eNeuro最新文献

{"title":"Novel Insights into the Social Functions of the Medial Prefrontal Cortex during Infancy.","authors":"Tobias Grossmann","doi":"10.1523/ENEURO.0458-24.2025","DOIUrl":"10.1523/ENEURO.0458-24.2025","url":null,"abstract":"<p><p>The medial prefrontal cortex (mPFC) is thought to play a central role in human social perception, cognition, and behavior. In adults, the mPFC is involved in representing and interpreting the mental states in self and others. Developmental research using neuroimaging techniques like functional near-infrared spectroscopy and functional magnetic resonance imaging has begun to extend these findings into infancy. Novel evidence reviewed in this opinion demonstrates that infant mPFC (1) plays a specialized, proactive, and evaluative role in social perception, (2) is involved in connecting with other minds while interacting and when watching other minds interact, and (3) predicts overt social behavior beyond infancy. These findings suggest that, from early in human ontogeny, the mPFC plays a multifaceted role in social perception, cognition, and behavior.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":"12 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12101719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144132196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An automatic domain-general error signal is shared across tasks and predicts confidence in different sensory modalities.","authors":"Matthew J Davidson, Sriraj Aiyer, Nick Yeung","doi":"10.1523/ENEURO.0124-25.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0124-25.2025","url":null,"abstract":"<p><p>Understanding the ability to self-evaluate decisions is an active area of research. This research has primarily focused on the neural correlates of self-evaluation during visual-tasks, and whether neural correlates before or after the primary decision contribute to self-reported confidence. This focus has been useful, yet the reliance on subjective confidence reports may confound our understanding of key every-day features of metacognitive self-evaluation: that decisions must be rapidly evaluated without explicit feedback, and unfold in a multisensory world. These considerations led us to hypothesise that an automatic domain-general metacognitive signal may be shared between sensory modalities, which we tested in the present study with multivariate decoding of electroencephalographic (EEG) data. Participants (N=21, 12 female) first performed a visual task with no request for self-evaluations of performance, prior to an auditory task that included rating decision confidence on each trial. A multivariate classifier trained to predict errors in the speeded visual-task generalised to distinguish correct and error trials in the subsequent non-speeded auditory discrimination. This generalisation did not occur for classifiers trained on the visual stimulus-locked data and further predicted subjective confidence on the subsequent auditory task. This evidence of overlapping response-locked neural activity provides evidence for automatic encoding of confidence independent of any explicit request for metacognitive reports, and a shared basis for metacognitive evaluations across sensory modalities.<b>Significance Statement</b> Understanding the neural basis of self-evaluation is an important and active area of research. Here we show that neural activity following speeded responses in a visual task can predict accuracy in a later auditory judgment. This neural activity further generalised to predict confidence in the later auditory decision. This automatic encoding of self-evaluation that is shared between sensory modalities is of theoretical and practical importance, for identifying a domain-general marker of confidence that can improve our understanding of human decision making.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144127024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two-dimensional perisaccadic visual mislocalization in rhesus macaque monkeys.","authors":"Matthias P Baumann, Ziad M Hafed","doi":"10.1523/ENEURO.0547-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0547-24.2025","url":null,"abstract":"<p><p>Perceptual localization of brief, high contrast perisaccadic visual probes is grossly erroneous. While this phenomenon has been extensively studied in humans, more needs to be learned about its underlying neural mechanisms. This ideally requires running similar behavioral paradigms in animals. However, during neurophysiology, neurons encountered in the relevant sensory and sensory-motor brain areas for visual mislocalization can have arbitrary, non-cardinal response field locations. This necessitates using mislocalization paradigms that can work with any saccade direction. Here, we first established such a paradigm in three male rhesus macaque monkeys. In every trial, the monkeys generated a visually-guided saccade towards an eccentric target. Once a saccade onset was detected, we presented a brief flash at one of three possible locations ahead of the saccade target location. After an experimentally-imposed delay period, we removed the saccade target, and the monkeys were then required to generate a memory-guided saccade towards the remembered flash location. All three monkeys readily learned the task, and, like humans, they all showed strong backward mislocalization towards the saccade target, which recovered for later flashes from the saccade time. Importantly, we then replicated a well-known property of human perisaccadic mislocalization, as revealed by two-dimensional mislocalization paradigms: that mislocalization is strongest for upward saccades. For horizontal saccades, we additionally found stronger mislocalization for upper visual field flashes, again consistent with humans. Our results establish a robust two-dimensional mislocalization paradigm in monkeys, and they pave the way for exploring the neural mechanisms underlying the dependence of perisaccadic mislocalization strength on saccade direction.<b>Significance statement</b> Visual perception is strongly altered around the time of saccades. Such alteration is often studied by characterizing how brief perisaccadic visual flashes are perceptually localized. While the properties of visual mislocalization have been exhaustively studied, the underlying neural mechanisms remain elusive, and this is due to a lack of suitable behavioral paradigms in animal models. We describe such a paradigm for macaques, which are ideal for exploring sensory-motor neural processes related to perisaccadic mislocalization.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144119250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilized Supralinear Network Model of Responses to Surround Stimuli in Primary Visual Cortex.","authors":"Dina Obeid, Kenneth D Miller","doi":"10.1523/ENEURO.0459-24.2025","DOIUrl":"10.1523/ENEURO.0459-24.2025","url":null,"abstract":"<p><p>In the mammalian primary visual cortex (V1), there are complex interactions between responses to stimuli present in the cell's classical receptive field (CRF) or \"center\" and in the surrounding region or \"surround.\" The circuit mechanisms underlying these behaviors are likely to represent more general cortical mechanisms for integrating information. Here, we develop a circuit model that accounts for three important features of surround suppression (suppression of response to a center stimulus by addition of a surround stimulus): (1) The surround stimulus suppresses the inhibitory and excitatory currents that the cell receives; (2) The strongest suppression arises when the surround orientation matches that of the center stimulus, even when the center stimulus orientation differs from the cell's preferred orientation; and (3) A surround stimulus of a given orientation most strongly suppresses that orientation's component of the response to a plaid center stimulus (\"feature-specific suppression\"). We show that a stabilized supralinear network (SSN) with biologically plausible connectivity and synaptic efficacies that depend on cortical distance and orientation difference between units can consistently reproduce phenomena (1) and (3), and, qualitatively, phenomenon (2). We explain the mechanism behind each result. We argue that phenomena (2) and (3) are independent: the model with some aspects of connectivity removed still produces phenomenon (3) but not (2). The model reproduces the rapid time scale of activity decay observed in mouse V1 when thalamic input to V1 is silenced. Finally, we show that these results hold both in networks with rate-based and conductance-based spiking units.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissociating Frontal Lobe Lesion Induced Deficits in Rule Value Learning Using Reinforcement Learning Models and a WCST Analog.","authors":"Lucie Capkova, Matthew Ainsworth, Farshad A Mansouri, Mark J Buckley","doi":"10.1523/ENEURO.0117-25.2025","DOIUrl":"10.1523/ENEURO.0117-25.2025","url":null,"abstract":"<p><p>Distinct frontal regions make dissociable contributions to rule-guided decision-making, including the ability to learn and exploit associations between abstract rules and reward value, maintain those rules in memory, and evaluate choice outcomes. Value-based learning can be quantified using reinforcement learning (RL) models predicting optimal trial-wise choices and estimating learning rates, which can then be related to the intact functioning of specific brain areas by combining a modeling approach with lesion-behavioral data. We applied a three-parameter feedback-dependent RL model to behavioral data obtained from macaques with circumscribed lesions to the principal sulcus (PS), anterior cingulate cortex (ACC), orbitofrontal cortex (OFC), superior dorsolateral prefrontal cortex (sdlPFC), and frontopolar cortex (FPC) performing a Wisconsin card sorting task (WCST) analog. Our modeling-based approach identified distinct lesion effects on component cognitive mechanisms contributing to WCST performance. OFC lesions decreased the rate of rule value updating following both positive and negative feedback. In contrast, we found no deficit in rule value updating following PS lesions, which instead made monkeys less likely to repeat correct choices when rule values were well established, suggesting a crucial role of the PS in the working memory maintenance of rule representations. Finally, ACC lesions produced a specific deficit in learning from negative feedback, as well as impaired the ability to repeat choices following highly surprising reward, supporting a proposed role for ACC in flexibly switching between a trial-and-error mode and a working memory mode in response to increased error likelihood.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":"12 5","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Demyelination produces a shift in the population of cortical neurons that synapse with callosal oligodendrocyte progenitor cells.","authors":"Benjamin S Summers, Catherine A Blizzard, Raphael P Ricci, Kimberley A Pitman, Bowen Dempsey, Simon McMullan, Brad A Sutherland, Kaylene M Young, Carlie L Cullen","doi":"10.1523/ENEURO.0113-25.2025","DOIUrl":"10.1523/ENEURO.0113-25.2025","url":null,"abstract":"<p><p>Oligodendrocyte progenitor cells (OPCs) receive synaptic input from a diverse range of neurons in the developing and adult brain. Understanding whether the neuronal populations that synapse with OPCs in the healthy brain is altered by demyelination and / or remyelination may support the advancement of neuroprotective or myelin repair strategies being developed for demyelinating diseases such as multiple sclerosis. To explore this possibility, we employed cre-lox transgenic technology to facilitate the infection of OPCs by a modified rabies virus, enabling the retrograde monosynaptic tracing of neuron-OPC connectivity. In the healthy adult mouse, OPCs in the corpus callosum primarily received synaptic input from ipsilateral cortical neurons. Of the cortical neurons, ∼50% were layer V pyramidal cells. Cuprizone demyelination reduced the total number of labelled neurons. However, the frequency / kinetics of mini excitatory post-synaptic currents recorded from OPCs appeared preserved. Of particular interest, demyelination increased the number of labelled layer II/III pyramidal neurons also increased at the expense of layer V pyramidal neurons; a change that was largely ameliorated by remyelination. These data suggest that in the healthy adult mouse brain, callosal OPCs primarily receive synaptic input from cortical layer V pyramidal neurons. However, callosal demyelination is associated with a population switch and OPCs equally synapse with layer II/III and V pyramidal neurons to synapse with OPCs, until myelin is restored.<b>Significance statement</b> In the CNS, myelination and remyelination involve the differentiation of oligodendrocyte progenitor cells (OPCs) into new oligodendrocytes (OLs), some of which survive to mature and myelinate axons. Throughout this process, neurons communicate with the OPCs and developing OLs. We show that OPCs in the corpus callosum of adult mice, predominantly receive synaptic input from layer V cortical pyramidal neurons. However, they synapse equally with layer II/III and layer V neurons following cuprizone demyelination, suggesting that the highly motile OPC processes select alternative pre-synaptic sites. 5-weeks of remyelination sees OPC connectivity bias return to layer V neurons. This provides critical insight into neuron-OPC communication and cellular interactions that are impacted in demyelinating diseases such as multiple sclerosis.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>Syngap^+/-</i> CA1 Pyramidal Neurons Exhibit Upregulated Translation of Long MRNAs Associated with LTP.","authors":"Aditi Singh, Manuela Rizzi, Sang S Seo, Emily K Osterweil","doi":"10.1523/ENEURO.0086-25.2025","DOIUrl":"10.1523/ENEURO.0086-25.2025","url":null,"abstract":"<p><p>In the <i>Syngap^+/-</i> model of SYNGAP1-related intellectual disability (SRID), excessive neuronal protein synthesis is linked to deficits in synaptic plasticity. Here, we use Translating Ribosome Affinity Purification and RNA-seq (TRAP-seq) to identify mistranslating mRNAs in <i>Syngap^+/-</i> CA1 pyramidal neurons that exhibit occluded long-term potentiation (LTP). We find the translation environment is significantly altered in a manner that is distinct from the <i>Fmr1^-/y</i> model of fragile X syndrome (FXS), another monogenic model of autism and intellectual disability. The <i>Syngap^+/-</i> translatome is enriched for regulators of DNA repair and mimics changes induced with chemical LTP (cLTP) in WT. This includes a striking upregulation in the translation of mRNAs with a longer-length (>2 kb) coding sequence (CDS). In contrast, long CDS transcripts are downregulated with induction of Gp1 metabotropic glutamate receptor-induced long-term depression (mGluR-LTD) in WT, and in the <i>Fmr1^-/y</i> model that exhibits occluded mGluR-LTD. Together, our results show the <i>Syngap^+/-</i> and <i>Fmr1^-/y</i> models mimic the translation environments of LTP and LTD, respectively, consistent with the saturation of plasticity states in each model. Moreover, we show that translation of >2 kb mRNAs is a defining feature of LTP that is oppositely regulated during LTD, revealing a novel mRNA signature of plasticity.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12091090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Development of Hypothalamic Neurons Expressing Proopiomelanocortin Peptides, Neuropeptide Y and Kisspeptin in Fetal Rhesus Macaques.","authors":"Oline K Rønnekleiv, Martha A Bosch","doi":"10.1523/ENEURO.0087-25.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0087-25.2025","url":null,"abstract":"<p><p>We have documented the early embryonic development of hypothalamic neurons expressing β-endorphin (β-End), α-melanocyte stimulating hormone (αMSH), neuropeptide Y (NPY) and kisspeptin (Kiss1) in Rhesus macaques, an animal model that is very similar to humans. Neurons expressing both β-End and αMSH are the first to develop and are initially located in the lateral basal hypothalamus (LBH) as early as day 32-34 of gestation. By day 45 of gestation, these neurons have migrated into the medial basal hypothalamic (MBH) area as their final destination. NPY neurons within the ARH develop later and are first documented at day 44 of fetal life, at which time a cluster of neurons are present within ARH-MBH area. NPY neurons continued to be expressed within the ARH area at all later fetal ages analyzed. Similarly, kisspeptin neurons develop later compared to β-End, although, only a few cells are present in the ARH by day 44 of gestation, at which time kisspeptin is also expressed in the developing anterior lobe of the pituitary. By day 70 of gestation, the rostral to caudal distribution and cell size of Kiss1 neurons within the MBH was found to be similar in females and males. In addition, Kiss1 fibers were also expressed in the POA by day 70. By day 130 of gestation, Kiss1 neurons exhibited a wider dorsal and lateral distribution within the MBH, with highly increased fiber distribution. Therefore, the development of these neurons is much earlier than what had been described previously for αMSH and NPY in primates.<b>Significance Statement</b> The arcuate nucleus of the hypothalamus express β-End/αMSH, NPY and kisspeptin neurons, which together are essential for feeding, metabolism, puberty and fertility. The early development of these neurons in Rhesus macaques, which have a long gestation period similar to humans, is not known. Here we show that these neurons start developing within the hypothalamus between day 32 and 44 of gestation and are almost fully developed by mid gestation in Rhesus macaques. Given that maternal high fat diet during pregnancy in primates has been shown to affect melanocortin expression and metabolic health in the mother's offspring, it would be important to know the birthdate and <i>in utero</i> development of these critical neurons in order to prevent postnatal health deficiencies.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AxoDen: An Algorithm for the Automated Quantification of Axonal Density in Defined Brain Regions.","authors":"Raquel Adaia Sandoval Ortega, Emmy Li, Oliver Joseph, Pascal A Dufour, Gregory Corder","doi":"10.1523/ENEURO.0233-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0233-24.2025","url":null,"abstract":"<p><p>The rodent brain contains 70,000,000+ neurons interconnected via complex axonal circuits with varying architectures. Neural pathologies are often associated with anatomical changes in these axonal projections and synaptic connections. Notably, axonal density variations of local and long-range projections increase or decrease as a function of the strengthening or weakening, respectively, of the information flow between brain regions. Traditionally, histological quantification of axonal inputs relied on assessing the fluorescence intensity in the brain region-of-interest. Despite yielding valuable insights, this conventional method is notably susceptible to background fluorescence, post-acquisition adjustments, and inter-researcher variability. Additionally, it fails to account for the non-uniform innervation across brain regions, thus overlooking critical data such as innervation percentages and axonal distribution patterns. In response to these challenges, we introduce AxoDen, an open-source semi-automated platform designed to increase the speed and rigor of axon quantifications for basic neuroscience discovery. AxoDen processes user-defined brain regions-of-interests incorporating dynamic thresholding of grayscales-transformed images to facilitate binarized pixel measurements. Here, in mice, we show that AxoDen segregates the image content into signal and non-signal categories, effectively eliminating background interference and enabling the exclusive measurement of fluorescence from axonal projections. AxoDen provides detailed and accurate representations of axonal density and spatial distribution. AxoDen's advanced yet user-friendly platform enhances the reliability and efficiency of axonal density analysis and facilitates access to unbiased high-quality data analysis with no technical background or coding experience required. AxoDen is freely available to everyone as a valuable neuroscience tool for dissecting axonal innervation patterns in precisely de-fined brain regions.<b>Significance statement</b> The rodent brain serves as a critical model for understanding brain connectivity and how neural pathologies change the anatomy of neural circuits, which reflect dynamic alterations in information flow. AxoDen, an open-source semi-automated platform, which enhances the speed, accuracy, and rigor of axonal density analysis by employing dynamic thresholding and user-defined regions-of-interest. AxoDen tool democratizes access to a high-quality, no-coding-required data analysis pipeline, thereby empowering researchers to unravel the complexities of axonal innervation in precise brain regions, ultimately advancing our understanding of neural circuitry in health and pathology.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experience-dependent neuroplasticity in the hippocampus of bilingual young adults.","authors":"Federico Gallo, Toms Voits, Jason Rothman, Jubin Abutalebi, Yury Shtyrov, Andriy Myachykov","doi":"10.1523/ENEURO.0128-25.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0128-25.2025","url":null,"abstract":"<p><p>Models of experience-dependent neuroplasticity predict that the acquisition and extensive use of a new skill trigger a nonlinear trajectory of neurostructural modifications, where initial expansion of relevant brain areas subsequently (once the skill is acquired) gives way to volumetric re-normalization. Such predictions also apply in the domain of language during learning and/or simultaneous management of two (or more) linguistic systems. In a sample of 69 young adult Russian-English bilinguals, we tested the hypothesis that individual differences in bilingual engagement non-linearly correlate with normalized volume of the hippocampus - a key learning-related brain region particularly amenable to experience-dependent plasticity. Results revealed an inverted-U shape association between second language engagement and left hippocampal gray matter volume. The present results replicate and expand the findings from aging populations, showing a non-linear pattern of structural hippocampal plasticity in healthy young adults. These findings support the role of bilingualism as a promoter of experience-dependent neuroplasticity.<b>Significance statement</b> Bilingual experience has been associated with neurocognitive adaptations and linked to more favorable cognitive aging. The hippocampus, crucial in aging, has been previously shown to exhibit volumetric increases in response to language learning with some reports of non-linear adaptations linked to bilingual experience. General models of neuroplasticity related to skill acquisition and bilingualism-specific models predict a morphological trajectory of volumetric expansions followed by renormalization of hippocampal volumes along the bilingual experience continuum. In this cross-sectional study we, for the first time, empirically tested this prediction in a sample of young individuals. In line with model predictions, our findings revealed an inverted-U shape relationship between second language engagement and left hippocampal volume, suggesting bilingualism as a source of experience-dependent neuroplasticity.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}