Journal of Neuroscience最新文献

{"title":"Serotonergic Input into the Cerebellar Cortex Modulates Anxiety-Like Behavior.","authors":"Pei Wern Chin, George J Augustine","doi":"10.1523/JNEUROSCI.1825-24.2024","DOIUrl":"10.1523/JNEUROSCI.1825-24.2024","url":null,"abstract":"<p><p>Because of the important roles of both serotonin (5-HT) and the cerebellum in regulating anxiety, we asked whether 5-HT signaling within the cerebellum is involved in anxiety behavior. Physiological 5-HT levels were measured in vivo by expressing a fluorescent sensor for 5-HT in lobule VII of the cerebellum, while using fiber photometry to measure sensor fluorescence during anxiety behavior on the elevated zero maze. Serotonin increased in lobule VII when male mice were less anxious and decreased when mice were more anxious. To establish a causal role for this serotonergic input in anxiety behavior, we photostimulated or photoinhibited serotonergic terminals in lobule VII while mice were in an elevated zero maze. Photostimulating these terminals reduced anxiety behavior in mice, while photoinhibiting them enhanced anxiety behavior. Our findings add to evidence that cerebellar lobule VII is a topographical locus for anxiety behavior and establish that 5-HT input into this lobule is necessary and sufficient to bidirectionally influence anxiety behavior. These results represent progress toward understanding how the cerebellum regulates anxiety behavior and provide new evidence for a functional connection between the cerebellum and the serotonin system within the anxiety circuit.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968536/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Distinct Timescales of Rapid Sensory Adaption in the Thalamocortical Circuit.","authors":"Yi Juin Liew, Elaida D Dimwamwa, Nathaniel C Wright, Yong Zhang, Garrett B Stanley","doi":"10.1523/JNEUROSCI.1057-24.2025","DOIUrl":"10.1523/JNEUROSCI.1057-24.2025","url":null,"abstract":"<p><p>Numerous studies have shown that neuronal representations in sensory pathways are far from static but are instead strongly shaped by the complex properties of the sensory inputs they receive. Adaptation dynamically shapes the neural signaling that underlies our perception of the world yet remains poorly understood. We investigated rapid adaptation across timescales from hundreds of milliseconds to seconds through simultaneous multielectrode recordings from the ventro-posteromedial nucleus of the thalamus (VPm) and layer 4 of the primary somatosensory cortex (S1) in male and female anesthetized mice in response to controlled, persistent whisker stimulation. Observations in VPm and S1 reveal a degree of adaptation that progresses through the pathway. Under these experimental conditions, signatures of two distinct timescales of rapid adaptation in the firing rates of both thalamic and cortical neuronal populations were revealed, also reflected in the synchrony of the thalamic population and in the thalamocortical synaptic efficacy that was measured in putatively monosynaptically connected thalamocortical pairs. Controlled optogenetic activation of VPm further demonstrated that the longer timescale adaptation observed in S1 is likely inherited from slow decreases in thalamic firing rate and synchrony. Despite the degraded sensory responses, adaptation induced by the controlled repetitive stimulation presented here resulted in a shift in coding strategy that favors theoretical discrimination over detection across the observed timescales of adaptation. Overall, although multiple mechanisms contribute to rapid adaptation at distinct timescales, they support a unifying framework on the role of adaptation in sensory processing.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400512","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Smell the Label: Odors Influence Label Perception and Their Neural Processing.","authors":"Doris Schicker, Putu A Khorisantono, Qëndresa Rramani Dervishi, Shirley X L Lim, Elodie Saruco, Burkhard Pleger, Johannes Schultz, Kathrin Ohla, Jessica Freiherr","doi":"10.1523/JNEUROSCI.1159-24.2024","DOIUrl":"10.1523/JNEUROSCI.1159-24.2024","url":null,"abstract":"<p><p>Providing nutrition or health labels on product packaging can be an effective strategy to promote a conscious and healthier diet. However, such labels also have the potential to be counterproductive by creating obstructive expectations about the flavor of the food and influencing odor perception. Conversely, olfaction could significantly influence label perception, whereby negative expectations could be mitigated by pleasant odors. This study explored the neural processing of the interplay between odors and nutrition labels using fMRI in 63 participants of either sex, to whom we presented beverage labels with different nutrition-related statements either with or without a congruent odor. On a behavioral level, the products for which the label was presented together with the odor were in general perceived as more positive than the same labels without an odor. Neuroimaging results revealed that added odors significantly altered activity in brain regions associated with flavor and label processing as well as decision-making, with higher activations in the right amygdala/piriform cortex (Amy/pirC) and orbitofrontal cortex. The presentation of odors induced pattern-based encoding in the right dorsolateral prefrontal cortex, the left ventral striatum/nucleus accumbens, and the right Amy/pirC when accounting for behavioral differences. This suggests that odors influence the effects of labels both on a neural and behavioral level and may offer the possibility of compensating for obstructive associations. The detailed mechanisms of odor and statement interactions within the relevant brain areas should be further investigated, especially for labels that evoke negative expectations.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143494331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of Individual Differences Encoded in Sequential Variations of Elements in Zebra Finch Songs.","authors":"Zhehao Cheng 程柘皓, Yoko Yazaki-Sugiyama 杉山 矢崎 陽子","doi":"10.1523/JNEUROSCI.1071-24.2025","DOIUrl":"10.1523/JNEUROSCI.1071-24.2025","url":null,"abstract":"<p><p>Zebra finches sing individually unique songs and recognize conspecific songs and individual identities in songs. Their songs comprise several syllables/elements that share acoustic features within the species, with unique sequential arrangements. However, the neuronal mechanisms underlying the detection of individual differences and species specificity have yet to be elucidated. Herein, we examined the neuronal auditory responsiveness of neurons in the higher auditory area, the caudal nidopallium (NCM), to songs and their elements in male zebra finches to understand the mechanism for detecting species and individual identities in zebra finch songs. We found that various adult male zebra finch songs share acoustically similar song elements but differ in their sequential arrangement between individuals. The broader spiking (BS) neurons in the NCM detected only a small subset of zebra finch songs, whereas NCM BS neurons, as a neuronal ensemble, responded to all zebra finch songs. Notably, distinct combinations of BS neurons responded to each of the 18 presented songs in one bird. Subsets of NCM BS neurons were sensitive to sequential arrangements of species-specific elements, which dramatically increasing the capacity for song variation with a limited number of species-specific elements. The naive Bayes decoder analysis further showed that the response of sequence-sensitive BS neurons increased the accuracy of song stimulus predictions based on the response strength of neuronal ensembles. Our results suggest the neuronal mechanisms that NCM neurons as an ensemble decode the individual identities of songs, while each neuron detects a small subset of song elements and their sequential arrangement.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968528/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143473185","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Excessive Alcohol Consumption Enhances Myelination in the Mouse Nucleus Accumbens.","authors":"Mirit Liran, Inbar Fischer, May Elboim, Nofar Rahamim, Tamar Gordon, Nataly Urshansky, Yaniv Assaf, Boaz Barak, Segev Barak","doi":"10.1523/JNEUROSCI.0280-24.2025","DOIUrl":"10.1523/JNEUROSCI.0280-24.2025","url":null,"abstract":"<p><p>Chronic excessive alcohol (ethanol) consumption induces neuroadaptations in the brain's reward system, including biochemical and structural abnormalities in white matter that are implicated in addiction phenotypes. Here, we demonstrate that long-term (12 week) voluntary ethanol consumption enhances myelination in the nucleus accumbens (NAc) of female and male adult mice, as evidenced by molecular, ultrastructural, and cellular alterations. Specifically, transmission electron microscopy analysis showed increased myelin thickness in the NAc following long-term ethanol consumption, while axon diameter remained unaffected. These changes were paralleled by increased mRNA transcript levels of key transcription factors essential for oligodendrocyte (OL) differentiation, along with elevated expression of critical myelination-related genes. In addition, diffusion tensor imaging revealed increased connectivity between the NAc and the prefrontal cortex, reflected by a higher number of tracts connecting these regions. We also observed ethanol-induced effects on OL lineage cells, with a reduction in the number of mature OLs after 3 weeks of ethanol consumption, followed by an increase after 6 weeks. These findings suggest that ethanol alters OL development prior to increasing myelination in the NAc. Finally, chronic administration of the promyelination drug clemastine to mice with a history of heavy ethanol consumption further elevated ethanol intake and preference, suggesting that increased myelination may contribute to escalated drinking behavior. Together, these findings suggest that heavy ethanol consumption disrupts OL development, induces enhanced myelination in the NAc, and may drive further ethanol intake, reinforcing addictive behaviors.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurophysiology of Perceptual Decision-Making and Its Alterations in Attention-Deficit Hyperactivity Disorder.","authors":"Mana Biabani, Kevin Walsh, Shou-Han Zhou, Joseph Wagner, Alexandra Johnstone, Julia Paterson, Beth P Johnson, Natasha Matthews, Gerard M Loughnane, Redmond G O'Connell, Mark A Bellgrove","doi":"10.1523/JNEUROSCI.0469-24.2025","DOIUrl":"10.1523/JNEUROSCI.0469-24.2025","url":null,"abstract":"<p><p>Despite the prevalence of attention-deficit hyperactivity disorder (ADHD), efforts to develop a detailed understanding of the neuropsychology of this neurodevelopmental condition are complicated by the diversity of interindividual presentations and the inability of current clinical tests to distinguish between its sensory, attentional, arousal, or motoric contributions. Identifying objective methods that can explain the diverse performance profiles across individuals diagnosed with ADHD has been a long-held goal. Achieving this could significantly advance our understanding of etiological processes and potentially inform the development of personalized treatment approaches. Here, we examine key neuropsychological components of ADHD within an electrophysiological (EEG) perceptual decision-making paradigm that is capable of isolating distinct neural signals of several key information processing stages necessary for sensory-guided actions from attentional selection to motor responses. Using a perceptual decision-making task (random dot motion), we evaluated the performance of 79 children (aged 8-17 years) and found slower and less accurate responses, along with a reduced rate of evidence accumulation (drift rate parameter of drift diffusion model), in children with ADHD (<i>n</i> = 37; 13 female) compared with typically developing peers (<i>n</i> = 42; 18 female). This was driven by the atypical dynamics of discrete electrophysiological signatures of attentional selection, the accumulation of sensory evidence, and strategic adjustments reflecting urgency of response. These findings offer an integrated account of decision-making in ADHD and establish discrete neural signals that might be used to understand the wide range of neuropsychological performance variations in individuals with ADHD.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptation with Naturalistic Textures in Macaque V1 and V2.","authors":"Aida Davila, Adam Kohn","doi":"10.1523/JNEUROSCI.2257-23.2025","DOIUrl":"10.1523/JNEUROSCI.2257-23.2025","url":null,"abstract":"<p><p>Adaptation affects neuronal responsivity and selectivity throughout the visual hierarchy. However, because most prior studies have tailored stimuli to a single brain area of interest, we have a poor understanding of how exposure to a particular image alters responsivity and tuning at different stages of visual processing. Here we assess how adaptation with naturalistic textures alters neuronal responsivity and selectivity in primary visual cortex (V1) and area V2 of macaque monkeys. Neurons in both areas respond to textures, but V2 neurons are sensitive to higher-order image statistics which do not strongly modulate V1 responsivity. We tested the specificity of adaptation in each area with textures and spectrally matched \"noise\" stimuli. Adaptation reduced responsivity in both V1 and V2, but only in V2 was the reduction dependent on the presence of higher-order texture statistics. Despite this specificity, the texture information provided by single neurons and populations was reduced after adaptation, in both V1 and V2. Our results suggest that adaptation effects for a given feature are induced at the stage of processing that tuning for that feature first arises and that stimulus-specific adaptation effects need not result in improved sensory encoding.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Theta oscillons in behaving rats.","authors":"M S Zobaer, N Lotfi, C M Domenico, C Hoffman, L Perotti, D Ji, Y Dabaghian","doi":"10.1523/JNEUROSCI.0164-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0164-24.2025","url":null,"abstract":"<p><p>Recently discovered constituents of the brain waves-the <i>oscillons</i>-provide a high-resolution representation of the extracellular field dynamics. Here, we study the most robust, highest-amplitude oscillons recorded in actively behaving male rats, which underlie the traditional <i>θ</i>-waves. The resemblances between <i>θ</i>-oscillons and the conventional <i>θ</i>-waves are manifested primarily at the ballpark level-mean frequencies, mean amplitudes, and bandwidths. In addition, both hippocampal and cortical oscillons exhibit a number of intricate, behavior-attuned, transient properties that suggest a new vantage point for understanding the <i>θ</i>-rhythms' structure, origins and functions. In particular, we demonstrate that oscillons are frequency-modulated waves, with speed-controlled parameters, embedded into a weak noise background. We also use a basic model of neuronal synchronization to contextualize and to interpret the oscillons. The results suggest that the synchronicity levels in physiological networks are fairly low and are modulated by the animal's physiological state.<b>Significance statement</b> Oscillatory extracellular fields modulate neural activity at multiple spatiotemporal scales and hence play major roles in physiology and cognition. Traditionally, these fields' organization is described via harmonic decompositions into <i>θ</i>, <i>γ</i> and other \"brain waves.\" Here we argue that these constructs are only approximations to the physical oscillatory motifs-the oscillons, which represent the actual temporal architecture of synchronized neural dynamics. Focusing on the low-frequency <i>θ</i>-oscillons, we demonstrate correspondences with the traditional <i>θ</i>-waves for averaged, lento-changing characteristics, and discuss several new properties and dynamics that heretofore remained unexplored. Specifically, speed-coupled frequency modulations support oscillatory models of brain wave dynamics, suggesting a novel, \"FM\" perspective on the information exchange in hippocampo-cortical network and linking electrophysiological data to theoretical models of neuronal synchronization.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterizing directional dynamics of semantic prediction based on inter-regional temporal generalization.","authors":"Fahimeh Mamashli, Sheraz Khan, Elaheh Hatamimajoumerd, Mainak Jas, Işıl Uluç, Kaisu Lankinen, Jonas Obleser, Angela D Friederici, Burkhard Maess, Jyrki Ahveninen","doi":"10.1523/JNEUROSCI.0230-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0230-24.2025","url":null,"abstract":"<p><p>The event-related potential/field component N400(m) is a widely accepted neural index for semantic prediction. Top-down input from inferior frontal areas to perceptual brain regions is hypothesized to play a key role in generating the N400, but testing this has been challenging due to limitations of causal connectivity estimation. We here provide new evidence for a predictive model of speech comprehension in which IFG activity feeds back to shape subsequent activity in STG/MTG. Magnetoencephalography (MEG) data was obtained from 21 participants (10 men, 11 women) during a classic N400 paradigm where the semantic predictability of a fixed target noun was manipulated in simple German sentences through the preceding verb. To estimate causality, we implemented a novel approach, based on machine learning and temporal generalization, to test the effect of inferior frontal gyrus (IFG) on temporal regions. A support vector machine (SVM) classifier was trained on IFG activity to classify less predicted (LP) and highly predicted (HP) nouns and tested on superior/middle temporal gyri (STG/MTG) activity, time-point by time-point. The reverse procedure was then performed to establish spatiotemporal evidence for or against causality. Significant decoding results were found in our bottom-up model, which were trained at hierarchically lower level areas (STG/MTG) and tested at the hierarchically higher IFG areas. Most interestingly, decoding accuracy also significantly exceeded chance level when the classifier was trained on IFG activity and tested on successive activity in STG/MTG. Our findings indicate dynamic top-down and bottom-up flow of information between IFG and temporal areas when generating semantic predictions.<b>Significance Statement</b> Semantic prediction helps anticipate the meaning of upcoming speech based on contextual information. How frontal and temporal cortices interact to enable this crucial function has remained elusive. We used novel data-driven MEG analyses to infer information flow from lower to higher areas (bottom-up) and vice versa (top-down) during semantic prediction. Using \"earlier\" MEG signals in one area to decode the \"later\" in another, we found that inferior frontal cortices feed predictions back to temporal cortices, to help decipher bottom-up signals going to the opposite direction. Our results provide experimental evidence on how top-down and bottom-up influences interact during language processing.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissociable causal roles of dorsolateral prefrontal cortex and primary motor cortex over the course of motor skill development.","authors":"Quynh N Nguyen, Katherine J Michon, Michael Vesia, Taraz G Lee","doi":"10.1523/JNEUROSCI.2015-23.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2015-23.2025","url":null,"abstract":"<p><p>Established models of motor skill learning posit that early stages of learning are dominated by an attentionally demanding, effortful mode of control supported by associative corticostriatal circuits involving the dorsolateral prefrontal cortex (DLPFC). As skill develops, automatic and \"effortless\" performance coincides with a transition to a reliance on sensorimotor circuits that include primary motor cortex (M1). However, the dynamics of how control evolves during the transition from novice to expert are currently unclear. This lack of clarity is due, in part, to the fact that most motor learning studies comprise a limited number of training sessions and rely on correlative techniques such as neuroimaging. Here, we train human participants (both sexes) on a discrete motor sequencing task over the course of six weeks, followed by an assessment of the causal roles of DLPFC and M1 at varying levels of expertise. We use repetitive transcranial magnetic stimulation to transiently disrupt activity in these regions immediately prior to performance in separate sessions. Our results confirm the dissociable importance of DLPFC and M1 as training progresses. DLPFC stimulation leads to larger behavioral deficits for novice skills than more highly trained skills, while M1 stimulation leads to relatively larger deficits as training progresses. However, our results also reveal that prefrontal disruption causes performance deficits at all levels of training. These findings challenge existing models and indicate an evolving rather than a strictly diminishing role for DLPFC throughout learning.<b>Significance Statement</b> Motor skills involve the sequential chaining of individual actions. For example, playing the piano involves learning to rapidly transition to from one finger press to another. Human neuroimaging studies have shown that primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) support novice motor sequencing skills, but activity in both regions declines over training. This has been interpreted as increased efficiency in M1 and yet a reduction in the involvement of DLPFC as expertise develops. We causally test this assumption by using non-invasive brain stimulation to transiently disrupt cortical activity following extended skill training. Although we confirm dissociable contributions of DLPFC and M1 as training progresses, we show that both regions are necessary for performance regardless of skill level.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143765619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}