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.

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.

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.

An item sorting heuristic to derive equivalent parallel test versions from multivariate items.

Parallel test versions require a comparable degree of difficulty and must capture the same characteristics using different items. This can become challenging when dealing with multivariate items, which are for example very common in language or image data. Here, we propose a heuristic to identify and select similar multivariate items for the generation of equivalent parallel test versions. This heuristic includes: 1. inspection of correlations between variables; 2. identification of outlying items; 3. application of a dimension-reduction method, such as for example principal component analysis (PCA); 4. generation of a biplot, in case of PCA of the first two principal components (PC), and grouping the displayed items; 5. assigning of the items to parallel test versions; and 6. checking the resulting test versions for multivariate equivalence, parallelism, reliability, and internal consistency. To illustrate the proposed heuristic, we applied it exemplarily on the items of a picture naming task. From a pool of 116 items, four parallel test versions were derived, each containing 20 items. We found that our heuristic can help to generate parallel test versions that meet requirements of the classical test theory, while simultaneously taking several variables into account.

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.

Face Perception and Pareidolia Production in Patients With Parkinson's Disease.

In Parkinson's disease (PD) patients, visual misperceptions are a major problem within the non-motor symptoms. Pareidolia, i.e., the tendency to perceive a specific, meaningful image in an ambiguous visual pattern, is a phenomenon that occurs also in healthy subjects. Literature suggests that the perception of face pareidolia may be increased in patients with neurodegenerative diseases. We aimed to examine, within the same experiment, face perception and the production of face pareidolia in PD patients and healthy controls (HC). Thirty participants (15 PD patients and 15 HC) were presented with 47 naturalistic photographs in which faces were embedded or not. The likelihood to perceive the embedded faces was modified by manipulating their transparency. Participants were asked to decide for each photograph whether a face was embedded or not. We found that PD patients were significantly less likely to recognize embedded faces than controls. However, PD patients also perceived faces significantly more often in locations where none were actually present than controls. Linear regression analyses showed that gender, age, hallucinations, and Multiple-Choice Vocabulary Intelligence Test (MWT) score were significant predictors of face pareidolia production in PD patients. Montreal Cognitive Assessment (MoCA) was a significant predictor for pareidolia production in PD patients in trials in which a face was embedded in another region [F (1, 13) = 24.4, p = <0.001]. We conclude that our new embedded faces paradigm is a useful tool to distinguish face perception performance between HC and PD patients. Furthermore, we speculate that our results observed in PD patients rely on disturbed interactions between the Dorsal (DAN) and Ventral Attention Networks (VAN). In photographs in which a face is present, the VAN may detect this as a behaviourally relevant stimulus. However, due to the deficient communication with the DAN in PD patients, the DAN would not direct attention to the correct location, identifying a face at a location where actually none is present.

Spatial asymmetries ("pseudoneglect") in free visual exploration-modulation of age and relationship to line bisection.

When humans visually explore an image, they typically tend to start exploring its left side. This phenomenon, so-called pseudoneglect, is well known, but its time-course has only sparsely been studied. Furthermore, it is unclear whether age influences pseudoneglect, and the relationship between visuo-spatial attentional asymmetries in a free visual exploration task and a classical line bisection task has not been established. To address these questions, 60 healthy participants, aged between 22 and 86, were assessed by means of a free visual exploration task with a series of naturalistic, colour photographs of everyday scenes, while their gaze was recorded by means of a contact-free eye-tracking system. Furthermore, a classical line bisection task was administered, and information concerning handedness and subjective alertness during the experiment was obtained. The results revealed a time-sensitive window during visual exploration, between 260 and 960 ms, in which age was a significant predictor of the leftward bias in gaze position, i.e., of pseudoneglect. Moreover, pseudoneglect as assessed by the line bisection task correlated with the average gaze position throughout a time-window of 300-1490 ms during the visual exploration task. These results suggest that age influences visual exploration and pseudoneglect in a time-sensitive fashion, and that the degree of pseudoneglect in the line bisection task correlates with the average gaze position during visual exploration in a time-sensitive manner.

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.

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.

Beta Electroencephalographic Oscillation Is a Potential GABAergic Biomarker of Chronic Peripheral Neuropathic Pain.

This preliminary investigation aimed to assess beta (ß) oscillation, a marker of the brain GABAergic signaling, as a potential objective pain marker, hence contributing at the same time to the mechanistic approach of pain management. This case-control observational study measured ß electroencephalographic (EEG) oscillation in 12 right-handed adult male with chronic neuropathic pain and 10 matched controls (∼55 years). Participants were submitted to clinical evaluation (pain visual analog scale, Hospital Anxiety, and Depression scale) and a 24-min high-density EEG recording (BIOSEMI). Data were analyzed using the EEGlab toolbox (MATLAB), SPSS, and R. The global power spectrum computed within the low (Lß, 13-20 Hz) and the high (Hß, 20-30 Hz) ß frequency sub-bands was significantly lower in patients than in controls, and accordingly, Lß was negatively correlated to the pain visual analog scale (R = -0.931, p = 0.007), whereas Hß correlation was at the edge of significance (R = -0.805; p = 0.053). Patients' anxiety was correlated to pain intensity (R = 0.755; p = 0.003). Normalization of the low and high ß global power spectrum (GPS) to the GPS of the full frequency range, while confirming the significant Lß power decrease in chronic neuropathic pain patients, vanished the significance of the Hß decrease, as well as the correlation between Lß power and pain intensity. Our results suggest that the GABAergic Lß EEG oscillation is affected by chronic neuropathic pain. Confirming the Lß GPS decrease and the correlation with pain intensity in larger studies would open new opportunities for the clinical application of gamma-aminobutyric acid-modifying therapies.

Anterior insula and inferior frontal gyrus: where ventral and dorsal visual attention systems meet.

The clinical link between spatial and non-spatial attentional aspects in patients with hemispatial neglect is well known; in particular, an increase in alerting can transitorily help to allocate attention towards the contralesional side. In models of attention, this phenomenon is postulated to rely on an interaction between ventral and dorsal cortical networks, subtending non-spatial and spatial attentional aspects, respectively. However, the exact neural underpinnings of the interaction between these two networks are still poorly understood. In the present study, we included 80 right-hemispheric patients with subacute stroke (50% women; age range: 24-96), 33 with and 47 without neglect, as assessed by paper-pencil cancellation tests. The patients performed a computerized task in which they were asked to respond as quickly as possible by button-press to central targets, which were either preceded or not preceded by non-spatial, auditory warning tones. Reaction times in the two different conditions were measured. In neglect patients, a warning tone, enhancing activity within the ventral attentional 'alerting' network, could boost the reaction (in terms of shorter reaction times) of the dorsal attentional network to a visual stimulus up to the level of patients without neglect. Critically, using voxel-based lesion-symptom mapping analyses, we show that this effect significantly depends on the integrity of the right anterior insula and adjacent inferior frontal gyrus, i.e., right-hemispheric patients with lesions involving these areas were significantly less likely to show shorter reaction times when a warning tone was presented prior to visual target appearance. We propose that the right anterior insula and inferior frontal gyrus are a critical hub through which the ventral attentional network can 'alert' and increase the efficiency of the activity of the dorsal attentional network.

"Tricking the Brain" Using Immersive Virtual Reality: Modifying the Self-Perception Over Embodied Avatar Influences Motor Cortical Excitability and Action Initiation.

To offer engaging neurorehabilitation training to neurologic patients, motor tasks are often visualized in virtual reality (VR). Recently introduced head-mounted displays (HMDs) allow to realistically mimic the body of the user from a first-person perspective (i.e., avatar) in a highly immersive VR environment. In this immersive environment, users may embody avatars with different body characteristics. Importantly, body characteristics impact how people perform actions. Therefore, alternating body perceptions using immersive VR may be a powerful tool to promote motor activity in neurologic patients. However, the ability of the brain to adapt motor commands based on a perceived modified reality has not yet been fully explored. To fill this gap, we "tricked the brain" using immersive VR and investigated if multisensory feedback modulating the physical properties of an embodied avatar influences motor brain networks and control. Ten healthy participants were immersed in a virtual environment using an HMD, where they saw an avatar from first-person perspective. We slowly transformed the surface of the avatar (i.e., the "skin material") from human to stone. We enforced this visual change by repetitively touching the real arm of the participant and the arm of the avatar with a (virtual) hammer, while progressively replacing the sound of the hammer against skin with stone hitting sound via loudspeaker. We applied single-pulse transcranial magnetic simulation (TMS) to evaluate changes in motor cortical excitability associated with the illusion. Further, to investigate if the "stone illusion" affected motor control, participants performed a reaching task with the human and stone avatar. Questionnaires assessed the subjectively reported strength of embodiment and illusion. Our results show that participants experienced the "stone arm illusion." Particularly, they rated their arm as heavier, colder, stiffer, and more insensitive when immersed with the stone than human avatar, without the illusion affecting their experienced feeling of body ownership. Further, the reported illusion strength was associated with enhanced motor cortical excitability and faster movement initiations, indicating that participants may have physically mirrored and compensated for the embodied body characteristics of the stone avatar. Together, immersive VR has the potential to influence motor brain networks by subtly modifying the perception of reality, opening new perspectives for the motor recovery of patients.