Biology subjects

Arnulf, I.

Publications and source records attributed to Arnulf, I..

9 recordsLinked to original sources

bioRxiv2025

Live access to the emotional dynamics of REM sleep dreams in lucid dreamers with narcolepsy

Sleep helps regulate emotions, but it is still unclear whether -and how- the emotions we experience in dreams contribute to this regulation. To uncover the potential function of dream emotions, we must first understand what they are and how they unfold in dreams. The emotional content of dreams has mostly been studied using post-sleep dream reports, which provide a biased and static snapshot of a complex and dynamic experience. In this study, we took a more direct approach, accessing dream emotions in real-time. We asked twenty-four lucid dreamers with narcolepsy to report the emotional valence of their dreams, - positive, negative or neutral-, while still asleep, using predefined facial codes during daytime naps monitored with polysomnography. Of the 126 naps recorded, 62 contained at least one emotional code during REM sleep, yielding 191 codes in total. The ratios of positive and negative codes were evenly balanced per nap. The 33 naps with at least two codes allowed us to track the dream emotional dynamics. Over half of these naps showed opposite emotional valences (positive and negative). By measuring the time elapsed between codes, we estimated the average duration of a given dreams emotional valence in REM sleep to be about one minute. Positive emotions emerged on average earlier than negative ones during lucid REM sleep. These findings confirm the highly emotional nature of dreams and, more importantly, highlight that emotions in REM sleep dreams are fluid and fast-changing. Such emotional dynamics during REM sleep dreams may help us to better understand the mechanisms of the emotional regulatory function of dreams.

neuroscience↗

bioRxiv2025

EEG Signature of Idiopathic Hypersomnia: Insights from Sleep Microarchitecture and Hypnodensity Metrics

Background and ObjectivesPatients with idiopathic hypersomnia with long sleep time (IH) report daytime hypersomnolence despite prolonged sleep time and normal sleep macrostructure. As they often have non-restorative sleep, we investigated whether the structure of their sleep is abnormal. MethodsIn polysomnography recordings from 80 IH participants and 48 controls, we quantified hypnodensity metrics across the night (macro level), periodic and aperiodic spectral properties, infraslow fluctuations of sigma power within the night (meso level), slow waves, sleep spindles and their clustering (microstructure). Multivariate machine-learning models were used to classify IH vs. control sleep. ResultsHypnodensity metrics were comparable between IH and controls, apart from more mixed wake/N1 sleep epochs in IH, and greater divergence between consecutive epochs of the same stage during NREM sleep in IH. Sigma power was increased in N2 sleep in IH and sleep spindles were more frequent and clustered. Slow wave density was higher in IH. Higher mean spindle cluster size correlated with higher Epworth Sleepiness Scale scores. Multivariate machine learning models incorporating these features achieved a balanced accuracy of 74% in distinguishing IH from controls. DiscussionWhile spindles and slow waves are typically associated with good sleep quality, they are increased in IH patients. This could reflect greater need for sleep and increased difficulty waking up in IH, which is also characterized by more mixed wake/N1 stages.

neuroscience↗

bioRxiv2025

How sleeping minds decide: state-specific reconfigurations of lexical decision-making

Decision-making is a core cognitive function that enables adaptive behavior across diverse contexts. While extensively studied in wakefulness, its persistence and reconfiguration across sleep states remain poorly understood. Here, we use computational modeling to examine lexical decision-making across wakefulness, N1 sleep, and lucid REM sleep in both healthy participants (HP) and participants with narcolepsy (NP). Using facial electromyography (EMG) to capture real-time behavioral responses to spoken words and pseudowords during sleep, we quantify how decision-making strategies adapt under different sleep and consciousness states. Our findings reveal two key insights. First, decision-making mechanisms are dynamically reconfigured across sleep states. In N1 sleep, the advantage for word (vs. pseudoword) judgments is supported by faster sensory encoding and motor preparation, combined with efficient evidence accumulation. In contrast, in lucid REM sleep, the word advantage is driven exclusively by enhanced evidence accumulation, while sensory encoding and motor preparation remain unchanged. Second, cross-state comparisons reveal distinct patterns of preservation and impairment. In N1 sleep, word judgment remains largely intact, whereas pseudoword judgment is significantly impaired, characterized by prolonged stimulus encoding, delayed motor preparation, and reduced evidence accumulation. In contrast, lucid REM sleep is marked by a global reduction in processing efficiency, reflected in slower evidence accumulation and elevated decision thresholds for both words and pseudowords. These results demonstrate that rather than being uniformly degraded, decision-making is dynamically reconfigured across sleep stages, reflecting adaptive neurocognitive strategies that sustain cognition in altered states of consciousness. By identifying state-specific computational mechanisms, this study provides new insights into the brains resilience and flexibility under changing cognitive and physiological conditions.

neuroscience↗

bioRxiv2024

The role of dopaminergic, cholinergic and noradrenergic networks in hyposmia in Parkinson's disease

BackgroundOlfactory impairment is frequently observed in Parkinsons disease (PD) before motor symptom onset. Patients with isolated rapid eye movement sleep behaviour disorder (iRBD) are at risk to develop PD and present olfactory dysfunction. Subcortical neuromodulatory nuclei including the substantia nigra, the nucleus basalis of Meynert, and the locus coeruleus, may all contribute to olfactory dysfunction. ObjectiveThe objective of this study was to understand the network alterations underlying olfactory dysfunction in PD and in the early prodromal iRBD patients using multimodal MRI. MethodsPD (n = 107), iRBD patients (n = 35) and healthy controls (HC, n = 39) were recruited from the ICEBERG cohort for a cross-sectional study. We separated subjects in Healthy Controls, iRBD patients, and PD patients with or without RBD and with or without anosmia. Olfactory, motor, and cognitive scores were assessed and combined with multimodal imaging. ResultsWe found that olfaction positively correlated with (i) striatal DaT signal in PD patients; (ii) neuromelanin contrast in the locus coeruleus and (iii) Nucleus Basalis of Meynert grey matter (GM) volume in all patients. These signals were uncorrelated with motor and cognitive scores. Functional connectivity was reduced in regions of the cholinergic olfactory network in anosmic patients. Functional connectivity was also reduced in the noradrenergic network of patients with RBD. DiscussionOur results indicate the implication of the cholinergic network in PD patients with anosmia and a contribution of the noradrenergic network to olfactory dysfunction, only in patients with RBD.

neuroscience↗

bioRxiv2024

Longitudinal neuromelanin changes in prodromal and early Parkinson's disease in humans and rat model

Studies in animal models of Parkinsons disease (PD) suggested that the accumulation of the neuromelanin (NM), a pigment contained in nigral dopaminergic neurons, could trigger neurodegeneration above a pathogenic threshold. Here we investigated this hypothesis using NM-sensitive MRI in rodents and in patients with isolated rapid eye movement sleep disorders (iRBD) subjects, a prodromal phase of parkinsonism, and early PD. We first combined NM-sensitive MRI and histology to study NM accumulation and neurodegeneration in a humanized rat model of PD. NM-MRI signal changes were biphasic with an initial increase due to the accumulation of NM in dopaminergic neurons, followed signal decrease due to neurodegeneration. In healthy subjects and patients with iRBD, NM-MRI signal increased initially and then decreased similarly as in rodents after reaching a similar maximum signal intensity in both groups. In early PD and converted iRBD patients, NM-MRI signal drop was greater than in healthy individuals. Results in animals and humans show that NM-sensitive MRI is a marker of the intracellular NM accumulation up to a threshold then of neuronal degeneration beyond this threshold and agree with the hypothesis of a pathogenic threshold of NM triggering neurodegeneration.

neuroscience↗

bioRxiv2022

Behavioral and brain responses to verbal stimuli reveal transient periods of cognitive integration of external world in all sleep stages

Sleep has long been considered as a state of disconnection from the environment, with absent reactivity to external stimuli. Here, we questioned this sleep disconnection dogma by directly investigating behavioral responsiveness in 49 napping subjects (27 with narcolepsy and 22 healthy volunteers) engaged in a lexical decision task. Participants were instructed to frown or smile depending on the stimulus type (words vs pseudo-words). We found accurate behavioral responses, visible via contractions of the corrugator or zygomatic muscles, in all sleep stages in both groups (except slow-wave sleep for healthy volunteers). Stimuli presented during states with high (vs. low) values of neural markers indexing rich cognitive states more often yielded responses. Our findings suggest that transient windows of reactivity to external stimuli exist in all sleep stages, even in healthy individuals. Such windows of reactivity could be used to probe sleep-related mental and cognitive processes in real-time across all sleep stages.

neuroscience↗

bioRxiv2022

Memory loss at sleep onset

Every night, we pass through a transitory zone at the borderland between wakefulness and sleep, named the first stage of non-rapid eye movement sleep (N1). N1 sleep is associated with an increased hippocampal activity and dreamlike experiences that incorporate recent wake materials, suggesting that it may be associated with memory processing. Here, we investigated the specific contribution of N1 sleep in the processing of memory traces. Participants were asked to learn the precise locations of 48 objects on a grid and were then tested on their memory for these items before and after a 30-minute rest during which participants either stayed fully awake, transitioned toward N1 or deeper (N2) sleep. We showed that memory recall was lower (10% forgetting) after a resting period including only N1 sleep compared to N2 sleep. Furthermore, the ratio of alpha/theta power (an EEG marker of the transition towards sleep) correlated negatively with the forgetting rate when taking into account all sleepers (N1 and N2 groups combined), suggesting a physiological index for memory loss that transcends sleep stages. Our findings suggest that interrupting sleep onset at N1 may alter sleep-dependent memory consolidation and promote forgetting.

neuroscience↗

bioRxiv2019

Fine-mapping of SNCA in REM sleep behavior disorder and overt synucleinopathies

ObjectiveREM-sleep behavior disorder (RBD) is a prodromal synucleinopathy, as >80% will eventually convert to overt synucleinopathy. We performed an in-depth analysis of the SNCA locus to identify RBD-specific risk variants.\n\nMethodsFull sequencing and genotyping of SNCA was performed in isolated/idiopathic RBD (iRBD, n=1,076), Parkinsons disease (PD, n=1,013), and dementia with Lewy bodies (DLB, n=415), and in control subjects (n=6,155). A replication cohort from 23andMe of PD patients with probable RBD (pRBD) was also analyzed (cases n=1,782, controls n=131,250). Adjusted logistic regression models and meta-analyses were performed. Effects on conversion rate were analyzed in 432 RBD patients with available data using Kaplan-Meier survival analysis.\n\nResultsA 5-region SNCA variant (rs10005233) was associated with iRBD (OR=1.43, p=1.1E-08), which was replicated in pRBD. This variant is in linkage disequilibrium (LD) with other 5 risk variants across the different synucleinopathies. An independent iRBD-specific suggestive association (rs11732740) was detected at the 3 of SNCA (OR=1.32, p=4.7E-04, not statistically significant after Bonferroni correction). Homozygous carriers of both iRBD-specific SNPs were at highly increased risk for iRBD (OR=5.74, p=2E-06). The known top PD-associated variant (3 variant rs356182) had an opposite direction of effect in iRBD compared to PD.\n\nInterpretationThere is a distinct pattern of association at the SNCA locus in RBD as compared to PD, with an opposite direction of effect at the 3 of SNCA. Several 5 SNCA variants are associated with iRBD and with pRBD in overt synucleinopathies, and may suggest a cognitive component to this region.

genetics↗

bioRxiv2018

Narcolepsy risk loci are enriched in immune cells and suggest autoimmune modulation of the T cell receptor repertoire

Type 1 narcolepsy (T1N) is a neurological condition, in which the death of hypocretin-producing neurons in the lateral hypothalamus leads to excessive daytime sleepiness and symptoms of abnormal Rapid Eye Movement (REM) sleep. Known triggers for narcolepsy are influenza-A infection and associated immunization during the 2009 H1N1 influenza pandemic. Here, we genotyped all remaining consented narcolepsy cases worldwide and assembled this with the existing genotyped individuals. We used this multi-ethnic sample in genome wide association study (GWAS) to dissect disease mechanisms and interactions with environmental triggers (5,339 cases and 20,518 controls). Overall, we found significant associations with HLA (2 GWA significant subloci) and 11 other loci. Six of these other loci have been previously reported (TRA, TRB, CTSH, IFNAR1, ZNF365 and P2RY11) and five are new (PRF1, CD207, SIRPG, IL27 and ZFAND2A). Strikingly, in vaccination-related cases GWA significant effects were found in HLA, TRA, and in a novel variant near SIRPB1. Furthermore, IFNAR1 associated polymorphisms regulated dendritic cell response to influenza-A infection in vitro (p-value =1.92*10-25). A partitioned heritability analysis indicated specific enrichment of functional elements active in cytotoxic and helper T cells. Furthermore, functional analysis showed the genetic variants in TRA and TRB loci act as remarkable strong chain usage QTLs for TRAJ*24 (p-value = 0.0017), TRAJ*28 (p-value = 1.36*10-10) and TRBV*4-2 (p-value = 3.71*10-117). This was further validated in TCR sequencing of 60 narcolepsy cases and 60 DQB1*06:02 positive controls, where chain usage effects were further accentuated. Together these findings show that the autoimmune component in narcolepsy is defined by antigen presentation, mediated through specific T cell receptor chains, and modulated by influenza-A as a critical trigger.

genetics↗