[IDENTIFYING BRAIN STRUCTURES THAT CONTRIBUTE TO UPPER-LIMB RECOVERY POST STROKE USING THREE DIFFERENT METHODS OF LESION-SYMPTOM MAPPING].

AIMS: The identification of brain structures that are critical for upper limb residual motor function following stroke is an essential step towards the development of advanced treatment modalities for improving rehabilitation outcomes among brain-injured patients, such as non-invasive brain stimulation techniques, which aim to induce neuroplasticity in motor-critical brain regions. In the current study we attempted to identify the critical brain regions for upper limb motor function among stroke patients, using three different methods of lesion-symptom mapping (LSM). METHODS: Brain imaging data and Fugl-Meyer Assessment for upper-limb (FMA) scores for 107 patients admitted to the neurological rehabilitation department at Loewenstein Rehabilitation Medical Center, were analyzed using 3 LSM methods: Voxel-based Lesion-Symptom Mapping (VLSM), Region-based Lesion-Symptom Mapping (RLSM), and Multi-perturbation Shapley-value Analysis (MSA). RESULTS: In left-hemispheric damaged (LHD) patients only a relatively small number of brain regions were found, in comparison with right-hemispheric damaged (RHD) patients. For LHD, two regions important for movement planning were found to be critical - the supplementary motor area and the premotor area. For RHD, parts of the temporal, frontal and insular cortices, as well as the cingulate gyrus were exclusively detected as critical. Sub-cortical brain structures (basal ganglia, corona radiata, internal capsule and superior longitudinal fasciculus) were detected in both hemispheres. CONCLUSIONS: Despite the variability between different LSM methods, all methods have consistently shown a difference between the critical brain-regions for upper-limb function following LHD vs. RHD. These findings support previous works suggesting that the left (motor-dominant) hemisphere is more inter-connected, thus it has higher redundancy and decreased vulnerability to focal damage.

Characteristics of unsuccessful reactive responses to lateral loss of balance in people with stroke.

PURPOSE: The effectiveness of reactive responses to a sudden loss of balance is a critical factor that determines whether a fall will occur. We examined the strategies and kinematics associated with successful and unsuccessful balance recovery following lateral loss of balance in people with stroke (PwS). METHODS: Eleven PwS were included in the analysis. They were exposed to unannounced right and left horizontal surface translations and demonstrated both successful and unsuccessful balance responses at the same perturbation magnitude. Reactive step strategies and kinematics were investigated comparatively in successful and unsuccessful recovery tests. RESULTS: The crossover strategy was used in most of the unsuccessful tests (7/11) while the unloaded-leg side-step in the successful tests (6/11). There were no significant differences in the reactive step initiation time in unsuccessful vs. successful tests. However, the step execution time, step length and center of mass displacement were significantly higher during the first recovery step in unsuccessful tests. CONCLUSIONS: PwS have difficulties in controlling and decelerating the moving center of mass following a lateral loss of balance. The increased step time and step length of the first reactive step in unsuccessful vs. successful tests suggest the crossover step strategy may be ineffective for PwS.

Kinematic descriptors of arm reaching movement are sensitive to hemisphere-specific immediate neuromodulatory effects of transcranial direct current stimulation post stroke.

Transcranial direct current stimulation (tDCS) exerts beneficial effects on motor recovery after stroke, presumably by enhancement of adaptive neural plasticity. However, patients with extensive damage may experience null or deleterious effects with the predominant application mode of anodal (excitatory) stimulation of the damaged hemisphere. In such cases, excitatory stimulation of the non-damaged hemisphere might be considered. Here we asked whether tDCS exerts a measurable effect on movement quality of the hemiparetic upper limb, following just a single treatment session. Such effect may inform on the hemisphere that should be excited. Using a single-blinded crossover experimental design, stroke patients and healthy control subjects were assessed before and after anodal, cathodal and sham tDCS, each provided during a single session of reaching training (repeated point-to-point hand movement on an electronic tablet). Group comparisons of endpoint kinematics at baseline-number of peaks in the speed profile (NoP; smoothness), hand-path deviations from the straight line (SLD; accuracy) and movement time (MT; speed)-disclosed greater NoP, larger SLD and longer MT in the stroke group. NoP and MT revealed an advantage for anodal compared to sham stimulation of the lesioned hemisphere. NoP and MT improvements under anodal stimulation of the non-lesioned hemisphere correlated positively with the severity of hemiparesis. Damage to specific cortical regions and white-matter tracts was associated with lower kinematic gains from tDCS. The study shows that simple descriptors of movement kinematics of the hemiparetic upper limb are sensitive enough to demonstrate gain from neuromodulation by tDCS, following just a single session of reaching training. Moreover, the results show that tDCS-related gain is affected by the severity of baseline motor impairment, and by lesion topography.

ENHANCE proof-of-concept three-arm randomized trial: effects of reaching training of the hemiparetic upper limb restricted to the spasticity-free elbow range.

Post-stroke motor recovery processes remain unknown. Timescales and patterns of upper-limb (UL) recovery suggest a major impact of biological factors, with modest contributions from rehabilitation. We assessed a novel impairment-based training motivated by motor control theory where reaching occurs within the spasticity-free elbow range. Patients with subacute stroke (≤ 6 month; n = 46) and elbow flexor spasticity were randomly allocated to a 10-day UL training protocol, either personalized by restricting reaching to the spasticity-free elbow range defined by the tonic stretch reflex threshold (TSRT) or non-personalized (non-restricted) and with/without anodal transcranial direct current stimulation. Outcomes assessed before, after, and 1 month post-intervention were elbow flexor TSRT angle and reach-to-grasp arm kinematics (primary) and stretch reflex velocity sensitivity, clinical impairment, and activity (secondary). Results were analyzed for 3 groups as well as those of the effects of impairment-based training. Clinical measures improved in both groups. Spasticity-free range training resulted in faster and smoother reaches, smaller (i.e., better) arm-plane path length, and closer-to-normal shoulder/elbow movement patterns. Non-personalized training improved clinical scores without improving arm kinematics, suggesting that clinical measures do not account for movement quality. Impairment-based training within a spasticity-free elbow range is promising since it may improve clinical scores together with arm movement quality.Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique Identifier: NCT02725853; Initial registration date: 01/04/2016.

Lesion-behavior mapping indicates a strategic role for parietal substrates of associative memory.

Numerous neuroimaging studies indicate that ventral parietal cortex (VPC), especially angular gyrus, plays an important role in episodic memory. However, the nature of the mnemonic processes supported by this region is far from clear. We previously found that stroke lesions in VPC and lateral temporal cortex caused deficits in cued recall of unimodal word pairs and picture pairs, and cross-modal picture-sound pairs, with larger deficits in the cross-modal task. However, those findings leave open the question whether those regions' integrity is necessary for maintenance of associative representations, or for strategic processes required for their recall. We addressed this question using associative recognition versions of those tasks. We additionally manipulated semantic relatedness of the associated memoranda, to assess VPC's involvement in semantic processing in the context of episodic memory. We analyzed performance of 62 first-event, sub-acute phase stroke patients (31 right- and 31 left-hemisphere damage) relative to 65 healthy participants, and employed voxel-based lesion-behavior mapping (VLBM) to identify task-relevant structures. Patients displayed greater false associative recognition of semantically related compared to unrelated recombined pairs. VLBM analysis implicated right lateral temporo-parietal regions in associative recognition deficits in the cross-modal pairs task, specifically for related recombined and new pairs, seemingly because of difficulty overcoming semantic relatedness bias effects on episodic discrimination. In contrast, damage to ventral parietal and lateral temporal cortex was not implicated in memory for unrelated memoranda. We interpret this pattern of lesion-behavior effects as indicating lateral temporo-parietal cortex involvement in strategic, rather than representational, roles in episodic associative memory.

Use of multi-perturbation Shapley analysis in lesion studies of functional networks: The case of upper limb paresis.

Understanding the impact of variation in lesion topography on the expression of functional impairments following stroke is important, as it may pave the way to modeling structure-function relations in statistical terms while pointing to constraints for adaptive remapping and functional recovery. Multi-perturbation Shapley-value analysis (MSA) is a relatively novel game-theoretical approach for multivariate lesion-symptom mapping. In this methodological paper, we provide a comprehensive explanation of MSA. We use synthetic data to assess the method's accuracy and perform parameter optimization. We then demonstrate its application using a cohort of 107 first-event subacute stroke patients, assessed for upper limb (UL) motor impairment (Fugl-Meyer Assessment scale). Under the conditions tested, MSA could correctly detect simulated ground-truth lesion-symptom relationships with a sensitivity of 75% and specificity of ~90%. For real behavioral data, MSA disclosed a strong hemispheric effect in the relative contribution of specific regions-of-interest (ROIs): poststroke UL motor function was mostly contributed by damage to ROIs associated with movement planning (supplementary motor cortex and superior frontal gyrus) following left-hemispheric damage (LHD) and by ROIs associated with movement execution (primary motor and somatosensory cortices and the ventral brainstem) following right-hemispheric damage (RHD). Residual UL motor ability following LHD was found to depend on a wider array of brain structures compared to the residual motor ability of RHD patients. The results demonstrate that MSA can provide a unique insight into the relative importance of different hubs in neural networks, which is difficult to obtain using standard univariate methods.

Impaired empathic accuracy following damage to the left hemisphere.

Failing to understand others accurately can be extremely costly. Unfortunately, events such as strokes can lead to a decline in emotional understanding. Such impairments have been documented in stroke patients and are widely hypothesized to be related to right-hemisphere lesions, as well as to the amygdala, and are thought to be driven in part by attentional biases, for example, less fixation on the eyes. Notably, most of the previous research relied on measurements of emotional understanding from simplified cues, such as facial expressions or prosody. We hypothesize that chronic damage to the left hemisphere could hinder empathic accuracy and emotion recognition in naturalistic social settings that require complex language comprehension, even after a patient regains core language capacities. To assess this notion, we use an empathic accuracy task and eye-tracking measurements with chronic stroke patients with either right (N = 13) or left (N = 11) hemispheric damage-together with aged-matched controls (N = 15)-to explore the patients' understanding of others' affect inferred from stimuli that separates audio and visual cues. While we find that patients with right-hemisphere lesions showed visual attention bias compared to the other two groups, we uncover a disadvantage for patients with left-hemisphere lesions in empathic accuracy, especially when only auditory cues are present. These results suggest that patients with left-hemisphere damage have long-lasting difficulties comprehending real-world complex emotional situations.

Shared and distinct voxel-based lesion-symptom mappings for spasticity and impaired movement in the hemiparetic upper limb.

Hemiparesis and spasticity are common co-occurring manifestations of hemispheric stroke. The relationship between impaired precision and force in voluntary movement (hemiparesis) and the increment in muscle tone that stems from dysregulated activity of the stretch reflex (spasticity) is far from clear. Here we aimed to elucidate whether variation in lesion topography affects hemiparesis and spasticity in a similar or dis-similar manner. Voxel-based lesion-symptom mapping (VLSM) was used to assess the impact of lesion topography on (a) upper limb paresis, as reflected by the Fugl-Meyer Assessment scale for the upper limb and (b) elbow flexor spasticity, as reflected by the Tonic Stretch Reflex Threshold, in 41 patients with first-ever stroke. Hemiparesis and spasticity were affected by damage to peri-Sylvian cortical and subcortical regions and the putamen. Hemiparesis (but not spasticity) was affected by damage to the corticospinal tract at corona-radiata and capsular levels, and by damage to white-matter association tracts and additional regions in the temporal cortex and pallidum. VLSM conjunction analysis showed only a minor overlap of brain voxels where the existence of damage affected both hemiparesis and spasticity, suggesting that control of voluntary movement and regulation of muscle tone at rest involve largely separate parts of the motor network.

Verbal tagging can impair memory of object location: Evidence from aphasia.

The impact of damage to different regions and functional systems of the brain on visual working memory is far from understood. Here we examined how impaired object naming due to brain damage affects object identity and location information in working memory. Ten first-event stroke patients with aphasia performed a "delayed estimation" task that examines memory of object location separately from memory of object identity, using a continuous reporting scale. Following a delay of 4 s, objects that could not be named by the aphasic patients were localized more precisely than objects that could be named. The results are interpreted with reference to classic models separating phonological from visuospatial working memory, and with reference to the "verbal overshadowing" effect that is typically associated with long-term memory.

Motor learning in hemi-Parkinson using VR-manipulated sensory feedback.

AIMS: Modalities for rehabilitation of the neurologically affected upper-limb (UL) are generally of limited benefit. The majority of patients seriously affected by UL paresis remain with severe motor disability, despite all rehabilitation efforts. Consequently, extensive clinical research is dedicated to develop novel strategies aimed to improve the functional outcome of the affected UL. We have developed a novel virtual-reality training tool that exploits the voluntary control of one hand and provides real-time movement-based manipulated sensory feedback as if the other hand is the one that moves. The aim of this study was to expand our previous results, obtained in healthy subjects, to examine the utility of this training setup in the context of neuro-rehabilitation. METHODS: We tested the training setup in patient LA, a young man with significant unilateral UL dysfunction stemming from hemi-parkinsonism. LA underwent daily intervention in which he intensively trained the non-affected upper limb, while receiving online sensory feedback that created an illusory perception of control over the affected limb. Neural changes were assessed using functional magnetic resonance imaging (fMRI) scans before and after training. RESULTS: Training-induced behavioral gains were accompanied by enhanced activation in the pre-frontal cortex and a widespread increase in resting-state functional connectivity. DISCUSSION: Our combination of cutting edge technologies, insights gained from basic motor neuroscience in healthy subjects and well-known clinical treatments, hold promise for the pursuit of finding novel and more efficient rehabilitation schemes for patients suffering from hemiplegia.Implications for rehabilitationAssistive devices used in hospitals to support patients with hemiparesis require expensive equipment and trained personnel - constraining the amount of training that a given patient can receive. The setup we describe is simple and can be easily used at home with the assistance of an untrained caregiver/family member. Once installed at the patient's home, the setup is lightweight, mobile, and can be used with minimal maintenance . Building on advances in machine learning, our software can be adapted to personal use at homes. Our findings can be translated into practice with relatively few adjustments, and our experimental design may be used as an important adjuvant to standard clinical care for upper limb hemiparesis.

Exercise intensity of the upper limb can be enhanced using a virtual rehabilitation system.

PURPOSE: Motor recovery of the upper limb (UL) is related to exercise intensity, defined as movement repetitions divided by minutes in active therapy, and task difficulty. However, the degree to which UL training in virtual reality (VR) applications deliver intense and challenging exercise and whether these factors are considered in different centres for people with different sensorimotor impairment levels is not evidenced. We determined if (1) a VR programme can deliver high UL exercise intensity in people with sub-acute stroke across different environments and (2) exercise intensity and difficulty differed among patients with different levels of UL sensorimotor impairment. METHODS: Participants with sub-acute stroke (<6 months) with Fugl-Meyer scores ranging from 14 to 57, completed 10 ∼ 50-min UL training sessions using three unilateral and one bilateral VR activity over 2 weeks in centres located in three countries. Training time, number of movement repetitions, and success rates were extracted from game activity logs. Exercise intensity was calculated for each participant, related to UL impairment, and compared between centres. RESULTS: Exercise intensity was high and was progressed similarly in all centres. Participants had most difficulty with bilateral and lateral reaching activities. Exercise intensity was not, while success rate of only one unilateral activity was related to UL severity. CONCLUSION: The level of intensity attained with this VR exercise programme was higher than that reported in current stroke therapy practice. Although progression through different activity levels was similar between centres, clearer guidelines for exercise progression should be provided by the VR application.Implications for rehabilitationVR rehabilitation systems can be used to deliver intensive exercise programmes.VR rehabilitation systems need to be designed with measurable progressions through difficulty levels.

Lesion-behaviour mapping reveals multifactorial neurocognitive processes in recognition memory for unfamiliar faces.

Face recognition abilities, which play a critical role in social interactions, involve face processing and identifying familiar faces, but also remembering one-off encounters with previously unfamiliar faces. Previous functional imaging and lesion studies have found evidence for temporal, frontal, and parietal contributions to episodic recognition memory for previously unfamiliar faces. However, the functional contributions of these regions remain unclear. We, therefore, conducted a systematic group analysis of this memory function using lesion-behavior mapping. 95 first-event stroke patients (53 with right- and 42 with left-hemisphere damage) in the sub-acute phase performed the Wechsler Memory Scale (WMS-III) face recognition memory subtest. We analyzed their performance relative to 75 healthy controls, using signal detection measures. To identify brain lesions specifically implicated in face recognition deficits, we used voxel-based lesion-behavior mapping (VLBM; an analysis comparing the performance of participants with and without damage affecting a given voxel). Behavioral analysis disclosed a pronounced impairment in the performance of patients with right hemisphere damage. Frontal damage was associated with an increased amount of false alarms (i.e., failed rejection of new face items) and overly liberal criterion setting, without affecting the recognition of studied faces. In contrast, parietal damage was associated with impaired recognition of studied faces, which was more pronounced in immediate than in delayed retrieval. These findings suggest the existence of multifactorial neurocognitive processes in recognition memory for unfamiliar faces.

Temporal But Not Spatial Gait Parameters Associated With Lower Balance Capacity in Moderate-High Functioning Persons With Stroke.

BACKGROUND AND PURPOSE: Falls are a major health concern after stroke. Spatial and temporal gait asymmetry and variability can contribute to instability and increased fall risk in persons with stroke (PwS). We aimed to quantify gait spatiotemporal symmetry and variability parameters in PwS undergoing rehabilitation in the subacute stage of the disease, by comparison to healthy participants, and to examine the associations between these parameters and patients' reactive and proactive balance capacity. METHODS: Twenty-two PwS and 12 healthy adults walked over a computerized treadmill system at their self-selected walking speed. Symmetry and variability of gait parameters (step length, swing time, and stance time) as well as upper extremity and lower extremity angular range of motion in the sagittal plane were extracted. In addition, the Berg Balance Scale (BBS) and the fall threshold in response to sudden surface translations at increasing intensities were assessed. RESULTS: PwS demonstrated significantly higher asymmetry in all gait parameters in comparison to controls. Also, PwS demonstrated increased stance time variability in comparison to healthy controls and increased swing time variability in the paretic lower extremity. Significant negative associations were found between fall threshold and stance time asymmetry in PwS (r = -0.48, P = 0.022), between the BBS and swing time asymmetry (r = -0.50, P = 0.018), and between the BBS and stance time variability of the paretic lower extremity (r = -0.56, P = 0.006). DISCUSSION AND CONCLUSIONS: Findings highlight the importance of gait temporal symmetry and variability measures for dynamic balance control after stroke. These parameters should be considered when assessing gait recovery and safety in PwS.Video Abstract available for more insight from the authors (see the Video, Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A355).

Unilateral Spatial Neglect without Hemiplegia: The Output-Mode Effect Revisited.

BACKGROUND: The occurrence of unilateral spatial neglect (USN) in non-hemiplegic right-hemisphere damaged patients is rare. Earlier studies of such patients revealed a significant advantage when typical neglect tests were performed by the patient's left hand as compared to the dominant right hand. The mechanism underlying this "output-mode effect" remains elusive. METHODS: We analyzed the temporal dynamics of this effect using line-bisection task in 9 non-hemiplegic stroke patients with left-USN. RESULTS: In 4 patients tested shortly after stroke onset (≤ 6 weeks), the impact of hand laterality was variable (left-hand advantage in one patient; right-hand advantage in 2 patients; similar performance in both hands in one patient). Only later (> 6 weeks) a clear advantage of the left hand emerged in the majority of patients, similar to the earlier reports which were all based on late testing. CONCLUSIONS: We found variable dynamics in the expression of the output-mode effect in the first weeks following stroke onset, which may reflect changes of inter-hemispheric balance, related to recovery processes. We propose that therapeutic interventions aiming to manipulate the inter-hemispheric balance (e.g., by non-invasive brain stimulation) take into account the existence of such dynamics and their highly variate nature.

Effect of post-stroke spasticity on voluntary movement of the upper limb.

BACKGROUND: Hemiparesis following stroke is often accompanied by spasticity. Spasticity is one factor among the multiple components of the upper motor neuron syndrome that contributes to movement impairment. However, the specific contribution of spasticity is difficult to isolate and quantify. We propose a new method of quantification and evaluation of the impact of spasticity on the quality of movement following stroke. METHODS: Spasticity was assessed using the Tonic Stretch Reflex Threshold (TSRT). TSRT was analyzed in relation to stochastic models of motion to quantify the deviation of the hemiparetic upper limb motion from the normal motion patterns during a reaching task. Specifically, we assessed the impact of spasticity in the elbow flexors on reaching motion patterns using two distinct measures of the 'distance' between pathological and normal movement, (a) the bidirectional Kullback-Liebler divergence (BKLD) and (b) Hellinger's distance (HD). These measures differ in their sensitivity to different confounding variables. Motor impairment was assessed clinically by the Fugl-Meyer assessment scale for the upper extremity (FMA-UE). Forty-two first-event stroke patients in the subacute phase and 13 healthy controls of similar age participated in the study. Elbow motion was analyzed in the context of repeated reach-to-grasp movements towards four differently located targets. Log-BKLD and HD along with movement time, final elbow extension angle, mean elbow velocity, peak elbow velocity, and the number of velocity peaks of the elbow motion were computed. RESULTS: Upper limb kinematics in patients with lower FMA-UE scores (greater impairment) showed greater deviation from normality when the distance between impaired and normal elbow motion was analyzed either with the BKLD or HD measures. The severity of spasticity, reflected by the TSRT, was related to the distance between impaired and normal elbow motion analyzed with either distance measure. Mean elbow velocity differed between targets, however HD was not sensitive to target location. This may point at effects of spasticity on motion quality that go beyond effects on velocity. CONCLUSIONS: The two methods for analyzing pathological movement post-stroke provide new options for studying the relationship between spasticity and movement quality under different spatiotemporal constraints.

Tonic stretch reflex threshold as a measure of spasticity after stroke: Reliability, minimal detectable change and responsiveness.

OBJECTIVE: To determine inter-rater reliability, minimal detectable change and responsiveness of Tonic Stretch Reflex Threshold (TSRT) as a quantitative measure of elbow flexor spasticity. METHODS: Elbow flexor spasticity was assessed in 55 patients with sub-acute stroke by determining TSRT, the angle of spasticity onset at rest (velocity = 0°/s). Elbow flexor muscles were stretched 20 times at different velocities. Dynamic stretch-reflex thresholds, the elbow angles corresponding to the onset of elbow flexor EMG at each velocity, were used for TSRT calculation. Spasticity was also measured with the Modified Ashworth Scale (MAS). In a sub-group of 44 subjects, TSRT and MAS were measured before and after two weeks of an upper-limb intervention. RESULTS: The intraclass correlation coefficient was 0.65 and the 95% minimal detectable change was 32.4°. In the treated sub-group, TSRT, but not MAS significantly changed. TSRT effect size and standardized response mean were 0.40 and 0.35, respectively. Detection of clinically meaningful improvements in upper-limb motor impairment by TSRT change scores ranged from poor to excellent. CONCLUSIONS: Evaluation of stroke-related elbow flexor spasticity by TSRT has good inter-rater reliability. Test responsiveness is low, but better than that of the MAS. SIGNIFICANCE: TSRT may be used to complement current scales of spasticity quantification.

Stroke Lesion Impact on Lower Limb Function.

The impact of stroke on motor functioning is analyzed at different levels. 'Impairment' denotes the loss of basic characteristics of voluntary movement. 'Activity limitation' denotes the loss of normal capacity for independent execution of daily activities. Recovery from impairment is accomplished by 'restitution' and recovery from activity limitation is accomplished by the combined effect of 'restitution' and 'compensation.' We aimed to unravel the long-term effects of variation in lesion topography on motor impairment of the hemiparetic lower limb (HLL), and gait capacity as a measure of related activity limitation. Gait was assessed by the 3 m walk test (3MWT) in 67 first-event chronic stroke patients, at their homes. Enduring impairment of the HLL was assessed by the Fugl-Meyer Lower Extremity (FMA-LE) test. The impact of variation in lesion topography on HLL impairment and on walking was analyzed separately for left and right hemispheric damage (LHD, RHD) by voxel-based lesion-symptom mapping (VLSM). In the LHD group, HLL impairment tended to be affected by damage to the posterior limb of the internal capsule (PLIC). Walking capacity tended to be affected by a larger array of structures: PLIC and corona radiata, external capsule and caudate nucleus. In the RHD group, both HLL impairment and walking capacity were sensitive to damage in a much larger number of brain voxels. HLL impairment was affected by damage to the corona radiata, superior longitudinal fasciculus and insula. Walking was affected by damage to the same areas, plus the internal and external capsules, putamen, thalamus and parts of the perisylvian cortex. In both groups, voxel clusters have been found where damage affected FMA-LE and also 3MWT, along with voxels where damage affected only one of the measures (mainly 3MWT). In stroke, enduring 'activity limitation' is affected by damage to a much larger array of brain structures and voxels within specific structures, compared to enduring 'impairment.' Differences between the effects of left and right hemisphere damage are likely to reflect variation in motor-network organization and post-stroke re-organization related to hemispheric dominance. Further studies with larger sample size are required for the validation of these results.

Characteristics of upper-extremity reactions to sudden lateral loss of balance in persons with stroke.

BACKGROUND: Upper-extremity reactions are part of a whole-body response to counterweight the falling center of mass after unexpected balance loss. Impairments in upper-extremity reactions due to unilateral hemiparesis may contribute to stroke survivors propensity for falling. We aimed to characterize upper-extremity (paretic and non-paretic sides) reactive movements in response to lateral balance perturbations in Persons with Stroke vs. healthy controls. METHODS: Twenty-six subacute persons with stroke and 15 healthy controls were exposed to multidirectional sudden unannounced surface translations in stance. Spatiotemporal parameters of upper- and lower-extremity balance responses to lateral perturbations were analyzed. FINDINGS: In both groups reactive upper-extremity movement initiation preceded reactive step initiation. In response to a loss of balance toward the paretic side, persons with stroke demonstrated delayed movement initiation of both upper- and lower-extremity compared with healthy controls (In persons with stroke: 234.7 ± 60.0 msec and 227.1 ± 39.6 msec for upper extremities vs. 272.1 ± 59.1 msec for lower-extremity; and in controls: 180.1 ± 39.9 msec and 197.8 ± 61.3 msec for upper-extremities vs. 219.3 ± 40.8 msec for lower-extremity; p = 0.001, Cohen's d's: 0.59-1.03) and a greater abduction excursion in the ipsilateral upper-extremity compared with the contralateral upper-extremity (In persons with stroke: 39.3 ± 23.6 cm vs. 24.9 ± 10.1 cm, respectively; In Controls: 42.6 ± 21.8 cm vs. 29.3 ± 17.3 cm, respectively). INTERPRETATION: The faster upper-extremity reactive movement reactions compared to reactive step initiation in both persons with stroke and healthy controls suggests that balance recovery is an automatic "reflex-like" response. Delayed upper-extremity reactive reactions in conditions of surface translation toward the non-paretic side in persons with stroke may increase the risk of falls in the direction of the paretic side.

Working Memory in Unilateral Spatial Neglect: Evidence for Impaired Binding of Object Identity and Object Location.

Working memory (WM) is known to be impaired in patients with stroke experiencing unilateral spatial neglect (USN). Here, we examined in a systematic manner three WM components: memory of object identity, memory of object location, and binding between object identity and location. Moreover, we used two different retention intervals to isolate maintenance from other mnemonic and perceptual processes. Fourteen USN first-event stroke patients with right-hemisphere damage were tested in two different WM experiments using long and short retention intervals and an analog response scale. Patients exhibited more identification errors for items displayed on the contralesional side. Localization errors were also more prominent in the contralesional side, especially after a long retention interval. These localization errors were often a result of swap errors, that is, erroneous localizations of correctly identified contralesional objects in correctly memorized locations of ipsilesional objects. We conclude that a key WM deficit in USN is a lateralized impairment in binding between the identity of an object and its spatial tag.

Lesion Topography Impact on Shoulder Abduction and Finger Extension Following Left and Right Hemispheric Stroke.

The existence of shoulder abduction and finger extension movement capacity shortly after stroke onset is an important prognostic factor, indicating favorable functional outcomes for the hemiparetic upper limb (HUL). Here, we asked whether variation in lesion topography affects these two movements similarly or distinctly and whether lesion impact is similar or distinct for left and right hemisphere damage. Shoulder abduction and finger extension movements were examined in 77 chronic post-stroke patients using relevant items of the Fugl-Meyer test. Lesion effects were analyzed separately for left and right hemispheric damage patient groups, using voxel-based lesion-symptom mapping. In the left hemispheric damage group, shoulder abduction and finger extension were affected only by damage to the corticospinal tract in its passage through the corona radiata. In contrast, following the right hemispheric damage, these two movements were affected not only by corticospinal tract damage but also by damage to white matter association tracts, the putamen, and the insular cortex. In both groups, voxel clusters have been found where damage affected shoulder abduction and also finger extension, along with voxels where damage affected only one of the two movements. The capacity to execute shoulder abduction and finger extension movements following stroke is affected significantly by damage to shared and distinct voxels in the corticospinal tract in left-hemispheric damage patients and by damage to shared and distinct voxels in a larger array of cortical and subcortical regions in right hemispheric damage patients.