A neural circuit state change underlying skilled movements.

In motor neuroscience, state changes are hypothesized to time-lock neural assemblies coordinating complex movements, but evidence for this remains slender. We tested whether a discrete change from more autonomous to coherent spiking underlies skilled movement by imaging cerebellar Purkinje neuron complex spikes in mice making targeted forelimb-reaches. As mice learned the task, millimeter-scale spatiotemporally coherent spiking emerged ipsilateral to the reaching forelimb, and consistent neural synchronization became predictive of kinematic stereotypy. Before reach onset, spiking switched from more disordered to internally time-locked concerted spiking and silence. Optogenetic manipulations of cerebellar feedback to the inferior olive bi-directionally modulated neural synchronization and reaching direction. A simple model explained the reorganization of spiking during reaching as reflecting a discrete bifurcation in olivary network dynamics. These findings argue that to prepare learned movements, olivo-cerebellar circuits enter a self-regulated, synchronized state promoting motor coordination. State changes facilitating behavioral transitions may generalize across neural systems.

Self-Organized Nuclear Positioning Synchronizes the Cell Cycle in Drosophila Embryos.

The synchronous cleavage divisions of early embryogenesis require coordination of the cell-cycle oscillator, the dynamics of the cytoskeleton, and the cytoplasm. Yet, it remains unclear how spatially restricted biochemical signals are integrated with physical properties of the embryo to generate collective dynamics. Here, we show that synchronization of the cell cycle in Drosophila embryos requires accurate nuclear positioning, which is regulated by the cell-cycle oscillator through cortical contractility and cytoplasmic flows. We demonstrate that biochemical oscillations are initiated by local Cdk1 inactivation and spread through the activity of phosphatase PP1 to generate cortical myosin II gradients. These gradients cause cortical and cytoplasmic flows that control proper nuclear positioning. Perturbations of PP1 activity and optogenetic manipulations of cortical actomyosin disrupt nuclear spreading, resulting in loss of cell-cycle synchrony. We conclude that mitotic synchrony is established by a self-organized mechanism that integrates the cell-cycle oscillator and embryo mechanics.

Nonreciprocal synchronization in embryonic oscillator ensembles.

Synchronization of coupled oscillators is a universal phenomenon encountered across different scales and contexts, e.g., chemical wave patterns, superconductors, and the unison applause we witness in concert halls. The existence of common underlying coupling rules defines universality classes, revealing a fundamental sameness between seemingly distinct systems. Identifying rules of synchronization in any particular setting is hence of paramount relevance. Here, we address the coupling rules within an embryonic oscillator ensemble linked to vertebrate embryo body axis segmentation. In vertebrates, the periodic segmentation of the body axis involves synchronized signaling oscillations in cells within the presomitic mesoderm (PSM), from which somites, the prevertebrae, form. At the molecular level, it is known that intact Notch-signaling and cell-to-cell contact are required for synchronization between PSM cells. However, an understanding of the coupling rules is still lacking. To identify these, we develop an experimental assay that enables direct quantification of synchronization dynamics within mixtures of oscillating cell ensembles, for which the initial input frequency and phase distribution are known. Our results reveal a "winner-takes-it-all" synchronization outcome, i.e., the emerging collective rhythm matches one of the input rhythms. Using a combination of theory and experimental validation, we develop a coupling model, the "Rectified Kuramoto" (ReKu) model, characterized by a phase-dependent, nonreciprocal interaction in the coupling of oscillatory cells. Such nonreciprocal synchronization rules reveal fundamental similarities between embryonic oscillators and a class of collective behaviors seen in neurons and fireflies, where higher-level computations are performed and linked to nonreciprocal synchronization.

Formation of recurring transient Ca2+-based intercellular communities during Drosophila hematopoiesis.

Tissue development occurs through a complex interplay between many individual cells. Yet, the fundamental question of how collective tissue behavior emerges from heterogeneous and noisy information processing and transfer at the single-cell level remains unknown. Here, we reveal that tissue scale signaling regulation can arise from local gap-junction mediated cell-cell signaling through the spatiotemporal establishment of an intermediate-scale of transient multicellular communication communities over the course of tissue development. We demonstrated this intermediate scale of emergent signaling using Ca2+ signaling in the intact, ex vivo cultured, live developing Drosophila hematopoietic organ, the lymph gland. Recurrent activation of these transient signaling communities defined self-organized signaling "hotspots" that gradually formed over the course of larva development. These hotspots receive and transmit information to facilitate repetitive interactions with nonhotspot neighbors. Overall, this work bridges the scales between single-cell and emergent group behavior providing key mechanistic insight into how cells establish tissue-scale communication networks.

The Dynamic Basis of Respiratory Rhythm Generation: One Breath at a Time.

Rhythmicity is a universal timing mechanism in the brain, and the rhythmogenic mechanisms are generally dynamic. This is illustrated for the neuronal control of breathing, a behavior that occurs as a one-, two-, or three-phase rhythm. Each breath is assembled stochastically, and increasing evidence suggests that each phase can be generated independently by a dedicated excitatory microcircuit. Within each microcircuit, rhythmicity emerges through three entangled mechanisms: ( a) glutamatergic transmission, which is amplified by ( b) intrinsic bursting and opposed by ( c) concurrent inhibition. This rhythmogenic triangle is dynamically tuned by neuromodulators and other network interactions. The ability of coupled oscillators to reconfigure and recombine may allow breathing to remain robust yet plastic enough to conform to nonventilatory behaviors such as vocalization, swallowing, and coughing. Lessons learned from the respiratory network may translate to other highly dynamic and integrated rhythmic systems, if approached one breath at a time.

Analytic relationship of relative synchronizability to network structure and motifs.

Synchronization phenomena on networks have attracted much attention in studies of neural, social, economic, and biological systems, yet we still lack a systematic understanding of how relative synchronizability relates to underlying network structure. Indeed, this question is of central importance to the key theme of how dynamics on networks relate to their structure more generally. We present an analytic technique to directly measure the relative synchronizability of noise-driven time-series processes on networks, in terms of the directed network structure. We consider both discrete-time autoregressive processes and continuous-time Ornstein-Uhlenbeck dynamics on networks, which can represent linearizations of nonlinear systems. Our technique builds on computation of the network covariance matrix in the space orthogonal to the synchronized state, enabling it to be more general than previous work in not requiring either symmetric (undirected) or diagonalizable connectivity matrices and allowing arbitrary self-link weights. More importantly, our approach quantifies the relative synchronization specifically in terms of the contribution of process motif (walk) structures. We demonstrate that in general the relative abundance of process motifs with convergent directed walks (including feedback and feedforward loops) hinders synchronizability. We also reveal subtle differences between the motifs involved for discrete or continuous-time dynamics. Our insights analytically explain several known general results regarding synchronizability of networks, including that small-world and regular networks are less synchronizable than random networks.

Stochastic transition in synchronized spiking nanooscillators.

This work reports that synchronization of Mott material-based nanoscale coupled spiking oscillators can be drastically different from that in conventional harmonic oscillators. We investigated the synchronization of spiking nanooscillators mediated by thermal interactions due to the close physical proximity of the devices. Controlling the driving voltage enables in-phase 1:1 and 2:1 integer synchronization modes between neighboring oscillators. Transition between these two integer modes occurs through an unusual stochastic synchronization regime instead of the loss of spiking coherence. In the stochastic synchronization regime, random length spiking sequences belonging to the 1:1 and 2:1 integer modes are intermixed. The occurrence of this stochasticity is an important factor that must be taken into account in the design of large-scale spiking networks for hardware-level implementation of novel computational paradigms such as neuromorphic and stochastic computing.

Challenges and Approaches in the Study of Neural Entrainment.

When exposed to rhythmic stimulation, the human brain displays rhythmic activity across sensory modalities and regions. Given the ubiquity of this phenomenon, how sensory rhythms are transformed into neural rhythms remains surprisingly inconclusive. An influential model posits that endogenous oscillations entrain to external rhythms, thereby encoding environmental dynamics and shaping perception. However, research on neural entrainment faces multiple challenges, from ambiguous definitions to methodological difficulties when endogenous oscillations need to be identified and disentangled from other stimulus-related mechanisms that can lead to similar phase-locked responses. Yet, recent years have seen novel approaches to overcome these challenges, including computational modeling, insights from dynamical systems theory, sophisticated stimulus designs, and study of neuropsychological impairments. This review outlines key challenges in neural entrainment research, delineates state-of-the-art approaches, and integrates findings from human and animal neurophysiology to provide a broad perspective on the usefulness, validity, and constraints of oscillatory models in brain-environment interaction.

Decreased Beta Power and OFC-STN Phase Synchronization during Reactive Stopping in Freely Behaving Rats.

During natural behavior, an action often needs to be suddenly stopped in response to an unexpected sensory input-referred to as reactive stopping. Reactive stopping has been mostly investigated in humans, which led to hypotheses about the involvement of different brain structures, in particular the hyperdirect pathway. Here, we directly investigate the contribution and interaction of two key regions of the hyperdirect pathway, the orbitofrontal cortex (OFC) and subthalamic nucleus (STN), using dual-area, multielectrode recordings in male rats performing a stop-signal task. In this task, rats have to initiate movement to a go-signal, and occasionally stop their movement to the go-signal side after a stop-signal, presented at various stop-signal delays. Both the OFC and STN show near-simultaneous field potential reductions in the beta frequency range (12-30 Hz) compared with the period preceding the go-signal and the movement period. These transient reductions (∼200 ms) only happen during reactive stopping, which is when the stop-signal was received after action initiation, and are well timed after stop-signal onset and before the estimated time of stopping. Phase synchronization analysis also showed a transient attenuation of synchronization between the OFC and STN in the beta range during reactive stopping. The present results provide the first direct quantification of local neural oscillatory activity in the OFC and STN and interareal synchronization specifically timed during reactive stopping.

Co-learning companionship benefits word learning in a new language: Evidence from a dual-brain EEG examination.

Companionship refers to one's being in the presence of another individual. For adults, acquiring a new language is a highly social activity that often involves learning in the context of companionship. However, the effects of companionship on new language learning have gone relatively underexplored, particularly with respect to word learning. Using a within-subject design, the current study employs electroencephalography to examine how two types of companionship (monitored and co-learning) affect word learning (semantic and lexical) in a new language. Dyads of Chinese speakers of English as a second language participated in a pseudo-word-learning task during which they were placed in monitored and co-learning companionship contexts. The results showed that exposure to co-learning companionship affected the early attention stage of word learning. Moreover, in this early stage, evidence of a higher representation similarity between co-learners showed additional support that co-learning companionship influenced attention. Observed increases in delta and theta interbrain synchronization further revealed that co-learning companionship facilitated semantic access. In all, the similar neural representations and interbrain synchronization between co-learners suggest that co-learning companionship offers important benefits for learning words in a new language.

Romantic relationships attenuated competition between lovers: evidence from brain synchronization.

Competition is an essential component of social interaction and is influenced by interpersonal relationships. This study is based on social exchange theory and explores the relationship between brain synchronization and competition in the binary system of romantic relationships through electroencephalogram hyperscanning technology. The results found that females had a greater win rate in the romantic and friend groups. During the early stage (0-200 ms), when the competitive target appeared, the stranger group exhibited greater interbrain synchronicity in the Alpha frequency band. However, during the later stage (600-800 ms), the romantic group showed higher Alpha band interbrain synchrony when the competitive target appeared. Significant interbrain synchronizations were observed in the Theta frequency band of the stranger and friend groups at 400-600 ms and 800-1000 ms. Moreover, these interbrain synchronizations were significantly positively correlated with the winning rates of females in the competition. These findings suggest a close relationship between interpersonal coordination and interbrain synchronization. Furthermore, romantic relationships reduce participants' willingness to compete, affecting their attention regulation, emotional processing, and goal orientation, thus influencing competition. This study investigated the impact of romantic relationships on competition, providing a theoretical foundation for promoting the positive and healthy development of romantic relationships.

Enhanced neural synchronization during social communications between dyads with high autistic traits.

Autism is characterized by atypical social communication styles. To investigate whether individuals with high autistic traits could still have effective social communication among each other, we compared the behavioral patterns and communication quality within 64 dyads of college students paired with both high, both low, and mixed high-low (HL) autistic traits, with their gender matched. Results revealed that the high-high (HH) autistic dyads exhibited atypical behavioral patterns during conversations, including reduced mutual gaze, communicational turns, and emotional sharing compared with the low-low and/or HL autistic dyads. However, the HH autistic dyads displayed enhanced interpersonal neural synchronization during social communications measured by functional near-infrared spectroscopy, suggesting an effective communication style. Besides, they also provided more positive subjective evaluations of the conversations. These findings highlight the potential for alternative pathways to effectively communicate with the autistic community, contribute to a deeper understanding of how high autistic traits influence social communication dynamics among autistic individuals, and provide important insights for the clinical practices for supporting autistic people.

EEG evidence for racial ingroup bias in collective empathy for pain.

Previous research on racial ingroup bias in empathy for pain focused on neural responses to a single person's suffering. It is unclear whether empathy for simultaneously perceived multiple individuals' pain (denoted as collective empathy in this study) is also sensitive to perceived racial identities of empathy targets. We addressed this issue by recording electroencephalography from Chinese adults who responded to racial identities of 2 × 2 arrays of Asian or White faces in which 4 faces, 1 face, or no face showed painful expressions. Participants reported greater feelings of others' pain and their own unpleasantness when viewing 4 compared to 1 (or no) painful faces. Behavioral responses to racial identities of faces revealed decreased speeds of information acquisition when responding to the face arrays with 4 (vs. 1 or no) painful expressions of Asian (but not White) faces. Moreover, Asian compared to White face arrays with 4 (vs. 1 or no) painful expressions elicited a larger positive neural response at 160-190 ms (P2) at the frontal/central electrodes and enhanced alpha synchronizations at 288-1,000 ms at the central electrodes. Our findings provide evidence for racial ingroup biases in collective empathy for pain and unravel its relevant neural underpinnings.

The shorter a man is, the more he defends fairness: relative height disadvantage promoting third-party punishment-evidence from inter-brain synchronization.

Third-party punishment occurs in interpersonal interactions to sustain social norms, and is strongly influenced by the characteristics of the interacting individuals. During social interactions, height is the striking physical appearance features first observed, height disadvantage may critically influence men's behavior and mental health. Herein, we explored the influence of height disadvantage on third-party punishment through time-frequency analysis and electroencephalography hyperscanning. Two participants were randomly designated as the recipient and third party after height comparison and instructed to complete third-party punishment task. Compared with when the third party's height is higher than the recipient's height, when the third party's height is lower, the punishment rate and transfer amount were significantly higher. Only for highly unfair offers, the theta power was significantly greater when the third party's height was lower. The inter-brain synchronization between the recipient and the third party was significantly stronger when the third party's height was lower. Compared with the fair and medium unfair offers, the inter-brain synchronization was strongest for highly unfair offers. Our findings indicate that the height disadvantage-induced anger and reputation concern promote third-party punishment and inter-brain synchronization. This study enriches research perspective and expands the application of the theory of Napoleon complex.

Beta rebound reduces subsequent movement preparation time by modulating of GABAA inhibition.

Post-movement beta synchronization is an increase of beta power relative to baseline, which commonly used to represent the status quo of the motor system. However, its functional role to the subsequent voluntary motor output and potential electrophysiological significance remain largely unknown. Here, we examined the reaction time of a Go/No-Go task of index finger tapping which performed at the phases of power baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds (ballistic/self-paced) in 13 healthy subjects. We found a correlation between the post-movement beta synchronization and reaction time that larger post-movement beta synchronization prolonged the reaction time during Go trials. To probe the electrophysiological significance of post-movement beta synchronization, we assessed intracortical inhibitory measures probably involving GABAB (long-interval intracortical inhibition) and GABAA (short-interval intracortical inhibition) receptors in beta baseline and post-movement beta synchronization peak induced by index finger abduction movements at different speeds. We found that short-interval intracortical inhibition but not long-interval intracortical inhibition increased in post-movement beta synchronization peak compared with that in the power baseline, and was negatively correlated with the change of post-movement beta synchronization peak value. These novel findings indicate that the post-movement beta synchronization is related to forward model updating, with high beta rebound predicting longer time for the preparation of subsequent movement by inhibitory neural pathways of GABAA.

Multitissue Circadian Proteome Atlas of WT and Per1-/-/Per2-/- Mice.

The molecular basis of circadian rhythm, driven by core clock genes such as Per1/2, has been investigated on the transcriptome level, but not comprehensively on the proteome level. Here we quantified over 11,000 proteins expressed in eight types of tissues over 46 h with an interval of 2 h, using WT and Per1/Per2 double knockout mouse models. The multitissue circadian proteome landscape of WT mice shows tissue-specific patterns and reflects circadian anticipatory phenomena, which are less obvious on the transcript level. In most peripheral tissues of double knockout mice, reduced protein cyclers are identified when compared with those in WT mice. In addition, PER1/2 contributes to controlling the anticipation of the circadian rhythm, modulating tissue-specific cyclers as well as key pathways including nucleotide excision repair. Severe intertissue temporal dissonance of circadian proteome has been observed in the absence of Per1 and Per2. The γ-aminobutyric acid might modulate some of these temporally correlated cyclers in WT mice. Our study deepens our understanding of rhythmic proteins across multiple tissues and provides valuable insights into chronochemotherapy. The data are accessible at https://prot-rhythm.prottalks.com/.

A hypothesis concerning distinct schemes of olfactory activation evoked by perceived versus nonperceived input.

SignificanceThe authors propose that odors are consciously perceived or not, depending on whether the olfactory cortex succeeds in activating the endopiriform nucleus-a structure that, in turn, is capable of activating multiple downstream brain areas. The authors further propose that the cellular mechanisms of endopiriform nucleus activation are an attenuated form of cellular events that occur during epileptic seizure initiation. If correct, the authors' hypothesis could help explain the mechanisms of action of certain general anesthetics.

A variable refractory period increases collective performance in noisy environments.

Synchronized oscillations are found in all living systems, from cellsto ecosystems and on varying time scales. A generic principlebehind the production of oscillations involves a delay in theresponse of one entity to stimulations from the others in the sys-tem. Communication among entities is required for the emergenceof synchronization, but its efficacy can be impaired by surroundingnoise. In the social spiderAnelosimus eximius, individuals coordi-nate their activity to catch large prey that are otherwise inaccessi-ble to solitary hunters. When hunting in groups, dozens of spidersmove rhythmically toward their prey by synchronizing movingand stopping phases. We proposed a mechanistic model imple-menting individual behavioral rules, all derived fromfield experi-ments, to elucidate the underlying principles of synchronization.We showed that the emergence of oscillations in spiders involvesa refractory state, the duration of which depends on the relativeintensity of prey versus conspecific signals. Thisflexible behaviorallows individuals to rapidly adapt to variations in their vibrationallandscapes. Exploring the model reveals that the benefits of syn-chronization resulting from improved accuracy in prey detectionand reduced latency to capture prey more than offset the cost ofthe delay associated with immobility phases. Overall, our studyshows that a refractory period whose duration is variable anddependent on information accessible to all entities in the systemcontributes to the emergence of self-organized oscillations innoisy environments. Ourfindings may inspire the design of artifi-cial systems requiring fast andflexible synchronization betweentheir components.

Annealing synchronizes the 70S ribosome into a minimum-energy conformation.

Researchers commonly anneal metals, alloys, and semiconductors to repair defects and improve microstructures via recrystallization. Theoretical studies indicate that simulated annealing on biological macromolecules helps predict the final structures with minimum free energy. Experimental validation of this homogenizing effect and further exploration of its applications are fascinating scientific questions that remain elusive. Here, we chose the apo-state 70S ribosome from Escherichia coli as a model, wherein the 30S subunit undergoes a thermally driven intersubunit rotation and exhibits substantial structural flexibility as well as distinct free energy. We experimentally demonstrate that annealing at a fast cooling rate enhances the 70S ribosome homogeneity and improves local resolution on the 30S subunit. After annealing, the 70S ribosome is in a nonrotated state with respect to corresponding intermediate structures in unannealed or heated ribosomes. Manifold-based analysis further indicates that the annealed 70S ribosome takes a narrow conformational distribution and exhibits a minimum-energy state in the free-energy landscape. Our experimental results offer a facile yet robust approach to enhance protein stability, which is ideal for high-resolution cryogenic electron microscopy. Beyond structure determination, annealing shows great potential for synchronizing proteins on a single-molecule level and can be extended to study protein folding and explore conformational and energy landscapes.

Neural synchronization predicts marital satisfaction.

Marital attachment plays an important role in maintaining intimate personal relationships and sustaining psychological well-being. Mate-selection theories suggest that people are more likely to marry someone with a similar personality and social status, yet evidence for the association between personality-based couple similarity measures and marital satisfaction has been inconsistent. A more direct and useful approach for understanding fundamental processes underlying marital satisfaction is to probe similarity of dynamic brain responses to maritally and socially relevant communicative cues, which may better reflect how married couples process information in real time and make sense of their mates and themselves. Here, we investigate shared neural representations based on intersubject synchronization (ISS) of brain responses during free viewing of marital life-related, and nonmarital, object-related movies. Compared to randomly selected pairs of couples, married couples showed significantly higher levels of ISS during viewing of marital movies and ISS between married couples predicted higher levels of marital satisfaction. ISS in the default mode network emerged as a strong predictor of marital satisfaction and canonical correlation analysis revealed a specific relation between ISS in this network and shared communication and egalitarian components of martial satisfaction. Our findings demonstrate that brain similarities that reflect real-time mental responses to subjective perceptions, thoughts, and feelings about interpersonal and social interactions are strong predictors of marital satisfaction, reflecting shared values and beliefs. Our study advances foundational knowledge of the neurobiological basis of human pair bonding.