The Cortical Response Evoked by Robotic Wrist Perturbations Reflects Level of Proprioceptive Impairment After Stroke.

Background: Proprioception is important for regaining motor function in the paretic upper extremity after stroke. However, clinical assessments of proprioception are subjective and require verbal responses from the patient to applied proprioceptive stimuli. Cortical responses evoked by robotic wrist perturbations and measured by electroencephalography (EEG) may be an objective method to support current clinical assessments of proprioception. Objective: To establish whether evoked cortical responses reflect proprioceptive deficits as assessed by clinical scales and whether they predict upper extremity motor function at 26 weeks after stroke. Methods: Thirty-one patients with stroke were included. In week 1, 3, 5, 12, and 26 after stroke, the upper extremity sections of the Erasmus modified Nottingham Sensory Assessment (EmNSA-UE) and the Fugl-Meyer Motor Assessment (FM-UE) and the EEG responses (64 channels) to robotic wrist perturbations were measured. The extent to which proprioceptive input was conveyed to the affected hemisphere was estimated by the signal-to-noise ratio (SNR) of the evoked response. The relationships between SNR and EmNSA-UE as well as SNR and time after stroke were investigated using linear regression. Receiver-operating-characteristic curves were used to compare the predictive values of SNR and EmNSA-UE for predicting whether patients regained some selective motor control (FM-UE > 22) or whether they could only move their paretic upper extremity within basic limb synergies (FM-UE ≤ 22) at 26 weeks after stroke. Results: Patients (N = 7) with impaired proprioception (EmNSA-UE proprioception score < 8) had significantly smaller SNR than patients with unimpaired proprioception (N = 24) [EmNSA-UE proprioception score = 8, t(29) = 2.36, p = 0.03]. No significant effect of time after stroke on SNR was observed. Furthermore, there was no significant difference in the predictive value between EmNSA-UE and SNR for predicting motor function at 26 weeks after stroke. Conclusion: The SNR of the evoked cortical response does not significantly change as a function of time after stroke and differs between patients with clinically assessed impaired and unimpaired proprioception, suggesting that SNR reflects persistent damage to proprioceptive pathways. A similar predictive value with respect to EmNSA-UE suggests that SNR may be used as an objective predictor next to clinical sensory assessments for predicting motor function at 26 weeks after stroke.

Smoothness metrics for reaching performance after stroke. Part 1: which one to choose?

BACKGROUND: Smoothness is commonly used for measuring movement quality of the upper paretic limb during reaching tasks after stroke. Many different smoothness metrics have been used in stroke research, but a 'valid' metric has not been identified. A systematic review and subsequent rigorous analysis of smoothness metrics used in stroke research, in terms of their mathematical definitions and response to simulated perturbations, is needed to conclude whether they are valid for measuring smoothness. Our objective was to provide a recommendation for metrics that reflect smoothness after stroke based on: (1) a systematic review of smoothness metrics for reaching used in stroke research, (2) the mathematical description of the metrics, and (3) the response of metrics to simulated changes associated with smoothness deficits in the reaching profile. METHODS: The systematic review was performed by screening electronic databases using combined keyword groups Stroke, Reaching and Smoothness. Subsequently, each metric identified was assessed with mathematical criteria regarding smoothness: (a) being dimensionless, (b) being reproducible, (c) being based on rate of change of position, and (d) not being a linear transform of other smoothness metrics. The resulting metrics were tested for their response to simulated changes in reaching using models of velocity profiles with varying reaching distances and durations, harmonic disturbances, noise, and sub-movements. Two reaching tasks were simulated; reach-to-point and reach-to-grasp. The metrics that responded as expected in all simulation analyses were considered to be valid. RESULTS: The systematic review identified 32 different smoothness metrics, 17 of which were excluded based on mathematical criteria, and 13 more as they did not respond as expected in all simulation analyses. Eventually, we found that, for reach-to-point and reach-to-grasp movements, only Spectral Arc Length (SPARC) was found to be a valid metric. CONCLUSIONS: Based on this systematic review and simulation analyses, we recommend the use of SPARC as a valid smoothness metric in both reach-to-point and reach-to-grasp tasks of the upper limb after stroke. However, further research is needed to understand the time course of smoothness measured with SPARC for the upper limb early post stroke, preferably in longitudinal studies.

Smoothness metric during reach-to-grasp after stroke: part 2. longitudinal association with motor impairment.

BACKGROUND: The cause of smoothness deficits as a proxy for quality of movement post stroke is currently unclear. Previous simulation analyses showed that spectral arc length (SPARC) is a valid metric for investigating smoothness during a multi-joint goal-directed reaching task. The goal of this observational study was to investigate how SPARC values change over time, and whether SPARC is longitudinally associated with the recovery from motor impairments reflected by the Fugl-Meyer motor assessment of the upper extremity (FM-UE) in the first 6 months after stroke. METHODS: Forty patients who suffered a first-ever unilateral ischemic stroke (22 males, aged 58.6 ± 12.5 years) with upper extremity paresis underwent kinematic and clinical measurements in weeks 1, 2, 3, 4, 5, 8, 12, and 26 post stroke. Clinical measures included amongst others FM-UE. SPARC was obtained by three-dimensional kinematic measurements using an electromagnetic motion tracking system during a reach-to-grasp movement. Kinematic assessments of 12 healthy, age-matched individuals served as reference. Longitudinal linear mixed model analyses were performed to determine SPARC change over time, compare smoothness in patients with reference values of healthy individuals, and establish the longitudinal association between SPARC and FM-UE scores. RESULTS: SPARC showed a significant positive longitudinal association with FM-UE (B: 31.73, 95%-CI: [27.27 36.20], P < 0.001), which encompassed significant within- and between-subject effects (B: 30.85, 95%-CI: [26.28 35.41], P < 0.001 and B: 50.59, 95%-CI: [29.97 71.21], P < 0.001, respectively). Until 5 weeks post stroke, progress of time contributed significantly to the increase in SPARC and FM-UE scores (P < 0.05), whereafter they levelled off. At group level, smoothness was lower in patients who suffered a stroke compared to healthy subjects at all time points (P < 0.05). CONCLUSIONS: The present findings show that, after stroke, recovery of smoothness in a multi-joint reaching task and recovery from motor impairments are longitudinally associated and follow a similar time course. This suggests that the reduction of smoothness deficits quantified by SPARC is a proper objective reflection of recovery from motor impairment, as reflected by FM-UE, probably driven by a common underlying process of spontaneous neurological recovery early post stroke.

Cortical dynamics during preparation and execution of reactive balance responses with distinct postural demands.

The contributions of the cerebral cortex to human balance control are clearly demonstrated by the profound impact of cortical lesions on the ability to maintain standing balance. The cerebral cortex is thought to regulate subcortical postural centers to maintain upright balance and posture under varying environmental conditions and task demands. However, the cortical mechanisms that support standing balance remain elusive. Here, we present an EEG-based analysis of cortical oscillatory dynamics during the preparation and execution of balance responses with distinct postural demands. In our experiment, participants responded to backward movements of the support surface either with one forward step or by keeping their feet in place. To challenge the postural control system, we applied participant-specific high accelerations of the support surface such that the postural demand was low for stepping responses and high for feet-in-place responses. We expected that postural demand modulated the power of intrinsic cortical oscillations. Independent component analysis and time-frequency domain statistics revealed stronger suppression of alpha (9-13 Hz) and low-gamma (31-34 Hz) rhythms in the supplementary motor area (SMA) when preparing for feet-in-place responses (i.e., high postural demand). Irrespective of the response condition, support-surface movements elicited broadband (3-17 Hz) power increase in the SMA and enhancement of the theta (3-7 Hz) rhythm in the anterior prefrontal cortex (PFC), anterior cingulate cortex (ACC), and bilateral sensorimotor cortices (M1/S1). Although the execution of reactive responses resulted in largely similar cortical dynamics, comparison between the bilateral M1/S1 showed that stepping responses corresponded with stronger suppression of the beta (13-17 Hz) rhythm in the M1/S1 contralateral to the support leg. Comparison between response conditions showed that feet-in-place responses corresponded with stronger enhancement of the theta (3-7 Hz) rhythm in the PFC. Our results provide novel insights into the cortical dynamics of SMA, PFC, and M1/S1 during the control of human balance.

The Reliance on Vestibular Information During Standing Balance Control Decreases With Severity of Vestibular Dysfunction.

The vestibular system is involved in gaze stabilization and standing balance control. However, it is unclear whether vestibular dysfunction affects both processes to a similar extent. Therefore, the objective of this study was to determine how the reliance on vestibular information during standing balance control is related to gaze stabilization deficits in patients with vestibular dysfunction. Eleven patients with vestibular dysfunction and twelve healthy subjects were included. Gaze stabilization deficits were established by spontaneous nystagmus examination, caloric test, rotational chair test, and head impulse test. Standing balance control was assessed by measuring the body sway (BS) responses to continuous support surface rotations of 0.5° and 1.0° peak-to-peak while subjects had their eyes closed. A balance control model was fitted on the measured BS responses to estimate balance control parameters, including the vestibular weight, which represents the reliance on vestibular information. Using multivariate analysis of variance, balance parameters were compared between patients with vestibular dysfunction and healthy subjects. Robust regression was used to investigate correlations between gaze stabilization and the vestibular weight. Our results showed that the vestibular weight was smaller in patients with vestibular dysfunction than in healthy subjects (F = 7.67, p = 0.011). The vestibular weight during 0.5° peak-to-peak support surface rotations decreased with increasing spontaneous nystagmus eye velocity (ρ = -0.82, p < 0.001). In addition, the vestibular weight during 0.5° and 1.0° peak-to-peak support surface rotations decreased with increasing ocular response bias during rotational chair testing (ρ = -0.72, p = 0.02 and ρ = -0.67, p = 0.04, respectively). These findings suggest that the reliance on vestibular information during standing balance control decreases with the severity of vestibular dysfunction. We conclude that particular gaze stabilization tests may be used to predict the effect of vestibular dysfunction on standing balance control.

Evidence in Support of the Independent Channel Model Describing the Sensorimotor Control of Human Stance Using a Humanoid Robot.

The Independent Channel (IC) model is a commonly used linear balance control model in the frequency domain to analyze human balance control using system identification and parameter estimation. The IC model is a rudimentary and noise-free description of balance behavior in the frequency domain, where a stable model representation is not guaranteed. In this study, we conducted firstly time-domain simulations with added noise, and secondly robot experiments by implementing the IC model in a real-world robot (PostuRob II) to test the validity and stability of the model in the time domain and for real world situations. Balance behavior of seven healthy participants was measured during upright stance by applying pseudorandom continuous support surface rotations. System identification and parameter estimation were used to describe the balance behavior with the IC model in the frequency domain. The IC model with the estimated parameters from human experiments was implemented in Simulink for computer simulations including noise in the time domain and robot experiments using the humanoid robot PostuRob II. Again, system identification and parameter estimation were used to describe the simulated balance behavior. Time series, Frequency Response Functions, and estimated parameters from human experiments, computer simulations, and robot experiments were compared with each other. The computer simulations showed similar balance behavior and estimated control parameters compared to the human experiments, in the time and frequency domain. Also, the IC model was able to control the humanoid robot by keeping it upright, but showed small differences compared to the human experiments in the time and frequency domain, especially at high frequencies. We conclude that the IC model, a descriptive model in the frequency domain, can imitate human balance behavior also in the time domain, both in computer simulations with added noise and real world situations with a humanoid robot. This provides further evidence that the IC model is a valid description of human balance control.

A Sensitivity Analysis of an Inverted Pendulum Balance Control Model.

Balance control models are used to describe balance behavior in health and disease. We identified the unique contribution and relative importance of each parameter of a commonly used balance control model, the Independent Channel (IC) model, to identify which parameters are crucial to describe balance behavior. The balance behavior was expressed by transfer functions (TFs), representing the relationship between sensory perturbations and body sway as a function of frequency, in terms of amplitude (i.e., magnitude) and timing (i.e., phase). The model included an inverted pendulum controlled by a neuromuscular system, described by several parameters. Local sensitivity of each parameter was determined for both the magnitude and phase using partial derivatives. Both the intrinsic stiffness and proportional gain shape the magnitude at low frequencies (0.1-1 Hz). The derivative gain shapes the peak and slope of the magnitude between 0.5 and 0.9 Hz. The sensory weight influences the overall magnitude, and does not have any effect on the phase. The effect of the time delay becomes apparent in the phase above 0.6 Hz. The force feedback parameters and intrinsic stiffness have a small effect compared with the other parameters. All parameters shape the TF magnitude and phase and therefore play a role in the balance behavior. The sensory weight, time delay, derivative gain, and the proportional gain have a unique effect on the TFs, while the force feedback parameters and intrinsic stiffness contribute less. More insight in the unique contribution and relative importance of all parameters shows which parameters are crucial and critical to identify underlying differences in balance behavior between different patient groups.

Brain activation is related to smoothness of upper limb movements after stroke.

It is unclear whether additionally recruited sensorimotor areas in the ipsilesional and contralesional hemisphere and the cerebellum can compensate for lost neuronal functions after stroke. The objective of this study was to investigate how increased recruitment of secondary sensorimotor areas is associated with quality of motor control after stroke. In seventeen patients (three females, fourteen males; age: 59.9 ± 12.6 years), cortical activation levels were determined with functional magnetic resonance imaging (fMRI) in 12 regions of interest during a finger flexion-extension task in weeks 6 and 29 after stroke. At the same time points and by using 3D kinematics, the quality of motor control was assessed by smoothness of the grasp aperture during a reach-to-grasp task, quantified by normalized jerk. Ipsilesional premotor cortex, insula and cerebellum, as well as the contralesional supplementary motor area, insula and cerebellum, correlated significantly and positively with the normalized jerk of grasp aperture at week 6 after stroke. A positive trend towards this correlation was observed in week 29. This study suggests that recruitment of secondary motor areas at 6 weeks after stroke is highly associated with increased jerk during reaching and grasping. As jerk represents the change in acceleration, the recruitment of additional sensorimotor areas seems to reflect a type of control in which deviations from an optimal movement pattern are continuously corrected. This relationship suggests that additional recruitment of sensorimotor areas after stroke may not correspond to restitution of motor function, but more likely to adaptive motor learning strategies to compensate for motor impairments.

Asymmetries in reactive and anticipatory balance control are of similar magnitude in Parkinson's disease patients.

Many Parkinson's disease (PD) patients show asymmetries in balance control during quiet stance and in response to perturbations (i.e., reactive balance control) in the sagittal plane. In addition, PD patients show a reduced ability to anticipate to self-induced disturbances, but it is not clear whether these anticipatory responses can be asymmetric too. Furthermore, it is not known how reactive balance control and anticipatory balance control are related in PD patients. Therefore, we investigated whether reactive and anticipatory balance control are asymmetric to the same extent in PD patients. 14 PD patients and 10 controls participated. Reactive balance control (RBC) was investigated by applying external platform and force perturbations and relating the response of the left and right ankle torque to the body sway angle at the excited frequencies. Anticipatory postural adjustments (APAs) were investigated by determining the increase in the left and right ankle torque just before the subjects released a force exerted with the hands against a force sensor. The symmetry ratio between the contribution of the left and right ankle was used to express the asymmetry in reactive and anticipatory balance control; the correlation between the two ratio's was investigated with Spearman's rank correlation coefficients. PD patients were more asymmetric in anticipatory (p=0.026) and reactive balance control (p=0.004) compared to controls and the symmetry ratios were significantly related (ρ=0.74; p=0.003) in PD patients. These findings suggest that asymmetric reactive balance control during bipedal stance may share a common pathophysiology with asymmetries in the anticipation of voluntary perturbations during, for instance, gait initiation.

Impact of time on quality of motor control of the paretic upper limb after stroke.

OBJECTIVE: To establish the time course of recovery regarding smoothness of upper limb movements in the first 6 months poststroke. DESIGN: Cohort study with 3-dimensional kinematic measurements in weeks 1, 2, 3, 4, 5, 8, 12, and 26 poststroke. SETTING: Onsite 3-dimensional kinematic measurements in stroke units, rehabilitation centers, nursing homes, and patients' homes. PARTICIPANTS: Patients (N=44; 19 women, 25 men; mean age ± SD, 58±12y) with a first-ever unilateral ischemic stroke and incomplete upper limb paresis (27 left sided, 17 right sided) were included. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: In each measurement, an electromagnetic motion tracker acquired hand and finger trajectories during a reach-to-grasp task. Movement duration was determined, and smoothness of hand transport and grasp aperture was quantified by normalized jerk. With the use of random coefficient analysis, the effect of progress of time on smoothness of hand transport and grasp aperture was investigated. RESULTS: During the first 5 weeks poststroke, there was a significant contribution of progress of time to reductions in movement duration and normalized jerk of hand transport and grasp aperture (P<.01). CONCLUSIONS: The present longitudinal 3-dimensional kinematic study showed that smoothness of paretic upper limb movements improves in the first 8 weeks poststroke. This improvement suggests that motor control normalizes in the first 8 weeks poststroke and can be mostly explained by spontaneous neurologic recovery that occurs typically in the first weeks poststroke. Future 3-dimensional kinematic studies should investigate whether therapies starting early after stroke can improve the quality of motor control beyond spontaneous neurologic recovery.

Understanding adaptive motor control of the paretic upper limb early poststroke: the EXPLICIT-stroke program.

BACKGROUND: During upper limb motor recovery after stroke, the greatest improvements occur typically in the first 5 weeks poststroke. It is unclear what patients learn during this early phase of recovery. OBJECTIVE: To investigate the hypothesis that, early poststroke, patients learn to master the degrees of freedom in the paretic upper limb as reflected by dissociated shoulder and elbow movements during reach-to-grasp. METHODS: Thirty-one patients with a first-ever ischemic stroke were included. Repeated 3-dimensional kinematic measurements were conducted at 14, 25, 38, 57, 92, and 189 days poststroke. Trunk, shoulder, elbow, and wrist rotations were measured during a reach-to-grasp task. Using principal component analysis the longitudinal changes in dissociated upper limb movements during reach-to-grasp were investigated. Twelve healthy subjects were included for comparison. RESULTS: The main coordination pattern during reach-to-grasp in patients with stroke and healthy subjects consisted mostly of horizontal shoulder adduction and elbow extension. The standard deviation of this main pattern increased over time, with the largest increase in the first 5 weeks poststroke (F = 5.5, P < .001), but remained smaller than in healthy individuals. The standard deviation increased by 0.46° per day between 14 and 38 days and tapered off to 0.05° per day between 38 and 189 days poststroke. CONCLUSIONS: Our results suggest that restitution of motor control by dissociation of shoulder and elbow movements occurs mainly early poststroke. However, compared with healthy adults, most patients did not achieve fully dissociated upper limb movements at 26 weeks poststroke, suggesting that upper limb motor control after stroke remains adaptive.

Characterizing the protocol for early modified constraint-induced movement therapy in the EXPLICIT-stroke trial.

Constraint-induced movement therapy (CIMT) is a commonly used rehabilitation intervention to improve upper limb function after stroke. CIMT was originally developed for patients with a chronic upper limb paresis. Although there are indications that exercise interventions should start as early as possible after stroke, only a few randomized controlled trials have been published on either CIMT or modified forms of CIMT (mCIMT) during the acute phase after stroke. The implementation of (m)CIMT in published studies is very heterogeneous in terms of content, timing and intensity of therapy. Moreover, mCIMT studies often fail to provide a detailed description of the protocol applied. The purpose of the present paper is therefore to describe the essential elements of the mCIMT protocol as developed for the EXplaining PLastICITy after stroke (EXPLICIT-stroke) study. The EXPLICIT-stroke mCIMT protocol emphasizes restoring body functions, while preventing the development of compensatory movement strategies. More specifically, the intervention aims to improve active wrist -and finger extension, which is assumed to be a key factor for upper limb function. The intervention starts within 2 weeks after stroke onset. The protocol retains two of the three key elements of the original CIMT protocol, that is, repetitive training and the constraining element. Repetitive task training is applied for 1 hour per working day, and the patients wear a mitt for at least 3 hours per day for three consecutive weeks.

Unraveling the interaction between pathological upper limb synergies and compensatory trunk movements during reach-to-grasp after stroke: a cross-sectional study.

The aim of the present study was to identify how pathological limb synergies between shoulder and elbow movements interact with compensatory trunk movements during a functional movement with the paretic upper limb after stroke. 3D kinematic joint and trunk angles were measured during a reach-to-grasp movement in 46 patients with stroke and 12 healthy individuals. We used principal component analyses (PCA) to identify components representing linear relations between the degrees of freedom of the upper limb and trunk across patients with stroke and healthy participants. Using multivariate logistic regression analysis, we investigated whether component scores were related to the presence or absence of basic limb synergies as indicated by the arm section of the Fugl-Meyer motor assessment (FMA). Four and three principal components were extracted in patients with stroke and healthy individuals, respectively. Visual inspection revealed that the contribution of joint and trunk angles to each component differed substantially between groups. The presence of the flexion synergy (Shoulder Abduction and Elbow Flexion) was reflected by component 1, whereas the compensatory role of trunk movements for lack of shoulder and elbow movements was reflected by components 2 and 3 respectively. The presence or absence of basic limb synergies as determined by means of the FMA was significantly related to components 2 (p = 0.014) and 3 (p = 0.003) in patients with stroke. These significant relations indicate that PCA is a useful tool to identify clinically meaningful interactions between compensatory trunk movements and pathological synergies in the elbow and shoulder during reach-to-grasp after stroke.

Assessing longitudinal change in coordination of the paretic upper limb using on-site 3-dimensional kinematic measurements.

BACKGROUND AND PURPOSE: It is largely unknown how adaptive motor control of the paretic upper limb contributes to functional recovery after stroke. This paucity of knowledge emphasizes the need for longitudinal 3-dimensional (3D) kinematic studies with frequent measurements to establish changes in coordination after stroke. A portable 3D kinematic setup would facilitate the frequent follow-up of people poststroke. This case report shows how longitudinal kinematic changes of the upper limb can be measured at a patient's home using a portable 3D kinematic system in the first 6 months poststroke. CASE DESCRIPTION: The outcomes of the upper-limb section of the Fugl-Meyer Motor Assessment (FMA), the Action Research Arm Test (ARAT), and 3D kinematic analyses were obtained from a 41-year-old man with a left hemispheric stroke. Three-dimensional kinematic data of the paretic upper limb were collected during a reach-to-grasp task using a portable motion tracker in 5 measurements during the first 6 months after stroke. Data from an individual who was healthy were used for comparison. OUTCOMES: The FMA and ARAT scores showed nonlinear recovery profiles, accompanied by significant changes in kinematic outcomes over time poststroke. Specifically, elbow extension increased, forward trunk motion decreased, peak hand speed increased, peak hand opening increased, and peak hand opening occurred sooner after peak hand speed. DISCUSSION: This case report illustrates the feasibility of frequently repeated, on-site 3D kinematic measurements of the paretic upper limb. Early after stroke, task performance was mainly driven by adaptive motor control, whereas adaptations were mostly reduced at 26 weeks poststroke. The presented approach allows the investigation of what is changing in coordination and how these changes are related to the nonlinear pattern of improvements in body functions and activities after stroke.

A comparison of two validated tests for upper limb function after stroke: The Wolf Motor Function Test and the Action Research Arm Test.

OBJECTIVE: To investigate the concurrent validity between the Action Research Arm Test (ARAT) and the Wolf Motor Function Test (WMFT) and to compare their reproducibility, internal consistency and floor and ceiling effects in the same sample of stroke patients. METHODS: Forty patients participated in this study. Concurrent validity was determined with Spearman's rank correlation coefficients. Reproducibility was assessed with intraclass correlation coefficients (ICCs) and Bland-Altman plots, internal consistency by means of Cronbach's alphas, and floor and ceiling effects were considered to be present if more than 20% of patients fell outside a preliminary set lower and upper boundary. RESULTS: Spearman's rank correlation coefficients ranged from 0.70 to 0.86. ICCs for inter-rater and intra-rater reliability ranged from 0.92 to 0.97. Bland-Altman plots showed a less stable way of scoring for the WMFT, compared with the ARAT. Cronbach's alpha was > 0.98 for both scales. No floor and ceiling effects were found. CONCLUSION: The present study showed good clinimetric properties for both assessments. The high concurrent validity suggests that ARAT and WMFT have significant overlap with regard to the underlying construct that is being measured.

Rhythm perturbations in acoustically paced treadmill walking after stroke.

BACKGROUND: In rehabilitation, acoustic rhythms are often used to improve gait after stroke. Acoustic cueing may enhance gait coordination by creating a stable coupling between heel strikes and metronome beats and provide a means to train the adaptability of gait coordination to environmental changes, as required in everyday life ambulation. OBJECTIVE: To examine the stability and adaptability of auditory-motor synchronization in acoustically paced treadmill walking in stroke patients. METHODS: Eleven stroke patients and 10 healthy controls walked on a treadmill at preferred speed and cadence under no metronome, single-metronome (pacing only paretic or nonparetic steps), and double-metronome (pacing both footfalls) conditions. The stability of auditory-motor synchronization was quantified by the variability of the phase relation between footfalls and beats. In a separate session, the acoustic rhythms were perturbed and adaptations to restore auditory-motor synchronization were quantified. RESULTS: For both groups, auditory-motor synchronization was more stable for double-metronome than single-metronome conditions, with stroke patients exhibiting an overall weaker coupling of footfalls to metronome beats than controls. The recovery characteristics following rhythm perturbations corroborated the stability findings and further revealed that stroke patients had difficulty in accelerating their steps and instead preferred a slower-step response to restore synchronization. CONCLUSIONS: In gait rehabilitation practice, the use of acoustic rhythms may be more effective when both footfalls are paced. In addition, rhythm perturbations during acoustically paced treadmill walking may not only be employed to evaluate the stability of auditory-motor synchronization but also have promising implications for evaluation and training of gait adaptations in neurorehabilitation practice.