bioRxiv : the preprint server for biology最新文献

{"title":"Pupil size predicts the onset of exploration and changes in prefrontal dynamics.","authors":"Akram Shourkeshti, Mojtaba Abbaszadeh, Gabriel Marrocco, Katarzyna Jurewicz, Tirin Moore, R Becket Ebitz","doi":"10.1101/2023.05.24.541981","DOIUrl":"10.1101/2023.05.24.541981","url":null,"abstract":"<p><p>In uncertain environments, intelligent decision-makers exploit actions that have been rewarding in the past, but also explore actions that could be even better. Several neuromodulatory systems are implicated in exploration, based, in part, on work linking exploration to pupil size-a peripheral correlate of neuromodulatory tone and index of arousal. However, pupil size could instead track variables that make exploration more likely, like volatility or reward, without directly predicting either exploration or its neural bases. Here, we simultaneously measured pupil size, exploration, and neural population activity in the prefrontal cortex while two rhesus macaques explored and exploited in a dynamic environment. We found that pupil size under constant luminance specifically predicted the onset of exploration, the first exploratory trial in a sequence, beyond what could be explained by reward history. Pupil size also predicted disorganized patterns of prefrontal neural activity at both the single neuron and population levels, even within periods of exploitation. Ultimately, our results support a model in which pupil-linked mechanisms promote the onset of exploration via driving the prefrontal cortex through a critical tipping point where prefrontal control dynamics become disorganized and exploratory decisions are possible.</p><p><strong>Significance statement: </strong>Humans and other animals learn about the world through exploration: through making decisions that offer the opportunity to learn and discover, even when these decisions are not the best option in the moment. Neuroscience research has historically focused on understanding good choices, delivering many key insights into the neural mechanisms involved in these calculations. However, much less is known about how the brain generates exploratory decisions. This study identifies certain \"early warning signs\" of exploratory decisions in the brain and body, including certain signals in size of the pupil and the speed of neural activity in the prefrontal cortex. These early warning signs suggest that exploration may be the result of a critical tipping point in prefrontal brain states.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d9/86/nihpp-2023.05.24.541981v1.PMC10245915.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9610679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blue light stimulated-autofluorescence green flash of lysosome-related organelles in the intestinal cells of nematodes.","authors":"Chieh-Hsiang Tan, Keke Ding, Mark G Zhang, Paul W Sternberg","doi":"10.1101/2023.10.16.562538","DOIUrl":"10.1101/2023.10.16.562538","url":null,"abstract":"<p><p>The lysosome-related organelles (\"gut granules\") in the intestinal cells of many nematodes, including <i>Caenorhabditis elegan</i>s, play an important role in metabolic and signaling processes, but they have not been fully characterized. We report here a previously undescribed phenomenon in which the autofluorescence of these granules displays a \"flash\" phenomenon in which fluorescence decreases are preceded by sharp increases in fluorescence intensity that expand into the surrounding area when the granules are stimulated with blue light. Autofluorescent granules are present in the intestinal cells of all six nematode species examined, with differences in morphology and distribution pattern. Five species exhibit the flash phenomenon: <i>Panagrellus redivivus</i> (Clade IV), <i>Steinernema hermaphroditum</i> (Clade IV), <i>C. elegans</i> (Clade V), <i>Oscheius tipulae</i> (Clade V), and <i>Pristionchus pacificus</i> (Clade V). The reaction of the granules to blue light stimulation greatly differs among different developmental stages and may also be dependent on physiological conditions. In addition, even within the same animal, the sensitivity of individual granules differs, with some of the variation associated with other characteristics of the granules, such as their overall location within the intestine. We hypothesize that the differences in response to blue light indicate the existence of different sub-populations of gut granules in nematode intestines, and the visually spectacular dynamic fluorescence phenomenon we describe might provide a handle on their eventual characterization.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prickle and Ror modulate Dishevelled-Vangl interaction to regulate non-canonical Wnt signaling during convergent extension.","authors":"Hwa-Seon Seo, Deli Yu, Ivan Popov, Jiahui Tao, Allyson Angermeier, Fei Yang, Sylvie Marchetto, Jean-Paul Borg, Bingdong Sha, Jeffrey D Axelrod, Chenbei Chang, Jianbo Wang","doi":"10.1101/2023.08.29.555374","DOIUrl":"10.1101/2023.08.29.555374","url":null,"abstract":"<p><p>Convergent extension (CE) is a fundamental morphogenetic process where oriented cell behaviors lead to polarized extension of diverse tissues. In vertebrates, regulation of CE requires both non-canonical Wnt, its co-receptor Ror, and several \"core members\" of the planar cell polarity (PCP) pathway. PCP was originally identified as a mechanism to coordinate the cellular polarity in the plane of static epithelium, where core proteins Frizzled (Fz)/ Dishevelled (Dvl) and Van Gogh-like (Vangl)/ Prickle (Pk) partition to opposing cell cortex. But how core PCP proteins interact with each other to mediate non-canonical Wnt/ Ror signaling during CE is not clear. We found previously that during CE, Vangl cell-autonomously recruits Dvl to the plasma membrane and keeps Dvl inactive. In this study, we show that non-canonical Wnt induces Dvl to transition from Vangl to Fz. Pk inhibits the transition, and functionally synergize with Vangl to suppress Dvl during CE. Conversely, Ror is required for the transition, and functionally antagonizes Vangl. Biochemically, Vangl interacts directly with both Ror and Dvl. Ror and Dvl do not bind directly, but can be cofractionated with Vangl. Collectively, we propose that Pk assists Vangl to function as an unconventional adaptor that brings Dvl and Ror into a complex to serves two functions: 1) simultaneously preventing both Dvl and Ror from ectopically activating non-canonical Wnt signaling; and 2) relaying Dvl to Fz for signaling activation upon non-canonical Wnt induced dimerization of Fz and Ror.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10491138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wake EEG oscillation dynamics reflect both sleep pressure and brain maturation across childhood and adolescence.","authors":"Sophia Snipes, Valeria Jaramillo, Elena Krugliakova, Carina Volk, Melanie Furrer, Mirjam Studler, Monique LeBourgeois, Salome Kurth, Oskar G Jenni, Reto Huber","doi":"10.1101/2024.02.24.581878","DOIUrl":"10.1101/2024.02.24.581878","url":null,"abstract":"<p><p>An objective measure of brain maturation is highly insightful for monitoring both typical and atypical development. Slow wave activity, recorded in the sleep electroencephalogram (EEG), reliably indexes age-related changes in sleep pressure as well as deficits related to developmental disorders such as attention-deficit hyperactivity disorder (ADHD). We aimed to determine whether wake EEG measured before and after sleep could index the same developmental changes in sleep pressure, using data collected from 163 participants 3-25 years old. We analyzed age- and sleep-dependent changes in two measures of oscillatory activity, amplitudes and density, as well as two measures of aperiodic activity, offsets and exponents. We then compared these wake measures to sleep slow wave amplitudes and slopes. Finally, we compared wake EEG in children with ADHD (N=58) to neurotypical controls. Of the four wake measures, only oscillation amplitudes consistently exhibited the same changes as sleep slow waves. Wake amplitudes decreased with age, decreased after sleep, and this overnight decrease decreased with age. Furthermore, wake amplitudes were significantly related to both sleep slow wave amplitudes and slopes. Wake oscillation densities decreased overnight in children but increased overnight in adolescents and adults. Aperiodic offsets decreased linearly with age, decreased after sleep, and were significantly related to sleep slow wave amplitudes. Aperiodic exponents also decreased with age, but increased after sleep. No wake measure showed significant effects of ADHD. Overall, our results indicate that wake oscillation amplitudes, and to some extent aperiodic offsets, behave like sleep slow waves across sleep and development. At the same time, overnight changes in oscillation densities independently reflect some yet-unknown shift in neural activity around puberty.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10925212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140095210","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy functions in lung macrophages and dendritic cells to regulate allergen-dependent inflammatory responses.","authors":"Neha Dubey, Reilly Woodson, Skyler V Hendrix, Anne L Rosen, Rachel L Kinsella, Samuel R McKee, Marick Starick, Nicole Rivera-Espinal, Sumanta K Naik, Asya Smirnov, Darren Kreamalmeyer, Andrew L Kau, Christina L Stallings","doi":"10.1101/2023.03.16.533006","DOIUrl":"10.1101/2023.03.16.533006","url":null,"abstract":"<p><p>Asthma affects 260 million people worldwide, with severe asthma cases that are associated with T_H17/T_H1 responses and neutrophil dominated inflammation being the most difficult to treat due to corticosteroid insensitivity. Single nucleotide polymorphisms in the <i>ATG5</i> gene, which encodes for a protein required for the cellular recycling process of autophagy, are associated with higher risk for developing severe asthma. However, the role for ATG5 during allergic inflammation remains mostly unknown. We have identified an autophagy-dependent role for ATG5 in lung macrophages and dendritic cells (DCs) for suppressing T_H17 responses and neutrophil accumulation in house dust mite (HDM)-challenged mice, a T_H17/T_H1 dominated model for allergic airway inflammation due to contamination of the HDM with lipopolysaccharide. In contrast, autophagy was required to promote eosinophil accumulation in the T_H2-dominated ovalbumin model of allergic airway inflammation, supporting a model where autophagy functions in lung macrophages and DCs to suppress T_H17 responses and promote T_H2 responses in an allergen-dependent manner. In addition, we discover that autophagy is also required in macrophages exposed to HDM to suppress the secretion of cytokines and chemokines that would otherwise recruit neutrophils to the lungs, independent of T cell responses. Together, our data identify multiple roles for autophagy in suppressing the neutrophil accumulation in lungs that is associated with severe asthma.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"2016 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340803/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82812979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antigen properties shape organization of FcεRI aggregates to tune mast cell signaling.","authors":"Derek A Rinaldi, William K Kanagy, Rachel M Grattan, Jon Christian David, Hannah C Kaye, Eric A Burns, Marelessis Palomino, Shayna R Lucero, Michael J Wester, Lydia Tapia, Bruna Jacobson, Keith A Lidke, Bridget S Wilson, Diane S Lidke","doi":"10.1101/2023.08.04.552060","DOIUrl":"10.1101/2023.08.04.552060","url":null,"abstract":"<p><p>Fc receptors containing immunoreceptor tyrosine-based activation motifs (ITAMs) are critical components of the innate immune system that bridge adaptive antibody recognition to cellular effector responses. In allergic responses, the high-affinity IgE receptor, FcεRI, is activated when multivalent antigens crosslink receptor-bound IgE, yet the molecular mechanisms linking antigen structure to signaling output remain incompletely understood. Here, we compare two antigens presenting identical IgE-binding haptens but differing in geometry: the high-valency, heterogeneous DNP-BSA and the defined trivalent antigen DF3. We find that these ligands elicit distinct patterns of degranulation and FcεRI γ-chain phosphorylation, correlating with differences in the recruitment of the inhibitory lipid phosphatase SHIP1. Monte Carlo simulations predicted that each antigen generates receptor aggregates with distinct size, complexity, and inter-receptor spacing. Using direct stochastic optical reconstruction microscopy (dSTORM) and Bayesian Grouping of Localizations (BaGoL) analysis, we directly visualized the nanoscale aggregate geometry and found that DF3 induced smaller, more linear aggregates with tighter receptor spacing than DNP-BSA. Together, our results show that antigen properties, including size, valency, and epitope spacing, modulate FcεRI aggregate architecture and tune the balance of positive and negative signaling to ultimately shape mast cell outcomes.</p><p><strong>Statement of significance: </strong>Allergic immune responses are initiated when multivalent antigens aggregate IgE-bound FcεRI on mast cells, yet the relationship between antigen structure and signaling strength remains unclear. This study combines biochemical assays, Monte Carlo modeling, and super-resolution imaging to show that allergen properties, specifically valency and nanoscale epitope spacing, govern the geometry of FcεRI aggregates and the balance of activating and inhibitory signals. These findings establish a direct mechanistic link between antigen structure and immune receptor output, providing new insight into how physical antigen features encode mast cell responses.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/59/nihpp-2023.08.04.552060v1.PMC10441289.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10103167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unique territorial and compartmental organization of chromosomes in the holocentric silkworm.","authors":"J Gil, E Navarrete, C Hockens, N Chowdhury, S Abraham, G Cornilleau, E P Lei, J Mozziconacci, E J Banigan, L F Rosin, L A Mirny, H Muller, I A Drinnenberg","doi":"10.1101/2023.09.14.557757","DOIUrl":"10.1101/2023.09.14.557757","url":null,"abstract":"<p><p>Hallmarks of multicellular eukaryotic genome organization are chromosome territories, compartments, and loop-extrusion-mediated structures, including TADs. However, these are mainly observed in model organisms, and most eukaryotes remain unexplored. Using Hi-C in the silkworm <i>Bombyx mori</i> we discover a novel chromatin folding structure, compartment S, which is \"secluded\" from the rest of the chromosome. This compartment exhibits loop extrusion features and a unique genetic and epigenetic landscape, and it localizes towards the periphery of chromosome territories. While euchromatin and heterochromatin display preferential compartmental contacts, S domains are remarkably devoid of contacts with other regions, including with other S domains. Polymer simulations show that this contact pattern can only be explained by high loop-extrusion activity within compartment S, combined with low extrusion elsewhere through the genome. This unique, targeted extrusion represents a novel phenomenon and underscores how evolutionarily conserved mechanisms-compartmentalization and loop extrusion-can be repurposed to create new 3D genome architectures.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10515926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41163337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social Closeness and Reward Sensitivity Enhance Corticostriatal Function during Experiences of Shared Rewards.","authors":"David V Smith, Ori Zaff, James B Wyngaarden, Jeffrey B Dennison, Daniel Sazhin, Jason Chein, Michael McCloskey, Lauren B Alloy, Johanna M Jarcho, Dominic S Fareri","doi":"10.1101/2023.10.19.562908","DOIUrl":"10.1101/2023.10.19.562908","url":null,"abstract":"<p><p>Although prior research has demonstrated enhanced striatal response when sharing rewards with close social connections, less is known about how individual differences affect ventral striatal (VS) activation and connectivity when experiencing rewards within social contexts. Given that self-reported reward sensitivity and level of substance use have been associated with differences in VS activation, we set out to investigate whether these factors would be independently associated with enhancements to neural reward responses within social contexts. In this pre-registered study, participants (N=45) underwent fMRI while playing a card guessing game in which correct or incorrect guesses resulted in monetary gains and losses that were shared evenly with either a close friend, stranger (confederate), or non-human partner. Consistent with our prior work, we found increased VS activation when sharing rewards with a socially close peer as opposed to an out-of-network stranger. As self-reported reward sensitivity increased, the difference in VS response to rewards shared with friends and strangers decreased. We also found enhanced connectivity between the VS and temporoparietal junction when sharing rewards with close friends as opposed to strangers. Finally, exploratory analyses revealed that as reward sensitivity and sub-clinical substance use increase, the difference in VS connectivity with the right fusiform face area increases as a function of social context. These findings demonstrate that responsivity to the context of close friends may be tied to individual reward sensitivity or sub-clinical substance use habits; together these factors may inform predictions of risk for future mental health disorders.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extrusion fountains are hallmarks of chromosome organization emerging upon zygotic genome activation.","authors":"Aleksandra Galitsyna, Sergey Ulianov, Mariia Bazarevich, Nikolai Bykov, Marina Veil, Meijiang Gao, Kristina Y Perevoshchikova, Mikhail S Gelfand, Sergey V Razin, Leonid A Mirny, Daria Onichtchouk","doi":"10.1101/2023.07.15.549120","DOIUrl":"10.1101/2023.07.15.549120","url":null,"abstract":"<p><p>The initiation of gene expression during development, known as zygotic genome activation (ZGA), is accompanied by massive changes in chromosome organization. However, the earliest events of chromosome folding and their functional roles remain unclear. Using Hi-C on zebrafish embryos, we discovered that chromosome folding begins early in development with the formation of \"fountains\", a novel element of chromosome organization. Emerging preferentially at enhancers, fountains exhibit an initial accumulation of cohesin, which later redistributes to CTCF sites at TAD borders. Knockouts of pioneer transcription factors driving ZGA enhancers result in the specific loss of fountains, establishing a causal link between enhancer activation and fountain formation. Polymer simulations demonstrate that fountains may arise as sites of facilitated cohesin loading, requiring two-sided but desynchronized loop extrusion, potentially caused by cohesin collisions with obstacles or internal switching. Moreover, we detected similar fountain patterns at enhancers in mouse cells. Fountains disappear upon acute cohesin depletion, as well as during mitosis, and reappear with cohesin loading in early G1. Altogether, fountains represent the first known enhancer-specific elements of chromosome organization and constitute starting points for chromosome folding during development, likely through facilitated cohesin loading.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/3d/nihpp-2023.07.15.549120v1.PMC10370019.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9915558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cortical structure in relation to empathy and psychopathy in 800 incarcerated men.","authors":"Marcin A Radecki, J Michael Maurer, Keith A Harenski, David D Stephenson, Erika Sampaolo, Giada Lettieri, Giacomo Handjaras, Emiliano Ricciardi, Samantha N Rodriguez, Craig S Neumann, Carla L Harenski, Sara Palumbo, Silvia Pellegrini, Jean Decety, Pietro Pietrini, Kent A Kiehl, Luca Cecchetti","doi":"10.1101/2023.06.14.543399","DOIUrl":"10.1101/2023.06.14.543399","url":null,"abstract":"<p><strong>Background: </strong>Reduced empathy is a hallmark of individuals with high psychopathy, who are overrepresented among incarcerated men. However, a comprehensive mapping of cortical structure in relation to empathy and psychopathy is lacking.</p><p><strong>Methods: </strong>In 804 incarcerated adult men, we administered the Perspective Taking (IRI-PT) and Empathic Concern (IRI-EC) subscales of the Interpersonal Reactivity Index, Hare Psychopathy Checklist-Revised (PCL-R; Interpersonal/Affective [F1] and Lifestyle/Antisocial [F2] factors), and T1-weighted MRI to quantify cortical thickness (CT) and surface area (SA). We also included the male sample from the Human Connectome Project (HCP; N = 501) to probe the replicability of structural-covariance gradients.</p><p><strong>Results: </strong>PCL-R F1 was uniquely negatively related to IRI-EC, while PCL-R F2 was uniquely negatively related to IRI-PT. Cortical structure was not related to either IRI subscale, although there was effect-size differentiation by cytoarchitectonic class and/or functional network. CT was related to PCL-R F1 (mostly positively), SA was related to both PCL-R factors (only positively), and both cortical indices demonstrated out-of-sample predictive utility for PCL-R F1. The high-psychopathy group (N = 178) scored uniquely lower on IRI-EC while having increased SA (but not CT); across the cortex, effect sizes were largest in the paralimbic class and somatomotor network, and meta-analytic task-based activations corroborated affective/sensory importance. Finally, the total sample revealed anterior-posterior gradients of covariance, which were replicated in the HCP sample. In the high-psychopathy group, the gradient of CT (but not SA) was globally compressed.</p><p><strong>Conclusions: </strong>Most notably, high-psychopathy men had reduced empathic concern, increased SA, and compressed macroscale organization of CT.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":"11 suppl_1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11996374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88667717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}