Zooming in on abnormal local and global processing biases after stroke: Frequency, lateralization, and associations with cognitive functions.

OBJECTIVES: The 'attentional spotlight' can be adjusted depending on the task requirements, resulting in processing information at either the local or global level. Stroke can lead to local or global processing biases, or the inability to simultaneously attend both levels. In this study, we assessed the (1) prevalence of abnormal local and global biases following stroke, (2) differences between left- and right-sided brain damaged patients, and (3) relations between local and global interference, the ability to attend local and global levels simultaneously, and lateralized attention, search organization, search speed, visuo-construction, executive functioning, and verbal (working) memory. METHODS: Stroke patients admitted for inpatient rehabilitation completed directed (N = 192 total; N = 46 left-sided/N = 48 right-sided lesion) and divided (N = 258 total; N = 67 left-sided/N = 66 right-sided lesion) local-global processing tasks, as well as a conventional neuropsychological assessment. Processing biases and interference effects were separately computed for directed and divided tasks. RESULTS: On the local-global tasks, 7.8-10.9% of patients showed an abnormal local bias and 6.3-8.3% an abnormal global bias for directed attention, and 5.4-10.1% an abnormal local bias and 6.6-15.9% an abnormal global bias for divided attention. There was no significant difference between patients with left- and right-sided brain damage. There was a moderate positive relation between local interference and search speed, and a small positive relation between global interference and neglect. CONCLUSIONS: Abnormal local and global biases can occur after stroke and might relate to a range of cognitive functions. A specific bias might require a different approach in assessment, psycho-education, and treatment.

Effects of a Stimulus Response Task Using Virtual Reality on Unilateral Spatial Neglect: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of a stimulus response task using virtual reality (VR) for unilateral spatial neglect (USN). DESIGN: Double-blind randomized controlled trial. SETTING: Acute phase hospital where stroke patients are hospitalized. PARTICIPANTS: The participants were 42 patients (N=42) with right-hemisphere cerebral damage who had been experiencing USN in their daily lives. They were randomly assigned to 3 groups: a stimulus response task with a background shift (SR+BS group), a stimulus response task without a background shift (SR group), and an object gazing task (control group). INTERVENTIONS: The stimulus response task was to search for balloons that suddenly appeared on the VR screen. A background shift was added to highlight the search in the neglected space. The control task was to maintain a controlled gaze on a balloon that appeared on the VR screen. The intervention period was 5 days. MAIN OUTCOME MEASURES: The primary outcome was the participants' scores on a stimulus-driven attention test (SAT) using the reaction time. The stimuli of the SAT were divided into 6 blocks of 3 lines on each side (-3 to +3). The secondary outcomes were their scores on the Behavioral Intention Test conventional, Catherine Bergego Scale, and straight ahead pointing tests. RESULTS: In the SAT, there were significant interaction effects of reaction time between time and group factors in left-2, right+2, and right+3. The SR+BS and SR groups showed significant improvements in the reaction time of left-2 and right+3 compared with the control group. Moreover, the SR+BS group showed a significant improvement in the reaction time of left-2, which was the neglected space, compared with the SR group. However, there were no significant interaction effects of Behavioral Intention Test conventional, Catherine Bergego Scale, and straight ahead pointing. CONCLUSIONS: Our results suggest that the use of stimulus response tasks using VR combined with background shifts may improve left-sided USN.

The effect of offline anosognosia for hemispatial neglect on neglect rehabilitation in patients with subacute and chronic right hemispheric brain injury. A retrospective cohort study.

CLINICAL TRIALS REGISTRATION NUMBER: NCT05145855.

Unilateral Spatial Neglect Recovery Poststroke.

Unilateral spatial neglect (USN) is a common and disabling cognitive consequence of stroke wherein individuals demonstrate decreased response to contralesional information. Here, we provide an updated narrative review of studies that shed light on the neural mechanisms and predictors of recovery of USN. Additionally, we report a rapid review of randomized controlled trials focusing on USN intervention, both nonpharmacological and pharmacological, published in the last 5 years. Randomized controlled trials are reviewed within the context of systematic reviews and meta-analyses of USN interventions published within the same time frame. The quality of randomized controlled trials of treatment is higher compared to quality reported in previous reviews and meta-analyses. However, remaining weaknesses in participant demographic reporting, as well as small, heterogenous samples, render generalizability and cross-study interpretation a challenge. Nevertheless, evidence regarding neural mechanisms underlying USN recovery and regarding the effectiveness of targeted USN interventions is accumulating and strengthening, setting the foundation for future investigations into patient-specific factors that may influence treatment response. We identify gaps and provide suggestions for future USN intervention research.

Hierarchical psychophysiological pathways subtend perceptual asymmetries in Neglect.

Stroke patients with left Hemispatial Neglect (LHN) show deficits in perceiving left contralesional stimuli with biased visuospatial perception towards the right hemifield. However, very little is known about the functional organization of the visuospatial perceptual neural network and how this can account for the profound reorganization of space representation in LHN. In the present work, we aimed at (1) identifying EEG measures that discriminate LHN patients against controls and (2) devise a causative neurophysiological model between the discriminative EEG measures. To these aims, EEG was recorded during exposure to lateralized visual stimuli which allowed for pre-and post-stimulus activity investigation across three groups: LHN patients, lesioned controls, and healthy individuals. Moreover, all participants performed a standard behavioral test assessing the perceptual asymmetry index in detecting lateralized stimuli. The between-groups discriminative EEG patterns were entered into a Structural Equation Model for the identification of causative hierarchical associations (i.e., pathways) between EEG measures and the perceptual asymmetry index. The model identified two pathways. A first pathway showed that the combined contribution of pre-stimulus frontoparietal connectivity and individual-alpha-frequency predicts post-stimulus processing, as measured by visual-evoked N100, which, in turn, predicts the perceptual asymmetry index. A second pathway directly links the inter-hemispheric distribution of alpha-amplitude with the perceptual asymmetry index. The two pathways can collectively explain 83.1% of the variance in the perceptual asymmetry index. Using causative modeling, the present study identified how psychophysiological correlates of visuospatial perception are organized and predict the degree of behavioral asymmetry in LHN patients and controls.

Monocular eye patching modulates ipsilesional reactive saccades and smooth pursuit in patients with left hemispatial neglect.

Patients with hemispatial neglect show multiple oculomotor deficits like delayed contralesional saccade latencies, hypometric saccade amplitudes, and impaired smooth pursuit. We aimed to investigate whether modulation of superior colliculus (SC) activity via monocular eye patching improves neglect patients' eye movements to the contralesional side of space. Thirteen neglect patients with left-hemispheric (LH) stroke, 22 neglect patients with right-hemispheric (RH) stroke, and 24 healthy controls completed a video-oculographic examination of horizontal smooth pursuit and reactive saccades twice, while the left or right eye was covered with an eye patch. Independent of the eye patch position, LH and RH patients showed enlarged saccade latencies toward contralesional stimuli. In addition, both during smooth pursuit and reactive saccades, RH patients made significantly fewer rightward saccades when the right than when the left eye was patched. Moreover, during reactive saccades, RH patients made significantly fewer right than left saccades, but only when the right eye was patched. These findings suggest that the ipsilesional eye patch modulated ipsilesional ocular performance in the RH group, presumably resulting from differences in SC activity. Yet, ipsilesional eye patching did not improve eye movements to the contralesional side of space, possibly due to the incomplete contralateral retinocollicular projection in humans.

Rapid screening for neglect following stroke: A systematic search and European Academy of Neurology recommendations.

BACKGROUND AND PURPOSE: Unilateral neglect is a common cognitive disorder following stroke. Neglect has a significant impact on functional outcomes, so it is important to detect. However, there is no consensus on which are the best screening tests to administer to detect neglect in time-limited clinical environments. METHODS: Members of the European Academy of Neurology Scientific Panel on Higher Cortical Functions, neuropsychologists, occupational therapists, and researchers produced recommendations for primary and secondary tests for bedside neglect testing based on a rigorous literature review, data extraction, online consensus meeting, and subsequent iterations. RESULTS: A total of 512 articles were screened, and 42 were included. These reported data from 3367 stroke survivors assessed using 62 neglect screens. Tests were grouped into cancellation, line bisection, copying, reading/writing, and behavioral. Cancellation tasks were most frequently used (97.6% of studies), followed by bisection, copying, behavioral, and reading/writing assessments. The panel recommended a cancellation test as the primary screening test if there is time to administer only one test. One of several cancellation tests might be used, depending on availability. If time permits, one or more of line bisection, figure copying, and baking tray task were recommended as secondary tests. Finally, if a functional and ecological test is feasible, the Catherine Bergego Scale was recommended. Overall, the literature suggests that no single test on its own is sufficient to exclude a diagnosis of neglect. Therefore, the panel recommended that multiple neglect tests should be used whenever possible. CONCLUSIONS: This study provides consensus recommendations for rapid bedside detection of neglect in real-world, clinical environments.

Visuomotor misalignment induced through immersive virtual reality to improve spatial neglect: a case-series study.

One evidence-based treatment for spatial neglect is prism adaptation (PA) treatment. PA after-effects, i.e., the implicit shifts in the arm reaching position toward the neglected side of space after prism removal, are considered fundamental to PA treatment effects. In the present study, the arm reaching position was shifted through a visuomotor misalignment procedure using immersive virtual reality (VR). To examine whether this procedure might have a beneficial impact on spatial neglect, we conducted a multi-baseline experiment in three individuals with chronic left-sided neglect post stroke. Improved spatial neglect was observed in all participants immediately after 5 sessions with two rounds in each. Two participants demonstrated lasting or continuous improvement two weeks later. Participants' pattern of brain lesions did not appear to clearly explain performance differences. The findings suggest that VR-induced visuomotor misalignment may improve spatial neglect immediately after a multi-session treatment course. The optimal number of sessions will be determined by future studies with a larger sample size, which may also elucidate the number of sessions sufficient for sustained improvement in most patients. Further investigations will identify the neural mechanisms underlying VR-induced visuomotor misalignment, which may or may not be identical to PA after-effects.

The Dutch Oxford Cognitive Screen (OCS-NL): psychometric properties in Flemish stroke survivors.

BACKGROUND AND PURPOSE: The Oxford Cognitive Screen is a stroke-specific screen to evaluate attention, executive functions, memory, praxis, language, and numeric cognition. It was originally validated in England for acute stroke patients. In this study, we examined the psychometric properties of the Dutch OCS (OCS-NL). METHODS: A total of 193 (99 acute stroke unit, 94 rehabilitation unit) patients were included in our study. A subset of patients (n = 128) completed a retest with the parallel version of the OCS-NL. RESULTS: First, we did not find evidence for a difference in prevalence of impairment between patients in the acute stroke versus rehabilitation unit on all but one of the subtests. For praxis, we observed a 14% lower prevalence of impairment in the rehabilitation than the acute stroke unit. Second, the parallel-form reliability ranged from weak to excellent across subtests. Third, in stroke patients below age 60, the OCS-NL had a 92% sensitivity relative to the MoCA, while the MoCA had a 55% sensitivity relative to the OCS-NL. Last, although left-hemispheric stroke patients performed worse on almost all MoCA subdomains, they performed similarly to right-hemispheric stroke patients on non-language domains on the OCS-NL. CONCLUSIONS: Our results suggest that the OCS-NL is a reliable cognitive screen that can be used in acute stroke and rehabilitation units. The OCS-NL may be more sensitive to detect cognitive impairment in young stroke patients and less likely to underestimate cognitive abilities in left-hemispheric stroke patients than the MoCA.

Editorial for special issue on neglect rehabilitation.

It is clear already that in current and future years more people will suffer from stroke, whether related to COVID-19 or not, and given its prevalence, many more people's lives will be affected by neglect. Here we hope to have contributed to its possible amelioration with highlights of the latest thinking on neglect diagnosis, prevalence and treatment.

Influence of right versus left unilateral spatial neglect on the functional recovery after rehabilitation in sub-acute stroke patients.

Unilateral spatial neglect (USN) may lead to poor functional rehabilitation outcomes. However, studies investigating the rehabilitation outcomes of right-sided USN are lacking. We aimed to investigate (1) the clinical impacts of USN, including right-sided USN, for stroke patients in sub-acute rehabilitation, and (2) evaluate the differences in clinical characteristics and rehabilitation outcomes between right- and left-sided USN patients. We retrospectively screened the medical records of 297 inpatients at the Tokyo-Bay Rehabilitation Hospital who experienced a cerebrovascular accident with supratentorial lesions between January 1st, 2014 and December 31st, 2016. We performed independent multiple regression analysis in patients with left and right hemisphere damage. The Behavioral Inattention Test was a significant independent variable for predicting the motor, cognitive, and total functional independence measure (FIM), compared to the Stroke Impairment Assessment Set and Mini-Mental State Examination. USN affects motor FIM recovery more than cognitive FIM recovery regardless of the damaged hemisphere. Our study results confirm that both right- and left-sided USN influence the functional recovery of stroke patients. USN occurs, slightly less frequently, following a left hemisphere stroke. However, USN negatively affected rehabilitation outcomes, regardless of the neglected side. Therefore, USN treatment is necessary for patients with left and right hemisphere damage.

The Fluff test: Improved scoring system to account for different degrees of contralesional and ipsilesional personal neglect in brain damaged patients.

The Fluff test is a simple test to assess evidence of personal neglect (PN) in brain-damaged patients. While blindfolded, patients are asked to remove targets previously attached to their body and the number of targets detached provides information about possible spatial bias. This test has been widely used for clinical and research purposes. However, the current scoring system presents some limitations, which make difficult to interpret patients' performance in terms of both contralalesional and ipsilesional PN when they omit targets on the ipsilesional side. Moreover, it does not consider possible confounding variables, such as non-spatial cognitive deficits or lack of compliance that may affect patients' performance and lead to incorrect diagnosis. The present paper proposes a new scoring method overcoming the limitations mentioned above and it analyses data from a large sample of 243 brain-damaged patients. Findings showed that contralesional PN was significantly more severe, but not more frequent, following right (31%) than left (21%) brain damage. We also found evidence of left ipsilesional PN and cases of potential mis-diagnosis that would have passed unnoticed with the original scoring system. The new scoring method allows to identify different degrees of contralesional and ipsilesional PN and potential confounding variable.

Rehabilitation of hemispatial neglect in stroke.

Hemi-spatial neglect (HSN) is a debilitating post stroke cognitive deficit resulting in reduced attention to stimuli presented in the contra-lateral hemi-visual field. It adversely impacts patient's medical recovery, activities of daily living and quality of life. Early referral to Rehabilitation Medicine specialist for thorough evaluation, prompt recognition of functional impairments and formulation of a comprehensive rehabilitation plan unique to patient is important. It is part of the comprehensive and holistic management of stroke patients with HSN. We summarize the current management strategies used for post-stroke HSN rehabilitation with the options including non-invasive brain stimulation, visuomotor feedback training, robotic rehabilitation and trans-dermal nicotine patch.

Immediate effects of head-mounted display adaptation in cases of unilateral spatial neglect: study of straight-ahead pointing.

[Purpose] This study aimed to clarify the effect of an adaptation of a deviation of the visual field in three axes on spatial cognition in patients with unilateral spatial neglect and distorted spatial perception in three dimensions. [Participants and Methods] Fifteen patients with cerebrovascular disease and symptoms of unilateral spatial neglect were included. Forty-eight pointing movements with a camera attached to a head-mounted display changed in three axes were compared with the control condition in which the camera was deflected only in the horizontal plane as with the prism adaptation. The main outcome measures were subjective straight-ahead pointing, line bisection, line cancellation, and star cancellation. [Results] The head-mounted display adaptive therapy was performed under conditions that varied in all three axes. The results indicated that it was possible to deflect the subjective straight-ahead pointing position to the lower left direction. [Conclusion] In contrast to the prism adaptation, which deflects the visual field in a single axis in the horizontal plane, the tri-axial adaptation corrected the median cognition in the left-right direction as well as the cognition of the body center, including the vertical direction.

Non-invasive brain stimulation in Stroke patients (NIBS): A prospective randomized open blinded end-point (PROBE) feasibility trial using transcranial direct current stimulation (tDCS) in post-stroke hemispatial neglect.

Up to 80% of people who experience a right-hemisphere stroke suffer from hemispatial neglect. This syndrome is debilitating and impedes rehabilitation. We carried out a clinical feasibility trial of transcranial direct current stimulation (tDCS) and a behavioural rehabilitation programme, alone or in combination, in patients with neglect. Patients >4 weeks post right hemisphere stroke were randomized to 10 sessions of tDCS, 10 sessions of a behavioural intervention, combined intervention, or a control task. Primary outcomes were recruitment and retention rates, with secondary outcomes effect sizes on measures of neglect and quality of life, assessed directly after the interventions, and at 6 months follow up. Of 288 confirmed stroke cases referred (representing 7% of confirmed strokes), we randomized 8% (0.6% of stroke cases overall). The largest number of exclusions (91/288 (34%)) were due to medical comorbidities that prevented patients from undergoing 10 intervention sessions. We recruited 24 patients over 29 months, with 87% completing immediate post-intervention and 67% 6 month evaluations. We established poor feasibility of a clinical trial requiring repeated hospital-based tDCS within a UK hospital healthcare setting, either with or without behavioural training, over a sustained time period. Future trials should consider intensity, duration and location of tDCS neglect interventions.Trial registration: ClinicalTrials.gov identifier: NCT02401724.

Real-time EEG Feedback on Alpha Power Lateralization Leads to Behavioral Improvements in a Covert Attention Task.

Visual attention can be spatially oriented, even in the absence of saccadic eye-movements, to facilitate the processing of incoming visual information. One behavioral proxy for this so-called covert visuospatial attention (CVSA) is the validity effect (VE): the reduction in reaction time (RT) to visual stimuli at attended locations and the increase in RT to stimuli at unattended locations. At the electrophysiological level, one correlate of CVSA is the lateralization in the occipital [Formula: see text]-band oscillations, resulting from [Formula: see text]-power increases ipsilateral and decreases contralateral to the attended hemifield. While this [Formula: see text]-band lateralization has been considerably studied using electroencephalography (EEG) or magnetoencephalography (MEG), little is known about whether it can be trained to improve CVSA behaviorally. In this cross-over sham-controlled study we used continuous real-time feedback of the occipital [Formula: see text]-lateralization to modulate behavioral and electrophysiological markers of covert attention. Fourteen subjects performed a cued CVSA task, involving fast responses to covertly attended stimuli. During real-time feedback runs, trials extended in time if subjects reached states of high [Formula: see text]-lateralization. Crucially, the ongoing [Formula: see text]-lateralization was fed back to the subject by changing the color of the attended stimulus. We hypothesized that this ability to self-monitor lapses in CVSA and thus being able to refocus attention accordingly would lead to improved CVSA performance during subsequent testing. We probed the effect of the intervention by evaluating the pre-post changes in the VE and the [Formula: see text]-lateralization. Behaviorally, results showed a significant interaction between feedback (experimental-sham) and time (pre-post) for the validity effect, with an increase in performance only for the experimental condition. We did not find corresponding pre-post changes in the [Formula: see text]-lateralization. Our findings suggest that EEG-based real-time feedback is a promising tool to enhance the level of covert visuospatial attention, especially with respect to behavioral changes. This opens up the exploration of applications of the proposed training method for the cognitive rehabilitation of attentional disorders.

Noninvasive brain stimulation in rehabilitation of hemispatial neglect after stroke.

BACKGROUND: Noninvasive brain stimulation can modulate neural processing within the motor cortex and thereby might be beneficial in the rehabilitation of hemispatial neglect after stroke. METHODS: We review the pertinent literature regarding the use of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation in order to facilitate recovery of hemispatial neglect after stroke. RESULTS: Twenty controlled trials (including 443 stroke patients) matched our inclusion criteria. Methodology and results of each study are presented in a comparative approach. Current data seem to indicate a better efficiency of repetitive transcranial magnetic stimulation, compared to tDCS to ameliorate hemispatial neglect after stroke. CONCLUSIONS: Noninvasive brain stimulation has the potential to facilitate recovery of hemispatial neglect after stroke, but until today, there are not enough data to claim its routine use.

Development of the Halifax Visual Scanning Test: A New Measure of Visual-Spatial Neglect for Personal, Peripersonal, and Extrapersonal Space.

OBJECTIVES: Visual-spatial neglect is a common attentional disorder after right-hemisphere stroke and is associated with poor rehabilitation outcomes. The presence of neglect symptoms has been reported to vary across personal, peripersonal, and extrapersonal space. Currently, no measure is available to assess neglect severity equally across these spatial regions and may be missing subsets of symptoms or patients with neglect entirely. We sought to provide initial construct validity for a novel assessment tool that measures neglect symptoms equally for these spatial regions: the Halifax Visual Scanning Test (HVST). METHODS: In Study I, the HVST was compared to conventional measures of neglect and functional outcome scores (wheelchair navigation) in 15 stroke inpatients and 14 healthy controls. In Study II, 19 additional controls were combined with the control data from Study I to establish cutoffs for impairment. Patterns of neglect in the stroke group were examined. RESULTS: In Study I, performance on all HVST subtests were correlated with the majority of conventional subtests and wheelchair navigation outcomes. In Study II, neglect-related deficits in visual scanning showed dissociations across spatial regions. Four inpatients exhibited symptoms of neglect on the HVST that were not detected on conventional measures, one of which showed symptoms in personal and extrapersonal space exclusively. CONCLUSIONS: The HVST appears a useful measure of neglect symptoms in different spatial regions that may not be detected with conventional measures and that correlates with functional wheelchair performance. Preliminary control data are presented and further research to add to this normative database appears warranted.

A Systematic Review and Meta-Analysis of Rehabilitative Interventions for Unilateral Spatial Neglect and Hemianopia Poststroke From 2006 Through 2016.

OBJECTIVE: To evaluate the effectiveness of activity-based, nonactivity-based, and combined activity- and nonactivity-based rehabilitative interventions for individuals presenting with unilateral spatial neglect (USN) and hemianopia. DATA SOURCES: We searched CINAHL, Cochrane Library, EMBASE, MEDLINE, and PubMed from 2006 to 2016. STUDY SELECTION: Randomized controlled trials (RCTs) with a score of 6 or more in the Physiotherapy Evidence Database Scale that examined the effects of activity-based and nonactivity-based rehabilitation interventions for people with USN or hemianopia. Two reviewers selected studies independently. DATA EXTRACTION: Extracted data from the published RCTs. Mean differences (MD) or standardized mean differences (SMD), and 95% confidence intervals (CIs) were calculated. Heterogeneity was assessed using the I2 statistic. DATA SYNTHESIS: A total of 20 RCTs for USN and 5 for hemianopia, involving 594 and 206 stroke participants respectively, were identified. Encouraging results were found in relation to activity-based interventions for visual scanning training and compensatory training for hemianopia (MD=5.11; 95% confidence intervals [95% CI], 0.83-9.4; P=.019; I2=25.16% on visual outcomes), and optokinetic stimulation and smooth pursuit training for USN (SMD=0.49; 95% CI, 0.01-0.97; P=.045; I2=49.35%) on functional performance in activities of daily living, (SMD=0.96; 95% CI, 0.09-1.82; P=.031; I2=89.57%) on neglect. CONCLUSIONS: Activity-based interventions are effective and commonly used in the treatment of USN and hemianopia. Nonactivity-based and combined approaches, for both impairments, have not been refuted, because more studies are required for substantiated conclusions to be drawn.

Efficacy of home-based visuomotor feedback training in stroke patients with chronic hemispatial neglect.

Hemispatial neglect is a severe cognitive condition frequently observed after a stroke, associated with unawareness of one side of space, disability and poor long-term outcome. Visuomotor feedback training (VFT) is a neglect rehabilitation technique that involves a simple, inexpensive and feasible training of grasping-to-lift rods at the centre. We compared the immediate and long-term effects of VFT vs. a control training when delivered in a home-based setting. Twenty participants were randomly allocated to an intervention (who received VFT) or a control group (n = 10 each). Training was delivered for two sessions by an experimenter and then patients self-administered it for 10 sessions over two weeks. Outcome measures included the Behavioural Inattention Test (BIT), line bisection, Balloons Test, Landmark task, room description task, subjective straight-ahead pointing task and the Stroke Impact Scale. The measures were obtained before, immediately after the training sessions and after four-months post-training. Significantly greater short and long-term improvements were obtained after VFT when compared to control training in line bisection, BIT and spatial bias in cancellation. VFT also produced improvements on activities of daily living. We conclude that VFT is a feasible, effective, home-based rehabilitation method for neglect patients that warrants further investigation with well-designed randomised controlled trials on a large sample of patients.