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The rhythmic priming effect (RPE) refers to improved language performance (typically grammaticality judgements) following regular rhythmic primes compared to various control conditions. This effect has been observed primarily in French, but also in English and Hungarian. However, a recent implementation by Kim, McLaren & Lee (2024), aiming to replicate the RPE in English (Chern, Tillmann, Vaughan & Gordon, 2018), was not successful, inviting a discussion about the conditions under which the RPE could be observed. We here discuss features of Kim et al.'s (2024) implementation that might have reduced the probability of observing the RPE. Compared to Chern et al. (2018), and numerous other studies reporting the RPE, additional delays after the primes and before each sentence were introduced by Kim et al. (2024). This change might have limited beneficial prime effects, which persist, but decay over time. Further, their instruction to "relax and have some rest" might have reduced attentive processing of the primes and related entrainment. Finally, their sample was small (n =16 per experiment) and with a large age range for investigating typically developing children (7-12y), potentially reducing experimental effects due to development-related individual variations. These methodological changes and sample characteristics are discussed in relation to previous research on the RPE, and entrainment in general. This discussion prompts the need for future research to investigate conditions leading to the RPE, with the aim to shed light on underlying mechanisms. Better understanding the RPE will be critical for the use of rhythmic priming within clinical and educational settings., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Daily life for humans and other animals requires switching between periods of threat- and reward-oriented behavior. We investigated neural activity associated with spontaneous switching, in a naturalistic task, between foraging for rewards and seeking information about potential threats with 7T fMRI in healthy humans. Switching was driven by estimates of likelihood of threat and reward. Both tracking of threat and switching to a vigilant mode in which people sought more information about potential threats were associated with specific but distributed patterns of activity spanning habenula, dorsal raphe nucleus (DRN), anterior cingulate cortex, and anterior insula cortex. Different aspects of the distributed activity patterns were linked to monitoring the threat level, seeking information about the threat, and actual threat detection. A distinct pattern of activity in the same circuit and elsewhere occurred during returns to reward-oriented behavior. Individual variation in DRN activity reflected individual variation in the seeking of information about threats., Competing Interests: Competing interests statement:The authors declare no competing interest.

This study aims to provide a comprehensive picture of auditory emotion perception in cochlear implant (CI) users by (1) investigating emotion categorization in both vocal (pseud-ospeech) and musical domains, and (2) how individual differences in residual acoustic hearing, sensitivity to voice cues (voice pitch, vocal tract length), and quality of life (QoL) might be associated with vocal emotion perception, and, going a step further, also with musical emotion perception. In 28 adult CI users, with or without self-reported acoustic hearing, we showed that sensitivity (d') scores for emotion categorization varied largely across the participants, in line with previous research. However, within participants, the d' scores for vocal and musical emotion categorization were significantly correlated, indicating similar processing of auditory emotional cues across the pseudo-speech and music domains and robustness of the tests. Only for musical emotion perception, emotion d' scores were higher in implant users with residual acoustic hearing compared to no acoustic hearing. The voice pitch perception did not significantly correlate with emotion categorization in either domain, while the vocal tract length significantly correlated in both domains. For QoL, only the subdomain of Sspeech production ability, but not the overall QoL scores, correlated with vocal emotion categorization, partially supporting previous findings. Taken together, results indicate that auditory emotion perception is challenging for some CI users, possibly a consequence of how available the emotion-related cues are via electric hearing. Improving these cues, either via rehabilitation or training, may also help auditory emotion perception in CI users.

Purpose: Radiomics-based machine learning (ML) models of amino acid positron emission tomography (PET) images have shown efficiency in glioma prediction tasks. However, their clinical impact on physician interpretation remains limited. This study investigated whether an explainable radiomics model modifies nuclear physicians' assessment of glioma aggressiveness at diagnosis., Methods: Patients underwent dynamic 6-[ 18 F]fluoro-L-DOPA PET acquisition. With a 75%/25% split for training (n = 63) and test sets (n = 22), an ensemble ML model was trained using radiomics features extracted from static/dynamic parametric PET images to classify lesion aggressiveness. Three explainable ML methods-Local Interpretable Model-agnostic Explanations (LIME), Anchor, and SHapley Additive exPlanations (SHAP)-generated patient-specific explanations. Eighteen physicians from eight institutions evaluated the test samples. During the first phase, physicians analyzed the 22 cases exclusively through magnetic resonance and static/dynamic PET images, acquired within a maximum interval of 30 days. In the second phase, the same physicians reevaluated the same cases (n = 22), using all available data, including the radiomics model predictions and explanations., Results: Eighty-five patients (54[39-62] years old, 41 women) were selected. In the second phase, physicians demonstrated a significant improvement in diagnostic accuracy compared to the first phase (0.775 [0.750-0.802] vs. 0.717 [0.694-0.737], p = 0.007). The explainable radiomics model augmented physician agreement, with a 22.72% increase in Fleiss's kappa, and significantly enhanced physician confidence (p < 0.001). Among all physicians, Anchor and SHAP showed efficacy in 75% and 72% of cases, respectively, outperforming LIME (p ≤ 0.001)., Conclusions: Our results highlight the potential of an explainable radiomics model using amino acid PET scans as a diagnostic support to assist physicians in identifying glioma aggressiveness., Competing Interests: Declarations. Ethics approval: This study was performed in line with the principles of the Declaration of Helsinki and was registered on ClinicalTrials.gov (NCT06472440). Consent to participate: Informed written consent was obtained from all individual participants included in the study. Competing interests: All authors declare that there are no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Objective Structured Clinical Examination (OSCE) is a stressful exam assessing medical competencies. Stress coping strategies are expected to enhance students' performance during OSCE. The objective was to determine the effect of short preventive coping interventions on performance of medical students., Materials and Methods: Double-blinded, randomized controlled trial with multiple arms and a superiority hypothesis. Enrolment was proposed to each fourth-year undergraduate medical student convened to the Lyon Est University OSCE in 2022. There was no exclusion criterion. Students were randomized to one of four groups: standardized breathing with cardiac biofeedback (BFB), mindfulness-based intervention (MBI), positive psychology intervention (PPI), or control (CTRL). Each intervention was video-guided, lasted six minutes, and occurred just before starting the OSCE. The primary outcome was the academic OSCE score, assessed through specific grids by university examiners blinded to the interventions. Secondary outcomes included specific performance scores, and student perception of the influence of the intervention on their performance., Results: A total of 482 students were included. No difference was found between BFB (-0.17 [95%CI, -1.20 to 0.86], p  = .749), MBI (0.32 [95%CI, -0.71 to 1.36], p  = .540), or PPI groups (-0.25 [95%CI, -1.29 to 0.79], p  = .637) on the academic OSCE score compared to the control group, nor regarding the specific performance scores. Compared to the control group, the students perceived that the intervention influenced more positively their performance (BFB +3 [95%CI, 0-8]), p  < .001; MBI +4 [95%CI, 1-9], p  = .040; PPI +1 [95%CI, 0-4], p  = .040])., Conclusions: A single six-minute cardiac biofeedback, mindfulness, or positive psychology intervention performed by fourth-year medical students just before an OSCE did not improve their following academic performance. Still, students reported that the interventions helped them to enhance their performance. Future research should aim to further explore the perception of intervention on performance and potential long-term effects for students., Trial Registration: The study protocol was registered on ClinicalTrials.gov Identifier: NCT05393219.

Objective : This study determined real-life care trajectories before and after initiation of noninvasive ventilation (NIV) in patients with amyotrophic lateral sclerosis (ALS). Caregiver adherence to respiratory management recommendations and the associated survival rate of people with ALS were also assessed. Methods : Data were obtained from a tertiary center prospective ALS database that included 10 years of follow-up data for people with ALS. Results are presented numerically and with graphical time sequence analysis through K clustering (TAK) representation. Kaplan Meier and Cox models were used to determine survival and associated prognostic factors. Results: 109 patients with ALS patients were included; median [interquartile range] follow-up was 25.0 months [15.3-43.3]. During study timeframe patients had a median of 4.0 [2.0-6.0] clinical visits; death occurred in 54.1%. Median time between clinical visits was 3.9 [2.8-6.5] months, between arterial blood gases was 4.3 months [3.0-6.6], between spirometry testing was 5.8 months [4.1-8.2], and between nocturnal oximetry was 4.4 months [3.0-7.8]. Visualization of care trajectories TAK show marked heterogeneity in survival, time to NIV initiation, and time from NIV initiation to death. Mortality was correlated with NIV initiation and arterial carbon dioxide pressure increase. Conclusions : The current framework in ALS guidelines should be adapted to the ALS disease stage and individual patient characteristics. Understanding how subgroups of patients with ALS use healthcare services over time could help to highlight fragility areas and priorities in the allocation of care resources and implementation of best practices.

Background: In older people, medications with anticholinergic or sedative properties are associated with falls, frailty, and functional and cognitive impairment. These medications are often described as a subset of potentially inappropriate medications (PIMs). We examined the prevalence of anticholinergic or sedative medications to avoid in older people in France in 2023., Methods: This cross-sectional study used anonymized data from a large electronic healthcare database, the French National Health Data System (Système National des Données de Santé, SNDS). All people aged 65 years or older from January 1, 2023, to December 31, 2023, were included in this study. Dispensations of anticholinergic and sedative medications were identified according to PIM criteria (2023 American Geriatrics Society Beers Criteria and REMEDI[e]S tool). The prevalence of anticholinergic or sedative medications was assessed for the study population and by age (65-84 and 85 or older) and living place (home and institutionalized patients) subgroups in terms of number and percentage of patients., Results: This study included 16,938,152 patients aged 65 years or older (55% women). Among all patients, 79.8% were aged between 65 and 84 years and 20.2% were aged 85 years or older. Most patients lived at home (97.0%), and 3.0% were institutionalized. The prevalence of anticholinergic or sedative medications was 32.8% among all patients, 32.3% among 65-84 patients, and 34.8% among 85 or older patients, 32.1% among home patients, and 54.5% among institutionalized patients. The most commonly dispensed anticholinergic or sedative medications were oxazepam (5.27%), alprazolam (5.27%), zopiclone (4.85%), bromazepam (4.23%), metopimazine (2.88%), paroxetine (2.70%), nefopam (2.57%), and hydroxyzine (2.17%)., Conclusions: This study highlighted that anticholinergic and sedative medications to avoid in older people are still frequently prescribed despite the development and regular updating of PIM criteria. Future studies are needed to assess whether this has led to worsened outcomes among older adults who utilized these medications, and new initiatives should be developed to further promote deprescribing by prescribers and pharmacists., (© 2025 The American Geriatrics Society.)

Objective: Visuo-attentional dyslexia has been associated with impaired simultaneous visual processing of multiple items made of separable features (i.e. symbols). We designed a visual search screening test, consisting to find the (unique) black circle among circles of various colours versus among circles combined with a bar of various length and location. We evaluated its reliability and its validity to detect visuo-attentional deficit prone to affect reading. RESULTS OF STUDY 1: Assessment of 2015 children between 3 and 11 years old established that the screening test was feasible from kindergarten, and that our index contrasting visual search performance for symbols relative to colours (the Temporal Gap) decreased with age. Satisfactory test-retest reliability of the standardised index (independent from age) was found on a sample of 69 individuals. RESULTS OF STUDY 2: Reading speed and inaccuracy assessed for 769 4th and 5th grades children were significantly correlated to the Temporal Gap. A Temporal Gap above 75th centile predicted reading efficiency deficit above 95th percentile with 63 % sensitivity and 71 % specificity., Perspectives: Our screening test can be used in clinic to detect whether a child with developmental dyslexia presents visuo-attentional fragility prone to contribute to the reading difficulties. Its validity as early predictor of a risk to develop visuo-attentional dyslexia needs further investigation., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Presurgical evaluation aims to localize the seizure onset zone (SOZ) for a tailored resection. Interictal [ 18 F]fluorodeoxyglucose PET is now an established test to lateralize and/or localize the SOZ, particularly if MR imaging is negative or if the noninvasive assessment shows discrepancies. PET can show hypometabolic areas associated with SOZ and the potential altered metabolic brain networks. It is very sensitive, and this is increased if images are read coregistered to the patient's MR imaging. PET hypometabolic intensity and pattern show prognostic value., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Precise localization of the epileptogenic zone is critical for successful epilepsy surgery. However, imbalanced datasets in terms of epileptic vs. normal electrode contacts and a lack of standardized evaluation guidelines hinder the consistent evaluation of automatic machine learning localization models., Methods: This study addresses these challenges by analyzing class imbalance in clinical datasets and evaluating common assessment metrics. Data from 139 drug-resistant epilepsy patients across two Institutions were analyzed. Metric behaviors were examined using clinical and simulated data., Results: Complementary use of Area Under the Receiver Operating Characteristic (AUROC) and Area Under the Precision-Recall Curve (AUPRC) provides an optimal evaluation approach. This must be paired with an analysis of class imbalance and its impact due to significant variations found in clinical datasets., Conclusions: The proposed framework offers a comprehensive and reliable method for evaluating machine learning models in epileptogenic zone localization, improving their precision and clinical relevance., Significance: Adopting this framework will improve the comparability and multicenter testing of machine learning models in epileptogenic zone localization, enhancing their reliability and ultimately leading to better surgical outcomes for epilepsy patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Background: Estimates suggest that approximatively 25% of the world population will be overweight in 2025. Better understanding of the pathophysiology of obesity will help to develop future therapeutics. Serotonin subtype 6 receptors (5-HT 6 ) have been shown to be critically involved in appetite reduction and weight loss. However, it is not known if the pathological cascade triggered by obesity modifies the density of 5-HT 6 receptors in the brain., Methods: Influence of diet-induced obesity (DIO) in Wistar rats was explored using MRI (whole-body fat) and PET ([ 18 F]2FNQ1P as a specific 5-HT 6 radiotracer). The primary goal was to monitor the 5-HT 6 receptor density before and after a 10-week diet (DIO group). The secondary goal was to compare 5-HT 6 receptor densities between DIO group, Wistar control diet group, Zucker rats (with genetic obesity) and Zucker lean strain rats., Results: Wistar rats fed with high-fat diet showed higher body fat gain than Wistar control diet rats on MRI. [ 18 F]2FNQ1P PET analysis highlighted significant clusters of voxels (located in hippocampus, striatum, cingulate, temporal cortex and brainstem) with increased binding after high-fat diet (p < 0.05, FWE corrected)., Conclusion: This study sheds a new light on the influence of high-fat diet on 5-HT 6 receptors. This study also positions [ 18 F]2FNQ1P PET as an innovative tool to explore neuronal consequences of obesity or eating disorder pathophysiology., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All experiments were carried out under a protocol approved by the local review board (“Comité d’éthique pour l’Expérimentation Animale Neurosciences Lyon”, registration code: C2EA—42), authorized by the French Ministry of Higher Education and Research (no. 25505-2020052514313066V6, and were in accordance with European directives on the protection and use of laboratory animals (Council Directive 2010/63/UE; French decree 2013-118)., (© 2024. The Author(s).)

The slowing and reduction of auditory responses in the brain are recognized side effects of increased pure tone thresholds, impaired speech recognition, and aging. However, it remains controversial whether central slowing is primarily linked to brain processes as atrophy, or is also associated with the slowing of temporal neural processing from the periphery. Here we analyzed electroencephalogram (EEG) responses that most likely reflect medial geniculate body (MGB) responses to passive listening of phonemes in 80 subjects ranging in age from 18 to 76 years, in whom the peripheral auditory responses had been analyzed in detail (Schirmer et al., 2024). We observed that passive listening to vowels and phonemes, specifically designed to rely on either temporal fine structure (TFS) for frequencies below the phase locking limit (<1500 Hz), or on the temporal envelope (TENV) for frequencies above phase locking limit, entrained lower or higher neural EEG responses. While previous views predict speech content, particular in noise to be encoded through TENV, here a decreasing phoneme-induced EEG amplitude over age in response to phonemes relying on TENV coding could also be linked to poorer speech-recognition thresholds in quiet. In addition, increased phoneme-evoked EEG delay could be correlated with elevated extended high-frequency threshold (EHF) for phoneme changes that relied on TFS and TENV coding. This may suggest a role of pure-tone threshold averages (PTA) of EHF for TENV and TFS beyond sound localization that is reflected in likely MGB delays. When speech recognition thresholds were normalized for pure-tone thresholds, however, the EEG amplitudes remained insignificant, and thereby became independent of age. Under these conditions, poor speech recognition in quiet was found together with a delay in EEG response for phonemes that relied on TFS coding, while poor speech recognition in ipsilateral noise was observed as a trend of shortened EEG delays for phonemes that relied on TENV coding. Based on previous analyses performed in these same subjects, elevated thresholds in extended high-frequency regions were linked to cochlear synaptopathy and auditory brainstem delays. Also, independent of hearing loss, poor speech-performing groups in quiet or with ipsilateral noise during TFS or TENV coding could be linked to lower or better outer hair cell performance and delayed or steeper auditory nerve responses at stimulus onset. The amplitude and latency of MGB responses to phonemes requiring TFS or TENV coding, dependent or independent of hearing loss, may thus be a new predictor of poor speech recognition in quiet and ipsilateral noise that links deficits in synchronicity at stimulus onset to neocortical activity. Amplitudes and delays of speech EEG responses to syllables should be reconsidered for future hearing-aid studies., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare. All co-authors have seen and agreed with the manuscript's contents, and there is no financial interest to report., (Copyright © 2024. Published by Elsevier Inc.)

Background and Purpose: Disabling dystonia despite optimal medical treatment is common in Wilson disease (WD). No controlled study has evaluated the effect of deep brain stimulation (DBS) on dystonia related to WD. This study was undertaken to evaluate the efficacy of DBS on dystonia related to WD., Methods: A meta-analysis of an N-of-1 prospective, randomized, double-blind, multicenter DBS study was conducted at two French WD reference centers. Main inclusion criteria were patients with WD, stabilized for at least 6 months with significant disability due to dystonia despite optimized medical treatment. The subthalamic nucleus (STN) was targeted for bradykinetic patients with tonic dystonia, and the internal globus pallidus (GPi) was chosen for patients with hyperkinetic dystonia. Each patient underwent two periods of DBS "on" and two periods of DBS "off," each lasting 4 months. The order of stimulation conditions was randomized. The primary outcome was the change in the Canadian Occupational Performance Measure Performance (COPM-P) and Satisfaction scores after each 4-month period. Secondary outcomes were changes in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) severity and disability scores and Unified Wilson's Disease Rating Scale (UWDRS) scores., Results: Between 12 May 2016 and 7 October 2022, three patients were included. Two patients received bilateral GPi DBS, and one received bilateral STN DBS. There was no change of COPM-P (p = 0.956), BFMDRS, and UWDRS scores. No serious adverse events were reported., Conclusions: STN or GPi DBS are ineffective on dystonia related to WD., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objectives: Catch-up saccades help to compensate for loss of gaze stabilization during rapid head rotation in case of vestibular deficit. While overt saccades observed after head rotation are obviously visually guided, some of these catch-up saccades occur with shorter latency while the head is still moving, anticipating the needed final eye position. These covert saccades seem to be generated based on the integration of multisensory inputs. Vision could be one of these inputs, but the known delay for triggering visually guided saccades questions this possibility. The main objective of this study is to evaluate the potential role of visual information for controlling (triggering and guiding) the first catch-up saccades in patients suffering from bilateral vestibulopathy. To investigate this, we used head impulse test in a virtual reality setting allowing to create different visuo-vestibular mismatch conditions., Design: Twelve patients with bilateral vestibulopathy were recruited. We assessed in our patient group the validity of our virtual reality head impulse testing approach by comparing recorded eye and head movement to classical video head impulse test. Then, using the virtual reality system, we tested head impulse test under both normal and three visuo-vestibular mismatch conditions. In these mismatch conditions, the movement of the visual scene relative to the head movement was altered: decreased in amplitude by 50% (half), nullified (freeze), or inverted in direction (inverse). Recorded eye and head movements during these different conditions were then analyzed, more specifically the characteristics of the first catch-up saccade., Results: Impaired vestibulo-ocular reflex required subjects to systematically perform catch-up saccades, which could be covert or overt. The latency of the first catch-up saccade increased along with the amount of visuo-vestibular mismatch between the four conditions (i.e., from normal to half to freeze to inverse) and, consequently, the mean percentage of covert saccades decreased with increasing visual feedback error. However, the freeze and inverse conditions allowed us to reveal the existence of many saccades performed in the wrong direction relative to visual feedback. These visually discordant saccades were present in over half of the trials, they were mainly covert and their percentage was inversely correlated with residual vestibulo-ocular reflex gain., Conclusions: Visual information significantly impacts catch-up saccade latency and the relative number of covert saccades during head impulse testing in vestibular deficit. However, in more than 50% of trials involving a visuo-vestibular mismatch, catch-up saccades remained directed in the compensatory direction relative to head movement, that is, they were visually discordant. Therefore, contrary to previously published proposals, visual information does not appear to be the primary component of the multisensory inputs required for the production of catch-up covert saccades in vestibular deficit. Finally, we discuss a new nomenclature of catch-up saccades in case of vestibular deficit introducing the terms of open and closed loop saccades., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The American Auditory Society.)

Purpose: Psychopharmacology prescriptions are complex, partly due to the complexity of the relationship between diagnosis and its etiology, as well as the iatrogenic impact on symptomatology. Many multidisciplinary tools exist to optimize their management and improve evidence-based practice. However, their multidisciplinary integration seems to be a challenge. This study aimed to collect information on barriers and facilitators perceived by hospital health professionals regarding the use of multidisciplinary tools to address complex situations in psychopharmacology., Research Design and Methods: A mixed-methods research approach using semi-structured interviews was conducted with physicians and pharmacists from 11 hospital institutions. An interview guide developed from the COM-B model (Capability, Opportunity, and Motivation - Behavior) was used to identify barriers and facilitators to the use of multidisciplinary tools. Data were analyzed using thematic analysis to identify emerging themes and mapped to the COM-B model., Results: 28 professionals were interviewed. Identified barriers were: lack of knowledge and time to address complex situations, incomplete medical records, lack of easily accessible multidisciplinary tools, insufficient levels of evidence in psychopharmacology. Identified facilitators were: continuing education, communication and networking among professionals, implementation of adapted and shared resources, deprescribing, awareness of medication-induced iatrogenesis, accessibility of tools for all populations., Conclusion: Identified barriers and facilitators in the use of multidisciplinary tools for complex situations in psychopharmacology helped to model factors that enable behavior change. Answers need to be provided to help professionals ensure and optimize psychopharmacological therapies., Competing Interests: The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties., (© 2024 Lebrat et al.)

Objectives: In patients with mesial temporal lobe epilepsy (mTLE) and normal MRI, anterior temporal lobectomy sparing the hippocampus might be considered because of the risk of post-operative memory deficit. However, it is unclear whether some patients with normal MRI and non-invasive EEG and semiological pattern highly suggestive of mesial temporal seizures demonstrate a seizure onset network sparing the hippocampus, potentially warranting surgery., Methods: A retrospective study of 17 patients with mTLE epilepsy and normal MRI who underwent SEEG. Only patients whose non-invasive presurgical data suggested an unilateral mesial temporal epileptogenic zone (EZ), as defined by combination of ictal semiology and ictal EEG during scalp video-EEG, were included. SEEG data were analyzed using both visual and quantitative approaches. Two EZ organization were defined: (i) EZ involved the hippocampus at the onset of the ictal discharge (HIP group): (ii) patients in whom a delay>1sec was observed between the seizure onset and the involvement of the hippocampus (nHIP group). Non-invasive clinical and functional imaging data, as well as post-operative outcomes, were compared across groups., Results: Eleven patients were included in HIP group and 6 in the nHIP group. In the nHIP group, the maximal epileptogenicity was in the amygdala in five patients and in the entorhinal cortex in one. The hippocampus normalized interictal spiking activity was not different between groups. None of the patients characteristics collected during the non-invasive presurgical workup was associated with the SEEG-based organization of the EZ. Twelve patients underwent a surgical resection, including temporal cortectomy sparing hippocampus in six. Seizure and neuropsychological post-operative outcomes were similar., Conclusion: In patients with MRI-normal mTLE, SEEG should be included in the surgical decision-making process because seizure organization cannot be predicted from non-invasive investigations. When hippocampus is not included in the EZ, temporal resection sparing the hippocampus can be considered., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Objective: What are young children trying to express when they cry at night? According to Sadeh, parental beliefs about why their child is crying may play a role in the development and persistence of their child's insomnia. The aim of this study was to create a scale that specifically assesses these parental interpretations in different dimensions., Methods: Children aged between 6 months and 3 years with either good sleep habits or behavioural insomnia were recruited. An initial, 20-item scale for the beliefs of why one's baby is crying at night was developed, with all items on a 7-point Likert span. The results of this scale from a large sample were then submitted to Exploratory (EFA) and confirmatory (CFA) factor analyses to converge on a final version and evaluate its psychometric properties and validity., Results: Among the 1009 subjects included in the analyses (46.2 % female, mean age: 1.63 ± 0.73, good sleepers n = 425 and bad sleepers n = 584). After the factor analysis was performed, a 14-item scale with 4 subscales quantifying each interpretation type resulted: namely, "Need for attachment" (5 items), "Need to cry before falling asleep" (3 items), "Leaving a child to cry during the night is traumatizing for the child" (4 items) and "Is in pain" (2 items). The CFA further confirmed an appropriate fit. The most divergent subscale between groups was the "Need for attachment" subscale., Conclusion: This study proposes the first scale known to focus exclusively on parent interpretations of their child's night-time crying, without taking into account their nursing behaviours. It provides a clinical tool for more effectively discussing with parents, in order to address potential dysfunctional beliefs in the context of early childhood insomnia complaints, as well as a research tool for considering cognitive dimensions in the aetiology and treatment of behavioural insomnia., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

In primates, the presence of a face in a visual scene captures attention and rapidly directs the observer's gaze to the face, even when the face is not relevant to the task at hand. Here, we explored a neural circuit that might potentially play a causal role in this powerful behavior. In our previous research, two monkeys received microinfusions of muscimol, a γ-aminobutyric acid type A (GABAA)-receptor agonist, or saline (as a control condition) in separate sessions into individual or pairs of four inferotemporal face patches (middle and anterior lateral and fundal), as identified by an initial localizer experiment. Then, using fMRI, we measured the impact of each inactivation condition on responses in the other face patches relative to the control condition. In this study, we used the same method and measured the impact of each inactivation condition on responses in the FEF and the lateral intraparietal area, two regions associated with attentional processing, while face and nonface object stimuli were viewed. Our results revealed potential relationships between inferotemporal face patches and these two attention-related regions: The inactivation of the middle lateral and anterior fundal face patches had a pronounced impact on FEF, whereas the inactivation of the middle and anterior lateral face patches had a noticeable influence on LIP. Together, these initial exploratory findings document a circuit that potentially underlies the attentional capture of faces. Confirmation of the role of this circuit remains to be accomplished in the context of a paradigm that explicitly tests the attentional capture of faces., (© 2024 Massachusetts Institute of Technology.)

The French migraine management recommendations were published in 2021. However, in the last three years, new data have come to light and new drugs have been approved (eptinezumab, rimegepant and atogepant) by the European Medicines Agency that require us to take a position on their use and to update certain elements of the recommendations. The first important message concerns the position of the French Headache Society on the use of preventive treatments (monoclonal antibodies and gepants) targeting the calcitonin gene-related peptide (CGRP) pathway. In terms of efficacy and safety, and as suggested by other national headache societies, these treatments can be offered as first-line treatment, although the scope defined by the French national health authority for possible reimbursement is limited to patients with severe migraine, at least eight headache days per month and for whom two previous preventive treatments have failed. Another important change concerns the position of topiramate as a preventive treatment for migraine in women of childbearing age. This treatment has been proposed as a first-line treatment for chronic migraine. However, recent pharmacovigilance data have highlighted a potential adverse effect on neurodevelopment in children exposed in utero. As a result, this treatment is formally contraindicated during pregnancy and must be used with extreme caution in women of childbearing age (effective contraception, no therapeutic alternative available and annual follow-up as with valproate). It can therefore no longer be offered as first-line treatment for women of childbearing age., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Serotonin 5-HT 1A receptor agonists are prime candidates for CNS drug discovery due to their involvement physiological and pathological processes relevant to neurology and psychiatry. However, the lack of target specificity of many previously characterized agonists has long been a barrier to pharmacological and therapeutic progress. Some of the obstacles may be overcome through the recent concept of biased agonism, which has attracted considerable attention to the development of novel chemical entities at 5-HT, and particularly 5-HT 1A receptors, by specifically targeting intracellular signalling pathways that may themselves be linked to specific brain regions and therapeutic indications. There is now abundant translational data demonstrating distinct molecular and functional pharmacological signatures between different 5-HT 1A receptor agonists, opening new opportunities for research in neurology and psychiatry. Nevertheless, important limitations need to be overcome, including understanding the precise molecular basis for biased agonism, the need for improved translatable models, and the currently limited clinical data on biased agonists. Here, we review the current limits of our knowledge of 5-HT 1A receptor biased agonists and the limitations of available pharmacological tools, counterbalanced by the translational possibilities and therapeutic perspectives opened by novel, highly selective 5-HT1A receptor drug-candidates. This article is part of the Special Issue on "Ligand Bias"., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Adrian Newman-Tancredi is an employee and stockholder of Neurolixis, Inc., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Meditation is a mental training approach that can improve mental health and well-being in aging. Yet the underlying mechanisms remain unknown. The Medit-Ageing model stipulates that three mechanisms - attentional, constructive, and deconstructive - upregulate positive psycho-affective factors and downregulate negative ones. To test this hypothesis, we measured brain structural MRI and perfusion, negative and positive psycho-affective composite scores, and meditation mechanisms in 27 older expert meditators and 135 meditation-naive older controls. We identified brain and psycho-affective differences and performed mediation analyses to assess whether and which meditation mechanisms mediate their links.Meditators showed significantly higher volume in fronto-parietal areas and perfusion in temporo-occipito-parietal areas. They also had higher positive and lower negative psycho-affective scores. Attentional and constructive mechanisms both mediated the links between brain differences and the positive psycho-affective score whereas the deconstructive mechanism mediated the links between brain differences and the negative psycho-affective score.Our results corroborate the Medit-Ageing model, indicating that, in aging, meditation leads to brain changes that decrease negative psycho-affective factors and increase positive ones through relatively specific mechanisms. Shedding light on the neurobiological and psycho-affective mechanisms of meditation in aging, these findings provide insights to refine future interventions., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Delirium, also known as acute confusional state, is an acute brain disorder characterized by cognitive disturbances, particularly attentional deficits, potential behavioral changes, and altered vigilance, with a sudden onset and fluctuating course. It is a common condition among hospitalized older patients and has serious consequences for the patient, their family, and the healthcare system. It is considered an "acute brain failure" that often occurs in the context of underlying cognitive and cerebral vulnerability, similar to how acute kidney injury complicates chronic kidney disease or how acute heart failure exacerbates chronic heart failure - usually in the presence of a precipitating medical factor, often infectious, metabolic, perioperative, or neurological. This narrative review aims to describe the symptoms that allow the diagnosis of delirium in older adults, the available diagnostic or screening tools, as well as the complex and bidirectional relationships between delirium and dementia. The management of delirium, including non-pharmacological measures, will be discussed, along with symptomatic pharmacological treatments, which should be reserved for severe cases despite their low level of evidence., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Tools can extend the sense of touch beyond the body, allowing the user to extract sensory information about distal objects in their environment. Though research on this topic has trickled in over the last few decades, little is known about the neurocomputational mechanisms of extended touch. In 2016, along with our late collaborator Vincent Hayward, we began a series of studies that attempted to fill this gap. We specifically focused on the ability to localize touch on the surface of a rod, as if it were part of the body. We have conducted eight behavioral experiments over the last several years, all of which have found that humans are incredibly accurate at tool-extended tactile localization. In the present article, we perform a model-driven re-analysis of these findings with an eye toward estimating the underlying parameters that map sensory input into spatial perception. This re-analysis revealed that users can almost perfectly localize touch on handheld tools. This raises the question of how humans can be so good at localizing touch on an inert noncorporeal object. The remainder of the paper focuses on three aspects of this process that occupied much of our collaboration with Vincent: the mechanical information used by participants for localization; the speed by which the nervous system can transform this information into a spatial percept; and whether body-based computations are repurposed for tool-extended touch. In all, these studies underscore the special relationship between bodies and tools.

Background: Cardiovascular risk factors represent an important health issue in older adults. Previous findings suggest that meditation training could have a positive impact on these risk factors. The objective of this study was to investigate the effects of an 18-month meditation-based intervention on cardiovascular health., Methods: Age-Well was a randomized, controlled superiority trial with blinded end point assessment, including community-dwelling cognitively unimpaired adults 65 years and older enrolled between November 24, 2016, and March 5, 2018, in France. One hundred and thirty-four participants were included in this secondary analysis. Participants were randomly affected to an intervention group that received an 18-month meditation-based program or to comparison groups (active control group i.e. non-native language training or passive control group i.e. no intervention). The main outcome was change in the Framingham Risk Score (FRS); other outcomes were changes in cardiovascular and metabolic risk factors., Results: There was no difference in FRS change after 18 months between trial arms (p = .38). When assessing individual cardiovascular or metabolic risk factors, meditation training was associated with a greater reduction in diastolic blood pressure than the comparison group in participants with intermediate to high cardiovascular risk (FRS > 10%) at baseline (p = .03)., Conclusion: An 18-month meditation training was not effective to increase overall cardiovascular health in older adults, but improved diastolic blood pressure in a subgroup analysis including at-risk participants. These results suggest a potential benefit of a long-term meditation intervention in older adults at-risk of cardiovascular diseases, and highlights the need for future research in more targeted populations., Trial Registration: ClinicalTrials.gov Identifier: NCT02977819., Competing Interests: Declarations Ethics approval and consent to participate The Age-Well RCT was approved by the ethics committee (Comité de Protection des Personnes CPP Nord-Ouest III, Caen; trial registration numbers: EudraCT: 2016–002441-36; IDRCB: 2016-A01767-44; ClinicalTrials.gov Identifier: NCT02977819). All participants gave their written informed consent to the study prior to enrollment. Consent for publication Not applicable. Competing interests Independent of this work, AGC is an unpaid sub-investigator or principal investigator in Alzheimer’s disease clinical trials: NCT04867616 (UCB Pharma), NCT04241068 (Biogen), NCT05310071 (Envision), NCT03446001 (TauRx Therapeutics), NCT03444870 (Roche), NCT04374253 (Roche), NCT04777396 (Novo Nordisk), NCT04777409 (Novo Nordisk), NCT04770220 (Alzheon), NCT05423522 (Medesis Pharma).GC reported grants, personal fees and non-financial support from Institut National de la Santé et de la Recherche Médicale (Inserm), grants from European Union’s Horizon 2020 Research and Innovation program under grant agreement No 667696 (PI), grants from Fondation d’entreprise MMA des Entrepreneurs du Futur, during the conduct of the study; personal fees from Fondation Entrepreneurs MMA, grants and personal fees from Fondation Alzheimer, grants from Région Normandie, grants from Fondation Recherche Alzheimer, grants from Association France Alzheimer, outside the submitted work.GP has received research support from the European Union’s Horizon 2020 Research and Innovation program under grant agreement No 667696, from the Institut National de la Santé et de la Recherche Médicale (Inserm) and from Région Normandie.GP, GC participated to the DSMB of the Age-Well trial and to the ExCom of Medit-Ageing.No other disclosures were reported., (© 2024. The Author(s).)

The complexity of natural environments requires highly flexible mechanisms for adaptive processing of single and multiple stimuli. Neuronal oscillations could be an ideal candidate for implementing such flexibility in neural systems. Here, we present a framework for structuring attention-guided processing of complex visual scenes in humans, based on multiplexing and phase coding schemes. Importantly, we suggest that the dynamic fluctuations of excitability vary rapidly in terms of magnitude, frequency and wave-form over time, i.e., they are not necessarily sinusoidal or sustained oscillations. Different elements of single objects would be processed within a single cycle (burst) of alpha activity (7-14 Hz), allowing for the formation of coherent object representations while separating multiple objects across multiple cycles. Each element of an object would be processed separately in time-expressed as different gamma band bursts (>30 Hz)-along the alpha phase. Since the processing capacity per alpha cycle is limited, an inverse relationship between object resolution and size of attentional spotlight ensures independence of the proposed mechanism from absolute object complexity. Frequency and wave-shape of those fluctuations would depend on the nature of the object that is processed and on cognitive demands. Multiple objects would further be organized along the phase of slower fluctuations (e.g., theta), potentially driven by saccades. Complex scene processing, involving covert attention and eye movements, would therefore be associated with multiple frequency changes in the alpha and lower frequency range. This framework embraces the idea of a hierarchical organization of visual processing, independent of environmental temporal dynamics., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Bonnefond et al.)

Social Facilitation/Inhibition (SFI) refers to how others' presence influences task performance positively or negatively. Our previous study revealed that peer presence modulated saccadic eye movements, a fundamental sensorimotor activity. Pro- and anti-saccades were either facilitated or inhibited depending on trial block complexity (Tricoche et al., 2020). In the present fMRI study, we adapted our paradigm to investigate the neural basis of SFI on saccades. Considering inter- and intra-individual variabilities, we evaluated the shared and distinct neural patterns between social facilitation and inhibition. We predicted an involvement of the saccade-related and attention networks, alongside the Theory-of-Mind (ToM) network, with opposite activity changes between facilitation and inhibition. Results confirmed peer presence modulation in fronto-parietal areas related to saccades and attention, in opposite directions for facilitation and inhibition. Additionally, the ventral attention network was modulated during inhibition. Default mode regions, including ToM areas, were also modulated. Finally, pupil size, often linked to arousal, increased with peers and correlated with dorsal attention regions and anterior insula activities. These results suggest that SFI engages task-specific and domain-general networks, modulated differently based on observed social effect. Attention network seemed to play a central role at both basic (linked to arousal or vigilance) and cognitive control levels., (© The Author(s) 2024. Published by Oxford University Press.)

Understanding the factors that predict why some individuals perceive to respond more to meditation training than others could impact the development, efficacy, adherence levels, and implementation of meditation-based interventions. We investigated individual-level variables associated with self- and teacher-perceived responsiveness to longer-term meditation training. This study presents a secondary analysis of the Age-Well trial (NCT02977819, 30/11/2016) and includes 90 healthy older adults (65-84 years) that were randomised to an 18-month meditation training or a non-native language (English) training. Responsiveness was measured post-intervention using participants' and teachers' ratings of four psychological domains (connection, positive/negative emotions, meta-awareness) in relation to two contexts (during sessions, in daily life), teachers' perception of overall benefit, and a global composite comprising all self- and teacher-perceived responsiveness measures. Linear regression modelling indicates that, when including baseline variables (sex, education, neuroticism, cognition, expectancy) and engagement (hours of formal practice during intervention), only higher levels of engagement were associated with higher global composite scores (standardised estimate = 0.50, 95% CI: 0.24-0.77, p < 0.001). Global composite scores were not correlated with pre-post changes in well-being. Findings indicate that more time spent practising meditation was related to greater perceived intervention effects. We suggest that future studies closely monitor levels of engagement and map reasons for disengagement., (© 2024. The Author(s).)

Background: Perceptual and speech production abilities of children with cochlear implants (CIs) are usually tested by word and sentence repetition or naming tests. However, these tests are quite far apart from daily life linguistic contexts., Aim: Here, we describe a way of investigating the link between language comprehension and anticipatory verbal behaviour promoting the use of more complex listening situations., Methods and Procedure: The setup consists in watching the audio-visual dialogue of two actors. Children's gaze switches from one speaker to the other serve as a proxy of their prediction abilities. Moreover, to better understand the basis and the impact of anticipatory behaviour, we also measured children's ability to understand the dialogue content, their speech perception and memory skills as well as their rhythmic skills, that also require temporal predictions. Importantly, we compared children with CI performances with those of an age-matched group of children with normal hearing (NH)., Outcomes and Results: While children with CI revealed poorer speech perception and verbal working memory abilities than NH children, there was no difference in gaze anticipatory behaviour. Interestingly, in children with CI only, we found a significant correlation between dialogue comprehension, perceptual skills and gaze anticipatory behaviour., Conclusion: Our results extend to a dialogue context of previous findings showing an absence of predictive deficits in children with CI. The current design seems an interesting avenue to provide an accurate and objective estimate of anticipatory language behaviour in a more ecological linguistic context also with young children., What This Paper Adds: What is already known on the subject Children with cochlear implants seem to have difficulties extracting structure from and learning sequential input patterns, possibly due to signal degradation and auditory deprivation in the first years of life. They also seem to have a reduced use of contextual information and slow language processing among children with hearing loss. What this paper adds to existing knowledge Here we show that when adopting a rather complex linguistic context such as watching a dialogue of two individuals, children with cochlear implants are able to use the speech and language structure to anticipate gaze switches to the upcoming speaker. What are the clinical implications of this work? The present design seems an interesting avenue to provide an accurate and objective estimate of anticipatory behaviour in a more ecological and dynamic linguistic context. Importantly, this measure is implicit and it has been previously used with very young (normal-hearing) children, showing that they spontaneously make anticipatory gaze switches by age two. Thus, this approach may be of interest to refine the speech comprehension assessment at a rather early age after cochlear implantation where explicit behavioural tests are not always reliable and sensitive., (© 2024 The Author(s). International Journal of Language & Communication Disorders published by John Wiley & Sons Ltd on behalf of Royal College of Speech and Language Therapists.)

Many recent studies indicate that control of decisions and actions is integrated during interactive behavior. Among these, several carried out in humans and monkeys conclude that there is a coregulation of choices and movements. Another perspective, based on human data only, proposes a decoupled control of decision duration and movement speed, allowing, for instance, trading decision duration for movement duration when time pressure increases. Crucially, it is not currently known whether this ability to flexibly dissociate decision duration from movement speed is specific to humans, whether it can vary depending on the context in which a task is performed, and whether it is stable over time. These are important questions to address, especially to rely on monkey electrophysiology to infer the neural mechanisms of decision-action coordination in humans. To do so, we trained two macaque monkeys in a perceptual decision-making task and analyzed data collected over multiple behavioral sessions. Our findings reveal a strong and complex relationship between decision duration and movement vigor. Decision duration and action duration can covary but also "compensate" each other. Such integrated but decoupled control of decisions and actions aligns with recent studies in humans, validating the monkey model in electrophysiology as a means of inferring neural mechanisms in humans. Crucially, we demonstrate for the first time that this control can evolve with experience, in an adapted manner. Together, the present findings contribute to deepening our understanding of the integrated control of decisions and actions during interactive behavior. NEW & NOTEWORTHY The mechanism by which the integrated control of decisions and actions occurs, coupled or interactive but decoupled, is debated. In the present study, we show in monkeys that decisions and actions influence each other in a decoupled way. For the first time, we also demonstrate that this control can evolve depending the subject's experience, allowing the trade of movement time for decision time and limiting the temporal discounting of reward value.

Body representations (BR) for action are critical to perform accurate movements. Yet, behavioral measures suggest that BR are distorted even in healthy people. However, the upper limb has mostly been used as a probe so far, making difficult to decide whether BR are truly distorted or whether this depends on the effector used as a readout. Here, we aimed to assess in healthy humans the accuracy of the eye and hand effectors in localizing somatosensory targets, to determine whether they may probe BR similarly. Twenty-six participants completed two localization tasks in which they had to localize an unseen target (proprioceptive or tactile) with either their eyes or hand. Linear mixed model revealed in both tasks a larger horizontal (but not vertical) localization error for the ocular than for the manual localization performance. However, despite better hand mean accuracy, manual and ocular localization performance positively correlated to each other in both tasks. Moreover, target position also affected localization performance for both eye and hand responses: accuracy was higher for the more flexed position of the elbow in the proprioceptive task and for the thumb than for the index finger in the tactile task, thus confirming previous results of better performance for the thumb. These findings indicate that the hand seems to beat the eyes along the horizontal axis when localizing somatosensory targets, but the localization patterns revealed by the two effectors seemed to be related and characterized by the same target effect, opening the way to assess BR with the eyes when upper limb motor control is disturbed., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Response inhibition is a crucial component of executive control. Although mainly studied in upper limb tasks, it is fully implicated in gait initiation. Here, we assessed the influence of proactive and reactive inhibitory control during gait initiation in healthy adult participants. For this purpose, we measured kinematics and electroencephalography (EEG) activity (event-related potential [ERP] and time-frequency data) during a modified Go/NoGo gait initiation task in 23 healthy adults. The task comprised Go-certain, Go-uncertain, and NoGo conditions. Each trial included preparatory and imperative stimuli. Our results showed that go-uncertainty resulted in delayed reaction time, without any difference for the other parameters of gait initiation. Proactive inhibition, that is, Go uncertain versus Go certain conditions, influenced EEG activity as soon as the preparatory stimulus. Moreover, both proactive and reactive inhibition influenced the amplitude of the ERPs (central P1, occipito-parietal N1, and N2/P3) and theta and alpha/low beta band activities in response to the imperative-Go-uncertain versus Go-certain and NoGo versus Go-uncertain-stimuli. These findings demonstrate that the uncertainty context; induced proactive inhibition, as reflected in delayed gait initiation. Proactive and reactive inhibition elicited extended and overlapping modulations of ERP and time-frequency activities. This study shows the protracted influence of inhibitory control in gait initiation., (© 2024 The Author(s). Psychophysiology published by Wiley Periodicals LLC on behalf of Society for Psychophysiological Research.)

Background: [ 18 F]F13640 is a new PET radiopharmaceutical for brain molecular imaging of serotonin 5-HT 1A receptors. Since we intend to use this radiopharmaceutical in psychiatric studies, it is crucial to establish possible sensitivity modification of 5-HT 1A receptors availability during an acute stress exposure. In this study, we first assessed the cerebrometabolic effects of a new animal model of stress with [ 18 F]FDG and then proceeded to test for effects of this model on the cerebral binding of [ 18 F]F13640, a 5-HT 1A receptors PET radiopharmaceutical., Methods: Four groups of male Sprague-Dawley were used to identify the optimal model: "stressed group" (n = 10), "post-traumatic stress disorder (PTSD) group" (n = 9) and "restraint group" (n = 8), compared with a control group (n = 8). All rats performed neuroimaging [ 18 F]FDG μPET-CT to decipher which model was the most appropriate to test effects of stress on radiotracer binding. Subsequently, a group of rats (n = 10) underwent two PET imaging acquisitions (baseline and PTSD condition) using the PET radiopharmaceutical [ 18 F]F13640 to assess influence of stress on its binding. Voxel-based analysis was performed to assess [ 18 F]FDG or [ 18 F]F13640 changes., Results: In [ 18 F]FDG experiments, the PTSD group showed a pattern of cerebrometabolic activation in various brain regions previously implicated in stress (amygdala, perirhinal cortex, olfactory bulb and caudate). [ 18 F]F13640 PET scans showed increased radiotracer binding in the PTSD condition in caudate nucleus and brainstem., Conclusions: The present study demonstrated stress-induced cerebrometabolic activation or inhibition of various brain regions involved in stress model. Applying this model to our radiotracer, [ 18 F]F13640 showed few influence of stress on its binding. This will enable to rule out any confounding effect of stress during imaging studies., Competing Interests: Declaration of competing interest Nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp + neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp + neurons, neurons expressing nitric oxide synthase 1 (Nos1 + neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit. Nos1 + neurons also project to areas that control wide forebrain activity. Ablating Crhbp + neurons reduces sleep and impairs REM sleep atonia. In Parkinson's disease patients with REM sleep behavior disorders, CRHBP-immunoreactive neurons are largely reduced and contain pathologic α-synuclein, providing insight into the mechanisms underlying the sleep deficits characterizing this disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Contrary to expert readers, children learning to read have limited ability to preprocess letters in parafoveal vision. Parafoveal letters induce crowding cost: the features of neighboring letters interfere with target letter identification. We longitudinally studied the weight of parafoveal cost and benefit in two group of children (N = 42), during their first school year (Group 1) and at the end of second school year (Groupe 2). Using a novel digit-tracking method, a blurred text was presented and rendered unblurred by touching the screen, allowing the user to discover a window of visible text as the finger moved along it. We compared two conditions: (1) a large window, where crowding was enhanced by the presence of parafoveal information; (2) a small window, where crowding was suppressed by blurred parafoveal information. Finger kinematics were simultaneously recorded. We found that at the beginning of first-grade, digital fixations - brief slowing or stopping of the finger on a specific point - are significantly longer in the large compared to the small window condition, as parafoveal crowding increases text processing difficulty. This effect diminishes and disappears at the end of second-grade as reading performance improves. In the large window condition, longer digital saccades - rapid movements of the finger changing position - appear by the end of first grade suggesting that parafoveal exposure become more beneficial than harmful when children acquire basic reading skills. Our results show that in beginning readers, crowding has a cognitive cost that interfere with the speed of the learning reading process. Our findings are relevant to the field of education by showing that visual crowding in first grade should not be underestimated., (© 2024. The Author(s).)

Introduction: Tetraplegia causes extensive sensorimotor deficits affecting activity, participation and quality of life. People with C6-C7 tetraplegia can learn to grasp objects by performing wrist extension movement (ie, tenodesis grasp), and motor imagery (MI) added to rehabilitation significantly improved tenodesis grasp. We hypothesise that this improvement can be further boosted by adding neurofeedback during MI. Thus, we design a randomised controlled trial investigating the effect of MI training on grasping ability in people with C6-C7 tetraplegia., Methods and Analysis: We will perform a bicentric, assessor-blinded, randomised controlled study. During rehabilitation, 21 inpatients with C6-C7 tetraplegia will be allocated to MI with neurofeedback (MI training with graphical display on a computer screen based on mu (8-13 Hz) and beta (18-25 Hz) frequency rhythms measured with 32-channel electroencephalography), MI alone (only MI training) and control (watching movies and visualisation of geometric shapes). All participants will receive three 45-min training sessions per week for 5 weeks.The primary outcome measure will be wrist extension angle immediately after the intervention during tenodesis grasp measured with a 3D motion analysis system (VICON). Secondary outcomes will include a range of measures: kinematic, grip strength, upper limb range of motion, upper limb strength (manual muscle test and hand-held dynamometer measure), dexterity (box and block test, 9-hole peg test, Jebsen test, capabilities of upper extremity questionnaire), quality of life (WHOQOL-Bref), daily life autonomy (Quadriplegic Index of Function), MI capacity and brain reorganisation (magnetoencephalography only available in Lyon, n=15). We will measure all outcomes five times: during weeks 1, 3 and 5 (baseline), week 11 (immediately after the intervention end) and week 18 (8 weeks after the intervention end)., Ethics and Dissemination: Ethical approval was granted on 29 September 2017 (CPP Nord-Ouest-IV 17/25, N°2017-A00990-53). Dissemination will occur via presentation of results in scientific meetings and publication in peer-reviewed academic journals., Trial Registration Number: NCT03190863 (ClinicalTrials.gov)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Bipolar disorder (BD) is a complex and heterogeneous psychiatric disorder. It has been suggested that neurodevelopmental factors contribute to the etiology of BD, but a specific neurodevelopmental phenotype (NDP) of the disorder has not been identified. Our objective was to define and characterize an NDP in BD and validate its associations with clinical outcomes, polygenic risk scores, and treatment responses., Methods: We analyzed the FondaMental Advanced Centers of Expertise for Bipolar Disorders cohort of 4468 patients with BD, a validation cohort of 101 patients with BD, and 2 independent replication datasets of 274 and 89 patients with BD. Using factor analyses, we identified a set of criteria for defining NDP. Next, we developed a scoring system for NDP load and assessed its association with prognosis, neurological soft signs, polygenic risk scores for neurodevelopmental disorders, and responses to treatment using multiple regressions, adjusted for age and gender with bootstrap replications., Results: Our study established an NDP in BD consisting of 9 clinical features: advanced paternal age, advanced maternal age, childhood maltreatment, attention-deficit/hyperactivity disorder, early onset of BD, early onset of substance use disorders, early onset of anxiety disorders, early onset of eating disorders, and specific learning disorders. Patients with higher NDP load showed a worse prognosis and increased neurological soft signs. Notably, these individuals exhibited a poorer response to lithium treatment. Furthermore, a significant positive correlation was observed between NDP load and polygenic risk score for attention-deficit/hyperactivity disorder, suggesting potential overlapping genetic factors or pathophysiological mechanisms between BD and attention-deficit/hyperactivity disorder., Conclusions: The proposed NDP constitutes a promising clinical tool for patient stratification in BD., (Copyright © 2024 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Adverse childhood events (ACEs) have been linked to widespread chronic pain (CP) in various cross-sectional studies, mainly in clinical populations. However, the independent role of different ACEs on the development of different types of CP remains elusive. Accordingly, we aimed to prospectively assess the associations between specific types of ACEs with the development of multisite CP in a large population-based cohort., Methods: Data stemmed from the three first follow-up evaluations of CoLaus|PsyCoLaus, a prospective population-based cohort study of initially 6734 participants (age range: 35-75 years). The present sample included 1537 participants with 2161 analyzable intervals (49.7% men, mean age 57.3 years). Diagnostic criteria for ACEs were elicited using semi-structured interviews and CP was assessed by self-rating questionnaires. Multinomial logistic regressions with generalized estimating equations method analyzed the relationship between the different ACEs measured in the beginning of the interval and the risk of developing multisite CP during the follow-up. Sensitivity analyses were performed to assess the predictive value of ACEs on multisite CP with neuropathic features., Results: Participants with a history of parental divorce or separation had an increased risk of developing multisite CP at during follow-up in comparison to those without (RR1.98; 95% CI 1.13-3.47). A strong association was highlighted between parental divorce or separation and the risk of subsequent CP with neuropathic characteristics (RR 4.21, 95% CI 1.45-12.18)., Conclusion: These results highlight the importance of psychotherapeutic management of people experiencing parental separation to prevent CP in the future.

Research investigating the neural processes related to music perception and production constitutes a well-established field within the cognitive neurosciences. While most neuroimaging tools have limitations in studying the complexity of musical experiences, functional Near-Infrared Spectroscopy (fNIRS) represents a promising, relatively new tool for studying music processes in both laboratory and ecological settings, which is also suitable for both typical and pathological populations across development. Here we systematically review fNIRS studies on music cognition, highlighting prospects and potentialities. We also include an overview of fNIRS basic theory, together with a brief comparison to characteristics of other neuroimaging tools. Fifty-nine studies meeting inclusion criteria (i.e., using fNIRS with music as the primary stimulus) are presented across five thematic sections. Critical discussion of methodology leads us to propose guidelines of good practices aiming for robust signal analyses and reproducibility. A continuously updated world map is proposed, including basic information from studies meeting the inclusion criteria. It provides an organized, accessible, and updatable reference database, which could serve as a catalyst for future collaborations within the community. In conclusion, fNIRS shows potential for investigating cognitive processes in music, particularly in ecological contexts and with special populations, aligning with current research priorities in music cognition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Evidence suggests that the most promising results in interictal localization of the epileptogenic zone (EZ) are achieved by a combination of multiple stereo-electroencephalography (SEEG) biomarkers in machine learning models. These biomarkers usually include SEEG features calculated in standard frequency bands, but also high-frequency (HF) bands. Unfortunately, HF features require extra effort to record, store, and process. Here we investigate the added value of these HF features for EZ localization and postsurgical outcome prediction., Methods: In 50 patients we analyzed 30 min of SEEG recorded during non-rapid eye movement sleep and tested a logistic regression model with three different sets of features. The first model used broadband features (1-500 Hz); the second model used low-frequency features up to 45 Hz; and the third model used HF features above 65 Hz. The EZ localization by each model was evaluated by various metrics including the area under the precision-recall curve (AUPRC) and the positive predictive value (PPV). The differences between the models were tested by the Wilcoxon signed-rank tests and Cliff's Delta effect size. The differences in outcome predictions based on PPV values were further tested by the McNemar test., Results: The AUPRC score of the random chance classifier was .098. The models (broad-band, low-frequency, high-frequency) achieved median AUPRCs of .608, .582, and .522, respectively, and correctly predicted outcomes in 38, 38, and 33 patients. There were no statistically significant differences in AUPRC or any other metric between the three models. Adding HF features to the model did not have any additional contribution., Significance: Low-frequency features are sufficient for correct localization of the EZ and outcome prediction with no additional value when considering HF features. This finding allows significant simplification of the feature calculation process and opens the possibility of using these models in SEEG recordings with lower sampling rates, as commonly performed in clinical routines., (© 2024 The Author(s). Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

During paradoxical sleep (PS, aka REM sleep) the cerebral cortex displays rapid electroencephalographic activity similar to that of wakefulness, whereas in the posterior associative thalamus, rapid activity is interrupted by frequent periods of slow-wave (delta) oscillations at 2-3 Hz, thereby dissociating the intrinsic frequency in thalamus and cortex. Here we studied the functional consequences of such a dissociation using intrathalamic and intracortical recordings in 21 epileptic patients, applying coherence analysis to examine changes in functional connectivity between the posterior thalamus (mainly medial pulvinar) and six cortical functional networks, and also between each cortical network with respect to the others. Periods of slow-wave thalamic activity ('delta PS') were more prevalent than phases of 'rapid PS,' and the delta/rapid thalamic alternance did not overlap with the classical tonic/phasic dichotomy based on rapid eye movements. Thalamo-cortical and cortico-cortical functional connectivity significantly decreased during delta PS, relative to both rapid PS periods and to wakefulness. The fact that delta thalamic activity and low thalamo-cortical binding coincided with a suppression of cortico-cortical connectivity supports a crucial role for the posterior associative thalamus, and particularly the medial pulvinar, in ensuring trans-thalamic communication between distant cortical areas. Disruption of such a trans-thalamic communication during delta PS compromises the functional binding between cortical areas, and consequently might contribute to the alteration of perceptual experiences commonly reported during dreams. KEY POINTS: During paradoxical, or REM, sleep (PS), rapid thalamic activity is interrupted by frequent periods of slow delta waves at 2-3 Hz. During these periods of thalamic delta activity there was a drastic drop of functional connectivity between associative thalamus and cortex, and also among different cortical networks. The delta/rapid alternance did not overlap with the classically defined 'tonic/phasic' periods and therefore suggests a distinct dichotomy of functional states in PS. Recurrent decrease in thalamo-cortical and cortico-cortical functional connectivity during PS may compromise the spatio-temporal binding between cortical areas, which in turn could hinder the formation of coherent mental content during dreams., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Adaptation of reactive saccades (RS), made toward the sudden appearance of stimuli in our environment, is a plastic mechanism thought to occur at the motor level of saccade generation. As saccadic oculomotor commands integrate multisensory information in the parietal cortex and superior colliculus, adaptation of RS should occur not only toward visual but also tactile targets. In addition, saccadic adaptation in one modality (vision or touch) should transfer cross-modally. To test these predictions, we used the double-step target paradigm to adapt rightward saccades made at two different eccentricities toward the participants' index and middle fingers, identified either visually ( experiment 1 ) or tactually ( experiment 2 ). In each experiment, the rate of adaptation induced for the adapted modality and the rate of adaptation transfer to the nonadapted modality were compared with that measured in a control (no adaptation) session. Results revealed that touch-triggered RS can be adapted as well as visually triggered ones. Moreover, the transfer pattern was asymmetric: visual saccadic adaptation transferred fully to tactile saccades, whereas tactile saccadic adaptation, despite full generalization to nonadapted fingers, transferred only partially to visual saccades. These findings disclose that in the case of tactile saccades, adaptation can be elicited in the absence of postsaccadic visual feedback. In addition, the asymmetric adaptation transfer across sensory modalities suggests that the adaptation locus for tactile saccades may occur in part upstream of the final motor pathway common to all saccades. These findings bring new insights both on the functional loci(us) and on the error signals of RS adaptation. NEW & NOTEWORTHY The present study revealed that, as predicted from a large literature, adaptation of visual reactive saccades transfers to tactile saccades of the same as well as neighboring amplitudes. Furthermore, in a modified double-step target paradigm, tactile saccades exposed to repeated errors adapt with a similar rate and spatial generalization as visual saccades, but this adaptation only slightly transfers to visual saccades. These findings bring new information on saccadic adaptation processes.

Background and Objectives: Sleepiness in patients with obstructive sleep apnea (OSA) is associated with accidental and economic burden, as well as cardiovascular risk. Despite OSA treatment, 10-28 % of patients report residual sleepiness. Its determinants, as well as those of objective impaired alertness remain poorly known. In this study, we investigated factors associated with residual subjective sleepiness and objective impaired alertness in patients treated for OSA., Methods: Consecutive OSA treated patients referred for maintenance of wakefulness tests (MWT) at a tertiary university center were recruited between 2017 and 2020. Clinical data and polysomnography parameters were compared between patients with vs without subjective sleepiness (Epworth Sleepiness Scale, ESS≥11) and those with vs without impaired alertness (at least one trial with sleep onset on MWT). A multivariate logistic model was used to assess explanatory variables of MWT and ESS results., Results: We included 141 patients, of whom 12.8 % had both subjective sleepiness and objective impaired alertness, 17.7 % objective impaired alertness only and 9.2 % subjective sleepiness only. Self-reported history of car accident/near miss, smoking history and ESS≥11 were significantly associated with objective impaired alertness whereas residual Apnea-hypopnea Index and CPAP use were not. The only significant variable associated with ESS at the time of MWT evaluation was initial ESS. Patients with objective impaired alertness only were more often smokers (52 % vs 19 %, p = 0.01), had a higher body mass index (BMI) (32 vs 29 kg/m 2 , p = 0.05), and showed lower initial ESS (11 vs 13, p < 0.01)., Conclusions: More than one third of OSA treated patients referred for MWT have objective impaired alertness and/or subjective sleepiness. Our findings highlight the need for a comprehensive medical assessment including accident history, subjective sleepiness and comorbidities. Particular attention should be paid to smoking patients with high BMI, who are at risk of impaired alertness with no report of subjective sleepiness., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Renaud Tamisier reports receiving lecture fees from ResMed, Inspire and Bioprojet and grant support through his institution from ResMed, Inspire, Agiradom and Bioprojet, and travel grants from Agiradom. Laure Peter-Derex reports receiving lecture fees from Bioprojet, Eisai, Zogenix and Roche, grant support through her institution from Asten Santé, Linde and Bioprojet, and travel grants from Bioprojet and Vitalaire. All other authors declare no competing interests related to this work., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Shorter telomeres are associated with increased risk of cognitive decline and age-related diseases. Developing interventions to promote healthy aging by preserving telomere integrity is of paramount importance. Here, we investigated the effect of an 18-month meditation intervention on telomere length (TL) measures in older people without cognitive impairment., Methods: A total of 137 adults age ≥65 years were randomized to one of the 3 groups (meditation training, non-native language training, or passive control). We evaluated the 50th and 20th percentile TL and the percentage of critically short telomeres (<3 kbp) in peripheral blood mononuclear cells., Results: Mixed model analysis showed a time effect indicating a general decrease on the 50th percentile TL ( F  = 80.72, p adjusted < .001), without a significant group effect or time × group interaction. No significant effect was detected in the 20th percentile TL or the percentage of critically short telomeres. Secondary analysis showed that only in the meditation training group 1) the 50th percentile TL positively correlated with class attendance time ( r  = 0.45, p adjusted < .011), 2) the 50th and 20th percentile TL positively correlated with responsiveness to the intervention, evaluated through a composite score ( r  = 0.46, p adjusted < .010 and r  = 0.41, p adjusted  = .029, respectively), and 3) lower scores on a measure of the personality trait "openness to experience" correlated with a lower percentage of critically short telomeres after the intervention ( r  = 0.44, p adjusted  = .015)., Conclusions: In older adults, we found no evidence for a main effect of an 18-month meditation training program on TL compared with the control groups. Our findings highlight the importance of considering the impact of moderating factors when measuring the effectiveness of meditation-based trainings., (© 2024 The Authors.)

Objective: To demonstrate the feasibility and efficacy  of a new video-observation training method (intensive visual simulation) to improve upper limb function., Design: Small sample, randomized, evaluator-blind, monocentric study., Patients: Seventeen early subacute ischaemic stroke patients with complete hemiplegia were  randomly assigned to the therapeutic group (n = 8) or control group (CG, n = 9)., Methods: Thirty sessions of intensive visual simulation combined with corrected visual feedback (therapeutic group) or uncorrected visual feedback (control group) were performed over 6 weeks on top of a standard rehabilitation programme., Main Outcome Measure: 400-point hand assessment test (400p-HA)., Secondary Outcome Measures: Box and Blocks (B&B), Purdue Pegboard test, Minnesota., Results: The 400p-HA test improved significantly from T0 to 6 months for both groups, with a significant difference between groups at 3 months (MW-UT p = 0.046) and 4 months (MW-UT p = 0.046) in favour of the therapeutic group. One-phase exponential modelling of 400p-HA showed a greater plateau for the therapeutic group (F test p = 0.0021). There was also faster recovery of the ability to perform the B&B tests for the therapeutic group (log-rank test p = 0.03)., Conclusion: This study demonstrated the feasibility and potential efficacy of an intensive visual simulation training programme to improve upper limb  function in subacute stroke patients. A larger study is needed to confirm these results.

The present study examined dream habits, and their relation to sleep patterns, in 1151 preteens (597 boys; 554 girls; 11.31 ± 0.62 years old). Dream questionnaires assessed the frequency of dream recall, nightmare, and lucid dream, as well as the intensity of emotions experienced in dreams. Sleep variables included sleep duration and efficiency, but also different measurements of nocturnal awakenings. Among the preteens, 49.21% of them reported that they recalled dreams several times a week or almost every morning over the past few months. In addition, 52.00% of the preteens reported that they experienced nightmares, and 45.48% lucid dreams, less than once a month or never over the past few months. No gender differences were observed in dream variables. Nocturnal awakenings were linked to all dream variables, while sleep duration and sleep efficiency were related to nightmare frequency and emotions in dreams. Importantly, sleep duration and sleep efficiency were not associated with dream recall nor lucid dream frequency, with Bayesian analyses supporting the null hypothesis. These findings offer a comprehensive understanding of preteens' dreams and their connection to key sleep aspects., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background: The rapid advancement of technology-focused strategies in neurorehabilitation has brought optimism to individuals with neurological disorders, caregivers, and physicians while reshaping medical practice and training., Objectives: We critically examine the implications of technology in neurorehabilitation, drawing on discussions from the 2021 and 2024 World Congress for NeuroRehabilitation. While acknowledging the value of technology, it highlights inherent limitations and ethical concerns, particularly regarding the potential overshadowing of humanistic approaches. The integration of technologies such as robotics, artificial intelligence, neuromodulation, and brain-computer interfaces enriches neurorehabilitation by offering interdisciplinary solutions. However, ethical considerations arise regarding the balance between compensation for deficits, accessibility of technologies, and their alignment with fundamental principles of care. Additionally, the pitfalls of relying solely on neuroimaging data are discussed, stressing the necessity for a more comprehensive understanding of individual variability and clinical skills in rehabilitation., Results: From a clinical perspective, the article advocates for realistic solutions that prioritize individual needs, quality of life, and social inclusion over technological allure. It underscores the importance of modesty and honesty in responding to expectations while emphasizing the uniqueness of each individual's experience. Moreover, it argues for the preservation of human-centric approaches alongside technological advancements, recognizing the invaluable role of clinical observation and human interaction in rehabilitation., Conclusion: Ultimately, the article calls for a balanced attitude that integrates both scientific and humanistic perspectives in neurorehabilitation. It highlights the symbiotic relationship between the sciences and humanities, advocating for philosophical questioning to guide the ethical implementation of new technologies and foster interdisciplinary dialogue., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Intracranial EEG data offer a unique spatio-temporal precision to investigate human brain functions. Large datasets have become recently accessible thanks to new iEEG data-sharing practices and tighter collaboration with clinicians. Yet, the complexity of such datasets poses new challenges, especially regarding the visualization and anatomical display of iEEG., New Method: We introduce HiBoP, a multi-modal visualization software specifically designed for large groups of patients and multiple experiments. Its main features include the dynamic display of iEEG responses induced by tasks/stimulations, the definition of Regions and electrodes Of Interest, and the shift between group-level and individual-level 3D anatomo-functional data., Results: We provide a use-case with data from 36 patients to reveal the global cortical dynamics following tactile stimulation. We used HiBoP to visualize high-gamma responses [50-150 Hz], and define three major response components in primary somatosensory and premotor cortices and parietal operculum., Comparison With Existing Methods(s): Several iEEG softwares are now publicly available with outstanding analysis features. Yet, most were developed in languages (Python/Matlab) chosen to facilitate the inclusion of new analysis by users, rather than the quality of the visualization. HiBoP represents a visualization tool developed with videogame standards (Unity/C#), and performs detailed anatomical analysis rapidly, across multiple conditions, patients, and modalities with an easy export toward third-party softwares., Conclusion: HiBoP provides a user-friendly environment that greatly facilitates the exploration of large iEEG datasets, and helps users decipher subtle structure/function relationships., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)