormally high theta band connectivity (relative to HCs, and 400 to 600 ms after target presentation) in a network connecting the orbitofrontal and occipitotemporal regions. CONCLUSIONS: In PD + FoG, the greater functional connectivity between the visual network and the regions to which executive function has been attributed might indicate greater reliance on environmental features when seeking to overcome the impairment in executive control. SIGNIFICANCE: FoG in PD involves cognitive, attentional and executive dysfunctions. Our observation of abnormally high connectivity in PD + FoG patients argues in favor of the interference model of FoG.

Functional networks underlying freezing of gait: a resting-state electroencephalographic study.

INTRODUCTION: The pathophysiology of freezing of gait in people with Parkinson's disease (PD) remains unclear, despite its association with motor, cognitive, limbic and sensory-perceptual impairments. Resting-state electroencephalography (EEG) may provide functional information for a better understanding of freezing of gait by studying spectral power and connectivity between brain regions in different frequency bands. METHODS: High-resolution EEG was recorded in 36 patients with PD (18 freezers, 18 non-freezers), and 18 healthy controls during a 5-min resting-state protocol with eyes open, followed by a basic spectral analysis in the sensor space and a more advanced analysis of functional connectivity at the source level. RESULTS: Freezers showed a diffusely higher theta-band relative spectral power than controls. This increased power was correlated with a deficit in executive control. Concerning resting-state functional connectivity, connectivity strength within a left fronto-parietal network appeared to be higher in freezers than in controls in the theta band, and to be correlated with freezing severity and a history of falls. CONCLUSION: We have shown that spectral power and connectivity analyses of resting-state EEG provide useful and complementary information to better understand freezing of gait in PD. The higher connectivity strength seen within the left ventral attention network in freezers is in keeping with an excessive guidance of behavior by external cues, due to executive dysfunction, and spectral analysis also found changes in freezers that was closely correlated with executive control deficits. This exaggerated influence of the external environment might result in behavioral consequences that contribute to freezing of gait episodes. These findings should be further investigated with a longitudinal study.

Anxiety in Parkinson's disease: A resting-state high density EEG study.

OBJECTIVE: To identify markers of Parkinson's disease (PD) related anxiety, using high density electroencephalography (hd-EEG). METHODS: 108 patients participated in the study. They were divided into two groups: with and without clinically relevant anxiety, according to their score on the Parkinson Anxiety Scale. Resting-state hd-EEG was recorded. Spectral and functional connectivity characteristics were compared between the two groups. RESULTS: Thirty-three patients (31%) had significant anxiety symptoms. In the spectral analysis, relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without. Functional connectivity analysis showed a stronger connectivity between the left insula and several regions of the right prefrontal cortex in patients with anxiety than in those without. CONCLUSION: This study shows the pivotal role of the insula and frontal cortex in the pathophysiology of anxiety in PD and extends the results of previous studies using magnetic resonance imaging or positron emission tomography imaging.

The frontostriatal subtype of mild cognitive impairment in Parkinson's disease, but not the posterior cortical one, is associated with specific EEG alterations.

BACKGROUND: The 'dual syndrome' hypothesis states that two cognitive subtypes can be distinguished in mild cognitive impairment in Parkinson's disease (PD-MCI): a frontostriatal one, characterized by attentional and/or executive deficits, and a posterior cortical one, characterized by visuospatial, memory and/or language deficits. The latter type has been associated with a higher risk of earlier development of PD dementia. The functional bases of these subtypes remain partly unknown. OBJECTIVE: To identify EEG modifications associated with PD-MCI subtypes. METHODS: 75 non-demented PD patients underwent a comprehensive neuropsychological assessment and a high-density EEG. They were classified as having normal cognition (PD-NC; n = 37), PD-MCI with a frontostriatal subtype (PD-FS; n = 11) or PD-MCI with a posterior cortical subtype (PD-PC; n = 27). Two EEG analyses were performed: (a) spectral powers quantification and (b) functional connectivity analysis. RESULTS: PD-FS patients displayed spectral and functional EEG alterations, namely (a) higher powers in the theta and delta bands, (b) lower powers in the beta2 band and (c) lower functional connectivity in the beta2 band compared to PD-NC and PD-PC patients. These alterations were mainly located in the frontal, limbic and parietal regions. There were no significant differences between PD-NC and PD-PC. CONCLUSION: EEG alterations previously reported in PD-MCI may only concern the frontostriatal subtype, and not the posterior-cortical subtype. This provides evidence for the dual syndrome hypothesis and emphasizes the importance of identifying PD-MCI subtypes. It also shows the promising potential of EEG to discriminate between PD-MCI subtypes.

Role of the peripheral nervous system for an appropriate postural preparation during gait initiation in patients with a chronic inflammatory demyelinating polyneuropathy: A pilot study.

BACKGROUND: Gait initiation is an automatized motor program that is preceded by anticipatory postural adjustments (APAs). During attentional tasks, these APAs can be modulated, producing multiple APAs. However, the role of the peripheral nervous system in the regulation of these APAs is unknown. RESEARCH QUESTION: The objective of our study was to investigate whether APAs are also regulated by peripheral nervous afferents. METHODS: We assessed 21 patients suffering from chronic inflammatory demyelinating neuropathy and 20 healthy controls. Participants initiated gait with the right or left leg either freely (in the standard condition) or according to a visual trigger (i.e., the select condition). Kinetic and kinematic parameters of APAs and step initiation were recorded. RESULTS: The select condition was related to a higher rate of multiple APAs compared to the standard condition, and was more attention-consuming in both groups. The group with a neuropathy showed longer APAs than the control group, associated with a longer time to recover from multiple APAs. Consequently, the step execution time was delayed in patients with a peripheral neuropathy. SIGNIFICANCE: The impairment of the peripheral nervous system is therefore responsible for an alteration of the mechanisms underlying the recovery from multiple APAs during gait initiation. Our results are in favor of a role of proprioceptive afferents in the early peripheral regulation of motor errors. Further study on gait initiation in peripheral nervous disease could be helpful to better explore sensory-motor coupling in tasks requiring balance control.

Initial center of pressure position prior to anticipatory postural adjustments during gait initiation in people with Parkinson's disease with freezing of gait.

INTRODUCTION: Freezing of gait (FOG) in Parkinson's disease (PD) is associated with an altered posture during quiet stance as well as an impaired preparation and execution of the gait initiation process. We aimed to investigate whether an altered initial posture impacts anticipatory postural adjustments (APAs) and first-step execution during gait initiation in people with PD with FOG (PD + FOG). METHODS: Twenty-seven PD+FOG, 30 PD patients without FOG and 27 age-matched healthy controls performed self-generated gait initiation. Initial mean center of pressure (COP) position prior to APA onset, characteristics of APAs and features of first-step execution were investigated. RESULTS: Contrarily to controls, PD patients showed a COP that was initially positioned more towards the stance leg (p = 0.007). Moreover, significantly smaller backward COP shift, longer duration of swing-foot unloading phase, and lower first-step length and velocity characterized PD+FOG compared to controls. While size and duration of backward COP shift during APA and lateral COP shift during the unloading phase were main predictors of first-step length and velocity in all groups, the medio-lateral shift of the initial COP position in PD+FOG was a main predictor of first-step execution (ß = -0.191, p = 0.001 for velocity). CONCLUSION: In PD+FOG, the more the COP was initially positioned towards the stance foot, the slower and shorter the first step. The initial medio-lateral COP position may be a compensatory strategy to address postural instability of PD+FOG. A specific training regarding postural control prior to gait preparation and execution could improve functional mobility in PD+FOG.

Cortical Oscillations during Gait: Wouldn't Walking be so Automatic?

Gait is often considered as an automatic movement but cortical control seems necessary to adapt gait pattern with environmental constraints. In order to study cortical activity during real locomotion, electroencephalography (EEG) appears to be particularly appropriate. It is now possible to record changes in cortical neural synchronization/desynchronization during gait. Studying gait initiation is also of particular interest because it implies motor and cognitive cortical control to adequately perform a step. Time-frequency analysis enables to study induced changes in EEG activity in different frequency bands. Such analysis reflects cortical activity implied in stabilized gait control but also in more challenging tasks (obstacle crossing, changes in speed, dual tasks…). These spectral patterns are directly influenced by the walking context but, when analyzing gait with a more demanding attentional task, cortical areas other than the sensorimotor cortex (prefrontal, posterior parietal cortex, etc.) seem specifically implied. While the muscular activity of legs and cortical activity are coupled, the precise role of the motor cortex to control the level of muscular contraction according to the gait task remains debated. The decoding of this brain activity is a necessary step to build valid brain-computer interfaces able to generate gait artificially.

Can dual-task paradigms predict Falls better than single task? - A systematic literature review.

With about one third of adults aged 65 years and older being reported worldwide to fall each year, and an even higher prevalence with advancing age, aged-related falls and the associated disabilities and mortality are a major public health concern. In this context, identification of fall risk in healthy older adults is a key component of fall prevention. Since dual-task outcomes rely on the interaction between cognition and motor control, some studies have demonstrated the role of dual-task walking performance or costs in predicting future fallers. However, based on previous reviews on the topic, (1) discriminative and (2) predictive powers of dual tasks involving gait and a concurrent task are still a matter of debate, as is (3) their superiority over single tasks in terms of fall-risk prediction. Moreover, less attention has been paid to dual tasks involving postural control and transfers (such as gait initiation and turns) as motor tasks. In the present paper, we therefore systematically reviewed recent literature over the last 7 years in order to answer the three above mentioned questions regarding the future of lab-based dual tasks (involving posture, gait initiation, gait and turning) as easily applicable tests for identifying healthy older adult fallers. Despite great heterogeneity among included studies, we emphasized, among other things, the promising added value of dual tasks including turns and other transfers, such as in the Timed Up and Go test, for prediction of falls. Further investigation of these is thus warranted.

The interaction between cognition and motor control: A theoretical framework for dual-task interference effects on posture, gait initiation, gait and turning.

Studies of dual-tasks (i.e. situations during which an individual performs two tasks simultaneously) and the subsequent inter-task interference have shown that locomotion and posture involves motor and cognitive components. Dual-tasks therefore constitute a promising avenue for improving the diagnosis, prevention and management of falls or cognitive impairment in populations at risk. However, tackling these major public health concerns with dual-task interventions requires a better understanding of the mechanisms underlying dual-task interference. In this context, we review (i) the main dual-task theories proposed to date and (ii) the factors that can influence dual-task interference effects in healthy young individuals and might therefore explain the current lack of consensus on the mechanisms of dual-tasks. We also consider cognitive-motor dual-tasks in which the motor task is a less frequently studied transition movement (such as gait initiation or turning), rather than only the often-studied gait and posture tasks. In general, the review focuses on the behavioral effects of dual-tasking.

Motor Preparation of Step Initiation: Error-related Cortical Oscillations.

Gait initiation can vary as a function of the available and engaged attentional resources. Conflict resolution can disrupt movement preparation and lead to "errors" in motor programming. These "errors" are physiologically useful by enabling us to adapt our motor behavior to situations with conflicting information. The objective of the present study was to analyze the patterns of cortical activation associated with motor programming errors and the corresponding error corrections. Incongruent flankers around a target arrow were used to trigger errors in anticipatory postural adjustments (APAs) prior to gait initiation; i.e. perturbed motor programming but normal execution. Thirty healthy adults performed a gait initiation task. The event-related potentials (ERPs) and event-related desynchronization (ERD) after target presentation were analyzed according to the presence or absence of an APA error. The ERP was similar in both conditions, except that the Ne and P300 peak latencies were longer for APA errors. Motor programming errors during gait initiation were characterized by longer, less intense low-beta-band ERD over the sensorimotor cortex and alpha ERS followed by stronger alpha ERD during errors. APA errors were associated with a specific alpha/beta oscillation profile over the sensorimotor cortex; these beta oscillations might be sensitive markers of non-conscious motor error and correction monitoring.