Pub Date : 2025-10-01DOI: 10.1016/j.bpsc.2024.10.014
Yahui Chen , Chen Yang , Bicheng Gao , Kehui Chen , R. Joanne Jao Keehn , Ralph-Axel Müller , Li-Xia Yuan , Yuqi You
Background
Atypical sensory processing is a prevalent feature of autism spectrum disorder (ASD) and constitutes a core diagnostic criterion in DSM-5. However, the neurocognitive underpinnings of atypical unimodal and multimodal sensory processing and their relationships with autism symptoms remain unclear.
Methods
In this study, we examined intrinsic functional connectivity (FC) patterns among 5 unimodal sensory and multisensory integration (MSI) networks in ASD using a large multisite dataset (N = 646) and investigated the relationships between altered FC, atypical sensory processing, social communicative deficits, and overall autism symptoms using correlation and mediation analyses.
Results
Compared with typically developing control participants, participants in the ASD group demonstrated increased FC of the olfactory network, decreased FC within the MSI network, and decreased FC of the MSI–unimodal sensory networks. Furthermore, altered FC was positively associated with autism symptom severity, and such associations were completely mediated by atypical sensory processing and social communicative deficits.
Conclusions
ASD-specific olfactory overconnectivity and MSI–unimodal sensory underconnectivity lend support to the intense world theory and weak central coherence theory, suggesting olfactory hypersensitivity at the expense of MSI as a potential neural mechanism underlying atypical sensory processing in ASD. These atypical FC patterns suggest potential targets for psychological and neuromodulatory interventions.
背景：非典型感觉处理是自闭症谱系障碍（ASD）的一个普遍特征，也是《精神障碍诊断与统计手册》第五版（DSM-5）的一个核心诊断标准。然而，非典型单模态和多模态感觉处理的神经认知基础及其与自闭症症状的关系仍不清楚：本研究利用大型多站点数据集（n = 646）研究了自闭症患者五种单模态感觉和多感觉统合（MSI）网络的内在功能连接（FC）模式，并通过相关性和中介分析研究了FC改变、非典型感觉处理、社会交往障碍和整体自闭症症状之间的关系：与发育正常（TD）对照组相比，ASD组的嗅觉网络FC增加，MSI网络内的FC减少，MSI-非模态-感觉网络的FC减少。此外，FC的改变与自闭症症状的严重程度呈正相关，而这种关联完全是由非典型感觉处理和社会交往障碍介导的：ASD特异性嗅觉过度连接和MSI-非模态感觉连接不足支持了 "强烈世界理论"（Intense World Theory）和 "弱中枢一致性理论"（Weak Central Coherence Theory），表明以牺牲多感觉整合为代价的嗅觉过敏是ASD非典型感觉处理的潜在神经机制。这些非典型的感觉处理模式进一步提出了心理和神经调节干预的潜在目标。
{"title":"Altered Functional Connectivity of Unimodal Sensory and Multisensory Integration Networks Is Related to Symptom Severity in Autism Spectrum Disorder","authors":"Yahui Chen , Chen Yang , Bicheng Gao , Kehui Chen , R. Joanne Jao Keehn , Ralph-Axel Müller , Li-Xia Yuan , Yuqi You","doi":"10.1016/j.bpsc.2024.10.014","DOIUrl":"10.1016/j.bpsc.2024.10.014","url":null,"abstract":"<div><h3>Background</h3><div>Atypical sensory processing<span> is a prevalent feature of autism spectrum disorder<span> (ASD) and constitutes a core diagnostic criterion in DSM-5. However, the neurocognitive underpinnings of atypical unimodal and multimodal sensory processing and their relationships with autism symptoms remain unclear.</span></span></div></div><div><h3>Methods</h3><div><span>In this study, we examined intrinsic functional connectivity<span> (FC) patterns among 5 unimodal sensory and multisensory integration (MSI) networks in ASD using a large multisite dataset (</span></span><em>N</em><span> = 646) and investigated the relationships between altered FC, atypical sensory processing, social communicative deficits, and overall autism symptoms using correlation and mediation analyses.</span></div></div><div><h3>Results</h3><div>Compared with typically developing control participants, participants in the ASD group demonstrated increased FC of the olfactory network, decreased FC within the MSI network, and decreased FC of the MSI–unimodal sensory networks. Furthermore, altered FC was positively associated with autism symptom severity, and such associations were completely mediated by atypical sensory processing and social communicative deficits.</div></div><div><h3>Conclusions</h3><div>ASD-specific olfactory overconnectivity and MSI–unimodal sensory underconnectivity lend support to the intense world theory and weak central coherence theory, suggesting olfactory hypersensitivity at the expense of MSI as a potential neural mechanism underlying atypical sensory processing in ASD. These atypical FC patterns suggest potential targets for psychological and neuromodulatory interventions.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 10","pages":"Pages 1045-1056"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570454","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 : 2025-10-01DOI: 10.1016/j.bpsc.2024.10.007
Margot Mangnus , Saskia B.J. Koch , Kexin Cai , Miriam Greidanus Romaneli , Peter Hagoort , Jana Bašnáková , Arjen Stolk
Background
While individuals with autism often face challenges in everyday social interactions, they may demonstrate proficiency in structured theory of mind (ToM) tasks that assess their ability to infer others’ mental states. Using functional magnetic resonance imaging and pupillometry, we investigated whether these discrepancies stem from diminished spontaneous mentalizing or broader difficulties in unstructured contexts.
Methods
Fifty-two adults diagnosed with autism and 52 neurotypical control participants viewed the animated short Partly Cloudy, a nonverbal animated film with a dynamic social narrative known to engage the ToM brain network during specific scenes. Analysis focused on comparing brain and pupil responses to these ToM events. Additionally, dynamic intersubject correlations were used to explore the variability of these responses throughout the film.
Results
Both groups showed similar brain and pupil responses to ToM events and provided comparable descriptions of the characters’ mental states. However, participants with autism exhibited significantly stronger correlations in their responses across the film’s social narrative, indicating reduced interindividual variability. This distinct pattern emerged well before any ToM events and involved brain regions beyond the ToM network.
Conclusions
Our findings provide functional evidence of spontaneous mentalizing in autism, demonstrating this capacity in a context that affords but does not require mentalizing. Rather than responses to ToM events, a novel neurocognitive signature—interindividual variability in brain and pupil responses to evolving social narratives—differentiated neurotypical individuals from individuals with autism. These results suggest that idiosyncratic narrative processing in unstructured settings, a common element of everyday social interactions, may offer a more sensitive scenario for understanding the autistic mind.
背景：虽然自闭症患者在日常社会交往中经常面临挑战，但他们在评估其推断他人心理状态的能力的结构化心智理论（ToM）任务中却能表现得游刃有余。我们使用功能性核磁共振成像和瞳孔测量法研究了这些差异是源于自发心智化的减弱，还是源于非结构化情境中更广泛的困难：52名被诊断患有自闭症的成年人和52名神经典型对照者观看了《多云》（Partly Cloudy），这是一部非语言动画电影，具有动态的社会叙事，已知在特定场景中会调动ToM大脑网络。分析的重点是比较大脑和瞳孔对这些 ToM 事件的反应。此外，受试者之间的动态相关性还探讨了这些反应在整部影片中的可变性：结果：两组受试者对 ToM 事件的大脑和瞳孔反应相似，对人物精神状态的描述也相当。然而，自闭症参与者的反应在整个影片的社会叙事中表现出明显更强的相关性，这表明个体间的变异性降低了。这种独特的模式出现在任何ToM事件之前，并涉及ToM网络以外的大脑区域：我们的研究结果为自闭症患者的自发心智化提供了功能性证据，证明了自闭症患者在能够但不需要心智化的情境中具有这种能力。一种新的神经认知特征--大脑和瞳孔对不断演变的社会叙事的反应的个体间差异性--而不是对ToM事件的反应，将神经畸形个体与自闭症患者区分开来。这些结果表明，非结构化环境中的特异性叙事处理是日常社交互动的常见元素，它可能为理解自闭症患者的心理提供了一个更敏感的场景。
{"title":"Preserved Spontaneous Mentalizing Amid Reduced Intersubject Variability in Autism During a Movie Narrative","authors":"Margot Mangnus , Saskia B.J. Koch , Kexin Cai , Miriam Greidanus Romaneli , Peter Hagoort , Jana Bašnáková , Arjen Stolk","doi":"10.1016/j.bpsc.2024.10.007","DOIUrl":"10.1016/j.bpsc.2024.10.007","url":null,"abstract":"<div><h3>Background</h3><div>While individuals with autism often face challenges in everyday social interactions, they may demonstrate proficiency in structured theory of mind (ToM) tasks that assess their ability to infer others’ mental states. Using functional magnetic resonance imaging and pupillometry, we investigated whether these discrepancies stem from diminished spontaneous mentalizing or broader difficulties in unstructured contexts.</div></div><div><h3>Methods</h3><div>Fifty-two adults diagnosed with autism and 52 neurotypical control participants viewed the animated short <em>Partly Cloudy</em>, a nonverbal animated film with a dynamic social narrative known to engage the ToM brain network during specific scenes. Analysis focused on comparing brain and pupil responses to these ToM events. Additionally, dynamic intersubject correlations were used to explore the variability of these responses throughout the film.</div></div><div><h3>Results</h3><div>Both groups showed similar brain and pupil responses to ToM events and provided comparable descriptions of the characters’ mental states. However, participants with autism exhibited significantly stronger correlations in their responses across the film’s social narrative, indicating reduced interindividual variability. This distinct pattern emerged well before any ToM events and involved brain regions beyond the ToM network.</div></div><div><h3>Conclusions</h3><div>Our findings provide functional evidence of spontaneous mentalizing in autism, demonstrating this capacity in a context that affords but does not require mentalizing. Rather than responses to ToM events, a novel neurocognitive signature—interindividual variability in brain and pupil responses to evolving social narratives—differentiated neurotypical individuals from individuals with autism. These results suggest that idiosyncratic narrative processing in unstructured settings, a common element of everyday social interactions, may offer a more sensitive scenario for understanding the autistic mind.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 10","pages":"Pages 1057-1066"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570467","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 : 2025-10-01DOI: 10.1016/j.bpsc.2025.05.010
Ana I. Silva , Ida E. Sønderby , George Kirov , Abdel Abdellaoui , Ingrid Agartz , David Ames , Nicola J. Armstrong , Eric Artiges , Tobias Banaschewski , Anne S. Bassett , Carrie E. Bearden , John Blangero , Rune Boen , Dorret I. Boomsma , Robin Bülow , Nancy J. Butcher , Vince Calhoun , Linda E. Campbell , Eva W.C. Chow , Simone Ciufolini , David E.J. Linden
Background
Copy number variants (CNVs) may increase the risk for neurodevelopmental conditions. The neurobiological mechanisms that link these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals who carry CNVs are associated with their degree of penetrance.
Methods
We investigated whether increased CNV penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-CNV consortium. In the main analyses, we included 9268 individuals (aged 7–90 years, 54% female), from which we identified 398 carriers of 36 neurodevelopmental CNVs at 20 distinct loci. A secondary analysis was performed including additional neuroimaging data from the ENIGMA-22q consortium, including 274 carriers of the 22q11.2 deletion and 291 noncarriers. CNV penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk of developing either schizophrenia or other developmental disorders (including developmental delay, autism spectrum disorder, and congenital malformations).
Results
For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume. For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus.
Conclusions
Our findings link global and regional cortical morphometric features with CNV penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.
{"title":"Penetrance of Neurodevelopmental Copy Number Variants Is Associated With Variations in Cortical Morphology","authors":"Ana I. Silva , Ida E. Sønderby , George Kirov , Abdel Abdellaoui , Ingrid Agartz , David Ames , Nicola J. Armstrong , Eric Artiges , Tobias Banaschewski , Anne S. Bassett , Carrie E. Bearden , John Blangero , Rune Boen , Dorret I. Boomsma , Robin Bülow , Nancy J. Butcher , Vince Calhoun , Linda E. Campbell , Eva W.C. Chow , Simone Ciufolini , David E.J. Linden","doi":"10.1016/j.bpsc.2025.05.010","DOIUrl":"10.1016/j.bpsc.2025.05.010","url":null,"abstract":"<div><h3>Background</h3><div>Copy number variants (CNVs) may increase the risk for neurodevelopmental conditions. The neurobiological mechanisms that link these high-risk genetic variants to clinical phenotypes are largely unknown. An important question is whether brain abnormalities in individuals who carry CNVs are associated with their degree of penetrance.</div></div><div><h3>Methods</h3><div>We investigated whether increased CNV penetrance for schizophrenia and other developmental disorders was associated with variations in cortical and subcortical morphology. We pooled T1-weighted brain magnetic resonance imaging and genetic data from 22 cohorts from the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis)-CNV consortium. In the main analyses, we included 9268 individuals (aged 7–90 years, 54% female), from which we identified 398 carriers of 36 neurodevelopmental CNVs at 20 distinct loci. A secondary analysis was performed including additional neuroimaging data from the ENIGMA-22q consortium, including 274 carriers of the 22q11.2 deletion and 291 noncarriers. CNV penetrance was estimated through penetrance scores that were previously generated from large cohorts of patients and controls. These scores represent the probability risk of developing either schizophrenia or other developmental disorders (including developmental delay, autism spectrum disorder, and congenital malformations).</div></div><div><h3>Results</h3><div>For both schizophrenia and developmental disorders, increased penetrance scores were associated with lower surface area in the cerebral cortex and lower intracranial volume. For both conditions, associations between CNV-penetrance scores and cortical surface area were strongest in regions of the occipital lobes, specifically in the cuneus and lingual gyrus.</div></div><div><h3>Conclusions</h3><div>Our findings link global and regional cortical morphometric features with CNV penetrance, providing new insights into neurobiological mechanisms of genetic risk for schizophrenia and other developmental disorders.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 10","pages":"Pages 1093-1106"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144868","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 : 2025-10-01DOI: 10.1016/j.bpsc.2025.08.006
Morton Ann Gernsbacher
{"title":"Challenging the Assumption That Autistic People Lack a Theory of Mind","authors":"Morton Ann Gernsbacher","doi":"10.1016/j.bpsc.2025.08.006","DOIUrl":"10.1016/j.bpsc.2025.08.006","url":null,"abstract":"","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 10","pages":"Pages 1001-1002"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227743","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 : 2025-10-01DOI: 10.1016/j.bpsc.2025.04.001
Ágota Vass , Kinga Farkas , Orsolya Lányi , Tamás Kói , Gábor Csukly , János M. Réthelyi , Máté Baradits
Background
Electroencephalography microstates are promising biomarkers for psychiatric conditions, although prior meta-analyses mainly focused on schizophrenia (SCH) and mood disorders. This study expands the analysis to a wider range of mental disorders, examining microstate variations across the psychosis and mood spectra and assessing medication effects in SCH.
Methods
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search, identifying 24 studies meeting inclusion criteria. Analyses were performed across 2 psychiatric subgroups: psychotic disorders and mood disorders. We further conducted a subgroup analysis within the SCH spectrum to examine differences in microstate properties between medicated and unmedicated patients.
Results
Microstate C demonstrated a significant increase in coverage and occurrence in patients with SCH, first-episode psychosis, and high risk of psychosis and increased duration in SCH. The absence of increased occurrence in medicated patients with SCH suggests that this feature may be state dependent or modulated by treatment. In contrast, microstate D exhibited significant decreases in duration and coverage in unmedicated patients with SCH, indicating potential links with acute psychotic states.
Conclusions
Our findings suggest that microstates C and D could serve as potential biomarkers in SCH, with microstate D alterations linked to acute psychotic symptoms and microstate C potentially reflecting a chronic course or treatment effects. These results emphasize the clinical potential of microstate analysis in psychotic disorder diagnosis and treatment monitoring. The literature on microstate variations in neurodevelopmental and mood disorders is limited, highlighting the need for further research to determine their biomarker potential in these conditions.
{"title":"Current Status of Electroencephalography Microstate in Psychiatric Disorders: A Systematic Review and Meta-Analysis","authors":"Ágota Vass , Kinga Farkas , Orsolya Lányi , Tamás Kói , Gábor Csukly , János M. Réthelyi , Máté Baradits","doi":"10.1016/j.bpsc.2025.04.001","DOIUrl":"10.1016/j.bpsc.2025.04.001","url":null,"abstract":"<div><h3>Background</h3><div>Electroencephalography microstates are promising biomarkers for psychiatric conditions, although prior meta-analyses mainly focused on schizophrenia (SCH) and mood disorders. This study expands the analysis to a wider range of mental disorders, examining microstate variations across the psychosis and mood spectra and assessing medication effects in SCH.</div></div><div><h3>Methods</h3><div>Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive literature search, identifying 24 studies meeting inclusion criteria. Analyses were performed across 2 psychiatric subgroups: psychotic disorders and mood disorders. We further conducted a subgroup analysis within the SCH spectrum to examine differences in microstate properties between medicated and unmedicated patients.</div></div><div><h3>Results</h3><div>Microstate C demonstrated a significant increase in coverage and occurrence in patients with SCH, first-episode psychosis, and high risk of psychosis and increased duration in SCH. The absence of increased occurrence in medicated patients with SCH suggests that this feature may be state dependent or modulated by treatment. In contrast, microstate D exhibited significant decreases in duration and coverage in unmedicated patients with SCH, indicating potential links with acute psychotic states.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that microstates C and D could serve as potential biomarkers in SCH, with microstate D alterations linked to acute psychotic symptoms and microstate C potentially reflecting a chronic course or treatment effects. These results emphasize the clinical potential of microstate analysis in psychotic disorder diagnosis and treatment monitoring. The literature on microstate variations in neurodevelopmental and mood disorders is limited, highlighting the need for further research to determine their biomarker potential in these conditions.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 10","pages":"Pages 1015-1024"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144059834","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 : 2025-10-01DOI: 10.1016/j.bpsc.2024.09.003
Annika C. Linke , Bosi Chen , Lindsay Olson , Michaela Cordova , Molly Wilkinson , Tiffany Wang , Meagan Herrera , Madison Salmina , Adriana Rios , Judy Mahmalji , Tess Do , Jessica Vu , Michelle Budman , Alexis Walker , Inna Fishman
Background
Atypical balance of excitation (E) and inhibition (I) in the brain is thought to contribute to the emergence and symptomatology of autism spectrum disorder (ASD). E/I ratio can be estimated from resting-state functional magnetic resonance imaging (fMRI) using the Hurst exponent, H. A recent study reported decreased ventromedial prefrontal cortex (vmPFC) H in male adults with ASD. Part of the default mode network (DMN), the vmPFC plays an important role in emotion regulation, decision making, and social cognition. It frequently shows altered function and connectivity in individuals with autism.
Methods
The current study presents the first fMRI evidence of altered early development of vmPFC H and its link to DMN functional connectivity and emotional control in toddlers and preschoolers with ASD. A total of 83 children (45 with ASD), ages 1.5–5 years, underwent natural sleep fMRI as part of a longitudinal study.
Results
In a cross-sectional analysis, vmPFC H decreased with age in children with ASD, reflecting increasing E/I ratio, but not in typically developing children. This effect remained significant when controlling for gestational age at birth, socioeconomic status, or ethnicity. The same pattern was also observed in a subset of children with longitudinal fMRI data acquired 2 years apart on average. Lower vmPFC H was also associated with reduced functional connectivity within the DMN as well as with higher emotional control deficits (although only significant transdiagnostically).
Conclusions
These results suggest an early onset of E/I imbalances in the vmPFC in ASD, with likely consequences for the maturation of the DMN.
{"title":"Altered Development of the Hurst Exponent in the Medial Prefrontal Cortex in Preschoolers With Autism","authors":"Annika C. Linke , Bosi Chen , Lindsay Olson , Michaela Cordova , Molly Wilkinson , Tiffany Wang , Meagan Herrera , Madison Salmina , Adriana Rios , Judy Mahmalji , Tess Do , Jessica Vu , Michelle Budman , Alexis Walker , Inna Fishman","doi":"10.1016/j.bpsc.2024.09.003","DOIUrl":"10.1016/j.bpsc.2024.09.003","url":null,"abstract":"<div><h3>Background</h3><div>Atypical balance of excitation (E) and inhibition (I) in the brain is thought to contribute to the emergence and symptomatology of autism spectrum disorder (ASD). E/I ratio can be estimated from resting-state functional magnetic resonance imaging (fMRI) using the Hurst exponent, <em>H</em>. A recent study reported decreased ventromedial prefrontal cortex (vmPFC) <em>H</em> in male adults with ASD. Part of the default mode network (DMN), the vmPFC plays an important role in emotion regulation, decision making, and social cognition. It frequently shows altered function and connectivity in individuals with autism.</div></div><div><h3>Methods</h3><div>The current study presents the first fMRI evidence of altered early development of vmPFC <em>H</em> and its link to DMN functional connectivity and emotional control in toddlers and preschoolers with ASD. A total of 83 children (45 with ASD), ages 1.5–5 years, underwent natural sleep fMRI as part of a longitudinal study.</div></div><div><h3>Results</h3><div>In a cross-sectional analysis, vmPFC <em>H</em> decreased with age in children with ASD, reflecting increasing E/I ratio, but not in typically developing children. This effect remained significant when controlling for gestational age at birth, socioeconomic status, or ethnicity. The same pattern was also observed in a subset of children with longitudinal fMRI data acquired 2 years apart on average. Lower vmPFC <em>H</em> was also associated with reduced functional connectivity within the DMN as well as with higher emotional control deficits (although only significant transdiagnostically).</div></div><div><h3>Conclusions</h3><div>These results suggest an early onset of E/I imbalances in the vmPFC in ASD, with likely consequences for the maturation of the DMN.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 10","pages":"Pages 1037-1044"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303305","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 : 2025-10-01DOI: 10.1016/j.bpsc.2025.06.002
Soohyun Jeon , Jae-eon Kang , Jundong Hwang , Vince D. Calhoun , Jong-Hwan Lee
Background
Impulsivity in highly heritable attention-deficit/hyperactivity disorder (ADHD) has been studied using neural activity via functional magnetic resonance imaging (fMRI) or genetic data, but rarely with multivariate methods that link both. We investigated coupled neural activity and gene expression signatures, using parallel independent component analysis (pICA) and ABCD (Adolescent Brain Cognitive Development) Study data.
Methods
Children with ADHD (n = 394; 63% male) and healthy control children (n = 1000; 47% male) of European ancestry were included. The participants were randomly divided into 80% discovery and 20% replication datasets with demographic stratification. We analyzed neural activity and gene expressions from the discovery datasets using pICA and extracted paired independent components (pICs). The loading coefficients of the pICs were utilized to predict behavioral and cognitive data for a stop signal task (SST) in replication datasets.
Results
We identified 3 pICs estimated from gene expression in the cortex, cerebellum, and nucleus accumbens. Significant neural activity was mainly localized to the orbital/inferior/middle frontal gyri, rectal gyrus, precuneus, inferior temporal gyrus, inferior parietal lobule, and cerebellum. Significant gene components were associated with immunoglobulin-, taste receptor–, and immunity-related terms and overlapped with ADHD-related genes. The extracted fMRI-/gene-ICs were significantly correlated with mean reaction time, stop signal reaction time on the SST, and behavioral inhibition, with a large boost in sensitivity when both the paired fMRI-/gene-ICs and their interaction were used in a multimodal regression analysis.
Conclusions
We reported biologically plausible pairs of neural activity and gene sets using pICA, which were significantly associated with ADHD impulsivity–related behavioral and cognitive data.
{"title":"Abnormal Association Between Neural Activity and Genetic Expressions of Impulsivity in Attention-Deficit/Hyperactivity Disorder: An Adolescent Brain Cognitive Development Study","authors":"Soohyun Jeon , Jae-eon Kang , Jundong Hwang , Vince D. Calhoun , Jong-Hwan Lee","doi":"10.1016/j.bpsc.2025.06.002","DOIUrl":"10.1016/j.bpsc.2025.06.002","url":null,"abstract":"<div><h3>Background</h3><div>Impulsivity in highly heritable attention-deficit/hyperactivity disorder (ADHD) has been studied using neural activity via functional magnetic resonance imaging (fMRI) or genetic data, but rarely with multivariate methods that link both. We investigated coupled neural activity and gene expression signatures, using parallel independent component analysis (pICA) and ABCD (Adolescent Brain Cognitive Development) Study data.</div></div><div><h3>Methods</h3><div>Children with ADHD (<em>n</em> = 394; 63% male) and healthy control children (<em>n</em> = 1000; 47% male) of European ancestry were included. The participants were randomly divided into 80% discovery and 20% replication datasets with demographic stratification. We analyzed neural activity and gene expressions from the discovery datasets using pICA and extracted paired independent components (pICs). The loading coefficients of the pICs were utilized to predict behavioral and cognitive data for a stop signal task (SST) in replication datasets.</div></div><div><h3>Results</h3><div>We identified 3 pICs estimated from gene expression in the cortex, cerebellum, and nucleus accumbens. Significant neural activity was mainly localized to the orbital/inferior/middle frontal gyri, rectal gyrus, precuneus, inferior temporal gyrus, inferior parietal lobule, and cerebellum. Significant gene components were associated with immunoglobulin-, taste receptor–, and immunity-related terms and overlapped with ADHD-related genes. The extracted fMRI-/gene-ICs were significantly correlated with mean reaction time, stop signal reaction time on the SST, and behavioral inhibition, with a large boost in sensitivity when both the paired fMRI-/gene-ICs and their interaction were used in a multimodal regression analysis.</div></div><div><h3>Conclusions</h3><div>We reported biologically plausible pairs of neural activity and gene sets using pICA, which were significantly associated with ADHD impulsivity–related behavioral and cognitive data.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 10","pages":"Pages 1078-1092"},"PeriodicalIF":4.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144295503","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 : 2025-09-01DOI: 10.1016/j.bpsc.2025.01.005
Xinyuan Yan , R. Becket Ebitz , Nicola Grissom , David P. Darrow , Alexander B. Herman
Background
Decision making in uncertain environments can lead to varied outcomes, and how we process those outcomes may depend on our emotional state. Understanding how individuals interpret the sources of uncertainty is crucial for understanding adaptive behavior and mental well-being. Uncertainty can be broadly categorized into 2 components: volatility and stochasticity. Volatility describes how quickly conditions change. Stochasticity, on the other hand, refers to outcome randomness. We investigated how anxiety and apathy influenced people’s perceptions of uncertainty and how uncertainty perception shaped explore-exploit decisions.
Methods
Participants (N = 1001, nonclinical sample) completed a restless 3-armed bandit task that was analyzed using both latent state and process models.
Results
Individuals with anxiety perceived uncertainty as resulting more from volatility, leading to increased exploration and learning rates, especially after reward omission. Conversely, individuals with apathy viewed uncertainty as more stochastic, resulting in decreased exploration and learning rates. The perceived volatility to stochasticity ratio mediated the anxiety-exploration relationship post adverse outcomes. Dimensionality reduction showed exploration and uncertainty estimation to be distinct but related latent factors shaping a manifold of adaptive behavior that is modulated by anxiety and apathy.
Conclusions
These findings reveal distinct computational mechanisms for how anxiety and apathy influence decision making, providing a framework for understanding cognitive and affective processes in neuropsychiatric disorders.
{"title":"Distinct Computational Mechanisms of Uncertainty Processing Explain Opposing Exploratory Behaviors in Anxiety and Apathy","authors":"Xinyuan Yan , R. Becket Ebitz , Nicola Grissom , David P. Darrow , Alexander B. Herman","doi":"10.1016/j.bpsc.2025.01.005","DOIUrl":"10.1016/j.bpsc.2025.01.005","url":null,"abstract":"<div><h3>Background</h3><div>Decision making in uncertain environments can lead to varied outcomes, and how we process those outcomes may depend on our emotional state. Understanding how individuals interpret the sources of uncertainty is crucial for understanding adaptive behavior and mental well-being. Uncertainty can be broadly categorized into 2 components: volatility and stochasticity. Volatility describes how quickly conditions change. Stochasticity, on the other hand, refers to outcome randomness. We investigated how anxiety and apathy influenced people’s perceptions of uncertainty and how uncertainty perception shaped explore-exploit decisions.</div></div><div><h3>Methods</h3><div>Participants (<em>N</em> = 1001, nonclinical sample) completed a restless 3-armed bandit task that was analyzed using both latent state and process models.</div></div><div><h3>Results</h3><div>Individuals with anxiety perceived uncertainty as resulting more from volatility, leading to increased exploration and learning rates, especially after reward omission. Conversely, individuals with apathy viewed uncertainty as more stochastic, resulting in decreased exploration and learning rates. The perceived volatility to stochasticity ratio mediated the anxiety-exploration relationship post adverse outcomes. Dimensionality reduction showed exploration and uncertainty estimation to be distinct but related latent factors shaping a manifold of adaptive behavior that is modulated by anxiety and apathy.</div></div><div><h3>Conclusions</h3><div>These findings reveal distinct computational mechanisms for how anxiety and apathy influence decision making, providing a framework for understanding cognitive and affective processes in neuropsychiatric disorders.</div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 9","pages":"Pages 954-963"},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142980880","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 : 2025-09-01DOI: 10.1016/j.bpsc.2025.03.008
Martin P. Paulus , Murray B. Stein
Anxiety disorders, affecting approximately 1 in 9 individuals globally, impose significant socioeconomic and health burdens, with many individuals failing to achieve symptom remission despite standard treatments. Difficult-to-treat anxiety (DTA) encompasses a broad spectrum of persistent anxiety disorders that remain refractory to conventional interventions, necessitating a shift from rigid response-based criteria to a mechanistically driven framework that integrates computational psychiatry and systems neuroscience. Dysregulated approach-avoidance decision making, where heightened punishment sensitivity, inflexible belief updating, and uncertainty misestimation drive persistent avoidance behaviors and reinforce maladaptive anxiety cycles, is central to DTA. Computational modeling of reinforcement learning tasks reveals exaggerated Pavlovian biases and impaired exploratory learning, while predictive processing models highlight overestimation of threat and rigidity in safety learning, perpetuating chronic anxiety. Neural dysfunction in default mode and negative affective networks, characterized by hyperstable attractor states in the amygdala and impaired top-down regulation by the prefrontal cortex, further sustains maladaptive anxiety states. Novel interventions that target these dysfunctions—such as neuromodulation, precision pharmacotherapy, and personalized digital therapeutics—offer potential breakthroughs in managing DTA. In this review, we synthesize current evidence on computational, neural, and behavioral mechanisms that underlie DTA and propose an integrative, process-targeted approach to assessment and treatment. Future research must refine biomarker-driven subtyping and individualized interventions, moving beyond trial-and-error approaches toward mechanistically informed precision psychiatry for persistent anxiety disorders.
{"title":"Difficult-to-Treat Anxiety: A Neurocomputational Framework","authors":"Martin P. Paulus , Murray B. Stein","doi":"10.1016/j.bpsc.2025.03.008","DOIUrl":"10.1016/j.bpsc.2025.03.008","url":null,"abstract":"<div><div>Anxiety disorders, affecting approximately 1 in 9 individuals globally, impose significant socioeconomic and health burdens, with many individuals failing to achieve symptom remission despite standard treatments. Difficult-to-treat anxiety (DTA) encompasses a broad spectrum of persistent anxiety disorders that remain refractory to conventional interventions, necessitating a shift from rigid response-based criteria to a mechanistically driven framework that integrates computational psychiatry<span><span><span> and systems neuroscience. Dysregulated approach-avoidance decision making, where heightened punishment sensitivity, inflexible belief updating, and uncertainty misestimation drive persistent avoidance </span>behaviors and reinforce maladaptive anxiety cycles, is central to DTA. Computational modeling of reinforcement learning tasks reveals exaggerated Pavlovian biases and impaired exploratory learning, while predictive processing models highlight overestimation of threat and rigidity in safety learning, perpetuating chronic anxiety. Neural dysfunction in default mode and negative affective networks, characterized by hyperstable attractor states in the </span>amygdala<span> and impaired top-down regulation by the prefrontal cortex<span><span>, further sustains maladaptive anxiety states. Novel interventions that target these dysfunctions—such as neuromodulation<span>, precision pharmacotherapy, and personalized digital therapeutics—offer potential breakthroughs in managing DTA. In this review, we synthesize current evidence on computational, neural, and behavioral mechanisms that underlie DTA and propose an integrative, process-targeted approach to assessment and treatment. Future research must refine biomarker-driven subtyping and individualized interventions, moving beyond trial-and-error approaches toward mechanistically informed precision </span></span>psychiatry for persistent anxiety disorders.</span></span></span></div></div>","PeriodicalId":54231,"journal":{"name":"Biological Psychiatry-Cognitive Neuroscience and Neuroimaging","volume":"10 9","pages":"Pages 918-925"},"PeriodicalIF":4.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143756451","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}
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