Bimal Lakhani

Impairments in Systems Underlying Control of Balance in COPD

BACKGROUND Although balance deficits are increasingly recognized in COPD, little is known regarding the disordered subcomponents underlying the control of balance. We aimed to determine the specific components of balance that are impaired in COPD and to investigate the association among balance, peripheral muscle strength, and physical activity. METHODS Balance, physical activity, and lower extremity muscle strength were assessed in 37 patients with COPD and 20 age-matched healthy control subjects using the Balance Evaluation Systems Test (BESTest), the Physical Activity Scale for the Elderly, and an isokinetic dynamometer, respectively. A subset of subjects (20 patients with COPD and 20 control subjects) underwent a second testing session in which postural perturbations were delivered using a lean-and-release system. RESULTS Subjects with COPD (age, 71 ± 7 years; FEV(1), 39% ± 16% predicted) exhibited significantly lower scores than did control subjects (age, 67 ± 9 years) on all of the BESTest subscales (all P < .001). In response to anterior perturbations, subjects with COPD showed a longer time to foot-off (P = .027) and foot contact (P = .018), and a longer duration anticipatory phase (P = .008) compared with control subjects. Muscle strength (P = .008) and self-reported physical activity (P = .033) explained 35% of the variance in balance in subjects with COPD. CONCLUSIONS Individuals with COPD exhibit impairments in all balance subcomponents and demonstrate slower reaction times in response to perturbations. Deficits in balance are associated with reduced physical activity levels and skeletal muscle weakness.

Determinants of Limb Preference for Initiating Compensatory Stepping Poststroke

OBJECTIVE To investigate the determinants of limb preference for initiating compensatory stepping poststroke. DESIGN Retrospective chart review. SETTING Inpatient rehabilitation. PARTICIPANTS Convenience sample of individuals admitted to inpatient rehabilitation with poststroke hemiparesis. INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Compensatory stepping responses were evoked using a lean-and-release postural perturbation. The limb used to initiate compensatory stepping was determined. The relationships between stepping with the paretic limb and premorbid limb dominance, weight bearing on the paretic limb in quiet standing, ability to bear weight on the paretic limb, preperturbation weight bearing on the paretic limb, and lower-limb motor recovery scores were determined. RESULTS The majority (59.1%) of responses were steps initiated with the nonparetic limb. Increased lower-limb motor recovery scores and preperturbation weight bearing on the nonparetic limb were significantly related to increased frequency of stepping with the paretic limb. When the preferred limb was physically blocked, an inappropriate response was initiated in 21% of trials (ie, nonstep responses or an attempt to step with the blocked limb). CONCLUSIONS This study reveals the challenges that individuals with poststroke hemiparesis face when executing compensatory stepping responses to prevent a fall after a postural perturbation. The inability or challenges to executing a compensatory step with the paretic limb may increase the risk for falls poststroke.

Characterizing the determinants of limb preference for compensatory stepping in healthy young adults

BACKGROUND Compensatory stepping responses are frequently observed following postural perturbations. Compensatory steps require extremely rapid onset timing while maintaining sophisticated control of limb placement. However, the influence of asymmetric limb loading on compensatory stepping limb preference and step characteristics is unknown. The purpose of this study was to gain an understanding of the factors that influence limb preference for compensatory stepping under symmetric and asymmetric loading. METHODS Ten healthy young individuals (mean age 24±3 years) experienced postural perturbations delivered using a lean-and-release system. Perturbations were delivered during three different loading conditions: (1) symmetric stance, (2) asymmetric stance with 30-70% body weight over the preferred limb and, (3) asymmetric stance with the unloaded (30% body weight) limb constrained. Kinematic and kinetic data were collected from three force plates mounted in the platform and a three-dimensional motion analysis system. RESULTS As stance loading on the preferred limb increased, step frequency with the preferred limb decreased. Forced stepping with the preferred limb loaded at 70% body weight resulted in shorter (p=0.005) and more laterally displaced (p<0.001) steps as well as non-significant trends towards faster swing time (p=0.057) and shorter time to foot-off (p=0.081) compared to steps taken from symmetric stance. DISCUSSION Healthy young adults prefer to step with the more unloaded limb. However, when forced to step with an asymmetrically vertically loaded limb, individuals demonstrate a number of spatio-temporal characteristics that may indicate increased instability.

Impaired Reactive Stepping Among Patients Ready for Discharge From Inpatient Stroke Rehabilitation

Background Individuals with stroke are at increased risk for falls soon after hospital discharge. The ability to react to a balance perturbation, specifically with a rapid step, is critical to maintain balance and prevent falls. Objective The purpose of the study was to determine the prevalence of impaired reactive stepping responses in an ambulatory group of patients with stroke who were preparing for discharge from inpatient rehabilitation and the relationship to patient performance on commonly used clinical measures of balance, mobility, and lower limb impairment. Design This study was a retrospective analysis of patient admissions over a 3-year period. Methods Charts were reviewed for patients who, at time of discharge, had completed a perturbation-evoked reactive stepping assessment. Results Ninety-nine (71%) of 139 patients had impaired stepping reactions characterized by the need for assistance, an inability to step with either lower limb, or the need for multiple-step responses. There was a statistically significant difference in clinical scores between those with and without impaired stepping, but groups were characterized by considerable variation in clinical profiles. For example, Berg Balance Scale scores ranged from 25 to 55 versus 20 to 56 and gait speeds ranged from 0.17 to 1.43 versus 0.26 to 1.55 m/s for patients who demonstrated a failed step versus a successful step, respectively. Limitations Not all patients who attended stroke rehabilitation received a reactive stepping assessment at discharge. Conclusions Impaired reactive stepping is a prevalent problem for ambulatory patients with stroke preparing for discharge, possibly increasing their risk of falling when faced with the challenges of community ambulation. Specific tests that target the capacity to perform perturbation-evoked stepping reactions may be important to identify those at risk for falls and to direct appropriate intervention strategies.

Electrophysiological correlates of changes in reaction time based on stimulus intensity

Background Although reaction time is commonly used as an indicator of central nervous system integrity, little is currently understood about the mechanisms that determine processing time. In the current study, we are interested in determining the differences in electrophysiological events associated with significant changes in reaction time that could be elicited by changes in stimulus intensity. The primary objective is to assess the effect of increasing stimulus intensity on the latency and amplitude of afferent inputs to the somatosensory cortex, and their relation to reaction time. Methods Median nerve stimulation was applied to the non-dominant hand of 12 healthy young adults at two different stimulus intensities (HIGH & LOW). Participants were asked to either press a button as fast as possible with their dominant hand or remain quiet following the stimulus. Electroencephalography was used to measure somatosensory evoked potentials (SEPs) and event related potentials (ERPs). Electromyography from the flexor digitorum superficialis of the button-pressing hand was used to assess reaction time. Response time was the time of button press. Results Reaction time and response time were significantly shorter following the HIGH intensity stimulus compared to the LOW intensity stimulus. There were no differences in SEP (N20 & P24) peak latencies and peak-to-peak amplitude for the two stimulus intensities. ERPs, locked to response time, demonstrated a significantly larger pre-movement negativity to positivity following the HIGH intensity stimulus over the Cz electrode. Discussion This work demonstrates that rapid reaction times are not attributable to the latency of afferent processing from the stimulated site to the somatosensory cortex, and those latency reductions occur further along the sensorimotor transformation pathway. Evidence from ERPs indicates that frontal planning areas such as the supplementary motor area may play a role in transforming the elevated sensory volley from the somatosensory cortex into a more rapid motor response.

Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis

In individuals with multiple sclerosis (MS), transcranial magnetic stimulation (TMS) may be employed to assess the integrity of corticospinal system and provides a potential surrogate biomarker of disability. The purpose of this study was to provide a comprehensive examination of the relationship between multiple measures corticospinal excitability and clinical disability in MS (expanded disability status scale (EDSS)). Bilateral corticospinal excitability was assessed using motor evoked potential (MEP) input-output (IO) curves, cortical silent period (CSP), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and transcallosal inhibition (TCI) in 26 individuals with MS and 11 healthy controls. Measures of corticospinal excitability were compared between individuals with MS and controls. We evaluated the relationship(s) between age and clinical demographics such as age at MS onset (AO), disease duration (DD) and clinical disability (EDSS) with measures of corticospinal excitability. Corticospinal excitability thresholds were higher, MEP latency and CSP onset delayed and MEP durations prolonged in individuals with MS compared to controls. Age, DD and EDSS correlated with corticospinal excitability thresholds. Also, TCI duration and the linear slope of the MEP amplitude IO curve correlated with EDSS. Hierarchical regression modeling demonstrated that combining multiple TMS-based measures of corticospinal excitability accounted for unique variance in clinical disability (EDSS) beyond that of clinical demographics (AO, DD). Our results indicate that multiple TMS-based measures of corticospinal and interhemispheric excitability provide insights into the potential neural mechanisms associated with clinical disability in MS. These findings may aid in the clinical evaluation, disease monitoring and prediction of disability in MS.

Motor Skill Acquisition Promotes Human Brain Myelin Plasticity

Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI), the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements) using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus). In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.

Evaluating interhemispheric cortical responses to transcranial magnetic stimulation in chronic stroke: A TMS-EEG investigation

TMS-evoked cortical responses can be measured using simultaneous electroencephalography (TMS-EEG) to directly quantify cortical connectivity in the human brain. The purpose of this study was to evaluate interhemispheric cortical connectivity between the primary motor cortices (M1s) in participants with chronic stroke and controls using TMS-EEG. Ten participants with chronic stroke and four controls were tested. TMS-evoked responses were recorded at rest and during a typical TMS assessment of transcallosal inhibition (TCI). EEG recordings from peri-central gyral electrodes (C3 and C4) were evaluated using imaginary phase coherence (IPC) analyses to quantify levels of effective interhemispheric connectivity. Significantly increased TMS-evoked beta (15-30Hz frequency range) IPC was observed in the stroke group during ipsilesional M1 stimulation compared to controls during TCI assessment but not at rest. TMS-evoked beta IPC values were associated with TMS measures of transcallosal inhibition across groups. These results suggest TMS-evoked EEG responses can index abnormal effective interhemispheric connectivity in chronic stroke.

Does the movement matter?: determinants of the latency of temporally urgent motor reactions.

BACKGROUND Extremely rapid movements are frequently executed in response to novel, potentially threatening stimuli. The mechanism by which these sophisticated responses are generated is a topic of debate. The current study investigates: 1) the importance of stimulus-response congruence in rapid responses and 2) the relationship between the autonomic nervous system (ANS) and response time. METHODS Sixteen participants were seated in a chair that could tilt backwards 13°. Participants were instructed to react as fast as possible in response to either an auditory cue (AUD) or balance perturbation (chair tilt) (PERT) and completed one of three different tasks: reach-to-grasp a fixed handle (FIXED), reach-to-grasp a free moving handle (FREE) or plantar flex the left foot (FOOT). Electromyography and electrodermal activity were recorded. RESULTS For all tasks, muscle onset latency was shorter and muscle response amplitude was greater following the PERT cue compared to the AUD cue. In contrast, there were no differences in onset latency between motor response conditions. Electrodermal response amplitude was greater in the FIXED and FREE conditions than in the FOOT condition. DISCUSSION Even in situations where the stimulus was incongruent with the response, muscle onset latencies were evoked faster following the perturbation. The response latencies were determined by stimulus characteristics and the most rapid responses were not reliant on stimulus-response congruence. It remains unclear how it is possible to achieve such rapid response latencies to whole body perturbations but we speculate there may exist similar pathways that are uniquely facilitated by a stimulus dependent ANS response.

Compensatory motor network connectivity is associated with motor sequence learning after subcortical stroke.

Following stroke, functional networks reorganize and the brain demonstrates widespread alterations in cortical activity. Implicit motor learning is preserved after stroke. However the manner in which brain reorganization occurs, and how it supports behavior within the damaged brain remains unclear. In this functional magnetic resonance imaging (fMRI) study, we evaluated whole brain patterns of functional connectivity during the performance of an implicit tracking task at baseline and retention, following 5 days of practice. Following motor practice, a significant difference in connectivity within a motor network, consisting of bihemispheric activation of the sensory and motor cortices, parietal lobules, cerebellar and occipital lobules, was observed at retention. Healthy subjects demonstrated greater activity within this motor network during sequence learning compared to random practice. The stroke group did not show the same level of functional network integration, presumably due to the heterogeneity of functional reorganization following stroke. In a secondary analysis, a binary mask of the functional network activated from the aforementioned whole brain analyses was created to assess within-network connectivity, decreasing the spatial distribution and large variability of activation that exists within the lesioned brain. The stroke group demonstrated reduced clusters of connectivity within the masked brain regions as compared to the whole brain approach. Connectivity within this smaller motor network correlated with repeated sequence performance on the retention test. Increased functional integration within the motor network may be an important neurophysiological predictor of motor learning-related change in individuals with stroke.