A bibliometric review of unilateral neglect: Trends, frontiers, and frameworks.

BACKGROUND: Owing to the adverse effects of unilateral neglect (UN) on rehabilitation outcomes, fall risk, and activities of daily living, this field has gradually got considerable interest. Notwithstanding, there is presently an absence of efficient portrayals of the entire research field; hence, the motivation behind this study was to dissect and evaluate the literature published in the field of UN following stroke and other nonprogressive brain injuries to identify hotspots and trends for future research. MATERIALS AND METHODS: Original articles and reviews related to UN from 1970 to 2022 were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection. CiteSpace, VOSviewer, and Bibliometrix software were used to observe publication fields, countries, and authors. RESULTS: A total of 1,202 publications were incorporated, consisting of 92% of original articles, with an overall fluctuating upward trend in the number of publications. Italy, the United Kingdom, and the United States made critical contributions, with Neuropsychologia being the most persuasive academic journal, and Bartolomeo P. ranked first in both the quantity of publications and co-citations. Keywords were divided into four clusters, and burst keyword detection demonstrated that networks and virtual reality might additionally emerge as frontiers of future development and warrant additional attention. CONCLUSIONS: UN is an emerging field, and this study presents the first bibliometric analysis to provide a comprehensive overview of research in the field. The insights and guidance garnered from our research on frontiers, trends, and popular topics could prove highly valuable in facilitating the rapid development of this field while informing future research directions.

Is Anosognosia for Left-Sided Hemiplegia Due to a Specific Self-Awareness Defect or to a Poorly Conscious Working Mode Typical of the Right Hemisphere?

This review aimed to evaluate whether the association between 'anosognosia for hemiplegia' and lesions of the right hemisphere points to a special self-awareness role of the right side of the brain, or could instead be due to a working mode typical of the right hemisphere. This latter viewpoint is consistent with a recently proposed model of human brain asymmetries that assumes that language lateralization in the left hemisphere might have increased the left hemisphere's level of consciousness and intentionality in comparison with the right hemisphere's less conscious and more automatic functioning. To assess these alternatives, I tried to ascertain whether anosognosia is greater for left-sided hemiplegia than for other disorders provoked by right brain lesions, or whether unawareness prevails in tasks more clearly related to the disruption of the right hemisphere's more automatic (and less conscious) functioning. Data consistent with the first alternative would support the existence of a specific link between anosognosia for hemiplegia and self-awareness, whereas data supporting the second option would confirm the model linking anosognosia to a poorly conscious working mode typical of the right hemisphere. Analysis results showed that the incidence of anosognosia of the highly automatic syndrome of unilateral neglect was greater than that concerning the unawareness of left hemiplegia, suggesting that anosognosia for left-sided hemiplegia might be due to the poorly conscious working mode typical of the right hemisphere.

[Clinical examination of spatial neglect and other disorders of spatial cognition]. / Klinische Untersuchung des unilateralen Neglects und weiterer Störungen der Raumkognition.

Neglect occurring after stroke, neoplasms or degenerative processes can lead to considerable disability in everyday life as can other disorders of spatial orientation. Therefore, a dedicated examination and early diagnostic classification are obligatory. Behavioral tests are helpful in this respect, enabling the clinician to obtain an initial overview of the existing deficits even at the patient's bedside. The clinical (bedside) examination of spatial neglect as well as the corresponding differential diagnostic procedure for the clarification of (possibly additionally or exclusively existing) hemianopia and extinction, as well as the examination of disorders of visuospatial perception, visuoconstructive disorders, topographic disorders, Bálint's syndrome, simultanagnosia, and optic ataxia are presented. The presentation is based on the newly revised (year 2023) guidelines of the Association of the Scientific Medical Societies in Germany (AWMF) on this subject area.

Uncovering the (un)attended: Pupil light responses index persistent biases of spatial attention in neglect.

Visuospatial neglect is a frequent and disabling disorder, mostly after stroke, that presents in impaired awareness to stimuli on one side of space. Neglect causes disability and functional dependence, even long after the injury. Improving measurements of the core attentional deficit might hold the key for better understanding of the condition and development of treatment. We present a rapid, pupillometry-based method that assesses automatic biases in (covert) attention, without requiring behavioral responses. We exploit the phenomenon that pupil light responses scale with the degree of covert attention to stimuli, and thereby reveal what draws (no) attention. Participants with left-sided neglect after right-sided lesions following stroke (n = 5), participants with hemianopia/quadrantanopia following stroke (n = 11), and controls (n = 22) were presented with two vertical bars, one of which was white and one of which was black, while fixating the center. We varied which brightness was left and right, respectively across trials. In line with the hypotheses, participants with neglect demonstrated biased pupil light responses to the brightness on the right side. Participants with hemianopia showed similar biases to intact parts of the visual field, whilst controls exhibited no bias. Together, this demonstrates that the pupil light response can reveal not only visual, but also attentional deficits. Strikingly, our pupillometry-based bias estimates were not in agreement with neuropsychological paper-and-pencil assessments conducted on the same day, but were with those administered in an earlier phase post-stroke. Potentially, we pick up on persistent biases in the covert attentional system that participants increasingly compensate for in classical neuropsychological tasks and everyday life. The here proposed method may not only find clinical application, but also advance theory and aid the development of successful restoration therapies by introducing a precise, longitudinally valid, and objective measurement that might not be affected by compensation.

The therapeutic effect of transcranial direct current stimulation combined with cognitive training on patients with unilateral neglect after stroke.

BACKGROUND: Unilateral neglect (UN) is a frequent cognitive disability following a stroke. Additional research is needed to determine the most effective cognitive rehabilitation techniques. OBJECTIVE: Based on the unilateral neglect neural network, we aim to explore the effect of a new model of transcranial direct current stimulation (tDCS) combined with cognitive training on stroke patients with unilateral neglect. METHODS: Thirty stroke patients with UN after stroke were randomly divided into three groups. All patients received cognitive training for UN and transcranial direct current stimulation with an anode placed on the corresponding part of the right hemisphere for 2 weeks. Treatment group A received multi-site tDCS from the inferior parietal lobule, middle temporal gyrus to prefrontal lobe. Group B received single-site tDCS of the inferior parietal lobule. The improvement of UN symptoms was evaluated by the scores of the Deviation index and Behavioral Inattention Test conventional tests. RESULTS: All groups showed improvements in all tests, and the scores of the treatment groups were statistically significant compared with the control group. CONCLUSION: Both single-site tDCS and multi-site tDCS have therapeutic effects on UN after stroke, and the difference in the therapeutic effects of the two modes still needs to be further explored.

Increased scene complexity during free visual exploration reveals residual unilateral neglect in recovered stroke patients.

Unilateral neglect is a common cognitive syndrome after stroke, which is defined as a spatially specific unawareness of the contralesional space. The syndrome is caused by disruptions of attentional networks in the brain, which impair the patients' ability to direct attention towards the contralesional space. During recovery, patients often learn to compensate by voluntarily directing their attention to the neglected side at the expense of cognitive resources. In this study, we examined the impact of the complexity of visual input on free visual exploration behavior of unilateral neglect and apparently recovered patients. We asked whether increasing scene complexity would allow the detection of residual unilateral neglect in recovered patients by increasing the amount of cognitive resources needed for visual processing and limiting capacities for compensation. Using virtual reality, we analyzed the spatial distribution of gaze of unilateral neglect patients, patients who had, according to conventional diagnostics, recovered from the syndrome, stroke patients with no history of unilateral neglect, and age-matched healthy controls. We manipulated the complexity of an immersive virtual scene presented on head mounted displays. We identified the orientation bias towards the ipsilesional side as a sensitive and specific marker of unilateral neglect, which was present in unilateral neglect and recovered patients but absent in stroke patients with no history of unilateral neglect and controls. Increasing scene complexity exacerbated the orientation shift in unilateral neglect patients and revealed that three out of nine (33%) recovered patients had a high probability of suffering from residual unilateral neglect as estimated by a generalized linear model using the median horizontal gaze position as a predictor.

A Complex Intervention Integrating Prism Adaptation and Neck Vibration for Unilateral Neglect in Patients of Chronic Stroke: A Randomised Controlled Trial.

Unilateral neglect in patients of chronic stroke reduces the quality of life and interferes with activities of daily living (ADL). This study aimed to investigate the effects of a complex rehabilitative programme that integrates prism adaptation (PA) and neck vibration (NV) for unilateral neglect in patients of chronic stroke. Thirty-six patients were randomised among the PA + NV group (Group A, n = 12), the NV-only group (Group B, n = 12), and the PA-only group (Group C, n = 12). The intervention was performed for 50 min/day, with five sessions per week, for 4 weeks. Albert's test and the Catherine Bergego Scale were used to measure the effects of each intervention on unilateral neglect, whereas the modified Barthel Index was used to assess the effect on ADL. All three groups exhibited a reduction in unilateral neglect and an improvement in activities of daily living after the intervention (p < 0.05). Notably, Group A (PA + NV) exhibited a significantly greater level of reduction in unilateral neglect than the other groups (p < 0.05); however, the improvement in ADL did not significantly vary across the three groups (p > 0.05). This novel complex intervention comprising PA + NV is recommended for the rehabilitation, in the clinical setting, of patients of chronic stroke with unilateral neglect.

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.

Noninvasive neuromodulation for unilateral neglect after stroke: a systematic review and network meta-analysis.

OBJECTIVE: To systematically evaluate the effect of noninvasive neuromodulation (NINM) on unilateral neglect (UN) after stroke and compare the effects of different NINMs. METHODS: Randomized controlled trials (RCTs) on the effect of NINM on UN after stroke were retrieved from the PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Data, VIP, and CBM databases from inception to January 2022. The risk of bias and quality of the trials were assessed following the Cochrane Handbook of Systematic Reviews and the physiotherapy evidence database PEDro Scale. Statistical analysis was conducted with Stata 16.0 and R 4.0.2. This study was registered on PROSPERO (No. CRD42021295336). RESULTS: A total of 12 RCTs involving 291 patients were included. Meta-analysis showed that NINM could reduce the line bisection test (LBT) score (SMD = - 1.56, 95% CI - 2.10 ~ - 1.03, P < 0.05), the line cancellation test score (SMD = - 1.83, 95% CI - 2.39 ~ - 1.27, P < 0.05), and the star cancellation test score (SMD = - 2.85, 95% CI - 4.93 ~ - 0.76, P < 0.05). Network meta-analysis showed that the best probabilistic ranking of the effects of different NINMs on the LBT score was theta-burst stimulation (TBS) (P = 0.915) > repetitive transcranial magnetic stimulation (P = 0.068) > transcranial direct current stimulation (P = 0.018). CONCLUSION: Existing evidence showed that NINM could improve UN after stroke and that TBS was best. Due to the number of included studies and sample size, more large-sample, multicenter, double-blinded, high-quality clinical RCTs are still needed in the future to further confirm the results of this research.

The mobility assessment course: A ready-to-use dynamic measure of visuospatial neglect.

The Mobility Assessment Course (MAC) is a tool to measure visuospatial neglect in a dynamic fashion. Although the MAC has been shown to dissociate between patients with and without neglect, it remains unclear whether it is applicable in clinical settings. We evaluated the MAC regarding its (1) feasibility as a diagnostic tool as part of standard care, (2) construct validity, and (3) underlying constructs and potential confounders. A consecutive sample of stroke patients admitted to inpatient rehabilitation completed the MAC, shape cancellation, line bisection, and/or Catherine Bergego Scale (CBS) as part of the standard assessment. To assess feasibility, we computed the percentage of patients who completed the MAC. Construct validity was tested by evaluating MAC performance between patients with and without neglect and controls. Finally, a regression analysis was conducted to assess underlying constructs and potential confounders of MAC performance (i.e., level of mobility and lesion side). The MAC was completed by 82% of patients (N = 182/223; of whom 145 completed all tasks). Patients with neglect performed worse on the MAC (indicating more severe neglect) compared to patients without neglect and controls. The MAC had a lower sensitivity and higher specificity than paper-and-pencil tasks and the CBS. Performance on shape cancellation, line bisection, and CBS were predictors of MAC performance. Level of mobility and lesion side did not predict MAC scores, indicating that these factors do not confound its reliability. To conclude, the MAC is an easy-to-implement tool to evaluate neglect in a dynamic manner, which can be administered in addition to conventional paper-and-pencil tasks.

The orienting response drives pseudoneglect-Evidence from an objective pupillometric method.

Spatial attention is generally slightly biased leftward ("pseudoneglect"), a phenomenon typically assessed with paper-and-pencil tasks, limited by the requirement of explicit responses and the inability to assess on a subsecond timescale. Pseudoneglect is often stable within experiments, but differs vastly between investigations and is sometimes directed to the left, sometimes to the right. To date, no exhaustive explanation to this phenomenon has been provided. Here, we objectively assessed lateralized attention over time, exploiting the phenomenon that changes in the pupil reflect the allocation of attention in space. Pupil sizes of 41 healthy participants fixating the center were influenced stronger by the differential background luminance of the left side compared to the right side of the visual display. These differences were mainly driven by visual information in the periphery. Differences in pupil sizes positively related with greyscales scores. Time-based analyses within trials show strongest effects early on. With increasing trial number (not time), the initial leftward bias shifted central in pupillometry-based and greyscales measures. This suggests that the orienting response determines the degree of attention bias. In our amplification hypothesis we pose that the quality of pseudoneglect (i.e., the direction) is determined by higher order factors such as hemispheric imbalances, whereas the quantity (i.e., the degree) is determined by the orienting network. This account might explain numerous-previously thought opposing-findings. We here show how pupil light responses reveal pseudoneglect, in a next step, this might allow clinical diagnosis of hemispatial neglect.

Linguistic structure modulates attention in reading: Evidence from negative concord in Italian.

We report the reading performance of an Italian speaker with egocentric Neglect Dyslexia on sentences with Negative Concord structures, which contain a linguistic cue to the presence of a preceding negative marker and compare it to sentences with no such cue. As predicted, the frequency of reading the whole sentence, including the initial negative marker non, was higher in Negative Concord structures than in sentences which also started with non, but crucially, lacked the medially positioned linguistic cue to the presence of non. These data support the claim that the presence of linguistic cues to sentence structure modulates attention during reading in Neglect Dyslexia.

Comparing the effectiveness of bimanual and unimanual mirror therapy in unilateral neglect after stroke: A pilot study.

BACKGROUND: Unilateral neglect in stroke patients is a major obstacle to rehabilitation, which is a great challenge for therapists. OBJECTIVE: This study aimed to compare the effectiveness of bimanual mirror therapy (BMT) and unimanual mirror therapy (UMT), the two protocols of mirror therapy, for the reduction of the symptoms of unilateral neglect in stroke patients. METHODS: Twenty-eight individuals were randomly assigned to the BMT or UMT groups. Both groups received mirror therapy for 30 minutes per day, 5 days a week, for a period of 4 weeks. The Star Cancelation Test (SCT), Line Bisection Test (LBT), Picture Scanning Test (PST), and Korean Catherine Bergego Scale (K-CBS) were used to measure the change in unilateral neglect, and the Korean version of the Modified Barthel Index (K-MBI) was used to evaluate activities of daily living (ADL). RESULTS: The results of SCT, LBT, PST, and K-CBS showed significant decreases in unilateral neglect in both groups (p < 0.05). K-MBI improved significantly in both groups (p < 0.05). There were significant differences between the two groups in the unilateral neglect tests (p < 0.05), but no significant difference in ADL evaluation (p > 0.05). CONCLUSIONS: Mirror therapy protocols can be applied to treat unilateral neglect in stroke patients. However, BMT may be more beneficial for reducing the symptoms of unilateral neglect.

Mirror therapy for unilateral neglect after stroke: A systematic review.

BACKGROUND AND PURPOSE: The effect of mirror therapy for unilateral neglect after stroke currently remains uncertain. METHODS: This systematic review investigated the effect of mirror therapy on neglect and daily living activities in patients with unilateral neglect after stroke when compared with no treatment, sham mirror therapy, or routinely applied therapies only. We performed a systematic electronic search of PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, and Wanfang Data to identify relevant randomized control trials (RCTs). RESULTS: We included five RCTs in the data synthesis. Mirror therapy (combined or not with other treatments) was more effective in improving neglect as compared with sham mirror therapy or no treatment (combined or not with the other therapies; standard mean difference [SMD] = 1.62, 95% confidence interval [CI] = 1.03-2.21, p < 0.00001). Mirror therapy (combined or not with other therapies) was effective in improving daily living activities as compared with sham mirror therapy or no treatment (combined or not with the other therapies; SMD = 2.09, 95% CI = 0.63-3.56, p = 0.005). CONCLUSIONS: Our results show that mirror therapy effectively improves neglect and daily living activities in patients with unilateral neglect after stroke. Future trials with high methodological quality and larger sample sizes are needed to determine the immediate and long-term effect of appropriate mirror therapy protocol for unilateral neglect.

Theta-burst transcranial magnetic stimulation for the treatment of unilateral neglect in stroke patients: A systematic review and best evidence synthesis.

BACKGROUND: Unilateral neglect (UN) is a common and disabling disorder after stroke. UN is a strong and negative predictor of functional rehabilitative outcome. Non-invasive brain stimulation, such as theta-burst transcranial magnetic stimulation (TBS), is a promising rehabilitation technique for treating stroke-induced UN. OBJECTIVE: To systematically review the available literature, researching whether TBS of the contra-lesional hemisphere is more effective than standard rehabilitation in improving symptoms of UN in patients with right hemisphere stroke. REVIEW METHODS: A systematic review was conducted to retrieve randomized controlled trials (RCTs) that were relevant to the objective of this review. PubMed, Ovid and Cochrane Library electronic databases were comprehensively searched from inception up to February 2021. Of the included studies, methodological quality was assessed using the PEDro scale, whereafter a best evidence synthesis (BES) was conducted to summarize the results. RESULTS: Nine RCTs investigating the effects of TBS on stroke-induced UN symptoms were included in this review. Seven studies assessing continuous TBS (cTBS) found significantly greater amelioration of UN symptoms in the TBS intervention group when compared to the control group; one study assessing cTBS found no such significant difference. One study assessing intermittent TBS (iTBS) found significant between-group differences in favor of the intervention. The BES yielded strong evidence in favor of cTBS, and limited evidence in favor of iTBS. CONCLUSIONS: The included studies in the present review allow the conclusion that TBS can have favorable effects on UN recovery in stroke patients. Its clinical use is recommended in conjunction with cognitive rehabilitation and occupational or physical rehabilitation as needed. However, many aspects for optimal usage of TBS therapy in clinical settings, such as exact TBS protocols, number of sessions, and treatment duration, are not clear.

From embodying tool to embodying alien limb: sensory-motor modulation of personal and extrapersonal space.

Years ago, it was demonstrated (e.g., Rizzolatti et al. in Handbook of neuropsychology, Elsevier Science, Amsterdam, 2000) that the brain does not encode the space around us in a homogeneous way, but through neural circuits that map the space relative to the distance that objects of interest have from the body. In monkeys, relatively discrete neural systems, characterized by neurons with specific neurophysiological responses, seem to be dedicated either to represent the space that can be reached by the hand (near/peripersonal space) or to the distant space (far/extrapersonal space). It was also shown that the encoding of spaces has dynamic aspects because they can be remapped by the use of tools that trigger different actions (e.g., Iriki et al. 1998). In this latter case, the effect of the tool depends on the modulation of personal space, that is the space of our body. In this paper, I will review and discuss selected research, which demonstrated that also in humans: 1 spaces are encoded in a dynamic way; 2 encoding can be modulated by the use of tool that the system comes to consider as parts of the own body; 3 body representations are not fixed, but they are fragile and subject to change to the point that we can incorporate not only the tools necessary for action, but even limbs belonging to other people. What embodiment of tools and of alien limb tell us about body representations is then briefly discussed.

Independence in Daily Activities after Stroke among Occupational Therapy Patients and Its Relationship with Unilateral Neglect.

More research is needed to better understand the impact of occupational therapy (OT) in stroke patients and syndromes of unilateral neglect (UN) and anosognosia. A prospective, observational, longitudinal design was conducted on a sample of 27 OT patients. The objectives were to examine: (1) the presence of UN and anosognosia; (2) the functional outcomes; and (3) the association of UN at baseline with functional status at discharge from OT. The outcomes were Barthel (functional independence) and the Rivermead Mobility Index (RMI). The baseline proportion of participants with UN was 33% according to the Star Cancellation Test (STC), and 48.1% according to the Catherine Bergego Scale (CBS) therapist-version. There was a significant difference between the therapist and participant-rated CBS scores (p = 0.004). Functional independence improved significantly between the initial and final assessments (p < 0.001); the effect size (r) was large (r = 0.61). There was a significant improvement in RMI scores (p < 0.001), which was large in size (r = 0.59). Both the STC and CBS-therapist scores were significantly correlated with the Barthel (p < 0.001, p = 0.005, respectively) and with the RMI (p = 0.004, p = 0.028, respectively). The participants substantially enhanced their functional status skills. UN and anosognosia were common problems, and neglect was associated with worse OT program outcomes.

DYNAMIC OF UPPER LIMB SENSORIMOTOR RECOVERY ASSESSED ON THE FUGL-MEYER SCALE IN POST-STROKE PATIENTS WITH NEGLECT SYNDROME RECEIVING COMBINED PHYSICAL THERAPY AND ERGOTHERAPY.

OBJECTIVE: The aim: To assess the effect of the modified combined program of physical therapy and ergotherapy on the indicators of upper limb recovery in the patients with the left unilateral neglect. PATIENTS AND METHODS: Materials and methods: The study involved 58 patients diagnosed with the right hemisphere stroke followed by neglect syndrome. Patients were randomly divided into main group (MG) and control group (CG) according to the ratio of 1:1. Physical therapy of CG patients included proprioceptive neuromuscular facilitation (PNF), balance training, ergotherapeutic intervention, and exercises improving fine motor skills. Specially developed intervention program of MG patients took into account patient's individual capabilities and needs. It included PNF, balance training and upright posture correction, constraint-induced movement therapy, dual task activities, stimulation of the affected side in daily activities, targeted therapy. The length of intervention comprised 3 months in both groups. RESULTS: Results: According to the results of the primary examination, the groups had no differences in demographic variables, clinical history (NIHSS scale, the Glasgow Coma Scale and Albert's Test) and Fugl-Meyer assessment of upper limb sensorimotor recovery. Statistical analysis of the final scores of the Fugl-Meyer scale confirmed that MG had statistical advantages in all measured items of the motor function domain, as well as in a number of proprioceptive sensitivity indicators. CONCLUSION: Conclusions: The obtained results confirm better efficacy of the modified program of physical therapy and ergotherapy, received by MG patients.