Functional neuroimaging of human postural control: A systematic review with meta-analysis.

Postural instability is a strong risk factor for falls that becomes more prominent with aging. To facilitate treatment and prevention of falls in an aging society, a thorough understanding of the neural networks underlying postural control is warranted. Here, we present a systematic review of the functional neuroimaging literature of studies measuring posture-related neural activity in healthy subjects. Study methods were overall heterogeneous. Eleven out of the 14 studies relied on postural simulation in a supine position (e.g. motor imagery). The key nodes of human postural control involved the brainstem, cerebellum, basal ganglia, thalamus and several cortical regions. An activation likelihood estimation meta-analysis revealed that the anterior cerebellum was consistently activated across the wide range of postural tasks. The cerebellum is known to modulate the brainstem nuclei involved in the control of posture. Hence, this systematic review with meta-analysis provides insight into the neural correlates which underpin human postural control and which may serve as a reference for future neural network and region of interest analyses.

Do Patients With Parkinson's Disease With Freezing of Gait Respond Differently Than Those Without to Treadmill Training Augmented by Virtual Reality?

Background. People with Parkinson's disease and freezing of gait (FOG+) have more falls, postural instability and cognitive impairment compared with FOG-. Objective. To conduct a secondary analysis of the V-TIME study, a randomized, controlled investigation showing a greater reduction of falls after virtual reality treadmill training (TT + VR) compared with usual treadmill walking (TT) in a mixed population of fallers. We addressed whether these treadmill interventions led to similar gains in FOG+ as in FOG-. Methods. A total of 77 FOG+ and 44 FOG- were assigned randomly to TT + VR or TT. Participants were assessed pre- and posttraining and at 6 months' follow-up. Main outcome was postural stability assessed by the Mini Balance Evaluation System Test (Mini-BEST) test. Falls were documented using diaries. Other outcomes included the New Freezing of Gait Questionnaire (NFOG-Q) and the Trail Making Test (TMT-B). Results. Mini-BEST scores and the TMT-B improved in both groups after training (P = .001), irrespective of study arm and FOG subgroup. However, gains were not retained at 6 months. Both FOG+ and FOG- had a greater reduction of falls after TT + VR compared with TT (P = .008). NFOG-Q scores did not change after both training modes in the FOG+ group. Conclusions. Treadmill walking (with or without VR) improved postural instability in both FOG+ and FOG-, while controlling for disease severity differences. As found previously, TT + VR reduced falls more than TT alone, even among those with FOG. Interestingly, FOG itself was not helped by training, suggesting that although postural instability, falls and FOG are related, they may be controlled by different mechanisms.

Falls Risk in Relation to Activity Exposure in High-Risk Older Adults.

BACKGROUND: Physical activity is linked to many positive health outcomes, stimulating the development of exercise programs. However, many falls occur while walking and so promoting activity might paradoxically increase fall rates, causing injuries, and worse quality of life. The relationship between activity exposure and fall rates remains unclear. We investigated the relationship between walking activity (exposure to risk) and fall rates before and after an exercise program (V-TIME). METHODS: One hundred and nine older fallers, 38 fallers with mild cognitive impairment (MCI), and 128 fallers with Parkinson's disease (PD) were randomly assigned to one of two active interventions: treadmill training only or treadmill training combined with a virtual reality component. Participants were tested before and after the interventions. Free-living walking activity was characterized by volume, pattern, and variability of ambulatory bouts using an accelerometer positioned on the lower back for 1 week. To evaluate that relationship between fall risk and activity, a normalized index was determined expressing fall rates relative to activity exposure (FRA index), with higher scores indicating a higher risk of falls per steps taken. RESULTS: At baseline, the FRA index was higher for fallers with PD compared to those with MCI and older fallers. Walking activity did not change after the intervention for the groups but the FRA index decreased significantly for all groups (p ≤ .035). CONCLUSIONS: This work showed that V-TIME interventions reduced falls risk without concurrent change in walking activity. We recommend using the FRA index in future fall prevention studies to better understand the nature of intervention programs.

Associations between daily-living physical activity and laboratory-based assessments of motor severity in patients with falls and Parkinson's disease.

INTRODUCTION: Recent work suggests that wearables can augment conventional measures of Parkinson's disease (PD). We evaluated the relationship between conventional measures of disease and motor severity (e.g., MDS-UPDRS part III), laboratory-based measures of gait and balance, and daily-living physical activity measures in patients with PD. METHODS: Data from 125 patients (age: 71.7 ±â€¯6.5 years, Hoehn and Yahr: 1-3, 60.5% men) were analyzed. The MDS-UPDRS-part III was used as the gold standard of motor symptom severity. Gait and balance were quantified in the laboratory. Daily-living gait and physical activity metrics were extracted from an accelerometer worn on the lower back for 7 days. RESULTS: In multivariate analyses, daily-living physical activity and gait metrics, laboratory-based balance, demographics and subject characteristics together explained 46% of the variance in MDS-UPDRS-part III scores. Daily-living measures accounted for 62% of the explained variance, laboratory measures 30%, and demographics and subject characteristics 7% of the explained variance. Conversely, demographics and subject characteristics, laboratory-based measures of gait symmetry, and motor symptom severity together explained less than 30% of the variance in total daily-living physical activity. MDS-UPDRS-part III scores accounted for 13% of the explained variance, i.e., <4% of all the variance in total daily-living activity. CONCLUSIONS: Our findings suggest that conventional measures of motor symptom severity do not strongly reflect daily-living activity and that daily-living measures apparently provide important information that is not captured in a conventional one-time, laboratory assessment of gait, balance or the MDS-UPDRS. To provide a more complete evaluation, wearable devices should be considered.

Analysis of Free-Living Gait in Older Adults With and Without Parkinson's Disease and With and Without a History of Falls: Identifying Generic and Disease-Specific Characteristics.

BACKGROUND: Falls are associated with gait impairments in older adults (OA) and Parkinson's disease (PD). Current approaches for evaluating falls risk are based on self-report or one-time assessment and may be suboptimal. Wearable technology allows gait to be measured continuously in free-living conditions. The aim of this study was to explore generic and specific associations in free-living gait in fallers and nonfallers with and without PD. METHODS: Two hundred and seventy-seven fallers (155 PD, 122 OA) who fell twice or more in the previous 6 months and 65 nonfallers (15 PD, 50 OA) were tested. Free-living gait was characterized as the volume, pattern, and variability of ambulatory bouts (Macro), and 14 discrete gait characteristics (Micro). Macro and Micro variables were quantified from free-living data collected using an accelerometer positioned on the low back for one week. RESULTS: Macro variables showed that fallers walked with shorter and less variable ambulatory bouts than nonfallers, independent of pathology. Micro variables within ambulatory bouts showed fallers walked with slower, shorter and less variable steps than nonfallers. Significant interactions showed disease specific differences in variability with PD fallers demonstrating greater variability (step length) and OA fallers less variability (step velocity) than their nonfaller counterparts (p < 0.004). CONCLUSIONS: Common and disease-specific changes in free-living Macro and Micro gait highlight generic and selective targets for intervention depending on type of faller (OA-PD). Our findings support free-living monitoring to enhance assessment. Future work is needed to confirm the optimal battery of measures, sensitivity to change and value for fall prediction.

Adaptations to Postural Perturbations in Patients With Freezing of Gait.

Introduction: Freezing of gait (FOG) is a powerful determinant of falls in Parkinson's disease (PD). Automatic postural reactions serve as a protective strategy to prevent falling after perturbations. However, differences in automatic postural reactions between patients with and without FOG in response to perturbation are at present unclear. Therefore, the present study aimed to compare the response patterns and neuromuscular control between PD patients with and without FOG and healthy controls (HCs) after postural perturbations. Methods: 28 PD patients (15 FOG+, 13 FOG-) and 22 HCs were included. Participants stood on a moveable platform while random perturbations were imposed. The first anterior platform translation was retained for analysis. Center of pressure (CoP) and center of mass (CoM) trajectories and trunk, knee and ankle angles were compared between the three groups using the Statistical Parametric Mapping technique, allowing to capture changes in time. In addition, muscle activation of lower leg muscles was measured using EMG. Results: At baseline, FOG+ stood with more trunk flexion than HCs (p = 0.005), a result not found in FOG-. Following a perturbation, FOG+ reacted with increased trunk extension (p = 0.004) in comparison to HCs, a pattern not observed in FOG-. The CoM showed greater backward displacement in FOG- and FOG+ (p = 0.008, p = 0.027). Both FOG+ and FOG- showed increased co-activation of agonist and antagonist muscles compared to HCs (p = 0.010), with no differences between FOG+ and FOG-. Conclusions: Automatic postural reactions after a sudden perturbation are similar between PD subgroups with and without FOG but different from HCs. Reactive postural control, largely regulated by brain stem centers, seems to be modulated by different mechanisms than those governing freezing of gait. Greater differences in initial stance position, enhanced by joint stiffening, could however underlie maladaptive postural responses and increase susceptibility for balance loss in FOG+ compared to FOG-.

Estimation of spatio-temporal parameters of gait from magneto-inertial measurement units: multicenter validation among Parkinson, mildly cognitively impaired and healthy older adults.

BACKGROUND: The use of miniaturized magneto-inertial measurement units (MIMUs) allows for an objective evaluation of gait and a quantitative assessment of clinical outcomes. Spatial and temporal parameters are generally recognized as key metrics for characterizing gait. Although several methods for their estimate have been proposed, a thorough error analysis across different pathologies, multiple clinical centers and on large sample size is still missing. The aim of this study was to apply a previously presented method for the estimate of spatio-temporal parameters, named Trusted Events and Acceleration Direct and Reverse Integration along the direction of Progression (TEADRIP), on a large cohort (236 patients) including Parkinson, mildly cognitively impaired and healthy older adults collected in four clinical centers. Data were collected during straight-line gait, at normal and fast walking speed, by attaching two MIMUs just above the ankles. The parameters stride, step, stance and swing durations, as well as stride length and gait velocity, were estimated for each gait cycle. The TEADRIP performance was validated against data from an instrumented mat. RESULTS: Limits of agreements computed between the TEADRIP estimates and the reference values from the instrumented mat were - 27 to 27 ms for Stride Time, - 68 to 44 ms for Stance Time, - 31 to 31 ms for Step Time and - 67 to 52 mm for Stride Length. For each clinical center, the mean absolute errors averaged across subjects for the estimation of temporal parameters ranged between 1 and 4%, being on average less than 3% (< 30 ms). Stride length mean absolute errors were on average 2% (≈ 25 mm). Error comparisons across centers did not show any significant difference. Significant error differences were found exclusively for stride and step durations between healthy elderly and Parkinsonian subjects, and for the stride length between walking speeds. CONCLUSIONS: The TEADRIP method was effectively validated on a large number of healthy and pathological subjects recorded in four different clinical centers. Results showed that the spatio-temporal parameters estimation errors were consistent with those previously found on smaller population samples in a single center. The combination of robustness and range of applicability suggests the use of the TEADRIP as a suitable MIMU-based method for gait spatio-temporal parameter estimate in the routine clinical use. The present paper was awarded the "SIAMOC Best Methodological Paper 2017".

The Impact of Dual-Tasking on Postural Stability in People With Parkinson's Disease With and Without Freezing of Gait.

BACKGROUND: Postural instability and freezing of gait (FOG) are major problems in patients with Parkinson's disease (PD), and both contribute to falls. However, the interrelationship between these 2 deficits is still unclear. OBJECTIVE: This study investigated whether dual-tasking influenced postural control differently in freezers (FOG+) and nonfreezers (FOG-). METHODS: Thirty-three patients with PD (19 FOG+, 14 FOG-, well-matched) and 28 healthy controls underwent 4 postural control tasks, consisting of standing on either stable or unstable surfaces with eyes open or closed. Each condition was performed with and without a cognitive dual-task (DT). Center of pressure and center of mass variables and cognitive DT performance outcomes were investigated. RESULTS: Postural stability decreased to a larger extent in FOG+ under DT conditions compared with the other groups, although overall most differences were found between FOG+ and controls. FOG+ exhibited worse postural control compared with FOG- under stable surface DT conditions, shown by higher medial-lateral sway measures (group × surface × task, P < .05). Also, postural DT cost (%) was higher in FOG+ than in FOG- in unstable surface conditions without vision. Controls performed better on the cognitive DT when balancing compared with sitting, whereas this improvement was absent in both PD subgroups and more so in FOG+. CONCLUSIONS: Postural stability in FOG+ deteriorated more than in FOG- and controls upon cognitive load. Our results extend earlier findings on gait that the compensatory mechanisms to cope with DT stance are insufficient in FOG+. The findings highlight the need for adapted rehabilitation programs for this subgroup, comprising motor-cognitive balance training.

Everyday Stepping Quantity and Quality Among Older Adult Fallers With and Without Mild Cognitive Impairment: Initial Evidence for New Motor Markers of Cognitive Deficits?

Background: Recent work demonstrated that the gait of people with mild cognitive impairment (MCI) differs from that of age-matched controls and, in general, that walking ability, as measured in the clinic, does not necessarily reflect actual, daily performance. We evaluated if the quantity and quality of everyday walking (ie, community ambulation) differs in older adults with MCI, compared to age-matched controls. Methods: Inclusion criteria included: age 65-90 years, able to walk at least 5 minutes unassisted, and ≥2 falls in the past 6 months. Subjects with MCI were included if they scored 0.5 on the Clinical Dementia Rating Scale. To assess stepping quantity and quality, subjects wore a tri-axial accelerometer on the lower-back for 7 days. Results: Age and gender were similar (p > .10) in MCI (n = 36, 77.8 ± 6.4 years; 27.8% men) and controls (n = 100, 76.0 ± 6.2 years; 22.0% men). As expected, Montreal Cognitive Assessment scores were lower (p < .001) in MCI (21.31 ± 4.05), compared to controls (25.81 ± 2.64). Walking time was lower (p = .016) in MCI (0.74 ± 0.48 hours/d), compared to controls (1.05 ± 0.66 hours/d). Within-bout walking (eg, stride regularity) was less consistent (p = .024) in MCI (0.51 ± 0.14), compared to controls (0.58 ± 0.14). Changes in stride regularity across bouts were lower (p < .001) in MCI (0.13 ± 0.04), compared to controls (0.17 ± 0.01). Conclusions: Older adults with MCI walk less and with a more variable within-bout and less variable across-bout walking pattern, as compared to cognitively-intact subjects matched with respect to age and gender. These findings extend previous clinical work and suggest that MCI affects both the quantity and quality of community ambulation.

Freezing-related perception deficits of asymmetrical walking in Parkinson's disease.

Patients with Parkinson's disease (PD), and especially those with freezing of gait (FOG), are known to experience impairments in gait rhythmicity, symmetry, and bilateral coordination between both legs. In the current study, we investigated whether deficits in perception of gait speed between limbs were more pronounced in freezers than in non-freezers and could explain some of these gait impairments. We also assessed cognitive ability and proprioception. Twenty-five PD patients (13 freezers, 12 non-freezers) and 12 healthy controls walked on a split-belt treadmill, while the speed of one of the belts was gradually increased. Participants had to indicate the moment at which they perceived belt speeds to be different. The main outcome variables were the number of correct responses (perception accuracy) and the difference in belt speeds at the moment the participants perceived belt speeds to be different (perception threshold). In addition, gait characteristics during both split- and tied-belt walking were determined. Results showed significantly lower perception accuracy in freezers, whereas the perception threshold did not differ between groups. During tied-belt walking, freezers exhibited more asymmetrical step lengths and limb excursions than non-freezers and healthy controls. Greater step length and limb excursions were associated with better perception, whereas more variable gait was associated with more impaired perception. The results confirm the hypothesis that freezers have impaired perception of locomotor asymmetry. While proprioceptive and cognitive ability did not explain these findings, the possible causal link with the occurrence of FOG needs further corroboration.

External input for gait in people with Parkinson's disease with and without freezing of gait: One size does not fit all.

Cueing or feedback provided when gait deviates from a predefined goal (intelligent input) can now be provided with wearable technology for Parkinson's disease (PD). As people with and without freezing of gait (FOG) have distinct cognitive profiles, they may respond differently to various types of input. This study compared the effects of four input modalities during prolonged walking and explored the relationship with cognition, subjective preference, and FOG. Participants (15 with and 13 without FOG) walked 30 min while exposed to continuous cueing; intelligent cueing; intelligent feedback; or no input. Cueing consisted of metronome beats matched to comfortable cadence. Intelligent input represented bouts of ten beats indicating comfortable cadence (intelligent cueing) or an instruction to adapt gait speed (intelligent feedback) when cadence deviated from the comfortable target. Preference for one condition over the other was gathered. Freezers produced most stable gait under continuous cueing, but the majority favored intelligent feedback. Non-freezers showed no differences between conditions, but gait was more stable under intelligent input than in freezers. Interestingly, lower cognitive scores were related to worse gait during intelligent input, most prominently seen in freezers. These results suggest that cognitive ability is an aspect to take into account when deciding on the most appropriate cueing modality in different PD subgroups.

Clinical balance scales indicate worse postural control in people with Parkinson's disease who exhibit freezing of gait compared to those who do not: A meta-analysis.

Postural instability and freezing of gait (FOG) are key features of Parkinson's disease (PD) that are closely related to falls. Uncovering the postural control differences between individuals with and without FOG contributes to our understanding of the relationship between these phenomena. The objective of this meta-analysis was to investigate whether postural control deficits, as detected by clinical balance scales, were more apparent in FOG+ compared to FOG-. Furthermore, we aimed to identify whether different scales were equally sensitive to detect postural control deficits and whether medication affected postural control differentially in each subgroup. Relevant articles were identified via five electronic databases. We performed a meta-analysis on nine studies which reported clinical balance scale scores in 249 freezers and 321 non-freezers. Methodological analysis showed that in 5/9 studies disease duration differed between subgroups. Despite this drawback, postural control was found to be significantly worse in FOG+ compared to FOG-. All included clinical balance scales were found to be sufficiently sensitive to detect the postural control differences. Levodopa did not differentially affect postural control (p=0.21), as in both medication states FOG+ had worse postural stability than FOG-. However, this finding warrants a cautious interpretation given the limitations of the studies included. From subscore analysis, we found that reactive and dynamic postural control were the most affected postural control systems in FOG+. We conclude that our findings provide important evidence for pronounced postural instability in individuals with FOG, which can be easily picked up with clinical evaluation tools. Posturographic measures in well-matched subgroups are needed to highlight the exact nature of these deficits.

Progression of postural control and gait deficits in Parkinson's disease and freezing of gait: A longitudinal study.

BACKGROUND AND AIMS: The relationship between impaired postural control and freezing of gait (FOG) in Parkinson's disease (PD) is still unclear. Our aim was to identify if postural control deficits and gait dysfunction progress differently in freezers compared to non-freezers and whether this relates to FOG development. METHODS: 76 PD patients, classified as freezer (n = 17) or non-freezer (n = 59), and 24 controls underwent a gait and postural control assessments at baseline and after 12 months follow-up. Non-freezers who developed FOG during the study period were categorized as FOG converters (n = 5). Gait was analyzed during walking at self-preferred pace. Postural control was assessed using the Mini-BESTest and its sub-categories: sensory orientation, anticipatory, reactive and dynamic postural control. RESULTS: Mini-BESTest scores were lower in PD compared to controls (p < 0.001), and in freezers compared to non-freezers (p = 0.02). PD has worse anticipatory (p = 0.01), reactive (p = 0.02) and dynamic postural control (p = 0.003) compared to controls. Freezers scored lower on dynamic postural control compared to non-freezers (p = 0.02). There were no baseline differences between converters and non-converters. Decline in postural control was worse in PD compared to controls (p = 0.02) as shown by a greater decrease in the total Mini-BESTest score. Similar patterns were found in freezers (p = 0.006), who also showed more decline in anticipatory (p < 0.001) and dynamic postural control (p = 0.02) compared to non-freezers. FOG converters had a greater decline in the total Mini-BESTest (p = 0.005) and dynamic postural control scores (p = 0.04) compared to non-converters. Gait outcomes showed no significant differences in any of the analyses. CONCLUSION: FOG is associated with more severe decline in postural control, which can be detected by the clinical Mini-BESTest.

The contribution of proprioceptive information to postural control in elderly and patients with Parkinson's disease with a history of falls.

Proprioceptive deficits negatively affect postural control but their precise contribution to postural instability in Parkinson's disease (PD) is unclear. We investigated if proprioceptive manipulations differentially affect balance, measured by force plates, during quiet standing in 13 PD patients and 13 age-matched controls with a history of falls. Perceived limits of stability (LoS) were derived from the differences between maximal center of pressure (CoP) displacement in anterior-posterior (AP) and medio-lateral (ML) direction during a maximal leaning task. Task conditions comprised standing with eyes open (EO) and eyes closed (EC): (1) on a stable surface; (2) an unstable surface; and (3) with Achilles tendon vibration. CoP displacements were calculated as a percentage of their respective LoS. Perceived LoS did not differ between groups. PD patients showed greater ML CoP displacement than elderly fallers (EF) across all conditions (p = 0.043) and tended to have higher postural sway in relation to the LoS (p = 0.050). Both groups performed worse on an unstable surface and during tendon vibration compared to standing on a stable surface with EO and even more so with EC. Both PD and EF had more AP sway in all conditions with EC compared to EO (p < 0.001) and showed increased CoP displacements when relying on proprioception only compared to standing with normal sensory input. This implies a similar role of the proprioceptive system in postural control in fallers with and without PD. PD fallers showed higher ML sway after sensory manipulations, as a result of which these values approached their perceived LoS more closely than in EF. We conclude that despite a similar fall history, PD patients showed more ML instability than EF, irrespective of sensory manipulation, but had a similar reliance on ankle proprioception. Hence, we recommend that rehabilitation and fall prevention for PD should focus on motor rather than on sensory aspects.