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International audience; Many studies have investigated the perception of tactile pleasantness over a range of stroking velocities. On average, pleasantness is low at slow (e.g. 0.3 cm/s) and fast (e.g. 30 cm/s) stroking velocities, but is rated highest at velocities between 1-10 cm/s. On a group level, this results in an inverted-U shape pleasantness ratings curve, which is described statistically by a negative quadratic equation. We reanalyzed the data from 5 earlier studies to investigate whether the inverted-U shape pleasantness curve at the group level is also present at the level of the individual-a precondition for using tactile pleasantness perception as a diagnostic marker. We pooled the data from five studies with a total of 127 participants. Each study included a 'standard condition' of stroking on the dorsal forearm over different velocities (0.3, 1, 3, 10, 30 cm/s) and participants rated the pleasantness. Factors other than stroking velocity were also varied in these studies. On the whole-group level and in each study, pleasantness ratings produced a significant negative quadratic pleasantness curve over the stroking velocities. In individual participants, ratings varied greatly and only 42% of the participants showed a significant negative quadratic curve. The steepness of the inverted-U correlated only moderately across other experimental conditions, showing that the experimental circumstances can influence pleasantness ratings. Our findings have important implications for future work, where differences in the tactile pleasantness curve should not be used to predict or diagnose issues at an individual level. Highlights • We conducted a reanalysis of 5 studies into variability of pleasant touch perception from stroking over the skin. • We asked whether the inverted-U shape pleasantness curve over slow to fast stroking existed at the level of the individual. • We pooled the data from 127 healthy participants who rated pleasantness of slow to fast stroking. • Group data clearly exhibited the inverted-U shaped pleasantness curve, but this was not found in individuals. • High inter-individual variability exists in tactile pleasantness and this should not be used diagnostically in individuals.

International audience; Third-person perspective full-body illusions (3PP-FBI) enable the manipulation, through multisensory stimulation, of perceived self-location. Perceived self-location is classically measured by a locomotion task. Yet, as locomotion modulates various sensory signals, we developed in immersive virtual reality a measure of self-location without locomotion. Tactile stimulation was applied on the back of twenty-five participants and displayed synchronously or asynchronously on an avatar's back seen from behind. Participants completed the locomotion task and a novel mental imagery task, in which they self-located in relation to a virtual ball approaching them. Participants self-identified with the avatar more during synchronous than asynchronous visuo-tactile stimulation in both tasks. This was accentuated for the mental imagery task, showing a larger self-relocation toward the avatar, together with higher reports of presence, bi-location and disembodiment in the synchronous condition only for the mental imagery task. In conclusion, the results suggest that avoiding multisensory updating during walking, and using a perceptual rather than a motor task, can improve measures of illusory self-location. Self-location, i.e. the experience that the self occupies a certain volume of space, is considered a core aspect of bodily self-consciousness, together with self-identification and first-person perspective 1-3. Self-location is typically experienced within the physical limits of the body 1,4 , but can be experienced as disembodied in various neurological and psychiatric conditions 5. Self-location has proven difficult to study empirically. Early measures of self-location consisted of introspective reports 6-8 , and pointing tasks on human silhouettes or toward the par-ticipant's body 9,10. They revealed that most participants located their self in the head or torso. Self-reports of self-location have also been collected during illusions with sets of mirrors 11,12 and video systems 13. These studies indicate the possibility to manipulate self-location through unusual visuo-spatial perspectives, in a way that the perceived self-location deviates from the location of the physical body. Whole-body adaptations of the rubber hand illusion 14 accelerated the empirical study of the multisensory foundations of self-location, especially with the development of full-body illusions (FBI) from a third-person perspective (here referred to as 3PP-FBI) 15-19. 3PP-FBIs are characterized by self-identification with a full body in extrapersonal space rather than with a body part in peripersonal space. In a seminal version of the 3PP-FBI, participants wore a head-mounted display (HMD) in which they observed a video of their body or a mannequin's body filmed from behind and projected to the front 18. Tactile stimulation was applied on the participants' back and the video was either shown in synchrony or with a delay relative to the stimulation, so that participants saw and felt the touch on the back synchronously or asynchronously. Results show that the integration of spatially dissociated, but synchronous, visual and tactile events increased self-identification with the virtual body. During such self-identification the participant's skin temperature was found to decrease 20. To date, very few studies have used immersive virtual reality (VR) technology to implement 3PP-FBIs 21-23. Most studies of self-location and self-identification were based on pre-recorded or online video-projections of bodies 16,18,24-28. Yet, the study of self-location should benefit from VR. First, VR allows interacting with avatars in realistic, ecological, and controlled environments 29-32. Second, VR is characterized by presence, the feeling of being "there", even when a virtual character is not shown in the VR environment, modifying the perceived self-location 30,33. How can self-location be measured in VR, other than with questionnaires? In most 3PP-FBI studies self-location was measured by a locomotion task (LT), an action-based (motor) judgement in which participants were moved backward and asked to walk to where they perceived to be located during the visuo-tactile stimulation 15,18,34. Participants relocated their self from 10 to 30 cm toward the seen body from their initial position after synchronous visuo-tactile stimulation 35,36. Thus, self-location was a compromise between the location of the physical body and the location of the seen body participants self-identified with.

Several studies have demonstrated the neural correlates of chronic tinnitus. However, we still do not understand what happens in the acute phase. Past studies have established Zwicker tone (ZT) illusions as a good human model for acute tinnitus. ZT illusions are perceived following the presentation of a notched noise stimulus, that is, broadband noise with a narrow band‐stop filter (notch). In the current study, we compared the neural correlates of the reliable perception of a ZT illusion to that which is not. We observed changes in evoked and total theta power in wide‐spread regions of the brain particularly in the temporal‐parietal junction, pregenual anterior cingulate cortex/ventromedial prefrontal cortex (pgACC/vmPFC), parahippocampus during perception of the ZT illusion. Furthermore, we observe that increased theta power significantly predicts a gradual positive change in the intensity of the ZT illusion. Such changes may suggest a malfunction of the sensory gating system that enables habituation to redundant stimuli and suppresses hyperactivity. It could also suggest a successful retrieval of the memory of the missing frequencies, resulting in their conscious perception indicating the role of higher‐order processing in the mechanism of action of ZT illusions. To establish a more concrete relationship between ZT illusion and chronic tinnitus, future longitudinal studies following up a much larger sample of participants who reliably perceive a ZT illusion to see if they develop tinnitus at a later stage is essential. This could inform us if the ZT illusion may be a precursor to chronic tinnitus.

Introduction: Subjective tinnitus (ST) and hyperacusis (HA) are common auditory symptoms that may become incapacitating in a subgroup of patients who thereby seek medical advice. Both conditions can result from many different mechanisms, and as a consequence, patients may report a vast repertoire of associated symptoms and comorbidities that can reduce dramatically the quality of life and even lead to suicide attempts in the most severe cases. The present exploratory study is aimed at investigating patients’ symptoms and complaints using an in-depth statistical analysis of patients’ natural narratives in a real-life environment in which, thanks to the anonymization of contributions and the peer-to-peer interaction, it is supposed that the wording used is totally free of any self-limitation and self-censorship. Methods: We applied a purely statistical, non-supervised machine learning approach to the analysis of patients’ verbatim exchanged on an Internet forum. After automated data extraction, the dataset has been preprocessed in order to make it suitable for statistical analysis. We used a variant of the Latent Dirichlet Allocation (LDA) algorithm to reveal clusters of symptoms and complaints of HA patients (topics). The probability of distribution of words within a topic uniquely characterizes it. The convergence of the log-likelihood of the LDA-model has been reached after 2,000 iterations. Several statistical parameters have been tested for topic modeling and word relevance factor within each topic. Results: Despite a rather small dataset, this exploratory study demonstrates that patients’ free speeches available on the Internet constitute a valuable material for machine learning and statistical analysis aimed at categorizing ST/HA complaints. The LDA model with K = 15 topics seems to be the most relevant in terms of relative weights and correlations with the capability to individualizing subgroups of patients displaying specific characteristics. The study of the relevance factor may be useful to unveil weak but important signals that are present in patients’ narratives. Discussion/Conclusion: We claim that the LDA non-supervised approach would permit to gain knowledge on the patterns of ST- and HA-related complaints and on patients’ centered domains of interest. The merits and limitations of the LDA algorithms are compared with other natural language processing methods and with more conventional methods of qualitative analysis of patients’ output. Future directions and research topics emerging from this innovative algorithmic analysis are proposed.

International audience; The GDR Vertige is a federative research group gathering the different components of the French neuro-otology community. The annual meeting of the GDR Vertige is an opportunity for interactive exchanges between scientists, clinicians and industrialists, on basic issues related to vestibular function, as well as translational questions regarding the management of vestibular disorders. For its fifth edition, the annual meeting of the GDR Vertige, which took place in September 2019 in Marseille (France), was devoted to one of the most peculiar phenomena of neuro-otology: endolymphatic hydrops. For two days, international scientists and clinicians presented the most recent advances regarding the biophysical correlates of endolymphatic hydrops, the genetic and endocrine tableaux that favor its manifestation, new methods of clinical imaging, and current and upcoming therapeutic strategies to overcome the associated clinical manifestations. This special issue of the Journal of Vestibular Research aims at providing the proceedings of this meeting.

IMPORTANCE: An infective etiology of acute peripheral vestibulopathy (APV) has long been hypothesized. In the context of coronavirus disease 2019 (COVID-19), we examined the possible comorbidity between these two entities. OBJECTIVES: APV is the second most common cause of vestibular disorders and results from a sudden and unilateral loss of vestibular inputs. The characteristic signs and symptoms include sudden and prolonged vertigo, absence of auditory symptoms, and absence of other neurological symptoms. An infective etiology of APV has long been hypothesized on the basis of its association with respiratory tract infections and its frequent occurrence in epidemics. Possible comorbidity with herpes simplex virus type 1 reactivation or influenza virus infection has also been proposed. This study was designed to assess the possible comorbidity between APV and COVID-19. DESIGN/SETTING/PARTICIPANTS: Quantification of the number of hospital admissions for APV over the period from February to May 2020 was carried out in 5 French hospitals. A comparison with 2018 and 2019 entries over the same period was made. Comorbidity between APV and COVID-19 infection was investigated. RESULTS: No significant increase in admission for APV was noticed over the examination period. No significant difference was noticed among hospitals located in COVID-19 high- and low-risk zones for SARS-CoV-2. No significant increase in the severity of the APV cases was noticed. No case of comorbidity between APV and SARS-CoV-2 infection was reported. Based on our observations, no correlation was made between APV and COVID-19. CONCLUSION: Based on our observations, COVID-19 is not statistically correlated with APV.

International audience; Perceptual representations are built through multisensory interactions underpinned by dense anatomical and functional neural networks that interconnect primary and associative cortical areas. There is compelling evidence that primary sensory cortical areas do not work in segregation, but play a role in early processes of multisensory integration. In this chapter, we firstly review previous and recent literature showing how multimodal interactions between primary cortices may contribute to refining perceptual representations. Secondly, we discuss findings providing evidence that, following peripheral damage to a sensory system, multimodal integration may promote sensory substitution in deprived cortical areas and favor compensatory plasticity in the spared sensory cortices.

International audience; Hyperacusis is defined as an increased sensitivity to sounds, i.e. sounds presented at moderate levels can produce discomfort or even pain. Existing diagnostic methods, like the Hyperacusis Questionnaire (HQ) and Loudness Discomfort Levels (LDLs), have been challenged because of their variability and lack of agreement on appropriate cutoff values. We propose a novel approach by using psychoacoustic ratings of natural sounds as an assessment tool for hyperacusis. Subjects (n = 81) were presented with natural and artificial (tone pips, noises) sounds (n = 69) in a controlled environment at four sound levels (60, 70, 80 and 90 dB SPL). The task was to rate them on a pleasant to unpleasant visual analog scale. The inherent challenge of this study was to create a new diagnostic tool when no gold standard of hyperacusis diagnosis exists. We labeled our subjects as hyperacusic (n = 26) when they were diagnosed as such by at least two of three methods (HQ, LDLs and self-report). There was a significant difference between controls (n = 23) and hyperacusics in the median global rating of pleasant sounds. Median global ratings of unpleasant sounds and artificial sounds did not differ significantly. Then we selected the subset of sounds that could best discriminate the controls from the hyperacusics, the Core Discriminant Sounds (CDS), and we used them to develop a new metric: The CDS score. A normalized global score and a score for each sound level can be computed with respect to a control population without hyperacusis. A receiver operating characteristic analysis showed that the accuracy of our method in distinguishing subjects with and without complaints of hyperacusis (86%, 95% Confidence Interval (CI): 76-93%) is comparable to that of existing methods such as the LDL (77%, CI: 67-86%) and the HQ (80%, CI: 69-88%). We believe that the CDS score is more relevant to subject's complaints than LDLs and that it could be applied in a clinical environment in a fast and effective way, while minimizing discomfort and biases.

The human brain is a dynamic modular network that can be decomposed into a set of modules and its activity changes permanently over time. At rest, several brain networks, known as Resting-State Networks (RSNs), emerge and cross-communicate even at sub-second temporal scale. Here, we seek to decipher the fast reshaping in spontaneous brain modularity and its relationship to RSNs. We use Electro/Magneto-Encephalography (EEG/MEG) to track dynamics of modular brain networks, in three independent datasets (N= 568) of healthy subjects at rest. We show the presence of striking spatiotemporal network pattern consistent over participants. We also show that some RSNs, such as default mode network and temporal network, are not necessary ‘unified units’ but rather can be divided into multiple sub-networks over time. Using the resting state questionnaire, our results revealed also that brain network dynamics are strongly correlated to mental imagery at rest. These findings add new perspectives to brain dynamic analysis and highlight the importance of tracking fast reconfiguration of electrophysiological networks at rest.

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International audience; To interact with the external world, incoming sensory information informs us about situational changes that are of relevance to our behavior and we act upon these accordingly, be it in a produced movement or an internal reaction (e.g. an emotion, paying attention). Humans efficiently interact with their world and each other and to do this, a system is required to promote relevant sensory feedback to allow fast, accurate, and appropriate actions. We review findings from single unit recordings of muscle afferents that demonstrate the effects of the descending γ-fusimotor system on their activity. This includes changes in firing from cognitive and emotional influences, which we postulate can prepare the body for responsive and appropriate action to a change in environment.

Cutaneous foot receptors are important for balance control, and their activation during quiet standing depends on the speed and the amplitude of postural oscillations. We hypothesized that the transmission of cutaneous input to the cortex is reduced during prolonged small postural sways due to receptor adaptation during continued skin compression. Central mechanisms would trigger large sways to reactivate the receptors. We compared the amplitude of positive and negative post-stimulation peaks (P50N90) somatosensory cortical potentials evoked by the electrical stimulation of the foot sole during small and large sways in 16 young adults standing still with their eyes closed. We observed greater P50N90 amplitudes during large sways compared with small sways consistent with increased cutaneous transmission during large sways. Postural oscillations computed 200 ms before large sways had smaller amplitudes than those before small sways, providing sustained compression within a small foot sole area. Cortical source analyses revealed that during this interval, the activity of the somatosensory areas decreased, whereas the activity of cortical areas engaged in motor planning (supplementary motor area, dorsolateral prefrontal cortex) increased. We concluded that large sways during quiet standing represent self-generated functional behavior aiming at releasing skin compression to reactivate mechanoreceptors. Such balance motor commands create sensory reafference that help control postural sway.

Background and purpose In this study, the question of whether egocentric representation of space is impaired in chronic unilateral vestibulopathies was examined. The objective was to test current theories attributing a predominant role to vestibular afferents in spatial cognition and to assess whether representational neglect signs are common in peripheral vestibular loss. Methods The subjective straight-ahead (SSA) direction was investigated using a horizontal rod allowing the translation and rotation components of the body midline representation to be dissociated in 21 patients with unilateral vestibular loss (right, 13; left, eight) and in 12 healthy controls. Results Compared to the controls, the patients with unilateral vestibulopathy showed a translation bias of their SSA, without rotation bias. The translation bias was not lateralized towards the lesioned side as typically found for biases reported after unilateral vestibular loss. Rather, the SSA bias was rightward whatever the side of the vestibular loss. The translation bias correlated with the vestibular loss, as measured by caloric response and vestibulo-ocular reflex gain, but not with the subjective visual vertical or the residual spontaneous nystagmus. Conclusion The present data suggest that the dysfunctions of neural networks involved in egocentred and allocentred representations of space are differentially compensated for in unilateral vestibular defective patients. In particular, they suggest that asymmetrical vestibular inputs to cortical regions lead to representational spatial disturbances as does defective cortical processing of vestibular inputs in spatial neglect after right hemisphere stroke. They also highlight the predominant role of symmetrical and unaltered vestibular inputs in spatial cognition.

International audience; Vestibular pathologies are difficult to diagnose. Existing devices make it possible to quantify and follow the evolution of posturo-locomotor symptoms following vestibular loss in static conditions. However, today, there are no diagnostic tools allowing the quantitative and spontaneous analysis of these symptoms in dynamic situations. With this in mind, we used an open-field video tracking test aiming at identifying specific posturo-locomotor markers in a rodent model of vestibular pathology. Using Ethovision XT 14 software (Noldus), we identified and quantified several behavioral parameters typical of unilateral vestibular lesions in a rat model of vestibular pathology. The unilateral vestibular neurectomy (UVN) rat model reproduces the symptoms of acute unilateral peripheral vestibulopathy in humans. Our data show deficits in locomotion velocity, distance traveled and animal mobility in the first day after the injury. We also highlighted alterations in several parameters, such as head and body acceleration, locomotor pattern, and position of the body, as well as “circling” behavior after vestibular loss. Here, we provide an enriched posturo-locomotor phenotype specific to full and irreversible unilateral vestibular loss. This test helps to strengthen the quantitative evaluation of vestibular disorders in unilateral vestibular lesion rat model. It may also be useful for testing pharmacological compounds promoting the restoration of balance. Transfer of these novel evaluation parameters to human pathology may improve the diagnosis of acute unilateral vestibulopathies and could better follow the evolution of the symptoms upon pharmacological and physical rehabilitation.

Vertigo and dizziness are a frequent reason for medical consultation. However, diagnostic and therapeutic management is sometimes limited, and clinicians are faced with many unmet needs. The purpose of this study was to identify and prioritize these needs.A questionnaire methodology was used to determine the need for innovation in vestibular disorder management. The questionnaire was sent to 19 teams in French-speaking ENT centers. We measured the concordance of the panel of experts on 56 questions related to the different vestibular pathologies encountered and the desired modalities of innovations.Thirteen questions were identified as priorities. The needs expressed by the experts had better knowledge of the pathophysiological mechanisms of the main diseases encountered and the development of new treatment modalities. Particular attention was paid to inner ear imaging techniques and the development of specific electrophysiology techniques.Some of the anticipated innovations are already under development, such as new inner ear fluid imaging techniques (hydrops visualization using MRI) or in situ treatments (transtympanic dexamethasone or gentamicin injections). Others, such as new electrophysiological techniques, are still not fully developed CONCLUSION: This study provides a snapshot of the needs of the medical profession in vestibular disorder management. It highlights a real concern of the attending personnel, as well as a critical need to optimize the means of diagnosing and treating patients with vestibular disorders.

Vestibular rehabilitation (VR) is practiced across Europe but little in this area has been quantified. The aim of this study was to investigate current VR assessment, treatment, education, and research practices. This was an online, cross-sectional survey with 39 VR specific questions and four sections: demographics, current practice, education, and research. The survey was disseminated through the Dizzynet network to individual therapists through country-specific VR special interest groups. Results were analysed descriptively. A thematic approach was taken to analyse open questions. A total of 471 individuals (median age 41, range 23 − 68 years, 73.4% women), predominately physiotherapists (89.4%) from 20 European countries responded to the survey. They had worked for a median of 4 years (range 80%), with virtual reality used by 15.6%. Over 70% reported knowledge/use of Semont, Epley and Barbeque-Roll manoeuvres for the treatment of BPPV. Most education regarding VR was obtained at post-registration level (89.5%) with only 19% reporting pre-registration education. There was strong (78%) agreement that therapists should have professionally accredited postgraduate certification in VR, with blended learning the most popular mode. Three major research questions were identified for priority: management of specific conditions, effectiveness of VR, and mechanisms/factors influencing vestibular compensation and VR. In summary, the survey quantified current clinical practice in VR across Europe. Knowledge and treatment of common vestibular diseases was high, but use of published subjective and objective outcome measures as well as vestibular assessment varied widely. The results stress the need of improving both training of therapists and standards of care. A European approach, taking advantage of best practices in some countries, seems a reasonable approach. Electronic supplementary material The online version of this article (10.1007/s00415-020-10228-4) contains supplementary material, which is available to authorized users.

International audience; There are tight functional and anatomical links between the vestibular and interoceptive systems, and both systems have shown to fundamentally underlie emotional processes and our sense of a bodily self. Yet, nothing is known about how long-term bilateral vestibulopathy (BVP) influences interoception and its relation to embodiment and the sense of self. We thus compared cardiac interoceptive accuracy, confidence in the performance, and general body awareness in 25 BVP patients and healthy controls using a heartbeat tracking task, self-reports about interoceptive awareness, as well as measures of self-localization and of self-body closeness. Resultsshowed no difference between patients and controls regarding interoceptive accuracy, confidence and body awareness, suggesting that long-term BVP does not influence cardiac interoception. Patients and controls did not differ either regarding self-location and self-body closeness. However, in our overall sample of patients and controls, we found thatinteroceptive accuracy increased with perceived self-body closeness, suggesting that anchoring the self to the body is generally linked with better cardiac interoception. This result is in line with previous suggestions of an important contribution of interoception to the sense of embodiment.

International audience; Unlike age-related brain changes linked to motor activity, neural alterations related to self-motion perception remain unknown. Using fMRI data, we investigated age-related changes in the central processing of somatosensory information by inducing illusions of right-hand rotations with specific proprioceptive and tactile stimulation. Functional connectivity during resting-state (rs-FC) was also compared between younger and older participants. Results showed common sensorimotor activations in younger and older adults during proprioceptive and tactile illusions, but less deactivation in various right frontal regions and the precuneus were found in the elderly. Older participants exhibited a less-lateralized pattern of activity across the primary sensorimotor cortices (SM1) in the proprioceptive condition only. This alteration of the interhemispheric balance correlated with declining individual performance in illusion velocity perception from a proprioceptive, but not a tactile, origin. By combining task-related data, rs-FC and behavioral performance, this study provided consistent results showing that hand movement perception was altered in the elderly, with a more pronounced deterioration of the proprioceptive system, likely due to the breakdown of inhibitory processes with aging. Nevertheless, older people could benefit from an increase in internetwork connectivity to overcome this kinesthetic decline.

While it is well known that the vestibular system is responsible for maintaining balance, posture and coordination, there is increasing evidence that it also plays an important role in cognition. Moreover, a growing number of epidemiological studies are demonstrating a link between vestibular dysfunction and cognitive deficits in older adults; however, the exact pathways through which vestibular loss may affect cognition are unknown. In this cross-sectional study, we sought to identify relationships between vestibular function and variation in morphometry in brain structures from structural neuroimaging. We used a subset of 80 participants from the Baltimore Longitudinal Study of Aging, who had both brain MRI and vestibular physiological data acquired during the same visit. Vestibular function was evaluated through the cervical vestibular-evoked myogenic potential (cVEMP). The brain structures of interest that we analyzed were the hippocampus, amygdala, thalamus, caudate nucleus, putamen, insula, entorhinal cortex (ERC), trans-entorhinal cortex (TEC) and perirhinal cortex, as these structures comprise or are connected with the putative “vestibular cortex.” We modeled the volume and shape of these structures as a function of the presence/absence of cVEMP and the cVEMP amplitude, adjusting for age and sex. We observed reduced overall volumes of the hippocampus and the ERC associated with poorer vestibular function. In addition, we also found significant relationships between the shape of the hippocampus (p = 0.0008), amygdala (p = 0.01), thalamus (p = 0.008), caudate nucleus (p = 0.002), putamen (p = 0.02), and ERC-TEC complex (p = 0.008) and vestibular function. These findings provide novel insight into the multiple pathways through which vestibular loss may impact brain structures that are critically involved in spatial memory, navigation and orientation., Vestibular, MRI, volume, Shape, Diffeomorphometry, Cognition, Aging, Epidemiology, Eye-Ear-Nose-Throat, Medical Imaging

Background: Tinnitus and its mechanisms are an ongoing subject of interrogation in the neuroscientific community. Although most current models agree that it encompasses multiple structures within and outside the auditory system, evidence provided in the literature suffers from a lack of convergence. To further our understanding of contributions to tinnitus lying outside the auditory system, we explored a new model based on a proprioceptive hypothesis specifically in subjects experiencing chronic nonbothersome tinnitus due to acoustic trauma. The present study addresses the role of the right operculum 3 (OP3) involved in this model. It also investigates classical models of tinnitus. Methods: A seed-based resting-state magnetic resonance imaging study explored the functional connectivity in an acoustic trauma group presenting slight to mild nonbothersome chronic tinnitus and compared it with a control group. Results: Group differences were found with two networks: with the sensorimotor-auditory and the frontoparietal, but not with the default mode network nor the limbic regions. In the auditory pathway, the inferior colliculus displayed group differences in connectivity with the right superior parietal lobule. Exploratory analysis elicited a significant increase in connectivity between two seeds in the right OP3 and two mirror regions of the dorsal prefrontal cortex, thought to correspond to the human homologue of the premotor ear-eye field bilaterally and the inferior parietal lobule involved in proprioception, in the tinnitus group. Conclusions: These new findings support the view that acoustic trauma tinnitus could bear a proprioceptive contribution and that a permanent cognitive control is required to filter out this chronic phantom percept.

We previously revealed adult reactive neurogenesis in deafferented vestibular nuclei following unilateral vestibular neurectomy (UVN) in the feline model. We recently replicated the same surgery in a rodent model and aimed to elucidate the origin and fate of newly generated cells following UVN. We used specific markers of cell proliferation, glial reaction, and cell differentiation in the medial vestibular nucleus (MVN) of adult rats. UVN induced an intense cell proliferation and glial reaction with an increase of GFAP-Immunoreactive (Ir), IBA1-Ir and Olig2-Ir cells 3 days after the lesion in the deafferented MVN. Most of the newly generated cells survived after UVN and differentiated into oligodendrocytes, astrocytes, microglial cells and GABAergic neurons. Interestingly, UVN induced a significant increase in a population of cells colocalizing SOX2 and GFAP 3 days after lesion in the deafferented MVN indicating the probable presence of multipotent cells in the vestibular nuclei. The concomitant increase in BrdU- and SOX2-Ir cells with the presence of SOX2 and GFAP colocalization 3 days after UVN in the deafferented MVN may support local mitotic activity of endemic quiescent neural stem cells in the parenchyma of vestibular nuclei.

Objective Unilateral labyrinthectomy (UL) and unilateral vestibular neurectomy (UVN) are two surgical methods to produce vestibular lesions in the mouse. The objective of this study was to describe the surgical technique of both methods, and compare functional compensation using vestibulo-ocular reflex-based tests. Methods UL and UVN were each performed on groups of seven and ten mice, respectively. Main surgical landmarks were the facial nerve, the external auditory canal and the sternomastoid and digastric muscles. For UL, the sternomastoid muscle was elevated to expose the mastoid, which was drilled to destroy the labyrinth. For UVN, the bulla was drilled opened and a transcochlear approach enabled the identification of the vestibulo-cochlear nerve exiting the brainstem, which was sectioned and the ganglion of Scarpa suctioned. Behaviour and vestibular function were analysed before surgery and at 1, 4, 7 days and at 1 month postlesion using sinusoidal rotation, off-vertical axis rotation, static head tilts and angular velocity steps. Results UL is a faster and safer procedure than UVN (operative time 16.3 vs 20.5 min, p = 0.19; survival rate 86% vs 60%, p = 0.25). UVN was more severe with significantly worse behavioural scores at day 4 and day 7 (p Conclusion Both UL and UVN procedures can routinely be performed in the mouse with similar post-operative recovery and behavioural compensation. The operative risk of vascular or neurological damage is smaller in UL compared to UVN. UVN may be required for specific research protocols studying central cellular process specifically related to the destruction of the ganglion of Scarpa and following vestibular nerve degeneration.

SCOPUS: ar.j, info:eu-repo/semantics/published

Motion perception is facilitated by the interplay of various sensory channels. In rodents, the cortical areas involved in multisensory motion coding remain to be identified. Using voltage-sensitive-dye imaging, we revealed a visuo–tactile convergent region that anatomically corresponds to the associative parietal cortex (APC). Single unit responses to moving visual gratings or whiskers deflections revealed a specific coding of motion characteristics strikingly found in both sensory modalities. The heteromodality of this region was further supported by a large proportion of bimodal neurons and by a classification procedure revealing that APC carries information about motion features, sensory origin and multisensory direction-congruency. Altogether, the results point to a central role of APC in multisensory integration for motion perception.

International audience; The vestibular system plays a crucial role in maintaining postural balance. Unilateral vestibular lesions result in a typical syndrome characterized by postural imbalance, altered locomotor patterns and gaze stabilization, as well as cognitive and neurovegetative disorders. One of the main difficulties encountered in the development of new anti-vertigo drugs is the lack of sensitivity in the evaluation of this syndrome. Qualitative assessments of the vestibular syndrome have been developed, but methods of conducting quantitative evaluations are critically lacking. Recently, assessments with a dynamic weight-bearing device (DWB®, Bioseb) revealed postural alterations in rats subjected to unilateral vestibular neurectomy (UVN). Our team is evaluating a new version of this device capable of quantifying additional parameters of postural and locomotor equilibrium. The objective of this study was to use this device to assess these new posturo-locomotor parameters in a rat model of a vestibular pathology. The biomarkers measured by this device are as follows: the barycenter, the support surface and the weight distribution of the rats when they were moving or stationary. Before UVN, the rats showed a symmetric distribution of their weight along the lateral axis. In the acute phase after UVN on the left side, the rats distributed more weight on the right side than on the left side and then distributed more weight on the left side. These results corroborate those presented in our previous study. The support surface of the rats increased between 1 day and 30 days after UVN, and the barycenter distribution reflected the weight distribution. In addition, our results show smaller changes in the weight distributions when the animals are moving compared with when they are stationary in the acute phase after UVN. This study provides new information on the static and dynamic postural balance patterns observed after unilateral vestibular loss in rats. These data are relevant because they objectively quantify the posturo-locomotor component of vestibular syndrome as well as the compensatory strategies used after vestibular loss. These results may guide the development of rehabilitation protocols for vestibular patients and the validation of pharmacological compounds favoring the restoration of equilibrium.

IntroductionIdentifying the neural substrates underlying the personality traits is a topic of great interest. On the other hand, it is now established that the brain is a dynamic networked system which can be studied using functional connectivity techniques. However, much of the current understanding of personality-related differences in functional connectivity has been obtained through the stationary analysis, which does not capture the complex dynamical properties of brain networks.ObjectiveIn this study, we aimed to evaluate the feasibility of using dynamic network measures to predict personality traits.MethodUsing the EEG/MEG source connectivity method combined with a sliding window approach, dynamic functional brain networks were reconstructed from two datasets: 1) Resting state EEG data acquired from 56 subjects. 2) Resting state MEG data provided from the Human Connectome Project. Then, several dynamic functional connectivity metrics were evaluated.ResultsSimilar observations were obtained by the two modalities (EEG and MEG) according to the neuroticism, which showed a negative correlation with the dynamic variability of resting state brain networks. In particular, a significant relationship between this personality trait and the dynamic variability of the temporal lobe regions was observed. Results also revealed that extraversion and openness are positively correlated with the dynamics of the brain networks.ConclusionThese findings highlight the importance of tracking the dynamics of functional brain networks to improve our understanding about the neural substrates of personality.

In homeostasis, somatosensory C fibre afferents are hypothesised to mediate input to the brain about interactions with external stimuli and sympathetic efference provides the output that regulates bodily functions. We aimed to test this hypothesis and whether different types of innocuous somatosensory input have differential effects. Healthy volunteers performed a muscle fatigue (hand-grip) task to exhaustion, which produces increased muscle sympathetic nerve activity (MSNA), as measured through microneurography. Participants completed the muscle fatigue task without concurrent cutaneous sensory stimulation (control) or we applied skin warming (heat pack) as a C fibre stimulation, slow brush stroking as C and Aβ fibre stimulation, or vibration as Aβ fibre stimulation, to the participant’s forearm. We also measured heart rate, the duration of the hand-grip task, and ratings of pain at the end of the task. Concurrent skin warming showed increased MSNA compared to the other conditions. Tactile stimuli (brushing, vibration) were not significantly different to the control (no intervention) condition. Warming increased the pain from the muscle contraction, whereas the tactile stimuli did not. We interpret the effect of warming on MSNA as providing relevant afferent information during muscle contraction, which needed to be counteracted via vasoconstriction to maintain homeostasis. Brushing and vibration were less homeostatically relevant stimuli for the muscle contraction and hence had no significant effect. The findings add sensory specificity to our current understanding of homeostatic regulation through somatosensory afferent and sympathetic efferent pathways.

International audience; Editorial on the Research Topic Role of Inner Ear in Self and Environment Perception Otoneurology and vestibular neuroscience recently advanced with a better understanding of the vestibular contributions to perceptual and cognitive functions, reaching far beyond balance, and eye-movement control. Pioneering clinical observations established connections between dizziness and altered sense of self, distortions of the body schema, and symptoms resembling depersonalization and derealization (1, 2). However, studies in large samples of patients with dizziness have only recently validated the assumption that the vestibular system is the main contributor to the bodily self (3, 4). Recent epidemiological studies have also linked vestibular disorders to cognitive deficits. For example, a survey in over 20,000 adults established that individuals reporting vestibular vertigo had an eight-fold increase in the odds of reporting impaired memory and attention, limiting their activities (5). Another survey conducted in adults over 60 years revealed that vestibular impairment partially mediated the association between age and cognitive impairment. It was estimated that vestibular impairment mediates 14.3% of the effects of age on cognition and that it accelerates cognitive decline by 5 years in a visuo-spatial test (6). These studies raise the necessity to investigate more carefully the effects of vestibular impairment in dementia and several psychiatric disorders (7, 8). Research in this area benefited from a better delineation of the human vestibular cortex. Functional MRI (fMRI) studies and meta-analyses of neuroimaging data have revealed that the cortical vestibular network is centered on the operculo-insular/retroinsular cortex (9) and that vestibular inputs also project to the temporo-parietal junction, cingulate cortex, somatosensory cortex, posterior parietal cortex, hippocampus, and frontal eye fields (10). These widespread vestibular projections to the brain were recently confirmed in whole-brain functional mapping in rodents using fMRI, local field potentials, and optogenetics (11, 12). We note that recent descriptions of functional connectivity, metabolic, and morphological brain alterations in peripheral vestibular disorders or chronic subjective dizziness [e.g., (13-15)] offer the possibility to evaluate, in a non-invasive manner, how various vestibular rehabilitation methods and drugs can improve brain plasticity. Finally, recent fMRI studies revealed the influence of cognition, emotion, and personality traits (such as neuroticism and introversion) on vestibular information processing [e.g., (16, 17)]. These observations suggest an expansion of the vestibular brain network into dimensions of emotion processing, mental health, and social cognition. This Research Topic collection includes 17 articles combining contributions from authors with a large range of expertise in medicine and basic science, including neurology, otorhinolaryngology, neurophysiology, physiotherapy, neuropsychology, cognitive neuroscience, and bioengineering.

To date, few studies have investigated the impact of organizational factors such as organizational status or the rank of firefighters on the development of posttraumatic stress disorder (PTSD) following a terrorist attack. To fill this gap in the scientific literature, this field study aimed to investigate the consequences of terrorist attacks on firefighters’ psychological health in terms of PTSD. Data were collected in France following two terrorist attacks. PTSD was assessed with the PCL-S (DSM-IV) 3 to 6 months after the events. Confirmatory factor analyses (CFAs) with existing PTSD models were inconclusive, leading us to find a two-factor model via an exploratory factor analysis (EFA). A cluster analysis showed different symptom profiles that were influenced by the exposure level. Elements for a structural model explaining PTSD symptoms are proposed and suggest a central role of the exposure level. Firefighters I/II represented an at-risk sub-population, suggesting that PTSD was mainly experienced among those who performed tasks not common to their occupation.

Tinnitus remains a scientific and clinical problem whereby, in spite of increasing knowledge on effective treatment and management for tinnitus, very little impact on clinical practice has been observed. There is evidence that prolonged, obscure and indirect referral trajectories persist in usual tinnitus care.ObjectiveIt is widely acknowledged that efforts to change professional practice are more successful if barriers are identified and implementation activities are systematically tailored to the specific determinants of practice. The aim of this study was to administer a health service evaluation survey to scope current practice and knowledge of standards in tinnitus care across Europe. The purpose of this survey was to specifically inform the development process of a European clinical guideline that would be implementable in all European countries.DesignA health service evaluation survey was carried out.SettingThe survey was carried out online across Europe.ParticipantsClinical experts, researchers and policy-makers involved in national tinnitus healthcare and decision-making.Outcome measuresA survey was developed by the study steering group, piloted on clinicians from the TINNET network and underwent two iterations before being finalised. The survey was then administered to clinicians and policy-makers from 24 European countries.ResultsData collected from 625 respondents revealed significant differences in national healthcare structures, use of tinnitus definitions, opinions on characteristics of patients with tinnitus, assessment procedures and particularly in available treatment options. Differences between northern and eastern European countries were most notable.ConclusionsMost European countries do not have national clinical guidelines for the management of tinnitus. Reflective of this, clinical practices in tinnitus healthcare vary dramatically across countries. This equates to inequities of care for people with tinnitus across Europe and an opportunity to introduce standards in the form of a European clinical guideline. This survey has highlighted important barriers and facilitators to the implementation of such a guideline.

Highlights • PTSD showed altered behavioral responses to potential monetary losses. • When avoiding monetary losses, PTSD depicted increased activation of basal ganglia. • When anticipating monetary gains, PTSD exhibited altered activation of basal ganglia. • During receipt of monetary gains PTSD showed altered activation of basal ganglia., Background Recent studies suggest that Posttraumatic Stress Disorder (PTSD) might be associated with dysfunctional reward circuitry. However, further research is needed to understand the key role of the reward system in PTSD symptomatology. Methods Twenty participants with PTSD and 21 Trauma-Exposed matched Controls (TECs) completed the Monetary Incentive Delay (MID) task during an MRI session. Reaction times (RTs) and hit rates were recorded. Brain activity was investigated during the anticipation and the outcome of monetary gains and losses. Results During the anticipation of monetary loss, PTSD participants had higher RTs than TECs. However, the groups did not differ at the neurofunctional level. During successful avoidance of monetary loss, PTSD patients showed higher activation than TECs in the left caudate nucleus. During the anticipation of monetary gains, no differences in RTs were found between groups. PTSD patients had specific activations in the right amygdala, nucleus accumbens, putamen, and middle frontal gyrus (p

International audience; Introduction Olfaction has an important role in physiological and affective processes, as well as the potential to have profound effects on activities such as sleep and learning. We investigated two commercially manufactured odors ("Deep Sleep" and "Oriental," from This Works) purported to promote sleep, compared with control odor, where we aimed to explore whether neural and behavioral differences existed after odor inhalation. Methods In a neuroimaging study, 30 healthy participants were exposed to the odors via an olfactometer during functional magnetic resonance imaging (fMRI). In a further behavioral study using 12 chronic insomniacs, we investigated whether the commercial odors showed effects on sleep during a double-blind, randomized home evaluation. Results In the neuroimaging, the odors were related to activation of olfactory-relevant areas, such as the orbitofrontal cortex, and we found positive connectivity between the piriform cortex and the hippocampus, amygdala, insula, and middle cingulate cortex. Deep Sleep specifically activated the superior temporal gyrus, whereas Oriental activated the caudate. Further, these commercial odors showed some beneficial impact on sleep. Conclusions The perceptual and neural impacts of the commercial odors showed that olfactory stimulation can potentially aid sleep and modify affective processes in a number of ways. Implications The present work opens up opportunities for further investigations into how different odors may lead to specific behavioral and physiological modifications, such as their impact on sleep and well-being, which may provide non-pharmacological alternative approaches.

Recent studies employing body illusions have shown that multisensory conflict can alter body representations and modulate low-level sensory processing. One defining feature of these body illusions is that they are sensory driven and thus passive on behalf of the participant. Thus, it remained to establish whether explicit alteration of own-body representations modulates low-level sensory processing. We investigated whether tibial nerve somatosensory-evoked potentials were modulated when participants imagined paralysis of their legs and arms. Imagined paralysis of the legs decreased P40 amplitude, but not imagined paralysis of the arms. These results show modulation of early somatosensory processing via explicit, top-down alteration to the internal representation of the body. Interestingly, P40 suppression positively correlated with bodily aware-ness scores whereas it negatively correlated with body dissociation scores. This suggests that the ability to actively alter own-body representation and its corresponding sensory processing depends upon dispositions to attend to and focus on bodily sensations.

International audience; Motor control and body representations in the central nervous system are built, i.e., patterned, during development by sensorimotor experience and somatosensory feedback/reafference. Yet, early emergence of locomotor disorders remains a matter of debate, especially in the absence of brain damage. For instance, children with developmental coordination disorders (DCD) display deficits in planning, executing and controlling movements, concomitant with deficits in executive functions. Thus, are early sensorimotor atypicalities at the origin of long-lasting abnormal development of brain anatomy and functions? We hypothesize that degraded locomotor outcomes in adulthood originate as a consequence of early atypical sensorimotor experiences that induce developmental disorganization of sensorimotor circuitry. We showed recently that postnatal sensorimotor restriction (SMR), through hind limb immobilization from birth to one month, led to enduring digitigrade locomotion with ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and clear signs of spinal hyperreflexia in adult rats, suggestive of spasticity; each individual disorder likely interplaying in self-perpetuating cycles. In the present study, we investigated the impact of postnatal SMR on the anatomical and functional organization of hind limb representations in the sensorimotor cortex and processes representative of maladaptive neuroplasticity. We found that 28 days of daily SMR degraded the topographical organization of somatosensory hind limb maps, reduced both somatosensory and motor map areas devoted to the hind limb representation and altered neuronal response properties in the sensorimotor cortex several weeks after the cessation of SMR. We found no neuroanatomical histopathology in hind limb sensorimotor cortex, yet increased glutamatergic neurotransmission that matched clear signs of spasticity and hyperexcitability in the adult lumbar spinal network. Thus, even in the absence of a brain insult, movement disorders and brain dysfunction can emerge as a consequence of reduced and atypical patterns of motor outputs and somatosensory feedback that induce maladaptive neuroplasticity. Our results may contribute to understanding the inception and mechanisms underlying neurodevelopmental disorders, such as DCD.

Purpose Although tinnitus is highly prevalent among patients receiving audiology services, audiologists are generally untrained in tinnitus management. Audiology graduate programs, as a rule, do not provide comprehensive instruction in tinnitus clinical care. Training programs that do exist are inconsistent in their recommendations. Furthermore, no standards exist to prevent the delivery of unvetted audiologic services, which can be expensive for patients. Patients seeking professional services by an audiologist, therefore, have no basis upon which to be assured they will receive research-based care. The purpose of this article is to describe the current status of tinnitus management services that exist within the general field of audiology and to suggest specific approaches for improving those services. Conclusion Audiologists may be in the best position to serve as the primary health care providers for patients experiencing tinnitus. Tinnitus care services by audiologists, however, must achieve a level of evidence-based standardization.

International audience; Introduction : Chez le sujet âgé, l’apparition de déséquilibres et le risque de chute ne résultent pas uniquement de l’altération avec l’âge des fonctions sensorielles et motrices. L’attention et les mécanismes exécutifs sont également essentiels au maintien de l’équilibre. Cette étude se situe dans le cadre théorique des interrelations entre fonctions motrices et cognitives. L’objectif a été d’analyser les effets d’un entraînement psychomoteur sur l’équilibration et la cognition chez le sujet vieillissant. Matériels et Méthodes : Nous avons réalisé une prise en charge psychomotrice de 5 semaines (à raison de 2 fois par semaine) portant sur l’équilibre, la force et la conscience corporelle. L’impact de cette prise en charge a été analysé sur les fonctions exécutives, les performances de marche et la qualité de vie chez 3 participants résidant en EHPAD et présentant une perte cognitive légère. Nous avons utilisé un protocole en cas unique pendant lequel nous avons effectué des mesures répétées cognitives et des paramètres de la marche, un bilan initial et un bilan final. Résultats : Selon les sujets, cet entraînement a permis une amélioration soit de certaines fonctions cognitives (l’attention soutenue, la flexibilité, la vitesse de traitement), soit des fonctions d’équilibration (la cadence et les paramètres temporaux de la marche), soit des deux conjointement. Discussion : Ces résultats montrent un impact de la prise en charge psychomotrice sur les performances de marche et met en évidence, pour la première fois, un transfert de ces bénéfices sur les performances cognitives.

International audience; Out-of-body experiences (OBEs) are states during which people experience their centre of awareness as located outside of their physical body, along with the sensation of seeing the environment from an elevated viewpoint. OBE is encountered in epilepsy, migraine and depersonalization, and it is not an uncommon experience in the general population. Current neuroscientific models of bodily self-consciousness consider that OBE are related to a failure to integrate visual, somatosensory and vestibular signals. These models have highlighted the importance of visual-vestibular mismatch in OBE. Case reports from older clinical literature suggest that vestibular disorders may precipitate OBE, but we were lacking population-based evidence that OBE is related to vestibular disorders. The present observational, prospective study describes otoneurological, neuropsychological and phenomenological correlates of OBE in the largest sample of patients with dizziness to date (n = 210) compared to a group of age- and gender-matched controls with no history of dizziness (n = 210). We show a significantly higher occurrence of OBE in patients with dizziness (14%) than in healthy participants (5%). Most of the patients experienced OBE only after they started having dizziness for the first time. OBE in patients with dizziness were mainly related to peripheral vestibular disorders. We also identify depersonalization-derealization, depression and anxiety as the main predictors of OBE in patients with dizziness, as well as a contribution of migraine. Depersonalization-derealization was the only significant predictor of OBE in healthy controls. Altogether, our data indicate that OBE in patients with dizziness may arise from a combination of perceptual incoherence evoked by the vestibular dysfunction with psychological factors (depersonalization-derealization, depression and anxiety) and neurological factors (migraine).

Impairment in fine hand motor dexterity is well established in older people, yet little is known, about the impaired perception of hand movement in the elderly. Only an age-related increase in movement detection threshold has been reported. Perception of hand movements relies on multiple sensory information, including touch and muscle proprioception. The present study aims to investigate to what extent aging impacts the ability to perceive hand movements accurately and whether this impairment is from a muscle touch and/or tactile origin. To disentangle proprioception and touch, we used specifically designed stimuli: a mechanical vibration applied to the wrist muscle tendon and a tactile-textured disk rotating under the participant’s hand, respectively. These two stimuli elicited illusions of hand rotations in two groups of young (20–30 years) and older (65–75 years) participants. Psychophysical testing showed that velocity discrimination thresholds of tactile and proprioceptive illusions were about twice lower in the young, than the older group. Also, relatively small isometric contractions were involuntarily elicited in wrist muscles during the illusions in both groups, but this motor response was positively correlated with the discrimination performance of the young, but not the older, participants. The present results show that muscle proprioception and touch are both functionally affected in kinesthesia after 65 years old, with a more pronounced alteration for muscle proprioception. This alteration in discriminative ability is likely due to impairment in the accurate encoding of the kinematic properties of hand movements. The possible central vs peripheral origin of these perceptive–motor changes with aging is discussed.

International audience; Rats with complete spinal cord transection (SCT) can recover hindlimb locomotor function under strategies combining exercise training and 5-HT agonist treatment. This recovery is expected to result from structural and functional reorganization within the spinal cord below the lesion. To begin to understand the nature of this reorganization, we examined synaptic changes to identified gastrocnemius (GS) or tibialis anterior (TA) moto-neurons (MNs) in SCT rats after a schedule of early exercise training and delayed 5-HT agonist treatment. In addition, we analyzed changes in distribution and number of lumbar interneurons (INs) presynaptic to GS MNs using retrograde transneuronal transport of rabies virus. In SCT-untrained rats, we found few changes in the density and size of inhibitory and excitatory inputs impinging on cell bodies of TA and GS MNs compared to intact rats, whereas there was a marked trend for a reduction in the number of premotor INs connected to GS MNs. In contrast, after training of SCT rats, a significant increase of the density of GABAergic and glycinergic axon terminals was observed on both GS and TA motoneuronal cell bodies, as well as of presynaptic P-boutons on VGLUT1 afferents. Despite these changes in innervation the number of premotor INs connected to GS MNs was similar to control values although some new connections to MNs were observed. These results suggest that adaptation of gait patterns in SCT-trained rats was accompanied by changes in the innervation of lumbar MNs while the distribution of the spinal premotor circuitry was relatively preserved.

Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VNVGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VNGAD2+ mice. This effect persisted when vestibular tactilo kinesthesic plantar inputs were removed. Posturo-locomotor alterations evoked in VNVGluT2+ animals were still present immediately after stimulation, while they disappeared 1 h later. Overall, these results indicate a fundamental role for VNVGluT2+ neurons in balance and posturo-locomotor functions, but not for VNGAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology.

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International audience; Positive affective touch plays a central role in social and inter-personal interactions. Low-threshold mechanoreceptive afferents, including slowly-conducting C-tactile (CT) afferents found in hairy skin, transmit such signals from gentle touch to the brain. Tactile signals are processed, in part, by the posterior insula, where it is the thought to be the primary target for CTs. We used magnetoencephalography (MEG) to assess brain activity evoked by gentle, naturalistic stroking touch on the arm delivered by a new MEG-compatible brush robot. We aimed to use high temporal resolution MEG to allow us to distinguish between brain responses from fast-conducting Aβ and slowly-conducting CT afferents. Brush strokes were delivered to the left upper arm and left forearm of 15 healthy participants. We hypothesized that late brain responses, due to slow CT afference, would appear with a time shift between the two different locations on the arm. Our results show that gentle touch rapidly activated somatosensory, motor, and cingulate regions within the first 100 ms of skin contact, which was driven by fast-conducting mechanoreceptive afference, and that these responses were sustained during touch. Peak latencies in the posterior insula were shifted as a function of stimulus location and temporally-separate posterior insula activations were induced by Aβ and CT afference that may modulate the emotional processing of gentle touch on hairy skin. We conclude that the detailed information regarding temporal and spatial brain activity from MEG provides new insights into the central processing of gentle, naturalistic touch, which is thought to underpin affective tactile interactions.

International audience; Cerebral palsy (CP) is a complex syndrome of various sensory, motor and cognitive deficits. Its prevalence has recently decreased in some developed countries and its symptoms have also shifted since the 1960s. From the 1990s, CP has been associated with prematurity, but recent epidemiologic studies show reduced or absent brain damage, which recapitulates developmental coordination disorder (DCD). In previous studies, we developed a rat model based on mild intrauterine hypoperfusion (MIUH) that recapitulated the diversity of symptoms observed in preterm survivors. Briefly, MIUH led to early inflammatory processes, diffuse brain damage, minor locomotor deficits, musculoskeletal pathologies, neuroanatomical and functional disorganization of the primary somatosensory (S1) cortex but not in the motor cortex (M1), delayed sensorimotor reflexes, spontaneous hyperactivity, deficits in sensory information processing, and memory and learning impairments in adult rats. Adult MIUH rats also exhibited changes in muscle contractile properties and phenotype, enduring hyperreflexia and spasticity, as well as hyperexcitability in the sensorimotor cortex. We recently developed a rat model of DCD based on postnatal sensorimotor restriction (SMR) without brain damage. Briefly, SMR led to digitigrade locomotion (i.e., “toe walking”) related to ankle-knee overextension, degraded musculoskeletal tissues (e.g., gastrocnemius atrophy), and lumbar hyperreflexia. The postnatal SMR then led to secondary degradation of the hind-limb maps in S1 and M1 cortices, altered cortical response properties and cortical hyperexcitability, but no brain damage. Thus, our 2 rat models appear to recapitulate the diversity of symptoms ranging from CP to DCD and contribute to understanding the emergence and mechanisms underlying the corresponding neurodevelopmental disorders. These preclinical models seem promising for testing strategies of rehabilitation based on both physical and cognitive training to promote adaptive brain plasticity and to improve physical body conditions.

International audience; Introduction The number of older people diagnosed with amnestic mild cognitive impairment (aMCI), the prodromal state of Alzheimer's disease (AD), is increasing worldwide. However, some patients with aMCI never convert to the AD type of dementia, with some remaining stable and others reverting to normal. This overdiagnosis bias has been largely overlooked and gone unexplained. There is ample evidence in the laboratory that negative ageing stereotypes (eg, the culturally shared belief that ageing inescapably causes severe cognitive decline) contribute to the deteriorating cognitive performances of healthy older adults, leading them to perform below their true abilities. The study described here is intended to test for the first time whether such stereotypes also impair patients’ cognitive performances during neuropsychological examinations in memory clinics, resulting in overdiagnosis of aMCI. Methods and analysis The ongoing study is a 4-year randomised clinical trial comparing patients’ physiological stress and cognitive performances during neuropsychological testing in memory clinics. A total of 260 patients attending their first cognitive evaluation will be randomised to either a standard condition of test administration, assumed here to implicitly activate negative ageing stereotypes or a reduced-threat instruction condition designed to alleviate the anxiety arising from these stereotypes. Both groups will be tested with the same test battery and stress biomarkers. For 30 patients diagnosed with aMCI in each group (n=60), biomarkers of neurodegeneration and amyloidopathy will be used to distinguish between aMCI with normal versus abnormal AD biomarkers. A 9-month follow-up will be performed on all patients to identify those whose cognitive performances remain stable, deteriorate or improve. Ethics and dissemination This protocol has been approved by the French National Agency for Medicines and Health Products Safety and the Sud-Est I French Ethics Committee (2017-A00946-47). Results will be published in peer-reviewed journals. Trial registration number NCT03138018 .

International audience; Many studies have investigated the perception of tactile pleasantness on the skin over a range of stroking velocities. On average, pleasantness is low at very slow (e.g. 0.3 cm/s) and very fast (e.g. 30 cm/s) velocities, but is highest at velocities between 1-10 cm/s. This results in a pleasantness ratings curve in an inverted-U shape that can be represented by a negative quadratic equation. We conducted a meta-analysis into the stability of the inverted-U shape pleasantness curve to investigate whether it can be found at the level of the individual, not just at a group level, which would make it a useful diagnostic tool. We chose five studies with similar design and a total of 127 participants. In all of these, the dorsal forearm was stroked with five different velocities ranging from 0.3 to30 cm/s and each velocity was repeated three times. Participants rated the pleasantness of the stimulation. In addition to touch velocity, other factors were varied in these studies (e.g. temperature of the stroke, stroking in the presence of an odour). For each study and condition and for each individual and condition, we calculated a quadratic regression between velocity and pleasantness ratings and determined the significance of the fit. On the group level and in each study, the rated pleasantness had a significant quadratic relation with velocity, following an inverted-U shaped curve. On the level of the individual, however, only ~ 40% of the participants showed a significant quadratic curve fit, irrespective of condition. Furthermore, the steepness of the inverted-U correlated only moderately across conditions. This has important implications for future work, where differences in the pleasantness curve cannot be used to predict or diagnose issues at an individual level.

International audience; Gentle touch of the hairy skin in humans activates both Aβ-and C-tactile (CT) mechanoreceptive afferents. Due to the different conduction velocities of Aβ-and CT afferents, their impulses reach the central nervous system with different latencies: Aβ afferents are fast conducting, and CT afferents are slowly conducting. Using the time-resolved neuroimaging methods of magnetoencephalography (MEG), and stereotactic electroencephalography (SEEG) we have investigated the spatiotemporal dynamics of brain activity elicited by concomitant activation of Aβ and CT afferents during gentle stroking touch. Our results from MEG indicate that Aβ afference rapidly activates the posterior insula (within ~100 ms post onset of the tactile stimulus) and that CT afference reaches the posterior insula with a delay. This finding suggests that Aβ and CT afference is co-processed within the posterior insula, and that both afferent types play a role in affective processing of tactile events. We also have preliminary SEEG results that indicate that Aβ afference induces gamma synchronization in the posterior insula during gentle touch of the forearm. Together, results from both MEG and SEEG highlight the importance of considering Aβ afferents in the affective processing of gentle stroking touch of the hairy skin in humans.

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International audience; The in vivo technique of microneurography allows the recording of peripheral nerve traffic in humans. In touch research, microneurography is used to record from single mechanoreceptive afferents during tactile interactions and their activity can be related to an associated percept. The precise firing of single mechanoreceptive afferents generates sufficient information to allow us to determine differences between a wide range of surfaces. I will present how microneurography works and focus on findings from unmyelinated tactile afferents, C-tactile (CT) afferents. CTs are only found only in hairy skin and are believed to signal affective touch. Their firing has been linked to tactile pleasantness and they are tuned to respond to a slow, gentle caress delivered around human skin temperature, thus play a key role in inter-personal interactions.

Damage to cochlear primary afferent synapses has been shown to be a key factor in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses might be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address this possibility, we selectively damaged the synaptic contacts between hair cells and primary vestibular neurons in mice through the transtympanic administration of a glutamate receptor agonist. Using a combination of histological and functional approaches, we demonstrated four key findings: (1) selective synaptic deafferentation is sufficient to generate acute vestibular syndrome with characteristics similar to those reported in patients; (2) the reduction of the vestibulo-ocular reflex and posturo-locomotor deficits mainly depends on spared synapses; (3) damaged primary vestibular synapses can be repaired over the days and weeks following deafferentation; and (4) the synaptic repair process occurs through the re-expression and re-pairing of synaptic proteins such as CtBP2 and SHANK-1. Primary synapse repair might contribute to re-establishing the initial sensory network. Deciphering the molecular mechanism that supports synaptic repair could offer a therapeutic opportunity to rescue full vestibular input and restore gait and balance in patients., Summary: The molecular rearrangements of the synaptic proteins that accompany the deafferentation and subsequent reafferentation of the inner ear sensors following an excitotoxic insult are demonstrated for the first time.