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.

Misperception of body verticality in neurological disorders: A systematic review and meta-analysis.

INTRODUCTION: The internal representation of verticality could be disturbed when a lesion in the central nervous system (CNS) affects the centers where information from the vestibular, visual, and/or somatosensory systems, increasing the risk of falling. OBJECTIVE: The aim was to evaluate the vestibular and somatosensory contribution to the verticality pattern in patients with stroke and other neurological disorders. METHODS: A literature search was performed in PubMed, Scopus, Web of Science, and CINAHL databases. Cross-sectional, case-control, and cohort studies comparing body verticality in patients with stroke or CNS diseases (CNSD) versus healthy controls were selected. Subjective postural vertical (SPV) in roll and pitch planes was used as the primary variable. RESULTS: Ten studies reporting data from 390 subjects were included. The overall effect for CNSD patients showed a misperception of body verticality in roll (standardized mean difference [SMD] = 1.05; 95% confidence interval [CI] .84-1.25) and pitch planes (SMD = 1.03; 95% CI .51-1.55). In subgroup analyses, a high effect was observed in the perception of SPV both in roll and pitch planes in stroke (p = .002) and other CNSD (p < .001). CONCLUSION: These findings suggest a potential misperception of SPV in patients with stroke and other neurological disturbances. Patients with CNSD could present an alteration of vestibular and somatosensory contribution to verticality construction, particularly stroke patients with pusher syndrome (PS), followed by those with PS combined with hemineglect.

Role of the medial agranular cortex in unilateral spatial neglect.

Unilateral spatial neglect (USN) results from impaired attentional networks and can affect various sensory modalities, such as visual and somatosensory. The rodent medial agranular cortex (AGm), located in the medial part of the forebrain from rostral to caudal direction, is considered a region associated with spatial attention. The AGm selectively receives multisensory input with the rostral AGm receiving somatosensory input and caudal part receiving visual input. Our previous study showed slower recovery from neglect with anterior AGm lesion using the somatosensory neglect assessment. Conversely, the functional differences in spatial attention across the entire AGm locations (anterior, intermediate, and posterior parts) are unknown. Here, we investigated the relationship between the severity of neglect and various locations across the entire AGm in a mouse stroke model using a newly developed program-based analysis method that does not require human intervention. Among various positions of the lesions, the recovery from USN during recovery periods (postoperative day; POD 10-18) tended to be slower in cases with more rostral lesions in the AGm (r = - 0.302; p = 0.028). Moreover, the total number of arm entries and maximum moving speed did not significantly differ between before and after AGm infarction. According to these results, the anterior lesions may slowly recover from USN-like behavior, and there may be a weak association between the AGm infarct site and recovery rate. In addition, all unilateral focal infarctions in the AGm induced USN-like behavior without motor deficits.

Disengagement of attention with spatial neglect: A systematic review of behavioral and anatomical findings.

The present review examined the consequences of focal brain injury on spatial attention studied with cueing paradigms, with a particular focus on the disengagement deficit, which refers to the abnormal slowing of reactions following an ipsilesional cue. Our review supports the established notion that the disengagement deficit is a functional marker of spatial neglect and is particularly pronounced when elicited by peripheral cues. Recent research has revealed that this deficit critically depends on cues that have task-relevant characteristics or are associated with negative reinforcement. Attentional capture by task-relevant cues is contingent on damage to the right temporo-parietal junction (TPJ) and is modulated by functional connections between the TPJ and the right insular cortex. Furthermore, damage to the dorsal premotor or prefrontal cortex (dPMC/dPFC) reduces the effect of task-relevant cues. These findings support an interactive model of the disengagement deficit, involving the right TPJ, the insula, and the dPMC/dPFC. These interconnected regions play a crucial role in regulating and adapting spatial attention to changing intrinsic values of stimuli in the environment.

The line bisection bias as a deficit of proportional reasoning - evidence from number line estimation in neglect.

This study aimed to investigate whether neurological patients presenting with a bias in line bisection show specific problems in bisecting a line into two equal parts or their line bisection bias rather reflects a special case of a deficit in proportional reasoning more generally. In the latter case, the bias should also be observed for segmentations into thirds or quarters. To address this question, six neglect patients with a line bisection bias were administered additional tasks involving horizontal lines (e.g., segmentation into thirds and quarters, number line estimation, etc.). Their performance was compared to five neglect patients without a line bisection bias, 10 patients with right hemispheric lesions without neglect, and 32 healthy controls. Most interestingly, results indicated that neglect patients with a line bisection bias also overestimated segments on the left of the line (e.g., one third, one quarter) when dissecting lines into parts smaller than halves. In contrast, such segmentation biases were more nuanced when the required line segmentation was framed as a number line estimation task with either fractions or whole numbers. Taken together, this suggests a generalization of line bisection bias towards a segmentation or proportional processing bias, which is congruent with attentional weighting accounts of line bisection/neglect. As such, patients with a line bisection bias do not seem to have specific problems bisecting a line, but seem to suffer from a more general deficit processing proportions.

Understanding Occupational Therapists' Knowledge and Confidence When Assessing for Spatial Neglect: A Special Issue Review.

IMPORTANCE: Spatial neglect (SN)-failure to respond to stimuli on the side of the body contralateral to a poststroke lesion-is one of the most disabling impairments for stroke survivors, and 80% of stroke survivors may have undetected SN. Occupational therapists' evaluations should include determining the impact of poststroke SN. OBJECTIVE: To investigate occupational therapists' confidence, knowledge, current practices, barriers, and facilitators when assessing for SN in adult stroke survivors. DESIGN: A 30-item survey was created with guidance from stroke rehabilitation occupational therapists who reviewed the survey for face and content validity. SETTING: Online survey. PARTICIPANTS: Occupational therapist survey responders (N = 76). OUTCOMES AND MEASURES: Self-report assessments were used to measure occupational therapists' confidence in identifying SN, SN assessment practices, and barriers to and facilitators of SN assessment. Knowledge of SN signs and symptoms, neuroanatomy, and clinical presentation were measured with a three-question quiz. RESULTS: Eighty-one percent of the respondents reported a high level of confidence in identifying SN, and 70% reported routinely assessing for SN, with 81% using clinical observation rather than standardized tools as the primary assessment method. Barriers to SN assessment included time and resources. CONCLUSIONS AND RELEVANCE: Most respondents, despite reporting high levels of confidence with routine SN assessments, did not use standardized SN measures and demonstrated suboptimal knowledge of SN. These results emphasize the need to increase clinical education about SN and its assessments. Plain-Language Summary: This study gathered baseline information on an underinvestigated topic-occupational therapists' education, confidence, current practices, barriers, and facilitators when assessing for spatial neglect in adult stroke survivors. The study results also contribute to future research on occupational therapists' current confidence and knowledge when assessing for spatial neglect.

Spatial Neglect: An Exploration of Clinical Assessment Behaviour in Stroke Rehabilitation.

OBJECTIVE: There is a large gap between evidence-based recommendations for spatial neglect assessment and clinical practice in stroke rehabilitation. We aimed to describe factors that may contribute to this gap, clinician perceptions of an ideal assessment tool, and potential implementation strategies to change clinical practice in this area. DESIGN: Qualitative focus group investigation. Focus group questions were mapped to the Theoretical Domains Framework and asked participants to describe their experiences and perceptions of spatial neglect assessment. SETTING: Online stroke rehabilitation educational bootcamp. PARTICIPANTS: A sample of 23 occupational therapists, three physiotherapists, and one orthoptist that attended the bootcamp. INTERVENTION: Prior to their focus group, participants watched an hour-long educational session about spatial neglect. MAIN MEASURES: A deductive analysis with the Theoretical Domains Framework was used to describe perceived determinants of clinical spatial neglect assessment. An inductive thematic analysis was used to describe perceptions of an ideal assessment tool and practice-change strategies in this area. RESULTS: Participants reported that their choice of spatial neglect assessment was influenced by a belief that it would positively impact the function of people with stroke. However, a lack of knowledge about spatial neglect assessment appeared to drive low clinical use of standardised functional assessments. Participants recommended open-source online education involving a multidisciplinary team, with live-skill practice for the implementation of spatial neglect assessment tools. CONCLUSIONS: Our results suggest that clinicians prefer functional assessments of spatial neglect, but multiple factors such as knowledge, training, and policy change are required to enable their translation to clinical practice.

Unilateral Spatial Neglect May Not Be Detected by Performance-Based Functional Neglect Assessment.

IMPORTANCE: Unilateral spatial neglect (neglect) poststroke is disabling. It is critical that people with neglect are identified so that treatment can be provided to maximize independence. However, there is some evidence to suggest that existing assessments may not adequately measure neglect. It is unclear whether assessments also fail to identify people with neglect entirely. OBJECTIVE: To determine whether there are stroke survivors who self-report neglect symptoms that are not detected by therapist-rated assessments and to compare self-report and therapist-ratings. DESIGN: Cross-sectional study. SETTING: U.S. university research center. PARTICIPANTS: Unilateral stroke survivors (N = 133). INTERVENTION: Not applicable. OUTCOMES AND MEASURES: The Catherine Bergego Scale (CBS) was administered to participants and scored by a trained occupational therapist. The parallel self-evaluation anosognosia form was also administered to participants to self-report and rate neglect symptoms. RESULTS: Forty-eight participants (36.1%) were classified as without neglect on the basis of therapist-rated total CBS scores, yet 30 (62.5%) of these 48 participants reported symptoms of neglect on the CBS self-evaluation anosognosia form. There was a significant difference (p < .001) between therapist-rated and self-rated total CBS scores. CONCLUSIONS AND RELEVANCE: Our results indicate that many stroke survivors report some level of disability associated with neglect yet do not meet the criteria to be classified as having neglect according to a commonly used therapist-rated performance-based measure. Plain-Language Summary: The findings of this study contribute to the evidence that existing assessments used by occupational therapists to measure performance-based neglect may not always detect neglect symptoms comprehensively in people poststroke. The finding also suggest that we may be missing neglect symptoms entirely. Occupational therapists should consider using various methods to assess for neglect, including patient self-report and comprehensive occupational profiles. Clinicians should also thoroughly screen all clients with stroke for neglect, regardless of lesion location.

Persistent aura, visual snow, and other visual symptoms.

In neurology practice, it is common to encounter a variety of visual complaints. Historically, in the absence of known ocular pathology, epilepsy, or insult to the central nervous system, positive symptoms were assumed to be migrainous in origin. This assumption was sometimes made even in the absence of a history of migraine. In the past decade, there has been considerable effort to better delineate and study nonmigrainous visual phenomena, with the most extensive focus on a newly defined syndrome, visual snow syndrome (VSS). The heightened awareness of visual snow as a symptom and syndrome has greatly enhanced the understanding of this visual phenomenon; however, in the last few years, there has been an almost pendulous swing in clinic, with patients now being given the diagnosis of VSS for any dots or flickering they may have in their vision. To avoid clinical misdiagnosis, it is critical that we expand our understanding not just of VSS but also of underlying pathologies that may present similarly. This chapter will review classical migraine aura, persistent migraine aura, visual snow and a number of positive and negative visual complaints that are on the differential when seeing patients with suspected aura or visual snow. This is followed by an in-depth discussion on the current understanding of the presenting symptoms, pathophysiology, evaluation and management of VSS. We also outline secondary causes of visual snow.

Task-based and Magnified Mirror Therapy for Unilateral Spatial Neglect among post-stroke subjects: Study protocol for a randomized controlled trial.

BACKGROUND: Unilateral spatial neglect (USN) is a commonly occurring neurocognitive disability after a stroke. The neglect may affect the motor recovery of the upper and lower limbs and functional performances. Mirror therapy, a simple and economical approach has the potential to reduce the USN and related impairments. AIM: The primary objective of this study is to determine the effectiveness of task-based and magnified mirror therapy on the USN and on the motor recovery of the post-stroke subjects. The secondary objective is to investigate the effectiveness of the intervention on the function and disability of the subjects. METHODS: In this randomized controlled, assessor-blinded trial, 86 post-stroke subjects will be recruited from the neuro-rehabilitation laboratory of a rehabilitation institute, located in northern India. The participants,aged20 to 80 years, with 1 to 36 months of stroke onset, hemiparesis, and the USN, will be considered eligible for the study. In addition to the conventional rehabilitation, the experimental group(n = 43) will receive 40 sessions (8 weeks) of Task-based and MAGnified Mirror Therapy for Unilateral Spatial Neglect (T-MAGUSN). The control group (n = 43) will undergo a dose-matched conventional program only. The participants will be assessed at baseline, post-intervention and 4-week follow-up using primary (Line Bisection Test, Letter Cancellation Test, and Fugl-Myer Assessment) and secondary (Catherine Bergego Scale, Berg Balance Scale, Functional Ambulation Classification, Modified Rankin Scale) outcome measures. DISCUSSION: This proposed study will lead to the development of a novel rehabilitation protocol for the management of USN, aiming to enhance motor and functional recovery. The investigation will consider both the upper and lower limbs for the intervention, reducing the impact of cognitive disability in stroke. TRIAL REGISTRATION: Clinical Trial Registry of India (CTRI) as CTRI/2023/05/053184 (www.ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=74659).

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.

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.

Spontaneous unilateral spatial neglect recovery after brain tumour resection: A multimodal diffusion and rs-fMRI case report.

Patients with unilateral spatial neglect (USN) are unable to explore or to report stimuli presented in the left personal and extra-personal space. USN is usually caused by lesion of the right parietal lobe: nowadays, it is also clear the key role of structural connections (the second and the third branch of the right Superior Longitudinal Fasciculus, respectively, SLF II and III) and functional networks (Dorsal and Ventral Attention Network, respectively, DAN and VAN) in USN. In this multimodal case report, we have merged those structural and functional information derived from a patient with a right parietal lobe tumour and USN before surgery. Functional, structural and neuropsychological data were also collected 6 months after surgery, when the USN was spontaneously recovered. Diffusion metrics and Functional Connectivity (FC) of the right SLF and DAN, before and after surgery, were compared with the same data of a patient with a tumour in a similar location, but without USN, and with a control sample. Results indicate an impairment in the right SLF III and a reduction of FC of the right DAN in patients with USN before surgery compared to controls; after surgery, when USN was recovered, patient's diffusion metrics and FC showed no differences compared to the controls. This single case and its multimodal approach reinforce the crucial role of the right SLF III and DAN in the development and recovery of egocentric and allocentric extra-personal USN, highlighting the need to preserve these structural and functional areas during brain surgery.

Impact of Spatial Neglect on Activity and Participation: A Mixed-Methods Study.

Post-stroke neglect is disabling, yet it is unclear whether existing assessments capture the extent neglect affects activity and participation. The objective of the study is to explore stroke survivor and caregiver perspectives on how neglect affects activity and participation and to compare their experiences to neglect assessments items. We conducted an explanatory sequential mixed-methods study by conducting semi-structured interviews with stroke survivors (n = 7) and caregivers (n = 7) analyzed using thematic analysis. Stroke survivors completed the Catherine Bergego Scale (CBS) and Behavioral Inattention Test (BIT). Descriptive analyses characterized participant's neglect. The standardized CBS and BIT tests indicated that stroke survivors demonstrated mild-to-moderate (CBS) or no-to-mild (BIT) neglect. In contrast, the qualitative data revealed serious safety concerns and significant ongoing difficulties participating in school, work, and family activities because of neglect. Current assessments may not measure the impact of neglect on activity or participation in life for stroke survivors.

Individuals with neglect after stroke experience disability. This study interviewed individuals with neglect and their caregivers to understand whether clinical assessments capture the impact that neglect has on their daily life. Results show that existing assessments may not fully measure the challenges that individuals experience.

Unilateral spatial neglect affected by right-sided stimuli in a three-dimensional virtual environment: A preliminary proof-of-concept study.

Unilateral spatial neglect (USN) is defined as the inability to attend and see on one side, which seriously interferes with daily life. Clinically, patients with left USN commonly demonstrate a striking immediate capture of attention from ipsilesional, right-sided items as soon as a visual scene unfolds (i.e., magnetic attraction [MA]). Therefore, this preliminary study utilized a three-dimensional (3D) virtual environment to evaluate the effects of eliminating stimuli in the rightward space and directing attention to the left on neglect symptoms. METHODS: Seven patients with USN participated in this study, and two types of visual stimuli were created: the numbers and objects in the 3D virtual environment. To eliminate the visual stimuli on the right side, a moving slit was introduced in the virtual environment. During the experiment, patients were required to orally identify each object and number both in moving and nonmoving slit conditions. RESULTS: A statistical comparison of scores with and without the moving slit in the 3D virtual space indicated significant changes in the object stimuli condition; however, no statistically significant difference was observed in the number stimuli condition. CONCLUSIONS: Masking the right side within the 3D virtual space increased the number of objects that can be recognized on the left side by patients with USN. The results may allow interventions in a virtual reality environment that closely resembles the patient's real-life space.Clinical Relevance-Magnetic attraction is a symptom seen in patients in clinical practice, but there is no method of rehabilitation. The proposed moving slit method is expected to be effective because it enables attention guidance in a three-dimensional space.

Immersive virtual reality gameplay detects visuospatial atypicality, including unilateral spatial neglect, following brain injury: a pilot study.

BACKGROUND: In neurorehabilitation, problems with visuospatial attention, including unilateral spatial neglect, are prevalent and routinely assessed by pen-and-paper tests, which are limited in accuracy and sensitivity. Immersive virtual reality (VR), which motivates a much wider (more intuitive) spatial behaviour, promises new futures for identifying visuospatial atypicality in multiple measures, which reflects cognitive and motor diversity across individuals with brain injuries. METHODS: In this pilot study, we had 9 clinician controls (mean age 43 years; 4 males) and 13 neurorehabilitation inpatients (mean age 59 years; 9 males) recruited a mean of 41 days post-injury play a VR visual search game. Primary injuries included 7 stroke, 4 traumatic brain injury, 2 other acquired brain injury. Three patients were identified as having left sided neglect prior to taking part in the VR. Response accuracy, reaction time, and headset and controller raycast orientation quantified gameplay. Normative modelling identified the typical gameplay bounds, and visuospatial atypicality was defined as gameplay beyond these bounds. RESULTS: The study found VR to be feasible, with only minor instances of motion sickness, positive user experiences, and satisfactory system usability. Crucially, the analytical method, which emphasized identifying 'visuospatial atypicality,' proved effective. Visuospatial atypicality was more commonly observed in patients compared to controls and was prevalent in both groups of patients-those with and without neglect. CONCLUSION: Our research indicates that normative modelling of VR gameplay is a promising tool for identifying visuospatial atypicality after acute brain injury. This approach holds potential for a detailed examination of neglect.

[Simultanagnosia caused by cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions].

A 76-year-old male patient was admitted to our hospital for the treatment of acute cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions. Although his overall cognitive function was almost normal, he exhibited reduced visual sensitivity in the homonymous lower left quadrant of the visual field, left unilateral spatial neglect (USN), and simultanagnosia. Left USN improved 4 months after the onset of infarction; however, simultanagnosia persisted. To the best of our knowledge, this is the first case of simultanagnosia caused by cerebral infarction in the right temporal stem, right lateral thalamus, and right pulvinar regions.

Comprehensive voxel-wise, tract-based, and network lesion mapping reveals unique architectures of right and left visuospatial neglect.

Visuospatial neglect is a common, post-stroke cognitive impairment which is widely considered to be a disconnection syndrome. However, the patterns of disconnectivity associated with visuospatial neglect remain unclear. Here, we had 480 acute stroke survivors [age = 72.8 (SD = 13.3), 44.3% female, 7.5 days post-stroke (SD = 11.3)] undertake routine clinical imaging and standardised visuospatial neglect testing. The data were used to conduct voxel-wise, tract-level, and network-level lesion-mapping analyses aimed at localising the neural correlates of left and right egocentric (body-centred) and allocentric (object-centred) visuospatial neglect. Only minimal anatomical homogeneity was present between the correlates of right and left egocentric neglect across all analysis types. This finding challenges previous work suggesting that right and left visuospatial neglect are anatomically homologous, and instead suggests that egocentric neglect may involve damage to a shared, but hemispherically asymmetric attention network. By contrast, egocentric and allocentric neglect was associated with disconnectivity in a distinct but overlapping set of network edges, with both deficits related to damage across the dorsal and ventral attention networks. Critically, this finding suggests that the distinction between egocentric and allocentric neglect is unlikely to reflect a simple dichotomy between dorsal versus ventral networks dysfunction, as is commonly asserted. Taken together, the current findings provide a fresh perspective on the neural circuitry involved in regulating visuospatial attention, and provide important clues to understanding the cognitive and perceptual processes involved in this common and debilitating neuropsychological syndrome.