Pub Date : 2026-01-01DOI: 10.1016/j.nicl.2025.103933
Sebastian König , Anna Tuiskula , Marjo Metsäranta , Susanna Stjerna , Emma Saure , Leena Haataja , Sampsa Vanhatalo , Anton Tokariev
Perinatal asphyxia can lead to clinical hypoxic-ischemic encephalopathy (HIE) associated with high morbidity and mortality, but less is known about long-lasting effects of perinatal asphyxia alone (PA). Here, we investigate how PA with versus without clinical HIE affects cortical activity networks at two years of age. Electroencephalographic (EEG) recordings were acquired during sleep from three cohorts of children (PA only (n = 10), PA with mild to moderate HIE (n = 8), and healthy controls (n = 37)), and we assessed the group differences in local cortical function and cortico-cortical networks. Compared with the healthy controls, both PA and HIE were linked to reduced frequency-specific amplitudes. In two-year-old children with PA, the amplitude-related networks were stronger at low frequencies and weaker at higher frequencies, however, two-year-olds with HIE showed decreased connectivity at all frequencies. Likewise, phase-related networks in children with PA were stronger at lower frequencies and weaker at higher frequencies. Local phase-amplitude coupling was affected by PA or HIE in only a few cortical regions. Our findings suggest that PA, even without clinical HIE, may be associated with long-lasting changes to both local cortical activity and the large-scale cortical networks, which could potentially affect normal brain functions.
{"title":"Effects of perinatal asphyxia on cortical activity in two-year-old children","authors":"Sebastian König , Anna Tuiskula , Marjo Metsäranta , Susanna Stjerna , Emma Saure , Leena Haataja , Sampsa Vanhatalo , Anton Tokariev","doi":"10.1016/j.nicl.2025.103933","DOIUrl":"10.1016/j.nicl.2025.103933","url":null,"abstract":"<div><div>Perinatal asphyxia can lead to clinical hypoxic-ischemic encephalopathy (HIE) associated with high morbidity and mortality, but less is known about long-lasting effects of perinatal asphyxia alone (PA). Here, we investigate how PA with versus without clinical HIE affects cortical activity networks at two years of age. Electroencephalographic (EEG) recordings were acquired during sleep from three cohorts of children (PA only (n = 10), PA with mild to moderate HIE (n = 8), and healthy controls (n = 37)), and we assessed the group differences in local cortical function and cortico-cortical networks. Compared with the healthy controls, both PA and HIE were linked to reduced frequency-specific amplitudes. In two-year-old children with PA, the amplitude-related networks were stronger at low frequencies and weaker at higher frequencies, however, two-year-olds with HIE showed decreased connectivity at all frequencies. Likewise, phase-related networks in children with PA were stronger at lower frequencies and weaker at higher frequencies. Local phase-amplitude coupling was affected by PA or HIE in only a few cortical regions. Our findings suggest that PA, even without clinical HIE, may be associated with long-lasting changes to both local cortical activity and the large-scale cortical networks, which could potentially affect normal brain functions.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103933"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913880","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 : 2026-01-01DOI: 10.1016/j.nicl.2025.103930
Mijntje M.I. Schellekens , Hao Li , Maartje Wijnands , Anastasia Papounidou , Esther M. Boot , Jamie I. Verhoeven , Merel S. Ekker , Mayte E. van Alebeek , Paul J.A.M. Brouwers , Renate M. Arntz , Gert W. van Dijk , Rob A.R. Gons , Inge W.M. van Uden , Tom den Heijer , Julia H. van Tuijl , Karlijn F. de Laat , Anouk G.W. van Norden , Sarah E. Vermeer , Marian S.G. van Zagten , Robert J. van Oostenbrugge , Anil M. Tuladhar
Introduction
Stroke location is an important determinant of post-stroke cognitive impairment (PSCI). In young adults, a comprehensive map of lesion patterns and their relations to PSCI is lacking. This study aims to identify lesion locations associated with poorer cognitive performance in patients with stroke at a young age.
Methods
We conducted a multicenter prospective cohort study between 2013 and 2021, enrolling patients aged 18–49 years with first-ever ischemic stroke and a visible stroke lesion on MRI. Cognitive assessments were performed within six months post-stroke, covering seven domains. We categorized patients as having no/mild or major vascular cognitive disorder (VCD), defined as a Z-score < -2.0 in one or more domains. We assessed aphasia by the NIHSS language subscale. We performed multivariate lesion-symptom mapping to identify lesion locations associated with major VCD, poorer cognitive performance in each domain, and aphasia.
Results
Among 522 patients (median age 44.3 years [IQR 37.7–41.5]; 257 [49.2 %] women), 168 (32.2 %) had major VCD. Lesions in both hemispheres and cerebellar regions were associated with presence of a major VCD, and lower performance in episodic memory, processing speed, executive functioning, language, and attention and working memory. Aphasia had the strongest relationship with left fronto-temporo-parietal regions, while the left angular gyrus was the region most associated with major VCD.
Discussion
We show that lesion locations associated with poorer cognitive performance in young stroke patients are widely distributed, including cerebellar regions. This study showcases the complexity in the relationships between affected brain regions and cognitive symptoms, explaining the variability in post-stroke cognitive outcome.
{"title":"Lesion locations are associated with cognitive impairment after ischemic stroke in young adults","authors":"Mijntje M.I. Schellekens , Hao Li , Maartje Wijnands , Anastasia Papounidou , Esther M. Boot , Jamie I. Verhoeven , Merel S. Ekker , Mayte E. van Alebeek , Paul J.A.M. Brouwers , Renate M. Arntz , Gert W. van Dijk , Rob A.R. Gons , Inge W.M. van Uden , Tom den Heijer , Julia H. van Tuijl , Karlijn F. de Laat , Anouk G.W. van Norden , Sarah E. Vermeer , Marian S.G. van Zagten , Robert J. van Oostenbrugge , Anil M. Tuladhar","doi":"10.1016/j.nicl.2025.103930","DOIUrl":"10.1016/j.nicl.2025.103930","url":null,"abstract":"<div><h3>Introduction</h3><div>Stroke location is an important determinant of post-stroke cognitive impairment (PSCI). In young adults, a comprehensive map of lesion patterns and their relations to PSCI is lacking. This study aims to identify lesion locations associated with poorer cognitive performance in patients with stroke at a young age.</div></div><div><h3>Methods</h3><div>We conducted a multicenter prospective cohort study between 2013 and 2021, enrolling patients aged 18–49 years with first-ever ischemic stroke and a visible stroke lesion on MRI. Cognitive assessments were performed within six months post-stroke, covering seven domains. We categorized patients as having no/mild or major vascular cognitive disorder (VCD), defined as a Z-score < -2.0 in one or more domains. We assessed aphasia by the NIHSS language subscale. We performed multivariate lesion-symptom mapping to identify lesion locations associated with major VCD, poorer cognitive performance in each domain, and aphasia.</div></div><div><h3>Results</h3><div>Among 522 patients (median age 44.3 years [IQR 37.7–41.5]; 257 [49.2 %] women), 168 (32.2 %) had major VCD. Lesions in both hemispheres and cerebellar regions were associated with presence of a major VCD, and lower performance in episodic memory, processing speed, executive functioning, language, and attention and working memory. Aphasia had the strongest relationship with left fronto-temporo-parietal regions, while the left angular gyrus was the region most associated with major VCD.</div></div><div><h3>Discussion</h3><div>We show that lesion locations associated with poorer cognitive performance in young stroke patients are widely distributed, including cerebellar regions. This study showcases the complexity in the relationships between affected brain regions and cognitive symptoms, explaining the variability in post-stroke cognitive outcome.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103930"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913896","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 : 2026-01-01DOI: 10.1016/j.nicl.2025.103937
Eric W Moffet , Sancharee Hom Chowdhury , Ediel Almeida , Xiangxiang Kong , Lujie Chen , Jiachen Zhuo , Nicholas A Morris , Gunjan Y Parikh , Neeraj Badjatia , Jamie E Podell
Paroxysmal sympathetic hyperactivity (PSH) is a clinically important manifestation of dysautonomia following traumatic brain injury (TBI). While it is thought to arise from central autonomic network disconnection, supporting evidence is limited. Here, we integrate clinically obtained magnetic resonance imaging (MRI) lesion data with human connectome data to identify specific white matter tract disconnections and gray matter parcel damage associated with PSH. Our sample included 117 patients who underwent susceptibility weighted imaging and 3D T1 MRI sequences as part of clinical care while admitted at our institution between January 1, 2016 and July 1, 2018. Susceptibility lesion masks were manually created and registered to standard template space. High quality registrations were obtained in 96 patients (50% with PSH), who were included in the study. Using the Matlab Lesion Quantification Toolkit, we assessed white matter tract disconnection severity and gray matter parcel damage for each patient. We compared results according to a binary PSH clinical diagnosis using Wilcoxon rank sum tests and a standard ordinal PSH diagnostic likelihood score (with 0–11 range) using Pearson correlations, Bonferroni-corrected for multiple comparisons. PSH diagnosis was associated with greater disconnection severity in nine tracts, two of which also correlated with higher diagnosis likelihood: the right uncinate fasciculus and the anterior corpus callosum. Damaged parcels associated with PSH included left prefrontal regions of the default mode network and the ventral salience network. In summary, our work implicates disconnection of fronto-limbic components of the central autonomic network in the pathophysiology of TBI-related PSH.
{"title":"Fronto-limbic disconnection correlates with paroxysmal sympathetic hyperactivity following traumatic brain injury: An indirect disconnection-symptom mapping study","authors":"Eric W Moffet , Sancharee Hom Chowdhury , Ediel Almeida , Xiangxiang Kong , Lujie Chen , Jiachen Zhuo , Nicholas A Morris , Gunjan Y Parikh , Neeraj Badjatia , Jamie E Podell","doi":"10.1016/j.nicl.2025.103937","DOIUrl":"10.1016/j.nicl.2025.103937","url":null,"abstract":"<div><div>Paroxysmal sympathetic hyperactivity (PSH) is a clinically important manifestation of dysautonomia following traumatic brain injury (TBI). While it is thought to arise from central autonomic network disconnection, supporting evidence is limited. Here, we integrate clinically obtained magnetic resonance imaging (MRI) lesion data with human connectome data to identify specific white matter tract disconnections and gray matter parcel damage associated with PSH. Our sample included 117 patients who underwent susceptibility weighted imaging and 3D T1 MRI sequences as part of clinical care while admitted at our institution between January 1, 2016 and July 1, 2018. Susceptibility lesion masks were manually created and registered to standard template space. High quality registrations were obtained in 96 patients (50% with PSH), who were included in the study. Using the Matlab Lesion Quantification Toolkit, we assessed white matter tract disconnection severity and gray matter parcel damage for each patient. We compared results according to a binary PSH clinical diagnosis using Wilcoxon rank sum tests and a standard ordinal PSH diagnostic likelihood score (with 0–11 range) using Pearson correlations, Bonferroni-corrected for multiple comparisons. PSH diagnosis was associated with greater disconnection severity in nine tracts, two of which also correlated with higher diagnosis likelihood: the right uncinate fasciculus and the anterior corpus callosum. Damaged parcels associated with PSH included left prefrontal regions of the default mode network and the ventral salience network. In summary, our work implicates disconnection of fronto-limbic components of the central autonomic network in the pathophysiology of TBI-related PSH.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103937"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913967","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 : 2026-01-01DOI: 10.1016/j.nicl.2026.103951
Lulu Ai , Zhiwei Li , Chaojuan Huang , Xia Zhou , Xiaoqun Zhu , Qiaoqiao Xu , Zhongwu Sun
Background and objective
The glymphatic system constitutes a brain-wide perivascular network responsible for brain metabolic waste removal, which may underlie pathogenesis in cerebral small vessel disease (CSVD). This study aimed to explore the associations of glymphatic function, assessed using multi-modal MRI indices, and both brain atrophy and cognitive impairment in CSVD.
Methods
The study included 160 participants comprising 120 patients with CSVD, including 52 without cognitive impairment (CSVD-NCI) and 68 with mild cognitive impairment (CSVD-MCI), alongside 40 healthy controls (HCs). All participants underwent neuropsychological and multi-modal neuroimaging assessments. Glymphatic function was assessed using four complementary MRI indices: choroid plexus (CP) volume, perivascular space (PVS) volume fraction, free water in white matter (FW-WM) fraction, and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Gray matter volume (GMV) was evaluated via voxel-based morphology (VBM) analysis. Partial correlation and mediation analyses explored the relationships among glymphatic function, brain structure and cognitive performance.
Results
Compared to HCs, CSVD-MCI patients showed increased CP volume, FW-WM fraction, BG/putamen-PVS volume, and reduced DTI-ALPS index, accompanied by multifocal gray matter atrophy involving temporal and frontal regions. Advanced age was associated with increased CP and BG-PVS volume, but decreased DTI-ALPS index. A main effect of sex was observed, where males exhibited larger BG-PVS and FW-WM fraction, with lower DTI-ALPS index compared to females. Impaired glymphatic function was linked to both GMV loss and cognitive deficits, with right superior temporal and left postcentral GMV mediating glymphatic-cognitive associations, particularly in executive function and processing speed.
Conclusion
Glymphatic dysfunction in CSVD, particularly in cognitive impairment stage, is closely related to brain atrophy and cognitive decline, supporting the potential utility of glymphatic metrics as clinically imaging biomarkers for assessing cognitive impairment risk and monitor disease progression in CSVD.
{"title":"Association of MRI indexes of glymphatic system with brain atrophy and cognitive impairment in cerebral small vessel disease","authors":"Lulu Ai , Zhiwei Li , Chaojuan Huang , Xia Zhou , Xiaoqun Zhu , Qiaoqiao Xu , Zhongwu Sun","doi":"10.1016/j.nicl.2026.103951","DOIUrl":"10.1016/j.nicl.2026.103951","url":null,"abstract":"<div><h3>Background and objective</h3><div>The glymphatic system constitutes a brain-wide perivascular network responsible for brain metabolic waste removal, which may underlie pathogenesis in cerebral small vessel disease (CSVD). This study aimed to explore the associations of glymphatic function, assessed using multi-modal MRI indices, and both brain atrophy and cognitive impairment in CSVD.</div></div><div><h3>Methods</h3><div>The study included 160 participants comprising 120 patients with CSVD, including 52 without cognitive impairment (CSVD-NCI) and 68 with mild cognitive impairment (CSVD-MCI), alongside 40 healthy controls (HCs). All participants underwent neuropsychological and multi-modal neuroimaging assessments. Glymphatic function was assessed using four complementary MRI indices: choroid plexus (CP) volume, perivascular space (PVS) volume fraction, free water in white matter (FW-WM) fraction, and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Gray matter volume (GMV) was evaluated via voxel-based morphology (VBM) analysis. Partial correlation and mediation analyses explored the relationships among glymphatic function, brain structure and cognitive performance.</div></div><div><h3>Results</h3><div>Compared to HCs, CSVD-MCI patients showed increased CP volume, FW-WM fraction, BG/putamen-PVS volume, and reduced DTI-ALPS index, accompanied by multifocal gray matter atrophy involving temporal and frontal regions. Advanced age was associated with increased CP and BG-PVS volume, but decreased DTI-ALPS index. A main effect of sex was observed, where males exhibited larger BG-PVS and FW-WM fraction, with lower DTI-ALPS index compared to females. Impaired glymphatic function was linked to both GMV loss and cognitive deficits, with right superior temporal and left postcentral GMV mediating glymphatic-cognitive associations, particularly in executive function and processing speed.</div></div><div><h3>Conclusion</h3><div>Glymphatic dysfunction in CSVD, particularly in cognitive impairment stage, is closely related to brain atrophy and cognitive decline, supporting the potential utility of glymphatic metrics as clinically imaging biomarkers for assessing cognitive impairment risk and monitor disease progression in CSVD.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103951"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146031770","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 : 2026-01-01DOI: 10.1016/j.nicl.2026.103944
Tuulia Malén , Jouni Tuisku , Marco Bucci , Severi Santavirta , Valtteri Kaasinen , Sakari Kaasalainen , Janne Isojärvi , Jarmo Hietala , Juha Rinne , Lauri Nummenmaa
Background
Positron emission tomography (PET) using radioligand [18F]fluorodopa detects reduced striatal dopamine synthesis capacity in Parkinson’s disease (PD) patients. Demographic factors such as sex and BMI are also associated with dopamine synthesis capacity. The combined contribution of demographic and clinical effects however remains elusive.
Material, aims, and methods
For this retrospective register-based study, we used baseline [18F]fluorodopa PET data acquired at the Turku PET Centre between the years 1988–2016 with three scanners (Ecat 931, GE Advance, HRRT). The data involved 350 adult human subjects, including 132 healthy controls, and 218 PD patients. The primary aim was to simultaneously investigate the effects of PD, age, sex and BMI on regional dopamine synthesis capacity (influx rate constant Kiref quantified with Patlak in atlas-based regions of interest) using Bayesian linear regression. Secondary aims were to assess (1) interregional correlations of dopamine synthesis capacity, (2) association between regional presynaptic dopamine synthesis and postsynaptic dopamine type 2 receptor (D2R) availability in subjects who also had a proximal [11C]raclopride PET scan, and (3) scanner effects and atlas- versus MRI-based quantification approaches. We provide the mean dopamine synthesis brain maps of healthy controls and PD patients in NeuroVault.
Results
Dopamine synthesis capacity was drastically reduced in PD patients, decreased with age, increased with BMI, and higher in females versus males. Across regions, the capacity was positively correlated in both patients and controls. We observed support for positive correlation between the dopamine synthesis capacity and the D2R in caudate nucleus. Scanner had a substantial influence on Kiref estimates. Atlas- and MRI-based normalization methods provide largely comparable Kiref estimates for most subjects.
Conclusions
Dopamine synthesis capacity is independently affected by PD and demographic factors and correlated between the striatal and thalamic regions in both controls and PD patients. Adjusting for scanner effects in multi-scanner datasets is recommended. When subject-specific MRI is unavailable, atlas-based normalization may be used with caution to prevent major data loss.
{"title":"Striatal dopamine synthesis capacity in Parkinson’s disease: Effects of age, sex, and body mass index in a large [18F]fluorodopa PET cohort","authors":"Tuulia Malén , Jouni Tuisku , Marco Bucci , Severi Santavirta , Valtteri Kaasinen , Sakari Kaasalainen , Janne Isojärvi , Jarmo Hietala , Juha Rinne , Lauri Nummenmaa","doi":"10.1016/j.nicl.2026.103944","DOIUrl":"10.1016/j.nicl.2026.103944","url":null,"abstract":"<div><h3>Background</h3><div>Positron emission tomography (PET) using radioligand [<sup>18</sup>F]fluorodopa detects reduced striatal dopamine synthesis capacity in Parkinson’s disease (PD) patients. Demographic factors such as sex and BMI are also associated with dopamine synthesis capacity. The combined contribution of demographic and clinical effects however remains elusive.</div></div><div><h3>Material, aims, and methods</h3><div>For this retrospective register-based study, we used baseline [<sup>18</sup>F]fluorodopa PET data acquired at the Turku PET Centre between the years 1988–2016 with three scanners (Ecat 931, GE Advance, HRRT). The data involved 350 adult human subjects, including 132 healthy controls, and 218 PD patients. The primary aim was to simultaneously investigate the effects of PD, age, sex and BMI on regional dopamine synthesis capacity (influx rate constant Ki<sup>ref</sup> quantified with Patlak in atlas-based regions of interest) using Bayesian linear regression. Secondary aims were to assess (1) interregional correlations of dopamine synthesis capacity, (2) association between regional presynaptic dopamine synthesis and postsynaptic dopamine type 2 receptor (D<sub>2</sub>R) availability in subjects who also had a proximal [<sup>11</sup>C]raclopride PET scan, and (3) scanner effects and atlas- versus MRI-based quantification approaches. We provide the mean dopamine synthesis brain maps of healthy controls and PD patients in NeuroVault.</div></div><div><h3>Results</h3><div>Dopamine synthesis capacity was drastically reduced in PD patients, decreased with age, increased with BMI, and higher in females versus males. Across regions, the capacity was positively correlated in both patients and controls. We observed support for positive correlation between the dopamine synthesis capacity and the D<sub>2</sub>R in caudate nucleus. Scanner had a substantial influence on Ki<sup>ref</sup> estimates. Atlas- and MRI-based normalization methods provide largely comparable Ki<sup>ref</sup> estimates for most subjects.</div></div><div><h3>Conclusions</h3><div>Dopamine synthesis capacity is independently affected by PD and demographic factors and correlated between the striatal and thalamic regions in both controls and PD patients. Adjusting for scanner effects in multi-scanner datasets is recommended. When subject-specific MRI is unavailable, atlas-based normalization may be used with caution to prevent major data loss.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103944"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145968088","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 : 2026-01-01DOI: 10.1016/j.nicl.2026.103958
Isaac David , Shuntaro Sasai , Felipe Branco de Paiva , Melanie Boly , Giulio Tononi , Larissa Albantakis
Background
Schizophrenia is associated with widespread functional dysconnectivity, but the spatial scale and structural correlates of these alterations remain unclear. While relevant to local dysfunction, short-range connectivity is not well captured by standard approaches due to methodological constraints.
Methods
We applied a vertex-wise, distance-dependent analysis of functional connectivity strength (FCS) to resting-state fMRI data from 86 schizophrenia patients and 99 healthy controls across two datasets. FCS was partitioned by geodesic distance on the cortical surface and analyzed by cortical hierarchy. We also assessed two proxies of intracortical microstructure: T1/T2 ratio and a novel signal-detection-based measure of individualized data-driven functional connectivity density (idFCD).
Results
Schizophrenia patients exhibited reductions in short-range FCS within the dorsal primary somatosensory cortex. These functional alterations colocalized with abnormalities in both microstructural proxies and were not evident in global FCS analysis. In contrast, longer-range FCS was increased in transmodal regions, particularly the precuneus, without associated microstructural differences. Hierarchical analysis confirmed this dissociation, with structure–function disruption in primary networks and increased relative FCS in transmodal regions without microstructural association.
Conclusions
Our findings support two distinct patterns of cortical dysconnectivity in schizophrenia: short-range reductions in primary sensory areas that colocalize with microstructural abnormalities, and longer-range increases in transmodal regions that appear structurally decoupled at the local level. By integrating distance-dependent functional measures with independent proxies of intracortical microstructure, this study highlights the role of short-range connectivity disruptions in primary areas and provides a complementary framework to conventional approaches based on regional or global analyses and diffusion-weighted imaging.
{"title":"Distance- and hierarchy-dependent functional dysconnectivity in schizophrenia and its association with cortical microstructure","authors":"Isaac David , Shuntaro Sasai , Felipe Branco de Paiva , Melanie Boly , Giulio Tononi , Larissa Albantakis","doi":"10.1016/j.nicl.2026.103958","DOIUrl":"10.1016/j.nicl.2026.103958","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia is associated with widespread functional dysconnectivity, but the spatial scale and structural correlates of these alterations remain unclear. While relevant to local dysfunction, short-range connectivity is not well captured by standard approaches due to methodological constraints.</div></div><div><h3>Methods</h3><div>We applied a vertex-wise, distance-dependent analysis of functional connectivity strength (FCS) to resting-state fMRI data from 86 schizophrenia patients and 99 healthy controls across two datasets. FCS was partitioned by geodesic distance on the cortical surface and analyzed by cortical hierarchy. We also assessed two proxies of intracortical microstructure: T1/T2 ratio and a novel signal-detection-based measure of individualized data-driven functional connectivity density (idFCD).</div></div><div><h3>Results</h3><div>Schizophrenia patients exhibited reductions in short-range FCS within the dorsal primary somatosensory cortex. These functional alterations colocalized with abnormalities in both microstructural proxies and were not evident in global FCS analysis. In contrast, longer-range FCS was increased in transmodal regions, particularly the precuneus, without associated microstructural differences. Hierarchical analysis confirmed this dissociation, with structure–function disruption in primary networks and increased relative FCS in transmodal regions without microstructural association.</div></div><div><h3>Conclusions</h3><div>Our findings support two distinct patterns of cortical dysconnectivity in schizophrenia: short-range reductions in primary sensory areas that colocalize with microstructural abnormalities, and longer-range increases in transmodal regions that appear structurally decoupled at the local level. By integrating distance-dependent functional measures with independent proxies of intracortical microstructure, this study highlights the role of short-range connectivity disruptions in primary areas and provides a complementary framework to conventional approaches based on regional or global analyses and diffusion-weighted imaging.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103958"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146167866","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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