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OBJECTIVE: The Clock Drawing Test (CDT) is a widely used test for cognitive screening as its execution taps into a large number of cognitive functions. Because of the involvement of visuospatial abilities, the CDT is also commonly used to assess hemispatial neglect. In the present study, we introduce a new quantitative scoring method for the CDT that aims to measure the use of space for each half of the clock face and asymmetries of space use. METHOD: Two measures are introduced: the explored space (ES) and used space (US) for each half of the clock, as well as two derived asymmetry indices. Such new measures were applied to CDTs of four groups of participants: right brain-damaged patients without visuospatial neglect, two groups of right brain-damaged patients with varying degrees of visuospatial neglect, and a group of neurologically healthy participants. RESULTS: Analyses showed that only neglect patients explored and used the left clock half significantly less than the right one. This result was also confirmed by the asymmetry indices, where neglect patients showed a stronger rightward bias. For neglect patients, the US asymmetry index correlated with the patients' scores on the neuropsychological tests. The analyses of receiver operating characteristic curves showed that left US and left ES scores had good accuracy in categorizing neglect patients. CONCLUSIONS: The present work provides new quantitative indices of CDT space usage in hemispatial neglect. Cutoffs are provided for clinical practice.

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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.

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In all vertebrates, visual signals from each visual field project to the opposite midbrain tectum (called the superior colliculus in mammals). The tectum/colliculus computes visual salience to select targets for context-contingent visually guided behavior: a frog will orient toward a small, moving stimulus (insect prey) but away from a large, looming stimulus (a predator). In mammals, visual signals competing for behavioral salience are also transmitted to the visual cortex, where they are integrated with collicular signals and then projected via the dorsal visual stream to the parietal and frontal cortices. To control visually guided behavior, visual signals must be encoded in body-centered (egocentric) coordinates, and so visual signals must be integrated with information encoding eye position in the orbit-where the individual is looking. Eye position information is derived from copies of eye movement signals transmitted from the colliculus to the frontal and parietal cortices. In the intraparietal cortex of the dorsal stream, eye movement signals from the colliculus are used to predict the sensory consequences of action. These eye position signals are integrated with retinotopic visual signals to generate scaffolding for a visual scene that contains goal-relevant objects that are seen to have spatial relationships with each other and with the observer. Patients with degeneration of the superior colliculus, although they can see, behave as though they are blind. Bilateral damage to the intraparietal cortex of the dorsal stream causes the visual scene to disappear, leaving awareness of only one object that is lost in space. This tutorial considers what we have learned from patients with damage to the colliculus, or to the intraparietal cortex, about how the phylogenetically older midbrain and the newer mammalian dorsal cortical visual stream jointly coordinate the experience of a spatially and temporally coherent visual scene.

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Objective: To make an initial assessment of the correlation between immersive virtual reality-based (ILBT) line bisection testing and paper-and-pencil-based line bisection (PLBT) testing in healthy subjects. Design: Diagnostic study. Setting: Research laboratory. Participants: Twenty healthy adults (51.5 [11.0] years old, 55% women; N=20). Interventions: Participants underwent an ILBT and a conventional PLBT in near space (NS) and more distant space (MDS). Correlations between the ILBT and PLBT, deviation rates in the NS and MDS, horizontal gaze distribution, and presence of virtual reality sickness (VRS) were evaluated. Main Outcome Measures: Correlation between the deviation rates of the PLBT and ILBT. Results: There was no significant correlation between the ILBT and PLBT for evaluating the deviation rate of the line bisection test (LBT). There was no significant difference in the deviation rate of the LBTs between the NS and MDS, but there was a significant difference in the horizontal line-of-sight distribution. VRS was not observed as an adverse event. Conclusions: In healthy adult subjects, our results suggested that there was no significant correlation between the deviation rates of the ILBT and PLBT. We also found that the ILBT is a useful and safe method for evaluating the horizontal line-of-sight distribution and percentage deviation of line segments from the center in the NS and MDS without inducing VRS.

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A 73-year-old woman with posterior cortical atrophy (PCA) presented with progressive apperceptive visual agnosia, alexia, agraphia, ventral simultanagnosia, prosopagnosia, and allocentric (stimulus-centered) left-sided hemispatial neglect. All of these symptoms were attributed to damage to the bilateral occipito-temporal cortices, consistent with ventral variant PCA. While the Pittsburgh compound B uptake was extensively distributed throughout the occipito-parietal (dorsal) and occipito-temporal (ventral) areas, the THK5351 (ligand binding to tau aggregates/astrocyte gliosis) accumulation was limited to the ventral area. These findings suggest that local accumulation of tau proteins and/or astrocyte gliosis over the occipito-temporal cortices can result in ventral variant PCA.

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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.

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CLINICAL TRIALS REGISTRATION NUMBER: NCT05145855.

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BACKROUND: Spatial neglect (SN) after traumatic brain injury (TBI) is common, hindering rehabilitation progress and functional outcomes. Most research has focused on SN treatment after stroke with few published instances of post-TBI SN treated using prism adaptation treatment (PAT) in inpatient rehabilitation. OBJECTIVE: This case series characterizes the dose, after-effect, and treatment response of PAT in patients with SN after severe TBI. METHODS: Six patients exhibiting severe (n = 2), moderate (n = 2), or mild (n = 2) SN after severe TBI received 5 to 10 PAT sessions during their inpatient rehabilitation stay. Functional improvement in SN was measured by the Catherine Bergego Scale (CBS). RESULTS: Patients presented with a mean initial CBS score of 16.8 (range: 8.8-24.3). Prism after-effect was present after PAT. Following 5-10 sessions, the mean CBS score improved by 11.6 points to 5.2 (range: 7.8-21.8); the change in initial versus final CBS scores was significant (P = 0.031). CONCLUSION: This study is the first to demonstrate prism after-effect and functional SN improvement in individual patients with TBI. Patients showed a clinically meaningful improvement in mild, moderate, and severe SN following 5 to 10 PAT sessions. Additional studies are needed to assess tolerability, benefit, and optimal PAT dose for SN after TBI.

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Background: Hemispatial neglect (HSN) was diagnosed using a virtual reality-based test (FOPR test) that explores the field of perception (FOP) and field of regard (FOR). Here, we developed virtual reality-visual exploration therapy (VR-VET) combining elements from the FOPR test and visual exploration therapy (VET) and examined its efficacy for HSN rehabilitation following stroke. Methods: Eleven participants were randomly assigned to different groups, training with VR-VET first then waiting without VR-VET training (TW), or vice versa (WT). The TW group completed 20 sessions of a VR-VET program using a head-mounted display followed by 4 weeks of waiting, while the WT group completed the opposite regimen. Clinical HSN measurements [line bisection test (LBT), star cancellation test (SCT), Catherine Bergego Scale (CBS), CBS perceptual-attentional (CBS-PA), and CBS motor-explanatory (CBS-ME)] and FOPR tests [response time (RT), success rate (SR), and head movement (HM) for both FOP and FOR] were assessed by blinded face-to-face assessments. Results: Five and six participants were allocated to the TW and WT groups, respectively, and no dropout occurred throughout the study. VR-VET considerably improved LBT scores, FOR variables (FOR-RT, FOR-SR), FOP-LEFT variables (FOP-LEFT-RT, FOP-LEFT-SR), and FOR-LEFT variables (FOR-LEFT-RT, FOR-LEFT-SR) compared to waiting without VR-VET. Additionally, VR-VET extensively improved FOP-SR, CBS, and CBS-PA, where waiting failed to make a significant change. The VR-VET made more improvements in the left hemispace than in the right hemispace in FOP-RT, FOP-SR, FOR-RT, and FOR-SR. Conclusion: The observed improvements in clinical assessments and FOPR tests represent the translatability of these improvements to real-world function and the multi-dimensional effects of VR-VET training. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT03463122, identifier NCT03463122.

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Objective: To provide a retrospective evaluation of a new eye and vision rehabilitation care pathway in a U.S. multi-site inpatient rehabilitation network involving the occupational therapy (OT) staff and a consulting doctor of optometry (OD) specializing in vision rehabilitation. Design: Retrospective study. Setting: Two Inpatient Rehabilitation Facilities (IRFs) and 1 Long Term Acute Care Hospital (LTACH). Participants: There were 2083 records reviewed (44% women, avg. age 59 years). The most common diagnoses were hemispatial neglect (19.2%), homonymous field defects (18.5%), and oculomotor cranial nerve palsies (16.7%) (N=2083). Interventions: Clinical care was reviewed where diagnosis-specific protocols were developed and training was provided to OTs in order to reinforce OD-prescribed interventions during daily treatment sessions, including (1) third, fourth, and sixth ocular cranial nerve palsies (OCNPs) with prisms fitted for full time, postural adaptation training, and oculomotor re-education using pursuits, saccades, head-rotations, and binocular vision exercises including alternate cover and vergence; (2) homonymous hemianopia with training awareness of field loss, eccentric viewing, and fitting of Peli lens for optical field expansion; and (3) prism adaptation therapy (PAT) for left hemispatial neglect. Main Outcome Measures: Frequency of diagnoses. Hypothesis: Diagnoses with developed protocols were most common. Secondarily, feasibility and efficacy by anonymous OT survey. Results: 2083 vision consults were performed over 5 years. The most common diagnoses were hemispatial neglect (n=399, 19.2%), homonymous field defects (n=386, 18.5%), and OCNPs (n=347, 16.7%). None of the OTs reported the protocols were infeasible and 63% (IQR 38%-69%) reported their patients benefited from the interventions. The survey suggested prism for OCNPs helped in 42%, and Peli lens and PAT both helped in 38%. Conclusions: Data support the feasibility of this inpatient eye and vision rehabilitation care pathway which may be used as a foundation for creating or refining similar programs elsewhere. Uniform administration of IRF-based visual neuro-rehabilitation care could provide a substrate for future clinical trials to evaluate efficacy.

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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.

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The present study examined the effects of unilateral stimulus presentation on the right hemisphere preponderance of the stimulus-preceding negativity (SPN) in the event-related potential (ERP) experiment, and aimed to elucidate whether unilateral stimulus presentation affected activations in the bilateral anterior insula in the functional magnetic resonance imaging (fMRI) experiment. Separate fMRI and ERP experiments were conducted using visual and auditory stimuli by manipulating the position of stimulus presentation (left side or right side) with the time estimation task. The ERP experiment revealed a significant right hemisphere preponderance during left stimulation and no laterality during the right stimulation. The fMRI experiment revealed that the left anterior insula was activated only in the right stimulation of auditory and visual stimuli whereas the right anterior insula was activated by both left and right stimulations. The visual condition retained a contralateral dominance, but the auditory condition showed a right hemisphere dominance in a localized area. The results of this study indicate that the SPN reflects perceptual anticipation, and also that the anterior insula is involved in its occurrence.

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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.

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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.

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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.

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We examined whether number of prism adaptation treatment (PAT) sessions in regular clinical practice would predict spatial neglect (SN) improvement and rehabilitation outcomes. We reviewed clinical records from 16 U.S. rehabilitation hospitals where neurological patients were assessed for SN using the Catherine Bergego Scale (CBS) and if SN was detected, and may have received PAT. Multiple linear regression was used to predict CBS Change (indicating SN improvement) in 520 patients who received PAT while considering age, sex, diagnosis, time post diagnosis, CBS at baseline, neglected side of space, and length of stay. Another set of regression models including the same variables and adding Function Independent Measure (FIM®) at admission was used to predict FIM Gains (indicating rehabilitation outcomes) in 1720 patients receiving PAT or not. We found that greater number of PAT sessions predicted greater CBS Change, especially in patients with moderate-to-severe neglect. Number of PAT sessions also positively correlated with Total FIM, Motor FIM, and Cognitive FIM Gains regardless of SN severity classification at baseline. Furthermore, number of PAT sessions predicted CBS Change and FIM Gains among patients completing ≤8 PAT sessions but not among patients with ≥8 sessions, who however, showed greater CBS Change with increased PAT frequency (i.e., fewer days between two consecutive sessions). Receiving more once-daily PAT sessions predicted greater improvement in SN and rehabilitation outcomes. Receiving PAT at a higher frequency for 8 or more sessions predicted better SN improvement. Thus, dosage matters. The study provides practice-based evidence that PAT is appropriate for inpatient rehabilitation.

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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.

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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.

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Hemispatial neglect is among the most disabling consequences of right hemisphere stroke. However, there is no consensus on the optimal assessments to identify neglect. We hypothesized that different tests for neglect given the same day (i) detect distinct aspects and types of neglect, (ii) are sensitive to different cognitive functions (beyond spatially specific processing) and (iii) are associated with distinct regions of hypoperfusion. We examined data from 135 participants with acute, right-hemispheric ischaemic stroke who received an MRI and neglect testing within 48 h of acute infarct in a cross-sectional study. The volume of infarct was calculated on diffusion-weighted imaging. We also scored severity and location of fluid-attenuated inversion recovery hyperintense vessels in six areas (anterior cerebral artery territory, posterior cerebral artery territory and four within the middle cerebral artery territory) to estimate the volume and location of hypoperfusion in acute stroke. Neglect tests included gap detection, scene copy, line bisection, line cancellation, oral reading and picture description. We found strong correlations between tests that evaluated viewer-centred processing, as well as strong correlations between tests that evaluated stimulus-centred processing. The error rate on different tests was associated with hypoperfusion in different vascular territories, even after controlling for the volume of an infarct. Our results confirm that it is essential to administer a battery of different tests of hemispatial neglect to capture various deficits in attention and spatially specific processing that underlies neglect. Our results also show the potential usefulness of hyperintense vessel ratings as an indication of dysfunction beyond the infarct, as the ratings (and not infarct volume) were highly associated with many clinical deficits. Finally, results underscore that diverse types of neglect are clinically important in acute stroke, as they reflect different areas of hypoperfused tissue, which may be salvageable in the absence of infarct in those areas. As such, neglect batteries may be useful for detecting patients with cortical hypoperfusion who are candidates for reperfusion therapies.

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[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.