eNeuro最新文献

{"title":"Energy constraints determine the selection of reaching movement trajectories in macaque monkeys.","authors":"Shrabasti Jana, Lucio Condro, Frédéric V Barthélemy, Junji Ito, Alexa Riehle, Sonja Grün, Thomas Brochier","doi":"10.1523/ENEURO.0385-24.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0385-24.2025","url":null,"abstract":"<p><p>Reaching movements, while seemingly simple, involve complex motor control mechanisms that select specific trajectories from infinite possibilities. Despite the inherent variability in volitional movements, both humans and monkeys frequently exhibit stereotyped trajectories. The literature has offered numerous explanations for invariant trajectory shapes, including a common planning space in hand-space or joint-space, as well as factors like kinetic energy (KE) minimization and sensory feedback. However, since most studies have relied on single-session data, crucial insights into the motor principles guiding trajectory selection and their evolution through extended practice remain underexplored. This study fills this gap by investigating how specific trajectories are selected and evolve with practice across multiple sessions, using data from two rhesus monkeys (one male, one female) performing a reaching task in a biomechanically constrained 2D setup. Our behavioral study challenges the idea of a common planning space, revealing instead a significant influence of KE on trajectory shapes. Through a novel biomechanical modeling, we quantified KE for a wide range of trajectory shapes. We discovered that trajectory selection and evolution is not simply about minimizing KE or achieving straight paths. Instead, the monkeys' motor systems appear to prioritize maintaining a \"safe KE range,\" where slight changes in trajectory shapes have minimal impact on energy expenditure. These findings provide new insights into the adaptive motor control strategies, suggesting that trajectory selection involves balancing energy efficiency and flexibility. Our study enhances the understanding of trajectory selection principles, with implications for rehabilitation strategies, robotics and broader study of motor control mechanisms.<b>Significance statement</b> This study provides new insights into motor control by analyzing and modeling monkey behavior, revealing that kinetic energy (KE) significantly influences trajectory shape. Our findings challenge the conventional views that trajectory selection primarily aims to maximize straightness or minimize KE. Instead, our analyses show that the motor system seeks to maintain a \"safe KE range,\" where small trajectory differences do not significantly impact energy expenditure. We reach this conclusion through a novel biomechanical modeling approach, which quantifies KE across a wide range of trajectory shapes for specific movements. By combining behavioral analysis with modeling, we demonstrate that trajectory selection balances efficiency and flexibility, offering valuable implications for developing rehabilitation strategies and robotic assistive devices that align with natural movement principles.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124401","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":"Paclitaxel Chemotherapy Disrupts Circadian Gene Transcription and Function of the Suprachiasmatic Nuclei in Female Mice.","authors":"Zoe M Tapp, Melina M Seng, Amiya K Ghosh, Karl H Obrietan, Leah M Pyter","doi":"10.1523/ENEURO.0061-25.2025","DOIUrl":"10.1523/ENEURO.0061-25.2025","url":null,"abstract":"<p><p>Cancer patients experience circadian rhythm disruptions during and after chemotherapy that can contribute to debilitating side effects. It is unknown how chemotherapy mediates circadian disruptions and specifically the extent to which these disruptions occur at the level of the principal clock, the suprachiasmatic nuclei (SCN) of the hypothalamus. In the present study, we assessed how the commonly used chemotherapeutic, paclitaxel, impacts the SCN molecular clock and SCN-dependent behavioral adaptations to circadian challenges in female mice. Following a repeated chemotherapy regimen, we measured rhythmic SCN expression of molecular clock and circadian-associated transcripts. Paclitaxel chemotherapy disrupted the SCN molecular clock through abolished rhythmicity (<i>Bmal1</i>, <i>Nr1d2</i>) and damped rhythmic transcription (<i>Ciart</i>, <i>Dbp</i>, <i>Nr1d1</i>, <i>Per2</i>) of key molecular clock genes. We further determined chemotherapy-induced changes to SCN function by measuring circadian wheel running adaptations to a jet lag phase-delay or phase-advance paradigm and by generating a phase response curve (PRC). Chemotherapy did not alter re-entrainment to a 6 h phase-advance, but after a 6 h phase-delay, chemotherapy-treated mice had a more stable and robust circadian rhythm than vehicle-treated mice, possibly indicative of a weakened or decoupled SCN. In the PRC, chemotherapy blunted light-induced phase-shift delays during subjective night compared with vehicle controls, also indicative of disrupted SCN-dependent entrainment. Together, this work demonstrates that paclitaxel chemotherapy disrupts both the molecular clock and functional re-entrainment of the SCN that could cause or contribute to observed circadian rhythm disruptions after treatment. This research could help guide application of circadian-mediated therapies to mitigate side effects of chemotherapy.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023083","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":"Differential encoding of odor and place in mouse piriform and entorhinal cortex.","authors":"Wilson Mena, Keeley Baker, Alon Rubin, Shaun Kohli, Yun Yoo, Brice Bathellier, Yaniv Ziv, Alexander Fleischmann, Shahab Rezaei-Mazinani","doi":"10.1523/ENEURO.0026-25.2025","DOIUrl":"10.1523/ENEURO.0026-25.2025","url":null,"abstract":"<p><p>The integration of olfactory and spatial information is critical for guiding animal behavior. The lateral entorhinal cortex (LEC) is reciprocally interconnected with cortical areas for olfaction and the hippocampus and thus ideally positioned to encode odor-place associations. Here, we used mini-endoscopes to record neural activity in the mouse piriform cortex (PCx) and LEC. We show that in head-fixed mice, odor identity could be decoded from LEC ensembles, but less accurately than from PCx. In male mice freely navigating a linear track, LEC ensemble activity at the odor ports was dominated by spatial information. Spatial position along the linear track could be decoded from LEC and PCx activity, however, PCx but not LEC exhibited strong behavior-driven modulation of positional information. Together, our data reveal that information about odor cues and spatial context is differentially encoded along the PCx-LEC axis.<b>Significance statement</b> For most animals, the sense of smell is essential for successfully navigating the environment to find food, shelter, and mates. However, how olfactory and spatial information is integrated in the brain to support olfactory-guided behaviors remains poorly understood. In mammals, candidate brain regions thought to support odor-place associations include the olfactory (piriform, PCx) cortex, entorhinal cortex, and hippocampus. We here characterize the activity of cells in the PCx and lateral entorhinal cortex (LEC) of freely moving mice in response to odor cues presented in a linear track. Using mini-endoscope microscopy and population coding analyses, we find that information about odors, spatial location, and behavior is differentially encoded along the PCx-LEC axis.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091347","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":"Parabrachial <i>Calca</i> neurons influence aversive and appetitive taste function.","authors":"Christian H Lemon, Jinrong Li, Md Sams Sazzad Ali, Neville M Ngum, Kyle T Zumpano, Catori J Roberts","doi":"10.1523/ENEURO.0191-25.2025","DOIUrl":"10.1523/ENEURO.0191-25.2025","url":null,"abstract":"<p><p>The parabrachial (PB) nucleus participates in taste processing and integration with other senses. PB neurons that express the <i>Calca</i> gene support sensory-integrative responses, albeit only limited data have addressed their influence on taste. Here we investigated how chemogenetic dampening of PB-<i>Calca</i> neurons affected mouse orosensory preferences for diverse taste stimuli in brief-access fluid exposure tests, which capture oral sensory/tongue control of licking behavior. Intracranial delivery of Cre-dependent viruses in female and male <i>Calca</i> ^Cre/+ mice induced expression of the inhibitory designer receptor hM4Di:mCherry (hM4Di mice) or fluorophore mCherry alone (mCherry control mice) in PB-<i>Calca</i> neurons. Several weeks later, hM4Di and mCherry mice entered brief-access tests where they could lick solutions during discrete, seconds-long trials. Stimuli included concentration series of the behaviorally avoided bitter taste stimuli quinine and cycloheximide, the appetitive sugar sucrose, and mildly cool water and less preferred innocuous warm water. Blinded experimenters administered the hM4Di ligand clozapine-N-oxide (CNO) to all hM4Di and mCherry mice prior to daily tests. With CNO, hM4Di mice displayed greater average licking (i.e., less avoidance) of quinine than mCherry mice (p < 0.05). Moreover, male hM4Di mice selectively showed reduced mean licking preferences for sucrose under CNO (p < 0.05). These data suggest that PB-<i>Calca</i> neurons participate in both aversive and appetitive taste-guided behaviors, with their role in appetitive taste dependent on sex. Finally, orosensory responses to cycloheximide and thermal-controlled water did not differ (p > 0.05) between hM4Di and mCherry mice under CNO. Results are discussed considering functional differences among stimuli and study limitations.<b>Significance statement</b> Parabrachial neurons that express the <i>Calca</i> gene are implicated in protective responses evoked by multiple senses, including taste. Using Cre-directed chemogenetics and lickometry assays in mice, we found evidence that parabrachial <i>Calca</i> neurons may support broader, more diverse functions in gustatory processing. Chemogenetic suppression targeted to these cells reduced licking avoidance of the bitter taste stimulus quinine and also decreased licking preference for the preferred sugar (sweet) sucrose, with the latter effect arising exclusively in male mice. Our results agree with recent studies reporting involvement of parabrachial <i>Calca</i> neurons in both aversive and appetitive sensory valence coding and suggest there is a sex-dependence to their role in appetitive taste.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091374","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":"Topographic organization of saccade-related response field properties in the marmoset posterior parietal cortex.","authors":"Joanita F D'Souza, Jessima M Rich, Shaun L Cloherty, Nicholas S C Price, Maureen A Hagan","doi":"10.1523/ENEURO.0287-25.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0287-25.2025","url":null,"abstract":"<p><p>Despite various histological, electrophysiological, and imaging studies, the topographic organization of saccade-related activity in the posterior parietal cortex (PPC) has been notoriously difficult to characterize. In part, this is because areas of interest in PPC are often embedded deep in sulci in macaques and humans. Understanding the extent of topographic organization in PPC can provide insights into the computation contributions of PPC. The lissencephalic cortex of the common marmoset offers a unique opportunity to investigate fine-scale topographic organization in PPC. Recordings were obtained from the PPC of two male marmosets performing a visually-guided center-out saccade task with 8 or 36 peripheral targets using multi-channel electrode arrays with 100 μm spacing. By plotting the pattern of saccade direction tuning preferences across all penetrations and cortical depths, uncovered topographic organizational features within PPC were uncovered. Like other primates, multiunits in marmoset PPC tend to prefer saccade targets in the contralateral visual field. The results detail how preference for saccadic direction changes in a systematic manner across cortical distance, such that response units closer in proximity tend to show systematic changes in their tuning preferences. Across cortical distance, the visual field was also systematically encoded but reversals in direction varied across penetrations. The analysis highlights the likelihood of multiple representations of the visual field for saccade-direction preference across PPC. These novel findings suggest a possible functional organization of saccade-related activity in marmoset PPC, giving insights into the computational capacity of the PPC.<b>Significance statement</b> Topographic maps are found across the primate brain, particularly in visual areas. A fundamental feature of these maps is that neurons involved in similar computations are spatially clustered. Moving from early sensory areas to higher-order areas, the degree of topographic organization decreases. This may allow high-order areas more flexibility and to respond to stimuli in a dynamic environment. The extent to which the posterior parietal cortex (PPC) shows topographic organization has been a subject of debate. This study presents the first detailed mapping of saccade direction topography in marmoset monkeys. These results provide novel insights into the topographic organization of the PPC in primates, and provide insights into its computational role in visual behavior.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091333","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":"Human Epileptic Neurons: They Are \"Sag\"-nificantly Different!","authors":"Mélina Scopin","doi":"10.1523/ENEURO.0278-25.2025","DOIUrl":"10.1523/ENEURO.0278-25.2025","url":null,"abstract":"","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":"12 9","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447861/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085454","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":"The Oviposition Inhibitory Neuron is a Potential Hub of Multi-Circuit Integration in the <i>Drosophila</i> Brain.","authors":"Rhessa A Weber-Langstaff, Pranjal Srivastava, Alexander B Kunin, Gabrielle J Gutierrez","doi":"10.1523/ENEURO.0123-25.2025","DOIUrl":"10.1523/ENEURO.0123-25.2025","url":null,"abstract":"<p><p>Understanding how neural circuits integrate sensory and state information to support context-dependent behavior is a central challenge in neuroscience. Oviposition is a complex process during which a fruit fly integrates context and sensory information to choose an optimal location to lay her eggs. The circuit that controls oviposition is known, but how the oviposition circuit integrates multiple sensory modalities and internal states is not. Using the Hemibrain connectome, we identified the oviposition inhibitory neuron (oviIN) as a key hub in the oviposition circuit and analyzed its inputs to uncover potential parallel pathways that may be responsible for computations related to sensory integration and decision-making. We applied a network analysis to the subconnectome of inputs to the oviIN to identify clusters of interconnected neurons-many of which are uncharacterized cell types. Our findings indicate that the inputs to oviIN form multiple parallel pathways through the unstructured neuropils of the superior protocerebrum, a region implicated in context-dependent processing.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12447867/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946925","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":"Characterization of Optimal Optogenetic Stimulation Paradigms to Evoke Calcium Events in Cortical Astrocytes.","authors":"Lakshmini Balachandar, Carolina Moncion, Alejandro Suarez, Jorge Riera Diaz","doi":"10.1523/ENEURO.0220-25.2025","DOIUrl":"10.1523/ENEURO.0220-25.2025","url":null,"abstract":"<p><p>Understanding the roles of astrocytic calcium signaling in multiple brain regulatory mechanisms including metabolism, blood flow, neuromodulation, and neuroinflammation has remained one of the enduring challenges in glial biology. To delineate astrocytic contribution from concurrent neuronal activity, it is vital to establish robust control and manipulate astrocytes using a technique like optogenetics due to its high cellular specificity and temporal resolution. The lack of an experimental paradigm to induce controlled calcium signaling in astrocytes has hindered progress in the field. To address this, in this study, we systematically characterize and identify light stimulation paradigms for inducing regulated, on-demand increases in astrocytic calcium in acute brain slice cortical astrocytes from MlC1-ChR2(C128S)-EYFP mice (of either sex). We identified paradigms 20, 40 and 60% (of <i>T</i> = 100 s) to elicit robust calcium responses upon periodic stimulations, while the 95% paradigm exhibited a response only during the first stimulation. We also quantified several parameters, including peak height, full-width at half-maximum (FWHM), and latencies, and observe that the 20% paradigm/duty cycle has the highest peak Δ<i>F</i>/<i>F</i> ₀ among the paradigms across all stimulations and the lowest FWHM during the first stimulation. To illustrate the impact of our study, we observed robust changes in cerebral blood flow, because of 20% optogenetic stimulation, in vivo, using laser Doppler flowmetry. Overall, the 20% paradigm is a favorable choice for eliciting robust astrocytic calcium responses in astrocytes while performing periodic stimulations.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12440239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946444","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":"Depression Levels Are Associated with Reduced Capacity to Learn to Actively Avoid Aversive Events in Young Adults.","authors":"Ryan J Tomm, Brandon J Forys, Liz Kalenteridis, Ian D Daly, Alex R Terpstra, Luke Clark, Stan B Floresco, Trisha Chakrabarty, Rebecca M Todd","doi":"10.1523/ENEURO.0034-25.2025","DOIUrl":"10.1523/ENEURO.0034-25.2025","url":null,"abstract":"<p><p>Depression and anxiety are often characterized by altered reward-seeking and avoidance, respectively. Yet less is known about the relationship between depressive symptoms and specific avoidance behaviors. To address this gap, we conducted two studies. In Study 1, undergraduates and online workers completed an uninstructed go/no-go avoidance task (<i>N</i> _Total = 465) as a reverse translation of a rodent paradigm. Participants exhibited a wide range of symptom scores on the Beck Depression Inventory-II (BDI-II), ranging from low to severe. In Study 1, cues were used to signal the response type (go/active vs no-go/inhibitory) required to avoid an aversive sound. Higher depressive scores were associated with poorer acquisition of active avoidance in undergraduates. Overall participants showed lower accuracy for active than inhibitory avoidance. To examine whether the better no-go trial performance reflected a prepotent response to avoid aversive outcomes, in Study 2, undergraduates (<i>N</i> _Total = 330) completed a version of the task that included reward-seeking. Here all participants showed higher accuracy for active reward-seeking and inhibitory avoidance, consistent with a prepotent response to inhibit action to avoid aversive consequences. These findings suggest that in young adults, depressive symptoms are associated with difficulty in overriding prepotent responses to actively avoid aversive outcomes in the absence of reward. This work bridges the gap between preclinical animal models and clinical research, offering insights that could guide the development of more targeted clinical interventions.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946481","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":"Online HD-tRNS over the right temporoparietal junction modulates social inference but not motor coordination.","authors":"Quentin Moreau, Vincent Chamberland, Lisane Moses, Gabriela Milanova, Guillaume Dumas","doi":"10.1523/ENEURO.0155-25.2025","DOIUrl":"https://doi.org/10.1523/ENEURO.0155-25.2025","url":null,"abstract":"<p><p>Social interactions are fundamental to human cognition, with the right temporoparietal junction (rTPJ) playing a key role in integrating motor coordination and social inference. While transcranial random noise stimulation (tRNS) is a promising technique for modulating cortical excitability in real time, its effect on dynamic social processes remains largely unexplored. This study applied high-definition tRNS (HD-tRNS) over the rTPJ during interaction with an adaptive virtual partner to modulate motor coordination and social inference. Eighty neurotypical adults (49 female) were assigned to one of two experiments: (Exp1) a block design with randomized active and sham stimulation blocks, or (Exp2) a trial-by-trial design with intermixed stimulation protocols. Participants performed a coordination task with a covert virtual partner programmed to behave cooperatively or competitively. Kinematic data and self-reported attributions of humanness and cooperativeness were analyzed. The results showed that HD-tRNS over the rTPJ did not affect motor coordination or overall task performance in either experiment. However, in Exp1, active stimulation progressively reduced attributed humanness and cooperativeness towards the competitive virtual partner, suggesting enhanced detection of antagonistic intent. This gradual modulation of social inference was absent in Exp2, where frequent protocol switching likely disrupted the buildup of stimulation effects. Together, these findings highlight the rTPJ's causal role in self-other distinction, underscore the importance of stimulation protocol design in shaping social cognition, and support the exploration of targeted neuromodulation in clinical and developmental populations with atypical social cognition.<b>Significance statement</b> Social interactions rely on our ability to infer others' intentions, including distinguishing between cooperative and competitive behavior: a process involving the right temporoparietal junction (rTPJ). Here, we used high-definition transcranial random noise stimulation (HD-tRNS) to test the rTPJ's causal role during live social interactions with an adaptive virtual partner. While stimulation did not affect motor coordination, repeated application led participants to gradually attribute less humanness and cooperativeness to a covertly competitive partner, suggesting enhanced sensitivity to competitive intent. These findings provide new insights into the rTPJ's contribution to self-other distinction, demonstrate the potential of HD-tRNS to investigate and modulate social inference, and have implications for understanding and potentially addressing social difficulties in conditions such as autism and schizophrenia.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":" ","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052552","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}