Alexithymia is a subclinical condition that affects individuals' processing of emotions. Emerging evidence suggests that alexithymia results from a multidomain and multidimensional interoceptive failure. Although extensive research has examined the relationship between alexithymia and interoception, less is known about how alexithymia modulates the brain activity evoked by interoceptive sensations. In this study, we used task-based functional magnetic resonance imaging (fMRI) to assess intersubject correlations in response to interoceptive sensation words in individuals with high alexithymia and low alexithymia. Participants with high alexithymia (n = 29) and low alexithymia (n = 28) were instructed to view words during MRI scanning, each word corresponding to a specific emotional category related to interoceptive sensations. Intersubject correlation analysis identified several brain regions exhibiting increased synchronization in individuals with high alexithymia, including those involved in cognitive control. Follow-up analyses revealed that the left middle occipital gyrus and the right inferior frontal gyrus (orbital part) were more active during interoceptive sensation events in individuals with high alexithymia. Validation analyses revealed that the amygdala and insula are also crucial in representing interoceptive sensations. These findings shed light on the neural basis of interoceptive deficits in high alexithymia and have significant implications for the mechanisms regulating these differences.
{"title":"Alexithymia shapes intersubject synchrony in brain activity during interoceptive sensation representations.","authors":"Xianrui Li, Xueyang Wang, Chuyao Peng, Zhiting Ren, Junlai Shan, Qian Luo, Dongtao Wei, Jiang Qiu","doi":"10.1093/cercor/bhaf060","DOIUrl":"https://doi.org/10.1093/cercor/bhaf060","url":null,"abstract":"<p><p>Alexithymia is a subclinical condition that affects individuals' processing of emotions. Emerging evidence suggests that alexithymia results from a multidomain and multidimensional interoceptive failure. Although extensive research has examined the relationship between alexithymia and interoception, less is known about how alexithymia modulates the brain activity evoked by interoceptive sensations. In this study, we used task-based functional magnetic resonance imaging (fMRI) to assess intersubject correlations in response to interoceptive sensation words in individuals with high alexithymia and low alexithymia. Participants with high alexithymia (n = 29) and low alexithymia (n = 28) were instructed to view words during MRI scanning, each word corresponding to a specific emotional category related to interoceptive sensations. Intersubject correlation analysis identified several brain regions exhibiting increased synchronization in individuals with high alexithymia, including those involved in cognitive control. Follow-up analyses revealed that the left middle occipital gyrus and the right inferior frontal gyrus (orbital part) were more active during interoceptive sensation events in individuals with high alexithymia. Validation analyses revealed that the amygdala and insula are also crucial in representing interoceptive sensations. These findings shed light on the neural basis of interoceptive deficits in high alexithymia and have significant implications for the mechanisms regulating these differences.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662443","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}
Alzheimer's disease tau pathology spreads through neuronal pathways and synaptic connections. Alteration in synaptic activity facilitates tau spreading. Multiple neurotransmitter systems are shown to be implicated in Alzheimer's disease, but their influence on the trans-synaptic spread of tau is not well understood. I aimed to combine resting-state functional magnetic resonance imaging connectomics, neurotransmitter receptor profiles, and tau-PET data to explain the regional susceptibility to tau accumulation. The tau-PET imaging data of 161 amyloid-beta-negative cognitively unimpaired participants as control and 259 amyloid-beta-positive subjects were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Linear regression analysis revealed that a higher tau-PET z-score is associated with a lower density of nine receptors in the serotonin, dopamine, gamma-aminobutyric acid (GABA), acetylcholine, and glutamate systems. Furthermore, adding four neurotransmitter receptor density z-scores significantly increased the proportion of explained variance by 3% to 7% compared to the epicenter-connectivity distance model in the group-level analysis. Also, adding nine neurotransmitter receptor density z-scores to the epicenter-connectivity distance model increased the explanatory power of variability in individual levels of tau-PET z-score by 3% to 8%. The current study demonstrated the additive value of atlas-based neurotransmitter receptor mapping and individual-level amyloid-beta-PET scans to enhance the connectivity-based explanation of tau accumulation.
阿尔茨海默病的 tau 病理变化通过神经元通路和突触连接扩散。突触活动的改变促进了 tau 的扩散。多种神经递质系统已被证明与阿尔茨海默病有关,但它们对tau经突触扩散的影响还不十分清楚。我的目的是结合静息态功能磁共振成像连接组学、神经递质受体图谱和 tau-PET 数据来解释 tau 累积的区域易感性。我们从阿尔茨海默病神经影像学倡议(ADNI)中招募了161名淀粉样蛋白-β阴性、认知功能未受损的受试者作为对照,并收集了259名淀粉样蛋白-β阳性受试者的tau-PET成像数据。线性回归分析表明,tau-PET z分数越高,血清素、多巴胺、γ-氨基丁酸(GABA)、乙酰胆碱和谷氨酸系统中九种受体的密度越低。此外,在组水平分析中,与震中-连接距离模型相比,增加四个神经递质受体密度 z 分数可显著增加 3% 至 7% 的解释变异比例。此外,在震中-连接距离模型的基础上增加九个神经递质受体密度z-分数,可将tau-PET z-分数个体水平变异的解释力提高3%至8%。目前的研究表明,基于地图集的神经递质受体图谱和个体水平的淀粉样蛋白-β-PET扫描具有附加价值,可增强基于连接性的对tau累积的解释。
{"title":"Connectomics and neurotransmitter receptor profile explain regional tau pathology in Alzheimer's disease.","authors":"Fardin Nabizadeh","doi":"10.1093/cercor/bhaf053","DOIUrl":"https://doi.org/10.1093/cercor/bhaf053","url":null,"abstract":"<p><p>Alzheimer's disease tau pathology spreads through neuronal pathways and synaptic connections. Alteration in synaptic activity facilitates tau spreading. Multiple neurotransmitter systems are shown to be implicated in Alzheimer's disease, but their influence on the trans-synaptic spread of tau is not well understood. I aimed to combine resting-state functional magnetic resonance imaging connectomics, neurotransmitter receptor profiles, and tau-PET data to explain the regional susceptibility to tau accumulation. The tau-PET imaging data of 161 amyloid-beta-negative cognitively unimpaired participants as control and 259 amyloid-beta-positive subjects were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Linear regression analysis revealed that a higher tau-PET z-score is associated with a lower density of nine receptors in the serotonin, dopamine, gamma-aminobutyric acid (GABA), acetylcholine, and glutamate systems. Furthermore, adding four neurotransmitter receptor density z-scores significantly increased the proportion of explained variance by 3% to 7% compared to the epicenter-connectivity distance model in the group-level analysis. Also, adding nine neurotransmitter receptor density z-scores to the epicenter-connectivity distance model increased the explanatory power of variability in individual levels of tau-PET z-score by 3% to 8%. The current study demonstrated the additive value of atlas-based neurotransmitter receptor mapping and individual-level amyloid-beta-PET scans to enhance the connectivity-based explanation of tau accumulation.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143623728","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}
Chih-Hao Lien, Thomas Vande Casteele, Maarten Laroy, Margot G A Van Cauwenberge, Ronald Peeters, Stefan Sunaert, Koen Van Laere, Patrick Dupont, Filip Bouckaert, Louise Emsell, Mathieu Vandenbulcke, Jan Van den Stock
This study investigates the relationship between resting-state functional magnetic resonance imaging (rs-fMRI) topological properties and synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) synaptic density (SD) in late-life depression (LLD). 18 LLD patients and 33 healthy controls underwent rs-fMRI, 3D T1-weighted MRI, and 11C-UCB-J PET scans to assess SD. The rs-fMRI data were utilized to construct weighted networks for calculating four global topological metrics, including clustering coefficient, characteristic path length, global efficiency, and small-worldness, and six nodal metrics, including nodal clustering coefficient, nodal characteristic path length, nodal degree, nodal strength, local efficiency, and betweenness centrality. The 11C-UCB-J PET provided standardized uptake value ratios as SD measures. LLD patients exhibited preserved global topological organization, with reduced nodal properties in regions associated with LLD, such as the medial prefrontal cortex (mPFC), and increased nodal properties in the basal ganglia and cerebellar regions. Notably, a negative correlation was observed between betweenness centrality in the mPFC and depressive symptom severity. No significant alterations in SD or associations between rs-fMRI topological properties and SD were found, challenging the hypothesis that SD alterations are the molecular basis for rs-fMRI topological changes in LLD. Our findings suggest other molecular mechanisms may underlie the observed functional connectivity alterations in these patients.
{"title":"Are resting-state network alterations in late-life depression related to synaptic density? Findings of a combined 11C-UCB-J PET and fMRI study.","authors":"Chih-Hao Lien, Thomas Vande Casteele, Maarten Laroy, Margot G A Van Cauwenberge, Ronald Peeters, Stefan Sunaert, Koen Van Laere, Patrick Dupont, Filip Bouckaert, Louise Emsell, Mathieu Vandenbulcke, Jan Van den Stock","doi":"10.1093/cercor/bhaf028","DOIUrl":"https://doi.org/10.1093/cercor/bhaf028","url":null,"abstract":"<p><p>This study investigates the relationship between resting-state functional magnetic resonance imaging (rs-fMRI) topological properties and synaptic vesicle glycoprotein 2A (SV2A) positron emission tomography (PET) synaptic density (SD) in late-life depression (LLD). 18 LLD patients and 33 healthy controls underwent rs-fMRI, 3D T1-weighted MRI, and 11C-UCB-J PET scans to assess SD. The rs-fMRI data were utilized to construct weighted networks for calculating four global topological metrics, including clustering coefficient, characteristic path length, global efficiency, and small-worldness, and six nodal metrics, including nodal clustering coefficient, nodal characteristic path length, nodal degree, nodal strength, local efficiency, and betweenness centrality. The 11C-UCB-J PET provided standardized uptake value ratios as SD measures. LLD patients exhibited preserved global topological organization, with reduced nodal properties in regions associated with LLD, such as the medial prefrontal cortex (mPFC), and increased nodal properties in the basal ganglia and cerebellar regions. Notably, a negative correlation was observed between betweenness centrality in the mPFC and depressive symptom severity. No significant alterations in SD or associations between rs-fMRI topological properties and SD were found, challenging the hypothesis that SD alterations are the molecular basis for rs-fMRI topological changes in LLD. Our findings suggest other molecular mechanisms may underlie the observed functional connectivity alterations in these patients.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613664","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}
Much of the research on the neural correlates of creativity has emphasized creative cognition, and growing evidence suggests that creativity is related to functional properties of the default and frontoparietal control networks. The present work expands on this body of evidence by testing associations of creative achievement with connectivity profiles of brain networks assessed using macroscale cortical gradients. Using resting-state connectivity functional magnetic resonance imaging in 2 community samples (N's = 236 and 234), we found evidence that creative achievement is positively associated with greater functional dissimilarity between core regions of the default and frontoparietal control networks. These results suggest that creative achievement is supported by the ability of these 2 networks to carry out distinct cognitive roles. This research provides further evidence, using a cortical gradient approach, that individual differences in creative achievement can be predicted from functional properties of brain networks involved in higher-order cognition, and it aligns with past research on the functional connectivity correlates of creative task performance.
{"title":"Functional differentiation of the default and frontoparietal control networks predicts individual differences in creative achievement: evidence from macroscale cortical gradients.","authors":"Tyler A Sassenberg, Rex E Jung, Colin G DeYoung","doi":"10.1093/cercor/bhaf046","DOIUrl":"10.1093/cercor/bhaf046","url":null,"abstract":"<p><p>Much of the research on the neural correlates of creativity has emphasized creative cognition, and growing evidence suggests that creativity is related to functional properties of the default and frontoparietal control networks. The present work expands on this body of evidence by testing associations of creative achievement with connectivity profiles of brain networks assessed using macroscale cortical gradients. Using resting-state connectivity functional magnetic resonance imaging in 2 community samples (N's = 236 and 234), we found evidence that creative achievement is positively associated with greater functional dissimilarity between core regions of the default and frontoparietal control networks. These results suggest that creative achievement is supported by the ability of these 2 networks to carry out distinct cognitive roles. This research provides further evidence, using a cortical gradient approach, that individual differences in creative achievement can be predicted from functional properties of brain networks involved in higher-order cognition, and it aligns with past research on the functional connectivity correlates of creative task performance.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cornelius Weiller, Marco Reisert, Pierre Levan, Jonas Hosp, Volker A Coenen, Michel Rijntjes
We must reconcile the needs of the internal world and the demands of the external world to make decisions relevant to homeostasis, well-being, and flexible behavior. Engagement with the internal (eg interoceptive) world is linked to medial brain systems, whereas the extrapersonal space (eg exteroceptive) is associated with lateral brain systems. Using Human Connectome Project data, we found three association tracts connecting the action-related frontal lobe with perception-related posterior lobes. A lateral dorsal tract and a medial dorsal tract interact independently with a ventral tract at frontal and posterior hubs. The two frontal and the two posterior hubs are interconnected, forming a meta-loop that integrates lateral and medial brain systems. The four anatomical hubs correspond to the common nodes of the intrinsic cognitive brain networks such as the default mode network. These functional networks depend on the integration of both realms. Thus, the positioning of functional cognitive networks can be understood as the intersection of long anatomical association tracts. The strength of structural connectivity within lateral and medial brain systems correlates with performance on behavioral tests assessing theory of mind. The meta-loop provides an anatomical framework to associate neurological and psychiatric symptoms with functional and structural changes.
{"title":"Hubs and interaction: the brain's meta-loop.","authors":"Cornelius Weiller, Marco Reisert, Pierre Levan, Jonas Hosp, Volker A Coenen, Michel Rijntjes","doi":"10.1093/cercor/bhaf035","DOIUrl":"10.1093/cercor/bhaf035","url":null,"abstract":"<p><p>We must reconcile the needs of the internal world and the demands of the external world to make decisions relevant to homeostasis, well-being, and flexible behavior. Engagement with the internal (eg interoceptive) world is linked to medial brain systems, whereas the extrapersonal space (eg exteroceptive) is associated with lateral brain systems. Using Human Connectome Project data, we found three association tracts connecting the action-related frontal lobe with perception-related posterior lobes. A lateral dorsal tract and a medial dorsal tract interact independently with a ventral tract at frontal and posterior hubs. The two frontal and the two posterior hubs are interconnected, forming a meta-loop that integrates lateral and medial brain systems. The four anatomical hubs correspond to the common nodes of the intrinsic cognitive brain networks such as the default mode network. These functional networks depend on the integration of both realms. Thus, the positioning of functional cognitive networks can be understood as the intersection of long anatomical association tracts. The strength of structural connectivity within lateral and medial brain systems correlates with performance on behavioral tests assessing theory of mind. The meta-loop provides an anatomical framework to associate neurological and psychiatric symptoms with functional and structural changes.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The fornix, playing a critical role in memory formation and maintenance, is recognized as an ultra-early biomarker for dementia. However, its trajectory during healthy aging remains incompletely understood. This study employed an ultra-high-field 5.0 T MRI to acquire high-resolution anatomical and multishell diffusion imaging data from 376 healthy adults aged 18 to 85. The aim was to correlate fornix characteristics with cognitive performance across multiple domains and map its lifespan trajectories. Using these data, we quantified fornix volume and tractography. Lifespan trajectories were identified by computing age-specific average patterns, which revealed distinct changes. Notably, nonlinear declines in fornix volume were observed, contrasting with fiber tract peaks between ages 18 to 40, which subsequently influenced volume-connectivity interactions. Additionally, a shift from predominant left-side to right-side fornix dominance was noted with aging. Regression analyses indicated that variations in fornix structure significantly moderated, rather than mediated, age-related differences in cognitive performance. These high-resolution imaging results provide novel insights into the role of the fornix's morphology and structural connectivity in individual cognitive differences and aging.
{"title":"Lifespan trajectories of fornix volume and tractography: a 5.0 T MRI study.","authors":"Qiang Hu, Jia Xu, Sirui Li, Xiaohui Chen, Xiaoli Zhong, Xitong Liu, Jinxia Ren, Huan Wang, Chenhong Fan, Chunyu Li, Liang Wang, Jinfeng Lv, Xueying Xiong, Yaowen Xing, Yaqiong Xiao, Xiaopeng Song, Lei Gao, Haibo Xu","doi":"10.1093/cercor/bhaf057","DOIUrl":"https://doi.org/10.1093/cercor/bhaf057","url":null,"abstract":"<p><p>The fornix, playing a critical role in memory formation and maintenance, is recognized as an ultra-early biomarker for dementia. However, its trajectory during healthy aging remains incompletely understood. This study employed an ultra-high-field 5.0 T MRI to acquire high-resolution anatomical and multishell diffusion imaging data from 376 healthy adults aged 18 to 85. The aim was to correlate fornix characteristics with cognitive performance across multiple domains and map its lifespan trajectories. Using these data, we quantified fornix volume and tractography. Lifespan trajectories were identified by computing age-specific average patterns, which revealed distinct changes. Notably, nonlinear declines in fornix volume were observed, contrasting with fiber tract peaks between ages 18 to 40, which subsequently influenced volume-connectivity interactions. Additionally, a shift from predominant left-side to right-side fornix dominance was noted with aging. Regression analyses indicated that variations in fornix structure significantly moderated, rather than mediated, age-related differences in cognitive performance. These high-resolution imaging results provide novel insights into the role of the fornix's morphology and structural connectivity in individual cognitive differences and aging.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656127","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}
Emmanuelle Bellot, Antoine Vandenberghe, Gilles Vannuscorps
Models of actor-specific range of motion (or biomechanical limits) shapes perception and (inter)actions. This functional magnetic resonance imaging study tested the hypothesis that these models are encoded in the extrastriate body area. Participants were first introduced with the maximal amplitude of arm and leg movements of a "rigid" and a "flexible" actor. Then, we measured the blood oxygenation level dependent response in 25 participants while they watched video clips depicting these actors performing either "small" movements that were "possible" to perform for both actors, "large" ones that were "impossible" for both actors and "intermediate" ones that were possible only for the "flexible" actor. Results aligned with the 2 predictions of our hypothesis: (i) extrastriate body area responded more strongly to impossible than possible movements; (ii) extrastriate body area categorized intermediate movements as "possible" or "impossible" depending on each actor's specific range of motion. The results of additional analyses suggested that extrastriate body area encodes actor-specific range of motion at the level of specific body parts, and as a probability function. Finally, the results of whole brain and functional connectivity analyses suggested that the right posterior superior temporal sulcus may also play an important role in encoding information about actor-specific biomechanical limits.
{"title":"Models of actor-specific range of motion are encoded in the extrastriate body area.","authors":"Emmanuelle Bellot, Antoine Vandenberghe, Gilles Vannuscorps","doi":"10.1093/cercor/bhaf027","DOIUrl":"https://doi.org/10.1093/cercor/bhaf027","url":null,"abstract":"<p><p>Models of actor-specific range of motion (or biomechanical limits) shapes perception and (inter)actions. This functional magnetic resonance imaging study tested the hypothesis that these models are encoded in the extrastriate body area. Participants were first introduced with the maximal amplitude of arm and leg movements of a \"rigid\" and a \"flexible\" actor. Then, we measured the blood oxygenation level dependent response in 25 participants while they watched video clips depicting these actors performing either \"small\" movements that were \"possible\" to perform for both actors, \"large\" ones that were \"impossible\" for both actors and \"intermediate\" ones that were possible only for the \"flexible\" actor. Results aligned with the 2 predictions of our hypothesis: (i) extrastriate body area responded more strongly to impossible than possible movements; (ii) extrastriate body area categorized intermediate movements as \"possible\" or \"impossible\" depending on each actor's specific range of motion. The results of additional analyses suggested that extrastriate body area encodes actor-specific range of motion at the level of specific body parts, and as a probability function. Finally, the results of whole brain and functional connectivity analyses suggested that the right posterior superior temporal sulcus may also play an important role in encoding information about actor-specific biomechanical limits.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656130","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}
Christi A Essex, Jenna L Merenstein, Devon K Overson, Trong-Kha Truong, David J Madden, Mayan J Bedggood, Helen Murray, Samantha J Holdsworth, Ashley W Stewart, Catherine Morgan, Richard L M Faull, Patria Hume, Alice Theadom, Mangor Pedersen
Evidence has linked head trauma to increased risk factors for neuropathology, including mechanical deformation of the sulcal fundus and, later, perivascular accumulation of hyperphosphorylated tau adjacent to these spaces related to chronic traumatic encephalopathy. However, little is known about microstructural abnormalities and cellular dyshomeostasis in acute mild traumatic brain injury in humans, particularly in the cortex. To address this gap, we designed the first architectonically motivated quantitative susceptibility mapping study to assess regional patterns of net positive (iron-related) and net negative (myelin-, calcium-, and protein-related) magnetic susceptibility across 34 cortical regions of interest following mild traumatic brain injury. Bilateral, between-group analyses sensitive to cortical depth and curvature were conducted between 25 males with acute (<14 d) sports-related mild traumatic brain injury and 25 age-matched male controls. Results suggest a trauma-induced increase in net positive susceptibility focal to superficial, perivascular-adjacent spaces in the parahippocampal sulcus. Decreases in net negative susceptibility values in distinct voxel populations within the same region indicate a potential dual pathology of neural substrates. These mild traumatic brain injury-related patterns were distinct from age-related processes revealed by correlation analyses. Our findings suggest depth- and curvature-specific deposition of biological substrates in cortical tissue convergent with features of misfolded proteins in trauma-related neurodegeneration.
{"title":"Characterizing positive and negative quantitative susceptibility values in the cortex following mild traumatic brain injury: a depth- and curvature-based study.","authors":"Christi A Essex, Jenna L Merenstein, Devon K Overson, Trong-Kha Truong, David J Madden, Mayan J Bedggood, Helen Murray, Samantha J Holdsworth, Ashley W Stewart, Catherine Morgan, Richard L M Faull, Patria Hume, Alice Theadom, Mangor Pedersen","doi":"10.1093/cercor/bhaf059","DOIUrl":"10.1093/cercor/bhaf059","url":null,"abstract":"<p><p>Evidence has linked head trauma to increased risk factors for neuropathology, including mechanical deformation of the sulcal fundus and, later, perivascular accumulation of hyperphosphorylated tau adjacent to these spaces related to chronic traumatic encephalopathy. However, little is known about microstructural abnormalities and cellular dyshomeostasis in acute mild traumatic brain injury in humans, particularly in the cortex. To address this gap, we designed the first architectonically motivated quantitative susceptibility mapping study to assess regional patterns of net positive (iron-related) and net negative (myelin-, calcium-, and protein-related) magnetic susceptibility across 34 cortical regions of interest following mild traumatic brain injury. Bilateral, between-group analyses sensitive to cortical depth and curvature were conducted between 25 males with acute (<14 d) sports-related mild traumatic brain injury and 25 age-matched male controls. Results suggest a trauma-induced increase in net positive susceptibility focal to superficial, perivascular-adjacent spaces in the parahippocampal sulcus. Decreases in net negative susceptibility values in distinct voxel populations within the same region indicate a potential dual pathology of neural substrates. These mild traumatic brain injury-related patterns were distinct from age-related processes revealed by correlation analyses. Our findings suggest depth- and curvature-specific deposition of biological substrates in cortical tissue convergent with features of misfolded proteins in trauma-related neurodegeneration.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11915090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Keita Tsujimura, Alpen Ortug, José Luis Alatorre Warren, Tadashi Shiohama, Christopher J McDougle, Rachel E Marcus, Chieh-En Jane Tseng, Nicole R Zürcher, Nathaniel D Mercaldo, Susan Faja, Alika Maunakea, Jacob Hooker, Emi Takahashi
Autism spectrum disorder is a neurodevelopmental condition characterized by reduced social communication and repetitive behaviors. Altered neurogenesis, including disturbed neuronal migration, has been implicated in autism spectrum disorder. Using diffusion MRI, we previously identified neuronal migration pathways in the human fetal brain and hypothesized that similar pathways persist into adulthood, with differences in volume and microstructural characteristics between individuals with autism spectrum disorder and controls. We analyzed diffusion MRI-based tractography of subventricular zone-related pathways in 15 young adult men with autism spectrum disorder and 18 controls at Massachusetts General Hospital, with validation through the Autism Imaging Data Exchange II dataset. Participants with autism spectrum disorder had reduced subventricular zone pathway volumes and fractional anisotropy compared to controls. Furthermore, subventricular zone pathway volume was positively correlated (r: 0.68; 95% CI: 0.25 to 0.88) with symptom severity, suggesting that individuals with more severe symptoms tended to have larger subventricular zone pathway volumes, normalized by brain size. Analysis of the Autism Imaging Data Exchange cohort confirmed these findings of reduced subventricular zone pathway volumes in autism spectrum disorder. While some of these pathways may potentially include inaccurately disconnected pathways that go through the subventricular zone, our results suggest that diffusion MRI-based tractography pathways anatomically linked to the periventricular region are associated with certain symptom types in adult males with autism spectrum disorder.
{"title":"Structural pathways related to the subventricular zone are decreased in volume with altered microstructure in young adult males with autism spectrum disorder.","authors":"Keita Tsujimura, Alpen Ortug, José Luis Alatorre Warren, Tadashi Shiohama, Christopher J McDougle, Rachel E Marcus, Chieh-En Jane Tseng, Nicole R Zürcher, Nathaniel D Mercaldo, Susan Faja, Alika Maunakea, Jacob Hooker, Emi Takahashi","doi":"10.1093/cercor/bhaf041","DOIUrl":"10.1093/cercor/bhaf041","url":null,"abstract":"<p><p>Autism spectrum disorder is a neurodevelopmental condition characterized by reduced social communication and repetitive behaviors. Altered neurogenesis, including disturbed neuronal migration, has been implicated in autism spectrum disorder. Using diffusion MRI, we previously identified neuronal migration pathways in the human fetal brain and hypothesized that similar pathways persist into adulthood, with differences in volume and microstructural characteristics between individuals with autism spectrum disorder and controls. We analyzed diffusion MRI-based tractography of subventricular zone-related pathways in 15 young adult men with autism spectrum disorder and 18 controls at Massachusetts General Hospital, with validation through the Autism Imaging Data Exchange II dataset. Participants with autism spectrum disorder had reduced subventricular zone pathway volumes and fractional anisotropy compared to controls. Furthermore, subventricular zone pathway volume was positively correlated (r: 0.68; 95% CI: 0.25 to 0.88) with symptom severity, suggesting that individuals with more severe symptoms tended to have larger subventricular zone pathway volumes, normalized by brain size. Analysis of the Autism Imaging Data Exchange cohort confirmed these findings of reduced subventricular zone pathway volumes in autism spectrum disorder. While some of these pathways may potentially include inaccurately disconnected pathways that go through the subventricular zone, our results suggest that diffusion MRI-based tractography pathways anatomically linked to the periventricular region are associated with certain symptom types in adult males with autism spectrum disorder.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":"35 3","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662448","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}
Brain functional networks are associated with parkinsonism in observational studies. However, the causal effects between brain functional networks and parkinsonism remain unclear. We aimed to assess the potential bidirectional causal associations between 191 brain resting-state functional magnetic resonance imaging (rsfMRI) phenotypes and parkinsonism including Parkinson's disease (PD) and drug-induced parkinsonism (DIP). We used Mendelian randomization (MR) to assess the bidirectional associations between brain rsfMRI phenotypes and parkinsonism, followed by several sensitivity analyses for robustness validation. In the forward MR analyses, we found that three rsfMRI phenotypes genetically determined the risk of parkinsonism. The connectivity in the visual network decreased the risk of PD (OR = 0.391, 95% CI = 0.235 ~ 0.649, P = 2.83 × 10-4, P_FDR = 0.039). The connectivity of salience and motor networks increased the risk of DIP (OR = 4.102, 95% CI = 1.903 ~ 8.845, P = 3.17 × 10-4, P_FDR = 0.044). The connectivity of limbic and default mode networks increased the risk of DIP (OR = 14.526, 95% CI = 3.130 ~ 67.408, P = 6.32 × 10-4, P_FDR = 0.0437). The reverse MR analysis indicated that PD and DIP had no effect on brain rsfMRI phenotypes. Our findings reveal causal relationships between brain functional networks and parkinsonism, providing important interventional and therapeutic targets for different parkinsonism.
在观察性研究中,脑功能网络与帕金森病有关。然而,脑功能网络与帕金森病之间的因果关系尚不清楚。我们旨在评估191种脑静息状态功能磁共振成像(rsfMRI)表型与帕金森病(包括帕金森病(PD)和药物性帕金森病(DIP))之间潜在的双向因果关系。我们使用孟德尔随机化(MR)来评估大脑rsfMRI表型与帕金森病之间的双向关联,随后进行了一些敏感性分析以进行稳健性验证。在前瞻性磁共振分析中,我们发现三种rsfMRI表型在遗传上决定了帕金森病的风险。视觉网络连通性降低PD发生风险(OR = 0.391, 95% CI = 0.235 ~ 0.649, P = 2.83 × 10-4, P_FDR = 0.039)。显著性和运动网络的连通性增加了DIP的风险(OR = 4.102, 95% CI = 1.903 ~ 8.845, P = 3.17 × 10-4, P_FDR = 0.044)。边缘网络和默认模式网络的连接增加了DIP的风险(OR = 14.526, 95% CI = 3.130 ~ 67.408, P = 6.32 × 10-4, P_FDR = 0.0437)。反向MR分析表明,PD和DIP对脑rsfMRI表型没有影响。我们的研究结果揭示了脑功能网络与帕金森病之间的因果关系,为不同帕金森病的介入和治疗提供了重要的靶点。
{"title":"Genetic analyses identify brain functional networks associated with the risk of Parkinson's disease and drug-induced parkinsonism.","authors":"Lin Chen, Ming-Juan Fang, Xu-En Yu, Yin Xu","doi":"10.1093/cercor/bhae506","DOIUrl":"10.1093/cercor/bhae506","url":null,"abstract":"<p><p>Brain functional networks are associated with parkinsonism in observational studies. However, the causal effects between brain functional networks and parkinsonism remain unclear. We aimed to assess the potential bidirectional causal associations between 191 brain resting-state functional magnetic resonance imaging (rsfMRI) phenotypes and parkinsonism including Parkinson's disease (PD) and drug-induced parkinsonism (DIP). We used Mendelian randomization (MR) to assess the bidirectional associations between brain rsfMRI phenotypes and parkinsonism, followed by several sensitivity analyses for robustness validation. In the forward MR analyses, we found that three rsfMRI phenotypes genetically determined the risk of parkinsonism. The connectivity in the visual network decreased the risk of PD (OR = 0.391, 95% CI = 0.235 ~ 0.649, P = 2.83 × 10-4, P_FDR = 0.039). The connectivity of salience and motor networks increased the risk of DIP (OR = 4.102, 95% CI = 1.903 ~ 8.845, P = 3.17 × 10-4, P_FDR = 0.044). The connectivity of limbic and default mode networks increased the risk of DIP (OR = 14.526, 95% CI = 3.130 ~ 67.408, P = 6.32 × 10-4, P_FDR = 0.0437). The reverse MR analysis indicated that PD and DIP had no effect on brain rsfMRI phenotypes. Our findings reveal causal relationships between brain functional networks and parkinsonism, providing important interventional and therapeutic targets for different parkinsonism.</p>","PeriodicalId":9715,"journal":{"name":"Cerebral cortex","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143001011","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}