Visual cortical plasticity during early postnatal life is profoundly shaped by species-specific ocular anatomy and ecological demands. This review synthesizes comparative evidence on how monocular deprivation (MD) —a classical model of amblyopia — affects visual system development in frontal- vs. lateral-eyed mammals. Frontal-eyed species, including cats and primates, exhibit extensive binocular field overlaps and columnar architecture in the primary visual cortex (V1), making them highly susceptible to MD-induced shifts in ocular dominance and synaptic remodeling. In contrast, lateral-eyed species such as rodents and ungulates possess limited binocular overlaps and lack well-defined ocular dominance columns yet still demonstrate significant MD-induced plasticity involving callosal reorganization, glial activation, and extracellular matrix remodeling. We examine shared and divergent cellular mechanisms underpinning these responses, including the role of parvalbumin-expressing interneurons, perineuronal nets, and neuromodulators like BDNF and NRG1. Rodent models support the notion that even in the absence of classical columnar organization, lateral-eyed species can undergo region-specific structural remodeling in V1 following MD. These distinctions underscore how binocular integration circuits are fine-tuned through extended critical periods in frontal-eyed species, whereas plasticity in lateral-eyed species is more diffusely distributed. The integration of cross-species data revealed conserved principles of visual cortical plasticity and identified mechanisms potentially targetable for amblyopia therapy. Understanding the ecological and anatomical context of plasticity allows for a more accurate interpretation of animal models and supports the development of precision strategies for visual rehabilitation. This comparative framework expands the scope of amblyopia research and offers new avenues for translational interventions.

Cerebrospinal fluid (CSF) flows play a main role in maintaining brain homeostasis, supporting waste clearance, nutrient delivery and interstitial solute exchange. Although current models emphasize mechanical drivers such as cardiac pulsation, respiration and ciliary motion, these mechanisms alone fall short of explaining the nuanced spatiotemporal regulation of CSF flow observed under physiological and pathological conditions—even when accounting for the glymphatic framework. We explore the hypothesis that electrostatic forces arising from charged cellular interfaces may contribute to CSF movement through electro-osmotic mechanisms. We begin by examining the biological basis for surface charge in the brain, highlighting the presence of charged glycoproteins, ion channels and dynamic membrane potentials on ependymal and glial cells interfacing directly with CSF pathways. Next, we describe key principles of electro-osmosis in confined geometries, emphasizing how nanoscale surface charges can modulate fluid motion without mechanical input. Drawing from nanofluidic research and electrohydrodynamic theory, we argue that the conditions required for electro-osmotic coupling, i.e., ionic fluid, narrow conduits and patterned surface charge, are present within brain microenvironments. To test plausibility, we present computational simulations demonstrating that surface charge patterns alone can induce structured fluid flow and solute transport, including nonlinear transitions and oscillatory behaviours that resemble physiological rhythms. These findings support the idea that electrostatics may play a modulatory role in CSF regulation, complementing mechanical drivers. Overall, by integrating concepts from neuroscience, biophysics and nanotechnology, we propose a testable, mechanistically grounded hypothesis reframing CSF dynamics as electrohydrodynamically sensitive processes, with potential implications for understanding brain function and dysfunction.

Resting-state fMRI (rsfMRI) is a widely used neuroimaging technique that measures spontaneous fluctuations in brain activity in the absence of specific external cognitive, motor, emotional or other stimuli, based on the blood-oxygen-level-dependent (BOLD) signal. Functional connectivity (FC) is a popular rsfMRI analysis examining BOLD signal correlations between brain regions. Nevertheless, there are alternative analyses that provide different but collectively informative characteristics of the BOLD signal and, thus, local brain activity. This narrative review aimed to provide a comprehensive conceptual, mathematical, and significance investigation of common rsfMRI analyses in addition to FC. To achieve this, a narrative review was conducted on studies using the most common rsfMRI analysis to investigate global, regional, and local brain activity in healthy and diseased populations. Five rsfMRI analyses were described, summarizing the common initial steps in data processing and explaining the main characteristics and how each metric is calculated. The rsfMRI analyses described are (1) FC, reflecting BOLD global connectivity; (2) the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF), representing the intensity of the BOLD signal; (3) regional homogeneity (ReHo), which reflects BOLD local connectivity; (4) entropy, depicting the BOLD predictability and (5) Hurst exponent (H), depicting autocorrelation of the BOLD signal. As rsfMRI is a vital tool for exploring brain function, selecting an analysis that aligns with the research question is essential. This review offers an initial catalog of standard rsfMRI analyses, highlighting their key features, concepts, and considerations to support informed decisions by researchers and clinicians.

Alongside models and methods, concepts are crucial tools to study and understand the brain. They help us pursue various goals, such as describing phenomena based on patterns in the data or explaining why these phenomena occur. Yet while terms such as “action potential” or “network” guide our efforts to reach these goals, other concepts have failed to advance our understanding of the brain. In this paper, we draw on recent work from philosophy of science to show that the success or failure of concepts in neuroscience depends on the epistemic goals the field aims to achieve. Looking at cases such as “default mode network”, “cortical column” and “hierarchy” we formulate conditions under which introducing, refining, or replacing a concept succeeds or fails. These cases suggest that to better evaluate our concepts, we should make explicit which goals we aim to achieve when using them.

Episodic memories contain information about the nature of an event, the place where it happened and the time when it occurred. In animals, the term “episodic-like memory” is preferred to refer to mnemonic instances containing these three features, commonly referred to as “what-where-when”. Models to study episodic-like memory have been proposed in corvidae and rodents, although their use in the neuroscience research has been limited due to certain limitations and potential ambiguities. While the neurological correlates of “what-where-when” have been identified in neuronal types such as place and time cells, it is unclear how they contribute to form a unitary representation, or how this information can be accessed during memory recall, either holistically or differentially. Here, we outline two new behavioural paradigms based on the everyday memory task that we have developed to model what and when components as well as ‘where’ information. In experiment 1 (E1), we demonstrate that rats are able to learn two distinct food positions on a daily basis and retrieve them independently. In E2, we establish that rats can learn that two flavours are replenished at different times after an initial sampling, thus use the temporal component to guide their decision making. These two tasks can therefore provide the basis to study how the item, location and time information of a memory are stored and accessed by the brain. This should be observable in single-unit recording or calcium-imaging studies.

Several theories have been proposed about the default configuration of the brain’s networks underlying unisensory and multisensory processing abilities and the development of multisensory integration during childhood. Recent empirical findings from animal models and behavioral data collected from typically developing (TD) children and children with autism spectrum disorder (ASD), however, are consistent with the idea that in the immature brain, prior to systematic cross-sensory exposures typically encountered in everyday life, that the individual sensory systems interact in a competitive manner. Which neural architecture and mechanisms best describe the brain’s naïve configuration are still unknown. To fill this gap, this study investigates how sensory modalities interact in the young brain by comparing the predictions of two alternative biologically plausible neuro-computational models to empirical data. The neural substrates responsible for the altered development of multisensory integrative processes observed in ASD children are also investigated. Linking the framework suggested by empirical data to a plausible neural implementation, our results challenge the classical notion of cross-sensory brain organization at birth, whereby the various sensory pathways do not initially interact. Instead, we suggest that direct inhibitory interactions between sensory modalities are taking place in the immature brain, and we suggest that these inhibitory interactions play a crucial role in the altered multisensory perceptual abilities of children with autism.

The human brain continuously forms predictions about the unfolding sensory environment, relying on contextual information to anticipate upcoming events while remaining sensitive to unexpected changes. This study examined how pupil-linked phasic arousal, a putative proxy for the locus coeruleus-norepinephrine system, reflects the interplay between tonal surprisal (unexpectedness) and precision (reliability of the inferred context) in dynamic auditory contexts. Twenty-eight participants passively listened to stochastic tone sequences transitioning between periods of low-entropy (informative context) and high-entropy (less informative context). We quantified tone-by-tone surprisal and precision using Bayesian modeling. Pupil dilation responses revealed sensitivity to both surprisal and precision, showing that arousal tracks momentary deviations and the stability of contextual predictions. Analyses of context boundaries showed that transitions between distinct low-entropy environments (LE-dLE) evoked significant pupil dilation, whereas shifts between low- and high-entropy environments (LE-HE, HE-LE) did not. These findings indicate that pupil-linked arousal primarily responds to salient contextual shifts involving stable environments rather than to changes in entropy per se. The results emphasize the role of the locus coeruleus–norepinephrine system in adaptive model updating during passive listening and demonstrate the brain’s continuous monitoring of uncertainty to navigate dynamic auditory environments.

Aging alters brain structure and function, and studying such changes may help understand the neural basis underlying aging and devise interventions to detect deviations from healthy progression. Electroencephalogram (EEG) offers an effective way to study healthy aging owing to its high temporal resolution and affordability. Recent studies have shown that narrow-band stimulus-induced gamma oscillations (20-70 Hz) in EEG, induced with cartesian gratings in a fixation task paradigm, weaken with healthy aging and onset of Alzheimer’s Disease (AD) while remaining highly reproducible for a given subject, and thus hold promise as potential biomarkers. However, functional connectivity (FC) sometimes changes in a different way compared to sensor power with aging. This difference could be potentially addressed by studying how underlying gamma sources change with aging, since either a reduction in source power or a shrinkage of the sources (or both) could reduce the power in the sensors but may have different effects on other measures such as FC. We therefore reconstructed EEG gamma sources through a linear inverse method called exact Low-resolution Tomography Analysis (eLORETA) on a large (N=217) cohort of healthy elderly subjects (>50 years). We further characterized gamma distribution in cortical space as an exponential fall-off from a seed voxel with maximal gamma source power to delineate a reduction in magnitude versus shrinkage. We found significant reduction in magnitude but not shrinkage with healthy aging. Overall, our results shed light on changes in EEG gamma source distribution with healthy aging, which could provide clues about underlying neural mechanisms.

Mammalian circadian rhythms are driven by the transcriptional-translational feedback loop of clock genes in the hypothalamic suprachiasmatic nucleus. However, chronic methamphetamine treatment induces circadian activity rhythms in arrhythmic animals with suprachiasmatic nucleus lesions or clock gene deletions. Activation of dopaminergic neurotransmission by methamphetamine is considered to induce activity rhythms. Adenosine antagonizes the actions of dopamine at heteromers of dopamine and adenosine receptors (dopamine D1 and adenosine A1 receptors, dopamine D2 and adenosine A2A receptors). In this study, we considered that adenosine inhibition acts similarly to methamphetamine, and administered an antagonist of adenosine A1 and A2A receptors, caffeine, in drinking water. Chronic caffeine treatment extended the circadian activity period of wild-type mice under constant darkness. The circadian period extension continued for three weeks after the replacement of caffeine with water. Chronic caffeine treatment induced circasemidian (~12 h), circadian, and longer-period activity rhythms in clock gene deficient, cryptochrome (Cry) 1 and Cry 2 double knockout mice under constant darkness. These activity rhythms changed periods spontaneously over time and became arrhythmic upon caffeine withdrawal. In humans, rhythms with shorter or longer than 24 h periods are hypothesized to cause internal desynchronization of the sleep-wake rhythm from the ~ 24 h body temperature rhythm under temporal isolation. Circasemidian rhythms are hypothesized to cause afternoon sleepiness and nap. Caffeine-induced rhythms may help in understanding rhythms with not around 24 h periods in humans.

Background and Aims: Demyelination is widely acknowledged as the underlying pathological mechanism of trigeminal neuralgia (TN), while ferroptosis has been implicated in neurodegenerative disorders associated with demyelination. However, the precise contribution of ferroptosis to TN-related demyelination has yet to be elucidated. Methods: To investigate the putative pathway implicated in the neuropathic pain, we conducted RNA-seq analysis in the IoN-CCI rat model that is deemed to simulate the pathology of TN. Subsequently, we explored the iron metabolism and ferroptosis-related pathway in this TN model. Finally, we utilized Ferrostatin-1 and Liproxstatin-1 to suppress ferroptosis and assessed alterations in iron metabolism and myelin sheath integrity through immunohistochemistry and transmission electron microscopy. Results: Our experiments showed that IoN-CCI induced ferroptosis, characterized by increased iron accumulation and decreased expression of GPX4, FPN, and SLC7A11. This resulted in mitochondrial shrinkage in Schwann cells and loosened wrapping of the myelin sheath, as well as activation of neuroinflammation and oxidative stress. Inhibition of ferroptosis reversed these effects and alleviated demyelination and neuropathic pain. Interpretation: In conclusion, our study has clarified the impact of ferroptosis-induced demyelination in TN, providing a potential strategy for treating TN and offering new insights into the study of peripheral nerve demyelination diseases.

Ensuring equitable access to research funding is crucial for fostering diversity, innovation, and excellence in science. Despite progress, significant disparities remain, with underrepresented researchers—including women, racial and ethnic minorities, LGBTQ+ individuals, and those with disabilities—continuing to receive disproportionately less funding. These disparities not only hinder individual careers but also limit the breadth of perspectives that drive scientific discovery. Through discussions with major funding agencies, including the Dana Foundation, European Research Council (ERC), and ERA-NET NEURON, we examine how equity, diversity, and inclusion (EDI) are integrated into research funding allocation. We focus on three key areas: how EDI is defined and prioritized, metrics for assessing and tracking progress, and strategies for mitigating bias in selection procedures. While agencies have implemented initiatives such as demographic data transparency, targeted funding mechanisms, and bias-awareness training, systemic challenges remain. Variability in data collection practices, barriers in peer review processes, and limitations of interventions like double-blind reviews highlight the need for ongoing reform. As EDI policies face growing political scrutiny and active efforts to dismantle existing frameworks, reinforcing and expanding strategies to ensure equitable funding distribution has never been more critical. The scientific community must continue advocating for evidence-based approaches that improve transparency, accountability, and fairness in research funding. Without sustained commitment, the progress made over the past decades is at risk of being reversed, undermining the diversity of thought and innovation essential to scientific advancement.

To improve the outcomes of current treatments for stuttering, researchers are looking at additional tools such as transcranial Direct Current Stimulation (tDCS). The purpose of this paper is to review the literature investigating the effectiveness of tDCS for people who stutter (PWS) and offer some directions for future research. To achieve the objective of this study, we conducted a narrative review of the existing literature. Articles were selected using these inclusion criteria: participants, tDCS protocol, control group, and primary outcomes. Our literature search was limited to studies published in English with no limits on the publication year. We only extracted data from studies that investigated the effects of tDCS on PWS. Systematic reviews, meta-analyses, and other forms of reviews regarding tDCS were not included. 101 studies were identified during the exploratory phase. Ultimately, 7 studies met our inclusion criteria. Of the included papers, five studies reported mixed effects, one study showed no effect, and one study showed positive effects of tDCS. We summarized the studies in terms of several methodological features and the observed effects from tDCS. We also used the SimNIBS software to compare the effects of different stimulation parameters on brain activity and outcomes. The studies reviewed in this study have reported a variable effectiveness of tDCS for enhancing speech fluency in PWS. As a result, it remains unclear whether tDCS is an effective tool for stuttering intervention, and the optimal stimulation parameters are not yet established. Several suggestions for future research are offered.

Human adolescents are frequently exposed to ethanol and/or to noise, agents that put brain development at risk. As the use of animal models has been demonstrated to reproduce human findings, the aim of the present study was to investigate if two weeks of ethanol intake, with an intermediate noise exposure, can affect different hippocampal-related behaviors in adolescent rats of both sexes. In addition, the enriched environment was used as an environmental housing strategy to prevent hippocampal-related behavioral changes. Importantly, although partial neuroprotection has been found in an animal model of brief ethanol intake, little is known about longer intake paradigms. Adolescent Wistar rats of both sexes were subjected to voluntary intermittent two-bottle choice paradigm of ethanol intake in for 2 weeks (6 sessions). A subgroup was exposed to noise for two hours after the third session. Some rats from both groups were housed in enriched environment cages. Finally, an assessment of hippocampal-related behaviors was performed. Data show different alterations in hippocampal-related behaviors, some of which were sex-specific and differ from those observed after a brief ethanol consumption. Most behavioral changes were prevented, at least partially, by enriched environment. These findings suggest that common environmental factors present in human adolescent venues may influence behavior that differs among sexes, as observed in the present animal model of extended ethanol intake. Additionally, an enriched environment proved to be a partially effective neuroprotective strategy in both sexes. Thus, implementation of non-pharmacological approaches may provide benefits against various challenges.

The paraventricular nucleus of the thalamus (PVT) is a central node in brain networks controlling motivated behaviors. It processes inputs from cerebral cortex, brainstem and hypothalamus and has efferents that project to a wide range of structures, including the nucleus accumbens (nAcc). It is known that PVT neurons projecting to the nAcc show c-Fos activation in response to reward-related cues, in well trained animals. We previously found that c-Fos expression is also increased early in the conditioning process, during the first session of learning a new cue-reward association in rats, but neurons with projections to nAcc were not identified in that study. Here we tested the hypothesis that nAcc-projecting PVT neurons would show this enhanced c-Fos expression following first exposure to the association of a visual cue with a subsequent food reward. Male rats were stereotaxically injected in the nAcc with a retrogradely transported adeno-associated virus construct leading to green fluorescent protein (GFP) expression in cell bodies of afferents from PVT. Following a single session of cue-reward training, processing of the brains with dual immunohistochemistry for c-Fos and GFP showed significantly higher density of double labelled neurons in the conditioned group, compared to controls in which the same number of cues and rewards were delivered at random intervals with respect to each other. Such activation of immediate early gene expression in PVT to nAcc projecting neurons very early in paired associative reward learning may have a role in modulating plasticity in the nAcc.

Introduction: Human movement involves a dynamic interplay of isometric, concentric, and eccentric muscle actions. There is a need to understand the contribution of the reticulospinal tract (RST) to human movement control during different muscle actions. This research aimed to determine the excitability of the RST during isometric, concentric and eccentric muscle actions. Methods: Fourteen neurologically intact participants (Age: 26 ± 7 years; Sex: 3 female, 11 male; Stature: 176 ± 8 cm; Mass: 78.5 ± 10.9 kg) performed isometric, concentric, and eccentric muscle actions with the biceps brachii. Participants performed a submaximal contraction at 25% of their isometric maximum voluntary contraction (MVC) during all muscle actions. Neurophysiological electrical stimulations to indirectly measure RST excitability consisted of conditioned (startling auditory stimulus of ≥110 dB) and unconditioned (no auditory stimulus) cervicomedullary motor evoked potentials (CMEPs). Results: Larger conditioned CMEP responses compared to unconditioned CMEPs were observed for all muscle actions (p = 0.008). However, no differences in RST excitability, inferred from the difference between conditioned and unconditioned CMEP responses, were observed across the three muscle actions (p = 0.319). Discussion: These results suggests that across isometric, concentric, and eccentric muscle actions, there are no differences in RST excitability whilst performing a submaximal contraction at 25% of their isometric MVC. It could therefore be inferred from this that RST input to motoneurons is not different between isometric, concentric, and eccentric muscle actions of the biceps brachii at relatively low contraction intensities.

Objectives: This research explores the interaction between circadian rhythms and the cellular mechanisms responsible for epileptic seizures, by integrating circadian modulation into the Epileptor-2 model. The aim is to improve understanding of the underlying dynamics and identify optimized therapeutic strategies in phase with biological circadian cycles. Methods: A circadian factor was integrated into the Epileptor-2 model to simulate daily fluctuations in neuronal excitability and seizure onset. These variations interact with pharmacological treatments, and we modeled their effects to evaluate dose adjustments and schedules aligned with circadian rhythms. The pharmacokinetics of anti-epileptic drugs were parameterized to analyze their interaction with periods of peak seizure risk. Results: Integrating circadian fluctuations in ionic dynamics into the model has provided deeper mechanistic insights into their effects on neuronal excitability and seizure onset. Our simulations indicate that adjusting drug doses and administration schedules according to patients’ biological rhythms enhances treatment efficacy and lowers seizure risk. These findings highlight the significance of personalized chronotherapy, tailored to periods of highest seizure susceptibility, for optimizing epilepsy management. Significance: This study demonstrates how circadian modulation of ion dynamics influences neuronal excitability, seizure onset, and interactions with pharmacological treatment, providing insight into the mechanisms underlying ictal discharges. By incorporating these fluctuations into the Epileptor-2 model, we offer a mechanistic understanding of circadian rhythms in epilepsy. Our approach, combining cellular with chronotherapy modeling, represents a first step toward developing a valuable tool for optimizing antiepileptic treatments based on patient’s biological rhythms, ultimately enhancing the precision and effectiveness of epilepsy management.

Valproate is an antiseizure drug required by many epileptic patients to manage their symptoms. During pregnancy, its use has been shown to increase the risk of neurobehavioral deficits in the offspring. The present study used a rat model of absence epilepsy, Genetic Absence Epilepsy Rat from Strasbourg (GAERS), to investigate effects of gestational valproate exposure on early postnatal brain cortex and lateral choroid plexus transcriptomes. Females were provided with either control diet or a valproate-laced diet (20 g/kg) from 2 weeks prior to mating and throughout gestation. At parturition, all dams received control diet. Pups at postnatal day 5 were used for RNA-sequencing. Differential expression analyses were conducted between transcriptomes from valproate exposed and control animals. In the choroid plexus, 5694 genes significantly altered their expression compared to 214 in the cortex, a difference of nearly 25 times. Dysregulation was identified in choroidal expression of ion channels and metal transporters including 6 members of the Slc4a family, Cacna1h and Kcne2. Several drug transporting ATP-binding cassette transporters and solute carriers were significantly upregulated and drug metabolising enzymes downregulated. In the cortex, 11 genes associated with development of the central nervous system were differentially expressed. Finally, in both tissues, fetal valproate exposure appeared to result in dysregulation of genes related to adaptive and innate immune responses. These results indicated that gestational exposure to valproate resulted in distinct and greater effects on the choroid plexus transcriptome compared to the cortex, potentially suggesting additional targets related to developmental valproate neurotoxicity.

Hyperscanning approaches represent a shift from single- to two-person neuroscience, enabling a more profound understanding of the neural mechanisms underlying interpersonal synchronization. In this context, fNIRS has emerged as a valuable tool for measuring brain activity in a natural, unconstrained environment. While interpersonal synchrony using fNIRS hyperscanning has been well studied using statistical association analysis, establishing causal relationships that elucidate the direction of influence remains challenging. This study aimed to investigate the feasibility of testing the direction of influence in dyadic interactions. Since the ground truth of such direction is not available in a natural setting, we validated our approach in an experimental setup in which we controlled the direction of influence between two subjects by assigning them the roles of ’Model’ and ’Imitator’ of specified motor tasks. A total of 22 participants, hence 11 dyads, completed the task in a within-subject design. We adapted concepts from spectral causal-effect decomposition theories to formulate a new measure of the direction and intensity of influence. The results of this study demonstrate that the direction of influence in the fNIRs data of motor tasks can be detected with an Accuracy in the range of 69-88%. Furthermore, the proposed spectral causality measure was shown to significantly reduce spurious causal relationships due to the confounding effects of physiological processes and measurement artifacts compared to time-domain causal analysis.