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Frontiers in Systems Neuroscience

Frontiers Media SA

Preprints posted in the last 30 days, ranked by how well they match Frontiers in Systems Neuroscience's content profile, based on 19 papers previously published here. The average preprint has a 0.02% match score for this journal, so anything above that is already an above-average fit.

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Synaptic pruning, myelination and the emergence of psychiatric disorders in late adolescence

Averbeck, B. B.; Brunel, N.

2026-05-21 neuroscience 10.64898/2026.05.20.726636 medRxiv
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Adolescence is an important developmental period during which there are diverse changes in the brain and behavior. Goal-directed behaviors and the component processes underlying those behaviors improve during adolescence, including working memory, response inhibition, and reinforcement learning. At the same time there is substantial pruning of excitatory connections in prefrontal cortex and ongoing myelination of axons. However, psychiatric disorders also become increasingly prevalent in late adolescence and early adulthood. In this study, we develop computational models that suggest a hypothesis for how the ongoing changes in the brain can give rise to the increased prevalence of psychiatric disorders. We show that both myelination and pruning during adolescence lead to attractor landscapes in which strongly encoded memories, driven by three-factor learning rules that modulate Hebbian plasticity, come to dominate the landscape of brain activity, at the expense of weakly encoded memories. Pruning and myelination lead to large, strong attractors which, if they are related to aversive emotions, can drive intrusive thoughts and compulsions in obsessive compulsive disorder, rumination in depression, and aversive memories in post-traumatic stress disorder. The link between pruning, myelination and the emergence of dominant attractors for emotionally salient memories is well supported by the models. The way these effects map onto forebrain circuits requires more work.

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Macroscale traveling waves link perception, response selection, and vocal production during marmoset vocal interactions

Yi, D.; Gao, X.; Tao, R.; Komatsu, M.; Tsunada, J.

2026-05-15 neuroscience 10.64898/2026.05.15.725341 medRxiv
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Vocal communication involves a series of cognitive processes, which can be broadly categorized into three components: perceiving communicative signals; deciding whether and how to respond; and generating vocal motor output. These processes must work harmoniously, with integration and bridging between components being crucial for effective communication. Previous research on vocal communication has typically focused on specific brain regions or isolated cognitive functions, often lacking a holistic perspective of macro-scale, whole-cortical dynamics and their role in the complete communication process. Therefore, although the cortical areas associated with each cognitive component have been localized in humans, the macro-scale cortical dynamics underlying the integration of these cognitive processes remain unknown. Building on recent findings linking macro-scale cortical dynamics to behavioral performance, we hypothesized that traveling wave like cross-areal interactions play a role in integrating the three communicative components. To test this hypothesis, we recorded whole-cortical activity using epidural electrocorticography (ECoG) while subject marmosets vocally interacted with partners. We found theta-band activation in several cortical areas, including the parietal and auditory cortices, while listening to partners calls. This activity was further modulated depending on whether the subjects engaged in vocal interactions, potentially representing the transformation of sensory processing into decision-making and vocal motor preparation. Given the widespread nature of this modulation, we next characterized whole-brain activity patterns by employing a novel analytical method, Weakly Orthogonal Conjugate Contrast Analysis (WOCCA). This analysis revealed that cortical activity could be decomposed into two distinct traveling wave like propagation patterns, a rotational and a translational wave, and both waves discriminated communicative conditions consistent with localized activity. The rotational wave further represented vocal motor preparation through trigger-like temporal pattern. In addition, the magnitude of the translational wave immediately before subjects vocal production correlated with the vocal production-induced suppression of high-gamma-band activity, particularly in the prefrontal and auditory cortices. As vocalization-induced suppression is believed to reflect sensory prediction, the translational wave may propagate specific decision-related or acoustic information necessary for subsequent vocal production to local cortical areas. These findings suggest that the brain orchestrates the sequential cognitive processes underlying vocal communication through macro-scale traveling waves.

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Inter-hemispheric connections modulate splitting in a computational model of the bilateral SCN

Zemlianova, K.; McDaniel, J.; Lander, A. G.; Nwaezeapu, J.; Gutierrez, G. J.

2026-05-05 neuroscience 10.64898/2026.04.30.722022 medRxiv
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The phenomenon of splitting was originally observed in hamsters which, after prolonged exposure to constant light, exhibit two rest/wake cycles within a subjective day. Splitting is a consequence of the left and right suprachiasmatic nuclei (SCN) falling out of synchrony. While it is known that split activity is characterized by an antiphase relationship between the left and right SCN and between the core and shell within each hemisphere, the role of the commissural projections that connect the right and left SCN is not known. In the present study, we investigate the impact of the inter-hemispheric connections on the split and unsplit dynamics of a computational model of the bilateral SCN. Our model has 4 nodes corresponding to each right and left core and shell. We simulated our bilateral model under different lighting conditions and measured its period and the phase relationships among the 4 nodes. To further characterize the dynamics of the system, we performed a bifurcation analysis. We found that the bilateral model automatically splits unless entrained by bright light/dark cycles, or unless it has excitatory inter-hemispheric connections. This suggests that excitatory cross-connections may be important for freerunning behavior. We found that constant light of varying intensities transitions the model between split and unsplit activity only in very limited conditions, but the strength and polarity of the contralateral connections play a much greater role in this dynamical transition. These findings suggest that splitting may involve plasticity of the inter-hemispheric connections of the SCN.

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Homeostatic regulation of intrinsic neuronal excitability in visual thalamic relay cells induced by brief monocular deprivation

Aziz, A.; Fronzaroli-Molinieres, L.; Iborra, C.; Dumenieu, M.; Zanin, E.; David, T.; Denis, D.; Garrido, J. J.; Brette, R.; Russier, M.; Debanne, D.

2026-05-21 neuroscience 10.64898/2026.05.19.726212 medRxiv
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Homeostatic plasticity of intrinsic excitability (IE) in the visual system has been essentially shown at the cortical level but whether thalamic nuclei also express homeostatic plasticity of IE is unknown. We show here that 4 days of monocular deprivation (MD) at eye opening induces a homeostatic change in IE in dorsal lateral geniculate nucleus (dLGN) neurons. Neurons recorded in the dLGN region activated by the deprived eye are more excitable than neurons recorded in the dLGN region activated by the open eye. No significant changes were observed following 7 days of MD, however. Enhanced excitability in neurons from the deprived side after 4 days of MD was associated with a reduced Kv1-dependent LTP-IE, a smaller voltage ramp, and a reduced inter-spike interval, suggesting that Kv1 channels are down-regulated in deprived dLGN neurons. Furthermore, the ankyrin G signal of the axon initial segment was larger in deprived dLGN neurons compared with open ones, indicating that Nav1 channel number also undergoes homeostatic regulation, and Kv1.1 channel signals were lower in deprived neurons compared to open ones. In addition, electrical coupling was found to be strengthened in neurons displaying enhanced IE following either brief (4 days) or long (10 days) MD. These results suggest that homeostatic and Hebbian plasticity in the dLGN share common expression mechanisms involving the regulation of Kv1 channels, Nav1 channels and electrical coupling between relay neurons.

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Differential maturation in vestibular neuronal groups related to developmental motor reorganization in amphibians

Barrios, G.; Olechowski-Bessaguet, A.; Cardoit, L.; Fevrier, T.; Wattignier, A.; Tostivint, H.; Cattaert, D.; Thoby-Brisson, M.; Lambert, F. M.

2026-05-13 neuroscience 10.64898/2026.05.12.724497 medRxiv
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Vestibular neurons are core elements of the pathways involved in vestibulo-motor functions, such as vestibulo-spinal and vestibulo-ocular reflexes. To meet behavioral needs, electrophysiological neuronal properties are adequately adapted to the sensory-motor computation sustaining these distinct vestibular reflexes. During frog metamorphosis, there is a complete reorganization of the posturo-locomotor system while the oculomotor system remains minimally changed, probably associated to so far unknown changes in vestibular neuronal properties. We used this unique model to investigate the central developmental mechanisms underlying such a reconfiguration of vestibular-associated behaviors. Central vestibular neurons exhibit two types of electrophysiological phenotypes: tonic neurons with a continuous discharge and phasic neurons with a transitory discharge mainly due to the activation of Kv1.1 channel. Electrophysiological recordings and Kv1.1 immunolabeling of vestibulospinal (VS) and vestibulo-ocular (VO) neurons at both larval and juvenile stages revealed that the majority of VS neurons exhibited a tonic discharge in larvae but a phasic discharge in juvenile, while VO neurons remained mainly tonic throughout development. Changes in phasic and tonic neurons proportions in VS population are partly explained by neurogenesis. But we provide evidences that an electrophysiological phenotype switch is a concomitant developmental mechanism participating in the maturation of these central vestibular neurons. All together our results showed that the maturation process in central vestibular neuronal groups is highly related to the metamorphosis-induced remodeling of vestibulo-motor functions they are involved in, with the ultimate purpose of ensuring an adequate adaptation of neuronal elements properties to the developmental changes of behavioral constrains.

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Membrane voltage multistability in coupled glial cells

Janjic, P.; Solev, D.; Zhou, M.; Kocarev, L.

2026-05-06 neuroscience 10.64898/2026.05.03.722503 medRxiv
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Growing interest to describe the electrical behavior of glial cells, mainly astrocytes, in intact brain tissue poses more and more challenges to commonly accepted belief they only respond in a linear manner in uptake of the excess of extracellular potassium and maintenance of their network equipotentiality. Their highly conductive mutual interconnections via gap junction (GJ) connections introduce yet another class of nonlinear elements. As more studies report nonlinearities in membrane voltage Vm dependence of both, the membrane and junctional conductances, the need to formulate minimal dynamical models of their transient behavior is getting more acute. Since ODE models of coupled cells, even in simplest 1-d arrays, require simplified descriptions and small set of parameters, rare quantitative studies on glia makes the task even more difficult. This study attempts to qualify a self-coupled cell, or a glial cell coupled to fixed voltage as useful system for detecting the nature of instabilities and transitions coming from coupling. In a novel biophysical model of coupled astrocyte, we introduce nonlinear kinetics of deactivation for large junctional voltages for the first time. We found that N-shaped nonlinearities and corresponding fold structure in the vector field of isolated cell serves as a baseline on top of which coupling nonlinearities enrich the bifurcation picture. Numerical simulations of 1-d array of coupled astrocytes show that coupling increases the propensity of astrocytic Vm to bistability and front propagation. We believe that presented illustrations of possible effects of coupling nonlinearities will motivate neurobiologists to further explore their impact in disease. Significance statementTransient changes in membrane voltage of glial cells may produce significant transient voltage difference between directly coupled cells. Nonlinear steady-state conductance of their interconnection elements, the gap junctions, introduce nonlinear current profiles which are very difficult to measure and quantitate using the available methods due to marked permeability of the junctions and leakiness of glial membrane in general. We propose a minimal model of glial membrane extended with a self-coupled feedback loop, which under realistic simplifying assumptions could serve for qualitative analysis of the impact of coupling, on the stability of resting membrane voltage. Neuronal cells of the brain and spinal cord cannot exist and function without supportive and neuromodulatory functions of the diverse population of glial cells. This applies to virtually all physiological processes on cell level - from cell development, metabolic support, membrane signaling, slow molecular signal transduction, ion homeostasis, neurovascular coupling, myelination, to mention only a few, manifest neuro-glial interaction. Even though all glial cell types are interconnected, the most abundant ones, the astrocytes are massively interconnected by gap junctions to form ordered networks. Electrically, astrocytic networks display membrane voltage equipotentiality, which is considered system-wide resting state for given neuro-glial circuit or unit. With molecular and cellular substrates of glial connectivity being slowly elucidated, network science and dynamical modeling are slowly "invading" that area with many important issues left open. In this study using classical dynamical systems approaches we give indications how nonlinear intercellular coupling between astrocytes affects physiological resting state and its instabilities compared to isolated, uncoupled cell. We strongly believe the suggested minimal model could fill the gap in ODE modeling of neuro-glial circuits, within broadest scope of hypothesis-driven research in cell-level neuroscience.

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Spatiotemporal dynamics of flow experience: an EEG microstate analysis

Khoshnoud, S.; Alvarez Igarzabal, F.; Wittmann, M.

2026-05-14 neuroscience 10.64898/2026.05.11.724329 medRxiv
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Flow, as defined by Mihalyi Csikszentmihalyi (1975), is a holistic sensation experienced when individuals are fully immersed in an activity, resulting in a mental state characterized by a diminished sense of self and altered perception of time. To investigate the global neural dynamics underlying flow, we employed EEG microstate analysis to capture the spatial and temporal properties of dominant transient global brain states (Lehmann et al., 1998). In a study involving 43 participants playing the video game Thumper for 25 minutes, we extracted three four-minute EEG segments from each session corresponding to reported experiences of flow, boredom, and frustration, as determined by self-reports and performance metrics. Across conditions, six distinct microstate topographies (A-F) accounted for most of the global variance. Given that reduced self-referential processing is a key feature of flow, we hypothesized that flow would modulate the properties of microstates C and E, which have been associated with brain regions resembling the default mode network (DMN). Compared to boredom and frustration, the flow condition showed significantly decreased global explained variance, mean duration, time coverage, and occurrence frequency of microstate E, as well as reduced mean duration and time coverage of microstate C. These findings suggest that microstates associated with self-referential processing are shorter and less frequent during flow than during boredom and frustration. This supports the notion that the flow experience modulates global brain dynamics, particularly within the DMN. Furthermore, our results align with previous research reporting reduced DMN activity during meditative and psychedelic states, reinforcing the idea of diminished self-awareness in such conditions.

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Greater gray matter volume in somatosensory and parietal regions in elite skiers compared with other athletes

Nakagawa, K.; Kanosue, K.

2026-05-13 neuroscience 10.64898/2026.05.10.724084 medRxiv
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Elite athletes exhibit sport-specific neural adaptations, yet it remains unclear whether such changes reflect general effects of training or the unique demands of individual sports. Skiing requires postural control and whole-body coordination under dynamically unstable environments, placing high demands on somatosensory processing and sensorimotor integration. The present study aimed to identify structural brain characteristics specific to elite skiers by comparing them with athletes from other sports disciplines and non-athletes. T1-weighted MRI data were analyzed using voxel-based morphometry in 13 skiers, 23 non-ski control athletes and 25 non-athletes. Whole-brain analysis comparing skiers with non-ski athletes revealed a significant cluster showing greater gray matter volume in skiers compared with non-ski athletes in the left postcentral gyrus, extending into the superior parietal lobule. The identified cluster primarily encompassed cytoarchitectonic Areas 2 and 5L. These regions are involved in higher-order somatosensory processing and multisensory integration. Importantly, region-of-interest analysis demonstrated that gray matter volume within this cluster was greater in skiers compared with non-ski athletes and non-athletes, with no difference between non-ski athletes and non-athletes. These findings highlight the relative prominence of structural adaptations within somatosensory-parietal networks, reflecting the unique integration of proprioceptive and other sensory information required for elite skiing. Overall, these findings provide evidence for sport-specific structural brain differences in elite athletes and highlight the importance of somatosensory and parietal regions in sensorimotor integration relevant to skiing. These findings may have implications for understanding neural markers of expertise and may inform future approaches to training and performance evaluation in skiing.

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Frontal P3 Potential as a Supramodal Marker of Imminent Attentional Lapses

Kenemans, J. L.; Canny, E.; Van der Haest, J.; Koevoet, D.

2026-05-22 neuroscience 10.64898/2026.05.20.726475 medRxiv
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Focusing on an organisms task at hand is instrumental for intelligent and goal-driven behavior. However, humans and other animals often fail to pay sustained attention across long time intervals. Failing to stay on-task may cause one to miss crucial task-relevant signals, leading to impaired performance, which can have serious consequences. Therefore, it is important to understand the neural basis of attentional lapses. One promising neural marker of attentional lapses is the frontal P3 (fP3) EEG component, which has been suggested to reflect the susceptibility to incoming sensory input. Following this, we hypothesized that the fP3 1) predicts imminent lapses of attention, and 2) that it should predict upcoming lapses of attention across modalities. In two experiments, we found that the fP3 reliably tracked lapses of attention of sustained attention already seconds preceding the crucial visual signal. We further extended this to the auditory domain: Already 1.5s ahead of the incoming auditory target, the fP3 revealed whether that target was detected or not. Detailed topographic analyses did, however, reveal a slight dissociation between modalities in underlying intracranial source configurations. In sum, this work revealed a supramodal neural signature of susceptibility, which tracks lapses of sustained attention seconds ahead of the critical incoming sensory input.

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A continuum of asynchronous states in cerebral cortex networks, and how they determine responsiveness

Bassat, M.; Tesler, F.; Destexhe, A.

2026-05-09 neuroscience 10.64898/2026.05.06.723408 medRxiv
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The awake brain is known to display asynchronous (AS) states during periods of attention and arousal, but the responsiveness properties of such states remain unclear. Here, we investigate this question using computational models of spiking networks of excitatory and inhibitory neurons, mimicking recurrently-connected networks in layer 2/3 of the cerebral cortex. The networks can generate a continuum of AS states, but with different responsiveness characteristics. By using a mean-field model to infer the dynamic properties of the system, we find that there are two families of AS states, which we call "underdamped" (UD) and "overdamped" (OD). Responsiveness is maximised at the transition between OD and UD states, which identifies a "working point" that may present advantageous computational properties.

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Hippocampal representations of partner and novel individuals in monogamous California mice during pair bond formation

Hernandez Palacios, K.; Golam, O.; Siegelbaum, S. A.; Bendesky, A.

2026-05-09 neuroscience 10.64898/2026.05.08.723922 medRxiv
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The hippocampal CA2 region is critical for social novelty recognition memory--the discrimination of whether a conspecific is novel or familiar. However, its role in forming a memory of a pair-bonded mate is unknown. To examine how social memories of pair-bonded individuals are encoded, we sought to understand if CA2 and the neighboring CA1 region participate in the memorization and recognition of a pair-bonded mate in monogamous Peromyscus californicus (California mice). Here, we report that CA2 and CA1 show distinct changes in social encoding of an opposite sex conspecific following pair-bonding. Using multi-channel silicon probes, we recorded single units from CA2 and CA1 in freely behaving male mice before and after pair bond formation during interactions with novel and partner females. We found that the strength of CA2 representations of a novel female mouse weakened after pair bond formation, indicating that CA2 may be preferentially important for novelty detection. In contrast, CA1 demonstrated an increase in the strength of encoding a female partner after pair-bond formation, suggesting that CA1 may encode partner memory. These findings indicate that pair bonding shifts the discrimination of social information from CA2 to CA1.

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Spontaneous locus coeruleus bursts coincide withtransient global brain state changes similar to thoseelicited by surprise

Somervail, R.; Yang, M.; Iannetti, G.; Eschenko, O.

2026-05-21 neuroscience 10.64898/2026.05.19.726177 medRxiv
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Sudden and isolated sensory stimuli (SISS) engage the extralemniscal system and elicit widespread electrocortical responses in the brain. These responses, consisting of both time-domain transients and spectral changes, reflect a switch of the global brain state that likely prepares the organism for subsequent urgent behaviours. Crucially, SISS also elicit a short-latency phasic response in a key component of the extralemniscal system in the brainstem, the noradrenergic Locus Coeruleus (LC) nucleus. Such stimulus-evoked LC firing is associated with the electrocortical markers of extralemniscal activation. LC neurons also display burst-like firing spontaneously, i.e., without imposed sensory stimuli, for example, during quiet wakefulness, sleep, or anaesthesia. However, this phenomenon remains underexplored. We therefore measured, in freely behaving rats, the prefrontal electrocorticogram (ECoG) responses following spontaneous LC bursts. In addition, we compared these ECoG responses to those triggered by electrical LC stimulation or auditory SISS. We found that ECoG responses were proportional to the magnitude of the spontaneous LC bursts or microstimulation, and remarkably similar to those elicited by SISS. Finally, suppression of noradrenergic transmission with systemic clonidine administration attenuated the auditory-evoked ECoG response. These results suggest that LC plays a role in generating the transient brain state changes elicited by SISS.

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Rapid connectivity alterations of thalamic nuclei during initial learning of goal-directed behaviour

Jarrett, C.; Fregni, S.; Kriegstein, K. v.; Ruge, H.

2026-05-16 neuroscience 10.64898/2026.05.15.725154 medRxiv
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The thalamus is essential for learning, dynamically engaging with other subcortical and cerebral cortex regions throughout the learning process. Here, the thalamus serves as a critical connector hub and synchroniser within the thalamocortical system of the brain. However, whilst higher order thalamic nuclei are known to be particularly important for this process, the exact contributions of individual higher order and first order thalamic nuclei, alongside their individual involvement with cortical networks and subcortical regions, remains unexplored within the initial phase of learning. In light of this, we analysed fMRI data obtained within a paradigm which is designed to examine initial learning processes within feedback-driven stimulus-response learning, in order to explore thalamic contributions. We investigated dynamic learning-related functional connectivity alterations between various thalamic nuclei with other subcortical regions and cortical networks. Our results show that the initial phase of learning was associated with: (1) decreasing functional connectivity between thalamic nuclei and frontoparietal and cingulo-opercular networks, (2) increasing functional connectivity between thalamic nuclei with default mode and salience networks, (3) decreasing functional connectivity between thalamic nuclei and the putamen, and (4) decreasing functional connectivity amongst higher order thalamic nuclei. Furthermore (5) these dynamic alterations were associated primarily by mediodorsal thalamus. Altogether, these results indicate that higher order thalamic nuclei play a crucial role within initial learning and in the generation of novel goal-directed behaviour. This was demonstrated through enhanced functional connectivity with selected cortical networks which drive goal-directed behaviour, alongside decreased functional connectivity with striatal regions which drive motor selectivity.

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Condition-Dependent Noise Correlations without Condition-Dependent Spike Counts

Kim, D.; Panichello, M.; Moore, T.

2026-05-09 neuroscience 10.64898/2026.05.08.723078 medRxiv
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The ability of the brain to encode information and control behavior depends on the coordinated activity of large and distributed neuronal populations. Correlations in neuronal spiking activity across trials of the same condition, or noise correlations (NCs), have been interpreted as a reflection of shared synaptic connectivity and as a contributing factor to the information capacity of neuronal populations. The impact of NCs on coding is most often considered in populations of neurons exhibiting robust condition-dependent information in their spike counts (SCs). However, theoretical work suggests that NCs could provide a source of condition-dependent information separate from SCs. We examined the activity of large neuronal populations in prefrontal cortex of macaques while they performed a spatial delayed response task composed of visual, memory, and motor epochs. We found that pairs of neurons that displayed visual, memory, and motor selectivity in their SCs often exhibited selectivity in their NCs, independent of spike count. However, we also found that pairs of neurons without SC selectivity during the different task epochs nonetheless exhibited condition-dependent NCs. Moreover, we found that the magnitude of condition-dependent NCs were largely comparable across neuronal pairs with or without SC selectivity. These results demonstrate that correlated variability in spiking activity can be condition-dependent even in the absence of condition-dependent SCs.

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A detailed investigation of Shared Variance Component Analysis as a tool to characterize neural dimensionality

Carballosa, A.; Torcini, A.

2026-05-04 neuroscience 10.64898/2026.04.30.721904 medRxiv
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BackgroundThe relevance of spontaneous activity has been unlocked thanks to recent large scale recordings that revealed, via Shared Variance Component Analysis (SVCA), the high-dimensional nature of the ongoing activity. A fundamental problem is how the dimension modifies when more neurons are included in the analysis. Contradictory results have been reported on this subject based on SVCA and Principal Component Analysis (PCA). New MethodWe investigate pro et contra of SVCA and PCA for the identification of reliable responses encoding underlying state variables. We focus on common features of the spectra of the reliable variances (RVs) and on their dimensionality. The analysis is demonstrated on previously published Ca2+ data from the visual and the dorsal cortex in head fixed mice during spontaneous behavior. ResultsRVs grow proportionally to the number N of neurons and show a power-law decay k- with the k-th SVC dimension over a range bounded by a maximal dimension kc, initially diverging as N 1/ and then saturating at sufficiently large N. The reliable dimensionality, estimated with different methodologies, also shows a clear saturation to an asymptotic value for large N. Furthermore, its value decreases when becomes larger, as demonstrated by employing experimental data as well as theoretical predictions. ConclusionWe have shown that SVCA is an extremely effective tool to extract reliable features from the neural signals, and that the exponent represents a biomarker able to reveal the level of correlation of the neurons as well as the dimensionality of the reliable space. HighlightsO_LIAdvantages and drawbacks of Shared Variance Component Analysis to extract reliable signals from neural data C_LIO_LIComparison of different methods to estimate reliable neural dimensionality associated to spontaneous activity C_LIO_LIAnalytical expressions of embedding dimensionality for power-law decaying reliable variances C_LIO_LIBounded growth of the dimensionality with the number of neurons C_LI

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A Competitive Framework for Modeling EEG Microstate Durations

GOMEZ, C. M.; Angulo Ruiz, B. Y.

2026-05-22 neuroscience 10.64898/2026.05.20.726605 medRxiv
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BackgroundThis study examines a competition-based model (C-model) designed to capture the temporal dynamics of successive brain microstates derived from electroencephalography (EEG) recordings during eyes-open conditions. The analyzed data were obtained from a public repository comprising microstate sequences from 60 sessions of a single subject [1]. When applied to microstate dynamics, the C-model posits a stochastic competition among neural circuits underlying the expression of individual microstates. MethodsThe model is formulated at a conceptual level (computational level in Marrs framework) and employs a geometric distribution to account for the long right tail of microstate duration distributions, interpreted as the probability of "failure" of the currently active microstate to persist. To account for the short-lived left tail, the model incorporates a transient increase in the stability of the currently active network, or equivalently, a temporary decrease in the activation probability of competing microstates (refractory period). ResultsThe model provides a good fit to the microstate duration distributions across all 60 sessions. One third of sessions showed microstate identity sequential dependency with respect to the previous microstates. DiscussionThese results suggest that the C-model captures key aspects of microstate temporal structure. Moreover, because microstate probabilities can be modulated by psychophysiological conditions--including the influence of previously active networks--the model may serve as a building block for more comprehensive neurobiological frameworks of neural and behavioral dynamics. In such frameworks, microstate sequences could emerge from structured competition and flow among neural networks supporting microstate expression.

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Bile acid chemosensation in mammals supports species and gut microbiome evaluation

Haran, V.; Wang, J.; Morimoto, M.; Wong, W. M.; Rouyer, L. S. F.; McDonald, J. G.; Meeks, J. P.

2026-05-05 neuroscience 10.64898/2026.04.30.721772 medRxiv
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The rodent accessory olfactory system (AOS) detects chemosignals emitted by conspecifics and other species to support beneficial behaviors. Peripheral vomeronasal sensory neurons (VSNs), the AOS chemical sensors, detect fecal bile acids in patterns that have unknown significance to the animal. We used a combination of mass spectrometry and VSN calcium imaging to investigate the AOS capacity to use bile acid information to discriminate between fecal samples from captive reptiles and mice with varying gut microbiome states. Mass spectrometry analysis revealed bile acid patterns that distinguished biologically relevant samples from one another, representing theoretical discrimination axes. We measured VSN response patterns to bile acid stimuli aligned with theoretical discrimination axes. We found that VSNs perform stimulus "whitening" via an inverse relationship between natural bile acid abundance and population response magnitude. VSNs showed maximum sensitivity to taurine-conjugated bile acids, which have high theoretical discriminatory value, but were found at low natural abundance levels. Individual taurine-conjugated bile acids drove threat assessment behavior when added to familiar mouse fecal extracts, suggesting high behavioral significance. Finally, we analyzed the degree to which the AOS utilizes the theoretical information about species, diet, and gut microbiome status from bile acids. We found that VSN tuning patterns align with theoretical axes for discriminating reptilian predators from vegetarians, and between mice with different gut microbiome states. VSN tuning was especially well-aligned with the information available about conspecific gut microbiome status. These results show that AOS bile acid chemosensation supports discrimination of multiple biologically relevant states. Short abstractThe rodent accessory olfactory system (AOS) detects fecal bile acids via combinatorial codes with unknown biological significance. We investigated whether AOS bile acid chemosensation supports species and gut microbiome evaluation using mass spectrometry, calcium imaging in vomeronasal sensory neurons (VSNs), and analytical modeling. Bile acid excretion patterns theoretically supported discrimination of reptilian predators from vegetarians, and germ-free mice from conventionally raised counterparts. VSNs demonstrated stimulus "whitening" via an inverse relationship between natural bile acid abundance and population response magnitude. VSNs had highest sensitivity to taurine-conjugated bile acids, a novel class of chemosignals that elicited behavioral aversion. VSN tuning aligned with ideal discrimination axes, which was especially strong for gut microbiome-associated bile acid abundance patterns. These results show that AOS bile acid chemosensation supports discrimination of multiple biologically relevant states.

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Sex-related differences in healthy aging: changes in neuroelectric brain activity reconstructed from resting-state MEG

Ustinin, M.; Boyko, A.; Rykunov, S.

2026-05-11 neuroscience 10.64898/2026.05.06.723197 medRxiv
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Sex-related differences in the aging of the human brain were studied using large array of experimental data. The open archive CamCan was used as a source of data: the magnetic encephalograms, co-registered with magnetic resonance images of the head, were obtained for each of 434 subjects (ages 18-87 years, mean age 54.7 {+/-}18.4): 217 females (ages 18-87 years, mean age 54.5 {+/-}18.4) and 217 males (ages 18-84 years, mean age 54.8 {+/-}18.3). Recordings were split in 10-year age cohorts, each cohort consisted of equal number of men and women to calculate average intersex characteristics correctly. By massively solving the inverse problem, functional tomograms were calculated - the spatial distribution of elementary spectral components. Physiological noise was eliminated by joint analysis of MEG-based functional tomogram and magnetic resonance image for each subject. Then multichannel spectra were transformed into time series of the power of elementary current dipoles. Summary electric powers were calculated in six conventional frequency bands (1-4 Hz - delta; 4-8 Hz - theta; 8-13 Hz - alpha; 13-21 Hz - beta1; 21-30 Hz - beta2; 30-48 Hz - gamma), and sex differences in age-related changes were examined. It was found that in the youngest age cohort (18-29 years) the summary electrical power of the brain for males is 1.5 times greater than such power for females. For adults (30-69 years), male and female powers are approximately equal, while in older cohorts (70-87 years), male total brain power is greater. Age dependencies in various frequency bands are generally different for men and women, excluding higher frequencies 21-48 Hz. Basic conclusion can be made that after intersex averaging total electric power of the human brain is invariant through the lifespan from 18 to 87 years. The proposed method of joint MEG and MRI analysis can be used for further study of the sex-related details of brain sources in their connection with age changes.

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Postweaning social isolation induces gene expression alterations and histone modification dysregulations in nucleus accumbens (NAc) neurons

You, J.; Uematsu, A.; Jouji-Nishino, A.; Saeki, M.; Kishi, Y.

2026-05-13 neuroscience 10.64898/2026.05.11.724160 medRxiv
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Lack of social interaction results in various behavioral abnormalities in rodents, including increased anxiety levels, altered sociability, and impaired cognitive ability. Epigenetic factors regulate gene expression, however, how they contribute to juvenile social isolation (jSI)-induced behavioral alterations remains largely unknown. Here, we focused on the nucleus accumbens (NAc), a critical brain region of the reward system that regulates motivation-related behaviors. We first performed RNA-seq on neuronal nuclei and found alterations in genes related to neuronal function, as well as in transcriptional and epigenetic regulation. Protein-protein interaction (PPI) analysis of differentially expressed genes (DEGs) showed that top key nodes among down-regulated genes include membrane receptors (Ntrk2, Grin3a, and Grik1) and an apoptosis regulator (Bcl2). To further investigate whether jSI-induced gene expression alterations are mediated by histone modifications, we next performed CUT&Tag for four histone modifications (H3K4me1, H3K4me3, H3K27ac, and H3K27me3), and the results implied that epigenetic alterations may also play a role in neuronal function as well as transcriptional regulation. Reanalysis of previously published RNA-seq data on the manipulation of histone modification-associated factors (including Kdm6b, Brd4, and Setd1a) suggested that these enzymes were probably involved in jSI-induced gene expression alterations. Taken together, our comprehensive analysis implies the involvement of histone modification regulation in jSI-related alterations of gene expression in NAc.

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From flexible to anticipatory processing: alpha and beta oscillatory signatures of feedback-guided strategy adaptation and memory updating

Al Safadi, M.; Chatburn, A.; Cross, Z.; Dawson, S.; bornkessel-schlesewsky, I.

2026-05-11 neuroscience 10.64898/2026.05.10.724182 medRxiv
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When humans learn under conditions of uncertainty, they dynamically adjust how they prepare for and respond to feedback. In navigating uncertain environments, the brain minimizes error by continuously refining internal models via memory updating (MU). Feedback is critical for MU, and anticipatory neural mechanisms shape how feedback is processed, likely reflecting learned environmental certainty. However, the literature has largely focused on post-feedback activity, leaving pre-feedback certainty-related mechanisms less understood. The present study aims to address this gap by examining how certainty modulates anticipatory states, preceding feedback and subsequent MU. We examined oscillatory activity prior to performance feedback in a reanalysis of EEG data previously published by Hassall and colleagues (2023). Twenty-one participants (16 female, Mage = 25.81 years) predicted the strength of cartoon characters with varying predictability levels which were learned through exposure. Feedback on prediction accuracy was presented via an animated rising bar. Results revealed that theta power is modulated by accumulative feedback. Linear mixed-effects models revealed an interaction between predictability-related certainty and learning stage: in late learning, higher performance was associated with increased pre-feedback alpha and beta power for low-certainty trials, whereas in early learning, higher performance was associated with decreased beta power. These learning-related modulations in alpha and beta power suggest that initial learning is marked by adaptable exploratory processing. Subsequent learning exhibited increased alpha-mediated inhibition and beta-related anticipatory activity for lower certainty trials, indicative of dynamic strategy refinement and selective engagement of task-relevant information. These results demonstrate that certainty shapes preparatory oscillatory activity associated with MU.