Macaque primary visual cortex (V1) exhibits exquisite columnar organization, while midlevel area V4 does not. Here we investigated the functional organization and representational bases of intervening area V2 in three macaques (one male, two females) with high-density Neuropixels recordings and a variety of visual stimuli-shape, texture, drifting grating, and translational motion patches. We observed dense clusters of similarly tuned neurons often spanning ∼500 µm, consistent with a columnar structure. In terms of representational bases, V2 responses were largely explained by stimulus features based on local image statistics: shape tuning is well-modeled by a linear combination of orientation filters, and direction selectivity is stronger with surface compared to object motion, in striking contrast to V4. Overall, our results support the progression from columns to sparse clusters as neuronal representations transform from encoding local features and feature conjunctions in V1/V2 to a high-dimensional object-based code in V4.Significance Statement By recording hundreds of neurons simultaneously across layers of macaque visual area V2, we show the first evidence of exquisite fine-scale functional clusters that encode higher-order shape, texture, and motion features, extending well beyond the classic orientation-selective columns seen in area V1. Comparative analyses with V4 further reveal distinct representational bases and organization patterns between adjacent cortical areas, demonstrating that columnar organization is preserved in early visual areas (V1 and V2) but is markedly attenuated in higher-order cortex such as V4.
{"title":"Functional clusters for shape, texture, and motion encoding in macaque V2.","authors":"Taekjun Kim, Rohit Kamath, Gaku Hatanaka, Tomoyuki Namima, Celeste Dylla, Wyeth Bair, Anitha Pasupathy","doi":"10.1523/JNEUROSCI.1994-25.2026","DOIUrl":"10.1523/JNEUROSCI.1994-25.2026","url":null,"abstract":"<p><p>Macaque primary visual cortex (V1) exhibits exquisite columnar organization, while midlevel area V4 does not. Here we investigated the functional organization and representational bases of intervening area V2 in three macaques (one male, two females) with high-density Neuropixels recordings and a variety of visual stimuli-shape, texture, drifting grating, and translational motion patches. We observed dense clusters of similarly tuned neurons often spanning ∼500 µm, consistent with a columnar structure. In terms of representational bases, V2 responses were largely explained by stimulus features based on local image statistics: shape tuning is well-modeled by a linear combination of orientation filters, and direction selectivity is stronger with surface compared to object motion, in striking contrast to V4. Overall, our results support the progression from columns to sparse clusters as neuronal representations transform from encoding local features and feature conjunctions in V1/V2 to a high-dimensional object-based code in V4.<b>Significance Statement</b> By recording hundreds of neurons simultaneously across layers of macaque visual area V2, we show the first evidence of exquisite fine-scale functional clusters that encode higher-order shape, texture, and motion features, extending well beyond the classic orientation-selective columns seen in area V1. Comparative analyses with V4 further reveal distinct representational bases and organization patterns between adjacent cortical areas, demonstrating that columnar organization is preserved in early visual areas (V1 and V2) but is markedly attenuated in higher-order cortex such as V4.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357057","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}
Pub Date : 2026-03-04DOI: 10.1523/JNEUROSCI.0303-25.2026
Vaclav Kremen, Vladimir Sladky, Vaclav Gerla, Yurui Cao, Filip Mivalt, Erik K St Louis, Mark R Bower, Benjamin H Brinkmann, Kai Miller, Jamie VanGompel, Mark Cook, Tim Denison, Kent Leyde, Gregory A Worrell
Bidirectional interactions between sleep, seizures, and epilepsy remain incompletely understood. Evidence from animal models and people with focal epilepsy suggest that seizures may engage mechanisms of memory consolidation during post-ictal sleep to reinforce and strengthen synaptic connections within the pathological networks that generates seizures, termed seizure-related consolidation (SRC). Human studies of post-ictal sleep changes supportive of SRC, however, are limited by small sample size and restricted observations of post-ictal sleep. We investigated the interplay between seizures and sleep by analyzing sleep-wake and seizure catalogs derived from continuous local field potential (LFP) recordings in 11 people (6 males and 5 females) with drug-resistant focal epilepsy implanted with novel investigational devices and living in their natural environments. Our findings demonstrate that post-ictal rapid-eye-movement sleep duration is reduced, whereas slow-wave sleep duration, slow-wave LFP spectral power, and waveform slope are increased compared with inter-ictal nights without preceding seizures. The most significant changes localize to the epileptogenic networks generating the participants' habitual seizures. These results reveal parallels between SRC and physiological memory consolidation, providing novel insights into the potential role of post-ictal sleep in strengthening epileptic neural engrams and may have implications for targeted disruption of post-ictal sleep and SRC in focal epilepsy.
{"title":"Post-Ictal Sleep Changes in Human Focal Epilepsy.","authors":"Vaclav Kremen, Vladimir Sladky, Vaclav Gerla, Yurui Cao, Filip Mivalt, Erik K St Louis, Mark R Bower, Benjamin H Brinkmann, Kai Miller, Jamie VanGompel, Mark Cook, Tim Denison, Kent Leyde, Gregory A Worrell","doi":"10.1523/JNEUROSCI.0303-25.2026","DOIUrl":"10.1523/JNEUROSCI.0303-25.2026","url":null,"abstract":"<p><p>Bidirectional interactions between sleep, seizures, and epilepsy remain incompletely understood. Evidence from animal models and people with focal epilepsy suggest that seizures may engage mechanisms of memory consolidation during post-ictal sleep to reinforce and strengthen synaptic connections within the pathological networks that generates seizures, termed seizure-related consolidation (SRC). Human studies of post-ictal sleep changes supportive of SRC, however, are limited by small sample size and restricted observations of post-ictal sleep. We investigated the interplay between seizures and sleep by analyzing sleep-wake and seizure catalogs derived from continuous local field potential (LFP) recordings in 11 people (6 males and 5 females) with drug-resistant focal epilepsy implanted with novel investigational devices and living in their natural environments. Our findings demonstrate that post-ictal rapid-eye-movement sleep duration is reduced, whereas slow-wave sleep duration, slow-wave LFP spectral power, and waveform slope are increased compared with inter-ictal nights without preceding seizures. The most significant changes localize to the epileptogenic networks generating the participants' habitual seizures. These results reveal parallels between SRC and physiological memory consolidation, providing novel insights into the potential role of post-ictal sleep in strengthening epileptic neural engrams and may have implications for targeted disruption of post-ictal sleep and SRC in focal epilepsy.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087812","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}
Pub Date : 2026-03-04DOI: 10.1523/jneurosci.1054-25.2026
Kara Parsons,Hannah Filmer,Shane E Ehrhardt,Matilda Gordon,Reuben Rideaux,Paul E Dux,Natasha Matthews
Mind-wandering is a frequent occurrence in daily life, diverting attention away from both goal-oriented behaviour and internal mental operations. The experience of mind-wandering varies both in the degree to which an individual is aware of their attentional state (meta-awareness) and in their intention to mind-wander. Prior research links mind-wandering with the brain's default mode network. However, the association between mind-wandering and the concentration of excitatory (glutamate) and inhibitory (GABA+) neurotransmitters has largely been unexplored. Here, in 46 (34 female and 12 male) human participants, we employed 7T magnetic resonance spectroscopy to explore associations between neurochemicals in left prefrontal cortex (PFC), right intraparietal sulcus (IPS) and right primary motor cortex (M1), and subtypes of mind-wandering. Across three behavioural paradigms, we employed self-caught mind-wandering probes as a proxy measure for meta-aware mind-wandering, and probe-caught to assess mind-wandering that occurs without meta-awareness. Results showed that mind-wandering associations with neurochemical concentrations varied by brain region, cognitive task, and the nature of mind-wandering. Specifically, probe-caught mind-wandering during the 2-back task and self-caught mind-wandering during the FT-RSGT was associated with neurochemical concentrations in the PFC. In addition, intentional mind-wandering was associated with GABA+ in the M1 for the 2-Back (probe caught) and FT-RSGT (self-caught). Unintentional mind-wandering was as associated with E/I balance in the PFC for the FT-RSGT (probe caught) and 2-Back (self-caught). These findings provide insights into the neurochemical basis of mind-wandering. The propensity to mind-wander, as well as meta-awareness and intentionality of mind-wandering, appear to depend on the demands of different tasks.Significance statement Mind-wandering - the failure to stay on task - has implications in a wide range of applied contexts. Further, when paired with neuroimaging, studying mind-wandering sheds light on the neurophysiological processes associated with cognitive control. A key neuroimaging research gap concerns the neurochemical basis of mind-wandering. Here, we explored associations between neurochemical concentrations across three cortical regions with mind-wandering, in three distinct tasks. The relationships varied across regions, tasks and the nature of the mind-wandering. These findings indicate that neurochemical concentrations, and particularly the excitatory balance of neurochemicals, predict mind-wandering propensity.
{"title":"Neurochemical correlates of mind-wandering and meta-awareness.","authors":"Kara Parsons,Hannah Filmer,Shane E Ehrhardt,Matilda Gordon,Reuben Rideaux,Paul E Dux,Natasha Matthews","doi":"10.1523/jneurosci.1054-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.1054-25.2026","url":null,"abstract":"Mind-wandering is a frequent occurrence in daily life, diverting attention away from both goal-oriented behaviour and internal mental operations. The experience of mind-wandering varies both in the degree to which an individual is aware of their attentional state (meta-awareness) and in their intention to mind-wander. Prior research links mind-wandering with the brain's default mode network. However, the association between mind-wandering and the concentration of excitatory (glutamate) and inhibitory (GABA+) neurotransmitters has largely been unexplored. Here, in 46 (34 female and 12 male) human participants, we employed 7T magnetic resonance spectroscopy to explore associations between neurochemicals in left prefrontal cortex (PFC), right intraparietal sulcus (IPS) and right primary motor cortex (M1), and subtypes of mind-wandering. Across three behavioural paradigms, we employed self-caught mind-wandering probes as a proxy measure for meta-aware mind-wandering, and probe-caught to assess mind-wandering that occurs without meta-awareness. Results showed that mind-wandering associations with neurochemical concentrations varied by brain region, cognitive task, and the nature of mind-wandering. Specifically, probe-caught mind-wandering during the 2-back task and self-caught mind-wandering during the FT-RSGT was associated with neurochemical concentrations in the PFC. In addition, intentional mind-wandering was associated with GABA+ in the M1 for the 2-Back (probe caught) and FT-RSGT (self-caught). Unintentional mind-wandering was as associated with E/I balance in the PFC for the FT-RSGT (probe caught) and 2-Back (self-caught). These findings provide insights into the neurochemical basis of mind-wandering. The propensity to mind-wander, as well as meta-awareness and intentionality of mind-wandering, appear to depend on the demands of different tasks.Significance statement Mind-wandering - the failure to stay on task - has implications in a wide range of applied contexts. Further, when paired with neuroimaging, studying mind-wandering sheds light on the neurophysiological processes associated with cognitive control. A key neuroimaging research gap concerns the neurochemical basis of mind-wandering. Here, we explored associations between neurochemical concentrations across three cortical regions with mind-wandering, in three distinct tasks. The relationships varied across regions, tasks and the nature of the mind-wandering. These findings indicate that neurochemical concentrations, and particularly the excitatory balance of neurochemicals, predict mind-wandering propensity.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"98 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350672","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}
Pub Date : 2026-03-04DOI: 10.1523/JNEUROSCI.1057-25.2026
Lina Teichmann, Martin N Hebart, Chris I Baker
Our visual world consists of an immense number of unique objects and yet, we are easily able to identify, distinguish, and reason about the things we see within a few hundred milliseconds. Here, we used a large-scale and comprehensively sampled stimulus set and developed an analysis approach to capture how rich, multidimensional object representations unfold over time in the human brain. We modeled time-resolved MEG signals of four humans (two females and two males) viewing single presentations of tens of thousands of object images based on millions of behavioral judgments. Extracting behavior-derived object dimensions from similarity judgments, we developed a data-driven approach to guide our understanding of the neural representation of the object space and found that every dimension is reflected in the neural signal. Studying the temporal profiles for different object dimensions, we found that the time courses fell into two broad types, with either a distinct and early peak (∼125 ms) or a slow rise to a late peak (∼300 ms). Further, early effects were stable across participants, in contrast to later effects which showed more variability, suggesting that early peaks may carry stimulus-specific and later peaks more participant-specific information. Dimensions with early peaks appeared to be primarily visual dimensions and those with later peaks more conceptual, suggesting that conceptual representations are more variable across people. Together, these data provide a comprehensive account of how behavior-derived object properties unfold in the human brain and form the basis for the rich nature of object vision.
{"title":"Dynamic Representation of Multidimensional Object Properties in the Human Brain.","authors":"Lina Teichmann, Martin N Hebart, Chris I Baker","doi":"10.1523/JNEUROSCI.1057-25.2026","DOIUrl":"10.1523/JNEUROSCI.1057-25.2026","url":null,"abstract":"<p><p>Our visual world consists of an immense number of unique objects and yet, we are easily able to identify, distinguish, and reason about the things we see within a few hundred milliseconds. Here, we used a large-scale and comprehensively sampled stimulus set and developed an analysis approach to capture how rich, multidimensional object representations unfold over time in the human brain. We modeled time-resolved MEG signals of four humans (two females and two males) viewing single presentations of tens of thousands of object images based on millions of behavioral judgments. Extracting behavior-derived object dimensions from similarity judgments, we developed a data-driven approach to guide our understanding of the neural representation of the object space and found that every dimension is reflected in the neural signal. Studying the temporal profiles for different object dimensions, we found that the time courses fell into two broad types, with either a distinct and early peak (∼125 ms) or a slow rise to a late peak (∼300 ms). Further, early effects were stable across participants, in contrast to later effects which showed more variability, suggesting that early peaks may carry stimulus-specific and later peaks more participant-specific information. Dimensions with early peaks appeared to be primarily visual dimensions and those with later peaks more conceptual, suggesting that conceptual representations are more variable across people. Together, these data provide a comprehensive account of how behavior-derived object properties unfold in the human brain and form the basis for the rich nature of object vision.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108157","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}
Pub Date : 2026-03-04DOI: 10.1523/JNEUROSCI.1414-25.2026
Gianina Cristian, Cece C Kooper, Arthur-Ervin Avramiea, Jennifer R Ramautar, Jordache Ramjith, Shilpa Anand, Marsh Königs, Gert Jan van der Wilt, Hilgo Bruining, Klaus Linkenkaer-Hansen
Neuronal network models have indicated that the so-called critical dynamics facilitate efficient information processing, while criticality disruptions were linked to neuropathology through excitation/inhibition (E/I) imbalances. However, there is limited empirical evidence for a relationship between critical brain dynamics and cognition in healthy children and adolescents. Here, we investigate how these dynamics relate to intelligence in a developing cohort. We recorded eyes-open resting EEG in 128 children (6-19 years, 72 female) and quantified near-critical dynamics in the alpha-band using functional excitation/inhibition ratio (fE/I) and in nonoscillatory activity using the 1/f aperiodic exponent of the power spectrum. We devised models relating intelligence to fE/I and 1/f exponent across seven Yeo7 functional brain networks ranked from lower-order sensorimotor to higher-order association networks. We observed significant correlations between fE/I and 1/f exponent and IQ in association cortices, in contrast to sensorimotor cortices. Children in the high-IQ group had fE/I ratios closer to the theoretical critical value of 1 in association cortices compared with the low-IQ group. The association-sensorimotor axis rank moderated the associations between 1/f exponent and IQ, these associations decreasing on a gradient across the hierarchy of the Yeo7 networks. Age and rank moderated the fE/I-IQ association, with the association-sensorimotor effect size gradient most visible in adolescents. Together, the results suggest that individual variation in criticality-sensitive biomarkers in association networks may be linked to IQ differences in an age-dependent manner, consistent with the hypothesis that developmental modulation of critical dynamics across the cortical hierarchy may support more efficient cognitive processing.
{"title":"Critical Dynamics in the Association Cortex Predict Higher Intelligence in Typically Developing Children.","authors":"Gianina Cristian, Cece C Kooper, Arthur-Ervin Avramiea, Jennifer R Ramautar, Jordache Ramjith, Shilpa Anand, Marsh Königs, Gert Jan van der Wilt, Hilgo Bruining, Klaus Linkenkaer-Hansen","doi":"10.1523/JNEUROSCI.1414-25.2026","DOIUrl":"10.1523/JNEUROSCI.1414-25.2026","url":null,"abstract":"<p><p>Neuronal network models have indicated that the so-called critical dynamics facilitate efficient information processing, while criticality disruptions were linked to neuropathology through excitation/inhibition (E/I) imbalances. However, there is limited empirical evidence for a relationship between critical brain dynamics and cognition in healthy children and adolescents. Here, we investigate how these dynamics relate to intelligence in a developing cohort. We recorded eyes-open resting EEG in 128 children (6-19 years, 72 female) and quantified near-critical dynamics in the alpha-band using functional excitation/inhibition ratio (<i>f</i>E/I) and in nonoscillatory activity using the 1/<i>f</i> aperiodic exponent of the power spectrum. We devised models relating intelligence to <i>f</i>E/I and 1/<i>f</i> exponent across seven Yeo7 functional brain networks ranked from lower-order sensorimotor to higher-order association networks. We observed significant correlations between <i>f</i>E/I and 1/<i>f</i> exponent and IQ in association cortices, in contrast to sensorimotor cortices. Children in the high-IQ group had <i>f</i>E/I ratios closer to the theoretical critical value of 1 in association cortices compared with the low-IQ group. The association-sensorimotor axis rank moderated the associations between 1/<i>f</i> exponent and IQ, these associations decreasing on a gradient across the hierarchy of the Yeo7 networks. Age and rank moderated the <i>f</i>E/I-IQ association, with the association-sensorimotor effect size gradient most visible in adolescents. Together, the results suggest that individual variation in criticality-sensitive biomarkers in association networks may be linked to IQ differences in an age-dependent manner, consistent with the hypothesis that developmental modulation of critical dynamics across the cortical hierarchy may support more efficient cognitive processing.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146108137","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}
Pub Date : 2026-03-04DOI: 10.1523/jneurosci.1251-25.2026
Junjie Hu,Pei-Yang Gao,Run Di,Ouyang Chen,Yi Tang
Chronic pain (CP) is increasingly recognized not only as a sensory and emotional condition but also as a significant contributor to cognitive dysfunction. Growing evidence indicates that CP-induced cognitive dysfunction arises from a cascade of neurobiological processes, including persistent neuroinflammation, neurotransmitter dysregulation, and impaired synaptic plasticity. These mechanisms particularly affect the hippocampus and medial prefrontal cortex (mPFC)-regions essential for memory, attention, and executive function. Neuroimaging studies have documented structural atrophy and disrupted network connectivity in these brain areas in CP patients. At the molecular level, pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) impair glutamatergic and GABAergic signaling, disrupt long-term potentiation (LTP), and inhibit neurogenesis. Additionally, dysregulation of brain-derived neurotrophic factor (BDNF) signaling exacerbates synaptic vulnerability, contributing to cognitive decline. These mechanistic overlaps are particularly relevant in aging populations and in Alzheimer's disease (AD), where CP may act as a risk factor. This review integrates clinical and preclinical findings on CP-related cognitive dysfunction, outlines key molecular mechanisms, and explores emerging therapeutic strategies targeting inflammation, neurotransmitter systems, and synaptic repair. Understanding the interaction between chronic pain and cognition is critical for developing precision treatments that address both nociceptive and neurodegenerative pathways.
{"title":"Chronic Pain and Cognitive Dysfunction: Clinical Implement, Mechanism, and Therapeutic Strategy.","authors":"Junjie Hu,Pei-Yang Gao,Run Di,Ouyang Chen,Yi Tang","doi":"10.1523/jneurosci.1251-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.1251-25.2026","url":null,"abstract":"Chronic pain (CP) is increasingly recognized not only as a sensory and emotional condition but also as a significant contributor to cognitive dysfunction. Growing evidence indicates that CP-induced cognitive dysfunction arises from a cascade of neurobiological processes, including persistent neuroinflammation, neurotransmitter dysregulation, and impaired synaptic plasticity. These mechanisms particularly affect the hippocampus and medial prefrontal cortex (mPFC)-regions essential for memory, attention, and executive function. Neuroimaging studies have documented structural atrophy and disrupted network connectivity in these brain areas in CP patients. At the molecular level, pro-inflammatory cytokines such as interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) impair glutamatergic and GABAergic signaling, disrupt long-term potentiation (LTP), and inhibit neurogenesis. Additionally, dysregulation of brain-derived neurotrophic factor (BDNF) signaling exacerbates synaptic vulnerability, contributing to cognitive decline. These mechanistic overlaps are particularly relevant in aging populations and in Alzheimer's disease (AD), where CP may act as a risk factor. This review integrates clinical and preclinical findings on CP-related cognitive dysfunction, outlines key molecular mechanisms, and explores emerging therapeutic strategies targeting inflammation, neurotransmitter systems, and synaptic repair. Understanding the interaction between chronic pain and cognition is critical for developing precision treatments that address both nociceptive and neurodegenerative pathways.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"12 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350669","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}
Pub Date : 2026-03-04DOI: 10.1523/jneurosci.1487-25.2026
Benjamin J Griffiths
By definition, episodic memory is a conscious phenomenon. Memory traces reactivated by the hippocampus and reinstated in the sensory cortices need to enter conscious awareness for them to be re-experienced and overtly recalled. However, it remains unclear whether such reactivation in-and-of-itself ensures that memories will be overtly recalled. To investigate this, magnetoencephalography (MEG) recordings were analysed from thirty-one participants (18 female, 13 male) completing a video-word pair associates memory task. When combining linear classifiers and spectral analyses, sensory cortical reactivation could be observed without overt recall occurring, suggesting reactivation does not guarantee overt recall. Instead, overt recall was additively predicted by (i) an increase in reactivated representations rhythmically fluctuating within the alpha band, and (ii) a decrease in total sensory neocortical alpha power. These results are consistent with accounts which propose that reactivation benefits from desynchronising the network to provide representational space for stimulus-specific information, and/or amplifying stimulus-specific information above residual noise. Altogether, these results suggest that representational reactivation can occur without overt recall, and suggest a role for alpha oscillations in projecting internally-generated representations into conscious awareness.Significance Statement Growing evidence suggests episodic recall can occur without conscious awareness, raising a fundamental question: how do memories enter awareness? Here, we investigate whether alpha oscillatory activity relates to this process. Using magnetoencephalography, we show that while episodic memories can be reinstated in the neocortex without overt recall occurring, rhythmic reactivation within the alpha band distinguishes memories that will be recalled from those that will not, suggesting reactivation must exceed a threshold for the memory contents to enter awareness. These findings challenge the idea that memory reactivation inherently results in conscious awareness and highlight a new target for brain-based interventions aimed at improving memory in both healthy individuals and clinical populations.
{"title":"Alpha oscillations track the projection of reactivated memories into conscious awareness.","authors":"Benjamin J Griffiths","doi":"10.1523/jneurosci.1487-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.1487-25.2026","url":null,"abstract":"By definition, episodic memory is a conscious phenomenon. Memory traces reactivated by the hippocampus and reinstated in the sensory cortices need to enter conscious awareness for them to be re-experienced and overtly recalled. However, it remains unclear whether such reactivation in-and-of-itself ensures that memories will be overtly recalled. To investigate this, magnetoencephalography (MEG) recordings were analysed from thirty-one participants (18 female, 13 male) completing a video-word pair associates memory task. When combining linear classifiers and spectral analyses, sensory cortical reactivation could be observed without overt recall occurring, suggesting reactivation does not guarantee overt recall. Instead, overt recall was additively predicted by (i) an increase in reactivated representations rhythmically fluctuating within the alpha band, and (ii) a decrease in total sensory neocortical alpha power. These results are consistent with accounts which propose that reactivation benefits from desynchronising the network to provide representational space for stimulus-specific information, and/or amplifying stimulus-specific information above residual noise. Altogether, these results suggest that representational reactivation can occur without overt recall, and suggest a role for alpha oscillations in projecting internally-generated representations into conscious awareness.Significance Statement Growing evidence suggests episodic recall can occur without conscious awareness, raising a fundamental question: how do memories enter awareness? Here, we investigate whether alpha oscillatory activity relates to this process. Using magnetoencephalography, we show that while episodic memories can be reinstated in the neocortex without overt recall occurring, rhythmic reactivation within the alpha band distinguishes memories that will be recalled from those that will not, suggesting reactivation must exceed a threshold for the memory contents to enter awareness. These findings challenge the idea that memory reactivation inherently results in conscious awareness and highlight a new target for brain-based interventions aimed at improving memory in both healthy individuals and clinical populations.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"42 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147350670","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}
Pub Date : 2026-03-04DOI: 10.1523/JNEUROSCI.1237-25.2026
Shir Hofstetter, Marcus Daghlian, Serge O Dumoulin
Processing ordinality, i.e., the rank of an item in a series such as 1st, 2nd, 3rd, etc., is a fundamental skill shared by humans and animals. While humans often use symbolic sequences like numbers or letters, ordinality does not depend on language or symbols. Across species, ordinality plays a critical role in behaviors such as decision-making, foraging, and social organization. We hypothesize that ordinality perception is supported by neuronal tuning, i.e., neurons selectively responsive to specific ranks. Using ultrahigh-field 7 T fMRI and population receptive field (pRF) modeling in human participants (both female and male), we identified neural populations in parietal and premotor cortices that are tuned to nonsymbolic ordinal positions. Comparable with other sensory domains, tuning width increased with preferred ordinal rank, suggesting reduced precision and potentially lower perceptual accuracy for higher ranks. Additionally, pRF measurements revealed that cortical territory devoted to higher ordinalities decreased with rank, reinforcing that neural precision is greatest for early positions (e.g., 1st and 2nd) and declines with rank. These responses did not generalize to symbolic ordinality. Similar tuning to nonsymbolic ordinality emerged spontaneously in hierarchical convolutional neural networks trained on visual tasks. Together, these results suggest that the tuning properties of these neuronal populations support nonsymbolic ordinality perception and may reflect an inherent feature of neural processing.
{"title":"Neural Tuning for Ordinal Processing: Convergent Patterns in Human Brains and Artificial Networks.","authors":"Shir Hofstetter, Marcus Daghlian, Serge O Dumoulin","doi":"10.1523/JNEUROSCI.1237-25.2026","DOIUrl":"10.1523/JNEUROSCI.1237-25.2026","url":null,"abstract":"<p><p>Processing ordinality, i.e., the rank of an item in a series such as 1st, 2nd, 3rd, etc., is a fundamental skill shared by humans and animals. While humans often use symbolic sequences like numbers or letters, ordinality does not depend on language or symbols. Across species, ordinality plays a critical role in behaviors such as decision-making, foraging, and social organization. We hypothesize that ordinality perception is supported by neuronal tuning, i.e., neurons selectively responsive to specific ranks. Using ultrahigh-field 7 T fMRI and population receptive field (pRF) modeling in human participants (both female and male), we identified neural populations in parietal and premotor cortices that are tuned to nonsymbolic ordinal positions. Comparable with other sensory domains, tuning width increased with preferred ordinal rank, suggesting reduced precision and potentially lower perceptual accuracy for higher ranks. Additionally, pRF measurements revealed that cortical territory devoted to higher ordinalities decreased with rank, reinforcing that neural precision is greatest for early positions (e.g., 1st and 2nd) and declines with rank. These responses did not generalize to symbolic ordinality. Similar tuning to nonsymbolic ordinality emerged spontaneously in hierarchical convolutional neural networks trained on visual tasks. Together, these results suggest that the tuning properties of these neuronal populations support nonsymbolic ordinality perception and may reflect an inherent feature of neural processing.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167854","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}
Pub Date : 2026-03-04DOI: 10.1523/JNEUROSCI.0124-25.2026
Sibaram Behera, Anindya Ghosh Roy
In adulthood, the regenerative capacity of the injured brain circuit is poor, thereby preventing functional restoration. Rehabilitative physical exercise is a promising approach for enhancing the behavioral recovery after neuronal injury to both the central and peripheral nervous systems. The metabolic energy sensor AMPK acts as a mediator for the exercise benefit in Caenorhabditis elegans axon regeneration. However, the mechanistic understanding of upstream and downstream components of AMPK signaling in the physical exercise-mediated enhancement of axon regeneration is still unclear. Here, we addressed this question by combining swimming exercise with laser axotomy of C. elegans posterior lateral microtubule (PLM) neurons. Using a genetically encoded ATP sensor iATPsnFR1.0, we observed that immediately after swimming exercise, ATP level is decreased both in neuron and muscle. Further, we found that AICAR-mediated AMPK activation is sufficient to promote axon regeneration and functional recovery. The PAR-4/Liver kinase B1 acts upstream of AMPK to improve functional recovery through swimming exercise. We also found that the transcriptional regulators DAF-16 and MDT-15 mediate the beneficial effects of swimming by acting downstream of AMPK. MDT-15 functions within neuron to mediate the benefit of AMPK activation, whereas DAF-16 acts both in neuron and muscle to promote functional restoration. Additionally, we demonstrated that swimming exercise induces nuclear localization of DAF-16 in an AMPK-dependent manner. Our results showed that neuronal and non-neuronal arms of AMPK signaling play an integrative role in response to physical exercise to promote functional recovery after axon injury.
{"title":"Exercise-Induced Differential Transcriptional Output of AMPK Signaling Improves Axon Regeneration and Functional Recovery.","authors":"Sibaram Behera, Anindya Ghosh Roy","doi":"10.1523/JNEUROSCI.0124-25.2026","DOIUrl":"10.1523/JNEUROSCI.0124-25.2026","url":null,"abstract":"<p><p>In adulthood, the regenerative capacity of the injured brain circuit is poor, thereby preventing functional restoration. Rehabilitative physical exercise is a promising approach for enhancing the behavioral recovery after neuronal injury to both the central and peripheral nervous systems. The metabolic energy sensor AMPK acts as a mediator for the exercise benefit in <i>Caenorhabditis elegans</i> axon regeneration. However, the mechanistic understanding of upstream and downstream components of AMPK signaling in the physical exercise-mediated enhancement of axon regeneration is still unclear. Here, we addressed this question by combining swimming exercise with laser axotomy of <i>C. elegans</i> posterior lateral microtubule (PLM) neurons. Using a genetically encoded ATP sensor iATPsnFR1.0, we observed that immediately after swimming exercise, ATP level is decreased both in neuron and muscle. Further, we found that AICAR-mediated AMPK activation is sufficient to promote axon regeneration and functional recovery. The PAR-4/Liver kinase B1 acts upstream of AMPK to improve functional recovery through swimming exercise. We also found that the transcriptional regulators DAF-16 and MDT-15 mediate the beneficial effects of swimming by acting downstream of AMPK. MDT-15 functions within neuron to mediate the benefit of AMPK activation, whereas DAF-16 acts both in neuron and muscle to promote functional restoration. Additionally, we demonstrated that swimming exercise induces nuclear localization of DAF-16 in an AMPK-dependent manner. Our results showed that neuronal and non-neuronal arms of AMPK signaling play an integrative role in response to physical exercise to promote functional recovery after axon injury.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"46 9","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12962777/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147357118","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}
Pub Date : 2026-03-03DOI: 10.1523/jneurosci.1452-25.2026
Linqing Sun,Enrico Zampese,Tristano Pancani,David Wokosin,Tatiana Tkatch,D James Surmeier
The basal forebrain cholinergic neurons (BFCNs) in substantia innominata (SI) and nucleus basalis magnocellularis (nBM) provide dense innervation to multiple cortical areas, shaping cognition, attention, and the sleep-wake cycle. However, the afferent connectome controlling the spiking of BFCNs is poorly characterized. Although biased toward the nearby ventral striatum, monosynaptic rabies virus mapping revealed that spiny projection neurons (SPNs) throughout the striatum innervated BFCNs in the SI/nBM. Roughly 1-5% of SPNs were retrogradely labeled, with both D1 dopamine receptor-expressing SPNs (D1R-SPNs) and D2 dopamine receptor-expressing SPNs (D2R-SPNs) making similar contributions to the total. Nevertheless, optogenetic activation of D1R-SPN axons in ex vivo brain slices from male mice evoked significantly more robust responses in BFCNs than did activation of D2R-SPNs. Interestingly, although the response to transient D1R-SPN stimulation was dominated by GABAergic inhibition of ongoing BFCN spiking, more sustained stimulation led to a significant elevation in BFCN spiking that outlasted the stimulation. This persistent excitation was attributable to engagement of tachykinin 1 receptors (NK1Rs) and acid-sensing cation channels (ASICs). These studies demonstrate that a spatially distributed population of D1R-SPNs exerts significant regulation of BFCN activity, which could play an important role in arousal, cognition, and sleep.Significance statement Basal forebrain cholinergic neurons (BFCNs) are the principal source of the cortical cholinergic innervation critical to shaping cognition, sleep and arousal. Although striatal spiny projection neurons (SPNs) constitute a significant component of the BFCN connectome, which SPN subtype contributes to this innervation, and their functional role is unclear. Here, we show that both D1 dopamine receptor (D1R)-expressing and D2 dopamine receptor (D2R)-expressing SPNs innervate BFCNs. However, optogenetic stimulation of D1R-SPNs resulted in a more robust GABAergic suppression of baseline BFCN activity. Furthermore, burst stimulation of D1R-SPNs resulted in a prolonged excitation of BFCNs attributable to activation of tachykinin receptors and acid-sensing ion channels. These studies point to a novel role for SPNs in the regulation of cognition, sleep, and arousal.
{"title":"Activity-dependent regulation of basal forebrain cholinergic neurons by striatal spiny projection neurons.","authors":"Linqing Sun,Enrico Zampese,Tristano Pancani,David Wokosin,Tatiana Tkatch,D James Surmeier","doi":"10.1523/jneurosci.1452-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.1452-25.2026","url":null,"abstract":"The basal forebrain cholinergic neurons (BFCNs) in substantia innominata (SI) and nucleus basalis magnocellularis (nBM) provide dense innervation to multiple cortical areas, shaping cognition, attention, and the sleep-wake cycle. However, the afferent connectome controlling the spiking of BFCNs is poorly characterized. Although biased toward the nearby ventral striatum, monosynaptic rabies virus mapping revealed that spiny projection neurons (SPNs) throughout the striatum innervated BFCNs in the SI/nBM. Roughly 1-5% of SPNs were retrogradely labeled, with both D1 dopamine receptor-expressing SPNs (D1R-SPNs) and D2 dopamine receptor-expressing SPNs (D2R-SPNs) making similar contributions to the total. Nevertheless, optogenetic activation of D1R-SPN axons in ex vivo brain slices from male mice evoked significantly more robust responses in BFCNs than did activation of D2R-SPNs. Interestingly, although the response to transient D1R-SPN stimulation was dominated by GABAergic inhibition of ongoing BFCN spiking, more sustained stimulation led to a significant elevation in BFCN spiking that outlasted the stimulation. This persistent excitation was attributable to engagement of tachykinin 1 receptors (NK1Rs) and acid-sensing cation channels (ASICs). These studies demonstrate that a spatially distributed population of D1R-SPNs exerts significant regulation of BFCN activity, which could play an important role in arousal, cognition, and sleep.Significance statement Basal forebrain cholinergic neurons (BFCNs) are the principal source of the cortical cholinergic innervation critical to shaping cognition, sleep and arousal. Although striatal spiny projection neurons (SPNs) constitute a significant component of the BFCN connectome, which SPN subtype contributes to this innervation, and their functional role is unclear. Here, we show that both D1 dopamine receptor (D1R)-expressing and D2 dopamine receptor (D2R)-expressing SPNs innervate BFCNs. However, optogenetic stimulation of D1R-SPNs resulted in a more robust GABAergic suppression of baseline BFCN activity. Furthermore, burst stimulation of D1R-SPNs resulted in a prolonged excitation of BFCNs attributable to activation of tachykinin receptors and acid-sensing ion channels. These studies point to a novel role for SPNs in the regulation of cognition, sleep, and arousal.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"25 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346309","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}