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.

Joint impact on attention, alertness and inhibition of lesions at a frontal white matter crossroad.

In everyday life, information from different cognitive domains-such as visuospatial attention, alertness and inhibition-needs to be integrated between different brain regions. Early models suggested that completely segregated brain networks control these three cognitive domains. However, more recent accounts, mainly based on neuroimaging data in healthy participants, indicate that different tasks lead to specific patterns of activation within the same, higher-order and 'multiple-demand' network. If so, then a lesion to critical substrates of this common network should determine a concomitant impairment in all three cognitive domains. The aim of the present study was to critically investigate this hypothesis, i.e. to identify focal stroke lesions within the network that can concomitantly affect visuospatial attention, alertness and inhibition. We studied an unselected sample of 60 first-ever right-hemispheric, subacute stroke patients using a data-driven, bottom-up approach. Patients performed 12 standardized neuropsychological and oculomotor tests, four per cognitive domain. A principal component analysis revealed a strong relationship between all three cognitive domains: 10 of 12 tests loaded on a first, common component. Analysis of the neuroanatomical lesion correlates using different approaches (i.e. voxel-based and tractwise lesion-symptom mapping, disconnectome maps) provided convergent evidence on the association between severe impairment of this common component and lesions at the intersection of superior longitudinal fasciculus II and III, frontal aslant tract and, to a lesser extent, the putamen and inferior fronto-occipital fasciculus. Moreover, patients with a lesion involving this region were significantly more impaired in daily living cognition, which provides an ecological validation of our results. A probabilistic functional atlas of the multiple-demand network was performed to confirm the potential relationship between patients' lesion substrates and observed cognitive impairments as a function of the multiple-demand network connectivity disruption. These findings show, for the first time, that a lesion to a specific white matter crossroad can determine a concurrent breakdown in all three considered cognitive domains. Our results support the multiple-demand network model, proposing that different cognitive operations depend on specific collaborators and their interaction, within the same underlying neural network. Our findings also extend this hypothesis by showing (i) the contribution of superior longitudinal fasciculus and frontal aslant tract to the multiple-demand network; and (ii) a critical neuroanatomical intersection, crossed by a vast amount of long-range white matter tracts, many of which interconnect cortical areas of the multiple-demand network. The vulnerability of this crossroad to stroke has specific cognitive and clinical consequences; this has the potential to influence future rehabilitative approaches.

The Flow State Scale for Rehabilitation Tasks: A New Flow Experience Questionnaire for Stroke Patients.

IMPORTANCE: Flow can be described as a subjective state that people report when they fully engage in an activity and experience pleasure, satisfaction, and enjoyment. Flow experiences are measured to determine the extent to which patients engage in therapy activities. Several flow questionnaires are used in neurorehabilitation. However, none have been validated for patients with (sub)acute stroke. OBJECTIVE: To develop and validate a new flow questionnaire for patients with (sub)acute stroke. DESIGN: Single-center prospective cohort study. SETTING: Neurorehabilitation unit of the Neurocenter of the Luzerner Kantonsspital in Lucerne, Switzerland. PARTICIPANTS: Fifty patients with (sub)acute stroke. OUTCOMES AND MEASURES: Development of the Flow State Scale for Rehabilitation Tasks (FSSRT) and determination of the psychometric properties of the FSSRT (internal consistency, test-retest reliability, structural and construct validity) in (sub)acute stroke patients. RESULTS: The FSSRT showed good internal consistency and excellent test-retest reliability. Composed of four components-concentration, pleasure, movement control, and absorption-the FSSRT correlated significantly negatively with the Hospital Anxiety and Depression Scale, indicating good divergent validity. CONCLUSIONS AND RELEVANCE: The FSSRT is a reliable and valid questionnaire measuring flow experience in patients with (sub)acute stroke. This questionnaire can be easily used in occupational therapy as well as in physical therapy and gives therapists important information about the flow experience of patients during therapy to adjust the therapy accordingly. Plain-Language Summary: Measuring flow experience, or the extent to which patients engage in therapy activities, in the context of occupational therapy and physical therapy is a new approach. This study confirmed that the Flow State Scale for Rehabilitation Tasks questionnaire is reliable and valid for measuring the flow experience of patients after (sub)acute stroke. Occupational therapists and physical therapists can use the FSSRT to optimally adjust the therapy program and increase patient engagement during therapy.

A case study of left visual neglect after right pontine lesion: pathophysiological evidence for the infratentorial involvement in human visual attention.

Hemispatial neglect, the inability to attend to the contralesional side of space, is the most common disturbance of visuospatial attention. Both hemispatial neglect and visuospatial attention are typically associated with extended cortical networks. Nevertheless, recent accounts challenge this so-called corticocentric view and postulate the participation of structures well beyond the telencephalic cortex, in particular advocating the role of the brainstem. However, to the best of our knowledge, hemispatial neglect after a brainstem lesion has not yet been described. We describe, for the first time in a human, the occurrence and remission of contralesional visual hemispatial neglect after a focal lesion in the right pons. Hemispatial neglect was assessed by means of video-oculography during free visual exploration, a very sensitive and established method, and its remission was followed up until 3 wk after stroke. Moreover, by means of a lesion-deficit approach complemented by imaging, we identify a pathophysiological mechanism involving the disconnection of cortico-ponto-cerebellar and/or tecto-cerebellar-tectal pathways passing through the pons. Our findings offer, for the first time in a human, causal, lesion-based support for recent seminal accounts postulating the role of infratentorial structures participating in the activity of cerebral cortical attentional networks mediating attentional processes.NEW & NOTEWORTHY Visuospatial attention and its most common disturbance, hemispatial neglect, are typically associated with extended cortical networks. However, recent accounts challenge this corticocentric view and advocate the role of infratentorial structures. We describe, for the first time in a human, the occurrence of contralesional visual hemispatial neglect after a focal lesion in the right pons. We provide causal, lesion-based evidence for a pathophysiological mechanism involving the disconnection of cortico-ponto-cerebellar and/or tecto-cerebellar-tectal pathways passing through the pons.

Feasibility of a combined intermittent theta-burst stimulation and video game-based dexterity training in Parkinson's disease.

BACKGROUND: Persons with Parkinson's disease (PD) often exhibit difficulties with dexterity during the performance of activities of daily living (ADL), inter alia due to dysfunctional supplementary motor area (SMA). Combined intermittent theta-burst stimulation (iTBS) over the SMA followed by video game-based training (VBT) may therefore improve dexterity related ADL. The VBT may induce high flow levels related to high performance during the training. The aim of this study is to evaluate the feasibility of a combined iTBS-VBT intervention in persons with PD. METHODS: A total of nine persons with PD (mean age 63.3 ± 8.76 years) with self-reported difficulties with dexterity related ADL were included in this pilot iTBS-VBT study. All participants received either iTBS or sham stimulation over the SMA followed by a 45-min VBT, three times a week for a total of three weeks. Feasibility was measured by means of the adherence rate and the system usability (System Usability Scale). Moreover, flow was measured after the last VBT session. RESULTS: Adherence rate was excellent with 100%. High system usability scores (i.e., mean 80%, range 55-97.5) and a significant Spearman's correlation with the Flow State Scale (r = .762, p = .017) further point to the high feasibility of the VBT. Neither demographic variables nor difficulties in dexterity related ADL affected the usability of the VBT. CONCLUSION: This study demonstrates the high feasibility of a combined iTBS-VBT intervention. Moreover, the level of self-reported usability was related to flow experience. Whether this kind of combined iTBS-VBT intervention improves dexterity will be evaluated in a randomized controlled trial. Trial registration clincaltrials.gov NCT04699149, date of registration 1. June 2021.

Getting into a "Flow" state: a systematic review of flow experience in neurological diseases.

BACKGROUND: Flow is a subjective psychological state that people report when they are fully involved in an activity to the point of forgetting time and their surrounding except the activity itself. Being in flow during physical/cognitive rehabilitation may have a considerable impact on functional outcome, especially when patients with neurological diseases engage in exercises using robotics, virtual/augmented reality, or serious games on tablets/computer. When developing new therapy games, measuring flow experience can indicate whether the game motivates one to train. The purpose of this study was to identify and systematically review current literature on flow experience assessed in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson's disease. Additionally, we critically appraised, compared and summarized the measurement properties of self-reported flow questionnaires used in neurorehabilitation setting. DESIGN: A systematic review using PRISMA and COSMIN guidelines. METHODS: MEDLINE Ovid, EMBASE Ovid, CINAHL EBSCO, SCOPUS were searched. Inclusion criteria were (1) peer-reviewed studies that (2) focused on the investigation of flow experience in (3) patients with neurological diseases (i.e., stroke, traumatic brain injury, multiple sclerosis and/or Parkinson's disease). A qualitative data synthesis was performed to present the measurement properties of the used flow questionnaires. RESULTS: Ten studies out of 911 records met the inclusion criteria. Seven studies measured flow in the context of serious games in patients with stroke, traumatic brain injury, multiple sclerosis and Parkinson's disease. Three studies assessed flow in other activities than gaming (song-writing intervention and activities of daily living). Six different flow questionnaires were used, all of which were originally validated in healthy people. None of the studies presented psychometric data in their respective research population. CONCLUSION: The present review indicates that flow experience is increasingly measured in the physical/cognitive rehabilitation setting in patients with neurological diseases. However, psychometric properties of used flow questionnaires are lacking. For exergame developers working in the field of physical/cognitive rehabilitation in patients with neurological diseases, a valid flow questionnaire can help to further optimize the content of the games so that optimal engagement can occur during the gameplay. Whether flow experiences can ultimately have positive effects on physical/cognitive parameters needs further study.

Theta burst stimulation in neglect after stroke: functional outcome and response variability origins.

Spatial neglect is a strong and negative predictor of general functional outcome after stroke, and its therapy remains a challenge. Whereas inhibitory non-invasive brain stimulation over the contralesional, intact hemisphere has generally been shown to ameliorate neglect on a group level, a conspicuous variability of the effects at the individual level is typically observed. We aimed to assess the characteristics and determinants of the effects of inhibitory non-invasive brain stimulation in neglect, identifying which patients would respond to this therapeutic approach and which not. To this end, we prospectively included 60 patients with a subacute right-hemispheric stroke. In 30 patients with spatial neglect, continuous theta burst stimulation (cTBS) was applied over the left posterior parietal cortex in a randomized clinical trial, either in eight or 16 trains, or as sham stimulation. Thirty patients without neglect served as a control group. Neglect severity was measured with a neuropsychological test battery and the Catherine Bergego Scale, at admission to and at discharge from inpatient neurorehabilitation, as well as at 3 months follow-up. General functional outcome was assessed by means of the Functional Independence Measure and the Lucerne ICF-based Multidisciplinary Observation Scale. The impact of clinical and demographic factors was evaluated, and the influence of lesion location and extension was assessed by means of voxel-based lesion-symptom mapping. On a group level, both cTBS protocols (i.e. eight and 16 trains) significantly reduced neglect severity in both the Catherine Bergego Scale and the neuropsychological tests, at discharge and 3 months later. Furthermore, cTBS significantly improved general functional outcome. On an individual level, hierarchical cluster and voxel-based lesion-symptom mapping analyses revealed that the variability in the responses to cTBS is determined by the integrity of interhemispheric connections within the corpus callosum, in particular parieto-parietal connections. In cTBS responders, in whom neglect and general functional outcome were significantly improved, the corpus callosum was intact, whereas this was not the case in cTBS non-responders. Moreover, analyses based on the proportional recovery rule and the Maugeri predictive stroke recovery model showed that the recovery of neglect and of the activities of daily living was accelerated only in cTBS responders. Furthermore, the level of activities of daily living recovery of these neglect patients was brought close to the one of right-hemispheric control patients without neglect. Hence, in neglect patients with intact interhemispheric connectivity, cTBS over the contralesional posterior parietal cortex significantly improves and accelerates neglect recovery and, associated with it, general functional outcome.

Re-fixation and perseveration patterns in neglect patients during free visual exploration.

The literature suggests that neglect patients not only show impairments in directing attention toward the left, contralesional space, but also present with perseverative behavior. Moreover, previous studies described re-fixations during visual search tasks, and interpreted this finding as an impairment of spatial working memory. The aim of the present study was to study re-fixations and perseverations (i.e., recurrent re-fixations to same locations) during free visual exploration, a task with high ecological validity. We hypothesized that: (1) neglect patient would perform re-fixations more frequently than healthy controls within the right hemispace; and, (2) the re-fixation behavior of neglect patients would be characterized by perseverative fixations. To test these hypotheses, we assessed 22 neglect patients and 23 healthy controls, measuring their eye movements during free exploration of naturalistic pictures. The results showed that neglect patients tend to re-fixate locations within the ipsilesional hemispace when they freely explore naturalistic pictures. Importantly, the saliency of discrete locations within the pictures has a stronger influence on fixation behavior within the contralesional than within the ipsilesional hemispace in neglect patients. Finally, the results indicated that, for re-fixations, saliency plays a more important role within the contralesional than the ipsilesional hemispace. Moreover, we found evidence that re-fixation behavior of neglect patients is characterized by frequent recurrent re-fixations back to the same spatial locations which may be interpreted as perseverations. Hence, with the present study, we could better elucidate the mechanism leading to re-fixations and perseverative behavior during free visual exploration in neglect patients.

Comprehensive ADL Outcome Measurement after Stroke: Rasch Validation of the Lucerne ICF-Based Multidisciplinary Observation Scale (LIMOS).

OBJECTIVE: To establish Rasch validation of the Lucerne International Classification of Functioning, Disability and Health (ICF)-based Multidisciplinary Observation Scale (LIMOS) in stroke. LIMOS measures the level of assistance in daily life activities related to motor function, communication, cognition, and domestic life. Rasch Measurement Theory (RMT) transforms an ordinal scale into an interval scale and thus the Rasch-based LIMOS scale captures a more accurate improvement of functional outcomes via Rasch-transformed scores. DESIGN: Cross-sectional study design. SETTING: Neurorehabilitation center, Luzerne, Switzerland. PARTICIPANTS: We recruited participants with stroke (N=407; age=63.2±16.0y; n=157 women) through consecutive sampling. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants were assessed with LIMOS at admission and discharge of rehabilitation. We used RMT to evaluate overall model fit, response dependency, floor and ceiling effect, reliability, and differential item functioning (DIF) for sex, age, type, and time of stroke on the 4 LIMOS subscales using the Rasch Unidimensional Measurement Model (RUMM) 2030 program. RESULTS: The Rasch-based LIMOS subscales fit the Rasch model after reducing and rescoring items: motor (from 20 to 18 items), communication (5 items), cognition (from 15 to 13 items), and domestic life (5 items). There was no floor or ceiling effect. Some artificial DIF was identified. Scoring at discharge was dependent on the scoring responses at admission, which means that without applying a correction factor to the discharge scores, there was an underestimation of change in scores between admission and discharge, ranging from 0.24 to 0.97 logits (10.79%-49.24%) on the different subscales. CONCLUSIONS: The Rasch-based LIMOS scale is recommended to measure functional outcome in people with acute or chronic stages of ischemic or hemorrhagic stroke.

The Influence of Alertness on the Spatial Deployment of Visual Attention is Mediated by the Excitability of the Posterior Parietal Cortices.

With a reduced level of alertness, healthy individuals typically show a rightward shift when deploying visual attention in space. The impact of alertness on the neural networks governing visuospatial attention is, however, poorly understood. By using a transcranial magnetic stimulation twin-coil approach, the present study aimed at investigating the effects of an alertness manipulation on the excitability of the left and the right posterior parietal cortices (PPCs), crucial nodes of the visuospatial attentional network. Participants' visuospatial attentional deployment was assessed with a free visual exploration task and concurrent eye tracking. Their alertness level was manipulated through the time of the day, that is, by testing chronotypically defined evening types both during their circadian on- and off-peak times. The results revealed an increased excitability of the left compared with the right PPC during low alertness. On the horizontal dimension, these results were accompanied by a significant rightward shift in the center and a bilateral narrowing in the periphery of the visual exploration field, as well as a central upward shift on the vertical dimension. The findings show that the manipulation of non-spatial attentional aspects (i.e., alertness) can affect visuospatial attentional deployment and modulate the excitability of areas subtending spatial attentional control.

Spatial Neglect Predicts Upper Limb Use in the Activities of Daily Living.

BACKGROUND AND PURPOSE: Motor tests performed at stroke onset have been shown to predict the recovery of upper limb motor impairment. Less is known about upper limb recovery at the level of functional activity or of participation and how spatial neglect may influence the integration of the upper limb in the activities of daily living (ADL). Our objective was to investigate whether the initial severity of spatial neglect may predict upper limb use in ADL. METHODS: Eighty-two patients with a right-hemispheric stroke (RHS) were prospectively included in the study. They were assessed twice in the acute/subacute and in the subacute/chronic phases (mean time interval of 45 days) after stroke. The Catherine Bergego Scale (CBS) was used to quantify the influence of spatial neglect on the ADL. Contralesional upper limb use in the ADL was evaluated with the Lucerne international classification of function, disability and health-based Multidisciplinary Observation Scale. Hand strength was measured using the Jamar, dexterity with the Nine Hole Peg test, and tactile perception using the stereognosis subtest of the Nottingham Sensory Assessment. Cognitive functions were assessed with the Montreal Cognitive Assessment. RESULTS: Regression analyses revealed that spatial neglect is an independent and a significant predictor of upper limb outcome. A CBS score of ≤5 at the time of admission to neurorehabilitation care was highly predictive for good upper limb use in the ADL 45 days later. CONCLUSIONS: This study demonstrates that spatial neglect severity, as observed in the ADL, is a significant and an independent predictor of upper limb outcome. Neglect therapy is thus needed to further improve contralesional upper limb use in the ADL in RHS patients.

Eye Gaze Behavior at Turn Transition: How Aphasic Patients Process Speakers' Turns during Video Observation.

The human turn-taking system regulates the smooth and precise exchange of speaking turns during face-to-face interaction. Recent studies investigated the processing of ongoing turns during conversation by measuring the eye movements of noninvolved observers. The findings suggest that humans shift their gaze in anticipation to the next speaker before the start of the next turn. Moreover, there is evidence that the ability to timely detect turn transitions mainly relies on the lexico-syntactic content provided by the conversation. Consequently, patients with aphasia, who often experience deficits in both semantic and syntactic processing, might encounter difficulties to detect and timely shift their gaze at turn transitions. To test this assumption, we presented video vignettes of natural conversations to aphasic patients and healthy controls, while their eye movements were measured. The frequency and latency of event-related gaze shifts, with respect to the end of the current turn in the videos, were compared between the two groups. Our results suggest that, compared with healthy controls, aphasic patients have a reduced probability to shift their gaze at turn transitions but do not show significantly increased gaze shift latencies. In healthy controls, but not in aphasic patients, the probability to shift the gaze at turn transition was increased when the video content of the current turn had a higher lexico-syntactic complexity. Furthermore, the results from voxel-based lesion symptom mapping indicate that the association between lexico-syntactic complexity and gaze shift latency in aphasic patients is predicted by brain lesions located in the posterior branch of the left arcuate fasciculus. Higher lexico-syntactic processing demands seem to lead to a reduced gaze shift probability in aphasic patients. This finding may represent missed opportunities for patients to place their contributions during everyday conversation.

Theta burst stimulation over premotor cortex in Parkinson's disease: an explorative study on manual dexterity.

Dorsal pre-motor cortex (PMd) is thought to play a role in fine motor control. The aim of the present study was to investigate whether inhibitory or excitatory stimulation of PMd would have an impact on manual dexterity in Parkinson's disease (PD). Fifteen patients with PD participated in this study. High resolution structural MRI was used for neuro-navigated TBS. Participants were targeted with one train of TBS in three experimental sessions: sham stimulation over vertex, continuous TBS (cTBS) over PMd and intermittent TBS (iTBS) over PMd, respectively. Dexterity was measured by a coin rotation task (CRT), which is a valid measure to detect limb kinetic apraxia (LKA). Neither cTBS or iTBS significantly interfered with CRT. Post hoc sub-analysis in a group of PD patients (n = 5) with stronger baseline impairment, indicating LKA, revealed further deterioration of dexterous performance for the cTBS condition (p = 0.04). This sham controlled pilot study demonstrates that TBS over PMd does not significantly interfere with dexterity in PD. However, patients with dexterous impairment qualifying for LKA may be more susceptible to TBS.

Cognitive Impairment in Multiple Sclerosis: Clinical Manifestation, Neuroimaging Correlates, and Treatment.

Cognitive impairment is found in up to 70% of patients with multiple sclerosis (MS). Once thought of as a variant of subcortical dementia with a characteristic set of deficits, we now know that MS-related cognitive impairment can have many faces. This conceptual change in neuropsychology is embedded in a paradigm shift in the neuroscientific understanding of MS over the past 25 years: Partly based on modern neuroimaging techniques, the classical view of MS as an inflammatory demyelinating disease affecting the white matter of the central nervous system has been extended. In particular, many studies have shown that the MS pathology also includes neurodegeneration, and that gray matter structures such as the cerebral cortex can also show focal lesions, atrophy, or both. The authors present an updated summary of the clinical manifestation and neuroimaging correlates of cognitive impairment in MS, and discuss the relatively few treatment options available to date.

Age-dependent visual exploration during simulated day- and night driving on a motorway: a cross-sectional study.

BACKGROUND: Central and peripheral vision is needed for object detection. Previous research has shown that visual target detection is affected by age. In addition, light conditions also influence visual exploration. The aim of the study was to investigate the effects of age and different light conditions on visual exploration behavior and on driving performance during simulated driving. METHODS: A fixed-base simulator with 180 degree field of view was used to simulate a motorway route under daylight and night conditions to test 29 young subjects (25-40 years) and 27 older subjects (65-78 years). Drivers' eye fixations were analyzed and assigned to regions of interests (ROI) such as street, road signs, car ahead, environment, rear view mirror, side mirror left, side mirror right, incoming car, parked car, road repair. In addition, lane-keeping and driving speed were analyzed as a measure of driving performance. RESULTS: Older drivers had longer fixations on the task relevant ROI, but had a lower frequency of checking mirrors when compared to younger drivers. In both age groups, night driving led to a less fixations on the mirror. At the performance level, older drivers showed more variation in driving speed and lane-keeping behavior, which was especially prominent at night. In younger drivers, night driving had no impact on driving speed or lane-keeping behavior. CONCLUSIONS: Older drivers' visual exploration behavior are more fixed on the task relevant ROI, especially at night, when driving performance becomes more heterogeneous than in younger drivers.

A new method to measure higher visual functions in an immersive environment.

BACKGROUND: Higher visual functions can be defined as cognitive processes responsible for object recognition, color and shape perception, and motion detection. People with impaired higher visual functions after unilateral brain lesion are often tested with paper pencil tests, but such tests do not assess the degree of interaction between the healthy brain hemisphere and the impaired one. Hence, visual functions are not tested separately in the contralesional and ipsilesional visual hemifields. METHODS: A new measurement setup, that involves real-time comparisons of shape and size of objects, orientation of lines, speed and direction of moving patterns, in the right or left visual hemifield, has been developed. The setup was implemented in an immersive environment like a hemisphere to take into account the effects of peripheral and central vision, and eventual visual field losses. Due to the non-flat screen of the hemisphere, a distortion algorithm was needed to adapt the projected images to the surface. Several approaches were studied and, based on a comparison between projected images and original ones, the best one was used for the implementation of the test. Fifty-seven healthy volunteers were then tested in a pilot study. A Satisfaction Questionnaire was used to assess the usability of the new measurement setup. RESULTS: The results of the distortion algorithm showed a structural similarity between the warped images and the original ones higher than 97%. The results of the pilot study showed an accuracy in comparing images in the two visual hemifields of 0.18 visual degrees and 0.19 visual degrees for size and shape discrimination, respectively, 2.56° for line orientation, 0.33 visual degrees/s for speed perception and 7.41° for recognition of motion direction. The outcome of the Satisfaction Questionnaire showed a high acceptance of the battery by the participants. CONCLUSIONS: A new method to measure higher visual functions in an immersive environment was presented. The study focused on the usability of the developed battery rather than the performance at the visual tasks. A battery of five subtasks to study the perception of size, shape, orientation, speed and motion direction was developed. The test setup is now ready to be tested in neurological patients.

Comparison of uni- and multimodal motion stimulation on visual neglect: A proof-of-concept study.

Spatial neglect is characterized by the failure to attend stimuli presented in the contralesional space. Typically, the visual modality is more severely impaired than the auditory one. This dissociation offers the possibility of cross-modal interactions, whereby auditory stimuli may have beneficial effects on the visual modality. A new auditory motion stimulation method with music dynamically moving from the right to the left hemispace has recently been shown to improve visual neglect. The aim of the present study was twofold: a) to compare the effects of unimodal auditory against visual motion stimulation, i.e., smooth pursuit training, which is an established therapeutical approach in neglect therapy and b) to explore whether a combination of auditory + visual motion stimulation, i.e., multimodal motion stimulation, would be more effective than unimodal auditory or visual motion stimulation. 28 patients with left-sided neglect due to a first-ever, right-hemispheric subacute stroke were included. Patients either received auditory, visual, or multimodal motion stimulation. The between-group effect of each motion stimulation condition as well as a control group without motion stimulation was investigated by means of a one-way ANOVA with the patient's visual exploration behaviour as an outcome variable. Our results showed that unimodal auditory motion stimulation is equally effective as unimodal visual motion stimulation: both interventions significantly improved neglect compared to the control group. Multimodal motion stimulation also significantly improved neglect, however, did not show greater improvement than unimodal auditory or visual motion stimulation alone. Besides the established visual motion stimulation, this proof-of-concept study suggests that auditory motion stimulation seems to be an alternative promising therapeutic approach to improve visual attention in neglect patients. Multimodal motion stimulation does not lead to any additional therapeutic gain. In neurorehabilitation, the implementation of either auditory or visual motion stimulation seems therefore reasonable.

Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke.

Background: This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS). Methods: Consecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke. Results: A total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th-75th percentiles 67-84 years versus 70 years, 25th-75th percentiles 60-80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01-2.19, value of p 0.044). Conclusion: This study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Network mechanisms of responsiveness to continuous theta-burst stimulation.

Continuous theta-burst stimulation (cTBS) can modify behavior, but effects are inconsistent and their mechanisms insufficiently understood. As coherence in resting-state networks influences human behavior, we hypothesized that cTBS may act via modulation of neural oscillation coherence. This study used electroencephalography (EEG) to investigate whether behavioral effects of cTBS on visuospatial attention are associated with coherence changes in the attention network. In healthy human subjects, cTBS of the right posterior parietal cortex (PPC) and the right frontal eye field was compared with sham stimulation. Effects on visuospatial attention were quantified with a visual exploration task, and network effects were assessed from surface EEG with inverse solutions and source coherence analyses. Before stimulation, left visual exploration was linearly correlated with alpha-band coherence between the right temporo-parietal cortex and the rest of the brain. Posterior parietal cortex stimulation induced neglect-like visual exploration behavior in the majority, but not all, subjects. It reduced alpha-band coherence between the stimulation site and the rest of the brain but also enhanced it between the contralateral left parietal cortex and the rest of the brain. The contralateral increase correlated with the induced reduction in left visual attention. The behavioral response of individual participants to cTBS could be predicted by coherence in the right temporo-parietal junction before stimulation. Behavioral effects of cTBS therefore depend on network states before stimulation and are linearly associated with changes in network interactions. In particular, cTBS modulates an interhemispheric competition in alpha-band coherence. EEG network imaging might help to optimize therapeutic cTBS in the future.