Investigating the effect of rivastigmine on postural control in Parkinson's disease dementia

Objectifs : Comparer l’efficacité et l'aspect sécuritaire de la rivastigmine sous forme orale et transdermique destinée au traitement des symptômes liés aux instabilités posturales de patients atteints de la démence de la maladie de Parkinson (PDD) et qui sont des candidats pour un inhibiteur de l’acétylcholinestérase. La principale variable de l'étude était le changement de vitesse moyenne du centre de pression (CoP) en position debout après 6 mois de traitement. Les variables secondaires étaient les paramètres structuraux de posturographie dynamique, des échelles d’évaluation cliniques et les effets secondaires nécessitant une réduction de la dose. Méthodes: Des patients avec PDD ont été randomisé dans un ratio de 1 :1 impliquant une prise de rivastigmine orale ou transdermique avec des doses cibles de 6 mg deux fois par jour et 9,5 mg/10 cm2 par jour, respectivement. Les variables dépendantes ont été comparées au départ de l’étude et après 6 mois (comparaisons intra-groupes), de même qu'entre les groupes. Résultats: Dix-neuf patients ont complété l’étude (n=8 orale; n=11 transdermique). Des doses quotidiennes moyennes de 9,4 mg (± 1,5 mg) et 16,4 mg (± 3,6 mg) ont été administrées aux groupes oral et transdermique, respectivement. Le groupe transdermique a démontré une réduction significative de la vitesse moyenne du CoP de 15.8% (timbre: p=0,02; orale: réduction de 10,0%, p=0,16) lors de la condition d'équilibre la plus difficile (yeux fermés en maintenant l'équilibre sur une plateforme mobile synchronisée avec les déplacements du corps). Aucune différence n’a été trouvée entre les groupes (p=0,27). Concernant les paramètres structuraux, des améliorations significatives ont été observées au niveau de la durée moyenne des pics de stabilité de l'équilibre (timbre) et de la distance entre les pics de stabilité (orale) dans la condition d'équilibre la plus difficile. Aucun changement n’a été observé par rapport aux échelles cliniques. Six patients ont eu des effets secondaires mineurs nécessitant une réduction de dose (n=5 orale; n=1 transdermique). Conclusions: La rivastigmine pourrait améliorer certains éléments du contrôle postural de patients atteints de PDD, notamment la vitesse moyenne du CoP en position debout. Les bienfaits sont plus évidents sous les conditions qui challengent davantage l'équilibre.Objectives: To compare the efficacy and safety of oral and transdermal rivastigmine for postural instability in patients with Parkinson’s disease dementia (PDD) who were candidates for a cholinesterase inhibitor. The primary outcome was the change in mean velocity of the centre of pressure (CoP) after 6 months. Secondary outcomes included structural parameters of dynamic posturography, clinical rating scales and adverse events requiring dose reduction. Methods: Patients with PDD were randomized in a 1:1 ratio to oral or transdermal rivastigmine with target doses of 6 mg twice daily and 9.5 mg/10 cm2 daily, respectively. Outcomes were assessed at baseline and 6 months. Results were compared within and between groups. Results: Nineteen patients completed the study (n=8 oral, n=11 transdermal). Mean daily doses of 9.4 mg (± 1.5 mg) and 16.4 mg (± 3.6 mg) were achieved in the oral and transdermal groups, respectively. The transdermal group demonstrated a significant 15.8% decrease in mean velocity of CoP (patch: p <0.05; oral: 10.0% decrease, p=0.16) in the most difficult scenario (eyes closed with sway-referenced support). There was no difference between groups (p=0.27). For structural parameters, significant improvements were seen in the mean duration of peaks (patch) and inter-peak distance (oral) in the most difficult condition. No changes were observed in clinical rating scales. Six patients experienced non-serious adverse events requiring dose reduction (n= 5 oral; n=1 transdermal). Conclusions: Rivastigmine may improve certain elements of postural control, notably the mean velocity of CoP. Benefits appear to be more obvious under more taxing sensory conditions

Fifteen years of wireless sensors for balance assessment in neurological disorders

Balance impairment is a major mechanism behind falling along with environmental hazards. Under physiological conditions, ageing leads to a progressive decline in balance control per se. Moreover, various neurological disorders further increase the risk of falls by deteriorating specific nervous system functions contributing to balance. Over the last 15 years, significant advancements in technology have provided wearable solutions for balance evaluation and the management of postural instability in patients with neurological disorders. This narrative review aims to address the topic of balance and wireless sensors in several neurological disorders, including Alzheimer's disease, Parkinson's disease, multiple sclerosis, stroke, and other neurodegenerative and acute clinical syndromes. The review discusses the physiological and pathophysiological bases of balance in neurological disorders as well as the traditional and innovative instruments currently available for balance assessment. The technical and clinical perspectives of wearable technologies, as well as current challenges in the field of teleneurology, are also examined

Age Differences in Vestibular Processing: Neural and Behavioral Evidence

The vestibular system is well known for its role in balance, but its mechanisms of action in this role are not well understood. My dissertation aims to provide a better understanding of vestibular brain function, its correlation with postural control, and its alteration with advancing age. This is an important topic considering that falls are the current leading cause of injuries in older adults in the U.S., and they have negative consequences on wellbeing and independence. In this dissertation, I first review the conventional methods for studying vestibular function in the human brain, and I evaluate a novel MRI-compatible method, which relies on a pneumatic tapper. This approach successfully induces vestibular responses, while preventing the aversive effects of stimulation that are common in other approaches. Next, I assess age differences in brain responses to pneumatic vestibular stimulation, and find that older adults demonstrate less sensitivity to stimulation. Also, those with better postural control exhibit less deactivation of cross-modal sensory regions (e.g. visual and somatosensory cortices). This greater engagement of non-vestibular sensory regions in older adults with better balance could be a mechanism to compensate for inefficient vestibular processing. Consistent with this hypothesis, the relationship between postural control and deactivation of sensory regions was only evident in tasks of low difficulty (i.e. normal stance) in which compensatory neural recruitment might be most effective. After assessing the brain responses to vestibular stimulation in terms of activation and deactivation, I examine connectivity of the vestibular cortex with other regions. This last experiment demonstrates that vestibular cortex connectivity increases in response to vestibular stimulation, and young adults exhibit greater connectivity relative to older adults. Also, connectivity predicts postural stability in high difficulty tasks for young adults, and in low difficulty tasks for older adults. Better balance in young adults is associated with less vestibular connectivity (i.e. they engaged vestibular cortex more selectively), whereas better balance in older adults is associated with higher connectivity (i.e. more recruitment of other sensory regions). These findings reinforce the conclusions from the second experiment, and provide more evidence in support of the compensation related utilization of neural circuits hypothesis (CRUNCH) of neural processing in older adults.PHDKines & Psychology PhDUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttps://deepblue.lib.umich.edu/bitstream/2027.42/145857/1/fnoohi_1.pd

ALTERATIONS IN VISUAL PROCESSING AND ITS IMPACT ON UPRIGHT POSTURAL STABILITY IN ATHLETES FOLLOWING SPORT-RELATED CONCUSSION

Athletes are at risk of sustaining a concussion in all sports and at all competitive levels which may lead to balance impairments. Balance results from the integration of visual, vestibular, and somatosensory information. The underlying pathophysiology for balance impairments is not well understood and visuo-motor processing impairments and how these impairments contribute to balance in concussed athletes has not been reported. Objectives: (1) to investigate the influence of visual perturbation on upright postural stability and balance in athletes who have recently suffered a sports-related concussion, (2) to establish the test-retest reliability of a simple visuo-motor processing task. Design: A longitudinal, cohort design. Setting: University research laboratory. Subjects: Fourteen interscholastic, club, and intercollegiate athletes (8 males, 6 females, age 17.21±2.97 years, height 176.43±12.73cm, mass 75.55±22.76kg) participated. Seven subjects with acute concussions (injury) were matched to seven control subjects. Intervention(s): All subjects completed a simple visuo-motor processing task (SVMP), Sensory Organization Test (SOT), and modified Clinical Test of Sensory Interaction in Balance (mCTSIB). Each subject’s balance was tested under two visual testing conditions: (1) standard testing methods with normal visual fields, and (2) visual distraction through optical flow motion using a computer-generated optical flow pattern. Testing was done 24-48 hours and ten days following injury. The order of the testing was counterbalanced (standard protocol or visual distraction) and day of testing. Main Outcome Measures: Reaction time, accuracy, number of errors on SVMP; composite equilibrium score, sensory system preference on SOT; and mean center of gravity sway velocity on mCTSIB. Results: Significant impairments were noted on day 1 of testingcompared to day 10 for SVMP reaction time (day 1=496.18±52.82ms, day 10=439.01±20.62ms, F=4.72, p=0.01), and SOT composite equilibrium score standard (day 1=73.14±5.73, day 10=83.57±2.15, F=7.60, p\u3c0.001). Conclusion: Physiological changes occur immediately following concussions that affect the visual system, more specifically, visuo-motor processing. The SVMP task provides unique information about visuo-motor processing following a concussion that is not currently being assessed. Visuo-motor processing is correlated with upright balance and should be evaluated following a sports-related concussion

EEG-based investigation of cortical activity during Postural Control

The postural control system regulates the ability to maintain a stable upright stance and to react to changes in the external environment. Although once believed to be dominated by low-level reflexive mechanisms, mounting evidence has highlighted a prominent role of the cortex in this process. Nevertheless, the high-level cortical mechanisms involved in postural control are still largely unexplored. The aim of this thesis is to use electroencephalography, a widely used and non-invasive neuroimaging tool, to shed light on the cortical mechanisms which regulate postural control and allow balance to be preserved in the wake of external disruptions to one’s quiet stance. EEG activity has been initially analysed during a well-established postural task - a sequence of proprioceptive stimulations applied to the calf muscles to induce postural instability – traditionally used to examine the posturographic response. Preliminary results, obtained through a spectral power analysis of the data, highlighted an increased activation in several cortical areas, as well as different activation patterns in the two tested experimental conditions: open and closed eyes. An improved experimental protocol has then been developed, allowing a more advanced data analysis based on source reconstruction and brain network analysis techniques. Using this new approach, it was possible to characterise with greater detail the topological structure of cortical functional connections during the postural task, as well as to draw a connection between quantitative network metrics and measures of postural performance. Finally, with the integration of electromyography in the experimental protocol, we were able to gain new insights into the cortico-muscular interactions which direct the muscular response to a postural challenge. Overall, the findings presented in this thesis provide further evidence of the prominent role played by the cortex in postural control. They also prove how novel EEG-based brain network analysis techniques can be a valid tool in postural research and offer promising perspectives for the integration of quantitative cortical network metrics into clinical evaluation of postural impairment.Kerfi stöðustjórnunar er afturvirkt stýrikerfi sem vinnur stöðugt að því að viðhalda uppréttri stöðu líkamans og bregðast við ójafnvægi. Vaxandi þekking á undanförnum árum hefur lýst því að úrvinnsla þessara upplýsinga á sér stað á öllum stigum miðtaugakerfisins, þá sérstaklega barkarsvæði heilahvela. Engu að síður, er nákvæmu hlutverk heilabarkar við stöðustjórnun enn óljóst að mörgu leyti. Tilgangur þessa verkefnis var að rannsaka nánar hlutverk heilabarkar við truflun og áreiti á kerfi stöðustjórnarinnar, með notkun hágæða heilarafrits (EEG). Við byrjuðum á því að mæla heilarit einstaklinga meðan á þekktri líkamsstöðu-æfingu stóð, til þess að skoða svörun líkamans við röð titringsáreita sem beitt var á kálfavöðvana til að framkalla óstöðugleika. Bráðabirgðaniðurstöður fengnar með PSD-aðferð (power spectral analysis) leiddu í ljós aukna virkni á ákveðnum svæðum í heilaberki og sérstakt viðbragðsmynstur við að framkvæma æfinguna, annars vegar með lokuð augu og hins vegar opin augu. Rannsókn okkar hélt áfram með nýrri og þróaðari tækni sem gerði okkur kleift að framkvæma fullkomnari greiningaraðferðir til að túlka, greina og skilja merki frá heilaritnu. Með fullkomnari greiningaraðferðum var hægt að lýsa með nákvæmari hætti staðfræðilega uppbyggingu starfrænna tenginga í heilaberki meðan á líkamsstöðu æfingunni stóð, sem og að draga tengsl á milli megindlegra netmælinga og mælinga á líkamsstöðu. Að lokum bætist við vöðvarafritsmæling við aðferðafræðina, sem gaf okkur innsýn inn í samskipti heilabarka og vöðvana sem stýra vöðvaviðbrögðum og viðhalda líkamsstöðu við utanaðkomandi áreiti. Á heildina litið gefa niðurstöðurnar sem settar eru fram í þessari ritgerð enn sterkari vísbendingar um það áberandi hlutverk sem heilabörkurinn gegnir við stjórnun líkamsstöðu. Niðurstöðurnar sanna einnig hvernig ný aðferð á greiningu á tengslaneti heilans sem byggir á heilariti getur verið gilt tæki í líkamsstöðu rannsóknum og er nytsamlegt tól fyrir mælingar á heilakerfisneti í klínískt mat á skerðingu líkamsstöðu

DIFFERENCES IN POSTURAL CONTROL RESPONSES TO LEVELS OF VISUAL OCCLUSION IN INDIVIDUALS WITH CHRONIC ANKLE INSTABILITY

Chronic ankle instability (CAI) is a condition characterized by recurrent ankle sprains. Those with CAI are described as visually reliant due to postural control deficits observed under fully occluded visual conditions. Little is known about the influence of partially occluded vision on postural control in those with CAI. The purpose of this study was to examine the effect of CAI on postural control under progressive levels of visual occlusion and relate postural control under these conditions to visual function and sensory integration in those with CAI. Thirty-five participants with CAI and sixteen controls completed postural control assessments under four visual conditions:1) eyes-open, 2) low-occlusion, 3) high-occlusion, and 4) eyes-closed. Participants also completed visual performance (Senaptec Sensory Station) and sensory integration (Sensory Organization Test) assessments. Both groups demonstrated worse postural control under limited-vision conditions compared to eyes-open. Some measures of visual performance predicted postural control under both eyes-open and limited-vision conditions.Master of Art

EEG-based investigation of cortical activity during Postural Control

The postural control system regulates the ability to maintain a stable upright stance and to react to changes in the external environment. Although once believed to be dominated by low-level reflexive mechanisms, mounting evidence has highlighted a prominent role of the cortex in this process. Nevertheless, the high-level cortical mechanisms involved in postural control are still largely unexplored. The aim of this thesis is to use electroencephalography, a widely used and non-invasive neuroimaging tool, to shed light on the cortical mechanisms which regulate postural control and allow balance to be preserved in the wake of external disruptions to one’s quiet stance. EEG activity has been initially analysed during a well-established postural task - a sequence of proprioceptive stimulations applied to the calf muscles to induce postural instability – traditionally used to examine the posturographic response. Preliminary results, obtained through a spectral power analysis of the data, highlighted an increased activation in several cortical areas, as well as different activation patterns in the two tested experimental conditions: open and closed eyes. An improved experimental protocol has then been developed, allowing a more advanced data analysis based on source reconstruction and brain network analysis techniques. Using this new approach, it was possible to characterise with greater detail the topological structure of cortical functional connections during the postural task, as well as to draw a connection between quantitative network metrics and measures of postural performance. Finally, with the integration of electromyography in the experimental protocol, we were able to gain new insights into the cortico-muscular interactions which direct the muscular response to a postural challenge. Overall, the findings presented in this thesis provide further evidence of the prominent role played by the cortex in postural control. They also prove how novel EEG-based brain network analysis techniques can be a valid tool in postural research and offer promising perspectives for the integration of quantitative cortical network metrics into clinical evaluation of postural impairment

Effects of balance training on balance, gait and non-motor symptoms in individuals with Parkinson's disease

Postural instability (PI) is one of the most disabling symptoms of Parkinson’s disease (PD). PI is a well-known risk factor for falls in individuals with PD that worsens with disease progression. About 50-70% of people with PD fall once or more in a year, which is much higher than the 30% fall rate reported for community dwelling older individuals. Impaired balance associated with PI and fear of falling are factors related to decreased mobility and poor quality of life in individuals with PD. Several studies have examined the effects of exercise particularly strengthening and aerobic training on various motor and non-motor symptoms of PD. However to date, few studies have examined effects of balance specific interventions on balance, spatiotemporal gait, and non-motor symptoms such as fatigue, pain and depression. Moreover, none have used a commercially available device, Biodex Balance System (BSS) to implement a challenging balance training protocol. BSS consists of a moving platform that can be used to progressively challenge one’s balance while providing visual feedback. Finally, most of the previous studies did not report information pertaining to clinically meaningful changes in balance and its implications to physical function and quality of life in individuals with PD. The overall objective of this study was to evaluate whether short term progressively challenging balance specific training using the BSS improves balance, spatiotemporal gait and non-motor symptoms including fatigue, pain and depression in individuals with PD compared to usual non-progressive balance exercises. The central hypothesis is that challenging balance exercises, where individuals with PD are challenged out of their comfort zone for static and dynamic balance can significantly improve balance and spatiotemporal gait. Chapter 2 describes aims 1 and 2, utilizing 4 weeks of BBS balance training to determine changes in sway measures and spatio-temporal gait variables in individuals with PD. Ten individuals in a balance exercise group using the BSS and 10 individuals in general balance exercise group without Biodex (Non-BSS) completed the study. This study showed that 4 weeks of balance exercises using BSS resulted in significant within group improvement in sway area, center of pressure (CoP), path length in antero-posterior (AP) direction in the BSS group. We also found significant within group improvements in the balance measured by Berg Balance Scale, gait velocity, and step length in both groups. Additionally, we found significant within group improvements in functional scores measured by the Timed Up and Go and 6 Minute Walk Test in both groups. However, we did not find significant between group differences for any of the outcome variables. Due to technical failure in the system, we were not able to report force plate data from the non-BSS group. Chapter 3 describes aim 3, where 4 weeks of BSS training was utilized to determine changes in fatigue, pain, depression, fear of falling and quality of life in individuals with PD. Although motor symptoms of PD are described widely in the literature, and several studies report improvement in motor symptoms following various exercise trainings, little has been done to determine the efficacy of exercise interventions on the non - motor symptoms of PD. Aerobic exercise, strengthening, gait, tai-chi, qigong, and yoga therapy have been shown to improve motor deficits in PD. However, no study has examined the effects of balance training with BSS on non-motor features such as depression, fatigue, pain and fear of falling in individuals with PD. In our study, we determined the effects of balance training on non - motor symptoms of PD. The results demonstrated that 4 weeks of balance training resulted in a non-significant trend toward improvement in depression, pain, and fear of falling, and only the BSS training group demonstrated statistically significant improvement in fatigue. In summary, this dissertation work provides evidence that the use of the BSS is feasible, safe, and effective in improving balance, gait, and function in individuals with PD. However further study with a larger sample size, randomized control design, and biomechanical (force plate) data in both groups is required to better understand the role of challenging balance training in this population. The findings of this dissertation work have implications about designing future studies with specific intensity of balance exercises needed to make meaningful changes in balance, gait and non-motor symptoms of not only the individuals with PD but also in individuals with other neurological disorders resulting in PI

Parkinsonian sensory integration for balance control : time based postural effects of alterations in sensory information

xii, 81 leaves ; 29 cm.Changes in postural stability following sensory manipulation were investigated among Parkinson's disease patients and healthy older adults. Sixteen Parkinson's disease patients (PD; mean age 68.2 + 2.7 years) and sixteen older adults (control; mean age 67.6 + 2.6 years) performed quiet standing trials that progressed through baseline, sensory manipulation, and reintegration. Postural control following visual deprivation was assessed following alternate removal and reinsertion of visual information. Postural recovery following sensory incongruence was assessed following the termination of visual, somatosensory, and visuosomatosensory incongruence. PD patients' balance was disrupted following visual deprivation, and was initially disrupted when visual information was returned. PD patients' pstural recovery was comparable to control subjects when sensory incongruence ended. These findings indicate that situations of visual deprivation in particular are initially disruptive for PD patients, and imply initial difficulty for sensory reorganization in these patients. Our results provide insight into environmental situations imposing greater fall risk among the parkinsonian population

The study of individual perception and neural control underlying movement in coordinating postural control when there is an increase in complexity of environmental and task constraints in CAI individuals compared to healthy controls

Individuals with Chronic Ankle Instability (CAI) commonly exhibit postural control (stability, adaptation) deficits and altered gait (walking, running) mechanics (Hertel, 2008; Hertel and Corbett, 2019). These impairments in motor behaviors have been hypothesized to be a result of inadequate, yet inherent interactions between individual perception (i.e., sensory systems) and movement (action) integrated at the central nervous system (CNS), resulting in less flexible and adaptable sensorimotor systems. Flexibility and adaptability of sensorimotor systems reflecting on underlying biological noise (movement variability) are critical to coordinate the sensory reweighting system. The sensory reweighting system assigns a relative weight to each sensory system based on the complexity of organismic, environmental, and task constraints to convey redundant and convergent sensory feedback at the CNS. An adequate sensory reweighting system results in sufficient multisensory integration by filtering all potential distractors, the irrelevant sensory information, to the context (e.g., task goals). Successful multisensory integration allows the CNS to integrate the context-relevant sensory information necessary to manage postural control that is the foundation of motor control to achieve suitable performance and adapt to a sudden environmental change. However, the gap exists in the literature to understand the integration phenomenon on how individual elements (i.e., sensory reweighting system, movement variability) contribute to the interaction between perception and movement, especially when environmental and task constraints increase in the same cohort of participants with and without CAI. Therefore, the primary purpose of this study was to understand the modulation of 1) the sensory reweighting system and postural control, 2) postural adaptation to a sudden change in the environment in the direction of lateral ankle sprain mechanisms, and 3) movement variability, an underlying biological noise pertaining to postural control, when the complexity of environmental and task constraints are manipulated in CAI individuals compared to healthy controls. A total of 44 physically active individuals, consisting of 22 individuals with CAI (13 females, 9 males; age: 26.09 ± 5.76 years; height: 172.25 ± 9.76 cm; weight: 76.18 ± 14.91 kg) and 22 individuals without CAI (13 females, 9 males; age: 25.41 ± 5.92 years; height: 169.70 ± 9.32 cm; weight: 71.98 ± 14.79 kg) volunteered to participate in this mixed-model repeated-measures study. The NeuroCom Sensory Organization Test (SOT) and Adaptation Test (SMART EquiTest, NeuroCom International Inc., Clackamas, OR) were utilized to examine postural control (equilibrium scores), postural adaptation (sway energy scores), the sensory reweighting system (sensory reweighting ratios), and movement variability (sample entropy) while controlling posture in double- and single-limb (injured, uninjured) stances in individuals with and without CAI. Interestingly, CAI individuals controlled posture very similar to healthy controls. The unique finding of this study was that group differences in the sensory reweighting system depended on both task constraints and sensory systems; CAI individuals upweighted on vestibular feedback when the SOT manipulated somatosensory and visual feedback while controlling posture in the injured-limb. Both groups weighted on somatosensory and visual feedback similarly with continuous emphasis on vision during individual tasks (stance limbs: double, injured, uninjured). Therefore, we contend CAI individuals upweighted on vestibular feedback, which is an independent sole veridical reference to self-motion, when sensory conflicts and task constraints became greater standing in the injured-limb. These findings also imply an effective multisensory integration among CAI. CAI individuals exhibited respective superior postural adaptation to a sudden environmental change in a support surface with plantarflexion rotation and in the uninjured-limb than healthy controls. Superior postural adaptation is indicative of pre-programmed feedforward motor control. In addition, lower movement variability in postural control was noted in the uninjured- and injured-limbs in CAI. Group differences in movement variability depended on task constraints: those individuals with CAI lowered variability in the uninjured-limb when no sensory feedback was manipulated, and in both the uninjured- and injured-limbs when they were forced to reweight on vestibular feedback with manipulation of somatosensory and visual feedback. Lowered movement variability exhibited with an increase in task constraints in the injured- and uninjured-limbs may be indicative of a mechanism that CAI implemented to provide a boundary to freeze the degree-of-freedom (redundancy in sensory feedback) to achieve effective multisensory integration. Collectively, our findings of superior postural adaptation and lower movement variability in postural control for CAI may imply an existent change in central organization and implementation of supraspinal mechanisms of postural control. Furthermore, postural control, postural adaptation, and movement variability in individuals with and without CAI depended on the environmental or task constraints. Environment- and task-dependent postural control, postural adaptation, and movement variability contribute to motor behaviors throughout the lifespan. Therefore, taking a multisensory-feedback approach by recognizing when to increase environmental and task constraints may optimize rehabilitation intervention to prevent subsequent ankle sprains in individuals with CAI