Severity-Dependent Interhemispheric White Matter Connectivity Predicts Poststroke Neglect Recovery.

Left-sided spatial neglect is a very common and challenging issue after right-hemispheric stroke, which strongly and negatively affects daily living behavior and recovery of stroke survivors. The mechanisms underlying recovery of spatial neglect remain controversial, particularly regarding the involvement of the intact, contralesional hemisphere, with potential contributions ranging from maladaptive to compensatory. In the present prospective, observational study, we assessed neglect severity in 54 right-hemispheric stroke patients (32 male; 22 female) at admission to and discharge from inpatient neurorehabilitation. We demonstrate that the interaction of initial neglect severity and spared white matter (dis)connectivity resulting from individual lesions (as assessed by diffusion tensor imaging, DTI) explains a significant portion of the variability of poststroke neglect recovery. In mildly impaired patients, spared structural connectivity within the lesioned hemisphere is sufficient to attain good recovery. Conversely, in patients with severe impairment, successful recovery critically depends on structural connectivity within the intact hemisphere and between hemispheres. These distinct patterns, mediated by their respective white matter connections, may help to reconcile the dichotomous perspectives regarding the role of the contralesional hemisphere as exclusively compensatory or not. Instead, they suggest a unified viewpoint wherein the contralesional hemisphere can - but must not necessarily - assume a compensatory role. This would depend on initial impairment severity and on the available, spared structural connectivity. In the future, our findings could serve as a prognostic biomarker for neglect recovery and guide patient-tailored therapeutic approaches.

Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke.

Background: This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS). Methods: Consecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke. Results: A total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th-75th percentiles 67-84 years versus 70 years, 25th-75th percentiles 60-80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01-2.19, value of p 0.044). Conclusion: This study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

The Flow State Scale for Rehabilitation Tasks: A New Flow Experience Questionnaire for Stroke Patients.

IMPORTANCE: Flow can be described as a subjective state that people report when they fully engage in an activity and experience pleasure, satisfaction, and enjoyment. Flow experiences are measured to determine the extent to which patients engage in therapy activities. Several flow questionnaires are used in neurorehabilitation. However, none have been validated for patients with (sub)acute stroke. OBJECTIVE: To develop and validate a new flow questionnaire for patients with (sub)acute stroke. DESIGN: Single-center prospective cohort study. SETTING: Neurorehabilitation unit of the Neurocenter of the Luzerner Kantonsspital in Lucerne, Switzerland. PARTICIPANTS: Fifty patients with (sub)acute stroke. OUTCOMES AND MEASURES: Development of the Flow State Scale for Rehabilitation Tasks (FSSRT) and determination of the psychometric properties of the FSSRT (internal consistency, test-retest reliability, structural and construct validity) in (sub)acute stroke patients. RESULTS: The FSSRT showed good internal consistency and excellent test-retest reliability. Composed of four components-concentration, pleasure, movement control, and absorption-the FSSRT correlated significantly negatively with the Hospital Anxiety and Depression Scale, indicating good divergent validity. CONCLUSIONS AND RELEVANCE: The FSSRT is a reliable and valid questionnaire measuring flow experience in patients with (sub)acute stroke. This questionnaire can be easily used in occupational therapy as well as in physical therapy and gives therapists important information about the flow experience of patients during therapy to adjust the therapy accordingly. Plain-Language Summary: Measuring flow experience, or the extent to which patients engage in therapy activities, in the context of occupational therapy and physical therapy is a new approach. This study confirmed that the Flow State Scale for Rehabilitation Tasks questionnaire is reliable and valid for measuring the flow experience of patients after (sub)acute stroke. Occupational therapists and physical therapists can use the FSSRT to optimally adjust the therapy program and increase patient engagement during therapy.

Comparison of uni- and multimodal motion stimulation on visual neglect: A proof-of-concept study.

Spatial neglect is characterized by the failure to attend stimuli presented in the contralesional space. Typically, the visual modality is more severely impaired than the auditory one. This dissociation offers the possibility of cross-modal interactions, whereby auditory stimuli may have beneficial effects on the visual modality. A new auditory motion stimulation method with music dynamically moving from the right to the left hemispace has recently been shown to improve visual neglect. The aim of the present study was twofold: a) to compare the effects of unimodal auditory against visual motion stimulation, i.e., smooth pursuit training, which is an established therapeutical approach in neglect therapy and b) to explore whether a combination of auditory + visual motion stimulation, i.e., multimodal motion stimulation, would be more effective than unimodal auditory or visual motion stimulation. 28 patients with left-sided neglect due to a first-ever, right-hemispheric subacute stroke were included. Patients either received auditory, visual, or multimodal motion stimulation. The between-group effect of each motion stimulation condition as well as a control group without motion stimulation was investigated by means of a one-way ANOVA with the patient's visual exploration behaviour as an outcome variable. Our results showed that unimodal auditory motion stimulation is equally effective as unimodal visual motion stimulation: both interventions significantly improved neglect compared to the control group. Multimodal motion stimulation also significantly improved neglect, however, did not show greater improvement than unimodal auditory or visual motion stimulation alone. Besides the established visual motion stimulation, this proof-of-concept study suggests that auditory motion stimulation seems to be an alternative promising therapeutic approach to improve visual attention in neglect patients. Multimodal motion stimulation does not lead to any additional therapeutic gain. In neurorehabilitation, the implementation of either auditory or visual motion stimulation seems therefore reasonable.

Profiling Daily Life Performance Recovery in the Early Subacute Phase After Stroke Using a Graphical Modeling Approach.

Background Laboratory-based assessments have shown that stroke recovery is heterogeneous between patients and affected domains such as motor and language function. However, laboratory-based assessments are not ecologically valid and do not necessarily reflect patients' daily life performance. Therefore, we aimed to give an innovative view on stroke recovery by profiling daily life performance recovery across domains in patients with early subacute stroke and determine their interrelatedness, taking stroke localization into account. Methods and Results Daily life performance was observed at neurorehabilitation admission and weekly thereafter until discharge, using a scale containing 7 daily life domains. Graphical modeling was applied to investigate the conditional independence between recovery of these domains depending on stroke localization. There were 592 patients analyzed. Four clusters of interrelated domains were identified within the first 6 weeks poststroke. The first cluster included recovery in learning and applying knowledge, general tasks and demands, and domestic life. The second cluster comprised recovery in self-care and general tasks and demands. The third cluster included recovery in mobility and self-care; it incorporated interpersonal interactions and relationships in left supratentorial stroke, and learning and applying knowledge in right supratentorial stroke. The final cluster included only communication recovery. Conclusions Daily life recovery dynamics early poststroke show that although impairments in body functions are anatomically determined, their impact on performance is comparable. Second, some, but by no means all, domains show an interrelated recovery. Domains requiring cognitive abilities are especially interrelated and seem to be essential for concomitant recovery in mobility and domestic life.

Rasch validation of a new scale to measure dependency in arm use in daily life: the Upper Limb Lucerne ICF-based Multidisciplinary Observation Scale.

Introduction: About 77% of adults with stroke have upper limb impairments. Many scales are available to measure the impairment and activity level of the affected limb. However, an observational scale to assess dependency on others in upper limb performance during daily life activities instead of laboratory settings is lacking. Therefore, we developed a new 5-item Upper Limb Lucerne ICF-based Multidisciplinary Observation Scale (UL-LIMOS). As next step in the psychometric analysis, we evaluated the unidimensionality and structural validity of the UL-LIMOS with Rasch Measurement Theory and we calculated a cut-off score for independent arm use in daily life activities at discharge. Methods: This is a single-center cross-sectional study in adults with (sub) acute stroke. We applied Rasch Measurement Theory (RMT) to analyze the structural validation and unidimensionality of the UL-LIMOS. The outputs provide evidence of unidimensionality, item and person fit, overall fit, differential item functioning (DIF), principal component analysis of residuals (PCAR), person separation reliability (PSR), and residual item correlations (to identify local item dependence). Person mean location, floor and ceiling effects identify proper targeting. Results: We recruited 407 adults with (sub) acute stroke (median age 63 years, 157 women). All items and persons fit the Rasch model. The PSR of 0.90 indicates that clinicians and researchers can reliably use the scale for individual decision-making. There were small floor (2.70%) and ceiling (13.00%) effects. The average person mean location was 1.32 ± 2.99 logits. There was no DIF. PCAR eigenvalue was 2.46 with 49.23% explained variance. Paired t-tests revealed that 0.89% of person locations were significantly different, confirming unidimensionality. One pair of items (arm and hand use and fine hand use) showed residual item correlations. The ROC's AUC was 0.90, CI95% = [0.85-0.96] with cut-off score of ≥14/20, and high sensitivity (87%, CI95% = [81%-91%]), specificity (83%, CI95% = [77%-87%]) for independent arm use in daily living at discharge. Discussion: The new Rasch-based UL-LIMOS is a valid ICF-based observation performance scale at the ICF-activity level, to evaluate dependency during upper limb use in daily life in adults with stroke. Additional psychometric analyses are warranted. The UL-LIMOS would be a valuable addition to the core assessments of adults with (sub) acute stroke.

A case study of left visual neglect after right pontine lesion: pathophysiological evidence for the infratentorial involvement in human visual attention.

Hemispatial neglect, the inability to attend to the contralesional side of space, is the most common disturbance of visuospatial attention. Both hemispatial neglect and visuospatial attention are typically associated with extended cortical networks. Nevertheless, recent accounts challenge this so-called corticocentric view and postulate the participation of structures well beyond the telencephalic cortex, in particular advocating the role of the brainstem. However, to the best of our knowledge, hemispatial neglect after a brainstem lesion has not yet been described. We describe, for the first time in a human, the occurrence and remission of contralesional visual hemispatial neglect after a focal lesion in the right pons. Hemispatial neglect was assessed by means of video-oculography during free visual exploration, a very sensitive and established method, and its remission was followed up until 3 wk after stroke. Moreover, by means of a lesion-deficit approach complemented by imaging, we identify a pathophysiological mechanism involving the disconnection of cortico-ponto-cerebellar and/or tecto-cerebellar-tectal pathways passing through the pons. Our findings offer, for the first time in a human, causal, lesion-based support for recent seminal accounts postulating the role of infratentorial structures participating in the activity of cerebral cortical attentional networks mediating attentional processes.NEW & NOTEWORTHY Visuospatial attention and its most common disturbance, hemispatial neglect, are typically associated with extended cortical networks. However, recent accounts challenge this corticocentric view and advocate the role of infratentorial structures. We describe, for the first time in a human, the occurrence of contralesional visual hemispatial neglect after a focal lesion in the right pons. We provide causal, lesion-based evidence for a pathophysiological mechanism involving the disconnection of cortico-ponto-cerebellar and/or tecto-cerebellar-tectal pathways passing through the pons.

Sex Differences in Outcomes of Intravenous Thrombolysis in Acute Ischemic Stroke Patients with Preadmission Use of Antiplatelets.

AIM: To compare safety and functional outcomes of intravenous thrombolysis (IVT) between females and males with acute ischaemic stroke (AIS) in relation to preadmission use of antiplatelets. METHODS: Multicentre cohort study of patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry, presenting with AIS and receiving IVT. Primary safety outcome was in-hospital symptomatic intracerebral haemorrhage (sICH). Primary functional outcome was functional independence at 3 months after discharge. Multivariable logistic regression models were fitted to assess the association between sex and each outcome according to preadmission use of antiplatelets. RESULTS: The study included 4996 patients (42.51 % females, older than males, median age 79 vs 71 years, p < 0.0001). Comparable proportions of females (39.92 %) and males (40.39 %) used antiplatelets before admission (p = 0.74). In total, 3.06 % females and 2.47 % males developed in-hospital sICH (p = 0.19), with similar odds (adjusted odds ratio, [AOR] 0.93, 95 % confidence interval, [CI] 0.63-1.39). No interaction was found between sex and preadmission use of either single or dual antiplatelets in relation to in-hospital sICH (p = 0.94 and p = 0.23). Males had higher odds of functional independence at 3 months (AOR 1.34, 95 % CI 1.09-1.65), regardless of preadmission use of antiplatelets (interaction between sex and preadmission use of either single or dual antiplatelets p = 0.41 and p = 0.58). CONCLUSION: No sex differences were observed in the safety of IVT regarding preadmission use of antiplatelets. Males showed more favourable 3-month functional independence than females; however, this sex difference was apparently not explained by a sex-specific mechanism related to preadmission use of antiplatelets.

Feasibility of a combined intermittent theta-burst stimulation and video game-based dexterity training in Parkinson's disease.

BACKGROUND: Persons with Parkinson's disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL), inter alia due to dysfunctional supplementary motor area (SMA). Combined intermittent theta-burst stimulation (iTBS) over the SMA followed by video game-based training (VBT) may therefore improve dexterity related ADL. The VBT may induce high flow levels related to high performance during the training. The aim of this study is to evaluate the feasibility of a combined iTBS-VBT intervention in persons with PD. METHODS: A total of nine persons with PD (mean age 63.3 ± 8.76 years) with self-reported difficulties with dexterity related ADL were included in this pilot iTBS-VBT study. All participants received either iTBS or sham stimulation over the SMA followed by a 45-min VBT, three times a week for a total of three weeks. Feasibility was measured by means of the adherence rate and the system usability (System Usability Scale). Moreover, flow was measured after the last VBT session. RESULTS: Adherence rate was excellent with 100%. High system usability scores (i.e., mean 80%, range 55-97.5) and a significant Spearman's correlation with the Flow State Scale (r = .762, p = .017) further point to the high feasibility of the VBT. Neither demographic variables nor difficulties in dexterity related ADL affected the usability of the VBT. CONCLUSION: This study demonstrates the high feasibility of a combined iTBS-VBT intervention. Moreover, the level of self-reported usability was related to flow experience. Whether this kind of combined iTBS-VBT intervention improves dexterity will be evaluated in a randomized controlled trial. Trial registration clincaltrials.gov NCT04699149, date of registration 1. June 2021.

Joint impact on attention, alertness and inhibition of lesions at a frontal white matter crossroad.

In everyday life, information from different cognitive domains-such as visuospatial attention, alertness and inhibition-needs to be integrated between different brain regions. Early models suggested that completely segregated brain networks control these three cognitive domains. However, more recent accounts, mainly based on neuroimaging data in healthy participants, indicate that different tasks lead to specific patterns of activation within the same, higher-order and 'multiple-demand' network. If so, then a lesion to critical substrates of this common network should determine a concomitant impairment in all three cognitive domains. The aim of the present study was to critically investigate this hypothesis, i.e. to identify focal stroke lesions within the network that can concomitantly affect visuospatial attention, alertness and inhibition. We studied an unselected sample of 60 first-ever right-hemispheric, subacute stroke patients using a data-driven, bottom-up approach. Patients performed 12 standardized neuropsychological and oculomotor tests, four per cognitive domain. A principal component analysis revealed a strong relationship between all three cognitive domains: 10 of 12 tests loaded on a first, common component. Analysis of the neuroanatomical lesion correlates using different approaches (i.e. voxel-based and tractwise lesion-symptom mapping, disconnectome maps) provided convergent evidence on the association between severe impairment of this common component and lesions at the intersection of superior longitudinal fasciculus II and III, frontal aslant tract and, to a lesser extent, the putamen and inferior fronto-occipital fasciculus. Moreover, patients with a lesion involving this region were significantly more impaired in daily living cognition, which provides an ecological validation of our results. A probabilistic functional atlas of the multiple-demand network was performed to confirm the potential relationship between patients' lesion substrates and observed cognitive impairments as a function of the multiple-demand network connectivity disruption. These findings show, for the first time, that a lesion to a specific white matter crossroad can determine a concurrent breakdown in all three considered cognitive domains. Our results support the multiple-demand network model, proposing that different cognitive operations depend on specific collaborators and their interaction, within the same underlying neural network. Our findings also extend this hypothesis by showing (i) the contribution of superior longitudinal fasciculus and frontal aslant tract to the multiple-demand network; and (ii) a critical neuroanatomical intersection, crossed by a vast amount of long-range white matter tracts, many of which interconnect cortical areas of the multiple-demand network. The vulnerability of this crossroad to stroke has specific cognitive and clinical consequences; this has the potential to influence future rehabilitative approaches.

Speed up discharge planning at the acute stroke unit: A development and external validation study for the early prediction of discharge home.

Background: To reduce healthcare costs, it has become increasingly important to shorten the length of stay in acute stroke units. The goal of this study was to develop and externally validate a decision tree model applicable < 48 h poststroke for discharge home from an acute stroke unit with a short length of stay, and to assess the inappropriate home discharge rate. Methods: A prospective study including two samples of stroke patients admitted to an acute stroke unit. The outcome was discharge home (yes/no). A classification and regression tree analysis was performed in Sample 1. The model's performance was tested in Sample 2. Results: In total, 953 patients were included. The final decision tree included the patients' activities of daily living (ADL) performance <48 h poststroke, including motor function, cognition, and communication, and had an area under the curve (AUC) of 0.84 (95% confidence interval 0.76, 0.91). External validation resulted in an AUC of 0.74 (95% confidence interval 0.72, 0.77). None of the patients discharged home were re-admitted < 2 months after discharge to a hospital or admitted to a rehabilitation center for symptoms that had needed inpatient neurorehabilitation. Conclusions: The developed decision tree shows acceptable external validity in predicting discharge home in a heterogeneous sample of stroke patients, only based on the patient's actual ADL performance <48 h poststroke. Importantly, discharge was safe, i.e., no re-hospitalization was registered. The tree's application to speed up discharge planning should now be further evaluated.

Development and Validation of the Short-LIMOS for the Acute Stroke Unit-A Short Version of the Lucerne ICF-Based Multidisciplinary Observation Scale.

Introduction: At hospital stroke units, the time available to assess the patient's limitations in activities and participation is limited, although being essential for discharge planning. Till date, there is no quick-to-perform instrument available that captures the patient's actual performance during daily activities from a motor, cognitive, and communication perspective within the International Classification of Functioning, Disability and Health (ICF) framework. Therefore, the aim was to develop and validate a shortened version of the Lucerne ICF-Based Multidisciplinary Observation Scale (Short-LIMOS) that observes the patient's performance across ICF-domains and is applicable in the context of an acute stroke unit. Methods: The Short-LIMOS was developed by reducing the original 45-item LIMOS to the ten most important items using a multivariable linear regression ANOVA with data of 836 stroke patients collected during inpatient neurorehabilitation. The Short-LIMOS's reliability, validity, and responsiveness were evaluated with data of 416 stroke patients in the acute stroke unit. Results: A significant equation [F (10,825) = 232.083] with R 2 of 0.738 was found for the following ten items for the Short-LIMOS: maintaining a body position (d415), changing basic body position (d410), climbing stairs (d4551), eating (d550), dressing (d540), communicating with-receiving-written messages (reading) (d325), applying knowledge, remembering facts (d179), solving complex problems (d1751), making simple decisions (d177), and undertaking a simple task (d2100). Principal component analysis revealed a Short-LIMOS motor and a Short-LIMOS cognition/communication component. The Short-LIMOS had a high internal consistency and good test-retest reliability. A moderate construct validity was shown by the significant correlation with the Barthel Index. The Short-LIMOS had neither floor nor ceiling effects. Discussion and Conclusion: The developed Short-LIMOS was found to be reliable and valid within a population of (hyper)acute and subacute stroke patients. The added value of this multidisciplinary assessment is its comprehensiveness by capturing the patient's actual performance on the motor, cognitive, and communication domain embedded in an ICF-framework in <10 mins.

Effects of Virtual Reality-Based Multimodal Audio-Tactile Cueing in Patients With Spatial Attention Deficits: Pilot Usability Study.

BACKGROUND: Virtual reality (VR) devices are increasingly being used in medicine and other areas for a broad spectrum of applications. One of the possible applications of VR involves the creation of an environment manipulated in a way that helps patients with disturbances in the spatial allocation of visual attention (so-called hemispatial neglect). One approach to ameliorate neglect is to apply cross-modal cues (ie, cues in sensory modalities other than the visual one, eg, auditory and tactile) to guide visual attention toward the neglected space. So far, no study has investigated the effects of audio-tactile cues in VR on the spatial deployment of visual attention in neglect patients. OBJECTIVE: This pilot study aimed to investigate the feasibility and usability of multimodal (audio-tactile) cueing, as implemented in a 3D VR setting, in patients with neglect, and obtain preliminary results concerning the effects of different types of cues on visual attention allocation compared with noncued conditions. METHODS: Patients were placed in a virtual environment using a head-mounted display (HMD). The inlay of the HMD was equipped to deliver tactile feedback to the forehead. The task was to find and flag appearing birds. The birds could appear at 4 different presentation angles (lateral and paracentral on the left and right sides), and with (auditory, tactile, or audio-tactile cue) or without (no cue) a spatially meaningful cue. The task usability and feasibility, and 2 simple in-task measures (performance and early orientation) were assessed in 12 right-hemispheric stroke patients with neglect (5 with and 7 without additional somatosensory impairment). RESULTS: The new VR setup showed high usability (mean score 10.2, SD 1.85; maximum score 12) and no relevant side effects (mean score 0.833, SD 0.834; maximum score 21). A repeated measures ANOVA on task performance data, with presentation angle, cue type, and group as factors, revealed a significant main effect of cue type (F30,3=9.863; P<.001) and a significant 3-way interaction (F90,9=2.057; P=.04). Post-hoc analyses revealed that among patients without somatosensory impairment, any cue led to better performance compared with no cue, for targets on the left side, and audio-tactile cues did not seem to have additive effects. Among patients with somatosensory impairment, performance was better with both auditory and audio-tactile cueing than with no cue, at every presentation angle; conversely, tactile cueing alone had no significant effect at any presentation angle. Analysis of early orientation data showed that any type of cue triggered better orientation in both groups for lateral presentation angles, possibly reflecting an early alerting effect. CONCLUSIONS: Overall, audio-tactile cueing seems to be a promising method to guide patient attention. For instance, in the future, it could be used as an add-on method that supports attentional orientation during established therapeutic approaches.

Visual Neglect after PICA Stroke-A Case Study.

After cerebellar stroke, cognition can be impaired, as described within the framework of the so-called Cerebellar Cognitive Affective Syndrome (CCAS). However, it remains unclear whether visual neglect can also be part of CCAS. We describe the case of a patient with a subacute cerebellar stroke after thrombosis of the left posterior inferior cerebellar artery (PICA), who showed a left-sided visual neglect, indicating that the cerebellum also has a modulatory function on visual attention. The neglect, however, was mild and only detectable when using the sensitive neuro-psychological Five-Point Test as well as video-oculography assessment, yet remained unnoticed when evaluated with common neglect-specific paper-pencil tests. Three weeks later, follow-up assessments revealed an amelioration of neglect symptoms. Therefore, these findings suggest that visual neglect may be a part of CCAS, but that the choice of neglect assessments and the time delay since stroke onset may be crucial. Although the exact underlying pathophysiological mechanisms remain unclear, we propose cerebellar-cerebral diaschisis as a possible explanation of why neglect can occur on the ipsilateral side. Further research applying sensitive assessment tools at different post-stroke stages is needed to investigate the incidence, lesion correlates, and pathophysiology of neglect after cerebellar lesions.

Improved gesturing in left-hemispheric stroke by right inferior parietal theta burst stimulation.

Objectives: Apraxia is a common syndrome of left hemispheric stroke. A parieto-premotor-prefrontal network has been associated with apraxia, in which the left inferior parietal lobe (IPL-L) plays a major role. We hypothesized that transcranial continuous theta burst stimulation (cTBS) over the right inferior parietal lobe (IPL-R) improves gesturing by reducing its inhibition on the contralateral IPL in left hemispheric stroke patients. It was assumed that this effect is independent of lesion volume and that transcallosal connectivity is predictive for gestural effect after stimulation. Materials and methods: Nineteen stroke patients were recruited. Lesion volume and fractional anisotropy of the corpus callosum were acquired with structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI). Each patient had pseudorandomised sessions with sham or with stimulation over the IPL-R or over the right inferior frontal gyrus IFG-R. Gesturing was assessed in a double-blinded manner before and after each session. We tested the effects of stimulation on gesture performance using a linear mixed-effects model. Results: Pairwise treatment contrasts showed, that, compared to sham, the behavioral effect was higher after stimulation over IPL-R (12.08, 95% CI 6.04 - 18.13, p < 0.001). This treatment effect was approximately twice as high as the contrasts for IFG-R vs. sham (6.25, 95% CI -0.20 - 12.70, p = 0.058) and IPL-R vs. IFG-R vs. sham (5.83, 95% CI -0.49 - 12.15, p = 0.071). Furthermore, higher fractional anisotropy in the splenium (connecting the left and right IPL) were associated with higher behavioral effect. Relative lesion volume did not affect the changes after sham or stimulation over IPL-R or IFG-R. Conclusion: One single session of cTBS over the IPL-R improved gesturing after left hemispheric stroke. Denser microstructure in the corpus callosum correlated with favorable gestural response. We therefore propose the indirect transcallosal modulation of the IPL-L as a promising model of restoring interhemispheric balance, which may be useful in rehabilitation of apraxia.

Development of a Search Task Using Immersive Virtual Reality: Proof-of-Concept Study.

BACKGROUND: Serious games are gaining increasing importance in neurorehabilitation since they increase motivation and adherence to therapy, thereby potentially improving its outcome. The benefits of serious games, such as the possibility to implement adaptive feedback and the calculation of comparable performance measures, can be even further improved by using immersive virtual reality (iVR), allowing a more intuitive interaction with training devices and higher ecological validity. OBJECTIVE: This study aimed to develop a visual search task embedded in a serious game setting for iVR, including self-adapting difficulty scaling, thus being able to adjust to the needs and ability levels of different groups of individuals. METHODS: In a two-step process, a serious game in iVR (bird search task) was developed and tested in healthy young (n=21) and elderly (n=23) participants and in a group of patients with impaired visual exploration behavior (ie, patients with hemispatial neglect after right-hemispheric stroke; n=11). Usability, side effects, game experience, immersion, and presence of the iVR serious game were assessed by validated questionnaires. Moreover, in the group of stroke patients, the performance in the iVR serious game was also considered with respect to hemispatial neglect severity, as assessed by established objective hemispatial neglect measures. RESULTS: In all 3 groups, reported usability of the iVR serious game was above 4.5 (on a Likert scale with scores ranging from 1 to 5) and reported side effects were infrequent and of low intensity (below 1.5 on a Likert scale with scores ranging from 1 to 4). All 3 groups equally judged the iVR serious game as highly motivating and entertaining. Performance in the game (in terms of mean search time) showed a lateralized increase in search time in patients with hemispatial neglect that varied strongly as a function of objective hemispatial neglect severity. CONCLUSIONS: The developed iVR serious game, "bird search task," was a motivating, entertaining, and immersive task, which can, due to its adaptive difficulty scaling, adjust and be played by different populations with different levels of skills, including individuals with cognitive impairments. As a complementary finding, it seems that performance in the game is able to capture typical patterns of impaired visual exploration behavior in hemispatial neglect, as there is a high correlation between performance and neglect severity as assessed with a cancellation task.

Getting into a "Flow" state: a systematic review of flow experience in neurological diseases.

BACKGROUND: Flow is a subjective psychological state that people report when they are fully involved in an activity to the point of forgetting time and their surrounding except the activity itself. Being in flow during physical/cognitive rehabilitation may have a considerable impact on functional outcome, especially when patients with neurological diseases engage in exercises using robotics, virtual/augmented reality, or serious games on tablets/computer. When developing new therapy games, measuring flow experience can indicate whether the game motivates one to train. The purpose of this study was to identify and systematically review current literature on flow experience assessed in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson's disease. Additionally, we critically appraised, compared and summarized the measurement properties of self-reported flow questionnaires used in neurorehabilitation setting. DESIGN: A systematic review using PRISMA and COSMIN guidelines. METHODS: MEDLINE Ovid, EMBASE Ovid, CINAHL EBSCO, SCOPUS were searched. Inclusion criteria were (1) peer-reviewed studies that (2) focused on the investigation of flow experience in (3) patients with neurological diseases (i.e., stroke, traumatic brain injury, multiple sclerosis and/or Parkinson's disease). A qualitative data synthesis was performed to present the measurement properties of the used flow questionnaires. RESULTS: Ten studies out of 911 records met the inclusion criteria. Seven studies measured flow in the context of serious games in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson's disease. Three studies assessed flow in other activities than gaming (song-writing intervention and activities of daily living). Six different flow questionnaires were used, all of which were originally validated in healthy people. None of the studies presented psychometric data in their respective research population. CONCLUSION: The present review indicates that flow experience is increasingly measured in the physical/cognitive rehabilitation setting in patients with neurological diseases. However, psychometric properties of used flow questionnaires are lacking. For exergame developers working in the field of physical/cognitive rehabilitation in patients with neurological diseases, a valid flow questionnaire can help to further optimize the content of the games so that optimal engagement can occur during the gameplay. Whether flow experiences can ultimately have positive effects on physical/cognitive parameters needs further study.

Video-Oculography During Free Visual Exploration to Detect Right Spatial Neglect in Left-Hemispheric Stroke Patients With Aphasia: A Feasibility Study.

Spatial neglect has been shown to occur in 17-65% of patients after acute left-hemispheric stroke. One reason for this varying incidence values might be that left-hemispheric stroke is often accompanied by aphasia, which raises difficulties in assessing attention deficits with conventional neuropsychological tests entailing verbal instructions. Video-oculography during free visual exploration (FVE) requires only little understanding of simple non-verbal instruction and has been shown to be a sensitive and reliable tool to detect spatial neglect in patients with right-hemispheric stroke. In the present study, we aimed to investigate the feasibility of FVE to detect neglect in 10 left-hemispheric stroke patients with mild to severe aphasia as assessed by means of the Token Test, Boston Naming Test and Aachener Aphasie Test. The patient's individual deviation between eye movement calibration and validation was recorded and compared to 20 age-matched healthy controls. Furthermore, typical FVE parameters such as the landing point of the first fixation, the mean gaze position (in ° of visual angle), the number and duration of visual fixations and the mean visual exploration area were compared between groups. In addition, to evaluate for neglect, the Bells cancellation test was performed and neglect severity in daily living was measured by means of the Catherine Bergego Scale (CBS). Our results showed that the deviation between calibration and validation did not differ between aphasia patients and healthy controls highlighting its feasibility. Furthermore, FVE revealed the typical neglect pattern with a significant leftward shift in visual exploration bahaviour, which highly correlated with neglect severity as assessed with CBS. The present study provides evidence that FVE has the potential to be used as a neglect screening tool in left-hemispheric stroke patients with aphasia in which compliance with verbal test instructions may be compromised by language deficits.