European Journal of Neuroscience最新文献

Rough-and-tumble play (RTP) is the form of play most often observed in juvenile mammals. In rats, RTP typically consists of competing for access to the partner's nape, with both sex and social contexts influencing its frequency and structure. Although most studies employ dyadic tests, this design limits partner choice. Here, we investigated sex differences in partner preference and play frequency in Wistar rats using a group play paradigm. Juvenile rats were tested in mixed-sex and same-sex triads, allowing individuals to select partners. We measured playful nape attacks, defensive responses, and the distribution of play across partners. Results revealed that both sexes formed partner preferences, but only males exhibited sex-based preferences, directing significantly more playful attacks toward females than males. Female rats showed no group-level sex preference, though most individuals displayed consistent preferences for one partner, often, but not exclusively, for the male partner. Importantly, females initiated fewer nape attacks than males in mixed-sex groups, but this sex difference disappeared in all-female groups, where females initiated playful attacks at levels comparable to males. Thus, sex differences in RTP frequency were context dependent, emerging only when females were tested alongside males. These findings demonstrate two distinct forms of sex differences in the play of rats: partner choice and play frequency. Whereas males preferentially engage with females, females appear more flexible, forming idiosyncratic preferences independent of the partner's sex. Moreover, female play initiation is particularly sensitive to social context, highlighting the importance of group-based testing for understanding naturalistic social decision-making.

Long-term memory (LTM) has been associated with neural oscillation in the theta (3–8 Hz) range. Although previous studies have suggested that the dorsomedial prefrontal cortex (dmPFC) is a core region for LTM retrieval, causal evidence is sparse and mixed. Furthermore, the moderating effects of stimulus memorability have not yet been explored. In the present study, we used transcranial alternating current stimulation (tACS) to modulate theta oscillation in the dmPFC during the retrieval of visual images with varying levels of memorability. Specifically, we included n = 33 healthy volunteers who were exposed to 300 images of faces, scenes and items, which they had to memorize. Recognition accuracy was assessed 1 h later. During the retrieval phase, participants received either sham or verum (4 Hz, 2.5 mA) tACS and were asked whether they had seen the pictures before (150 new and 150 old). Contrary to our preregistered hypotheses, we found no significant effect of 4-Hz tACS applied during retrieval on LTM recognition. Furthermore, although the memorability effect was observed, it did not interact with tACS, indicating that stimulation neither improved nor worsened performance on low- and high-memorable images. Altogether, the present study does not support an active role of 4-Hz oscillations in the dmPFC for the recognition of images with varying levels of memorability, under the specific task and stimulation parameters used here. However, this null effect may be specific to the task and particular parameters used in this study.

Freezing of gait is a common, debilitating symptom that affects many patients with Parkinson's disease. The lack of a standard, objective method to quantify freezing obstructs research and treatment. Wearable sensors combined with automatic detection algorithms have demonstrated increasingly promising results; nonetheless, video annotation remains the gold standard. After organizing a global machine learning contest to expedite the development of acceleration-based algorithms designed to automatically detect freezing, we tested the transferability of the winning models to a new dataset. Experts reviewed and annotated a test protocol conducted and videotaped in the homes of 12 patients. The models were applied to acceleration data from a lower back sensor worn by the patients. F1-scores, accuracy, recall, specificity, and precision were computed. Intraclass correlations quantified the agreement between model-estimated and annotation-based gold standard outcomes, including the percent time frozen, the number of episodes, and the total freezing duration. While there was a relatively large drop in performance for some of the models, the performance of the third place model showed good transferability to new data. Indeed, the agreement between the third place model and gold standard annotations was similar to or better than that seen when comparing two raters. These results further support the idea that if the goal is to detect freezing duration or percent time frozen, the combination of a single, lower back sensor and the third place model can be used to automatically detect freezing. Still, if the goal is to count episodes or detect freezing subtypes, additional sensors or other modelling approaches are needed.

Auditory event-related brain potentials such as the mismatch negativity (MMN) and the frequency-following response (FFR) allow exploring speech sound encoding along the auditory pathway. Here, we collected event-related brain potential (ERP) and FFR neural responses to syllables in healthy full-term newborns (N = 17, mean age = 3 days) and adults (N = 21, mean age = 22.7). Participants were passively exposed to alternating blocks of syllables presented at either fast or slow stimulation rates while we recorded electroencephalography (EEG). Specifically, blocks containing the synthetic /oa/ syllable alternated with “oddball” blocks containing three natural syllables differing in place of articulation (one standard /da/ and two deviants /ba/ and /ga/). At the FFR level, we found that 3-day-old newborns (i) exhibit an already functional encoding of vowel pitch, (ii) show an immature encoding of vowel formant structure, replicating previous observations. At the ERP level, the two deviants elicited clear MMN in the two groups, although with different topographies, suggesting an immature sensitivity to place of articulation in newborns. These results confirm the role of experience-dependent developmental factors that may differentially shape FFR and ERPs of speech sound features. Furthermore, this study highlights the feasibility of assessing the hierarchy of neural speech sound encoding in a short experimental session.

Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse that can benefit from multimodal treatment monitoring. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome are not only limited but also computationally complex. Therefore, we developed an analytical pipeline to investigate the connection between drug use behaviors during abstinence and change in the blood transcriptome. We conducted a longitudinal study with CUD (n = 12 subjects) and collected behavioral metrics and blood RNA-seq at baseline, 3, 6, and 9 months. Our analytical pipeline of the high-dimensional data encompasses hierarchical k-means clustering to classify subjects to responder groups based on behavioral scores and abstinence duration, in silico cell deconvolution, differential analysis with correlated multivariate testing over time, gene set enrichment analysis, and gene co-expression with time splines and RNA-seq data. The pipeline captured dynamic changes in behavioral scores and abstinence duration in responder groups. Genes showing differential transcript-level expression were enriched in substance use and cardiovascular disease-associated genetic risk loci in responder groups. Lastly, time-dependent gene co-expression revealed dynamic changes related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. This is a preliminary investigation, providing an innovative and scalable pipeline for blood-based longitudinal RNA-seq studies in CUD, potentially applicable to other substance use disorders. It outlines a data-driven approach for analyzing composite longitudinal drug use behavioral phenotypes with blood-based transcriptomics. We also demonstrate changes in drug use behaviors and the blood transcriptome during drug abstinence.

The glutamate delta 1 receptor (GluD1) remained largely unexplored since its cloning three decades ago because it lacked typical ligand-gated ion channel activity. In the last decade, much progress has been made in identifying its potential function. This research has been greatly enhanced by the development of specific tools to determine receptor expression and distribution and genetic mouse models to explore region specific roles in regulating circuits and behavior. Major strides have also been taken in understanding the structure–function of the receptor. These studies demonstrate that GluD1 has many distinctive characteristics including synaptogenic activity at both excitatory and inhibitory synapses, the ability of the ligand-binding domain to bind not only D-serine but also GABA, its unique structural arrangement among the ionotropic glutamate receptor family in relation to domain swapping and the ability to induce tonic currents in the native system. Studies have also identified its role in regulating the postsynaptic content of AMPA and NMDA receptors and synaptic plasticity. Finally, human genetic studies revealed the relationship of GluD1 with neuropsychiatric disorders, including schizoaffective disorders and intellectual disability, which is consistent with the phenotypes observed in mice upon GluD1 ablation. The role of GluD1 is also becoming evident in neurological disorders, particularly chronic pain. Thus, GluD1 has quickly emerged as a receptor with multifaceted roles in physiology and pathology.

The proper interpretation of environmental information is necessary for effective decision-making. The resulting cognitive burden may affect the entire process if interpretation is not instantaneous. In this study, we investigated how numerical distance (ND), a measure of cognitive demand in numerical comparisons, influences movement initiation and inhibition. To this end, 32 participants completed a novel numerical comparison stop-signal task (NC-SST), in which the cognitive demand of each trial was manipulated by varying the ND between pairs of numbers presented in both Go and Stop signals. Participants were required to initiate or stop a movement if the number was higher or smaller than the one indicated as reference. Results showed that larger NDs (i.e., easier comparisons) facilitated faster and more accurate responses during movement initiation and enhanced stopping performance. Using a generalized drift-diffusion model, we found that drift rates increased with Go ND and were modulated by the spatial location of numerical stimuli, consistent with a left-to-right space number association. A generalized linear mixed-effects model further revealed that Go process parameters, particularly the drift rate, strongly predicted successful stopping and interacted with Stop ND and stop-signal delay (SSD). These findings demonstrate that greater cognitive difficulty impairs both movement initiation and inhibition, and that motor decisions result from the integration of cognitive information onto perceptual features, extending the classical race model framework.

This study examined the effect of brain hemisphere stimulation on effort intensity. We applied high-definition transcranial direct current stimulation (HD-tDCS) to the dorsolateral prefrontal cortex (dlPFC) to manipulate left or right hemispheric activity and assess its impact on cardiovascular responses reflecting effort. In total, 102 participants (65 women, 37 men) performed a mental concentration task under right cathodal, left cathodal, or sham stimulation conditions. We recorded cardiovascular responses, including pre-ejection period (PEP), systolic blood pressure (SBP), heart rate (HR), and diastolic blood pressure (DBP). Preregistered hypotheses predicted right cathodal stimulation to lead to greater left frontal hemispheric activity. This should result in higher effort during a mental concentration task of unclear difficulty by increasing approach motivation and thus success importance. As predicted, right cathodal stimulation increased PEP and SBP reactivity, indicating higher effort compared to the left cathodal and sham stimulation conditions. However, this effect was only evident in women, with men exhibiting a contrasting pattern. Our findings highlight the sex-specific effects of brain stimulation on cardiovascular responses reflecting effort, with the anticipated effects appearing in women.