European Journal of Neuroscience最新文献

Binaural unmasking is a remarkable phenomenon that it is substantially easier to detect a signal in noise when the interaural parameters of the signal are different from those of the noise - a useful mechanism in so-called cocktail party scenarios. In this study, we investigated the effect of binaural unmasking on neural tracking of the speech envelope. We measured EEG in 8 participants who listened to speech in noise at a fixed signal-to-noise ratio, in two conditions: one where speech and noise had the same interaural phase difference (both speech and noise having an opposite waveform across ears, SπNπ), and one where the interaural phase difference of the speech was different from that of the noise (only the speech having an opposite waveform across ears, SπN). We measured a clear benefit of binaural unmasking in behavioural speech understanding scores, accompanied by increased neural tracking of the speech envelope. Moreover, analysing the temporal response functions revealed that binaural unmasking also resulted in decreased peak latencies and increased peak amplitudes. Our results are consistent with previous research using auditory evoked potentials and steady-state responses to quantify binaural unmasking at cortical levels. Moreover, they confirm that neural tracking of speech is associated with speech understanding, even if the acoustic signal-to-noise ratio is kept constant. From a clinical perspective, these results offer the potential for the objective evaluation of binaural speech understanding mechanisms, and the objective detection of pathologies sensitive to binaural processing, such as asymmetric hearing loss, auditory neuropathy and age-related deficits.

Reduced hippocampal volumes are a feature of many mental disorders. Childhood maltreatment is a known risk factor for the development of psychopathology and has consistently been linked to hippocampal volume reductions in adults, but not in children and adolescents. We propose that maltreatment-related difficulties in coping with developmental tasks in adolescence and young adulthood might underlie the delayed emergence of hippocampal volume reductions in maltreated individuals. In a study with 196 healthy young adults (mean age [years]: 24.0 ± 3.2, 50% female, 20.6% living with a partner (missings: n = 2)), we investigated the interaction between childhood maltreatment (Childhood Trauma Screener) and the breakup of a steady romantic relationship (List of Threatening Experiences Questionnaire) on hippocampal magnetic resonance imaging grey matter volumes. The experience of a romantic relationship breakup moderated the association between childhood maltreatment and bilateral hippocampal volumes, revealing more negative associations with hippocampal volumes in participants with at least one breakup compared to those with no breakup experience (right hippocampus: β = - 0.05 ± 0.02, p = 0.031, p (FDR) = 0.031; left hippocampus: β = -0.06 ± 0.02, p = 0.005, p (FDR) = 0.009). Moreover, our findings provide some evidence that childhood maltreatment is related to smaller bilateral hippocampal volumes only in those adults who suffered from a relationship breakup (right hippocampus: β = -0.23 ± 0.10, p = 0.018, p (FDR) = 0.018; left hippocampus: β = -0.24 ± 0.10, p = 0.016, p (FDR) = 0.018;). Our study highlights the interaction of adult social bonds with early adversity on vulnerability to psychopathology.

The misfolding and aggregation of TAR DNA binding protein-43 (TDP-43), leading to the formation of cytoplasmic inclusions, emerge as a key pathological feature in a spectrum of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). TDP-43 shuttles between the nucleus and cytoplasm but forms nuclear bodies (NBs) in response to stress. These NBs partially colocalise with nuclear speckles and paraspeckles that sequester RNAs and proteins, thereby regulating many cellular functions. The laboratory of Steven Brown has recently found that the non-POU domain-containing octamer-binding protein (NONO), a component of paraspeckles, forms novel nuclear speckle-like structures in mouse cortical neurons in response to stress and sleep deprivation. These findings suggest the possibility of a functional link between NONO and TDP-43, potentially contributing to TDP-43 proteinopathy. Here, we demonstrate that pathological phenotypes caused by TDP-43 gain of function-locomotor defects and life span shortening-are exacerbated by silencing the Drosophila homolog of NONO, no on or off transient A (NonA). Additionally, NonA silencing results in an increase in nuclear TDP-43 NBs. These results provide supporting evidence for the functional link between NONO and TDP-43 and lay the foundation for dissecting underlying mechanisms.

Conceptual review is a method to address issues of task comparability and task validity in cognitive neuroscience. Meta-analyses within cognitive neuroscience (CNS) as well as integration of neuroscientific findings with findings from adjacent disciplines both involve gathering studies that have purportedly investigated the same mental concept. After all, it is no use comparing apples and oranges. Tasks, and in particular the experimental contrasts implemented through tasks, determine whether studies are in fact comparable. Yet studies tend to be grouped together or kept apart based on the mental label researchers have applied and unfortunately, labels are an unreliable proxy for experimental contrasts. Different contrasts may receive the same label: 'working memory' studies rely on a variety of contrasts, derived from a variety of tasks. Vice versa, the same contrast may receive different labels: 'task switching' and 'working memory' studies can be exactly the same in terms of their experimental contrast. Label use thus obscures comparability problems. What is more, even when experimental contrasts are comparable, they may be invalid operationalizations of the mental label attached to them. In this paper, I introduce conceptual review as a method for task analysis. It can stand on its own or be combined with a cognitive ontology. Conceptual review applies philosophical strategies for analysing concepts to methodological choices in CNS studies, to uncover their conceptual implications. Conceptual review thus sheds light on the precise concept that was studied and thereby, on the comparability of CNS studies and the validity of tasks.

Target odorant detection in mixtures has been shown to become more difficult as the number of background odorants increases and falls below chance level in mixtures with 16 components. Our aim was to investigate target odorant detection in mixtures among healthy people and compare it between dysosmic patients and age- and gender-matched controls. Participants underwent extensive olfactory testing and performed two target odorant detection tasks. Eugenol ('clove') and phenylethanol (PEA, 'rose') were target odorants for all participants, whereas a third target was randomised. For each target odorant in task one (task two), there were four steps. Mixtures contained two (three) odorants in the first step and up to seven (eight) odorants in the fourth step. In each step, participants were asked to choose the sample with the target odorant from the three (two) jars presented. The study included 90 healthy people and 40 patients. As expected, probability of successful target odorant detection decreased as the number of odorants in the mixture increased. However, even when there were seven (eight) odorants in the mixture, around 50% (50%) of healthy people detected Eugenol and around 30% (40%) detected PEA. Furthermore, both distributions of successful target odorant detection differed from the expected binominal distribution of chance (p < 0.001). Patients performed worse at detecting Eugenol or PEA at each step than controls. Furthermore, there were significant positive correlations between task scores and olfactory function. In conclusion, target odorant detection is influenced by the target odorant, number of background odorants, and individual olfactory function.

Through the lens of preclinical research on substance use disorders (SUD), I propose a reflection aimed at re-evaluating animal models in neuroscience, with a focus on ecological relevance. While rodent models have provided valuable insights into the neurobiology of SUD, the field currently faces a validation crisis, with findings often failing to translate into effective human treatments. Originally designed to address the lack of reproducibility in animal studies, the current global gold standard of rigorous standardization has led to increasingly controlled environments. This growing disconnection between laboratory settings and real-world scenarios exacerbates the validation crisis. Rodent models have also revealed various environmental influences on drug use and its neural mechanisms, highlighting parallels with human behaviour and underscoring the importance of ecological relevance in behavioural research. Drawing inspiration from inquiries in ethology and evolutionary biology, I advocate for incorporating greater environmental complexity into animal models. In line with this idea, the neuroethological approach involves studying spontaneous behaviours in seminatural habitats while utilizing advanced technologies to monitor neural activity. Although this framework offers new insights into human neuroscience, it does not adequately capture the complex human conditions that lead to neuropsychiatric diseases. Therefore, preclinical research should prioritize understanding the environmental factors that shape human behaviour and neural architecture, integrating these insights into animal models. By emphasizing ecological relevance, we can achieve deeper insights into neuropsychiatric disorders and develop more effective treatment strategies. This approach highlights significant benefits for both scientific inquiry and ethical considerations. The controlled environment is a chimera; it is time to rethink our models. Here, I have chosen the prism of preclinical research on SUD to present, in a nonexhaustive manner, advances enabled by the use of rodent models, the crises faced by animal experimentation, the reflections and responses provided by laboratories, to finally propose rethinking our models around questions of ecological relevance, in order to improve both ethics and scientific quality. Although my discussion is illustrated by the situation in preclinical research on SUD, the observation drawn from it and the proposals made can extend to many other domains and species.

To summarise the clinical characteristics, radiological features, treatments and prognosis of patients with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) overlapped with NMDA receptor (NMDAR) encephalitis. We retrospectively analysed patients who exhibited dual positivity for MOG antibodies and NMDAR antibodies in serum/CSF from Jan 2018 to Jun 2023. Ten patients with MOGAD and NMDAR encephalitis were enrolled. The median age of initial attacks was 23 (range: 10-43) years old. Common symptoms were cortical encephalopathies (8/10), focal neurological deficits (4/10), as well as other presentations including headache, fever, optic neuritis and transverse myelitis. CSF pleocytosis was general (9/10, median 63.9 cells/μl). Lesions on brain MRI included brainstem (37.5%), cerebral cortex (33.3%), basal ganglia (25.0%) and hippocampus (20.8%). The average follow-up duration was 25.4 months. 10/10 patients developed more than one relapse attacks, with MOG positivity before (10%), simultaneous (40%) or after anti-NMDAR encephalitis (50%). Most patients (7/10) had good response to first-line therapy but experienced next relapse with an average interval of 6.7 (range: 2-14) months. We conducted initial analysis of lymphocyte subsets in these patients, which revealed that CD3+ and CD4 + T cells increased after immunosuppressants medication (p < 0.01 and p < 0.05, respectively). We concluded that MOGAD overlapping with NMDAR encephalitis presents a distinct clinical phenotype which differs from either MOGAD or NMDAR encephalitis. Brainstem in combination with cortical lesions might be warning signs for this overlapping syndrome. Due to the high recurrent rates, we recommend early diagnosis and timely treatment with efficient immunosuppressants at onset.

The low-density lipoprotein receptor (LDLr) is the first member of a closely related transmembrane protein family. It is known for its involvement in various physiological processes, mainly in the regulation of lipid metabolism, especially in the brains of mammals and zebrafish. In zebrafish, two ldlr genes (ldlra and b) have been identified and their distribution in the brain is not well documented. Recently, the roles of ldlr and its inhibitor pcsk9 in regenerative process after telencephalic brain injury have been discussed. In this study, we explored the expression patterns of these genes during zebrafish development. We found that ldlra expression was detected at the end of the pharyngula period (48 hpf) and increased during the larval stage. Conversely, ldlrb expression was observed from zygotic to larval stages. Using techniques like in situ hybridization and taking advantage of transgenic fish, we demonstrated the widespread distribution of ldlra, ldlrb and pcsk9 in the brain of adult zebrafish. Specifically, these genes were expressed in neurons and neural stem cells and also at lower levels in endothelial cells. As expected, intraperitoneal injection of fluorescent-labelled LDLs resulted in their uptake by cerebral endothelial cells in a homeostatic context, whereas they diffused within the brain parenchyma after telencephalic injury. However, after intracerebroventricular injections into animals, LDL particles were not taken up by neural stem cells. In conclusion, our results provide additional evidence for LDLr expression in the brain of adult zebrafish. These results raise the question of the role of LDLr in the cholesterol/lipid imbalance in cerebral complications.

Information conveyed through feedback enables individuals to learn new routines and better adapt to their environment. However, the neural mechanisms of rule-related information of feedback have not been fully elucidated. Herein, we quantified the effect of informative value on feedback via a rule induction task (RIT), in which participants were required to find the correct sorting rule based on feedback. To disengage the effects of informative value and valence on feedback in the RIT, a control task was developed in which feedback only involved the valence aspect and no reference for subsequent selections. We measured power and intertrial phase clustering (ITPC) values via EEG to determine the neural mechanisms of rule-related feedback. The results revealed that (1) differences in oscillatory activities between positive and negative feedback were only observed during the control task, and no such effect was found in the RIT task. This finding suggests that the participants paid more attention to rule-related information than to the correctness of feedback during rule learning. (2) The task differences under positive or negative feedback were associated with the delta-theta and alpha-beta bands, and this pattern was similar within the frontal and parietal regions. These findings suggest that the processing of rule-related information of feedback relies on broad frequency bands within the frontoparietal cortex to facilitate rule information integration. In summary, these findings indicate that multiple frequency bands are involved in encoding the informative value aspect of feedback, and individuals rely on this aspect of feedback rather than valence during rule learning.

'Opponent channels model' (OCM) is the widely accepted model for cortical representation of sound lateralization. Stimulus-specific 'release from adaptation' (RFA) in cortical responses has been used in previous studies to test the predictions of this model. However, these attempts were shown to be prone to confounds of spurious responses such as those to auditory motion and sound onset. The present study aims to determine whether a multiple-adaptor RFA algorithm could be employed for relatively confound-free quantification of the population response of lateralization-specific auditory cortical neurons, and provide useful data for estimation of the OCM hemifield tuning curves. Two experiments were conducted on 12 volunteers with normal hearing. In Exp.1, quadruple tone pips of either low or high frequency were presented as adaptor, followed by a single tone pip of either frequency as probe. In Exp.2, tone pips were replaced with dichotic click train pips with left-leading and right-leading interaural time difference (ITD). Frequency- and ITD-specific RFA in cortical responses N1 and P2 was quantified using global field magnitude difference between ERPs to mismatched and matched adaptor-probe pairs. RFA level measured was lower for ITD mismatch than frequency mismatch. Nonetheless, it allowed measurement of ITD-specific cortical neurons' population response, without any spurious response confound. We proposed a method for extraction of ITD-specific response magnitude from the N1 response to a lateralized sound. Using it, one can reliably measure the activity of lateralization-specific cortical neurons, i.e. elicited by moderate ITD changes. This allows estimation of hemifield tuning curves in OCM using ERP data.