Journal of Neuroscience最新文献

{"title":"The Extralemniscal System Modulates Early Somatosensory Cortical Processing.","authors":"Sofija Perovic, Richard Somervail, Diego Benusiglio, Gian Domenico Iannetti","doi":"10.1523/JNEUROSCI.1815-24.2025","DOIUrl":"10.1523/JNEUROSCI.1815-24.2025","url":null,"abstract":"<p><p>Sudden and surprising sensory changes signal environmental events that may require immediate behavioral reactions. In mammals, these changes engage nonspecific \"extralemniscal\" thalamocortical pathways and evoke large and widespread cortical vertex potentials (VPs). Extralemniscal activity modulates cortical motor output in a variety of tasks and facilitates purposeful and immediate behavioral responses. In contrast, whether the extralemniscal system also affects cortical processing of sensory input transmitted through canonical \"lemniscal\" thalamocortical pathways remains unknown. Here we tested this hypothesis. In 23 healthy human participants (11 females) we continuously probed lemniscal processing in the primary somatosensory cortex (S1) by measuring the early-latency evoked potentials elicited by a stream of high-frequency (9.5 Hz) somatosensory electrical stimuli. We concurrently recorded extralemniscal activity by measuring the large VPs elicited by fast-rising and infrequent (∼0.1 Hz) auditory pure tones. We observed that the amplitude of S1 responses changes as a function of the phase of the VP, an effect consequent to a modulation of lemniscal input at the cortical rather than subcortical level. These findings demonstrate that a transient activation of the extralemniscal system interferes with ongoing cortical functions across different brain systems-i.e., not only at the level of the motor output but already at the sensory input-and thereby influences global brain dynamics.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849535","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":"Attention Defines the Context for Implicit Sensorimotor Adaptation.","authors":"Tianhe Wang, Jialin Li, Richard B Ivry","doi":"10.1523/JNEUROSCI.0117-25.2025","DOIUrl":"10.1523/JNEUROSCI.0117-25.2025","url":null,"abstract":"<p><p>The sensorimotor system continuously uses error signals to remain precisely calibrated. We examined how attention influences this automatic and implicit learning process in humans (male and female). Focusing first on spatial attention, we compared conditions in which attention was oriented either toward or away from the visual feedback that defined the error signal. Surprisingly, this manipulation had no effect on the rate of sensorimotor adaptation. Using dual-task methods, we next examined the influence of attentional resources on adaptation. Again, we found no effect of attention, with the rate of adaptation similar under focused and divided attention conditions. However, we found that attention modulates adaptation in an indirect manner: The rate of adaptation was significantly attenuated when the attended stimulus changed from the end of one trial to the start of the next trial. In contrast, similar changes to unattended stimuli had no impact on adaptation. These results suggest that visual attention defines the cues that establish the context for sensorimotor learning.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12491766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144977102","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":"Beta and High Gamma Oscillations in the Cortico-striatal Network Reflect Reward Certainty on a Probabilistic Reversal Learning Task.","authors":"Miranda F Koloski, Morteza Salimi, Sidharth Hulyalkar, Tianzhi Tang, Sam A Barnes, Joyti Mishra, Dhakshin S Ramanathan","doi":"10.1523/JNEUROSCI.0858-25.2025","DOIUrl":"10.1523/JNEUROSCI.0858-25.2025","url":null,"abstract":"<p><p>Behavioral outcomes are rarely certain, requiring subjects to discriminate between available choices by using feedback to guide future decisions. Probabilistic reversal learning (PRL) tasks test subjects' ability to learn and flexibly adapt to changes in reward contingencies. Cortico-striatal circuitry has been broadly implicated in flexible decision-making-though what role these circuits play remains complicated. In this study we leveraged the fast temporal dynamics of local field potentials to precisely identify the role that cortico-striatal networks play during PRL reward feedback. We measured widespread (32-CH) local field potential activity of male Long-Evans rats during a PRL task wherein a target response delivered reward on 80% of trials while a non-target response delivered reward on 20% of trials. When subjects learned those reward probabilities, contingencies were reversed. We found that reward-evoked oscillations at beta (15-30 Hz) and high gamma (>70 Hz) frequencies marked positive reward valence and reflected probability of reward. Activity and connectivity at beta frequencies between orbitofrontal cortex, anterior insula, medial prefrontal cortex, and ventral striatum during expected rewards were correlated with behavioral performance and specific aspects of value/exploitative behavior as defined by a reinforcement learning computational model. Finally, we found that modulating beta activity in orbitofrontal cortex with optogenetic (20 Hz) stimulation promoted maladaptive behavior when stimulation was provided during non-target responses, consistent with our data and computational model predictions. Reward-evoked beta oscillations may reflect a crucial component underlying reward learning, and erroneous elevations in this physiological signal may contribute to maladaptive task performance and behavioral disruptions.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144975901","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":"Sharp waves, bursts, and coherence: Activity in a songbird vocal circuit is influenced by behavioral state.","authors":"Corinna Lorenz,Anindita Das,Eduarda Gervini Zampieri Centeno,Hamed Yeganegi,Robin Duvoisin,Roman Ursu,Aude Retailleau,Nicolas Giret,Arthur Leblois,Richard H R Hahnloser,Janie M Ondracek","doi":"10.1523/jneurosci.1903-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1903-24.2025","url":null,"abstract":"Similar to motor skill learning in mammals, vocal learning in songbirds requires a set of interconnected brain areas that make up an analogous basal ganglia-thalamocortical circuit known as the anterior forebrain pathway (AFP). Although neural activity in the AFP has been extensively investigated during awake singing, very little is known about its neural activity patterns during other behavioral states. Here, we used chronically implanted Neuropixels probes to investigate spontaneous neural activity in the AFP during natural sleep and awake periods in male zebra finches. We found that during sleep, neuron populations in the pallial region LMAN (lateral magnocellular nucleus of the nidopallium) spontaneously exhibited synchronized bursts that were characterized by a negative sharp deflection in the local field potential (LFP) and a transient increase in gamma power. LMAN population bursts occurred primarily during non-rapid eye movement (NREM) sleep and were highly reminiscent of sharp-wave ripple (SWR) activity observed in rodent hippocampus. We also examined the functional connectivity within the AFP by calculating the pairwise LFP coherence. As expected, delta and theta band coherence within LMAN and Area X was higher during sleep compared to awake periods. Contrary to our expectations, we did not observe strong coherence between LMAN and Area X during sleep, suggesting that the input from LMAN into Area X is spatially restricted. Overall, these results provide the first description of spontaneous neural dynamics within the AFP across behavioral states.Significance statement Although cortical and basal ganglia circuits are known to be required for learning in both mammals and birds, little is known about the ongoing spontaneous activity patterns within these circuits, or how they are modulated by behavioral state. Here we prove the first description of cortical-basal ganglia network activity during sleep and awake periods in birds. Within the pallial area LMAN, we observed population-wide bursting events that were highly reminiscent of hippocampal sharp-wave ripple (SWR) activity, suggesting that large-scale population events have diverse functions across vertebrates.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"102 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194791","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":"Common Mechanism Underlying Synaptic Dysfunction Caused by Preformed Fibril-Induced Accumulation of α-Synuclein or Tau in a Culture Propagation Model.","authors":"Dimitar Dimitrov,Sruthi Raja,Humaira Noor,Tomoyuki Takahashi","doi":"10.1523/jneurosci.0394-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0394-25.2025","url":null,"abstract":"In sporadic neurodegenerative diseases, the endogenous proteins α-synuclein in Parkinson's disease and tau in Alzheimer's disease undergo pathogenic prion-like propagation over many years, accumulating in both soluble and insoluble forms in neurons including synapses, where they impair synaptic transmission and potentially cause various neuronal symptoms. To investigate the functional outcome of such synaptic accumulation, we induced accumulation of endogenous proteins in murine and human synapses by incubating mouse (of either sex) neuronal cultures with pathogenic preformed fibrils (pffs). Two weeks after treatment with human α-synuclein or tau pff, the respective endogenous proteins accumulated in neurons including presynaptic terminals, where we also observed tubulin accumulation, suggesting microtubule over-assembly. These were not associated with mRNA upregulation and were prevented by pharmacological stimulation of autophagy. Both pffs caused accumulation of p62 in cell bodies, suggesting compromised protein degradation. pHluorin imaging in synapses indicated a marked prolongation of vesicular endocytic time, which was rescued by pharmacological depolymerization of microtubules or by the over-expression of full-length dynamin 1. Since dynamin is a high-affinity binding partner of microtubules as well as an endocytic key molecule, over-assembled microtubules can sequester dynamin, thereby inhibiting endocytosis. We conclude that pff-induced accumulation of α-synuclein or tau in presynaptic terminals can disrupt vesicle endocytosis through a common mechanism. Since endocytosis-dependent vesicle recycling is critical for maintaining neurotransmitter release, its disruption can affect the neurocircuitry operations involved, thereby causing diverse symptoms associated with neurodegenerative diseases. Thus, our data suggest a common molecular mechanism underlying synaptic dysfunctions associated with Parkinson's and Alzheimer's diseases.Significance statement The accumulation of the pathogenic proteins α-synuclein and tau drives prion-like trans-neuronal propagation and underlies distinct neurodegenerative diseases, such as Parkinson's and Alzheimer's disease. Using a synaptic culture model of protein propagation, we identified a shared mechanism of synaptic dysfunction caused by these otherwise distinct proteins. In our models, propagated α-synuclein or tau disrupt protein degradation pathways, leading to their accumulation. These accumulated proteins promote excessive microtubule assembly and sequester the key endocytic protein dynamin, eventually impairing synaptic vesicle endocytosis. This cascade results in synaptic dysfunction that could compromise neurocircuit operations critical for brain functions. Our clarification of these mechanistic steps will improve our understanding of the synaptic pathophysiology underlying diverse symptoms of distinct neurodegenerative diseases.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"19 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194790","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":"Microsaccade direction reveals the variation in auditory selective attention processes.","authors":"Shimpei Yamagishi,Shigeto Furukawa","doi":"10.1523/jneurosci.1623-24.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.1623-24.2025","url":null,"abstract":"Selective spatial attention plays a critical role in perception in the daily environment where multiple sensory stimuli exist. Even covertly directing attention to a specific location facilitates the brain's information processing of stimuli at the attended location. Previous behavioral and neurophysiological studies have shown that microsaccades, tiny involuntary saccadic eye movements, reflect such a process in terms of visual space and can be a marker of spatial attention. However, it is unclear whether auditory spatial attention processes that are supposed to interact with visual attention processes influence microsaccades and vice versa. Here, we examine the relationship between microsaccade direction and auditory spatial attention during dichotic oddball sound detection tasks with human participants of both sexes. The results showed that the microsaccade direction was generally biased contralateral to the ear to which the oddball sound was presented or that to which sustained auditory attention was directed. The post-oddball modulation of microsaccade direction was associated with the behavioral performance of the detection task. The results suggest that the inhibition of stimulus-directed microsaccade occurs to reduce erroneous orientation of ocular responses during selective detection tasks. We also found that the correlation between microsaccade direction and neural response to the tone originated from the auditory brainstem (frequency-following response: FFR). Overall, the present study suggests that microsaccades can be a marker of auditory spatial attention and that the auditory neural activity fluctuates over time with the states of attention and the oculomotor system, also involving the auditory subcortical processes.Significance statement Microsaccades, tiny involuntary saccadic eye movements, reflect covert visual attention and influence neural activity in the visual pathway depending on the attention states. However, we lack convincing evidence of whether and how microsaccades reflect auditory spatial attention and/or neural activity along the auditory pathway. Intriguingly, we showed that the microsaccade direction exhibited systematic stimulus-related change and correlated with auditory brainstem frequency-following response (FFR) during the dichotic selective attention task. These results suggest that microsaccades are associated with general spatial attention processes, not restricted to the visual domain, and can be a good tool for accessing fluctuating neural activity that may covary with the attention states.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"5 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145194816","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":"The Top-down of Prefrontal cortex to the Hippocampus Glutamatergic Pathway Regulates Reward memory of Methamphetamine.","authors":"Dongdong Zhao, Wenjing Shi, Minyu Li, Rui Xue, Aogang Wang, Hang Wang, Le Zhang, Mengbing Huang, Liping Bai, Rou Gu, Ye Li, Xianwen Zhang, Peter W Kalivas, Jie Bai","doi":"10.1523/JNEUROSCI.0374-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0374-25.2025","url":null,"abstract":"<p><p>Methamphetamine (METH) is a widely abused psychoactive drug that readily establishes reward memories contributing to METH relapse. The medial prefrontal cortex (mPFC) is central to cognition, motivation, reward and emotion and the hippocampus is critically involved reward memory. The mPFC possesses an enormous variety of projection neurons. However, the direct projection from the mPFC to the hippocampus involved in METH addiction has not been studied well. To explore the role of a mPFC-hippocampus pathway of regulating METH reward memory, conditioned place preference (CPP) was used to detect reward memory and recombinant adeno-associated virus 2/9s (rAAV2/9s) were used to label neurons, identify projections, and optogenetically explore involvement of the male mice mPFC-hippocampus pathway in regulating METH-CPP. We found that a novel prelimibic prefrontal cortex (PrL) projection directly to the dorsal hippocampus CA1 (dCA1) regulated CPP induced by METH. Moreover, optogenetic activation or inhibition, and silencing the PrL to dCA1 glutamatergic pathway with tetanus neurotoxin (TeNT) modulated METH-CPP. Our results reveal a PrL to dCA1 glutamatergic pathway that regulates METH-CPP and could serve as a potential target for treating METH use disorder.<b>Significance Statement</b> This study elucidated the intricate molecular, circuit, and functional architecture of the prelimibic prefrontal cortex (PrL) to dorsal hippocampus CA 1(dCA1) and identify CaMKIIα-expressing glutamatergic neurons in the medial prefrontal cortex (mPFC) as a key inversely driver of reward and methamphetamine addiction. These findings open new avenues for exploring how the prefrontal cortex to the hippocampus regulates reward and addiction.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145202021","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":"Walking modulates active auditory sensing.","authors":"Xinyu Chen, Liyu Cao, Roy Eric Wieske, Juan Prada, Klaus Gramann, Barbara F Haendel","doi":"10.1523/JNEUROSCI.0489-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.0489-25.2025","url":null,"abstract":"<p><p>Walking provides the motor foundation for navigation, while navigation ensures that walking is purposeful and adaptive to environmental contexts. Sensory processing of environmental information acts as the informational bridge that connects walking and adaptive navigation. In the current study, we assessed if walking and the walking direction influences neuronal dynamics underlying environmental information processing. To this end, we conducted two experiments with 12 male and 18 female participants while they walked along an 8-shaped path. Auditory entrainment stimuli were continuously presented, and mobile EEG (electroencephalogram) was recorded. We found increased auditory entrainment (auditory steady-state response) and early auditory evoked responses during walking compared to standing or stepping-in-place. We also replicated the well-established reduction of occipital alpha power during walking. The increase of auditory entrainment and the decrease of alpha power were correlated across participants. In the second experiment, randomly presented transient burst tones led to a perturbation of the auditory entrainment response. The perturbation response was stronger during walking compared to standing, however, only when the burst tones were presented to one ear but not to both ears. Most importantly, we found that the auditory entrainment was systematically modulated dependent on the walking path. The entrainment responses changed as a function of the turning direction. In general, the current work shows that walking changes auditory processing in a walking path-dependent way which might serve to optimize navigation. The walking path related modulation might further reflect a shift of attention, marking a form of higher-order active sensing.<b>Significance Statement</b> In this mobile EEG walking study, we uncovered a dynamic shift in auditory attention that aligns with changes in walking trajectory. Specifically, during turns, the brain prioritizes auditory input from the side of turn direction before the turn apex, then shifts preference to the opposite side. These findings reveal an active sensing mechanism that goes beyond simple motor adjustments to adjust sensory input but suggests that the brain dynamically optimizes the processing of sensory input e.g. to facilitate navigation. This study offers potential applications for understanding spatial awareness in real-world environments and improving navigational aids.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193487","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":"Origins of the Auditory Brainstem Response in Mice Using Source Localization of Topographic Multichannel EEG.","authors":"Xue Wang,Andrej Kral,Rüdiger Land","doi":"10.1523/jneurosci.0651-25.2025","DOIUrl":"https://doi.org/10.1523/jneurosci.0651-25.2025","url":null,"abstract":"The auditory brainstem response (ABR) is a critical tool for assessing auditory brainstem function in biomedical mouse models. Remarkably, despite its importance, the origins of ABR waves specific to mice remain poorly identified. Here, we used EEG source reconstruction to reevaluate the mouse-specific ABR origins. We recorded the topography of ABRs using high-density EEG from the skull of adult mice of either sex combined with parallel multielectrode recordings in the auditory cortex. Individual ABR waves showed a series of distinct spatial topographies across the skull. Wave I' was strongly lateralized, supporting its auditory nerve origin. Waves II/III were also lateralized but had a more frontal distribution, supporting an origin in the cochlear nucleus and olivary complex. A distinct shift in wave IV topography showed focused activity directly above the inferior colliculus (IC). Source localization with beamforming confirmed the origin of wave IV and V in the IC. In addition, the slow IC wave, P0, temporally overlapped with responses in the auditory cortex. We identify ABR wave IV as an IC marker differentiating olivary complex and cochlear nucleus, as well as thalamic and cortical contributions to the ABR. This improves the specificity of the mouse ABR as a non-invasive tool in biomedical mouse models.Significance Statement Mice are an important model in auditory neuroscience, central to the development of gene therapy for hearing restoration or studying the age-related effects of hearing loss. For this, the auditory brainstem response (ABR) is an invaluable tool to assess not only auditory thresholds, but also auditory brainstem integrity. However, despite its widespread use, only a single study to date has addressed the ABR origins specifically in mice, which has never been independently validated. Here, we provide an updated account of the origins of ABR waves specific to mice using modern innovative methodology and place them in comparative context of ABR sources across species. These results improve the ABR as an important tool for mouse models in auditory neuroscience.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"66 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145153438","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":"Theta activity supports landmark-based correction of naturalistic human path integration.","authors":"Clément Naveilhan, Raphaël Zory, Klaus Gramann, Stephen Ramanoël","doi":"10.1523/JNEUROSCI.1005-25.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1005-25.2025","url":null,"abstract":"<p><p>How do humans integrate landmarks to update their spatial position during active navigation? Using immersive virtual reality and high-density mobile EEG, we investigated the neural underpinnings of landmark-based recalibration during path integration in freely moving male and female humans. Participants navigated predefined routes, indicated the start position to quantify accumulated errors, and once per route corrected their estimate using a visual landmark. Our findings reveal that homing error accumulated along the course of navigation, but a briefly presented intra-maze landmark effectively corrected accumulated errors. However, this effect was transient and less pronounced when participants were highly confident in their self-motion-based spatial representation suggesting that internal priors can hinder the assimilation of novel spatial cues. Theta activity in the retrosplenial complex supported the realignment of internal spatial representations by anchoring self-motion-derived estimates to visual landmark cues. Increased theta power and phase resetting upon landmark presentation accompanied subtle corrections, supporting a smooth realignment of spatial representations, whereas diminished synchronization marked the need for more extensive spatial updating. In addition, we identified motor-related theta response that scaled with rotational acceleration. Taken together, these findings highlight the dual role of theta oscillations in flexibly integrating multimodal signals, supporting both the recalibration of spatial representations to external cues and the encoding of self-motion information during naturalistic human navigation.<b>Significance Statement</b> Spatial navigation depends on the continuous integration of internally generated self-motion cues with external environmental landmarks to construct and maintain spatial representations. Despite its central role in adaptive behavior, the neural dynamics underlying this intermodal integration in humans remain unclear. Using noninvasive mobile EEG with immersive virtual reality, we identify a dynamic mechanism within the retrosplenial complex that realigns internal and external spatial representations based on visual landmarks during naturalistic navigation. This process is mediated by theta-band activity, which not only supports visuo-spatial realignment but also encodes vestibular signals. These dual theta signatures demonstrate how the human brain flexibly integrates multimodal information to update spatial representations, highlighting theta oscillations as a unifying neural substrate for both perceptual and motor components of navigation.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145180281","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}