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.
Parkinson's disease patients with freezing of gait also experience sudden motor blocks (freezing) during other repetitive motor tasks. We assessed the proportion of patients with advanced PD and ...freezing of gait who also displayed segmental "freezing" in tapping tasks.
Fifteen Parkinson's disease patients with freezing of gait were assessed. Freezing of gait was evaluated using a standardized gait trajectory with the usual triggers. Patients performed repetitive tapping movements (as described in the MDS-UPDRS task) with the hands or the feet in the presence or absence of a metronome set to 4 Hz. Movements were recorded with a video motion system. The primary endpoint was the occurrence of segmental freezing in these tapping tasks. The secondary endpoints were (i) the relationship between segmental episodic phenomena and FoG severity, and (ii) the reliability of the measurements.
For the upper limbs, freezing was observed more frequently with a metronome (21% of trials) than without a metronome (5%). For the lower limbs, the incidence of freezing was higher than for the upper limbs, and was again observed more frequently in the presence of an auditory cue (47%) than in its absence (14%).
Although freezing of the lower limbs was easily assessed during an MDS-UPDRS task with a metronome, it was not correlated with the severity of freezing of gait (as evaluated during a standardized gait trajectory). Only this latter was a reliable measurement in patients with advanced Parkinson's disease.
Type 1 diabetes (T1D) is an autoimmune disease that results from the destruction of pancreatic β-cells by the immune system that involves innate and adaptive immune cells. Mucosal-associated ...invariant T cells (MAIT cells) are innate-like T-cells that recognize derivatives of precursors of bacterial riboflavin presented by the major histocompatibility complex (MHC) class I-related molecule MR1. Since T1D is associated with modification of the gut microbiota, we investigated MAIT cells in this pathology. In patients with T1D and mice of the non-obese diabetic (NOD) strain, we detected alterations in MAIT cells, including increased production of granzyme B, which occurred before the onset of diabetes. Analysis of NOD mice that were deficient in MR1, and therefore lacked MAIT cells, revealed a loss of gut integrity and increased anti-islet responses associated with exacerbated diabetes. Together our data highlight the role of MAIT cells in the maintenance of gut integrity and the control of anti-islet autoimmune responses. Monitoring of MAIT cells might represent a new biomarker of T1D, while manipulation of these cells might open new therapeutic strategies.
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.
•Patients with Parkinson's disease and freezing of gait (FoG) presented executive dysfunction.•When combining conflict resolution with step initiation, patients with FoG were slower but didn’t ...freeze.•Cortical activation reflecting conflict resolution and motor preparation was similar in all populations.
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.
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.
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.
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.
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.
•Gait initiation is impaired in patients with polyneuropathy.•Mechanisms underlying the recovery from multiple APAs are implied.•Role of proprioceptive afferents is suggested.
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.
The objective of our study was to investigate whether APAs are also regulated by peripheral nervous afferents.
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.
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.
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.
Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive, debilitating disease often resulting in early-onset, life-impacting autonomic dysfunction. The effect of the RNAi therapeutic, ...patisiran, on autonomic neuropathy manifestations in patients with hATTR amyloidosis with polyneuropathy in the phase III APOLLO study is reported. Patients received patisiran 0.3 mg/kg intravenously (
n
= 148) or placebo (
n
= 77) once every 3 weeks for 18 months. Patisiran halted or reversed polyneuropathy and improved quality of life from baseline in the majority of patients. At baseline, patients in APOLLO had notable autonomic impairment, as demonstrated by the Composite Autonomic Symptom Score-31 (COMPASS-31) questionnaire and Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire autonomic neuropathy domain. At 18 months, patisiran improved autonomic neuropathy symptoms compared with placebo COMPASS-31, least squares (LS) mean difference, − 7.5; 95% CI: − 11.9, − 3.2; Norfolk QOL-DN autonomic neuropathy domain, LS mean difference, − 1.1; − 1.8, − 0.5, nutritional status (modified body mass index, LS mean difference, 115.7; − 82.4, 149.0), and vasomotor function (postural blood pressure, LS mean difference, − 0.3; − 0.5, − 0.1). Patisiran treatment also led to improvement from baseline at 18 months for COMPASS-31 (LS mean change from baseline, − 5.3; 95% CI: − 7.9, − 2.7) and individual domains, orthostatic intolerance (− 4.6; − 6.3, − 2.9) and gastrointestinal symptoms (− 0.8; − 1.5, − 0.2). Rapid worsening of all study measures was observed with placebo, while patisiran treatment resulted in stable or improved scores compared with baseline. Patisiran demonstrates benefit across a range of burdensome autonomic neuropathy manifestations that deteriorate rapidly without early and continued treatment.
•Attention disrupts movement preparation and leads to errors in motor programming.•Errors are associated with a prolonged beta power decrease over the sensorimotor cortex.•Alpha/beta oscillations are ...sensitive markers of non-conscious motor error monitoring.
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.
•Accuracy of clinical evaluation for distinguishing between fallers and non-fallers was of 94%.•Incorporating additional gait parameters improved the accuracy of up to 97%.•Foot clearance appeared ...useful for distinguishing between fallers and non-fallers.
Although a number of clinical factors have been linked to falls in Parkinson’s disease (PD), the diagnostic value of gait parameters remains subject to debate. The objective of this retrospective study was to determine to what extent the combination of gait parameters with clinical characteristics can distinguish between fallers and non-fallers.
Using a video motion system, we recorded gait in 174 patients with PD. The patients’ clinical characteristics (including motor status, cognitive status, disease duration, dopaminergic treatment and any history of falls or freezing of gait) were noted. The considered kinematic gait parameters included indices of gait bradykinesia and hypokinesia, asymmetry, variability, and foot clearance. After a parameters selection using an ANCOVA analysis, support vector machine algorithm was used to build classification models for distinguishing between fallers and non-fallers. Two models were built, the first included clinical data only while the second incorporated the selected gait parameters.
The “clinical-only” model had an accuracy of 94% for distinguishing between fallers and non-fallers. The model incorporating additional gait parameters including stride time and foot clearance performed even better, with an accuracy of up to 97%.
Although fallers differed significantly from non-fallers with regard to disease duration, motor impairment or dopaminergic treatment, the addition of gait parameters such as foot clearance or stride time to clinical variables increased the model’s discriminant power. Significance: This predictive model now needs to be validated in prospective cohorts.
Highlights • Parkinson’s disease (PD) patients present failure to link anticipatory postural adjustments and step execution. • Deficient postural adjustments in PD are associated with freezing of ...gait (FOG). • Auditory cueing improves the preparation of gait initiation in PD patients with FOG but not its execution.
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