Lyon Neuroscience Research Center

Eye movements and spatial attention are both crucial to visual perception. Orienting gaze to objects of interest is achieved by voluntary saccades (VSs) driven by internal goals or reactive saccades (RSs) triggered automatically by sudden environmental changes. Both VSs and RSs are known to undergo plastic adjustments to maintain their accuracy throughout life, driven by saccadic adaptation processes. Spatial attention enhances visual processing within a restricted zone, and it can be shifted voluntarily following our internal goals (endogenous) or automatically in response to unexpected changes in sensory stimulation (exogenous). Despite the widely accepted notion that saccadic and attention shifts are governed by distinct but highly interconnected systems, the relationship between saccadic adaptation and spatial attention is still unclear. To address this relationship, we conducted two experiments combining modified versions of the double-step adaptation paradigm and the attention-orienting paradigm. Experiment 1 tested the effect of shifting exogenous attention by a tactile cue near or away from the saccade's target on RS adaptation. Experiment 2 also used tactile cueing but now to investigate the effect of shifting endogenous attention on VS adaptation. Although we were unable to obtain direct evidence for an effect of spatial attention on saccadic adaptation, correlation analyses indicated that both the rate and magnitude of saccadic adaptation were positively correlated with the allocation of attention toward the saccade target and negatively correlated with attention directed away from the target.

Functional connectomics is a popular approach to investigate the neural underpinnings of developmental disorders of which attention deficit hyperactivity disorder (ADHD) is one of the most prevalent. Nonetheless, neuronal mechanisms driving the aberrant functional connectivity resulting in ADHD symptoms remain largely unclear. Whereas resting state activity reflecting intrinsic tonic background activity is only vaguely connected to behavioral effects, naturalistic neuroscience has provided means to measure phasic brain dynamics associated with overt manifestation of the symptoms. Here we collected functional magnetic resonance imaging (fMRI) data in three experimental conditions, an active virtual reality (VR) task where the participants execute goal-directed behaviors, a passive naturalistic Video Viewing task, and a standard Resting State condition. Thirty-nine children with ADHD and thirty-seven typically developing (TD) children participated in this preregistered study. Functional connectivity was examined with network-based statistics (NBS) and graph theoretical metrics. During the naturalistic VR task, the ADHD group showed weaker task performance and stronger functional connectivity than the TD group. Group differences in functional connectivity were observed in widespread brain networks: particularly subcortical areas showed hyperconnectivity in ADHD. More restricted group differences in functional connectivity were observed during the Video Viewing, and there were no group differences in functional connectivity in the Resting State condition. These observations were consistent across NBS and graph theoretical analyses, although NBS revealed more pronounced group differences. Furthermore, during the VR task and Video Viewing, functional connectivity in TD controls was associated with task performance during the measurement, while Resting State activity in TD controls was correlated with ADHD symptoms rated over six months. We conclude that overt expression of the symptoms is correlated with aberrant brain connectivity in ADHD. Furthermore, naturalistic paradigms where clinical markers can be coupled with simultaneously occurring brain activity may further increase the interpretability of psychiatric neuroimaging findings.

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.

ObjectivesIn 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. MethodsA 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. ResultsEleven 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. ConclusionIn 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.

Because of its involvement in breathing control and neuronal excitability, dysregulation of the serotonin (5-HT) 2C receptor (5-HT2C) might play a key role in sudden unexpected death in epilepsy. Seizure-induced respiratory arrest is thus prevented by a 5-HT2B/C agonist in different seizure model. However, the specific contribution of 5-HT2C in chronic epilepsy-related respiratory dysfunction remains unknown. In a rat model of temporal lobe epilepsy (EPI rats), in which we previously reported interictal respiratory dysfunctions and a reduction of brainstem 5-HT tone, quantitative reverse transcriptase polymerase chain reaction showed overexpression of TPH2 (5-HT synthesis enzyme), SERT (5-HT reuptake transporter), and 5-HT2C transcript levels in the brainstem of EPI rats, and of RNA-specific adenosine deaminase (ADAR1, ADAR2) involved in the production of 5-HT2C isoforms. Interictal ventilation was assessed with whole-body plethysmography before and 2 h after administration of SB242084 (2 mg/kg), a specific antagonist of 5-HT2C. As expected, SB242084 administration induced a progressive decrease in ventilatory parameters and an alteration of breathing stability in both control and EPI rats. However, the size of the SB242084 effect was lower in EPI rats than in controls. Increased 5-HT2C gene expression in the brainstem of EPI rats could be part of a compensatory mechanism against epilepsy-related low 5-HT tone and expression of 5-HT2C isoforms for which 5-HT affinity might be lower.

Adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT) are two structurally related enzymes involved in purine recycling in humans. Inherited mutations that suppress HGPRT activity are associated with Lesch–Nyhan disease (LND), a rare X-linked metabolic and neurological disorder in children, characterized by hyperuricemia, dystonia, and compulsive self-injury. To date, no treatment is available for these neurological defects and no animal model recapitulates all symptoms of LND patients. Here, we studied LND-related mechanisms in the fruit fly. By combining enzymatic assays and phylogenetic analysis, we confirm that no HGPRT activity is expressed in Drosophila melanogaster, making the APRT homolog (Aprt) the only purine-recycling enzyme in this organism. Whereas APRT deficiency does not trigger neurological defects in humans, we observed that Drosophila Aprt mutants show both metabolic and neurobehavioral disturbances, including increased uric acid levels, locomotor impairments, sleep alterations, seizure-like behavior, reduced lifespan, and reduction of adenosine signaling and content. Locomotor defects could be rescued by Aprt re-expression in neurons and reproduced by knocking down Aprt selectively in the protocerebral anterior medial (PAM) dopaminergic neurons, the mushroom bodies, or glia subsets. Ingestion of allopurinol rescued uric acid levels in Aprt-deficient mutants but not neurological defects, as is the case in LND patients, while feeding adenosine or N6-methyladenosine (m6A) during development fully rescued the epileptic behavior. Intriguingly, pan-neuronal expression of an LND-associated mutant form of human HGPRT (I42T), but not the wild-type enzyme, resulted in early locomotor defects and seizure in flies, similar to Aprt deficiency. Overall, our results suggest that Drosophila could be used in different ways to better understand LND and seek a cure for this dramatic disease.

Words are not processed in isolation; instead, they are commonly embedded in phrases and sentences. The sentential context influences the perception and processing of a word. However, how this is achieved by brain processes and whether predictive mechanisms underlie this process remain a debated topic. Here, we employed an experimental paradigm in which we orthogonalized sentence context constraints and predictive validity, which was defined as the ratio of congruent to incongruent sentence endings within the experiment. While recording electroencephalography, participants read sentences with three levels of sentential context constraints (high, medium, and low). Participants were also separated into two groups that differed in their ratio of valid congruent to incongruent target words that could be predicted from the sentential context. For both groups, we investigated modulations of alpha power before, and N400 amplitude modulations after target word onset. The results reveal that the N400 amplitude gradually decreased with higher context constraints and cloze probability. In contrast, alpha power was not significantly affected by context constraint. Neither the N400 nor alpha power were significantly affected by changes in predictive validity.

Olfactory perception begins when odorous substances interact with specialized receptors located on the surface of dedicated sensory neurons. The recognition of smells depends on a complex mechanism involving a combination of interactions between an odorant and a set of odorant receptors (ORs), where molecules are recognized according to a combinatorial activation code of ORs. Although these interactions have been studied for decades, the rules governing this ligand recognition remain poorly understood, and the complete combinatorial code is only known for a handful of odorants. We have carefully analyzed experimental results regarding the interactions between ORs and molecules to provide a status report on the deorphanization of ORs, i.e. the identification of the first agonist for a given sequence. This meticulous analysis highlights the influence of experimental methodology (cell line or readout) on molecule-receptor association results and shows that 83% of the results are conserved regardless of experimental conditions. The distribution of another key parameter, EC50, indicates that most OR ligand activities are in the micromolar range and that impurities could lead to erroneous conclusions. Focusing on the human ORs, our study shows that 88% of the documented sequences still need to be deorphanized. Finally, we also estimate the size of the ORs' recognition range, or broadness, as the number of odorants activating a given OR. By analogously estimating molecular broadness and combining the two estimates we propose a basic framework that can serve as a comparison point for future machine learning algorithms predicting OR-molecule activity.

Negative symptoms in schizophrenia impose a significant burden with limited effective pharmacological treatment options. Recent trials have shown preliminary evidence for the efficacy of using intermittent theta burst stimulation (iTBS) in treating negative symptoms in schizophrenia. We aim to systematically review the current evidence of iTBS in the treatment of the negative symptoms of schizophrenia as an augmentation therapy. The study protocol was developed and registered on Prospero (registration ID: 323381). MEDLINE, EMBASE, Web of Science (Scopus), PsycINFO and Wan Fang databases were searched for sham-controlled, randomized trials of iTBS among patients with schizophrenia. The mean difference in major outcome assessments for negative symptoms was calculated. The quality of evidence was assessed using the Cochrane Risk of Bias Tool (version 1) and the GRADE system. Moreover, 12 studies including a total of 637 participants were included. Compared to sham treatment, the pooled analysis was in favor of iTBS treatment for negative symptoms (mean weight effect size: 0.59, p = 0.03) but not for positive symptoms (mean weight effect size: 0.01, p = 0.91) and depressive symptoms (mean weight effect size: 0.35, p = 0.16). A significant treatment effect was also observed on the iTBS target site left dorsal prefrontal cortex (mean weight effect size: 0.86, p = 0.007) and for stimulation with 80% motor threshold (mean weight effect size: 0.86, p = 0.02). Thus, our synthesized data support iTBS as a potential treatment for negative symptoms among patients with schizophrenia. However, the long-term efficacy and safety issues of iTBS in a larger population have yet to be examined.