Brain Research Bulletin最新文献

{"title":"Heat stress-induced genomic instability in neural stem cells and its association with neuronal developmental deficits","authors":"Zeze Wang ,&nbsp;Zhen Luo ,&nbsp;Yulong Tan ,&nbsp;Xue Luo ,&nbsp;Xuesen Yang","doi":"10.1016/j.brainresbull.2025.111517","DOIUrl":"10.1016/j.brainresbull.2025.111517","url":null,"abstract":"<div><h3>Background</h3><div>Maternal hyperthermia, an increasingly prevalent environmental stressor linked to global climate change, is epidemiologically associated with a higher risk of neurodevelopmental disorders, including autism and schizophrenia. However, the molecular mechanisms underlying this neurotoxicity, particularly those leading to long-term neurological deficits, remain poorly understood. This study tested the novel hypothesis that hyperthermia acts not only as an acute physiological stressor but also as a potent genotoxic agent, inducing persistent genomic alterations in neural progenitor cells.</div></div><div><h3>Methods</h3><div>We established an in vitro model using mouse embryonic neural stem cells (eNSCs) differentiated into developing neurons. These cells were subjected to acute hyperthermic stress (40–43°C for 2 h). We employed a multi-omics approach to assess the consequences, including high-content neuromorphometrics, strand-specific RNA sequencing (RNA-seq) for transcriptomic and genomic variant analysis, and immunofluorescence for DNA double-strand breaks (DSBs) using the γH2AX marker.</div></div><div><h3>Results</h3><div>Hyperthermia exposure at a clinically relevant temperature of 41°C induced a dose-dependent inhibition of neurite outgrowth and branching complexity. This morphological defect was underpinned by the induction of DNA DSBs, which triggered a robust p53-mediated DNA damage response, characterized by the upregulation of cell cycle arrest genes like Cdkn1a (p21). Critically, we uncovered evidence of lasting genomic damage. Hyperthermia-exposed neurons exhibited a significant increase in the frequency of single-nucleotide polymorphisms (SNPs), a lower transition-to-transversion (Ti/Tv) ratio indicative of genomic instability, and the formation of novel gene fusions. We identified a \"heat stress signature\" of unique mutations in key neurodevelopmental genes, including a missense variant in the inflammasome component Nlrp3 and structural rearrangements involving the axon guidance receptor Robo2 and the actin cytoskeleton regulator Cyth3.</div></div><div><h3>Conclusion</h3><div>Our findings reveal that hyperthermia impairs neuronal development through a \"double-hit\" mechanism. The \"first hit\" is an acute disruption of developmental programming via a p53-p21-mediated response to DNA damage. The \"second hit\" consists of permanent \"genomic scars\"—including SNPs and gene fusions—that can irreversibly alter the function of critical neurodevelopmental genes. By demonstrating that a transient environmental stressor can induce lasting genomic instability in neural progenitors, this study provides a compelling mechanistic framework linking maternal fever to the etiology of neurodevelopmental disorders and highlights a potentially crucial pathway for gene-environment interactions in brain development.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111517"},"PeriodicalIF":3.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144892127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocytic glucocorticoid receptors in the ventral hippocampus modulate anxiety-like behaviors","authors":"Cheng-Lin Lu ,&nbsp;Jing Ren ,&nbsp;Wei Wang ,&nbsp;Liang-Yu Chen ,&nbsp;Xiao-Ying Lian ,&nbsp;Xiong Cao","doi":"10.1016/j.brainresbull.2025.111518","DOIUrl":"10.1016/j.brainresbull.2025.111518","url":null,"abstract":"<div><div>Stress exposure is associated with the development of anxiety disorders, and astrocytes have emerged as critical mediators of stress responses and anxiety pathogenesis. While astrocytic dysfunction has been implicated in these processes, the specific molecular mechanisms remain elusive. In this study, we demonstrate a crucial role for astrocytic glucocorticoid receptors (GRs) in the ventral hippocampus (vHPC) in modulating anxiety-like behaviors. We found that chronic restraint stress specifically reduced the GR expression in the vHPC, with no significant changes observed in the amygdala or dorsal hippocampus. Consistent with this finding, chronic corticosterone administration was found to induce anxiety-like behaviors in mice, accompanied by a significant reduction in the GR expression in the vHPC. The GR reduction, while prominent and functionally significant in astrocytes, is not exclusive to them in the vHPC under these stress conditions. Targeted deletion of GRs in astrocytes resulted in the development of anxiety-like behaviors in mice. Notably, selective ablation of astrocytic GRs specifically within the vHPC region produced similar behavioral phenotypes. RNA sequencing analysis of the vHPC from astrocytic GR-depletion mice identified potential molecular mechanisms underlying the pathomechanisms of astrocytic GRs in anxiety. These findings establish a novel pathway through which astrocytic GRs in the vHPC regulate anxiety-like behaviors, providing new insights into the neurobiological basis of stress-related anxiety disorders and identifying potential therapeutic targets.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111518"},"PeriodicalIF":3.7,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144890560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advanced neuromonitoring techniques for medical and neurological ICU patients","authors":"Reza Eshraghi ,&nbsp;Mohammad Sepehr Yazdani ,&nbsp;Ashkan Bahrami ,&nbsp;Reza Amani-Beni ,&nbsp;Bahar Darouei ,&nbsp;Majid Mokhtari ,&nbsp;Seyed MohammadReza Hashemian","doi":"10.1016/j.brainresbull.2025.111513","DOIUrl":"10.1016/j.brainresbull.2025.111513","url":null,"abstract":"<div><div>Newly developed neurological complications are not confined to patients admitted to the neurology ICU but also occur in the medical ICU. In addition to patients with traumatic brain injuries, critically ill patients with sepsis, encephalopathy, and post-cardiopulmonary resuscitation are at risk of developing neurological complications. The situation can worsen when patients are sedated and intubated, which prevents the clinical manifestations to be presented. In this regard, non-convulsive seizures and status epilepticus, new onset strokes, and neuromuscular weakness syndromes could be missed which escalates the prognosis. The advancement of neuromonitoring technology enables real-time, multimodal assessments of brain functions, improving the ability of clinicians to detect and preemptively address potential neurological complications. In this study, we reviewed which certain neurological and medical conditions pose a high risk for developing secondary or new-onset neurological complications. Additionally, we reviewed various approaches that can assist in detecting these complications, including automated pupillometry, Bispectral Index monitoring, electroencephalogram, somatosensory evoked potentials monitoring, jugular venous oxygen saturation monitoring, PbO2 monitoring, near-infrared spectroscopy, transcranial Doppler sonography, thermal diffusion flowmetry, cerebral perfusion pressure monitoring, and biomarkers associated with neuronal damage. Last but not least, we reviewed the potential of integrating artificial intelligence in the ICU.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111513"},"PeriodicalIF":3.7,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144882234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional reorganization of the visual cortex in patients with Charcot–Marie–Tooth disease: A multimodal neuroimaging study","authors":"Ling Zhang ,&nbsp;Yanbin Liang ,&nbsp;Yan Huang ,&nbsp;Wen Qi ,&nbsp;Le Xia ,&nbsp;Qingling Zhao ,&nbsp;Xu Han ,&nbsp;Ruowei Tang ,&nbsp;Ning Xu ,&nbsp;Zhenghan Yang ,&nbsp;Yawen Liu ,&nbsp;Pengfei Zhao","doi":"10.1016/j.brainresbull.2025.111514","DOIUrl":"10.1016/j.brainresbull.2025.111514","url":null,"abstract":"<div><div>Charcot–Marie–Tooth disease (CMT), an inherited peripheral nervous system disorder, causes muscle weakness, sensory deficits, decreased or absent tendon reflexes, and skeletal deformities. Although primarily a peripheral disorder, some studies indicate central nervous system (CNS) involvement. This study systematically investigated the potential structural and functional brain alterations in patients with CMT without overt CNS symptoms using magnetic resonance imaging (MRI) techniques. In this prospective cross-sectional study, 14 patients with clinically and genetically confirmed CMT and 14 age- and sex-matched healthy controls (HCs) underwent 3 T brain MRI. Gray/white matter volume, cortical thickness, amplitude of low-frequency fluctuations (ALFF), and regional homogeneity (ReHo) were compared between groups. Compared to HCs, patients with CMT exhibited increased gray matter volume in the left cerebellar lobules IV–VI and right orbital part of the inferior frontal gyrus. The CMT group demonstrated significantly higher ALFF in the bilateral cuneus regions and decreased ALFF values in the left middle frontal gyrus. Additionally, enhanced ReHo was observed in the right middle occipital and right fusiform gyri in patients with CMT compared to that in HCs. No significant differences were observed in global brain volume or cortical thickness. Patients with CMT exhibited a CNS remodeling pattern and functional hyperactivation of the visual cortex. This phenomenon potentially underlies the neural basis of patients’ increased reliance on visual feedback to compensate for proprioceptive deficits. This study provides insights into CNS involvement and neuroplastic adaptations in CMT, highlighting the importance of neuroimaging for understanding the multimodal pathophysiological mechanisms of this disorder.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111514"},"PeriodicalIF":3.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abnormal brain functional activity and changes in c-Fos expression of propofol dependence in rats","authors":"Zelin Zhuang ,&nbsp;Zikai Huang ,&nbsp;Lei Xie ,&nbsp;Yuehua Huang ,&nbsp;Xiaoyan Shi ,&nbsp;Baowen Guo ,&nbsp;Ziquan Xu ,&nbsp;Yanbin Chen ,&nbsp;Yuyin Cao ,&nbsp;Yanmin Zheng ,&nbsp;Rufeng Bai ,&nbsp;Renhua Wu ,&nbsp;Shuhua Ma","doi":"10.1016/j.brainresbull.2025.111512","DOIUrl":"10.1016/j.brainresbull.2025.111512","url":null,"abstract":"<div><div>Propofol demonstrates dependence at subclinical anesthetic doses, however, the underlying neural mechanisms remain unclear. In this study, we established a self-administration model of propofol in Sprague-Dawley (SD) rats, used a combination of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis approach of resting-state functional magnetic resonance imaging (rs-fMRI) to examine the local brain functional activity changes, Western Blot (WB) was used to detect the change of c-Fos protein expression in the prefrontal cortex and hippocampus. Results showed that the propofol-dependent rats exhibited enhanced seeking behaviour and decreased spontaneous locomotor activity compared to saline control group, while increased ALFF values in the bilateral prefrontal cortex and right hippocampus, and increased ReHo values in the left striatum and pons. c-Fos gene expression in the prefrontal cortex was significantly increased in propofol-dependent rats compared with controls. In conclusion, enhanced seeking behaviour and decreased spontaneous locomotor activity in propofol-dependent rats may lead to abnormal functional activity and upregulation of c-Fos expression in the prefrontal cortex. These findings may shed light on propofol-dependent brain dysfunction from the perspective of local brain activity, emphasizing the potential usefulness of combining functional MRI and c-Fos expression in elucidating the neuropathological mechanisms of propofol dependence and may ultimately inform future disease treatment of propofol addiction.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111512"},"PeriodicalIF":3.7,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of SIRT3 / PRDX5 signaling inhibits apoptosis after acute spinal cord injury in mice","authors":"Hui Ni ,&nbsp;Weiping Sha ,&nbsp;Tianli Xu ,&nbsp;Qiancheng Zhu ,&nbsp;Qun Huang ,&nbsp;Jin Wang ,&nbsp;Qi Gu ,&nbsp;Yi Zhu ,&nbsp;Liming Wang ,&nbsp;Shoujin Tian ,&nbsp;Rong Gao ,&nbsp;Jianfei Ge ,&nbsp;Xiaolong Lin","doi":"10.1016/j.brainresbull.2025.111510","DOIUrl":"10.1016/j.brainresbull.2025.111510","url":null,"abstract":"<div><div>Spinal cord injury (SCI), a traumatic condition affecting the nervous system, constitutes an orthopedic emergency that is closely associated with a significantly elevated disability rate. Excessive apoptosis not only hinders neuronal repair, but also exacerbates the deterioration of the local microenvironment, thereby impeding the treatment of SCI. The present study comprehensively investigated the dynamic expression of mitochondrial deacetylase sirtuin 3 (SIRT3) in a murine model of SCI. Activation of SIRT3 with the natural agonist honokiol (HKL) facilitated neurological functional recovery by mitigating neuronal apoptosis and oxidative stress injury in vivo. Mechanistically, through comparative analysis of transcriptome alterations after global deletion of SIRT3 (<em>Sirt3</em>^<em>-/-</em>), mitochondrion localized protein peroxidase peroxiredoxin 5 (PRDX5) was identified as the direct downstream effector of SIRT3. Spatially, SIRT3 and PRDX5 were colocalized within neurons in the anterior horn of the spinal cord. Genetic silencing of PRDX5 partially attenuated the protective effects of SIRT3 against neuronal apoptosis and the promotion of functional recovery. Overall, this study is the first to reveal the pivotal role of the SIRT3<img>PRDX5 axis in modulating neuronal apoptosis after SCI, and thus offers a novel perspective on the restoration of function after SCI.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111510"},"PeriodicalIF":3.7,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tweety-homolog 1 protein overexpression alters dendritic complexity and dendritic spine morphology of CA1 and CA3 pyramidal neurons in organotypic slices in vitro","authors":"Malgorzata Gorniak-Walas ,&nbsp;Dorota Nowicka ,&nbsp;Aleksandra Kaliszewska ,&nbsp;Szymon Leski ,&nbsp;Katarzyna Lukasiuk","doi":"10.1016/j.brainresbull.2025.111511","DOIUrl":"10.1016/j.brainresbull.2025.111511","url":null,"abstract":"<div><div>Tweety-homolog 1 protein (Ttyh1) is a presumed volume-regulated chloride channel that is widely expressed in neurons <em>in vitro</em> and <em>in vivo</em>. It was previously implicated in regulating dendrite morphology in dissociated hippocampal neurons <em>in vitro</em>, indicating its possible role in structural neuronal plasticity. This study tested the hypotheses that (<em>i</em>) Ttyh1 influences dendritic tree formation in rat organotypic hippocampal slice cultures in an <em>in vitro</em> model with preserved cytoarchitecture and synaptic circuits, and (<em>ii</em>) Ttyh1 influences dendritic spine morphology in the same experimental model. Neurons were transfected via a Helios gene gun with a plasmid that carried Ttyh1-EGFP under control of the synapsin promoter (or green fluorescent protein as a control) and a plasmid that encoded red fluorescent protein under a β-actin promoter. To evaluate dendritic tree morphology, transfected neurons were reconstructed using Neuromantic software and morphometrically analyzed using the Sholl method and L-measure software. To quantify dendritic spine density and the distributions of thin, mushroom, and stubby spines on basilar dendrites and proximal and distal apical dendrites, we used SpineMagick! software. The results indicated that Ttyh1 impacted dendritic spine morphology and density on apical and basilar dendrites of CA1 and CA3 pyramidal neurons, and moderately regulated the complexity of their apical and basilar dendritic arbors. Our findings support the hypothesis that Ttyh1 participates in shaping neuronal morphology.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111511"},"PeriodicalIF":3.7,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144842220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sensory thalamus function, plasticity and neuromodulation in health and disease","authors":"Ricardo Paricio-Montesinos ,&nbsp;Jan Gründemann","doi":"10.1016/j.brainresbull.2025.111508","DOIUrl":"10.1016/j.brainresbull.2025.111508","url":null,"abstract":"<div><div>For each of the many sensory channels through which animals perceive the world, sensory thalamus is an important processing station whose role lies between faithful stimulus encoding and cognitive interpretation. Located deep in the brain, sensory thalamus neurons must receive and transmit peripheral information reliably, while modulating it based on valence, internal states and memory from previous experience. It has to speak to the neocortex with the appropriate volume, and in an orderly way, to prioritize attention to what matters most in each circumstance. In this review, we recapitulate classic and recent findings on the sensory thalamus, and how its plasticity and modulation allow it to provide a basis not only for perception, but also memory and cognition. Finally, we discuss how alterations in sensory thalamus may underlie pathogenesis or contribute to specific symptoms of cognitive and neuropsychiatric disorders.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111508"},"PeriodicalIF":3.7,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144854643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased DNA methylation of Igf2 in the male hippocampus regulates age-related deficits in synaptic plasticity and memory","authors":"Shannon Kincaid ,&nbsp;Courtney P. Stickling ,&nbsp;Kayla Farrell ,&nbsp;Yeeun Bae ,&nbsp;Morgan B. Patrick ,&nbsp;Gitali Bhanot ,&nbsp;Adam Cummings ,&nbsp;Jennifer Abraham ,&nbsp;Abby Alisesky ,&nbsp;Nicole Ferrara ,&nbsp;J. Amiel Rosenkranz ,&nbsp;Timothy J. Jarome","doi":"10.1016/j.brainresbull.2025.111509","DOIUrl":"10.1016/j.brainresbull.2025.111509","url":null,"abstract":"<div><div>The aging process is characterized by a general decline in cognitive abilities, which affects nearly 33 % of U.S. adults over the age of 70 and is a risk factor for the development of dementia and Alzheimer’s disease. Numerous studies have reported increased neuroinflammation and impaired synaptic plasticity and memory with age in the hippocampus, a major brain region involved in the formation and storage of most memories. However, much remains unknown about the mechanisms that contribute to age-related deficits in synaptic plasticity and memory. The Insulin-like growth factor 2 (<em>Igf2</em>) is a genomic imprinted gene that is expressed from a single allele in all species. Though IGF2 has been shown to be important in development, synaptic plasticity, and memory formation in the hippocampus and administration of IGF2 can improve memory late in life, whether changes in regulation of this gene contribute to age-related memory decline have yet to be explored. Here, we show that aged (24 months) male rats have increased CpG-site specific promoter methylation and reduced expression of <em>Igf2</em> in the hippocampus relative to young adult (3 months) and middle-aged (12 months) rats. Importantly, CRISPR-dCas9 mediated increase of DNA 5-hydroxymethylation, an active transcriptional mark, of the <em>Igf2</em> promoter in the hippocampus improved memory and long-term potentiation in aged, but not middle-aged, rats. These data indicate that increased DNA methylation of <em>Igf2</em> in the hippocampus contributes to age-related deficits in synaptic plasticity and memory.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111509"},"PeriodicalIF":3.7,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144827545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimensions of childhood maltreatment and neural circuits of affective inhibitory control: An fMRI study","authors":"Nadia Bounoua ,&nbsp;Jeffrey M. Spielberg ,&nbsp;Naomi Sadeh","doi":"10.1016/j.brainresbull.2025.111507","DOIUrl":"10.1016/j.brainresbull.2025.111507","url":null,"abstract":"<div><h3>Background</h3><div>Research suggests that the neurobiological consequences of early life adversity, including circuits supporting inhibitory control in emotional contexts, are important mechanisms of risk transmission for later psychiatric problems. However, different types of adversity may have separable impacts on the brain. Using a dimensional approach, we examined the unique and interactive effects of childhood deprivation (i.e., neglect) and threat (i.e., abuse) on neural circuits supporting affective inhibitory control in adulthood.</div></div><div><h3>Methods</h3><div>110 community adults [M/SDage= 31.92/10.58 years old, 52.7 % male], recruited predominately from communities with high rates of socioeconomic disadvantage, reported on childhood maltreatment and completed Go/No-Go fMRI tasks that assessed inhibitory control during emotional (reward cues, negative mood) and neutral contexts.</div></div><div><h3>Results</h3><div>Childhood deprivation uniquely moderated inhibition-related neural activation in prefrontal cortex in the Reward Cues and Negative Mood context. Conversely, childhood experiences of threat moderated inhibition-related neural activation in the bilateral amygdala during the Negative Mood condition. No interaction effects between childhood deprivation and threat were found.</div></div><div><h3>Conclusions</h3><div>Results provide initial support for dimensional models of childhood maltreatment. Childhood deprivation and threat were associated with affect related control in separate regions of the brain, suggesting that these dimensions of childhood maltreatment may be associated with distinct neurobiological correlates in circuits supporting affective inhibitory control, illuminating potential mechanisms of risk transmission. Findings are discussed in the context of existing literature and areas for future directions.</div></div>","PeriodicalId":9302,"journal":{"name":"Brain Research Bulletin","volume":"230 ","pages":"Article 111507"},"PeriodicalIF":3.7,"publicationDate":"2025-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144820614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}