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.

Markers of limbic system damage following SARS-CoV-2 infection.

Alterations of the limbic system may be present in the chronic phase of SARS-CoV-2 infection. Our aim was to study the long-term impact of this disease on limbic system-related behaviour and its associated brain functional connectivity, according to the severity of respiratory symptoms in the acute phase. To this end, we investigated the multimodal emotion recognition abilities of 105 patients from the Geneva COVID-COG Cohort 223 days on average after SARS-CoV-2 infection (diagnosed between March 2020 and May 2021), dividing them into three groups (severe, moderate or mild) according to respiratory symptom severity in the acute phase. We used multiple regressions and partial least squares correlation analyses to investigate the relationships between emotion recognition, olfaction, cognition, neuropsychiatric symptoms and functional brain networks. Six to 9 months following SARS-CoV-2 infection, moderate patients exhibited poorer recognition abilities than mild patients for expressions of fear (P = 0.03 corrected), as did severe patients for disgust (P = 0.04 corrected) and irritation (P < 0.01 corrected). In the whole cohort, these performances were associated with decreased episodic memory and anosmia, but not with depressive symptoms, anxiety or post-traumatic stress disorder. Neuroimaging revealed a positive contribution of functional connectivity, notably between the cerebellum and the default mode, somatosensory motor and salience/ventral attention networks. These results highlight the long-term consequences of SARS-Cov-2 infection on the limbic system at both the behavioural and neuroimaging levels.

[Long-term cognitive impairment in autoimmune encephalitis]. / Troubles cognitifs séquellaires dans le cadre d'une encéphalite auto-immune.

Autoimmune encephalitis (AE) are a group of rare inflammatory diseases of the central nervous system that can manifest as subacute cognitive impairment. Despite the presence of diagnostic criteria, it can be challenging to identify this disease in certain age groups. In this article, we present the two main clinical phenotypes of AE associated with cognitive impairment, the factors contributing to the long-term cognitive outcome and its management after the acute phase.

Les encéphalites auto-immunes (EAI) sont un groupe de maladies inflammatoires rares du système nerveux central (CNS) pouvant se manifester par une atteinte cognitive d'apparition subaiguë. Malgré la présence des critères diagnostiques, leur identification peut représenter un défi dans certains groupes d'âge. Dans cet article, nous exposons les deux principaux phénotypes cliniques d'EAI s'associant à des troubles cognitifs, les facteurs contribuant au pronostic cognitif et la prise en charge après la phase aiguë.

Dysfunctional cerebello-cerebral network associated with vocal emotion recognition impairments.

Vocal emotion recognition, a key determinant to analyzing a speaker's emotional state, is known to be impaired following cerebellar dysfunctions. Nevertheless, its possible functional integration in the large-scale brain network subtending emotional prosody recognition has yet to be explored. We administered an emotional prosody recognition task to patients with right versus left-hemispheric cerebellar lesions and a group of matched controls. We explored the lesional correlates of vocal emotion recognition in patients through a network-based analysis by combining a neuropsychological approach for lesion mapping with normative brain connectome data. Results revealed impaired recognition among patients for neutral or negative prosody, with poorer sadness recognition performances by patients with right cerebellar lesion. Network-based lesion-symptom mapping revealed that sadness recognition performances were linked to a network connecting the cerebellum with left frontal, temporal, and parietal cortices. Moreover, when focusing solely on a subgroup of patients with right cerebellar damage, sadness recognition performances were associated with a more restricted network connecting the cerebellum to the left parietal lobe. As the left hemisphere is known to be crucial for the processing of short segmental information, these results suggest that a corticocerebellar network operates on a fine temporal scale during vocal emotion decoding.

Explicit and Implicit Emotion Processing in the Cerebellum: A Meta-analysis and Systematic Review.

The cerebellum's role in affective processing is increasingly recognized in the literature, but remains poorly understood, despite abundant clinical evidence for affective disruptions following cerebellar damage. To improve the characterization of emotion processing and investigate how attention allocation impacts this processing, we conducted a meta-analysis on task activation foci using GingerALE software. Eighty human neuroimaging studies of emotion including 2761 participants identified through Web of Science and ProQuest databases were analyzed collectively and then divided into two categories based on the focus of attention during the task: explicit or implicit emotion processing. The results examining the explicit emotion tasks identified clusters within the posterior cerebellar hemispheres (bilateral lobule VI/Crus I/II), the vermis, and left lobule V/VI that were likely to be activated across studies, while implicit tasks activated clusters including bilateral lobules VI/Crus I/II, right Crus II/lobule VIII, anterior lobule VI, and lobules I-IV/V. A direct comparison between these categories revealed five overlapping clusters in right lobules VI/Crus I/Crus II and left lobules V/VI/Crus I of the cerebellum common to both the explicit and implicit task contrasts. There were also three clusters activated significantly more for explicit emotion tasks compared to implicit tasks (right lobule VI, left lobule VI/vermis), and one cluster activated more for implicit than explicit tasks (left lobule VI). These findings support previous studies indicating affective processing activates both the lateral hemispheric lobules and the vermis of the cerebellum. The common and distinct activation of posterior cerebellar regions by tasks with explicit and implicit attention demonstrates the supportive role of this structure in recognizing, appraising, and reacting to emotional stimuli.

Principles of Brain and Emotion: Beyond the Cortico-Centric Bias.

Affective neurosciences have largely contributed to the elaboration of theoretical and neuroanatomical models through research conducted in non-primate animals and human beings. However, for methodological and historical reasons, knowledge has developed by focusing mainly on the cerebral cortex, resulting in a lack of investigations of the functional aspects of subcortical structures such as the cerebellum and the basal ganglia. The close anatomical connections revealed between these two structures, as well as their reciprocal connections with the cerebral cortex, lead to a vertically organized model of the brain. Both the cerebellum and the basal ganglia are involved in the different components required during an emotional episode. Their respective specificity in the analysis of temporal patterns contributes to the optimal processing of emotional signals such as those that can be conveyed by the voice (emotional prosody). Internal temporally structured event representation, built from the salient modulation extractions performed by the cerebellum, is used by the basal ganglia to recruit and synchronize the activity of the cortical and subcortical structures required for the relevant processes.

Crossed functional specialization between the basal ganglia and cerebellum during vocal emotion decoding: Insights from stroke and Parkinson's disease.

There is growing evidence that both the basal ganglia and the cerebellum play functional roles in emotion processing, either directly or indirectly, through their connections with cortical and subcortical structures. However, the lateralization of this complex processing in emotion recognition remains unclear. To address this issue, we investigated emotional prosody recognition in individuals with Parkinson's disease (model of basal ganglia dysfunction) or cerebellar stroke patients, as well as in matched healthy controls (n = 24 in each group). We analysed performances according to the lateralization of the predominant brain degeneration/lesion. Results showed that a right (basal ganglia and cerebellar) hemispheric dysfunction was likely to induce greater deficits than a left one. Moreover, deficits following left hemispheric dysfunction were only observed in cerebellar stroke patients, and these deficits resembled those observed after degeneration of the right basal ganglia. Additional analyses taking disease duration / time since stroke into consideration revealed a worsening of performances in patients with predominantly right-sided lesions over time. These results point to the differential, but complementary, involvement of the cerebellum and basal ganglia in emotional prosody decoding, with a probable hemispheric specialization according to the level of cognitive integration.

Functional connectivity underlying cognitive and psychiatric symptoms in post-COVID-19 syndrome: is anosognosia a key determinant?

Lack of awareness of cognitive impairment (i.e. anosognosia) could be a key factor for distinguishing between neuropsychological post-COVID-19 condition phenotypes. In this context, the 2-fold aim of the present study was to (i) establish the prevalence of anosognosia for memory impairment, according to the severity of the infection in the acute phase and (ii) determine whether anosognosic patients with post-COVID syndrome have a different cognitive and psychiatric profile from nosognosic patients, with associated differences in brain functional connectivity. A battery of neuropsychological, psychiatric, olfactory, dyspnoea, fatigue and quality-of-life tests was administered 227.07 ± 42.69 days post-SARS-CoV-2 infection to 102 patients (mean age: 56.35 years, 65 men, no history of neurological, psychiatric, neuro-oncological or neurodevelopmental disorder prior to infection) who had experienced either a mild (not hospitalized; n = 45), moderate (conventional hospitalization; n = 34) or severe (hospitalization with intensive care unit stay and mechanical ventilation; n = 23) presentation in the acute phase. Patients were first divided into two groups according to the presence or absence of anosognosia for memory deficits (26 anosognosic patients and 76 nosognosic patients). Of these, 49 patients underwent an MRI. Structural images were visually analysed, and statistical intergroup analyses were then performed on behavioural and functional connectivity measures. Only 15.6% of patients who presented mild disease displayed anosognosia for memory dysfunction, compared with 32.4% of patients with moderate presentation and 34.8% of patients with severe disease. Compared with nosognosic patients, those with anosognosia for memory dysfunction performed significantly more poorly on objective cognitive and olfactory measures. By contrast, they gave significantly more positive subjective assessments of their quality of life, psychiatric status and fatigue. Interestingly, the proportion of patients exhibiting a lack of consciousness of olfactory deficits was significantly higher in the anosognosic group. Functional connectivity analyses revealed a significant decrease in connectivity, in the anosognosic group as compared with the nosognosic group, within and between the following networks: the left default mode, the bilateral somatosensory motor, the right executive control, the right salient ventral attention and the bilateral dorsal attention networks, as well as the right Lobules IV and V of the cerebellum. Lack of awareness of cognitive disorders and, to a broader extent, impairment of the self-monitoring brain system, may be a key factor for distinguishing between the clinical phenotypes of post-COVID syndrome with neuropsychological deficits.

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.

Sensitivity to Emotion Intensity and Recognition of Emotion Expression in Neurotypical Children.

This study assessed two components of face emotion processing: emotion recognition and sensitivity to intensity of emotion expressions and their relation in children age 4 to 12 (N = 216). Results indicated a slower development in the accurate decoding of low intensity expressions compared to high intensity. Between age 4 and 12, children discriminated high intensity expressions better than low ones. The intensity of expression had a stronger impact on overall face expression recognition. High intensity happiness was better recognized than low intensity up to age 11, while children 4 to 12 had difficulties discriminating between high and low intensity sadness. Our results suggest that sensitivity to low intensity expressions acts as a complementary mediator between age and emotion expression recognition, while this was not the case for the recognition of high intensity expressions. These results could help in the development of specific interventions for populations presenting socio-cognitive and emotion difficulties.

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.

Relation between processing facial identity and emotional expression in typically developing school-age children and those with Down syndrome.

The main purposes of this research were to examine the relation between the processing of face identity and emotion expressions and then discern the significance of emotional expressions using Bruce et al. tasks. Two studies were conducted. Study 1 examined 225 typically developing (TD) children age 4 to 12. Results suggested that early recognition of complete faces and interpretation of emotional expression might depend on local processing abilities, while the recognition of masked faces and emotion expression matching seemed to share configural processing. Study 2 compared 22 children with Down syndrome (DS) to two TD groups matched on mental age (MA group) and chronological age (CA group). Results showed that children with DS processed the identity of complete faces (local processing) similarly to the MA and CA groups. In contrast, their performances for masked faces (configural processing) indicated a developmental delay as they were only comparable to the MA group. Children with DS were also able to identify the emotion expressions according to labels as well as the two control groups, while they had more difficulties on the matching condition. Furthermore, specific difficulties in processing the surprise expression were observed, rather than general difficulties in encoding emotion expressions. Finally, their performances on emotion matching tasks seemed to be supported by local information processing, which might explain their lower scores compared to CA controls that mainly used configural information. These results could aid in the development of targeted interventions for DS to improve their social skills.

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.

Cerebellar contribution to vocal emotion decoding: Insights from stroke and neuroimaging.

While the role of the cerebellum in emotion recognition has been explored with facial expressions, its involvement in the auditory modality (i.e., emotional prosody) remains to be demonstrated. The present study investigated the recognition of emotional prosody in 15 patients with chronic cerebellar ischaemic stroke and 15 matched healthy controls, using a validated task, as well as clinical, motor, neuropsychological, and psychiatric assessments. We explored the cerebellar lesion-behaviour relationship using voxel-based lesion-symptom mapping. Results showed a significant difference between the stroke and healthy control groups, with patients giving erroneous ratings on the Surprise scale when they listened to fearful stimuli. Moreover, voxel-based lesion-symptom mapping revealed that these emotional misattributions correlated with lesions in right Lobules VIIb, VIIIa,b and IX. Interestingly, the posterior cerebellum has previously been found to be involved in affective processing, and Lobule VIIb in rhythm discrimination. These results point to the cerebellum's functional involvement in vocal emotion decoding.