Digital Gait Measures Capture 1-Year Progression in Early-Stage Spinocerebellar Ataxia Type 2.

BACKGROUND: With disease-modifying drugs in reach for cerebellar ataxias, fine-grained digital health measures are highly warranted to complement clinical and patient-reported outcome measures in upcoming treatment trials and treatment monitoring. These measures need to demonstrate sensitivity to capture change, in particular in the early stages of the disease. OBJECTIVE: Our aim is to unravel gait measures sensitive to longitudinal change in the-particularly trial-relevant-early stage of spinocerebellar ataxia type 2 (SCA2). METHODS: We performed a multicenter longitudinal study with combined cross-sectional and 1-year interval longitudinal analysis in early-stage SCA2 participants (n = 23, including nine pre-ataxic expansion carriers; median, ATXN2 CAG repeat expansion 38 ± 2; median, Scale for the Assessment and Rating of Ataxia [SARA] score 4.8 ± 4.3). Gait was assessed using three wearable motion sensors during a 2-minute walk, with analyses focused on gait measures of spatio-temporal variability that have shown sensitivity to ataxia severity (eg, lateral step deviation). RESULTS: We found significant changes for gait measures between baseline and 1-year follow-up with large effect sizes (lateral step deviation P = 0.0001, effect size rprb = 0.78), whereas the SARA score showed no change (P = 0.67). Sample size estimation indicates a required cohort size of n = 43 to detect a 50% reduction in natural progression. Test-retest reliability and minimal detectable change analysis confirm the accuracy of detecting 50% of the identified 1-year change. CONCLUSIONS: Gait measures assessed by wearable sensors can capture natural progression in early-stage SCA2 within just 1 year-in contrast to a clinical ataxia outcome. Lateral step deviation represents a promising outcome measure for upcoming multicenter interventional trials, particularly in the early stages of cerebellar ataxia. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Digital Gait Outcomes for Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS): Discriminative, Convergent, and Ecological Validity in a Multicenter Study (PROSPAX).

BACKGROUND: With treatment trials on the horizon, this study aimed to identify candidate digital-motor gait outcomes for autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), capturable by wearable sensors with multicenter validity, and ideally also ecological validity during free walking outside laboratory settings. METHODS: Cross-sectional multicenter study (four centers), with gait assessments in 36 subjects (18 ARSACS patients; 18 controls) using three body-worn sensors (Opal, APDM) in laboratory settings and free walking in public spaces. Sensor gait measures were analyzed for discriminative validity from controls, and for convergent (ie, clinical and patient relevance) validity by correlations with SPRSmobility (primary outcome) and Scale for the Assessment and Rating of Ataxia (SARA), Spastic Paraplegia Rating Scale (SPRS), and activities of daily living subscore of the Friedreich Ataxia Rating Scale (FARS-ADL) (exploratory outcomes). RESULTS: Of 30 hypothesis-based digital gait measures, 14 measures discriminated ARSACS patients from controls with large effect sizes (|Cliff's δ| > 0.8) in laboratory settings, with strongest discrimination by measures of spatiotemporal variability Lateral Step Deviation (δ = 0.98), SPcmp (δ = 0.94), and Swing CV (δ = 0.93). Large correlations with the SPRSmobility were observed for Swing CV (Spearman's ρ = 0.84), Speed (ρ = -0.63), and Harmonic Ratio V (ρ = -0.62). During supervised free walking in a public space, 11/30 gait measures discriminated ARSACS from controls with large effect sizes. Large correlations with SPRSmobility were here observed for Swing CV (ρ = 0.78) and Speed (ρ = -0.69), without reductions in effect sizes compared with laboratory settings. CONCLUSIONS: We identified a promising set of digital-motor candidate gait outcomes for ARSACS, applicable in multicenter settings, correlating with patient-relevant health aspects, and with high validity also outside laboratory settings, thus simulating real-life walking with higher ecological validity. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Using Smartphone Sensors for Ataxia Trials: Consensus Guidance by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

Smartphone sensors are used increasingly in the assessment of ataxias. To date, there is no specific consensus guidance regarding a priority set of smartphone sensor measurements, or standard assessment criteria that are appropriate for clinical trials. As part of the Ataxia Global Initiative Digital-Motor Biomarkers Working Group (AGI WG4), aimed at evaluating key ataxia clinical domains (gait/posture, upper limb, speech and oculomotor assessments), we provide consensus guidance for use of internal smartphone sensors to assess key domains. Guidance was developed by means of a literature review and a two stage Delphi study conducted by an Expert panel, which surveyed members of AGI WG4, representing clinical, research, industry and patient-led experts, and consensus meetings by the Expert panel to agree on standard criteria and map current literature to these criteria. Seven publications were identified that investigated ataxias using internal smartphone sensors. The Delphi 1 survey ascertained current practice, and systems in use or under development. Wide variations in smartphones sensor use for assessing ataxia were identified. The Delphi 2 survey identified seven measures that were strongly endorsed as priorities in assessing 3/4 domains, namely gait/posture, upper limb, and speech performance. The Expert panel recommended 15 standard criteria to be fulfilled in studies. Evaluation of current literature revealed that none of the studies met all criteria, with most being early-phase validation studies. Our guidance highlights the importance of consensus, identifies priority measures and standard criteria, and will encourage further research into the use of internal smartphone sensors to measure ataxia digital-motor biomarkers.

Quantitative Gait and Balance Outcomes for Ataxia Trials: Consensus Recommendations by the Ataxia Global Initiative Working Group on Digital-Motor Biomarkers.

With disease-modifying drugs on the horizon for degenerative ataxias, ecologically valid, finely granulated, digital health measures are highly warranted to augment clinical and patient-reported outcome measures. Gait and balance disturbances most often present as the first signs of degenerative cerebellar ataxia and are the most reported disabling features in disease progression. Thus, digital gait and balance measures constitute promising and relevant performance outcomes for clinical trials.This narrative review with embedded consensus will describe evidence for the sensitivity of digital gait and balance measures for evaluating ataxia severity and progression, propose a consensus protocol for establishing gait and balance metrics in natural history studies and clinical trials, and discuss relevant issues for their use as performance outcomes.

Consensus Paper: Ataxic Gait.

The aim of this consensus paper is to discuss the roles of the cerebellum in human gait, as well as its assessment and therapy. Cerebellar vermis is critical for postural control. The cerebellum ensures the mapping of sensory information into temporally relevant motor commands. Mental imagery of gait involves intrinsically connected fronto-parietal networks comprising the cerebellum. Muscular activities in cerebellar patients show impaired timing of discharges, affecting the patterning of the synergies subserving locomotion. Ataxia of stance/gait is amongst the first cerebellar deficits in cerebellar disorders such as degenerative ataxias and is a disabling symptom with a high risk of falls. Prolonged discharges and increased muscle coactivation may be related to compensatory mechanisms and enhanced body sway, respectively. Essential tremor is frequently associated with mild gait ataxia. There is growing evidence for an important role of the cerebellar cortex in the pathogenesis of essential tremor. In multiple sclerosis, balance and gait are affected due to cerebellar and spinal cord involvement, as a result of disseminated demyelination and neurodegeneration impairing proprioception. In orthostatic tremor, patients often show mild-to-moderate limb and gait ataxia. The tremor generator is likely located in the posterior fossa. Tandem gait is impaired in the early stages of cerebellar disorders and may be particularly useful in the evaluation of pre-ataxic stages of progressive ataxias. Impaired inter-joint coordination and enhanced variability of gait temporal and kinetic parameters can be grasped by wearable devices such as accelerometers. Kinect is a promising low cost technology to obtain reliable measurements and remote assessments of gait. Deep learning methods are being developed in order to help clinicians in the diagnosis and decision-making process. Locomotor adaptation is impaired in cerebellar patients. Coordinative training aims to improve the coordinative strategy and foot placements across strides, cerebellar patients benefiting from intense rehabilitation therapies. Robotic training is a promising approach to complement conventional rehabilitation and neuromodulation of the cerebellum. Wearable dynamic orthoses represent a potential aid to assist gait. The panel of experts agree that the understanding of the cerebellar contribution to gait control will lead to a better management of cerebellar ataxias in general and will likely contribute to use gait parameters as robust biomarkers of future clinical trials.

Dysfunctional neuro-muscular mechanisms explain gradual gait changes in prodromal spastic paraplegia.

BACKGROUND: In Hereditary Spastic Paraplegia (HSP) type 4 (SPG4) a length-dependent axonal degeneration in the cortico-spinal tract leads to progressing symptoms of hyperreflexia, muscle weakness, and spasticity of lower extremities. Even before the manifestation of spastic gait, in the prodromal phase, axonal degeneration leads to subtle gait changes. These gait changes - depicted by digital gait recording - are related to disease severity in prodromal and early-to-moderate manifest SPG4 participants. METHODS: We hypothesize that dysfunctional neuro-muscular mechanisms such as hyperreflexia and muscle weakness explain these disease severity-related gait changes of prodromal and early-to-moderate manifest SPG4 participants. We test our hypothesis in computer simulation with a neuro-muscular model of human walking. We introduce neuro-muscular dysfunction by gradually increasing sensory-motor reflex sensitivity based on increased velocity feedback and gradually increasing muscle weakness by reducing maximum isometric force. RESULTS: By increasing hyperreflexia of plantarflexor and dorsiflexor muscles, we found gradual muscular and kinematic changes in neuro-musculoskeletal simulations that are comparable to subtle gait changes found in prodromal SPG4 participants. CONCLUSIONS: Predicting kinematic changes of prodromal and early-to-moderate manifest SPG4 participants by gradual alterations of sensory-motor reflex sensitivity allows us to link gait as a directly accessible performance marker to emerging neuro-muscular changes for early therapeutic interventions.

Real-Life Turning Movements Capture Subtle Longitudinal and Preataxic Changes in Cerebellar Ataxia.

BACKGROUND: Clinical and regulatory acceptance of upcoming molecular treatments in degenerative ataxias might greatly benefit from ecologically valid endpoints that capture change in ataxia severity in patients' real life. OBJECTIVES: This longitudinal study aimed to unravel quantitative motor biomarkers in degenerative ataxias in real-life turning movements that are sensitive for changes both longitudinally and at the preataxic stage. METHODS: Combined cross-sectional (n = 30) and longitudinal (n = 14, 1-year interval) observational study in degenerative cerebellar disease (including eight preataxic mutation carriers) compared to 23 healthy controls. Turning movements were assessed by three body-worn inertial sensors in three conditions: (1) instructed laboratory assessment, (2) supervised free walking, and (3) unsupervised real-life movements. RESULTS: Measures that quantified dynamic balance during turning-lateral velocity change (LVC) and outward acceleration-but not general turning measures such as speed, allowed differentiating ataxic against healthy subjects in real life (effect size δ = 0.68), with LVC also differentiating preataxic against healthy subjects (δ = 0.53). LVC was highly correlated with clinical ataxia severity (scale for the assessment and rating of ataxia [SARA] score, effect size ρ = 0.79) and patient reported balance confidence (activity-specific balance confidence scale [ABC] score, ρ = 0.66). Moreover, LVC in real life-but not general turning measures or the SARA score-allowed detecting significant longitudinal change in 1-year follow-up with high effect size (rprb  = 0.66). CONCLUSIONS: Measures of turning allow capturing specific changes of dynamic balance in degenerative ataxia in real life, with high sensitivity to longitudinal differences in ataxia severity and to the preataxic stage. They thus present promising ecologically valid motor biomarkers, even in the highly treatment-relevant early stages of degenerative cerebellar disease. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Specific Gait Changes in Prodromal Hereditary Spastic Paraplegia Type 4: preSPG4 Study.

BACKGROUND: In hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients realize gait disturbances. The prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested. OBJECTIVE: The objective of this study was to identify specific movement abnormalities before the manifestation of gait impairment and quantify disease progression in the prodromal phase. METHODS: Seventy subjects participated in gait assessment, including 30 prodromal SPAST pathogenic variant carriers, 17 patients with mild-to-moderate manifest SPG4, and 23 healthy control subjects. An infrared-camera-based motion capture system assessed gait to analyze features such as range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale, neurofilament light chain as a fluid biomarker indicating neurodegeneration, and motor-evoked potentials. RESULTS: Compared with healthy control subjects, we found an altered gait pattern in prodromal pathogenic variant carriers during the swing phase in the segmental angle of the foot (Dunn's post hoc test, q = 3.1) and heel ground clearance (q = 2.8). Furthermore, range of motion of segmental angle was reduced for the foot (q = 3.3). These changes occurred in prodromal pathogenic variant carriers without quantified leg spasticity in clinical examination. Gait features correlated with neurofilament light chain levels, central motor conduction times of motor-evoked potentials, and Spastic Paraplegia Rating Scale score. CONCLUSIONS: Gait analysis can quantify changes in prodromal and mild-to-moderate manifest SPG4 patients. Thus, gait features constitute promising motor biomarkers characterizing the subclinical progression of spastic gait and might help to evaluate interventions in early disease stages. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Digital Gait Biomarkers Allow to Capture 1-Year Longitudinal Change in Spinocerebellar Ataxia Type 3.

Measures of step variability and body sway during gait have shown to correlate with clinical ataxia severity in several cross-sectional studies. However, to serve as a valid progression biomarker, these gait measures have to prove their sensitivity to robustly capture longitudinal change, ideally within short time frames (eg, 1 year). We present the first multicenter longitudinal gait analysis study in spinocerebellar ataxias. We performed a combined cross-sectional (n = 28) and longitudinal (1-year interval, n = 17) analysis in Spinocerebellar Ataxia type 3 subjects (including seven preataxic mutation carriers). Longitudinal analysis showed significant change in gait measures between baseline and 1-year follow-up, with high effect sizes (stride length variability: P = 0.01, effect size rprb  = 0.66; lateral sway: P = 0.007, rprb  = 0.73). Sample size estimation for lateral sway indicates a required cohort size of n = 43 for detecting a 50% reduction of natural progression, compared with n = 240 for the clinical ataxia score Scale for the Assessment and Rating of Ataxia (SARA). These measures thus present promising motor biomarkers for upcoming interventional studies. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The SSTeP-KiZ System-Secure Real-Time Communication Based on Open Web Standards for Multimodal Sensor-Assisted Tele-Psychotherapy.

In this manuscript, we describe the soft- and hardware architecture as well as the implementation of a modern Internet of Medical Things (IoMT) system for sensor-assisted telepsychotherapy. It enables telepsychotherapy sessions in which the patient exercises therapy-relevant behaviors in their home environment under the remote supervision of the therapist. Wearable sensor information (electrocardiogram (ECG), movement sensors, and eye tracking) is streamed in real time to the therapist to deliver objective information about specific behavior-triggering situations and the stress level of the patients. We describe the IT infrastructure of the system which uses open standards such as WebRTC and OpenID Connect (OIDC). We also describe the system's security concept, its container-based deployment, and demonstrate performance analyses. The system is used in the ongoing study SSTeP-KiZ (smart sensor technology in telepsychotherapy for children and adolescents with obsessive-compulsive disorder) and shows sufficient technical performance.

Resection of cerebellar tumours causes widespread and functionally relevant white matter impairments.

Several diffusion tensor imaging studies reveal that white matter (WM) lesions are common in children suffering from benign cerebellar tumours who are treated with surgery only. The clinical implications of WM alterations that occur as a direct consequence of cerebellar disease have not been thoroughly studied. Here, we analysed structural and diffusion imaging data from cerebellar patients with chronic surgical lesions after resection for benign cerebellar tumours. We aimed to elucidate the impact of focal lesions of the cerebellum on WM integrity across the entire brain, and to investigate whether WM deficits were associated with behavioural impairment in three different motor tasks. Lesion symptom mapping analysis suggested that lesions in critical cerebellar regions were related to deficits in savings during an eyeblink conditioning task, as well as to deficits in motor action timing. Diffusion imaging analysis of cerebellar WM indicated that better behavioural performance was associated with higher fractional anisotropy (FA) in the superior cerebellar peduncle, cerebellum's main outflow path. Moreover, voxel-wise analysis revealed a global pattern of WM deficits in patients within many cerebral WM tracts critical for motor and non-motor function. Finally, we observed a positive correlation between FA and savings within cerebello-thalamo-cortical pathways in patients but not in controls, showing that saving effects partly depend on extracerebellar areas, and may be recruited for compensation. These results confirm that the cerebellum has extended connections with many cerebral areas involved in motor/cognitive functions, and the observed WM changes likely contribute to long-term clinical deficits of posterior fossa tumour survivors.

Individual changes in preclinical spinocerebellar ataxia identified via increased motor complexity.

BACKGROUND: Movement changes in autosomal-dominant spinocerebellar ataxias are suggested to occur many years before clinical manifestation. Detecting and quantifying these changes in the preclinical phase offers a window for future treatment interventions and allows the clinician to decipher the earliest dysfunctions starting the evolution of spinocerebellar ataxia. We hypothesized that quantitative movement analysis of complex stance and gait tasks allows to (i) reveal movement changes already at early stages of the preclinical phase when clinical ataxia signs are still absent and to (ii) quantify motor progression in this phase. METHODS: A total of 46 participants (14 preclinical spinocerebellar ataxia mutation carriers [spinocerebellar ataxias 1,2,3,6], 9 spinocerebellar ataxia patients at an early stage; 23 healthy controls) were assessed by quantitative movement analyses of increasingly complex stance and walking tasks in a cross-sectional design. RESULTS: Body sway in stance and spatiotemporal variability in tandem walking differentiated between preclinical mutation carriers and healthy controls (P < .01). Complex movement conditions allowed one to discriminate even those mutation carriers without any clinical signs in posture and gait (SARAposture&gait = 0; P < .04). Multivariate regression analysis categorized preclinical mutation carriers on a single-subject level with 100% accuracy within a range of 10 years to the estimated onset. Movement features in stance and gait correlated significantly with genetically estimated time to onset, indicating a gradual increase of motor changes with increasing proximity to disease manifestation. CONCLUSION: Our results provide evidence for subclinical motor changes in spinocerebellar ataxia, which allow to discriminate patients without clinical signs even on a single-subject basis and may help capture disease progression in the preclinical phase. © 2016 International Parkinson and Movement Disorder Society.

An intact action-perception coupling depends on the integrity of the cerebellum.

It is widely accepted that action and perception in humans functionally interact on multiple levels. Moreover, areas originally suggested to be predominantly motor-related, as the cerebellum, are also involved in action observation. However, as yet, few studies provided unequivocal evidence that the cerebellum is involved in the action perception coupling (APC), specifically in the integration of motor and multisensory information for perception. We addressed this question studying patients with focal cerebellar lesions in a virtual-reality paradigm measuring the effect of action execution on action perception presenting self-generated movements as point lights. We measured the visual sensitivity to the point light stimuli based on signal detection theory. Compared with healthy controls cerebellar patients showed no beneficial influence of action execution on perception indicating deficits in APC. Applying lesion symptom mapping, we identified distinct areas in the dentate nucleus and the lateral cerebellum of both hemispheres that are causally involved in APC. Lesions of the right ventral dentate, the ipsilateral motor representations (lobules V/VI), and most interestingly the contralateral posterior cerebellum (lobule VII) impede the benefits of motor execution on perception. We conclude that the cerebellum establishes time-dependent multisensory representations on different levels, relevant for motor control as well as supporting action perception. Ipsilateral cerebellar motor representations are thought to support the somatosensory state estimate of ongoing movements, whereas the ventral dentate and the contralateral posterior cerebellum likely support sensorimotor integration in the cerebellar-parietal loops. Both the correct somatosensory as well as the multisensory state representations are vital for an intact APC.

Multifeature quantitative motor assessment of upper limb ataxia including drawing and reaching.

OBJECTIVE: Voluntary upper limb movements are an ecologically important yet insufficiently explored digital-motor outcome domain for trials in degenerative ataxia. We extended and validated the trial-ready quantitative motor assessment battery "Q-Motor" for upper limb movements with clinician-reported, patient-focused, and performance outcomes of ataxia. METHODS: Exploratory single-center cross-sectional assessment in 94 subjects (46 cross-genotype ataxia patients; 48 matched controls), comprising five tasks measured by force transducer and/or position field: Finger Tapping, diadochokinesia, grip-lift, and-as novel implementations-Spiral Drawing, and Target Reaching. Digital-motor measures were selected if they discriminated from controls (AUC >0.7) and correlated-with at least one strong correlation (rho ≥0.6)-to the Scale for the Assessment and Rating of Ataxia (SARA), activities of daily living (FARS-ADL), and the Nine-Hole Peg Test (9HPT). RESULTS: Six movement features with 69 measures met selection criteria, including speed and variability in all tasks, stability in grip-lift, and efficiency in Target Reaching. The novel drawing/reaching tasks best captured impairment in dexterity (|rho9HPT| ≤0.81) and FARS-ADL upper limb items (|rhoADLul| ≤0.64), particularly by kinematic analysis of smoothness (SPARC). Target hit rate, a composite of speed and endpoint precision, almost perfectly discriminated ataxia and controls (AUC: 0.97). Selected measures in all tasks discriminated between mild, moderate, and severe impairment (SARA upper limb composite: 0-2/>2-4/>4-6) and correlated with severity in the trial-relevant mild ataxia stage (SARA ≤10, n = 20). INTERPRETATION: Q-Motor assessment captures multiple features of impaired upper limb movements in degenerative ataxia. Validation with key clinical outcome domains provides the basis for evaluation in longitudinal studies and clinical trial settings.

Effects of cerebellar lesions on working memory interacting with motor tasks of different complexities.

We examined the influence of focal cerebellar lesions on working memory (n-back task), gait, and the interaction between working memory and different gait tasks in a dual-task paradigm. The analysis included 17 young patients with chronic focal lesions after cerebellar tumor resection and 17 age-matched controls. Patients have shown mild to moderate ataxia. Lesion sites were examined on the basis of structural magnetic resonance imaging. N-back tasks were executed with different levels of difficulty (n = 1-4) during sitting (baseline), treadmill walking, and treadmill tandem walking (dual-task conditions). Patients exhibited decreased n-back performance particularly at difficult n-back levels and in dual-task conditions. Voxel-based lesion-symptom mapping revealed that decreased baseline n-back performance was associated with lesions of the posterolateral cerebellar hemisphere and the dentate nucleus. By contrast, decreased n-back performance in dual-task conditions was more associated with motor-related areas including dorsal portions of the dentate and the interposed nucleus, suggesting a prioritization of the motor task. During baseline walking, increased gait variability was associated with lesions in medial and intermediate regions, whereas for baseline tandem gait, lesions in the posterolateral hemispheres and the dentate nucleus became important. Posterolateral regions overlapped with regions related to baseline n-back performance. Consistently, we observed increased tandem gait variability with growing n-back difficulty in the dual-task condition. These findings suggest that dual-task effects in cerebellar patients are at least partially caused by a common involvement of posterolateral cerebellar regions in working memory and complex motor tasks.

Gait ataxia--specific cerebellar influences and their rehabilitation.

It is well known that the cerebellum is important for movement control and plays a critical role in balance and locomotion. As such, one of the most characteristic and sensitive signs of cerebellar damage is gait ataxia. However, characterizing ataxic gait is no easy task, because gait patterns are highly variable. This variability seems to result from the interaction of different factors, namely, (1) the primary motor deficits in balance control and multi-joint coordination and oculomotor dysfunction, (2) the safety strategies used, and (3) inaccurate adjustments in patients with loss of balance. In this report, we review different approaches to analyzing ataxic gait and studies to identify and quantify the different factors contributing to this movement disorder. We also discuss the influence of the cerebellum in adaptive locomotor control, the interaction between cognitive load and gait in dual-task paradigms, and the recent advances in rehabilitation of gait and posture for patients with cerebellar degeneration. In the second part, we discuss open questions concerning cerebellar mechanisms in multi-joint coordination during different walking conditions. Furthermore, we point out potential future directions in motor rehabilitation, with the objective of identifying predictors of rehabilitation outcome and the development of individualized training programs that potentially involve rehabilitation technology.

Spatiotemporal tuning of the facilitation of biological motion perception by concurrent motor execution.

The execution of motor behavior influences concurrent visual action observation and especially the perception of biological motion. The neural mechanisms underlying this interaction between perception and motor execution are not exactly known. In addition, the available experimental evidence is partially inconsistent because previous studies have reported facilitation as well as impairments of action perception by concurrent execution. Exploiting a novel virtual reality paradigm, we investigated the spatiotemporal tuning of the influence of motor execution on the perception of biological motion within a signal-detection task. Human observers were presented with point-light stimuli that were controlled by their own movements. Participants had to detect a point-light arm in a scrambled mask, either while executing waving movements or without concurrent motor execution (baseline). The temporal and spatial coherence between the observed and executed movements was parametrically varied. We found a systematic tuning of the facilitatory versus inhibitory influences of motor execution on biological motion detection with respect to the temporal and the spatial congruency between observed and executed movements. Specifically, we found a gradual transition between facilitatory and inhibitory interactions for decreasing temporal synchrony and spatial congruency. This result provides evidence for a spatiotemporally highly selective coupling between dynamic motor representations and neural structures involved in the visual processing of biological motion. In addition, our study offers a unifying explanation that reconciles contradicting results about modulatory effects of motor execution on biological motion perception in previous studies.

Tilted 3D visual scenes influence lateropulsion: A single case study of pusher syndrome.

INTRODUCTION: Hemiparetic stroke patients with so-called "pusher syndrome" (synonyms: contraversive lateropulsion, contraversive pushing) use their non-paretic extremities to push toward their paralyzed side and actively resist external posture correction. The disorder is associated with a distorted perception of postural vertical combined with a maintained, or little deviating perception of visual upright. With the aim of reducing this mismatch, and thus reducing contraversive lateropulsion, we manipulated the orientation of visual input in a virtual reality setup. METHOD: We presented healthy subjects and an acute stroke patient with severe pusher syndrome a 3D visual scene that was either upright or tilted in roll plane by 20°. By moving the sitting participants in roll plane to the left and right, we assessed the occurrence of contraversive lateropulsion, namely the active resistance to external posture manipulation. RESULTS: With the 3D visual scene oriented upright, the patient with pusher syndrome showed the typical active resistance against tilts toward the ipsilesional side. He used his non-paretic arm to block the examiner's attempt to move the body axis toward that side. With the visual scene tilted to the ipsiversive left, his pathological resistance was significantly reduced. Statistically, the tolerated body tilt angles no longer differed from those of healthy subjects. CONCLUSIONS: We conclude that even short presentations of tilted 3D visual input can reduce symptoms of severe contraversive lateropulsion. The technique provides potential for a new treatment method of pusher syndrome and offers a simple, straightforward approach that can be effortlessly integrated in clinical practice. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00026700).