Pub Date : 2026-01-02DOI: 10.1038/s41583-025-01015-z
Monray. E. Williams, Lindokuhle Thela, Charles Wood, Robert H. Paul, Vurayai Ruhanya, Petrus J. W. Naude, Eliseo Eugenin
Despite advances in HIV-1 treatment, half of all people living with HIV-1 experience HIV-associated neurocognitive disorders (HAND). Most of our understanding of HAND neuropathogenesis comes from studies of individuals with HIV-1 subtype B, which is responsible for a small proportion of global HIV-1 infections. By contrast, HIV-1 subtype C, which predominates in sub-Saharan Africa, affects many more people but remains poorly characterized, limiting our understanding of HAND at a global level.
{"title":"HIV-1 subtype diversity in the pathogenesis of neuroHIV","authors":"Monray. E. Williams, Lindokuhle Thela, Charles Wood, Robert H. Paul, Vurayai Ruhanya, Petrus J. W. Naude, Eliseo Eugenin","doi":"10.1038/s41583-025-01015-z","DOIUrl":"10.1038/s41583-025-01015-z","url":null,"abstract":"Despite advances in HIV-1 treatment, half of all people living with HIV-1 experience HIV-associated neurocognitive disorders (HAND). Most of our understanding of HAND neuropathogenesis comes from studies of individuals with HIV-1 subtype B, which is responsible for a small proportion of global HIV-1 infections. By contrast, HIV-1 subtype C, which predominates in sub-Saharan Africa, affects many more people but remains poorly characterized, limiting our understanding of HAND at a global level.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"81-82"},"PeriodicalIF":26.7,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145889776","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 : 2025-12-10DOI: 10.1038/s41583-025-01011-3
Erfan Nozari
In this Journal Club, Erfan Nozari discusses work detailing a simple, transparent algorithm for iEEG mapping of seizure onset zones and the emergent property of neural fragility at its core.
{"title":"On the power of simple models: when emergent properties predict clinical outcomes","authors":"Erfan Nozari","doi":"10.1038/s41583-025-01011-3","DOIUrl":"10.1038/s41583-025-01011-3","url":null,"abstract":"In this Journal Club, Erfan Nozari discusses work detailing a simple, transparent algorithm for iEEG mapping of seizure onset zones and the emergent property of neural fragility at its core.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"86-86"},"PeriodicalIF":26.7,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717614","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 : 2025-12-08DOI: 10.1038/s41583-025-00998-z
Moritz Helmstaedter
Neuronal circuits are the key target of both evolutionary and individual adaptation that enable organisms to successfully navigate, predict and shape their environment. Synaptic-resolution connectomics has the ambition to map neuronal circuits at scale to uncover the phylogenetic and ontogenetic implementations realized across the animal kingdom. The past 20 years have seen an ambitious methodological agenda using large-scale 3D electron microscopy and machine learning that have expanded, by a factor of 1,000, the connectomically accessible volumes at synaptic resolution from about 100 µm3 to about 1 mm3. This implies that the field can now move beyond specialized miniature circuits to a large range of local neuropil in mice, including areas of cortical grey matter. Resolving the local cortical circuits of larger brains, including human, and whole-brain synaptic connectomes of small reptiles, rodents, birds and non-human primates is the next major target. In this Review, the critical methodological innovations in brain tissue preparation, ablation or sectioning, imaging and artificial intelligence-based 3D image analysis are discussed alongside remaining challenges, in particular for connectomic mapping of centimetre-scale circuits such as a whole adult mouse brain. Importantly, these advances at the connectomic frontier are now enabling the multifold mapping of comparably smaller circuits. This will enable connectomic screening for the study of complex interactions between evolutionary determinism, individual experience and behavioural performance, as well as age-dependent and pathological alterations of connectomes. Connectomics has delivered on its promise to map neuronal circuits at scale and at synaptic resolution. In this Review, Helmstaedter describes recent methodological achievements and remaining challenges in synaptic-resolution connectomics while synthesizing expanding connectomic mapping ambitions that include resolving local circuits of larger brains and screening of connectomes.
{"title":"Synaptic-resolution connectomics: towards large brains and connectomic screening","authors":"Moritz Helmstaedter","doi":"10.1038/s41583-025-00998-z","DOIUrl":"10.1038/s41583-025-00998-z","url":null,"abstract":"Neuronal circuits are the key target of both evolutionary and individual adaptation that enable organisms to successfully navigate, predict and shape their environment. Synaptic-resolution connectomics has the ambition to map neuronal circuits at scale to uncover the phylogenetic and ontogenetic implementations realized across the animal kingdom. The past 20 years have seen an ambitious methodological agenda using large-scale 3D electron microscopy and machine learning that have expanded, by a factor of 1,000, the connectomically accessible volumes at synaptic resolution from about 100 µm3 to about 1 mm3. This implies that the field can now move beyond specialized miniature circuits to a large range of local neuropil in mice, including areas of cortical grey matter. Resolving the local cortical circuits of larger brains, including human, and whole-brain synaptic connectomes of small reptiles, rodents, birds and non-human primates is the next major target. In this Review, the critical methodological innovations in brain tissue preparation, ablation or sectioning, imaging and artificial intelligence-based 3D image analysis are discussed alongside remaining challenges, in particular for connectomic mapping of centimetre-scale circuits such as a whole adult mouse brain. Importantly, these advances at the connectomic frontier are now enabling the multifold mapping of comparably smaller circuits. This will enable connectomic screening for the study of complex interactions between evolutionary determinism, individual experience and behavioural performance, as well as age-dependent and pathological alterations of connectomes. Connectomics has delivered on its promise to map neuronal circuits at scale and at synaptic resolution. In this Review, Helmstaedter describes recent methodological achievements and remaining challenges in synaptic-resolution connectomics while synthesizing expanding connectomic mapping ambitions that include resolving local circuits of larger brains and screening of connectomes.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"101-120"},"PeriodicalIF":26.7,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696661","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 : 2025-12-05DOI: 10.1038/s41583-025-01010-4
N. Alex Cayco-Gajic
In this Journal Club, N. Alex Cayco-Gajic discusses a study published in 2004 that modelled the pyloric network of the lobster stomatogastric ganglion.
在这个杂志俱乐部中，N. Alex Cayco-Gajic讨论了2004年发表的一项研究，该研究模拟了龙虾口胃神经节的幽门网络。
{"title":"Learning in the overparametrized brain","authors":"N. Alex Cayco-Gajic","doi":"10.1038/s41583-025-01010-4","DOIUrl":"10.1038/s41583-025-01010-4","url":null,"abstract":"In this Journal Club, N. Alex Cayco-Gajic discusses a study published in 2004 that modelled the pyloric network of the lobster stomatogastric ganglion.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"85-85"},"PeriodicalIF":26.7,"publicationDate":"2025-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680118","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 : 2025-12-04DOI: 10.1038/s41583-025-00992-5
Matthew C. Rosen, David J. Freedman
Half a century of neurophysiological recordings from single electrodes established a ‘localized’ viewpoint on function in the brain — that complex behaviour results from computations that are carried out and representations that occur across distinct brain areas, each of which has a specialized role. Data generated from new techniques for specific, high-throughput measurement of neuronal activity and behaviour in rodents have prompted an alternative viewpoint, which posits that neural encoding of behavioural variables is distributed across a wide range of areas: ‘everything, everywhere, all at once’. After briefly introducing these paradigms, we evaluate which of them better describes cognition — the manipulation of internal variables that enables flexible behaviour. Measurements of neuronal activity in both rodents and primates suggest that cognitive variables are reflected broadly but not ubiquitously across the brain, including, to a surprising degree, in regions engaged in controlling movement. We close by discussing why cognitive signals may appear in such areas, as well as the factors that affect the breadth of the brain-wide network that is recruited for cognition. Both localized and distributed views on the functional organization of the brain have been put forward. In this Perspective, Rosen and Freedman examine the degree to which these two views account for abstract cognition.
{"title":"How distributed is the brain-wide network that is recruited for cognition?","authors":"Matthew C. Rosen, David J. Freedman","doi":"10.1038/s41583-025-00992-5","DOIUrl":"10.1038/s41583-025-00992-5","url":null,"abstract":"Half a century of neurophysiological recordings from single electrodes established a ‘localized’ viewpoint on function in the brain — that complex behaviour results from computations that are carried out and representations that occur across distinct brain areas, each of which has a specialized role. Data generated from new techniques for specific, high-throughput measurement of neuronal activity and behaviour in rodents have prompted an alternative viewpoint, which posits that neural encoding of behavioural variables is distributed across a wide range of areas: ‘everything, everywhere, all at once’. After briefly introducing these paradigms, we evaluate which of them better describes cognition — the manipulation of internal variables that enables flexible behaviour. Measurements of neuronal activity in both rodents and primates suggest that cognitive variables are reflected broadly but not ubiquitously across the brain, including, to a surprising degree, in regions engaged in controlling movement. We close by discussing why cognitive signals may appear in such areas, as well as the factors that affect the breadth of the brain-wide network that is recruited for cognition. Both localized and distributed views on the functional organization of the brain have been put forward. In this Perspective, Rosen and Freedman examine the degree to which these two views account for abstract cognition.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"138-150"},"PeriodicalIF":26.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664511","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 : 2025-12-04DOI: 10.1038/s41583-025-01007-z
Li Ji-An
In this Tools of the Trade article, Li Ji-An describes tiny recurrent neural networks, an interpretable and flexible modelling framework for discovering cognitive algorithms that govern biological decision-making.
{"title":"Tiny recurrent neural networks for discovering cognitive strategies","authors":"Li Ji-An","doi":"10.1038/s41583-025-01007-z","DOIUrl":"10.1038/s41583-025-01007-z","url":null,"abstract":"In this Tools of the Trade article, Li Ji-An describes tiny recurrent neural networks, an interpretable and flexible modelling framework for discovering cognitive algorithms that govern biological decision-making.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"83-83"},"PeriodicalIF":26.7,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674445","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 : 2025-12-03DOI: 10.1038/s41583-025-00996-1
Mackenzie Weygandt Mathis, Alexander Mathis
Artificial intelligence has created tremendous advances for many scientific and engineering applications. In this Review, we synthesize recent advances in joint brain–behaviour modelling of neural and behavioural data, with a focus on methodological innovations, scientific and technical motivations, and key areas for future innovation. We discuss how these tools reveal the shared structure between the brain and behaviour and how they can be used for both science and engineering aims. We highlight how three broad classes with differing aims — discriminative, generative and contrastive — are shaping joint modelling approaches. We also discuss recent advances in behavioural analysis approaches, including pose estimation, hierarchical behaviour analysis and multimodal-language models, which could influence the next generation of joint models. Finally, we argue that considering not only the performance of models but also their trustworthiness and interpretability metrics can help to advance the development of joint modelling approaches. Artificial intelligence is rapidly advancing our mechanistic understanding of the shared structure between the brain and higher-order behaviours. In this Review, Mathis and Mathis synthesize state-of-the-art methods in joint modelling of neural activity and behaviour, emphasizing both the technical innovations and the conceptual frameworks driving progress in this rapidly evolving field.
{"title":"Joint modelling of brain and behaviour dynamics with artificial intelligence","authors":"Mackenzie Weygandt Mathis, Alexander Mathis","doi":"10.1038/s41583-025-00996-1","DOIUrl":"10.1038/s41583-025-00996-1","url":null,"abstract":"Artificial intelligence has created tremendous advances for many scientific and engineering applications. In this Review, we synthesize recent advances in joint brain–behaviour modelling of neural and behavioural data, with a focus on methodological innovations, scientific and technical motivations, and key areas for future innovation. We discuss how these tools reveal the shared structure between the brain and behaviour and how they can be used for both science and engineering aims. We highlight how three broad classes with differing aims — discriminative, generative and contrastive — are shaping joint modelling approaches. We also discuss recent advances in behavioural analysis approaches, including pose estimation, hierarchical behaviour analysis and multimodal-language models, which could influence the next generation of joint models. Finally, we argue that considering not only the performance of models but also their trustworthiness and interpretability metrics can help to advance the development of joint modelling approaches. Artificial intelligence is rapidly advancing our mechanistic understanding of the shared structure between the brain and higher-order behaviours. In this Review, Mathis and Mathis synthesize state-of-the-art methods in joint modelling of neural activity and behaviour, emphasizing both the technical innovations and the conceptual frameworks driving progress in this rapidly evolving field.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"87-100"},"PeriodicalIF":26.7,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664345","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 : 2025-12-02DOI: 10.1038/s41583-025-01004-2
Sander van Bree, David Poeppel
{"title":"Top-down and bottom-up neuroscience as collections of practices","authors":"Sander van Bree, David Poeppel","doi":"10.1038/s41583-025-01004-2","DOIUrl":"10.1038/s41583-025-01004-2","url":null,"abstract":"","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"79-79"},"PeriodicalIF":26.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656989","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 : 2025-12-02DOI: 10.1038/s41583-025-01006-0
Andrea I. Luppi, Fernando E. Rosas
{"title":"Reply to ‘Top-down and bottom-up neuroscience as collections of practices’","authors":"Andrea I. Luppi, Fernando E. Rosas","doi":"10.1038/s41583-025-01006-0","DOIUrl":"10.1038/s41583-025-01006-0","url":null,"abstract":"","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 1","pages":"80-80"},"PeriodicalIF":26.7,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656990","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}
{"title":"Mixed selectivity: when neurons stopped looking like specialists","authors":"Fanny Cazettes","doi":"10.1038/s41583-025-01009-x","DOIUrl":"10.1038/s41583-025-01009-x","url":null,"abstract":"In this Journal Club, Fanny Cazettes highlights a 2013 paper that demonstrated the importance of mixed selectivity for cortical computations.","PeriodicalId":49142,"journal":{"name":"Nature Reviews Neuroscience","volume":"27 2","pages":"84-84"},"PeriodicalIF":26.7,"publicationDate":"2025-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145599443","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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