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.

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.

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).

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.

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.

Inter-observer Reliability and Concurrent Validity of Reactive Balance Strategies after Stroke.

BACKGROUND: Falls are a common complication in persons with stroke (PwS). Reliable assessment of balance responses to unexpected loss of balance has the potential to identify risk for falls. OBJECTIVES: To examine inter-observer reliability of balance responses to unannounced surface perturbations in PwS and to explore the concurrent validity of a balance recovery assessment protocol. METHODS: Two observers evaluated balance recovery strategies and fall threshold (a fall into a harness system) in 15 PwS and 15 healthy adults who were exposed to forward, backward, right, and left unannounced surface translations in six increasing intensities while standing. RESULTS: Observer agreement was 100% for the fall threshold. Kappa coefficients for step strategies were 0.960-0.988 in PwS and 0.886-0.938 in healthy adults, 0.905-0.988 for arm reactions in PwS and 0.754-0.926 in healthy adults. Significant correlations were found between fall threshold and Berg Balance Scale (r = 0.691), 6-minute walk test (r = 0.599), and fall efficacy scale-international (r= -0.581). CONCLUSIONS: A trained examiner can reliably classify reactive balance responses to surface perturbations. The high frequency of falls observed in PwS highlights the importance of assessing reactive balance responses to different directions and intensities of surface translations.

Comparing set summary statistics and outlier pop out in vision.

Visual scenes are too complex to perceive immediately in all their details. Two strategies (among others) have been suggested as providing shortcuts for evaluating scene gist before its details: (a) Scene summary statistics provide average values that often suffice for judging sets of objects and acting in their environment. Set summary perception spans simple/complex dimensions (circle size, face emotion), various statistics (mean, variance, range), and separate statistics for discernible sets. (b) Related to set summary perception is detecting outliers from sets, called "pop out," which allows rapid perception of presence and properties of unusual, and thus, possibly salient items in the scene. To understand better visual system mechanisms underlying these two set-related perceptual phenomena, we now study their properties and the relationship between them. We present observers with two clouds of bars with distributed orientations and ask them to discriminate their mean orientations, reporting which cloud is oriented more clockwise, on average. In the second experiment, the two clouds had the same mean orientation, but one had a bar with an outlier orientation, which observers detected. We find that cloud mean orientation discrimination depends mainly on the difference in means, whereas outlier detection depends mainly on the distance of the outlier orientation from the edge of the cloud orientation range. Neither percept depends largely on the range of the set itself. A unified model of a population-code mechanism underlying these two phenomena is discussed.

Association between cardiac autonomic control and cognitive performance among patients post stroke and age-matched healthy controls-an exploratory pilot study.

Associations between autonomic nervous system health and cognitive performance have been described in different populations. Autonomic disturbances are a common phenomenon in patients post stroke. Little is known about the relationship between post stroke disturbances of the autonomic nervous system and the commonly occurring disturbances of cognitive functions revealed by victims of stroke. To assess the association between heart rate variability (HRV) and cognitive performance among patients post ischemic stroke and healthy age-matched controls, 13 patients post first-ever ischemic stroke aged 40-80 years and 15 age-matched healthy controls were evaluated. HRV was monitored during sustained handgrip, while breathing at a rate of six breaths per minute, while performing the serial-3 subtraction task sitting at rest, and while cycling. Patients post stroke had greater error rate in the serial-3 subtraction task, and lower HRV (both at rest and during task performance) relative to healthy controls (at rest 26 ms [10-53] vs. 43 ms [29-88]). The HRV of stroke patients showed less sensitivity to changes in testing conditions, and also failed to show the correlation with cognitive performance exhibited by the healthy subjects. Stroke patients experience autonomic nervous system dysfunction in parallel to their motor and cognitive impairments. Too often only the latter receive appropriate treatment consideration in the rehabilitation setting. The current results, and earlier research, point to the importance of focusing clinical attention to the status of the autonomic nervous system, as amelioration of its functioning is likely to enhance motor and cognitive functioning as well.

Dysfunction of the Human Mirror Neuron System in Ideomotor Apraxia: Evidence from Mu Suppression.

Stroke patients with ideomotor apraxia (IMA) have difficulties controlling voluntary motor actions, as clearly seen when asked to imitate simple gestures performed by the examiner. Despite extensive research, the neurophysiological mechanisms underlying failure to imitate gestures in IMA remain controversial. The aim of the current study was to explore the relationship between imitation failure in IMA and mirror neuron system (MNS) functioning. Mirror neurons were found to play a crucial role in movement imitation and in imitation-based motor learning. Their recruitment during movement observation and execution is signaled in EEG recordings by suppression of the lower (8-10 Hz) mu range. We examined the modulation of EEG in this range in stroke patients with left (n = 21) and right (n = 15) hemisphere damage during observation of video clips showing different manual movements. IMA severity was assessed by the DeRenzi standardized diagnostic test. Results showed that failure to imitate observed manual movements correlated with diminished mu suppression in patients with damage to the right inferior parietal lobule and in patients with damage to the right inferior frontal gyrus pars opercularis-areas where major components of the human MNS are assumed to reside. Voxel-based lesion symptom mapping revealed a significant impact on imitation capacity for the left inferior and superior parietal lobules and the left post central gyrus. Both left and right hemisphere damages were associated with imitation failure typical of IMA, yet a clear demonstration of relationship to the MNS was obtained only in the right hemisphere damage group. Suppression of the 8-10 Hz range was stronger in central compared with occipital sites, pointing to a dominant implication of mu rather than alpha rhythms. However, the suppression correlated with De Renzi's apraxia test scores not only in central but also in occipital sites, suggesting a multifactorial mechanism for IMA, with a possible impact for deranged visual attention (alpha suppression) beyond the effect of MNS damage (mu suppression).

Autonomic Cardiac Response to Static and Dynamic Muscle Contractions in Post-Stroke and Healthy Subjects.

AIM: To describe the response of the cardiac autonomic nervous system to static and dynamic muscle contractions in post ischemic stroke patients 2 and 7 weeks post event, compared with the response of age- and gender-matched healthy controls. PARTICIPANTS: 12 patients post first stroke at the subacute phase and 12 healthy age-matched controls. TOOLS: the Polar Advanced Heart Rate Monitor (RS800CX) was used to record inter bit intervals at rest and during grip and cycling. RESULTS: Patients post stroke, both at 2 and 7 weeks post onset time, had higher heart rate and lower heart rate variability (HRV) values at rest compared to controls. A significant reduction in HRV values was noted among healthy controls during static and dynamic muscle contractions compared to baseline. In contrast, stroke patients 2 weeks after onset did not show a cardiac reaction to static contractions. At 7 weeks post onset examination, the stroke patients showed a significant reduction in HRV both during static and dynamic contractions compared to the rest state. CONCLUSION: Patients post stroke in the subacute phase have alterations in cardiac rhythm regulation both at rest and during muscle effort. The extent of the cardiac autonomic response to muscle contraction is associated with contraction type and time post event. Simple measurement of HRV in different conditions enables monitoring of recovery of autonomic nervous system cardiac control.

Computing an average when part of the population is not perceived.

The syndrome of unilateral spatial neglect (USN) after right-hemisphere damage is characterized by failure of salient left-sided stimuli to activate an orienting response, attract attention, and gain access to conscious awareness. The explicit failure processing left-sided visual information is not uniform, however, and patients seem to be more successful performing certain visual tasks than others. The source of this difference is still not clear. We focus on processing of visual scene statistical properties, asking whether, in computing the average size of an array of objects, USN patients give appropriate weight to objects on the left; disregard left-side objects entirely; or assign them an intermediate, lower weight, in accord with their tendency to neglect these objects. The interest in testing this question stems from a series of studies in healthy individuals that led Chong and Treisman [Chong, S. C., & Treisman, A. Statistical processing: Computing the average size in perceptual groups. Vision Research, 45, 891-900, 2005a; Chong, S. C., & Treisman, A. Attentional spread in the statistical processing of visual displays. Perception & Psychophysics, 67, 1-13, 2005b] to propose that processing of statistical properties (like the average size of visual scene elements) is carried out in parallel, with no need for serial allocation of focal attention to the different scene elements. Our results corroborate this suggestion, showing that objects in the left ("neglected") hemispace contribute to average size computation, despite a marked imbalance in spatial distribution of attention, which leads to a reduced weight of left-side elements in the averaging computation. This finding sheds light on the nature of the impairment in USN and on basic mechanisms underlying statistical processing in vision. We confirm that statistical processing depends mainly on spread-attention mechanisms, which are largely spared in USN.

Global statistics are not neglected.

In the framework of Reverse Hierarchy Theory it was suggested that initial vision at a glance brings the gist of the scene to conscious perception using explicit high cortical level representations, which are initially built by implicit bottom-up processing (Hochstein & Ahissar, 2002). Only later return to lower cortical level representations introduces local details to conscious perception. Global statistics of similar elements are perceived rapidly and accurately, suggesting they are included in the initial perception of the gist of the scene, not depending on prior conscious perception of local details. Patients with unilateral spatial neglect have difficulty responding to elements in their contralesional hemifield. However, this deficit is especially pronounced for tasks that require focused attention, i.e., are dependent on the reverse-hierarchy return. We review recent studies that indicate that perception of global statistics is among the spread attention tasks that are somewhat spared from this deficit. Combining these results, we suggest that perhaps the function of global statistics perception might include serving as a basic percept required for finding salient deviants from the mean, as in rapid odd element feature search paradigms, and perhaps subsequently focusing attention to them.

Visual memory in unilateral spatial neglect: immediate recall versus delayed recognition.

Patients with unilateral spatial neglect (USN) often show impaired performance in spatial working memory tasks, apart from the difficulty retrieving "left-sided" spatial data from long-term memory, shown in the "piazza effect" by Bisiach and colleagues. This study's aim was to compare the effect of the spatial position of a visual object on immediate and delayed memory performance in USN patients. Specifically, immediate verbal recall performance, tested using a simultaneous presentation of four visual objects in four quadrants, was compared with memory in a later-provided recognition task, in which objects were individually shown at the screen center. Unlike healthy controls, USN patients showed a left-side disadvantage and a vertical bias in the immediate free recall task (69% vs. 42% recall for right- and left-sided objects, respectively). In the recognition task, the patients correctly recognized half of "old" items, and their correct rejection rate was 95.5%. Importantly, when the analysis focused on previously recalled items (in the immediate task), no statistically significant difference was found in the delayed recognition of objects according to their original quadrant of presentation. Furthermore, USN patients were able to recollect the correct original location of the recognized objects in 60% of the cases, well beyond chance level. This suggests that the memory trace formed in these cases was not only semantic but also contained a visuospatial tag. Finally, successful recognition of objects missed in recall trials points to formation of memory traces for neglected contralesional objects, which may become accessible to retrieval processes in explicit memory.

Mirror-neuron system recruitment by action observation: effects of focal brain damage on mu suppression.

Mu suppression is the attenuation of EEG power in the alpha frequency range (8-12 Hz), recorded over the sensorimotor cortex during execution and observation of motor actions. Based on this dual characteristic mu suppression is thought to signalize activation of a human analogue of the mirror neuron system (MNS) found in macaque monkeys. However, much uncertainty remains concerning its specificity and full significance. To further explore the hypothesized relationship between mu suppression and MNS activation, we investigated how it is affected by damage to cortical regions, including areas where the MNS is thought to reside. EEG was recorded in 33 first-event stroke patients during observation of video clips showing reaching and grasping hand movements. We examined the modulation of EEG oscillations at central and occipital sites, and analyzed separately the lower (8-10 Hz) and higher (10-12 Hz) segments of the alpha/mu range. Suppression was determined relative to observation of a non-biological movement. Normalized lesion data were used to investigate how damage to regions of the fronto-parietal cortex affects the pattern of suppression. The magnitude of mu suppression during action observation was significantly reduced in the affected hemisphere compared to the unaffected hemisphere. Differences between the hemispheres were significant at central (sensorimotor) sites but not at occipital (visual) sites. Total hemispheric volume loss did not correlate with mu suppression. Suppression in the lower mu range in the unaffected hemisphere (C3) correlated with lesion extent within the right inferior parietal cortex. Our lesion study supports the role of mu suppression as a marker of MNS activation, confirming previous studies in normal subjects.

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.

Sniffing enables communication and environmental control for the severely disabled.

Paradoxically, improvements in emergency medicine have increased survival albeit with severe disability ranging from quadriplegia to "locked-in syndrome." Locked-in syndrome is characterized by intact cognition yet complete paralysis, and hence these individuals are "locked-in" their own body, at best able to communicate using eye blinks alone. Sniffing is a precise sensory-motor acquisition entailing changes in nasal pressure. The fine control of sniffing depends on positioning the soft palate, which is innervated by multiple cranial nerves. This innervation pattern led us to hypothesize that sniffing may remain conserved following severe injury. To test this, we developed a device that measures nasal pressure and converts it into electrical signals. The device enabled sniffs to control an actuator with speed similar to that of a hand using a mouse or joystick. Functional magnetic resonance imaging of device usage revealed a widely distributed neural network, allowing for increased conservation following injury. Also, device usage shared neural substrates with language production, rendering sniffs a promising bypass mode of communication. Indeed, sniffing allowed completely paralyzed locked-in participants to write text and quadriplegic participants to write text and drive an electric wheelchair. We conclude that redirection of sniff motor programs toward alternative functions allows sniffing to provide a control interface that is fast, accurate, robust, and highly conserved following severe injury.

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.

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.

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.

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.