Gait Asymmetry in People With Parkinson’s Disease Is Linked to Reduced Integrity of Callosal Sensorimotor Regions

Background: Individuals with Parkinson’s disease (PD) often manifest significant temporal and spatial asymmetries of the lower extremities during gait, which significantly contribute to mobility impairments. While the neural mechanisms underlying mobility asymmetries within this population remain poorly understood, recent evidence points to altered microstructural integrity of white matter fiber tracts within the corpus callosum as potentially playing a substantial role. Objectives: The purpose of this study was to quantify spatial and temporal gait asymmetries as well as transcallosal microstructural integrity of white matter fiber tracts connecting the primary and secondary sensorimotor cortices in people with PD and age-matched control participants. Methods: Spatial and temporal gait asymmetry in the levodopa off state was assessed using an instrumented walkway. On the next day, diffusion-weighted images were collected to assess white matter microstructural integrity in transcallosal fibers connecting the homologous sensorimotor cortical regions. Results: People with PD exhibited significantly more temporal and spatial gait asymmetry than healthy control subjects. Furthermore, people with PD had significantly reduced white matter microstructural integrity of transcallosal fibers connecting homologous regions of the pre-supplementary motor and supplementary motor areas (SMAs), but not the primary motor or somatosensory cortices. Finally, reduced transcallosal fiber tract integrity of the pre-SMA and S1 was associated with greater step length asymmetry in people with PD. Conclusion: People with PD showed increased step length asymmetries and decreased microstructural integrity of callosal white matter tracts connecting the higher-order sensorimotor cortices (pre-SMA and SMA). The strong association between gait asymmetries and corpus collosum integrity, supports the hypothesis that reduced transcallosal structural connectivity is a significant mechanism underlying gait asymmetries in people with PD

Sensory Re-weighting for Postural Control in Parkinson’s Disease

Postural instability in Parkinson’s disease (PD) is characterized by impaired postural responses to transient perturbations, increased postural sway in stance and difficulty transitioning between tasks. In addition, some studies suggest that loss of dopamine in the basal ganglia due to PD results in difficulty in using proprioceptive information for motor control. Here, we quantify the ability of subjects with PD and age-matched control subjects to use and re-weight sensory information for postural control during steady-state conditions of continuous rotations of the stance surface or visual surround. We measure the postural sway of subjects in response to a pseudorandom, surface-tilt stimulus with eyes closed, and in response to a pseudorandom, visual-tilt stimulus. We use a feedback control model of the postural control system to interpret our results, focusing on sensory weighting as a function of stimulus amplitude. We find that subjects with PD can re-weight their dependence upon sensory information in response to changes in surface- or visual-stimulus amplitude. Specifically, subjects with PD behaved like age-matched control subjects by decreasing proprioceptive contribution to stance control with increasing surface-tilt amplitude and decreasing visual contribution with increasing visual-tilt amplitude. However, subjects with PD do not decrease their reliance on proprioception as much as age-matched controls for small increases in surface-stimulus amplitudes. Levodopa medication did not affect sensory re-weighting behaviors for postural control. The impairment in PD subject’s ability to respond differently to small changes in surface rotation amplitudes is consistent with an increased threshold for perceiving proprioceptive signals, which may result from decreased signal-to-noise in the dopaminergic pathways associated with sensory processing and/or sensory integration

Cognitive function in people with and without freezing of gait in Parkinson’s disease

Freezing of gait (FOG) is common in people with Parkinson’s disease (PD) which is extremely debilitating. One hypothesis for the cause of FOG episodes is impaired cognitive control, however, this is still in debate in the literature. We aimed to assess a comprehensive range of cognitive tests in older adults and people with Parkinson’s with and without FOG and associate FOG severity with cognitive performance. A total of 227 participants took part in the study which included 80 healthy older adults, 81 people with PD who did not have FOG and 66 people with PD and FOG. A comprehensive battery of neuropsychological assessments tested cognitive domains of global cognition, executive function/attention, working memory, and visuospatial function. The severity of FOG was assessed using the new FOG questionnaire and an objective FOG severity score. Cognitive performance was compared between groups using an ANCOVA adjusting for age, gender, years of education and disease severity. Correlations between cognitive performance and FOG severity were analyzed using partial correlations. Cognitive differences were observed between older adults and PD for domains of global cognition, executive function/attention, and working memory. Between those with and without FOG, there were differences for global cognition and executive function/attention, but these differences disappeared when adjusting for covariates. There were no associations between FOG severity and cognitive performance. This study identified no significant difference in cognition between those with and without FOG when adjusting for covariates, particularly disease severity. This may demonstrate that complex rehabilitation programs may be undertaken in those with FOG

CONTINUOUS MONITORING OF MOVEMENT IN PATIENTS WITH PARKINSON'S DISEASE USING INERTIAL SENSORS

Gait impairment is a hallmark of Parkinson's disease (PD). The assessment of gait and balance in the clinic may not adequately reflect mobility in daily life. It is often reported that patients with PD walk better when they are examined in an outpatient clinic or in a research laboratory than at home. Continuous monitoring of mobility during spontaneous daily activities may provide clinicians and patients with objective measures of the quality of their mobility. We show that continuous monitoring of spontaneous gait with wearable inertial sensors during daily activities is feasible for patients with PD. We tested 13 patients with PD and 8 healthy controls to evaluate the feasibility of using wearable inertial sensors at home for one week. The inertial system successfully detects walking bouts and provides sixteen objective measures that can characterize gait changes in patients with PD

Influence of vision on adaptive postural responses following standing on an incline

Previous studies demonstrated a leaning after-effect (LAE) following standing or walking on an inclined surface consistent with a long-lasting, somatosensory memory for body orientation relative to the surface. Here, we asked whether providing a brief visual reference during LAE resets postural orientation to the new visual reference. The results showed that subjects immediately return to upright when eyes were opened briefly during the post-incline period. However, the subjects also immediately resumed leaning after closing their eyes again following 20 s of eyes open. The duration of LAE was not influenced by 1 or 2 brief periods of vision. Also, the amplitude of the lean following the brief vision period was often larger than when subjects had their eyes closed for the entire post-incline period. These results suggest a powerful somatosensory memory contribution to postural orientation in space that is not eliminated or recalibrated with brief exposure to a visual reference

Podokinetic stimulation causes shifts in perception of straight ahead

Podokinetic after-rotation (PKAR) is a phenomenon in which subjects inadvertently rotate when instructed to step in place after a period of walking on a rotating treadmill. PKAR has been shown to transfer between different forms of locomotion, but has not been tested in a non-locomotor task. We conducted two experiments to assess effects of PKAR on perception of subjective straight ahead and on quiet standing posture. Twenty-one healthy young right-handed subjects pointed to what they perceived as their subjective straight ahead with a laser pointer while they were recorded by a motion capture system both before and after a training period on the rotating treadmill. Subjects performed the pointing task while standing, sitting on a chair without a back, and a chair with a back. After the training period, subjects demonstrated a significant shift in subjective straight ahead, pointing an average of 29.1 ± 10.6 degrees off of center. The effect was direction-specific, depending on whether subjects had trained in the clockwise or counter-clockwise direction. Postures that limited subjects’ ability to rotate the body in space resulted in reduction, but not elimination, of the effect. The effect was present in quiet standing and even in sitting postures where locomotion was not possible. The robust transfer of PKAR to non-locomotor tasks, and across locomotor forms as demonstrated previously, is in contrast to split-belt adaptations that show limited transfer. We propose that, unlike split-belt adaptations, podokinetic adaptations are mediated at supraspinal, spatial orientation areas that influences spinal-level circuits for locomotion

Method to Measure Tone of Axial and Proximal Muscle

The control of tonic muscular activity remains poorly understood. While abnormal tone is commonly assessed clinically by measuring the passive resistance of relaxed limbs1, no systems are available to study tonic muscle control in a natural, active state of antigravity support. We have developed a device (Twister) to study tonic regulation of axial and proximal muscles during active postural maintenance (i.e. postural tone). Twister rotates axial body regions relative to each other about the vertical axis during stance, so as to twist the neck, trunk or hip regions. This twisting imposes length changes on axial muscles without changing the body's relationship to gravity. Because Twister does not provide postural support, tone must be regulated to counteract gravitational torques. We quantify this tonic regulation by the restive torque to twisting, which reflects the state of all muscles undergoing length changes, as well as by electromyography of relevant muscles. Because tone is characterized by long-lasting low-level muscle activity, tonic control is studied with slow movements that produce "tonic" changes in muscle length, without evoking fast "phasic" responses. Twister can be reconfigured to study various aspects of muscle tone, such as co-contraction, tonic modulation to postural changes, tonic interactions across body segments, as well as perceptual thresholds to slow axial rotation. Twister can also be used to provide a quantitative measurement of the effects of disease on axial and proximal postural tone and assess the efficacy of intervention

The quality of turning in Parkinson's disease: a compensatory strategy to prevent postural instability?

The ability to turn while walking is essential for daily living activities. Turning is slower and more steps are required to complete a turn in people with Parkinson's disease (PD) compared to control subjects but it is unclear whether this altered strategy is pathological or compensatory. The aim of our study is to characterize the dynamics of postural stability during continuous series of turns while walking at various speeds in subjects with PD compared to control subjects. We hypothesize that people with PD slow their turns to compensate for impaired postural stability

Postural Compensation for Unilateral Vestibular Loss

Postural control of upright stance was investigated in well-compensated, unilateral vestibular loss (UVL) subjects compared to age-matched control subjects. The goal was to determine how sensory weighting for postural control in UVL subjects differed from control subjects, and how sensory weighting related to UVL subjects’ functional compensation, as assessed by standardized balance and dizziness questionnaires. Postural control mechanisms were identified using a model-based interpretation of medial–lateral center-of-mass body-sway evoked by support-surface rotational stimuli during eyes-closed stance. The surface-tilt stimuli consisted of continuous pseudorandom rotations presented at four different amplitudes. Parameters of a feedback control model were obtained that accounted for each subject’s sway response to the surface-tilt stimuli. Sensory weighting factors quantified the relative contributions to stance control of vestibular sensory information, signaling body-sway relative to earth-vertical, and proprioceptive information, signaling body-sway relative to the surface. Results showed that UVL subjects made significantly greater use of proprioceptive, and therefore less use of vestibular, orientation information on all tests. There was relatively little overlap in the distributions of sensory weights measured in UVL and control subjects, although UVL subjects varied widely in the amount they could use their remaining vestibular function. Increased reliance on proprioceptive information by UVL subjects was associated with their balance being more disturbed by the surface-tilt perturbations than control subjects, thus indicating a deficiency of balance control even in well-compensated UVL subjects. Furthermore, there was some tendency for UVL subjects who were less able to utilize remaining vestibular information to also indicate worse functional compensation on questionnaires

Comparing the Mini-BESTest with the Berg Balance Scale to Evaluate Balance Disorders in Parkinson's Disease

Objective. The purpose of this study was to explore the usefulness of the Mini-BESTest compared to the Berg Balance Scale in evaluating balance in people with PD of varying severity. We evaluated (1) the distribution of patients scores to look for ceiling effects, (2) concurrent validity with severity of disease, and (3) the sensitivity/specificity of separating people with or without postural response deficits. Subjects. Ninety-seven people with PD were tested for balance deficits using the Berg, Mini-BESTest, Unified Parkinson's Disease Rating Scale (UPDRS) III and the Hoehn & Yahr (H&Y) disease severity classification. Setting. Clinical research facility at Oregon Health & Science University. Results. The Mini-BESTest is highly correlated with the Berg (r = 0.79, P < 0.001), but avoids the ceiling compression effect of the Berg for mild PD (skewness −2.30 Berg, −0.93 Mini-BESTest). Consequently, the Mini-BESTest is more effective than the Berg for predicting UPDRS Motor score (P < 0.001 Mini-BESTest versus P = 0.86 Berg), and for discriminating between those with and without postural response deficits as measured by the H&Y (ROC differential P = 0.06). Conclusion. The Mini-BESTest is a promising tool for discerning balance deficits in patients with PD, most importantly those with more subtle deficits