One for all, all for one: neuro-HIV multidisciplinary platform for the assessment and management of neurocognitive complaints in people living with HIV.

BACKGROUND: With ageing, comorbidities such as neurocognitive impairment increase among people living with HIV (PLWH). However, addressing its multifactorial nature is time-consuming and logistically demanding. We developed a neuro-HIV clinic able to assess these complaints in 8 h using a multidisciplinary approach. METHODS: People living with HIV with neurocognitive complaints were referred from outpatient clinics to Lausanne University Hospital. Over 8 h participants underwent formal infectious disease, neurological, neuropsychological and psychiatric evaluations, with opt-out magnetic resonance imaging (MRI) and lumbar puncture. A multidisciplinary panel discussion was performed afterwards, with a final report weighing all findings being produced. RESULTS: Between 2011 and 2019, a total of 185 PLWH (median age 54 years) were evaluated. Of these, 37 (27%) had HIV-associated neurocognitive impairment, but they were mainly asymptomatic (24/37, 64.9%). Most participants had non-HIV-associated neurocognitive impairment (NHNCI), and depression was prevalent across all participants (102/185, 79.5%). Executive function was the principal neurocognitive domain affected among both groups (75.5% and 83.8% of participants impaired, respectively). Polyneuropathy was found in 29 (15.7%) participants. Abnormalities in MRI were found in 45/167 participants (26.9%), being more common among NHNCI (35, 77.8%), and HIV-1 RNA viral escape was detected in 16/142 participants (11.2%). Plasma HIV-RNA was detectable in 18.4% out of 185 participants. CONCLUSIONS: Cognitive complaints remain an important problem among PLWH. Individual assessment from a general practitioner or HIV specialist is not enough. Our observations show the many layers of HIV management and suggest that a multidisciplinary approach could be helpful in determining non-HIV causes of NCI. A 1-day evaluation system is beneficial for both participants and referring physicians.

Reading Covered Faces.

Covering faces with masks, due to mandatory pandemic safety regulations, we can no longer rely on the habitual daily-life information. This may be thought-provoking for healthy people, but particularly challenging for individuals with neuropsychiatric and neurodevelopmental conditions. Au fait research on reading covered faces reveals that: 1) wearing masks hampers facial affect recognition, though it leaves reliable inferring basic emotional expressions; 2) by buffering facial affect, masks lead to narrowing of emotional spectrum and dampen veridical evaluation of counterparts; 3) masks may affect perceived face attractiveness; 4) covered (either by masks or other veils) faces have a certain signal function introducing perceptual biases and prejudices; 5) reading covered faces is gender- and age-specific, being more challenging for males and more variable even in healthy aging; 6) the hampering effects of masks on social cognition occur over the globe; and 7) reading covered faces is likely to be supported by the large-scale assemblies of the neural circuits far beyond the social brain. Challenges and limitations of ongoing research and parallels to the Reading the Mind in the Eyes Test are assessed. Clarification of how masks affect face reading in the real world, where we deal with dynamic faces and have entrée to additional valuable social signals such as body language, as well as the specificity of neural networks underlying reading covered faces calls for further tailored research.

Brain circuits signaling the absence of emotion in body language.

Adaptive social behavior and mental well-being depend on not only recognizing emotional expressions but also, inferring the absence of emotion. While the neurobiology underwriting the perception of emotions is well studied, the mechanisms for detecting a lack of emotional content in social signals remain largely unknown. Here, using cutting-edge analyses of effective brain connectivity, we uncover the brain networks differentiating neutral and emotional body language. The data indicate greater activation of the right amygdala and midline cerebellar vermis to nonemotional as opposed to emotional body language. Most important, the effective connectivity between the amygdala and insula predicts people's ability to recognize the absence of emotion. These conclusions extend substantially current concepts of emotion perception by suggesting engagement of limbic effective connectivity in recognizing the lack of emotion in body language reading. Furthermore, the outcome may advance the understanding of overly emotional interpretation of social signals in depression or schizophrenia by providing the missing link between body language reading and limbic pathways. The study thus opens an avenue for multidisciplinary research on social cognition and the underlying cerebrocerebellar networks, ranging from animal models to patients with neuropsychiatric conditions.

[Cognitive exergames: cognitive-motor synergies in neurorehabilitation]. / Exergames cognitifs: les synergies cognitivo-motrices dans la neuroréhabilitation.

Research on cognitive neurorehabilitation has shown the benefits of both neuropsychological therapy and physical activity on cognitive performance. In this article, we highlight the synergies between these approaches, particularly in the context of "cognitive exergames" that are video games combining cognitive and physical exercise. Even though this area of research is rather novel, the available data suggests cognitive and physical benefits in the elderly, as well as people with brain lesions or neurodegeneration, and point towards the development of multimodal cognitive neurorehabilitation.

La recherche scientifique sur la neuroréhabilitation cognitive a démontré les avantages des prises en charge en neuropsychologie, ainsi que de l'activité physique, sur les performances cognitives. Dans cet article, nous présentons les synergies entre ces deux types d'exercice, notamment dans le contexte des « exergames cognitifs ¼, c'est-à-dire des jeux vidéo combinant tâches cognitives et entraînement physique. Bien qu'il s'agisse d'un domaine de recherche récent, les données indiquent des bénéfices cognitifs et physiques chez les personnes âgées, cérébrolésées ou atteintes de maladies neurodégénératives, et semblent prometteuses pour le développement d'une neuroréhabilitation cognitive multimodale.

Influence of periaqueductal gray on other salience network nodes predicts social sensitivity.

The intrinsic connectivity of the salience network (SN) plays an important role in social behavior, however the directional influence that individual nodes have on each other has not yet been fully determined. In this study, we used spectral dynamic causal modeling to characterize the effective connectivity patterns in the SN for 44 healthy older adults and for 44 patients with behavioral variant frontotemporal dementia (bvFTD) who have focal SN dysfunction. We examined the relationship of SN effective connections with individuals' socioemotional sensitivity, using the revised self-monitoring scale, an informant-facing questionnaire that assesses sensitivity to expressive behavior. Overall, average SN effective connectivity for bvFTD patients differs from healthy older adults in cortical, hypothalamic, and thalamic nodes. For the majority of healthy individuals, strong periaqueductal gray (PAG) output to right cortical (p < .01) and thalamic nodes (p < .05), but not PAG output to other central pattern generators contributed to sensitivity to socioemotional cues. This effect did not exist for the majority of bvFTD patients; PAG output toward other SN nodes was weak, and this lack of output negatively influenced socioemotional sensitivity. Instead, input to the left vAI from other SN nodes supported patients' sensitivity to others' socioemotional behavior (p < .05), though less effectively. The key role of PAG output to cortical and thalamic nodes for socioemotional sensitivity suggests that its core functions, that is, generating autonomic changes in the body, and moreover representing the internal state of the body, is necessary for optimal social responsiveness, and its breakdown is central to bvFTD patients' social behavior deficits.

Structural and effective brain connectivity underlying biological motion detection.

The perception of actions underwrites a wide range of socio-cognitive functions. Previous neuroimaging and lesion studies identified several components of the brain network for visual biological motion (BM) processing, but interactions among these components and their relationship to behavior remain little understood. Here, using a recently developed integrative analysis of structural and effective connectivity derived from high angular resolution diffusion imaging (HARDI) and functional magnetic resonance imaging (fMRI), we assess the cerebro-cerebellar network for processing of camouflaged point-light BM. Dynamic causal modeling (DCM) informed by probabilistic tractography indicates that the right superior temporal sulcus (STS) serves as an integrator within the temporal module. However, the STS does not appear to be a "gatekeeper" in the functional integration of the occipito-temporal and frontal regions: The fusiform gyrus (FFG) and middle temporal cortex (MTC) are also connected to the right inferior frontal gyrus (IFG) and insula, indicating multiple parallel pathways. BM-specific loops of effective connectivity are seen between the left lateral cerebellar lobule Crus I and right STS, as well as between the left Crus I and right insula. The prevalence of a structural pathway between the FFG and STS is associated with better BM detection. Moreover, a canonical variate analysis shows that the visual sensitivity to BM is best predicted by BM-specific effective connectivity from the FFG to STS and from the IFG, insula, and STS to the early visual cortex. Overall, the study characterizes the architecture of the cerebro-cerebellar network for BM processing and offers prospects for assessing the social brain.

Serious video games and virtual reality for prevention and neurorehabilitation of cognitive decline because of aging and neurodegeneration.

PURPOSE OF REVIEW: Cognitive decline because of aging and neurodegeneration has become increasingly prevalent. This calls for the implementation of efficacious, motivating, standardized and widely available cognitive interventions for the elderly. In this context, serious video games and virtual reality may represent promising approaches. Here, we review recent research on their potential for cognitive prevention and neurorehabilitation of age-related cognitive decline and mild cognitive impairment (MCI). RECENT FINDINGS: The majority of currently available data in this evolving domain lacks the methodological quality to draw reliable conclusions on the potential of novel technology for cognitive training in older people. However, single well designed randomized controlled trials have reported promising effects of cognitive interventions involving serious video games and virtual reality. The cognitive benefits of exergames promoting physical exercise with and without combined cognitive training remain unclear. SUMMARY: The immersion into stimulating and motivating environments along with training content based on neuroscientific and neuropsychological models may represent a significant advance as compared with conventional computerized cognitive training. Additional research with sound methodology including sufficient sample sizes, active control groups and meaningful outcome measures of everyday function is needed to elucidate the potential of serious video games and virtual reality in multifactorial neurorehabilitation of cognitive decline in aging and neurodegeneration.

Consensus Paper: Cerebellum and Social Cognition.

The traditional view on the cerebellum is that it controls motor behavior. Although recent work has revealed that the cerebellum supports also nonmotor functions such as cognition and affect, only during the last 5 years it has become evident that the cerebellum also plays an important social role. This role is evident in social cognition based on interpreting goal-directed actions through the movements of individuals (social "mirroring") which is very close to its original role in motor learning, as well as in social understanding of other individuals' mental state, such as their intentions, beliefs, past behaviors, future aspirations, and personality traits (social "mentalizing"). Most of this mentalizing role is supported by the posterior cerebellum (e.g., Crus I and II). The most dominant hypothesis is that the cerebellum assists in learning and understanding social action sequences, and so facilitates social cognition by supporting optimal predictions about imminent or future social interaction and cooperation. This consensus paper brings together experts from different fields to discuss recent efforts in understanding the role of the cerebellum in social cognition, and the understanding of social behaviors and mental states by others, its effect on clinical impairments such as cerebellar ataxia and autism spectrum disorder, and how the cerebellum can become a potential target for noninvasive brain stimulation as a therapeutic intervention. We report on the most recent empirical findings and techniques for understanding and manipulating cerebellar circuits in humans. Cerebellar circuitry appears now as a key structure to elucidate social interactions.

[Neurology]. / Neurologie.

In 2015, cerebral stimulation becomes increasingly established in the treatment of pharmacoresistant epilepsy. Efficacy of endovascular treatment has been demonstrated for acute ischemic stroke. Deep brain stimulation at low frequency improves dysphagia and freezing of gait in Parkinson patients. Bimagrumab seems to increase muscular volume and force in patients with inclusion body myositis. In cluster-type headache, a transcutaneous vagal nerve stimulator is efficient in stopping acute attacks and also reducing their frequency. Initial steps have been undertaken towards modulating memory by stimulation of the proximal fornix. Teriflunomide is the first oral immunomodulatory drug for which efficacy has been shown in preventing conversion from clinical isolated syndrome to multiple sclerosis.

Consensus paper: the role of the cerebellum in perceptual processes.

Various lines of evidence accumulated over the past 30 years indicate that the cerebellum, long recognized as essential for motor control, also has considerable influence on perceptual processes. In this paper, we bring together experts from psychology and neuroscience, with the aim of providing a succinct but comprehensive overview of key findings related to the involvement of the cerebellum in sensory perception. The contributions cover such topics as anatomical and functional connectivity, evolutionary and comparative perspectives, visual and auditory processing, biological motion perception, nociception, self-motion, timing, predictive processing, and perceptual sequencing. While no single explanation has yet emerged concerning the role of the cerebellum in perceptual processes, this consensus paper summarizes the impressive empirical evidence on this problem and highlights diversities as well as commonalities between existing hypotheses. In addition to work with healthy individuals and patients with cerebellar disorders, it is also apparent that several neurological conditions in which perceptual disturbances occur, including autism and schizophrenia, are associated with cerebellar pathology. A better understanding of the involvement of the cerebellum in perceptual processes will thus likely be important for identifying and treating perceptual deficits that may at present go unnoticed and untreated. This paper provides a useful framework for further debate and empirical investigations into the influence of the cerebellum on sensory perception.

Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia.

Nervous system involvement in Lyme disease often mimics other conditions and thus represents a diagnostic challenge, especially in an emergency department setting. We report a case of a female teenager presenting with sudden-onset aphasia and transient right-sided faciobrachial hemiplegia, along with headache and agitation. Ischemia, vasculitis, or another structural lesion was excluded by brain imaging. Toxicologic evaluation results were negative. Cerebral perfusion computed tomography and electroencephalography showed left parietotemporal brain dysfunction. Lumbar puncture result, although atypical, suggested bacterial infection and intravenous ceftriaxone was initiated. Finally, microbiological cerebrospinal fluid analysis revealed Lyme neuroborreliosis, showing specific intrathecal antibody production and high level of C-X-C motif chemokine 13. The patient rapidly recovered. To our knowledge, this report for the first time illustrates that acute-onset language and motor symptoms may be directly related to Lyme neuroborreliosis. Neuroborreliosis may mimic other acute neurologic events such as stroke and should be taken into diagnostic consideration even in the absence of classic symptoms and evolution.

Structural loop between the cerebellum and the superior temporal sulcus: evidence from diffusion tensor imaging.

The cerebellum is believed to play an essential role in a variety of motor and cognitive functions through reciprocal interaction with the cerebral cortex. Recent findings suggest that cerebellar involvement in the network specialized for visual body motion processing may be mediated through interaction with the right superior temporal sulcus (STS). Yet, the underlying pattern of structural connectivity between the STS and the cerebellum remains unidentified. In the present work, diffusion tensor imaging analysis on seeds derived from functional magnetic resonance imaging during a task on point-light biological motion perception uncovers a structural pathway between the right posterior STS and the left cerebellar lobule Crus I. The findings suggest existence of a structural loop underpinning bidirectional communication between the STS and cerebellum. This connection might also be of potential value for other visual social abilities.

Biological motion processing: the left cerebellum communicates with the right superior temporal sulcus.

The cerebellum is thought to be engaged not only in motor control, but also in the neural network dedicated to visual processing of body motion. However, the pattern of connectivity within this network, in particular, between the cortical circuitry for observation of others' actions and the cerebellum remains largely unknown. By combining functional magnetic resonance imaging (fMRI) with functional connectivity analysis and dynamic causal modelling (DCM), we assessed cerebro-cerebellar connectivity during a visual perceptual task with point-light displays depicting human locomotion. In the left lateral cerebellum, regions in the lobules Crus I and VIIB exhibited increased fMRI response to biological motion. The outcome of the connectivity analyses delivered the first evidence for reciprocal communication between the left lateral cerebellum and the right posterior superior temporal sulcus (STS). Through communication with the right posterior STS that is a key node not only for biological motion perception but also for social interaction and visual tasks on theory of mind, the left cerebellum might be involved in a wide range of social cognitive functions.

Reading language of the eyes.

The need for assessment of social skills in clinical and neurotypical populations has led to the widespread, and still increasing use of the 'Reading the Mind in the Eyes Test' (RMET) developed more than two decades ago by Simon Baron-Cohen and colleagues for evaluation of social cognition in autism. By analyzing most recent clinical and brain imaging data, we illuminate a set of factors decisive for using the RMET. Converging evidence indicates: (i) In neurotypical individuals, RMET scores are tightly correlated with other social skills (empathy, emotional intelligence, and body language reading); (ii) The RMET assesses recognition of facial affect, but also heavily relies on receptive language skills, semantic knowledge, and memory; (iii) RMET performance is underwritten by the large-scale ensembles of neural networks inside and well-outside the social brain; (iv) The RMET is limited in its capacity to differentiate between neuropsychiatric conditions as well as between stages and severity of a single disorder, though it reliably distinguishes individuals with altered social cognition or elevated pathological traits from neurotypical persons; (v) Merely gender (as a social construct) rather than neurobiological sex influences performance on the RMET; (vi) RMET scores do not substantially decline in healthy aging, and they are higher with higher education level, cognitive abilities, literacy, and mental well-being; (vii) Accuracy on the RMET, and engagement of the social brain, are greater when emotions are expressed and recognized by individuals with similar cultural/ethnic background. Further research is required to better inform usage of the RMET as a tool for swift and reliable examination of social cognition. In light of comparable visual input from the RMET images and faces covered by masks due to COVID-19 regulations, the analysis is of value for keeping efficient social interaction during the current pandemic, in particular, in professional settings related to social communication.

Body and peripersonal space representations in chronic stroke patients with upper limb motor deficits.

The continuous stream of multisensory information between the brain and the body during body-environment interactions is crucial to maintain the updated representation of the perceived dimensions of body parts (metric body representation) and the space around the body (the peripersonal space). Such flow of multisensory signals is often limited by upper limb sensorimotor deficits after stroke. This would suggest the presence of systematic distortions of metric body representation and peripersonal space in chronic patients with persistent sensorimotor deficits. We assessed metric body representation and peripersonal space representation in 60 chronic stroke patients with unilateral upper limb motor deficits, in comparison with age-matched healthy controls. We also administered a questionnaire capturing explicit feelings towards the affected limb. These novel measures were analysed with respect to patients' clinical profiles and brain lesions to investigate the neural and functional origin of putative deficits. Stroke patients showed distortions in metric body representation of the affected limb, characterized by an underestimation of the arm length and an alteration of the arm global shape. A descriptive lesion analysis (subtraction analysis) suggests that these distortions may be more frequently associated with lesions involving the superior corona radiata and the superior frontal gyrus. Peripersonal space representation was also altered, with reduced multisensory facilitation for stimuli presented around the affected limb. These deficits were more common in patients reporting pain during motion. Explorative lesion analyses (subtraction analysis, disconnection maps) suggest that the peripersonal space distortions would be more frequently associated with lesions involving the parietal operculum and white matter frontoparietal connections. Moreover, patients reported altered feelings towards the affected limb, which were associated with right brain damage, proprioceptive deficits and a lower cognitive profile. These results reveal implicit and explicit distortions involving metric body representation, peripersonal space representation and the perception of the affected limb in chronic stroke patients. These findings might have important clinical implications for the longitudinal monitoring and the treatments of often-neglected deficits in body perception and representation.

Cerebellar engagement in an action observation network.

The cerebellum has traditionally been viewed as a brain structure subserving skilled motor behaviors. However, the cerebellum might be involved not only in movement coordination, but also in action observation and understanding of others' actions. Veridical visual perception of human body motion is of immense importance for a variety of daily-life situations and for successful social interactions. Here, by combining visual psychophysics with a lesion analysis, we assessed visual sensitivity to human walking in patients with lesions to the left cerebellum. Patients with left lateral cerebellar lesions exhibit deficits in visual sensitivity to body motion, whereas medial lesions do not substantially affect visual perception of human locomotion. The findings point to left lateral cerebellar involvement in an action observation network. We discuss possible mechanisms of cerebellar engagement in visual social perception revealed by body motion.

Asymmetric high-order anatomical brain connectivity sculpts effective connectivity.

Bridging the gap between symmetric, direct white matter brain connectivity and neural dynamics that are often asymmetric and polysynaptic may offer insights into brain architecture, but this remains an unresolved challenge in neuroscience. Here, we used the graph Laplacian matrix to simulate symmetric and asymmetric high-order diffusion processes akin to particles spreading through white matter pathways. The simulated indirect structural connectivity outperformed direct as well as absent anatomical information in sculpting effective connectivity, a measure of causal and directed brain dynamics. Crucially, an asymmetric diffusion process determined by the sensitivity of the network nodes to their afferents best predicted effective connectivity. The outcome is consistent with brain regions adapting to maintain their sensitivity to inputs within a dynamic range. Asymmetric network communication models offer a promising perspective for understanding the relationship between structural and functional brain connectomes, both in normalcy and neuropsychiatric conditions.

Linking structural and effective brain connectivity: structurally informed Parametric Empirical Bayes (si-PEB).

Despite the potential for better understanding functional neuroanatomy, the complex relationship between neuroimaging measures of brain structure and function has confounded integrative, multimodal analyses of brain connectivity. This is particularly true for task-related effective connectivity, which describes the causal influences between neuronal populations. Here, we assess whether measures of structural connectivity may usefully inform estimates of effective connectivity in larger scale brain networks. To this end, we introduce an integrative approach, capitalising on two recent statistical advances: Parametric Empirical Bayes, which provides group-level estimates of effective connectivity, and Bayesian model reduction, which enables rapid comparison of competing models. Crucially, we show that structural priors derived from high angular resolution diffusion imaging on a dynamic causal model of a 12-region network-based on functional MRI data from the same subjects-substantially improve model evidence (posterior probability 1.00). This provides definitive evidence that structural and effective connectivity depend upon each other in mediating distributed, large-scale interactions in the brain. Furthermore, this work offers novel perspectives for understanding normal brain architecture and its disintegration in clinical conditions.

Cognitive Deficits in Multiple Sclerosis: Recent Advances in Treatment and Neurorehabilitation.

PURPOSE OF REVIEW: This article highlights recent progress in research on treatment and neurorehabilitation of cognitive impairment in multiple sclerosis (MS) including pharmacological interventions, physical exercise, and neuropsychological rehabilitation, both in conventional and technology-assisted settings. RECENT FINDINGS: The most consistent evidence in terms of improvement or preservation of circumscribed cognitive scores in MS patients comes from moderately sampled randomized clinical trials on multimodal approaches that combine conventional or computerized neuropsychological training with psychoeducation or cognitive behavioral therapy. Disease-modifying treatments also appear to have beneficial effects in preventing or attenuating cognitive decline, whereas there is little evidence for agents such as donepezil or stimulants. Finally, physical exercise may yield some cognitive improvement in MS patients. Despite substantial and often promising research efforts, there is a lack of validated and widely accepted clinical procedures for cognitive neurorehabilitation in MS. Development of such approaches will require collaborative efforts towards the design of interventions that are fundamentally inspired by cognitive neuroscience, potentially guided by neuroimaging, and composed of conventional neuropsychological training and cognitive behavioral therapy as well as physical exercise and therapeutic video games. Subsequently, large-scale validation will be needed with meaningful outcome measures reflecting transfer to everyday cognitive function and maintenance of training effects.