Journal of Neuroscience最新文献

{"title":"VIP-to-SST Cell Circuit Motif Shows Differential Short-Term Plasticity across Sensory Areas of Mouse Cortex.","authors":"Jenifer Rachel, Martin Möck, Tanya L Daigle, Bosiljka Tasic, Mirko Witte, Jochen F Staiger","doi":"10.1523/JNEUROSCI.0949-24.2025","DOIUrl":"10.1523/JNEUROSCI.0949-24.2025","url":null,"abstract":"<p><p>Inhibition of GABAergic interneurons has been found to critically fine-tune the excitation-inhibition balance of the cortex. Inhibition is mediated by many connectivity motifs formed by GABAergic neurons. One such motif is the inhibition of somatostatin (SST)-expressing neurons by vasoactive intestinal polypeptide (VIP)-expressing neurons. We studied the synaptic properties of layer (L) 2/3 VIP cells onto L4 SST cells in somatosensory (S1) and visual (V1) cortices of mice of either sex using paired whole-cell patch-clamp recordings, followed by morphological reconstructions. We identified strong differences in the morphological features of L4 SST cells, wherein cells in S1 fell into the non-Martinotti cell (nMC) subclass, while in V1 presented with Martinotti cell (MC)-like features. Approximately 40-45% of tested SST cells were inhibited by VIP cells in both cortices. While unitary connectivity properties of the VIP-to-nMC and VIP-to-MC motifs were comparable, we observed stark differences in short-term plasticity. During high-frequency stimulation of both motifs, some connections showed short-term facilitation while others showed a stable response, with a fraction of VIP-to-nMC connections showing short-term depression. We thus provide evidence that VIP cells target morphological subclasses of SST cells differentially, forming cell-type-specific inhibitory motifs.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371429","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":"Contribution of Rat Insular Cortex to Stimulus-Guided Action.","authors":"Yacine Tensaouti, Louis Morel, Shauna L Parkes","doi":"10.1523/JNEUROSCI.1923-24.2025","DOIUrl":"10.1523/JNEUROSCI.1923-24.2025","url":null,"abstract":"<p><p>Anticipating rewards is fundamental for decision-making. Animals often use cues to assess reward availability and to make predictions about future outcomes. The gustatory region of the insular cortex (IC), the so-called gustatory cortex, has a well-established role in the representation of predictive cues, such that IC neurons encode both a general form of outcome expectation and anticipatory outcome-specific knowledge. Here, we used pavlovian-instrumental transfer (PIT) in male rats to assess if the IC is also required for predictive cues to exert both a general and specific influence over instrumental actions. Chemogenetic inhibition of IC impaired the ability of a reward-predictive stimulus to energize instrumental responding for reward. This deficit in general transfer was evident whether the same or different outcomes were used in the pavlovian and instrumental conditioning phases. We observed a similar deficit in specific PIT, such that rats with IC inhibition failed to use a reward-predictive stimulus to guide choice toward actions that deliver the same food reward. Finally, we show that rats with IC inhibition also fail to show outcome-selective reinstatement. Together, these data suggest a crucial role for IC in the representation of appetitive outcomes and particularly in using this representation to guide instrumental action.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069311","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":"Volitional Regulation and Transferable Patterns of Midbrain Oscillations.","authors":"Hung-Yun Lu 呂宏耘, Yi Zhao 趙懿, Hannah M Stealey, Cole R Barnett, Philippe N Tobler, Samantha R Santacruz","doi":"10.1523/JNEUROSCI.1808-24.2025","DOIUrl":"10.1523/JNEUROSCI.1808-24.2025","url":null,"abstract":"<p><p>Dopaminergic brain areas are crucial for cognition and their dysregulation is linked to neuropsychiatric disorders typically treated with pharmacological interventions. These treatments often have side effects and variable effectiveness, underscoring the need for alternatives. We introduce the first demonstration of neurofeedback using local field potentials (LFP) from the ventral tegmental area (VTA). This approach leverages the real-time temporal resolution of LFP and ability to target deep brain. In our study, two male rhesus macaque monkeys (Macaca mulatta) learned to regulate VTA beta power using a customized normalized metric to stably quantify VTA LFP signal modulation. The subjects demonstrated flexible and specific control with different strategies for specific frequency bands, revealing new insights into the plasticity of VTA neurons contributing to oscillatory activity that is functionally relevant to many aspects of cognition. Excitingly, the subjects showed transferable patterns, a key criterion for clinical applications beyond training settings. This work provides a foundation for neurofeedback-based treatments, which may be a promising alternative to conventional approaches and open new avenues for understanding and managing neuropsychiatric disorders.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143256762","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":"ACC reward location information is carried by hippocampal theta synchrony and suppressed in a Type 2 Diabetes model.","authors":"Guncha Bhasin, Emmanuel Flores, Lauren A Crew, Ryan A Wirt, Andrew A Ortiz, Jefferson W Kinney, James M Hyman","doi":"10.1523/JNEUROSCI.1546-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1546-24.2025","url":null,"abstract":"<p><p>The anterior cingulate cortex (ACC) is important for higher order cognitive functions, emotional responses, and monitoring internal states. ACC dysfunction has been implicated in an array of psychiatric and neurodegenerative disorders which have a bidirectional relationship with the metabolic disorder Type 2 diabetes (T2D). T2D is a chronic disease characterized by hyperglycemia, loss of insulin signaling, neuroinflammation, and increased morbidity and mortality chances. To better understand the functional effects of T2D on ACC information processing, we delivered an intermittent, low dose streptozotocin (STZ) protocol to rats (all male due to female insensitivity to STZ) which led to lasting hyperglycemia and recorded single neurons during a delayed alternation task. We observed changes in spatial and reward processing in spite of no differences in overall behavioral accuracy, though we did find hyperglycemic animals spent less time at the reward site. Hyperglycemic animal (n=5) ACC neurons had higher spatial information scores and changes in the allotment of spatial coding assets. Specifically, the hyperglycemic group had greatest spatial information during the reward approach, while in controls (n=3) it was uniformly distributed. We found that state space separation and decoding accuracy were greater in control ensembles at the reward location. Furthermore, control hippocampal theta phase-locked cells had the strongest reward coding and this effect was absent in hyperglycemic animals, leading to a muted reward representation, despite increased reward approach coding. T2D inferred a nuanced and layered effect on ACC activity, leading to reward coding deficits and a differential change in spatial coding properties.<b>Significance Statement</b> Type 2 diabetes (T2D) is a major health challenge in the 21st century and makes patients more prone to psychiatric and neurodegenerative disorders. In this paper, we show that neural information processing in the anterior cingulate cortex (ACC), a central area for goal directed behavior, is altered in multiple ways in a T2D rodent model during a spatial working memory task. Notably, data reveal altered spatial information in ACC cells and muted reward location coding specifically in hippocampal theta modulated ACC neurons and ensembles. The finding of altered reward processing in the ACC that manifested as a shorter post-reinforcement pause, invites profound questions given the importance of lifestyle interventions to treat T2D.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702024","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":"Acoustic enrichment prevents early life stress-induced disruptions in sound azimuth processing.","authors":"Pengying An, Yue Fang, Yuan Cheng, Hui Liu, Wenjing Yang, Ye Shan, Etienne de Villers-Sidani, Guimin Zhang, Xiaoming Zhou","doi":"10.1523/JNEUROSCI.2287-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.2287-24.2025","url":null,"abstract":"<p><p>Early life stress (ELS) has been shown to disrupt cognitive and limbic functions, yet its impact on sensory systems, particularly the auditory system, remains insufficiently understood. In this study, we investigated the enduring effects of ELS induced by neonatal maternal separation (MS) on behavioral and cortical processing of sound azimuth in adult male rats. We found that MS significantly impairs sound-azimuth discrimination, paralleled by broader azimuth tuning and reduced dendritic branching and spine density in neurons within the primary auditory cortex. Notably, exposure to an enriched acoustic environment during the stress period effectively protects against these MS-induced alterations, restoring behavioral performance, cortical tuning, and dendritic spine density of neurons to levels comparable to controls. Further analyses reveal that epigenetic regulation of cortical brain-derived neurotrophic factor by histone H3 lysine 9 dimethylation may underlie the observed changes in cortical structure and function. These results underscore the profound and lasting impact of MS-induced ELS on auditory processing, particularly within cortical circuits involved in spatial processing. They suggest that sensory enrichment is a potential therapeutic strategy to ameliorate the adverse effects of ELS on sensory processing, with broader implications for understanding and treating sensory deficits in stress-related disorders.<b>Significance Statement</b> The contribution of early life stress (ELS) to sensory deficits in stress-related disorders remains largely unexplored. Here we show that ELS induced by neonatal maternal separation (MS) disrupts behavioral and cortical processing of sound azimuth in adult rats. Moreover, pairing MS with enriched acoustic exposure during the stress period alleviates these deficits in maternally separated rats. Epigenetic modulation of brain-derived neurotrophic factor gene expression by histone H3 lysine 9 dimethylation in the cortex may underlie the MS-effects and their reversal through acoustic enrichment. These findings reveal the enduring effects of ELS on sensory processing, emphasizing its broader implications for understanding stress-related disorders. Importantly, they highlight sensory enrichment as a promising therapeutic strategy to prevent sensory deficits associated with such conditions.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701941","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":"Spike rate inference from mouse spinal cord calcium imaging data.","authors":"Peter Rupprecht, Wei Fan, Steve J Sullivan, Fritjof Helmchen, Andrei D Sdrulla","doi":"10.1523/JNEUROSCI.1187-24.2025","DOIUrl":"10.1523/JNEUROSCI.1187-24.2025","url":null,"abstract":"<p><p>Calcium imaging is a key method to record the spiking activity of identified and genetically targeted neurons. However, the observed calcium signals are only an indirect readout of the underlying electrophysiological events (single spikes or bursts of spikes) and require dedicated algorithms to recover the spike rate. These algorithms for spike inference can be optimized using ground truth data from combined electrical and optical recordings, but it is not clear how such optimized algorithms perform on cell types and brain regions for which ground truth does not exist. Here, we use a state-of-the-art algorithm based on supervised deep learning (CASCADE) and a non-supervised algorithm based on non-negative deconvolution (OASIS) to test spike rate inference in spinal cord neurons. To enable these tests, we recorded specific ground truth from glutamatergic and GABAergic somatosensory neurons in the superficial dorsal horn of spinal cord in mice of both sexes. We find that CASCADE and OASIS algorithms that were designed for cortical excitatory neurons generalize well to both spinal cord cell types. However, CASCADE models re-trained on our ground truth further improved the performance, resulting in a more accurate inference of spiking activity from spinal cord neurons. We openly provide re-trained models that can be applied to spinal cord data with variable noise levels and frame rates. Together, our ground-truth recordings and analyses provide a solid foundation for the interpretation of calcium imaging data from spinal cord dorsal horn and showcase how spike rate inference can generalize between different regions of the nervous system.<b>Significance Statement</b> Calcium imaging is a powerful method for measuring the activity of genetically identified neurons. However, accurate interpretation of calcium transients depends on having a detailed understanding of how neuronal activity correlates with fluorescence. Such calibration recordings have been performed for cerebral cortex but not yet for most other CNS regions and neuron types. Here, we obtained ground truth data in spinal cord by conducting simultaneous calcium and electrophysiology recordings in excitatory and inhibitory neurons. We systematically investigated the transferability of cortical algorithms to spinal neuron subpopulations and generated inference algorithms optimized to excitatory and inhibitory neurons. Our study provides a foundation for the rigorous interpretation of calcium imaging data from spinal cord.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702059","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":"Leptin activates dopamine and GABA neurons in the substantia nigra via a local pars compacta-pars reticulata circuit.","authors":"Maria Mancini, Takuya Hikima, Paul Witkovsky, Jyoti C Patel, Dominic W Stone, Alison H Affinati, Margaret E Rice","doi":"10.1523/JNEUROSCI.1539-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1539-24.2025","url":null,"abstract":"<p><p>Adipose-derived leptin contributes to energy homeostasis by balancing food intake and motor output, but how leptin acts in brain motor centers remains poorly understood. We investigated the influence of leptin on neuronal activity in two basal ganglia nuclei involved in motor control: the substantia nigra pars compacta (SNc) and pars reticulata (SNr). Using a mouse reporter line to identify cells expressing leptin receptors (LepRs), we found that in both sexes, a majority of SNc dopamine neurons express a high level of LepR. Whole-cell recording in ex vivo midbrain slices from male wild-type mice showed that leptin activates SNc dopamine neurons directly and increases somatodendritic dopamine release. Although LepR expression in SNr GABA output neurons was low, leptin also activated these cells. Additional experiments showed that the influence of leptin on SNr neurons is indirect and involves D1 dopamine receptors and TRPC3 channels. Administration of leptin to male mice increased locomotor activity, consistent with activation of dopamine neurons in the SNc coupled to previously reported amplification of axonal dopamine release by leptin in striatal slices. These findings indicate that in addition to managing energy homeostasis through its actions as a satiety hormone, leptin also promotes axonal and somatodendritic dopamine release that can influence motor output.<b>Significance statement</b> Dopamine neurons regulate motivated behaviors, but how they are influenced by metabolic hormones, like leptin, is incompletely understood. We show here that leptin increases the activity of substantia nigra (SN) pars compacta dopamine neurons directly, and that this enhances somatodendritic dopamine release. Leptin also increases the activity of GABAergic neurons in the SN pars reticulata, but does so indirectly via D1 dopamine receptors activated by locally released dopamine. Consistent with increased nigral dopamine neuron activity and previous evidence showing that leptin amplifies striatal dopamine release, systemic leptin increases locomotor behavior. This increase in motor activity complements the well-established inhibitory effect of leptin on food intake and adds an additional dimension to the regulation of energy balance by this hormone.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702057","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":"Anatomically distinct regions in the inferior frontal cortex are modulated by task and reading skill.","authors":"Hannah L Stone, Jamie L Mitchell, Mia Fuentes-Jimenez, Jasmine E Tran, Jason D Yeatman, Maya Yablonski","doi":"10.1523/JNEUROSCI.1767-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1767-24.2025","url":null,"abstract":"<p><p>Inferior frontal cortex (IFC) is a critical region for reading and language. This part of the cortex is highly heterogeneous in its structural and functional organization and shows high variability across individuals. Despite decades of research, the relationship between specific IFC regions and reading skill remains unclear. To shed light on the function of IFC in reading, we aim to (1) characterize the functional landscape of text-selective responses in IFC, while accounting for interindividual variability; and (2) examine how text-selective regions in the IFC relate to reading proficiency. To this end, children with a wide range of reading ability (N=66; age 7-14 years, 34 female, 32 male) completed functional MRI scans while performing two tasks on text and non-text visual stimuli. Importantly, both tasks do not explicitly require reading, and can be performed on all visual stimuli. This design allows us to tease apart stimulus-driven responses from task-driven responses and examine where in IFC task and stimulus interact. We were able to identify three anatomically-distinct, text-selective clusters of activation in IFC, in the inferior frontal sulcus (IFS), and dorsal and ventral precentral gyrus (PrG). ​​These three regions showed a strong task effect that was highly specific to text. Furthermore, text-selectivity in the IFS and dorsal PrG was associated with reading proficiency, such that better readers showed higher selectivity to text. These findings suggest that text-selective regions in the IFC are sensitive to both stimulus and task, and highlight the importance of this region for proficient reading.<b>Significance statement</b> The inferior frontal cortex (IFC) is a critical region for language processing, yet despite decades of research, its relationship with reading skill remains unclear. In a group of children with a wide range of reading skills, we were able to identify three anatomically distinct text-selective clusters of activation in the IFC. ​​These regions showed a strong task effect that was highly selective to text. Text-selectivity was positively correlated with reading proficiency, such that better readers showed higher selectivity to text, even in tasks that did not require reading. These findings suggest that multiple text-selective regions within IFC are sensitive to both stimulus and task, and highlight the critical role of IFC for reading proficiency.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702013","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":"CCKergic Tufted Cells Regulate Odor Sensitivity by Controlling Mitral Cell Output in the Mouse Olfactory Bulb.","authors":"Eric Starr, Rashika Budhathoki, Dylan Gilhooly, Laura Castillo, Meigeng Hu, Dan Zhao, Yaping Li, Shaolin Liu","doi":"10.1523/JNEUROSCI.1243-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1243-24.2025","url":null,"abstract":"<p><p>Despite the importance of odor detection to the survival of most animals, mechanisms governing olfactory sensitivity remain unclear, especially beyond the olfactory sensory neurons (OSNs). Here we leverage opto- and chemo-genetics to selectively modulate activities of CCKergic tufted cells (TCs) in the mouse olfactory bulb (OB) of either sex, which form the intrabulbar associational system (IAS) to link isofunctional glomeruli, to determine the functional impact on OB output via mitral cells (MCs) and odor detection in behaving animals. NMDA receptors in CCKergic TCs remarkably amplify the OSN-evoked monosynaptic responses in these excitatory neurons, which provide a long-lasting feedforward excitation to MCs via both chemical transmission and electrical synapses between their apical dendrites. NMDA receptors in MCs mediate late components of the dendrodendritic TC→MC transmission to significantly boost MC outcome. Congruently, optogenetic inhibition of the CCKerigic TCs dramatically reduces the OSN-evoked MC responses. Unexpectedly, optogenetic activation of the axons projecting from CCKergic TCs on the opposite side of the same bulb produces a mainly AMPA receptor-mediated excitatory responses in MCs, leading us to speculate that CCKergic TCs functionally synchronize MC output from mirror glomeruli. Furthermore, chemogenetic inhibition of CCKergic TCs reduces animal's sensitivity to odors by elevating detection threshold, consistent with the key role of these TCs in functionally controlling MC output. Collectively, our results delineate the cellular and circuit mechanisms allowing the CCKergic TCs to regulate MC output from glomeruli on both medial and lateral side of each OB and the system's sensitivity to odors possibly via the IAS.<b>Significance Statement</b> The detection and processing of chemical stimuli, such as environmental odorants, are essential for the central nervous system to generate appropriate behavioral responses in animals. Most of our current knowledge about odor detection comes from studies on the interactions between chemical stimuli and odorant receptors on olfactory sensory neurons (OSNs) at the periphery. In this study, we have identified a specific subpopulation of nerve cells that play a crucial role in converting sensory input into biological signals within the olfactory bulb, the downstream target of OSNs and the initial site of synaptic odor processing. Our findings provide new insights into the cellular and circuit-level mechanisms that regulate olfactory detection beyond sensory neurons.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702015","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":"Overlapping Cortical Substrate of Biomechanical Control and Subjective Agency.","authors":"John P Veillette, Alfred F Chao, Romain Nith, Pedro Lopes, Howard C Nusbaum","doi":"10.1523/JNEUROSCI.1673-24.2025","DOIUrl":"https://doi.org/10.1523/JNEUROSCI.1673-24.2025","url":null,"abstract":"<p><p>Every movement requires the nervous system to solve a complex biomechanical control problem, but this process is mostly veiled from one's conscious awareness. Simultaneously, we also have conscious experience of controlling our movements-our sense of agency (SoA). Whether SoA corresponds to those neural representations that implement actual neuromuscular control is an open question with ethical, medical, and legal implications. If SoA is the conscious experience of control, this predicts that SoA can be decoded from the same brain structures that implement the so-called \"inverse dynamics\" computations for planning movement. We correlated human (male and female) fMRI measurements during hand movements with the internal representations of a deep neural network (DNN) performing the same hand control task in a biomechanical simulation-revealing detailed cortical encodings of sensorimotor states, idiosyncratic to each subject. We then manipulated SoA by usurping control of participants' muscles via electrical stimulation, and found that the same voxels which were best explained by modeled inverse dynamics representations-which, strikingly, were located in canonically visual areas-also predicted SoA. Importantly, model-brain correspondences and robust SoA decoding could both be achieved within single subjects, enabling relationships between motor representations and awareness to be studied at the level of the individual.<b>Significance Statement</b> The inherent complexity of biomechanical control problems is belied by the seeming simplicity of directing movements in our subjective experience. This aspect of our experience suggests we have limited conscious access to the neural and mental representations involved in controlling the body - but of which of the many possible representations are we, in fact, aware? Understanding which motor control representations percolate into awareness has taken on increasing importance as emerging neural interface technologies push the boundaries of human autonomy. In our study, we leverage machine learning models that have learned to control simulated bodies to localize biomechanical control representations in the brain. Then, we show that these brain regions predict perceived agency over the musculature during functional electrical stimulation.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143702058","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}