Pub Date : 2026-03-19DOI: 10.1038/s41593-026-02208-0
Mukund Kabbe,Eneritz Agirre,Karl E Carlström,Özge Dumral,Yuk Kit Lor,Fabio Baldivia Pohl,Nicolas Ruffin,David van Bruggen,Mandy Meijer,Luise A Seeker,Nadine Bestard-Cuche,Alex R Lederer,Jilin Zhang,Virpi Ahola,Steven A Goldman,Erik Edström,Lisa Arvidsson,Tiago Holm Moreira,Marek Bartosovic,Maja Jagodic,Anna Williams,Gonçalo Castelo-Branco
Neural cells in the adult human central nervous system (CNS) display extensive transcriptional heterogeneity. How different layers of epigenetic regulation underpin this heterogeneity is poorly understood. Here we profile, at the single-nuclei epigenomic level, distinct regions of the adult human CNS, for chromatin accessibility and simultaneously for the histone modifications H3K27me3 and H3K27ac. We unveil a putative SOX10 enhancer and primed chromatin signatures at HOX loci in spinal-cord-derived human oligodendroglia (OLG) and astrocytes, but not microglia. These signatures in adult OLG were reminiscent of developmental profiles but were decoupled from robust gene expression. Moreover, using high-resolution Micro-C, we show that induced pluripotent stem-cell-derived human OLGs exhibit a HOX chromatin architecture compatible with the primed chromatin in adult OLGs, bearing a strong resemblance not only to OLG developmental architecture but also to high-grade pontine gliomas. Thus, epigenetic memory from developmental states in adult OLG not only enables them to promptly transcribe Hox family genes during regeneration but also makes them susceptible to gliomagenesis.
{"title":"Single-nucleus epigenomic profiling of the adult human central nervous system unveils epigenetic memory of developmental programs.","authors":"Mukund Kabbe,Eneritz Agirre,Karl E Carlström,Özge Dumral,Yuk Kit Lor,Fabio Baldivia Pohl,Nicolas Ruffin,David van Bruggen,Mandy Meijer,Luise A Seeker,Nadine Bestard-Cuche,Alex R Lederer,Jilin Zhang,Virpi Ahola,Steven A Goldman,Erik Edström,Lisa Arvidsson,Tiago Holm Moreira,Marek Bartosovic,Maja Jagodic,Anna Williams,Gonçalo Castelo-Branco","doi":"10.1038/s41593-026-02208-0","DOIUrl":"https://doi.org/10.1038/s41593-026-02208-0","url":null,"abstract":"Neural cells in the adult human central nervous system (CNS) display extensive transcriptional heterogeneity. How different layers of epigenetic regulation underpin this heterogeneity is poorly understood. Here we profile, at the single-nuclei epigenomic level, distinct regions of the adult human CNS, for chromatin accessibility and simultaneously for the histone modifications H3K27me3 and H3K27ac. We unveil a putative SOX10 enhancer and primed chromatin signatures at HOX loci in spinal-cord-derived human oligodendroglia (OLG) and astrocytes, but not microglia. These signatures in adult OLG were reminiscent of developmental profiles but were decoupled from robust gene expression. Moreover, using high-resolution Micro-C, we show that induced pluripotent stem-cell-derived human OLGs exhibit a HOX chromatin architecture compatible with the primed chromatin in adult OLGs, bearing a strong resemblance not only to OLG developmental architecture but also to high-grade pontine gliomas. Thus, epigenetic memory from developmental states in adult OLG not only enables them to promptly transcribe Hox family genes during regeneration but also makes them susceptible to gliomagenesis.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"11 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147483704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-18DOI: 10.1038/s41593-026-02237-9
Tingting Zhou,Yi-Yun Ho,Nolan D Hartley,Ray X Lee,Amanda B Fath,Kathleen He,Xun Yuan,Sam Merrow,Jonathan Scott,Navdeep Bajwa,Jonathan Wilde,Xian Gao,Cui Li,Evan Hong,Zhanyan Fu,Matthew R Nassar,Ralf D Wimmer,Tarjinder Singh,Michael M Halassa,Guoping Feng
Belief updating is thought to be impaired in schizophrenia, leading to delusions. The neural substrates underlying belief updating are unknown, in part due to a lack of appropriate animal models and behavior readouts. We generated mice bearing a schizophrenia-associated point mutation in Grin2a (Grin2aY700X+/-) and developed a computationally trackable foraging task to assess belief-driven decision strategies in mice. Grin2aY700X+/- mice performed less optimally than their wild-type (WT) littermates, due to unstable cognitive states related to noisy representation of dynamic task values. We identified the mediodorsal (MD) thalamus as being hypofunctional in Grin2aY700X+/- mice and showed that MD neurons encode dynamic task values and cognitive states in WT mice. Optogenetic inhibition of MD neurons in WT mice phenocopied Grin2aY700X+/- mice and enhancing MD activity rescued task deficits in Grin2aY700X+/- mice. Together, our study identifies the MD thalamus as a key node for schizophrenia-relevant cognitive dysfunction and a potential target for future therapeutics.
{"title":"Reduced mediodorsal thalamus activity underlies aberrant belief dynamics in a genetic mouse model of schizophrenia.","authors":"Tingting Zhou,Yi-Yun Ho,Nolan D Hartley,Ray X Lee,Amanda B Fath,Kathleen He,Xun Yuan,Sam Merrow,Jonathan Scott,Navdeep Bajwa,Jonathan Wilde,Xian Gao,Cui Li,Evan Hong,Zhanyan Fu,Matthew R Nassar,Ralf D Wimmer,Tarjinder Singh,Michael M Halassa,Guoping Feng","doi":"10.1038/s41593-026-02237-9","DOIUrl":"https://doi.org/10.1038/s41593-026-02237-9","url":null,"abstract":"Belief updating is thought to be impaired in schizophrenia, leading to delusions. The neural substrates underlying belief updating are unknown, in part due to a lack of appropriate animal models and behavior readouts. We generated mice bearing a schizophrenia-associated point mutation in Grin2a (Grin2aY700X+/-) and developed a computationally trackable foraging task to assess belief-driven decision strategies in mice. Grin2aY700X+/- mice performed less optimally than their wild-type (WT) littermates, due to unstable cognitive states related to noisy representation of dynamic task values. We identified the mediodorsal (MD) thalamus as being hypofunctional in Grin2aY700X+/- mice and showed that MD neurons encode dynamic task values and cognitive states in WT mice. Optogenetic inhibition of MD neurons in WT mice phenocopied Grin2aY700X+/- mice and enhancing MD activity rescued task deficits in Grin2aY700X+/- mice. Together, our study identifies the MD thalamus as a key node for schizophrenia-relevant cognitive dysfunction and a potential target for future therapeutics.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"96 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-18DOI: 10.1038/s41593-026-02224-0
Tara Raam,Qin Li,Linfan Gu,Gabrielle M Elagio,Kayla Y Lim,Jay Y Taimish,Xingjian Zhang,Norma P Sandoval,Stephanie M Correa,Weizhe Hong
Animal groups often collectively coordinate their behavior to withstand environmental challenges, yet the neural circuitry underlying such collective social dynamics remains unclear. Here we show that groups of mice self-organize into huddles under cold stress. We quantified the thermoregulatory benefits of huddling using thermal imaging and internal temperature loggers, which revealed that it stabilized core body temperature by increasing thermal contact points and reducing heat loss. We next characterized decision-making processes that govern huddling dynamics and found that mice employed both active (self-initiated) and passive (partner-initiated) strategies to enter or exit a huddle. Microendoscopic calcium imaging revealed that active and passive decisions are encoded in distinct neuronal ensembles within the dorsomedial prefrontal cortex. Chemogenetic silencing of dorsomedial prefrontal cortex activity selectively reduced active decisions in targeted mice but elicited compensatory increases in non-manipulated partners, preserving overall group-level huddle time. These findings uncover a cortical mechanism by which social groups collectively adapt to maintain homeostasis under environmental challenge.
{"title":"Cortical regulation of collective social dynamics during environmental challenge.","authors":"Tara Raam,Qin Li,Linfan Gu,Gabrielle M Elagio,Kayla Y Lim,Jay Y Taimish,Xingjian Zhang,Norma P Sandoval,Stephanie M Correa,Weizhe Hong","doi":"10.1038/s41593-026-02224-0","DOIUrl":"https://doi.org/10.1038/s41593-026-02224-0","url":null,"abstract":"Animal groups often collectively coordinate their behavior to withstand environmental challenges, yet the neural circuitry underlying such collective social dynamics remains unclear. Here we show that groups of mice self-organize into huddles under cold stress. We quantified the thermoregulatory benefits of huddling using thermal imaging and internal temperature loggers, which revealed that it stabilized core body temperature by increasing thermal contact points and reducing heat loss. We next characterized decision-making processes that govern huddling dynamics and found that mice employed both active (self-initiated) and passive (partner-initiated) strategies to enter or exit a huddle. Microendoscopic calcium imaging revealed that active and passive decisions are encoded in distinct neuronal ensembles within the dorsomedial prefrontal cortex. Chemogenetic silencing of dorsomedial prefrontal cortex activity selectively reduced active decisions in targeted mice but elicited compensatory increases in non-manipulated partners, preserving overall group-level huddle time. These findings uncover a cortical mechanism by which social groups collectively adapt to maintain homeostasis under environmental challenge.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"409 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-17DOI: 10.1038/s41593-026-02236-w
Eric G. Ceballos, Asa Farahani, Zhen-Qi Liu, Filip Milisav, Justine Y. Hansen, Alain Dagher, Bratislav Misic
Neuropeptides are functionally diverse signaling molecules in the brain, regulating a wide range of basal bodily and cognitive processes. Despite their importance, the distribution and function of neuropeptides in the human brain remains underexplored. Here we comprehensively map the organization of human whole-brain neuropeptide receptors across multiple levels of description, including molecular and cellular embedding, mesoscale connectivity and macroscale cognitive specialization. Using gene transcription as a proxy, we reconstruct a topographical cortical and subcortical atlas of 38 neuropeptide receptors across 14 different neuropeptide families. We find that most neuropeptide receptors are highly expressed either in the cortex or subcortex, delineating an anatomical cortical–subcortical gradient. Mapping neuropeptide receptors onto hypothalamic nuclei, we demonstrate that neuropeptide receptor gene expression recapitulates fundamental anatomical divisions in the hypothalamus. Neuropeptides preferentially colocalize with metabotropic neurotransmitters, suggesting a system-wide correspondence between slow-acting molecular signaling mechanisms. To investigate the behavioral consequences of distributed neuropeptide systems, we apply meta-analytical decoding to neuropeptide maps and show a spectrum of functions, from sensory-cognitive to reward and bodily functions. Finally, using evolutionary analysis we find extended positive selection for neuropeptides in early mammals, suggesting that refinement of neuropeptides coincides with the emergence of neocortex and higher cognitive function. Collectively, these results show that neuropeptide receptors are highly organized across the human brain and closely intertwined with multiple features of brain structure and function.
{"title":"Organization of neuropeptide systems in the human brain","authors":"Eric G. Ceballos, Asa Farahani, Zhen-Qi Liu, Filip Milisav, Justine Y. Hansen, Alain Dagher, Bratislav Misic","doi":"10.1038/s41593-026-02236-w","DOIUrl":"https://doi.org/10.1038/s41593-026-02236-w","url":null,"abstract":"Neuropeptides are functionally diverse signaling molecules in the brain, regulating a wide range of basal bodily and cognitive processes. Despite their importance, the distribution and function of neuropeptides in the human brain remains underexplored. Here we comprehensively map the organization of human whole-brain neuropeptide receptors across multiple levels of description, including molecular and cellular embedding, mesoscale connectivity and macroscale cognitive specialization. Using gene transcription as a proxy, we reconstruct a topographical cortical and subcortical atlas of 38 neuropeptide receptors across 14 different neuropeptide families. We find that most neuropeptide receptors are highly expressed either in the cortex or subcortex, delineating an anatomical cortical–subcortical gradient. Mapping neuropeptide receptors onto hypothalamic nuclei, we demonstrate that neuropeptide receptor gene expression recapitulates fundamental anatomical divisions in the hypothalamus. Neuropeptides preferentially colocalize with metabotropic neurotransmitters, suggesting a system-wide correspondence between slow-acting molecular signaling mechanisms. To investigate the behavioral consequences of distributed neuropeptide systems, we apply meta-analytical decoding to neuropeptide maps and show a spectrum of functions, from sensory-cognitive to reward and bodily functions. Finally, using evolutionary analysis we find extended positive selection for neuropeptides in early mammals, suggesting that refinement of neuropeptides coincides with the emergence of neocortex and higher cognitive function. Collectively, these results show that neuropeptide receptors are highly organized across the human brain and closely intertwined with multiple features of brain structure and function.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"4 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-16DOI: 10.1038/s41593-026-02218-y
Justin J. Jude, Hadar Levi-Aharoni, Alexander J. Acosta, Shane B. Allcroft, Claire Nicolas, Bayardo E. Lacayo, Nicholas S. Card, Maitreyee Wairagkar, Alisa D. Levin, David M. Brandman, Sergey D. Stavisky, Francis R. Willett, Ziv M. Williams, John D. Simeral, Leigh R. Hochberg, Daniel B. Rubin
Here, recognizing keyboard typing as a familiar, high information rate communication paradigm, we developed an intracortical brain–computer interface (iBCI) typing neuroprosthesis providing bimanual QWERTY keyboard functionality for people with paralysis. Typing with this iBCI involves only attempted finger movements, which are decoded accurately with as few as 30 calibration sentences. Sentence decoding is improved using a 5-gram language model. This typing neuroprosthesis performed well for two iBCI clinical trial participants with tetraplegia—one with amyotrophic lateral sclerosis and one with spinal cord injury. Typing speed is user-regulated, reaching 110 characters per minute, resulting in 22 words per minute with a word error rate of 1.6%. This resembles able-bodied typing accuracy and provides higher throughput than current state-of-the-art hand motor iBCI decoding. In summary, a typing neuroprosthesis decoding finger movements, provides an intuitive, familiar and easy-to-learn paradigm for individuals with impaired communication due to paralysis.
{"title":"Restoring rapid natural bimanual typing with a neuroprosthesis after paralysis","authors":"Justin J. Jude, Hadar Levi-Aharoni, Alexander J. Acosta, Shane B. Allcroft, Claire Nicolas, Bayardo E. Lacayo, Nicholas S. Card, Maitreyee Wairagkar, Alisa D. Levin, David M. Brandman, Sergey D. Stavisky, Francis R. Willett, Ziv M. Williams, John D. Simeral, Leigh R. Hochberg, Daniel B. Rubin","doi":"10.1038/s41593-026-02218-y","DOIUrl":"https://doi.org/10.1038/s41593-026-02218-y","url":null,"abstract":"Here, recognizing keyboard typing as a familiar, high information rate communication paradigm, we developed an intracortical brain–computer interface (iBCI) typing neuroprosthesis providing bimanual QWERTY keyboard functionality for people with paralysis. Typing with this iBCI involves only attempted finger movements, which are decoded accurately with as few as 30 calibration sentences. Sentence decoding is improved using a 5-gram language model. This typing neuroprosthesis performed well for two iBCI clinical trial participants with tetraplegia—one with amyotrophic lateral sclerosis and one with spinal cord injury. Typing speed is user-regulated, reaching 110 characters per minute, resulting in 22 words per minute with a word error rate of 1.6%. This resembles able-bodied typing accuracy and provides higher throughput than current state-of-the-art hand motor iBCI decoding. In summary, a typing neuroprosthesis decoding finger movements, provides an intuitive, familiar and easy-to-learn paradigm for individuals with impaired communication due to paralysis.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"33 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147465482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) but its neural mechanisms remain poorly understood. A mechanistic understanding requires precise characterization of functional responses to various stimulation conditions within the same individual. Here we use 3-T magnetic resonance imaging (MRI)-compatible DBS and precision imaging to collect extensive data from 14 patients with PD who received DBS. Across five timepoints spanning 1 year, each patient underwent 11.7 hours of functional MRI (fMRI) under seven stimulation conditions (30-172 min per session), 2.2 hours of structural MRI (26 min per session), 1.3 hours of diffusion-weighted MRI (16 min per session) and neurological assessments. Imaging data were also collected from 27 healthy participants. DBS normalizes connectivity in the somatocognitive action network and evokes differential responses in two distinct neurocircuits: the primary motor and globus pallidus circuits. Target cortical functional connectivity predicts clinical outcomes. This densely sampled dataset provides reliable, individually specific functional measures and is shared with the community to accelerate research into DBS mechanisms and improve personalized treatment strategies.
{"title":"Circuit response to neuromodulation characterized with simultaneous deep brain stimulation and precision neuroimaging in humans.","authors":"Jianxun Ren,Changqing Jiang,Wei Zhang,Louisa Dahmani,Lunhao Shen,Feng Zhang,Shenshen Li,Changgeng He,Yilin Yin,Xiaoxuan Fu,Jianting Huang,Yang Long,Dantong Liu,Yi Guo,Yiming Liu,Shujun Xu,Fangang Meng,Jianguo Zhang,Danhong Wang,Luming Li,Hesheng Liu","doi":"10.1038/s41593-026-02228-w","DOIUrl":"https://doi.org/10.1038/s41593-026-02228-w","url":null,"abstract":"Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD) but its neural mechanisms remain poorly understood. A mechanistic understanding requires precise characterization of functional responses to various stimulation conditions within the same individual. Here we use 3-T magnetic resonance imaging (MRI)-compatible DBS and precision imaging to collect extensive data from 14 patients with PD who received DBS. Across five timepoints spanning 1 year, each patient underwent 11.7 hours of functional MRI (fMRI) under seven stimulation conditions (30-172 min per session), 2.2 hours of structural MRI (26 min per session), 1.3 hours of diffusion-weighted MRI (16 min per session) and neurological assessments. Imaging data were also collected from 27 healthy participants. DBS normalizes connectivity in the somatocognitive action network and evokes differential responses in two distinct neurocircuits: the primary motor and globus pallidus circuits. Target cortical functional connectivity predicts clinical outcomes. This densely sampled dataset provides reliable, individually specific functional measures and is shared with the community to accelerate research into DBS mechanisms and improve personalized treatment strategies.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"8 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-11DOI: 10.1038/s41593-026-02230-2
Clément Pouget, Flora Morier, Livia Autore, Nadja Treiber, Pablo Fernández García, Nina Mazza, Run Zhang, Isaiah L. Reeves, Stephen M. Winston, Mark A. Brimble, Christina K. Kim, Gisella Vetere
The mechanisms of associative memory formation, including which cells encode a memory and the timing of their engagement, remain poorly understood. By visualizing and tagging cells based on their calcium influx with unparalleled temporal precision, we identified nonoverlapping dorsal CA1 neuronal ensembles that are differentially active during associative fear memory acquisition. We dissected the acquisition experience into periods during which salient stimuli were presented, or certain mouse behaviors occurred, and found that cells associated with specific acquisition periods are sufficient alone to drive memory expression and contribute to fear engram formation. This study delineated the distinct identities of the cell ensembles active during learning and revealed which ones form the core engram and are essential for memory formation and recall.
{"title":"Deconstruction of a memory engram reveals distinct ensembles recruited at learning","authors":"Clément Pouget, Flora Morier, Livia Autore, Nadja Treiber, Pablo Fernández García, Nina Mazza, Run Zhang, Isaiah L. Reeves, Stephen M. Winston, Mark A. Brimble, Christina K. Kim, Gisella Vetere","doi":"10.1038/s41593-026-02230-2","DOIUrl":"https://doi.org/10.1038/s41593-026-02230-2","url":null,"abstract":"The mechanisms of associative memory formation, including which cells encode a memory and the timing of their engagement, remain poorly understood. By visualizing and tagging cells based on their calcium influx with unparalleled temporal precision, we identified nonoverlapping dorsal CA1 neuronal ensembles that are differentially active during associative fear memory acquisition. We dissected the acquisition experience into periods during which salient stimuli were presented, or certain mouse behaviors occurred, and found that cells associated with specific acquisition periods are sufficient alone to drive memory expression and contribute to fear engram formation. This study delineated the distinct identities of the cell ensembles active during learning and revealed which ones form the core engram and are essential for memory formation and recall.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"76 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147394050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-11DOI: 10.1038/s41593-026-02205-3
Andrea I Luppi,Yonatan Sanz Perl,Jakub Vohryzek,Hana Ali,Pedro A M Mediano,Fernando E Rosas,Filip Milisav,Laura E Suárez,Silvia Gini,Daniel Gutierrez-Barragan,Yohan Yee,Seán Froudist-Walsh,Alessandro Gozzi,Bratislav Misic,Gustavo Deco,Morten L Kringelbach
How does brain network architecture balance cooperation and competition between distributed circuits? Here we use computational whole-brain modeling to examine the dynamical and computational relevance of cooperative and competitive interactions in the mammalian connectome. Across human, macaque and mouse, we show that to faithfully reproduce brain activity, model architecture consistently combines modular cooperative interactions with diffuse, long-range competitive interactions. Across species, competitive interactions preferentially link regions characterized by opposite profiles of cytoarchitecture, gene expression and receptor expression. The model with competitive interactions provides superior subject specificity, consistently outperforming the cooperative-only model and exhibiting excellent fit to the spatiotemporal properties of the living brain. These properties were not explicitly optimized, instead emerging spontaneously. Competitive interactions in the generative connectivity produce more synergistic and hierarchical dynamics, leading to enhanced performance for neuromorphic computing. Altogether, this work provides a generative link among network architecture, dynamical properties and computational performance in the mammalian brain.
{"title":"Competitive interactions shape mammalian brain network dynamics and computation.","authors":"Andrea I Luppi,Yonatan Sanz Perl,Jakub Vohryzek,Hana Ali,Pedro A M Mediano,Fernando E Rosas,Filip Milisav,Laura E Suárez,Silvia Gini,Daniel Gutierrez-Barragan,Yohan Yee,Seán Froudist-Walsh,Alessandro Gozzi,Bratislav Misic,Gustavo Deco,Morten L Kringelbach","doi":"10.1038/s41593-026-02205-3","DOIUrl":"https://doi.org/10.1038/s41593-026-02205-3","url":null,"abstract":"How does brain network architecture balance cooperation and competition between distributed circuits? Here we use computational whole-brain modeling to examine the dynamical and computational relevance of cooperative and competitive interactions in the mammalian connectome. Across human, macaque and mouse, we show that to faithfully reproduce brain activity, model architecture consistently combines modular cooperative interactions with diffuse, long-range competitive interactions. Across species, competitive interactions preferentially link regions characterized by opposite profiles of cytoarchitecture, gene expression and receptor expression. The model with competitive interactions provides superior subject specificity, consistently outperforming the cooperative-only model and exhibiting excellent fit to the spatiotemporal properties of the living brain. These properties were not explicitly optimized, instead emerging spontaneously. Competitive interactions in the generative connectivity produce more synergistic and hierarchical dynamics, leading to enhanced performance for neuromorphic computing. Altogether, this work provides a generative link among network architecture, dynamical properties and computational performance in the mammalian brain.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"31 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147393746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-03-10DOI: 10.1038/s41593-026-02207-1
Binxu Wang, Carlos R. Ponce
Visual neurons respond to a vast range of images, from textures to objects, but the rules linking these responses remain unclear. Although tuning to simple features is well established in the primary visual cortex, this framework breaks down in higher areas, where neurons encode diverse and unpredictable features. To ask what features neurons prioritize, we used generative models (deep networks that synthesize new images from a learned latent space), allowing neurons in V1, V4 and the posterior inferotemporal cortex (PIT) to guide image synthesis through closed-loop optimization. We compared models that emphasize texture versus those that emphasize object structure. Although V1 and V4 aligned more strongly with texture-based spaces, many PIT neurons responded equally well to both types of optimized images, revealing a focus on shared local motifs rather than whole-object templates, and this alignment to objects emerged later in their response. These findings reveal coding principles across the ventral stream and clarify the limits of current vision models.
{"title":"Neuronal tuning aligns dynamically with object and texture manifolds across the visual hierarchy","authors":"Binxu Wang, Carlos R. Ponce","doi":"10.1038/s41593-026-02207-1","DOIUrl":"https://doi.org/10.1038/s41593-026-02207-1","url":null,"abstract":"Visual neurons respond to a vast range of images, from textures to objects, but the rules linking these responses remain unclear. Although tuning to simple features is well established in the primary visual cortex, this framework breaks down in higher areas, where neurons encode diverse and unpredictable features. To ask what features neurons prioritize, we used generative models (deep networks that synthesize new images from a learned latent space), allowing neurons in V1, V4 and the posterior inferotemporal cortex (PIT) to guide image synthesis through closed-loop optimization. We compared models that emphasize texture versus those that emphasize object structure. Although V1 and V4 aligned more strongly with texture-based spaces, many PIT neurons responded equally well to both types of optimized images, revealing a focus on shared local motifs rather than whole-object templates, and this alignment to objects emerged later in their response. These findings reveal coding principles across the ventral stream and clarify the limits of current vision models.","PeriodicalId":19076,"journal":{"name":"Nature neuroscience","volume":"52 1","pages":""},"PeriodicalIF":25.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381750","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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