Molecular Autism最新文献

{"title":"Flexible nonlinear modeling reveals age-related differences in resting-state functional brain connectivity in autistic males from childhood to mid-adulthood.","authors":"Daniel Feldman, Molly Prigge, Andrew Alexander, Brandon Zielinski, Janet Lainhart, Jace King","doi":"10.1186/s13229-025-00657-1","DOIUrl":"10.1186/s13229-025-00657-1","url":null,"abstract":"<p><strong>Background: </strong>Divergent age-related functional brain connectivity in autism spectrum disorder (ASD) has been observed using resting-state fMRI, although the specific findings are inconsistent across studies. Common statistical regression approaches that fit identical models across functional brain networks may contribute to these inconsistencies. Relationships among functional networks have been reported to follow unique nonlinear developmental trajectories, suggesting the need for flexible modeling. Here we apply generalized additive models (GAMs) to flexibly adapt to distinct network trajectories and simultaneously describe divergent age-related changes from childhood into mid-adulthood in ASD.</p><p><strong>Methods: </strong>1107 males, aged 5-40, from the ABIDE I & II cross-sectional datasets were analyzed. Functional connectivity was extracted using a network-based template. Connectivity values were harmonized using COMBAT-GAM. Connectivity-age relationships were assessed with thin-plate spline GAMs. Post-hoc analyses defined the age-ranges of divergent aging in ASD.</p><p><strong>Results: </strong>Typically developing (TD) and ASD groups shared 15 brain connections that significantly changed with age (FDR-corrected p < 0.05). Network connectivity exhibited diverse nonlinear age-related trajectories across the functional connectome. Comparing ASD and TD groups, default mode to central executive between-network connectivity followed similar nonlinear paths with no group differences. Contrarily, the ASD group had chronic hypoconnectivity throughout default mode-ventral attentional (salience) and default mode-somatomotor aging trajectories. Within-network somatomotor connectivity was similar between groups in childhood but diverged in adolescence with the ASD group showing decreased within-network connectivity. Network connectivity between the somatomotor network and various other functional networks had fully disrupted age-related pathways in ASD compared to TD, displaying significantly different model curvatures and fits.</p><p><strong>Limitations: </strong>The present analysis includes only male participants and has a restricted age range, limiting analysis of early development and later life aging, years 40 and beyond. Additionally, our analysis is limited to large-scale network cortical functional parcellation. To parse more specificity of brain region connectivity, a fine-grained functional parcellation including subcortical areas may be warranted.</p><p><strong>Conclusion: </strong>Flexible non-linear modeling minimizes statistical assumptions and allows diagnosis-related brain connections to follow independent data-driven age-related pathways. Using GAMs, we describe complex age-related pathways throughout the human connectome and observe distinct periods of divergence in autism.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"24"},"PeriodicalIF":5.7,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11998146/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144027283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of imitation abilities on social communication in autistic children: evidence from an Early Start Denver Model intervention study.","authors":"Shihua Xiao, Jing Li","doi":"10.1186/s13229-025-00656-2","DOIUrl":"10.1186/s13229-025-00656-2","url":null,"abstract":"<p><p>Imitation is foundational to early social learning, yet autistic children often exhibit significant impairments in imitation, potentially impacting their social communication skills. This study examined the relationship between imitation abilities and social communication in autistic children and evaluated the effectiveness of the Early Start Denver Model (ESDM) intervention. The study included 52 autistic children aged 2-5, divided into an experimental group receiving ESDM intervention and a control group undergoing standard rehabilitation. We assessed the children's imitation and social communication skills before and after the intervention. Results indicated a significant positive correlation between imitation and social communication skills both before and after the intervention. Specifically, various forms of imitation (e.g., vocal, gestural, object-related) were closely linked to different domains of social communication (e.g., expressive communication, joint attention, social skills). Baseline imitation levels and improvements in imitation were significant predictors of enhanced social communication, jointly accounting for over half of the observed improvements in social communication, with imitation improvement being the strongest predictor. Age positively moderated the relationship between imitation and social communication, with older children showing a stronger impact of imitation on social communication. Although these effects were evident across groups, the ESDM group showed greater gains in imitation skills compared to the control group. However, we did not find evidence of an intervention effect on social communication skills. This study underscores the critical role of imitation in the social communication development of autistic children. These findings support the enhancement of imitation skills in early interventions for autistic children, highlighting the effectiveness of ESDM in fostering imitation abilities.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"23"},"PeriodicalIF":5.5,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Atypical maturation of the functional connectome hierarchy in autism.","authors":"Jong-Eun Lee, Sunghun Kim, Shinwon Park, Hyoungshin Choi, Bo-Yong Park, Hyunjin Park","doi":"10.1186/s13229-025-00641-9","DOIUrl":"10.1186/s13229-025-00641-9","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is marked by disruptions in low-level sensory processing and higher-order sociocognitive functions, suggesting a complex interplay between different brain regions across the cortical hierarchy. However, the developmental trajectory of this hierarchical organization in ASD remains underexplored. Herein, we investigated the maturational abnormalities in the cortical hierarchy among individuals with ASD.</p><p><strong>Methods: </strong>Resting-state functional magnetic resonance imaging data from three large-scale datasets were analyzed: Autism Brain Imaging Data Exchange I and II and Lifespan Human Connectome Project Development (aged 5-22 years). The principal functional connectivity gradient representing cortical hierarchy was estimated using diffusion map embedding. By applying normative modeling with the generalized additive model for location, scale, and shape (GAMLSS), we captured the nonlinear trajectories of the developing functional gradient, as well as the individual-level deviations in ASD from typical development based on centile scores measured as deviations from the normative curves. A whole-brain summary metric, the functional hierarchy score, was derived to measure the extent of abnormal maturation in individuals with ASD. Finally, through a series of mediation analyses, we examined the potential role of network-level connectomic disruptions between the diagnoses and deviations in the cortical hierarchy.</p><p><strong>Results: </strong>The maturation of cortical hierarchy in individuals with ASD followed a non-linear trajectory, showing delayed maturation during childhood compared to that of typically developing individuals, followed by an accelerated \"catch-up\" phase during adolescence and a subsequent decline in young adulthood. The nature of these deviations varied across networks, with sensory and attention networks displaying the most pronounced abnormalities in childhood, while higher-order networks, particularly the default mode network (DMN), remaining impaired from childhood to adolescence. Mediation analyses revealed that the persistent reduction in DMN segregation throughout development was a key contributor to the atypical development of cortical hierarchy in ASD.</p><p><strong>Limitations: </strong>The uneven distribution of samples across age groups, particularly in the later stages of development, limited our ability to fully capture developmental trajectories among older individuals.</p><p><strong>Conclusions: </strong>These findings highlight the importance of understanding the developmental trajectories of cortical organization in ASD, collectively suggesting that early interventions aimed at promoting the normative development of higher-order networks may be critical for improving outcomes in individuals with ASD.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"21"},"PeriodicalIF":5.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The \"Tetris effect\": autistic and non-autistic people share an implicit drive for perceptual cohesion.","authors":"Nazia Jassim, Brónagh McCoy, Esther Wing-Chi Yip, Carrie Allison, Simon Baron-Cohen, Rebecca P Lawson","doi":"10.1186/s13229-025-00654-4","DOIUrl":"10.1186/s13229-025-00654-4","url":null,"abstract":"<p><strong>Background: </strong>When working on jigsaw puzzles, we mentally \"combine\" two pieces to form a composite image even before physically fitting them together. This happens when the separate pieces could logically create a cohesive picture and not when they are mismatched or incoherent. The capacity of the brain to combine individual elements to form possible wholes serves as the basis of perceptual organisation. This drive for perceptual cohesion-the \"Tetris effect\"-can be seen in the famous game, where people automatically perceive logical combinations from separate pieces. However, it is unclear how this presents in populations known to have perceptual differences, such as autistic people. Theories on the inclination to process local over global details in autism and autistic strengths in pattern recognition lead to conflicting predictions regarding the drive for perceptual cohesion in autistic compared to non-autistic people.</p><p><strong>Methods: </strong>In this large-scale (n = 470) pre-registered online behavioural study, we aimed to replicate previous research conducted on neurotypical participants and to extend this work to autistic participants. We used two tasks with Tetris-style stimuli to examine how autistic (n = 196) and non-autistic (n = 274) adults implicitly perceive possible wholes from individual parts. Data were analysed using logistic mixed-effects regression models and hierarchical Signal Detection Theory modelling.</p><p><strong>Results: </strong>Overall, we replicated the results from the original study in finding participants are more likely to perceive parts as wholes when there is the potential to form a whole, compared to when there is not. However, we found no differences between autistic and non-autistic participants across both tasks.</p><p><strong>Limitations: </strong>Although power calculations were carried out to assess sample sizes needed to detect a group difference, given the small effect size (Cohen's d = 0.37) in the original study, it may be that any existing group differences are still undetectable with the current sample size.</p><p><strong>Conclusions: </strong>We conclude that the \"Tetris effect\" is ubiquitous and seen in both neurotypical and neurodiverse populations. Our findings challenge the deficit-focussed narrative often seen in the autism literature and highlight the similarities in task performance between autistic and non-autistic participants.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"22"},"PeriodicalIF":5.5,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11948850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Obsessional thinking and autistic traits are each uniquely associated with greater traits of gender dysphoria in clinical and nonclinical adult samples.","authors":"Karl Mears, Dheeraj Rai, Punit Shah, Chris Ashwin","doi":"10.1186/s13229-025-00649-1","DOIUrl":"10.1186/s13229-025-00649-1","url":null,"abstract":"<p><strong>Background: </strong>Research has demonstrated a strong relationship between autism and gender dysphoria (GD) and that this relationship could be explained by obsessional interests which are characteristic of autism. However, these studies often measured obsessions using either single items which questions the reliability of the findings, or within autistic trait measures meaning the findings may simply index a more general relationship between autistic traits and GD. Therefore, the present study aimed to investigate the relationships between obsessional thoughts and traits of GD using a measure of obsessional thoughts alongside a measure of autistic traits, which was investigated in both non-clinical and clinical samples.</p><p><strong>Methods: </strong>A total of 145 non-clinical participants took part in Study 1 and all completed the Autism-Spectrum Quotient (AQ) as a measure of autistic traits, the Obsessive-Compulsive Inventory-Revised (OCI-R) obsessional thoughts subscale as a measure of obsessional thoughts, and the Gender-Identity/Gender-Dysphoria Questionnaire (GIDYQ) to measure traits of GD. For Study 2, a total of 226 participants took part in Study 2 and all completed the same measures as in Study 1. They included participants diagnosed with GD (N = 49), autism (N = 65), OCD (N = 46) and controls with no diagnosis (N = 66).</p><p><strong>Results: </strong>The hierarchical linear regression for Study 1 showed that both total AQ and OCI-R obsessional thoughts scores were uniquely associated with GIDYQ scores, with no interaction effect between the scores. The results for Study 2, from a hierarchical linear regression, once again found that obsessional thoughts and autistic traits were each uniquely associated with GIDYQ scores, but not their interaction. The GD and autistic groups both reported significantly greater traits of GD than the OCD and control groups, with the GD group reporting higher scores than the autistic group.</p><p><strong>Limitations: </strong>Participants self-reported their diagnoses for Study 2, but diagnostic tests to verify these were not administered. Traits of GD were also measured at a single point in time, despite such traits being transient and continuous.</p><p><strong>Conclusions: </strong>The results show both obsessional thoughts and autistic traits are uniquely associated with GD, and that autistic people experience greater traits of GD than other clinical groups.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"20"},"PeriodicalIF":5.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11916952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Somatostatin-expressing interneurons of prefrontal cortex modulate social deficits in the Magel2 mouse model of autism.","authors":"Xiaona Wang, Mengyuan Chen, Daoqi Mei, Shengli Shi, Jisheng Guo, Chao Gao, Qi Wang, Shuai Zhao, Xingxue Yan, Huichun Zhang, Yanli Wang, Bin Guo, Yaodong Zhang","doi":"10.1186/s13229-025-00653-5","DOIUrl":"10.1186/s13229-025-00653-5","url":null,"abstract":"<p><p>Dysfunction in social interactions is a core symptom of autism spectrum disorder (ASD). Nevertheless, the neural mechanisms underlying social deficits in ASD are poorly understood. By integrating electrophysiological, in vivo fiber photometry, viral-mediated tracing, optogenetic and pharmacological stimulation, we show reduced intrinsic excitability and hypoactivity of SOM interneurons in medial prefrontal cortex (mPFC) in Magel2-deficient mice, an established ASD model, were required to social defects. Chemogenetic inhibition of mPFC SOM-containing interneurons resulted in reduced social interaction in wild-type Magel2 mice. These sociability deficits can be rescued by optogenetic activation by excitability of SOM in the mPFC and mPFC^SOM-LS inhibitory pathway in Magel 2 knockout mice. These results demonstrate the hypoactivity for SOM action in the mPFC in social impairments, and suggest targeting this mechanism that may prove therapeutically beneficial for mitigating social behavioral disturbances observed in ASD.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"18"},"PeriodicalIF":5.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605715","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"White matter microstructure as a potential contributor to differences in resting state alpha activity between neurotypical and autistic children: a longitudinal multimodal imaging study.","authors":"Guannan Shen, Heather L Green, Marybeth McNamee, Rose E Franzen, Marissa DiPiero, Jeffrey I Berman, Matthew Ku, Luke Bloy, Song Liu, Megan Airey, Sophia Goldin, Lisa Blaskey, Emily S Kuschner, Mina Kim, Kimberly Konka, Gregory A Miller, J Christopher Edgar","doi":"10.1186/s13229-025-00646-4","DOIUrl":"10.1186/s13229-025-00646-4","url":null,"abstract":"<p><p>We and others have demonstrated the resting-state (RS) peak alpha frequency (PAF) as a potential clinical marker for young children with autism spectrum disorder (ASD), with previous studies observing a higher PAF in school-age children with ASD versus typically developing (TD) children, as well as an association between the RS PAF and measures of processing speed in TD but not ASD. The brain mechanisms associated with these findings are unknown. A few studies have found that in children more mature optic radiation white matter is associated with a higher PAF. Other studies have reported white matter and neural activity associations in TD but not ASD. The present study hypothesized that group differences in the RS PAF are due, in part, to group differences in optic radiation white matter and PAF associations. The maturation of the RS PAF (measured using magnetoencephalography(MEG)), optic radiation white matter (measured using diffusion tensor imaging(DTI)), and associations with processing speed were assessed in a longitudinal cohort of TD and ASD children. Time 1 MEG and DTI measures were obtained at 6-8 years old (59TD and 56ASD) with follow-up brain measures collected ~ 1.5 and ~ 3 years later. The parietal-occipital PAF increased with age in both groups by 0.13 Hz/year, with a main effect of group showing the expected higher PAF in ASD than TD (an average of 0.26 Hz across the 3 time points). Across age, the RS PAF predicted processing speed in TD but not ASD. Finally, more mature optic radiation white matter measures (FA, RD, MD, AD) were associated with a higher PAF in both groups. Present findings provide additional evidence supporting the use of the RS PAF as a brain marker in children with ASD 6-10 years old, and replicate findings of an association between the RS PAF and processing speed in TD but not ASD. The hypothesis that the RS PAF group differences (with ASD leading TD by about 2 years) would be explained by group differences in optic radiation white matter was not supported, with brain structure-function associations indicating that more mature optic radiation white matter is associated with a higher RS PAF in both groups.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"19"},"PeriodicalIF":5.5,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11895156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Postnatal downregulation of Fmr1 in microglia promotes microglial reactivity and causes behavioural alterations in female mice.","authors":"Mehdi Hooshmandi, David Ho-Tieng, Kevin C Lister, Weihua Cai, Calvin Wong, Nicole Brown, Jonathan Fan, Volodya Hovhannisyan, Sonali Uttam, Masha Prager-Khoutorsky, Nahum Sonenberg, Christos G Gkogkas, Arkady Khoutorsky","doi":"10.1186/s13229-025-00648-2","DOIUrl":"10.1186/s13229-025-00648-2","url":null,"abstract":"<p><strong>Background: </strong>Fragile X syndrome is caused by the loss of the Fmr1 gene expression. Deletion of Fmr1 in various neuronal and non-neuronal subpopulations in the brain of mice leads to cell-type-specific effects. Microglia, immune cells critical for the refinement of neuronal circuits during brain development, have been implicated in various neurodevelopmental disorders, including fragile X syndrome. However, it is unknown whether reduced Fmr1 expression in microglia leads to molecular and behavioral phenotypes.</p><p><strong>Methods: </strong>We downregulated Fmr1 in microglia during early and late postnatal development and studied the effect on microglial morphology and distinct behaviours.</p><p><strong>Results: </strong>Female, but not male, adult mice with downregulation of Fmr1 in microglia during early development exhibited reactive microglia and behavioral phenotypes, including enhanced self-grooming and alterations in social interaction. Downregulation of Fmr1 in microglia during late development induced a milder phenotype, characterized by impaired preference for social novelty without affecting microglia morphology.</p><p><strong>Conclusions: </strong>The downregulation of Fmr1 and its encoded protein FMRP in microglia contributes to behavioural phenotypes in a sex-specific manner.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"17"},"PeriodicalIF":5.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11887208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcallosal white matter and cortical gray matter variations in autistic adults aged 30-73 years.","authors":"Young Seon Shin, Danielle Christensen, Jingying Wang, Desirae J Shirley, Ann-Marie Orlando, Regilda A Romero, David E Vaillancourt, Bradley J Wilkes, Stephen A Coombes, Zheng Wang","doi":"10.1186/s13229-025-00652-6","DOIUrl":"10.1186/s13229-025-00652-6","url":null,"abstract":"<p><strong>Background: </strong>Autism spectrum disorder (ASD) is a lifelong condition that profoundly impacts health, independence, and quality of life. However, research on brain aging in autistic adults is limited, and microstructural variations in white and gray matter remain poorly understood. To address this critical gap, we assessed novel diffusion MRI (dMRI) biomarkers, free water, and free water corrected fractional anisotropy (fwcFA), and mean diffusivity (fwcMD) across 32 transcallosal tracts and their corresponding homotopic grey matter origin/endpoint regions of interest (ROIs) in middle and old aged autistic adults.</p><p><strong>Methods: </strong>Forty-three autistic adults aged 30-73 and 43 age-, sex-, and IQ-matched neurotypical controls underwent dMRI scans. We examined free water, fwcFA, fwcMD differences between the two groups and age-related pattern of each dMRI metric across the whole brain for each group. The relationships between clinical measures of ASD and free water in regions that significantly differentiated autistic adults from neurotypical controls were also explored. In supplementary analyses, we also assessed free water uncorrected FA and MD using conventional single tensor modeling.</p><p><strong>Results: </strong>Autistic adults exhibited significantly elevated free water in seven frontal transcallosal tracts compared to controls. In controls, age-related increases in free water and decreases in fwcFA were observed across most transcallosal tracts. However, these age-associated patterns were entirely absent in autistic adults. In gray matter, autistic adults showed elevated free water in the calcarine cortices and lower fwcMD in the dorsal premotor cortices compared to controls. Lastly, age-related increases in free water were found across all white matter and gray matter ROIs in neurotypical controls, whereas no age-related associations were detected in any dMRI metrics for autistic adults.</p><p><strong>Limitations: </strong>We only recruited cognitively capable autistic adults, which limits the generalizability of our findings across the full autism spectrum. The cross-sectional design precludes inferences about microstructural changes over time in middle and old aged autistic adults.</p><p><strong>Conclusions: </strong>Our findings revealed increased free water load in frontal white matter in autistic adults and identified distinct age-associated microstructural variations between the two groups. These findings highlight more heterogeneous brain aging profiles in autistic adults. Our study also demonstrated the importance of quantifying free water in dMRI studies of ASD.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"16"},"PeriodicalIF":5.7,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Do autistic individuals show atypical performance in probabilistic learning? A comparison of cue-number, predictive strength, and prediction error.","authors":"Jia Hoong Ong, Lei Zhang, Fang Liu","doi":"10.1186/s13229-025-00651-7","DOIUrl":"10.1186/s13229-025-00651-7","url":null,"abstract":"<p><strong>Background: </strong>According to recent models of autism, autistic individuals may find learning probabilistic cue-outcome associations more challenging than deterministic learning, though empirical evidence for this is mixed. Here we examined the mechanism of probabilistic learning more closely by comparing autistic and non-autistic adults on inferring a target cue from multiple cues or integrating multiple target cues and learning from associations with various predictive strengths.</p><p><strong>Methods: </strong>52 autistic and 52 non-autistic participants completed three tasks: (i) single-cue probabilistic learning, in which they had to infer a single target cue from multiple cues to learn cue-outcome associations; (ii) multi-cue probabilistic learning, in which they had to learn associations of various predictive strengths via integration of multiple cues; and (iii) reinforcement learning, which required learning the contingencies of two stimuli with a probabilistic reinforcement schedule. Accuracy on the two probabilistic learning tasks was modelled separately using a binomial mixed effects model whereas computational modelling was performed on the reinforcement learning data to obtain a model parameter on prediction error integration (i.e., learning rate).</p><p><strong>Results: </strong>No group differences were found in the single-cue probabilistic learning task. Group differences were evident for the multi-cue probabilistic learning task for associations that are weakly predictive (between 40 and 60%) but not when they are strongly predictive (10-20% or 80-90%). Computational modelling on the reinforcement learning task revealed that, as a group, autistic individuals had a higher learning rate than non-autistic individuals.</p><p><strong>Limitations: </strong>Due to the online nature of the study, we could not confirm the diagnosis of our autistic sample. The autistic participants were likely to have typical intelligence, and so our findings may not be generalisable to the entire autistic population. The learning tasks are constrained by a relatively small number of trials, and so it is unclear whether group differences will still be seen when given more trials.</p><p><strong>Conclusions: </strong>Autistic adults showed similar performance as non-autistic adults in learning associations by inferring a single cue or integrating multiple cues when the predictive strength was strong. However, non-autistic adults outperformed autistic adults when the predictive strength was weak, but only in the later phase. Autistic individuals were also more likely to incorporate prediction errors during decision making, which may explain their atypical performance on the weakly predictive associations. Our findings have implications for understanding differences in social cognition, which is often noisy and weakly predictive, among autistic individuals.</p>","PeriodicalId":18733,"journal":{"name":"Molecular Autism","volume":"16 1","pages":"15"},"PeriodicalIF":5.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877734/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143542635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}