I don't feel sick: Cognitive and affective processing of self-health associations using the Implicit Association Test.

Measuring implicit associations of self-concept with health or illness attributes may offer valuable insight into the mechanisms entailing the perception of one's own health, as explicit measures of self-reported health are usually influenced by social desirability or response bias. In this study, healthy participants performed a modified version of the implicit association test (IAT) investigating implicit associations between the self and either health or illness related representations. Behaviorally, implicit associations dominated for self-health pairing, and their strength was inversely correlated with depressive traits. Neurally, concomitant EEG recording showed significant modulations of the P1, LPP, and N4 components evoked by such pairings, suggesting a facilitation of sensory responses to self-related stimuli and differential emotional processes engaged to integrate health versus illness information into self-related representations. These data offer new clues to better understand the cognitive and affective mechanisms underlying unrealistic optimism and pathological awareness of health conditions in various clinical populations.

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.

Editorial: Advances in Understanding and Rehabilitating Unilateral Spatial Neglect.

Unilateral Spatial Neglect (USN) is a frequent, very debilitating cognitive syndrome, in which patients fail to pay attention, perceive, and represent a part of the space in the side contralateral to the brain lesion [...].

[Recovery of unilateral spatial neglect after stroke over the time]. / Récupération de la négligence post-AVC dans le temps.

Unilateral spatial neglect (USN) can have severe functional consequences for patients. Many rehabilitation tools have been proposed in the literature, but only a few well-controlled systematic studies are available. Also, there is no consensus on the effectiveness of these rehabilitation techniques. Yet, left USN is one of the most common neuropsychological symptoms after right hemispheric stroke. This article reviews the main tools available to clinicians, their limitations, and prospects for the development of new rehabilitation options.

La négligence spatiale unilatérale (NSU) est un déficit qui peut avoir de lourdes conséquences fonctionnelles pour les patients qui en sont atteints. De nombreux outils ont été proposés dans la littérature mais peu d'études systématiques bien contrôlées sont disponibles. Aussi, il n'existe pas de consensus dans la littérature à propos de l'efficacité de la rééducation. Pourtant, la NSU gauche est un des symptômes les plus fréquents après un AVC de l'hémisphère droit. Cet article fait le point sur les principaux outils à disposition des cliniciens, leurs limites et les perspectives de développement de nouvelles alternatives de rééducation.

An immersive virtual reality system for ecological assessment of peripersonal and extrapersonal unilateral spatial neglect.

BACKGROUND: Unilateral spatial neglect (USN) is a debilitating neuropsychological syndrome that often follows brain injury, in particular a stroke affecting the right hemisphere. In current clinical practice, the assessment of neglect is based on old-fashioned paper-and-pencil and behavioral tasks, and sometimes relies on the examiner's subjective judgment. Therefore, there is a need for more exhaustive, objective and ecological assessments of USN. METHODS: In this paper, we present two tasks in immersive virtual reality to assess peripersonal and extrapersonal USN. The tasks are designed with several levels of difficulty to increase sensitivity of the assessment. We then validate the feasibility of both assessments in a group of healthy adult participants. RESULTS: We report data from a study with a group of neurologically unimpaired participants (N = 39). The results yield positive feedback on comfort, usability and design of the tasks. We propose new objective scores based on participant's performance captured by head gaze and hand position information, including, for instance, time of exploration, moving time towards left/right and time-to-reach, which could be used for the evaluation of the attentional spatial bias with neurological patients. Together with the number of omissions, the new proposed parameters can result in lateralized index ratios as a measure of asymmetry in space exploration. CONCLUSIONS: We presented two innovative assessments for USN based on immersive virtual reality, evaluating the far and the near space, using ecological tasks in multimodal, realistic environments. The proposed protocols and objective scores can help distinguish neurological patients with and without USN.

Neglecting the bottom space: an object-based disorder? A two-case observational study.

Altitudinal neglect is an atypical form of spatial neglect where brain-damaged patients neglect the lower, or sometimes the upper, part of the space. Our understanding of this phenomena is limited, with unknown occurrence across different reference frames, such as distance (peripersonal vs. extrapersonal) and system of reference (egocentric vs. allocentric). Two patients with acute bilateral (P1) or right hemispheric (P2) stroke, with signs of bottom altitudinal neglect, underwent an extensive evaluation of neglect within 10 days post-stroke. Assessments involved altitudinal neglect and unilateral spatial neglect (USN) in peripersonal space, exploring egocentric and allocentric signs and in extrapersonal space. Compared to a control group of 15 healthy age-matched subjects, patients showed allocentric and egocentric left USN in peripersonal space, and mostly allocentric signs of altitudinal neglect. No signs of neglect were evidenced in extrapersonal space. Altitudinal neglect could thus present as an allocentric form of spatial neglect, suggesting that allocentric representations may not only affect the deployment of attentional resources along horizontal dimensions but also operate along vertical dimensions. Future studies should deepen our understanding of altitudinal neglect, eventually leading to further unravel spatial processes that control attention, their corresponding brain mechanisms, and implications for patients' rehabilitation and functional outcome.

A novel computerized assessment of manual spatial exploration in unilateral spatial neglect.

Unilateral spatial neglect is a neuropsychological syndrome commonly observed after stroke and defined by the inability to attend or respond to contralesional stimuli. Typically, symptoms are assessed using clinical tests that rely upon visual/perceptual abilities. However, neglect may affect high-level representations controlling attention in other modalities as well. Here we developed a novel manual exploration test using a touch screen computer to quantify spatial search behaviour without visual input. Twelve chronic stroke patients with left neglect and 27 patients without neglect (based on clinical tests) completed our task. Four of the 12 "neglect" patients exhibited clear signs of neglect on our task as compared to "non-neglect" patients and healthy controls, and six other patients (from both groups) also demonstrated signs of neglect compared to healthy controls only. While some patients made asymmetrical responses on only one task, generally, patients with the strongest neglect performed poorly on multiple tasks. This suggests that representations associated with different modalities may be affected separately, but that severe forms of neglect are more likely related to damage in a common underlying representation. Our manual exploration task is easy to administer and can be added to standard neglect screenings to better measure symptom severity.

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.

Sensory contribution to vocal emotion deficit in patients with cerebellar stroke.

In recent years, there has been increasing evidence of cerebellar involvement in emotion processing. Difficulties in the recognition of emotion from voices (i.e., emotional prosody) have been observed following cerebellar stroke. However, the interplay between sensory and higher-order cognitive dysfunction in these deficits, as well as possible hemispheric specialization for emotional prosody processing, has yet to be elucidated. We investigated the emotional prosody recognition performances of patients with right versus left cerebellar lesions, as well as of matched controls, entering the acoustic features of the stimuli in our statistical model. We also explored the cerebellar lesion-behavior relationship, using voxel-based lesion-symptom mapping. Results revealed impairment of vocal emotion recognition in both patient subgroups, particularly for neutral or negative prosody, with a higher number of misattributions in patients with right-hemispheric stroke. Voxel-based lesion-symptom mapping showed that some emotional misattributions correlated with lesions in the right Lobules VIIb and VIII and right Crus I and II. Furthermore, a significant proportion of the variance in this misattribution was explained by acoustic features such as pitch, loudness, and spectral aspects. These results point to bilateral posterior cerebellar involvement in both the sensory and cognitive processing of emotions.

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.

Disownership of body parts as revealed by a visual scale evaluation. An observational study.

The disownership of body parts, that most frequently occurs on the left side of the body, contralateral to right-hemispheric lesions, is an infrequent disorder, as usually assessed by interviews asking for dichotomic "yes/no" responses. This observational study in right-brain-damaged stroke patients investigated the efficacy of a continuous Visual Analog Scale (VAS) to detect body disownership after right brain damage, compared to dichotomic questions. Thirty-two right-handed right-brain-damaged stroke patients were given a Standardized Interview (SI), asking "Whose hand/arm/leg is this?", followed by a VAS (asking patients to mark on a vertical line their agreement with the statement that a body part belonged to them). The neural correlates of this disorder and measures of extra-personal and personal spatial neglect were also assessed. Control data were recorded from 18 neurologically unimpaired right-handed participants. During the interview, no patient showed disownership of body parts. Conversely, on the VAS eight out of 32 (25%) patients' scores, but none of the controls' scores, indicated a judgement of disownership for left body parts, with a left-right difference larger than that of control participants. VAS-detected disownership was not systematically associated with extra-personal and personal unilateral spatial neglect. Lesion sites associated with disownership of left body parts included the caudate nucleus and the anterior part of the internal capsule. To conclude, the VAS task, compared to the interview, is a novel tool to detect disownership of left body parts in right brain-damaged patients. A revised classification of body-ownership disorders is proposed. The present variant, assessed and detected by the VAS task, is termed Covert disownership and distinguished from the Overt disownership assessed by a SI.

A home-based prism adaptation training for neglect patients.

Spatial neglect is a debilitating disorder frequently observed after damage to the right cerebral hemisphere. Previous investigations have revealed that prism adaptation (PA) therapy can lead to improvements in neglect-related symptoms. In the typical PA protocol patients repeatedly point toward a visual target while wearing prism goggles. A few years ago, a novel PA procedure, involving a variety of more "ecological" visuo-motor activities during adaptation, less repetitive than a sequence of pointings, was introduced by our research group, and shown to be able to improve neglect-related symptoms to the same extent as the standard pointing task. The ecological procedure was easy to administer and pleasant for the patients. In all previous studies, patients were treated by specialized personnel during hospitalization. In the current study, we investigated the effectiveness of the ecological PA method when performed in a home-based setting, with the help of caregivers and family members. Seven right-brain-damaged patients with chronic left spatial neglect underwent a two-week ecological PA treatment, extended, for two extra weeks, in 6 patients, who were available for this additional rehabilitation session. As a control treatment, patients performed the same activities while wearing neutral goggles, before the PA procedure. Two weeks of ecological PA training proved to be able to significantly improve performance in neuropsychological tests (BIT, Cancellation tasks), a neurological scale (NIH), and functional abilities (CBS), when compared to both the baseline and the neutral control treatment, with improvements being maintained over 6 months. The ecological home-based PA training is effective in alleviating signs of spatial neglect. Importantly, this training is affordable, pleasant, and feasible to be performed in the comfort of the patient's home. Easily extendable to larger patient populations and prolonged periods, this method has a real potential to benefit the quality of life of brain-damaged patients with left spatial neglect.

Rightward exogenous attentional shifts impair perceptual memory of spatial locations in patients with left unilateral spatial neglect.

Spatial remapping implies the updating and maintaining of the spatial position of objects in successive visual images across time, despite their displacement on the retina due to eye movements. In the parietal cortex, the representation of spatial locations appears to be partly centered on gaze direction, and thus modulated by current eye-gaze position. It has been suggested that short-term memory for spatial locations across delays might be impaired in right brain-injured patients with left spatial neglect, but more so after rightward than leftward gaze shifts - an asymmetry attributed to a loss of spatial representations normally transferred from left to right hemisphere during remapping. Because several studies point to a strong link between attentional and oculomotor circuits in the brain, we hypothesized that similar remapping effects might result from attentional displacements without overt eye movements. We tested this hypothesis in right-brain damaged patients with and without left neglect in a visuo-spatial memory task. As predicted, neglect patients showed a selective deficit in location memory following an exogenous attentional shift caused by a brief flash in the periphery of their right (but not left) visual field. We conclude that an attentional displacement without eye movements is sufficient to remap spatial representations across hemifields, and that this process is impaired in neglect patients when a location has to be transferred to the neglected/left side relative to current gaze or attention focus. More generally, these results support the notion of neural overlap between oculomotor and attentional mechanisms, and confirm a role for impaired remapping in the neglect syndrome, wherein spatial representations of contralesional locations may fail to be maintained during active attentional behavior.

Exploring prism exposure after hemispheric damage: Reduced aftereffects following left-sided lesions.

Prism adaptation is a well-known method used to investigate brain plasticity, and a promising technique for the rehabilitation of unilateral spatial neglect (USN). Only little evidence about the mechanisms of prism adaptation (PA) in patients with left-brain damage is on record, and about putative differences of PA, and the aftereffects (AEs), between patients with left and right brain damage. In the present study, PA and the AEs were assessed in 30 brain-damaged patients, 20 with right-sided lesions (10 with and 10 without USN), and 10 with left-sided lesions without USN, as well as in a control group of 24 age-matched participants. All patients underwent adaptation to lenses shifting the field of vision towards the side of the lesion, followed by two measures for detecting AEs: the proprioceptive (P) and the visuo-proprioceptive (VP) straight-ahead tasks. To investigate the temporal course of AEs in the different groups, the two measures were recorded immediately and 10 min after PA. Before PA, and at the end of the 10-min delayed evaluation, two tasks to assess USN (target cancellation and drawing) were also administered. All patients adapted to prisms. However, left-brain-damaged (LBD) patients presented with reduced AEs, as compared with right-brain-damaged (RBD) patients with USN. Moreover, while both controls and LBD patients adapting to left-shifting prisms had reduced VP AEs in the delayed condition, AEs were not different from zero (i.e., no AEs) in LBD patients. Finally, in the delayed condition USN patients showed an improvement in the drawing, but not in the cancellation, tasks. These results suggest that adaptation to leftward shifting lenses is associated with larger decay of VP AEs, and a role of the left hemisphere in maintaining these AEs after PA. These findings can be of relevance for the clinical application of this technique in neurological populations.

Heartbeat-enhanced immersive virtual reality to treat complex regional pain syndrome.

OBJECTIVES: To develop and test a new immersive digital technology for complex regional pain syndrome (CRPS) that combines principles from mirror therapy and immersive virtual reality and the latest research from multisensory body processing. METHODS: In this crossover double-blind study, 24 patients with CRPS and 24 age- and sex-matched healthy controls were immersed in a virtual environment and shown a virtual depiction of their affected limb that was flashing in synchrony (or in asynchrony in the control condition) with their own online detected heartbeat (heartbeat-enhanced virtual reality [HEVR]). The primary outcome measures for pain reduction were subjective pain ratings, force strength, and heart rate variability (HRV). RESULTS: HEVR reduced pain ratings, improved motor limb function, and modulated a physiologic pain marker (HRV). These significant improvements were reliable and highly selective, absent in control HEVR conditions, not observed in healthy controls, and obtained without the application of tactile stimulation (or movement) of the painful limb, using a readily available biological signal (the heartbeat) that is most often not consciously perceived (thus preventing placebo effects). CONCLUSIONS: Next to these specific and well-controlled analgesic effects, immersive HEVR allows the application of prolonged and repeated doses of digital therapy, enables the automatized integration with existing pain treatments, and avoids application of painful bodily cues while minimizing the active involvement of the patient and therapist. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that HEVR reduces pain and increases force strength in patients with CRPS.

Bodily self-consciousness and its disorders.

Research in clinical and human neuroscience indicates that important brain mechanisms of self-consciousness are based on the integration of multisensory bodily signals (i.e., bodily self-consciousness: BSC), including signals coming from outside our body (i.e., exteroceptive signals, such as tactile, auditory, and visual information) and the inside of our body (i.e., interoceptive signals). In this chapter, we discuss selected behavioral and neuroimaging studies about how multisensory integration generates and modulates BSC in humans, with particular relevance to parietal mechanisms. We then review the neurology of disorders of BSC after acquired brain damage or dysfunction, ranging from body attentional disorders to delusional and illusory deficits about the patient's own body, associated with a breakdown of the link between the body and the self.

Insula mediates heartbeat related effects on visual consciousness.

Interoceptive signals, such as the heartbeat, are processed in a network of brain regions including the insular cortex. Recent studies have shown that such signals modulate perceptual and cognitive processing, and that they impact visual awareness. For example, visual stimuli presented synchronously to the heartbeat take longer to enter visual awareness than the same stimuli presented asynchronously to the heartbeat, and this is reflected in anterior insular activation. This finding demonstrated a link between the processing of interoceptive and exteroceptive signals as well as visual awareness in the insular cortex. The advantage for visual stimuli which are asynchronous to the heartbeat to enter visual consciousness may indicate a role for the anterior insula in the suppression of the sensory consequences of cardiac signals. Here, we present data from the detailed investigation of two patients with insular lesions (as well as four patients with non-insular lesions and healthy age matched controls) indicating that a lesion of the anterior insular cortex, but not of other regions, abolished this cardio-visual suppression effect. The present data provide causal evidence for the role of the anterior insula in the integration of internal interoceptive and external sensory signals for visual awareness.

Illusory hand ownership in a patient with personal neglect for the upper limb, but no somatoparaphenia.

The symptoms of patients with left personal neglect are characterized by inattention towards contralesional (left) body parts while at the same time explicitly ascertaining ownership for the neglected hemibody. It is currently unknown if personal neglect is associated with more subtle or implicit disturbances of own body perception and body ownership as measured with the rubber hand illusion. In this study, we report data from a patient with a right hemispheric lesion and personal neglect, without associated somatosensory deficits. We administered to the patient (and to 12 age-matched controls) the rubber hand illusion paradigm to the right and left hands, to elicit illusory ownership for a fake hand, before and after recovery from personal neglect for the left arm. In a first session, run when the patient showed personal neglect affecting the left arm, he experienced a significantly enhanced subjective illusion of embodiment for the left fake hand as compared to the right hand (as assessed through a standard questionnaire). After recovery from personal neglect for the left arm (second session), the results of the left and right rubber hand illusion experiments were comparable, with no modulation of hand ownership. We argue that personal neglect may consist not only in an inattentional disorder, but also in a deficit of multisensory body representation characterized by a high sensitivity to experimental manipulations of subjective aspects of body ownership.

Virtual reality improves embodiment and neuropathic pain caused by spinal cord injury.

OBJECTIVE: To investigate changes in body ownership and chronic neuropathic pain in patients with spinal cord injury (SCI) using multisensory own body illusions and virtual reality (VR). METHODS: Twenty patients with SCI with paraplegia and 20 healthy control participants (HC) participated in 2 factorial, randomized, repeated-measures design studies. In the virtual leg illusion (VLI), we applied asynchronous or synchronous visuotactile stimulation to the participant's back (either immediately above the lesion level or at the shoulder) and to the virtual legs as seen on a VR head-mounted display. We tested the effect of the VLI on the sense of leg ownership (questionnaires) and on perceived neuropathic pain (visual analogue scale pain ratings). We compared illusory leg ownership with illusory global body ownership (induced in the full body illusion [FBI]), by applying asynchronous or synchronous visuotactile stimulation to the participant's back and the back of a virtual body as seen on a head-mounted display. RESULTS: Our data show that patients with SCI are less sensitive to multisensory stimulations inducing illusory leg ownership (as compared to HC) and that leg ownership decreased with time since SCI. In contrast, we found no differences between groups in global body ownership as tested in the FBI. VLI and FBI were both associated with mild analgesia that was only during the VLI specific for synchronous visuotactile stimulation and the lower back position. CONCLUSIONS: The present findings show that VR exposure using multisensory stimulation differently affected leg vs body ownership, and is associated with mild analgesia with potential for SCI neurorehabilitation protocols.

Interoceptive signals impact visual processing: Cardiac modulation of visual body perception.

Multisensory perception research has largely focused on exteroceptive signals, but recent evidence has revealed the integration of interoceptive signals with exteroceptive information. Such research revealed that heartbeat signals affect sensory (e.g., visual) processing: however, it is unknown how they impact the perception of body images. Here we linked our participants' heartbeat to visual stimuli and investigated the spatio-temporal brain dynamics of cardio-visual stimulation on the processing of human body images. We recorded visual evoked potentials with 64-channel electroencephalography while showing a body or a scrambled-body (control) that appeared at the frequency of the on-line recorded participants' heartbeat or not (not-synchronous, control). Extending earlier studies, we found a body-independent effect, with cardiac signals enhancing visual processing during two time periods (77-130 ms and 145-246 ms). Within the second (later) time-window we detected a second effect characterised by enhanced activity in parietal, temporo-occipital, inferior frontal, and right basal ganglia-insula regions, but only when non-scrambled body images were flashed synchronously with the heartbeat (208-224 ms). In conclusion, our results highlight the role of interoceptive information for the visual processing of human body pictures within a network integrating cardio-visual signals of relevance for perceptual and cognitive aspects of visual body processing.