An immersive virtual reality tool for assessing left and right unilateral spatial neglect.

The reported rate of the occurrence of unilateral spatial neglect (USN) is highly variable likely due to the lack of validity and low sensitivity of classical tools used to assess it. Virtual reality (VR) assessments try to overcome these limitations by proposing immersive and complex environments. Nevertheless, existing VR-based tasks are mostly focused only on near space and lack analysis of psychometric properties and/or clinical validation. The present study evaluates the clinical validity and sensitivity of a new immersive VR-based task to assess USN in the extra-personal space and examines the neuronal correlates of deficits of far space exploration. The task was administrated to two groups of patients with right (N = 28) or left (N = 11) hemispheric brain lesions, also undergoing classical paper-and-pencil assessment, as well as a group of healthy participants. Our VR-based task detected 44% of neglect cases compared to 31% by paper-and-pencil tests in the total sample. Importantly, 30% of the patients (with right or left brain lesions) with no clear sign of USN on the paper-and-pencil tests performed outside the normal range in the VR-based task. Voxel lesion-symptom mapping revealed that deficits detected in VR were associated with lesions in insular and temporal cortex, part of the neural network involved in spatial processing. These results show that our immersive VR-based task is efficient and sensitive in detecting mild to strong manifestations of USN affecting the extra-personal space, which may be undetected using standard tools.

Real-time fMRI and EEG neurofeedback: A perspective on applications for the rehabilitation of spatial neglect.

Spatial neglect is a neuropsychological syndrome characterized by a failure to orient, perceive, and act toward the contralesional side of the space after brain injury. Neglect is one of the most frequent and disabling neuropsychological syndromes following right-hemisphere damage, often persisting in the chronic phase and responsible for a poor functional outcome at hospital discharge. Different rehabilitation approaches have been proposed over the past 60 years, with a variable degree of effectiveness. In this point-of-view article, we describe a new rehabilitation technique for spatial neglect that directly targets brain activity and pathological physiological processes: namely, neurofeedback (NFB) with real-time brain imaging methodologies. In recent proof-of-principle studies, we have demonstrated the potential of this rehabilitation technique. Using real-time functional MRI (rt-fMRI) NFB in chronic neglect, we demonstrated that patients are able to upregulate their right visual cortex activity, a response that is otherwise reduced due to losses in top-down attentional signals. Using real-time electroencephalography NFB in patients with acute or chronic condition, we showed successful regulation with partial restoration of brain rhythm dynamics over the damaged hemisphere. Both approaches were followed by mild, but encouraging, improvement in neglect symptoms. NFB techniques, by training endogenous top-down modulation of attentional control on sensory processing, might induce sustained changes at both the neural and behavioral levels, while being non-invasive and safe. However, more properly powered clinical studies with control groups and longer follow-up are needed to fully establish the effectiveness of the techniques, identify the most suitable candidates, and determine how the techniques can be optimized or combined in the context of rehabilitation.

Deficits in cognitive and affective theory of mind relate to dissociated lesion patterns in prefrontal and insular cortex.

Neuroimaging studies suggest that understanding emotions in others engages brain regions partially common to those associated with more general cognitive Theory-of-Mind (ToM) functions allowing us to infer people's beliefs or intentions. However, neuropsychological studies on brain-damaged patients reveal dissociations between the ability to understand others' emotions and ToM. This discrepancy might underlie the fact that neuropsychological investigations often correlate behavioural impairments only to the lesion site, without considering the impact that the insult might have on other interconnected brain structures. Here we took a network-based approach, and investigated whether deficits in understanding people's emotional and cognitive states relate to damage to similar or differential structures. By combining information from 40 unilateral stroke damaged patients, with normative connectome data from 92 neurotypical individuals, we estimated lesion-induced dysfunctions across the whole brain, and modeled them in relation to patients' behavior. We found a striking dissociation between networks centered in the insular and prefrontal cortex, whose dysfunctions led to selective impairments in understanding emotions and beliefs respectively. Instead, no evidence was observed for neural structures shared between the two conditions. Overall, our data provide novel evidence of segregation between brain networks subserving social inferential abilities.

An exploratory cohort study of sensory extinction in acute stroke: prevalence, risk factors, and time course.

Most studies on sensory extinction have focused on selected patients with subacute and chronic right hemisphere lesions. In studies conducted on acute stroke patients, risk factors and time course were not evaluated. Our aim was to determine the prevalence, risk factors, and time course of sensory extinction in the acute stroke setting. Consecutive patients with acute stroke were tested for tactile, visual, auditory, and auditory-tactile cross-modal extinction, as well as for peripersonal visuospatial neglect (PVN). Tests were repeated at 2, 7, 15, 30, and 90 days after initial examination. A multivariable logistic regression analysis was performed to test the association between sensory extinction and demographic and clinical risk factors. Seventy-three patients (38.4% women) were recruited: 64 with ischemic stroke and nine with haemorrhagic stroke. Mean age was 62.3 years (95% CI 58.8-65.7), mean NIHSS score was 1.6 (95% CI 1.2-2.1), and mean time to first examination was 4.1 days (95% CI 3.5-4.8). The overall prevalence of all subtypes of sensory extinction was 13.7% (95% CI 6.8-23.8). Tactile extinction was the most frequent subtype with a prevalence of 8.2% (95% CI 3.1-17.0). No extinction was found beyond 15 days after the first examination. After adjustment for age, sex, lesion side, type of stroke, time to first examination and stroke severity, a lesion volume ≥2 mL (adjusted OR = 38.88, p = 0.04), and presence of PVN (adjusted OR = 24.27, p = 0.04) were independent predictors of sensory extinction. The insula, the putamen, and the pallidum were the brain regions most frequently involved in patients with sensory extinction. Extinction is a rare and transient phenomenon in patients with minor stroke. The presence of PVN and lesion volume ≥2 mL are independent predictors of sensory extinction in acute stroke.

Incidence, Risk Factors and Anatomy of Peripersonal Visuospatial Neglect in Acute Stroke.

AIM: The study aims to describe the epidemiology and the neural correlates of peripersonal visuospatial neglect (PVN) in patients admitted to the Geneva Stroke Unit for an acute stroke or a transient ischemic attack (TIA). METHODS: Eligible subjects were tested for PVN using both the Ota's discriminative cancellation task and a line bisection task. Brain lesions were identified on diffusion-weighted imaging. A multivariate analysis was performed to identify risk factors of PVN. RESULTS: Ninety-eight consecutive patients (40.8% females) were recruited: 64 cases of ischemic stroke, 9 cases of hemorrhagic stroke and 25 cases of TIAs. The mean age was 61.9 ± 2.86 years. The incidence of PVN was 23.5% (95% CI 15.5-33.1) and was not significantly different between patients with right and left hemisphere stroke. There were 5 cases of ipsilesional neglect. There was no association between PVN and age, sex, stroke severity, handedness, lesion type, lesion volume and time to first examination. Lesions of temporal and parietal lobes were the most frequent in patients with PVN. CONCLUSION: PVN has a low incidence in the acute stroke settings and there is no particular predictor of its presence. It is most often associated with temporo-parietal lesions.

Anatomical and psychometric relationships of behavioral neglect in daily living.

Spatial neglect has been related to both cortical (predominantly at the temporal-parietal junction) and subcortical (predominantly of the superior longitudinal fasciculus) lesions. The objectives of this observational study were to specify the anatomical relationships of behavioral neglect in activities of daily living (N-ADLs), and the anatomical and psychometric relationships of N-ADLs on one hand and components of neglect (peripersonal neglect and personal neglect) and anosognosia on the other. Forty five patients were analyzed for behavioral difficulties in daily living (on the Catherine Bergego scale) and the main components of neglect (using conventional clinical assessments) during the first months post right hemisphere stroke. Voxel-based lesion-symptom mapping was used to identify brain areas within which lesions explained the severity of bias in each assessment (non-parametric permutation test; p<0.01, one tailed). N-ADLs was associated with lesions centered on the posterior part of the superior temporal gyrus and extending to the temporo-parietal junction, temporo-occipital junction and subcortical white matter (including the superior longitudinal fasciculus). Peripersonal neglect resulted from extended cortical lesions centered on the superior temporal gyrus and the inferior parietal gyrus, with subcortical extension. Personal neglect resulted predominantly from lesions centered on the somatosensory cortex and at a lesser degree on the superior temporal sulcus. Anosognosia resulted from lesions of the posterior inferior temporal gyrus and superior temporal gyrus. In anatomic terms, N-ADLs was strongly related to peripersonal neglect, and those relationships were also shown by the psychometric analysis. In conclusions, superior temporal gyrus and superior longitudinal fasciculus lesions have a pivotal role in N-ADLs. N-ADLs is principally related (anatomically and psychometrically) to peripersonal neglect, and at a lesser degree to anosognosia and personal neglect.

Mislocalization of tactile stimuli applied to the trunk in spatial neglect.

INTRODUCTION: In patients with spatial neglect, body perception and representation are impaired - especially the projection of the anterior body midline in anterior space (the subjective "straight ahead"). However, data on more lateral body parts and the posterior body surface are scarce. We explored deviations of the perception of different body points located to the left or right of the midline and on the anterior and posterior body surfaces, and their lesion correlates in right hemisphere stroke patients. METHODS: Nine patients with neglect (diagnosed with paper and pencil and behavioural tests) were compared with six non-neglect patients and 13 healthy controls. The subjects had to use a mannequin to designate the body location that had been stimulated by a blunt pencil tip. Four horizontally arranged series of locations were traced on the anterior and posterior body surfaces at shoulder and navel levels. Each horizontal series comprised five equidistant test points, from left to right and corresponded to eleven labelled points on the mannequin. Patient errors were confronted to their anatomic lesions (MRI). RESULTS: We found a significant (p ≤ .05) rightward deviation of the left-side points and midpoint and a significant leftward deviation of the right-most point in neglect patients. Non-neglect patients and control subjects designated all the test points accurately. The body side (anterior or posterior) and the line (shoulder or navel) did not influence performance. Controls showed a definite reduction in variability for the midline points, which disappeared in neglect patients who showed a severe global increase of this variability. Errors depended on lesions centred on the intraparietal sulcus. CONCLUSIONS: These observations were compatible with a complex bias in body perception-representation extending to various lateral body points, with a left to right gradient. The right parietal cortex likely participates in processing such information.

Influence of spatial neglect, hemianopia and hemispace on the subjective vertical.

The perception of the vertical is frequently shifted to the contralesional side in patients with hemispheric lesions, and this is amplified by spatial neglect. However, we do not know the specific influence of hemianopia and space of perception on this phenomenon. Here, we analyzed the respective influences of spatial neglect, hemianopia and hemispace on the subjective vertical in patients with right hemispheric stroke. Twelve neglect patients with and 5 without hemianopia were compared to 3 non-neglect patients with and 13 without hemianopia. They had to match a luminous rod to the vertical, either in the mid-sagittal plane or in the right or the left hemispace. Patients showed a counter-clockwise deviation, and this was exaggerated by both neglect and hemianopia. In patients with neglect, the error was greater in the left hemispace. In conclusion, neglect and hemianopia had additive effects on the contralesional bias of the subjective vertical.

Time since stroke influences the impact of hemianopia and spatial neglect on visual-spatial tasks.

OBJECTIVE: Spatial neglect results in an ipsilesional misorientation of attention in visual-spatial tasks. Hemianopia impairs visual perception but its influence on visual-spatial tasks is subject to debate. Here, we investigated the influence of the time since stroke on the respective impacts of hemianopia and spatial neglect. METHOD: A total of 29 patients with a right hemisphere stroke were included in the study. Nine had severe neglect and hemianopia, six had severe neglect only, four showed hemianopia with little or no neglect after infarction of the posterior cerebral artery, and 10 had neither neglect nor hemianopia. We investigated the spatial bias in the subjective straight ahead (SSA) test and in clinical tests (bell cancellation, line bisection, and scene copy). Each task was administered twice (at S1 and S2: 41.4 and 67.2 days [on average] after the stroke, respectively). RESULTS: At S1, spatial neglect and hemianopia had an additive influence on SSA test performance (rightward translation). Similar rightward biases were observed in the clinical tests. At S2, the influence of hemianopia had disappeared, whereas that of neglect was still present. Furthermore, loss of bias in the SSA test correlated with the improvements seen in most of the clinical tests. CONCLUSIONS: In patients with recent stroke, hemianopia aggravates the visual-spatial bias when neglect is present or may lead to visual-neglect-like behavior when classically defined neglect is absent. However, the influence of hemianopia disappears relatively quickly over time, due to compensation.

The pusher syndrome reverses the orienting bias caused by spatial neglect.

Spatial neglect can be accompanied by a pusher syndrome (PS) which is characterized by a postural deviation towards the contralesional side. In this study, the representation of the body orientation in the horizontal plane was evaluated in neglect patients with and without PS. The participants had to align a luminous rod with the straight ahead direction, a method allowing the measure of both horizontal components of subjective straight ahead, i.e. lateral shift and yaw rotation. Eighteen patients with a lesion of the right hemisphere were compared with ten healthy participants. Patients had neglect and PS (P+N+; n=3), neglect only (P-N+; n=10), or neither neglect nor PS (P-N-; n=5). P+N+ patients showed a significant leftward shift contrasting with the rightward shift of P-N+. No shift occurred in patients without neglect and controls. No significant yaw error was recorded in any groups. The original result of this study was an inversion of the sign of the bias in neglect patients with PS. This could be related to the postural disorders characterizing this syndrome, and which are opposite to those usually observed in spatial neglect. Thus, these data suggest a link between disorders of spatial representations and disorders of posture.

Ineffectiveness of prism adaptation on spatial neglect signs.

BACKGROUND AND PURPOSE: To evaluate the effect of prism adaptation (PA) on spatial neglect signs. METHODS: Ten patients (hemianopia in 6) and 8 control subjects were included. Tasks were reading single words, nonwords, and a text, bell cancellation, line bisection, and scene drawing, before and after adaptation, with either deviating or neutral prisms. RESULTS: Errors were more frequent in patients but without any specific effect of PA. We found partial improvement at the late sessions, independent of prisms. CONCLUSIONS: We did not confirm the efficacy of PA on spatial neglect.

Subjective visual vertical in pitch and roll in right hemispheric stroke.

BACKGROUND AND PURPOSE: Patients with right hemispheric stroke usually present an anticlockwise deviation of the subjective visual vertical (SVV) in the frontal (roll) plane. However, the occurrence of a similar disorder in the sagittal (pitch) plane has never been assessed. We investigated the subjective visual vertical in both planes in those patients. METHODS: Eight patients, 4 with spatial neglect (N+) and 4 without neglect (N-), were compared with 4 healthy participants (C). They sat facing a luminous bar adjustable in rotation, either in the roll or in the pitch plane, and had to orient it in a vertical position, in the dark. RESULTS: Compared with N- (-0.1 degrees) and C (+1.1 degrees) groups, N+ patients presented with a significant backward deviation (-4.5 degrees) of the SVV in pitch. In accordance with other studies, they also showed a significant anticlockwise deviation (-8.8 degrees) of the SVV in roll, as compared with N- (-1.9 degrees) and C (+0.4 degrees) subjects. This was associated with an opposite trunk deviation in both planes. CONCLUSIONS: While confirming the anticlockwise deviation already reported in the frontal plane, we showed for the first time to our knowledge a backward deviation of the SVV in neglect patients, which has to be put in relation with their balance disorders.

Straight-ahead pointing correlates with long-line bisection in neglect patients.

The spatial bias of neglect patients has been assumed to result from the alteration of a body-centred representation which underlies actions within personal and extra-personal spaces. This deficit seems to correspond to the ipsilesional deviation of the subjective straight-ahead (SSA), often described in neglect patients. However, several recent studies have failed to show significant correlations between the SSA deviation and performance in standard visuo-spatial tests of neglect. Since methodological choices could explain these negative results, the present study re-investigated the question. SSA, assessed by manual pointing, was anchored by instructions to a precise median body part. A body-centred line bisection task was also carried out, during the same session and in similar experimental conditions. Sixteen right brain-damaged patients with (n = 8) or without (n = 8) neglect, and 8 control subjects free of any neurological problem were included. Taken as a group, the neglect group stood out from the others in both tasks. Moreover, in neglect patients only, SSA position significantly correlated with bisection error for long lines, even if dissociations between SSA shift and bisection error were found in two cases. Results are discussed with regard to the nature of the tasks proposed in the different studies and to methodological aspects that could at least partly explain the aforementioned failures.