Pub Date : 2026-01-01DOI: 10.1016/j.nicl.2025.103934
Malla Mononen , Mehrbod Mohammadian , Iftakher Hossain , Timo Roine , Olli Tenovuo , Kaj Blennow , Jessica Gill , Mark van Gils , Peter Hutchinson , Teemu M. Luoto , Henna-Riikka Maanpää , David K. Menon , Virginia F.J. Newcombe , Rahul Raj , Jean-Charles Sanchez , Riikka S.K. Takala , Jussi Tallus , Henrik Zetterberg , Jussi P. Posti
The aim of the study was to assess the association between blood-based biomarkers of different cellular origins and later white matter integrity, measured using post-acute diffusion tensor metrics, and their relation to outcome in patients presenting with Glasgow Coma Scale of 13–15 after traumatic brain injury (TBI).
Admission plasma samples for glial fibrillary acidic protein (GFAP), interleukin 10 (IL-10), heart fatty-acid binding protein (H-FABP), S100 calcium-binding protein B (S100B), total tau (T-tau), and amyloid beta 40 and 42 (Aβ40 and Aβ42) were taken for 92 patients. Diffusion-weighted magnetic resonance imaging (DW-MRI) and outcome evaluation was done ≥ 90 days post-injury. Outcome was assessed using Glasgow Outcome Scale-Extended (GOSE) and dichotomized as complete (GOSE 8) and incomplete (GOSE < 8) recovery. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized white matter tracts of the whole brain.
IL-10 and T-tau showed significant weak-moderate negative correlations with FA, and significant positive correlations with MD and RD in incompletely recovered patients. GFAP showed significant weak positive correlations with MD and RD, while its correlation with FA was slightly below significance threshold after correction for multiple comparison in incompletely recovered patients. Similar trends were observed in the whole cohort and in the CT-positive cohort, although these did not reach statistical significance.
Higher acute levels of GFAP, IL-10 and T-tau may be associated with the development of axonal injury. If validated in future studies, these biomarkers may help identify patients who require closer follow-up and DW-MRI.
{"title":"Association of acute blood biomarkers with diffusion tensor imaging and outcome in patients with traumatic brain injury presenting with GCS of 13–15","authors":"Malla Mononen , Mehrbod Mohammadian , Iftakher Hossain , Timo Roine , Olli Tenovuo , Kaj Blennow , Jessica Gill , Mark van Gils , Peter Hutchinson , Teemu M. Luoto , Henna-Riikka Maanpää , David K. Menon , Virginia F.J. Newcombe , Rahul Raj , Jean-Charles Sanchez , Riikka S.K. Takala , Jussi Tallus , Henrik Zetterberg , Jussi P. Posti","doi":"10.1016/j.nicl.2025.103934","DOIUrl":"10.1016/j.nicl.2025.103934","url":null,"abstract":"<div><div>The aim of the study was to assess the association between blood-based biomarkers of different cellular origins and later white matter integrity, measured using post-acute diffusion tensor metrics, and their relation to outcome in patients presenting with Glasgow Coma Scale of 13–15 after traumatic brain injury (TBI).</div><div>Admission plasma samples for glial fibrillary acidic protein (GFAP), interleukin 10 (IL-10), heart fatty-acid binding protein (H-FABP), S100 calcium-binding protein B (S100B), total tau (T-tau), and amyloid beta 40 and 42 (Aβ40 and Aβ42) were taken for 92 patients. Diffusion-weighted magnetic resonance imaging (DW-MRI) and outcome evaluation was done ≥ 90 days post-injury. Outcome was assessed using Glasgow Outcome Scale-Extended (GOSE) and dichotomized as complete (GOSE 8) and incomplete (GOSE < 8) recovery. Mean fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were calculated from the skeletonized white matter tracts of the whole brain.</div><div>IL-10 and T-tau showed significant weak-moderate negative correlations with FA, and significant positive correlations with MD and RD in incompletely recovered patients. GFAP showed significant weak positive correlations with MD and RD, while its correlation with FA was slightly below significance threshold after correction for multiple comparison in incompletely recovered patients. Similar trends were observed in the whole cohort and in the CT-positive cohort, although these did not reach statistical significance.</div><div>Higher acute levels of GFAP, IL-10 and T-tau may be associated with the development of axonal injury. If validated in future studies, these biomarkers may help identify patients who require closer follow-up and DW-MRI.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103934"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913935","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.2025.103920
Sandhya Narikuzhy , Sherain Harricharan , Daniela Rabellino , Maria Densmore , Jean Théberge , Jonathan Lieberman , Margaret C. McKinnon , Andrew A. Nicholson , Ruth A. Lanius
Background
The temporoparietal junction (TPJ) is a cross-network hub involved in social cognition and attention, processes which are directly impacted by symptoms observed in clinical profiles of post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS).
Methods
Using SPM12 and CONN, seed-based TPJ resting-state functional connectivity patterns were analyzed in individuals with PTSD (n = 81), PTSD + DS (n = 49), and healthy controls (n = 54) using four seeds [right anterior TPJ (raTPJ), left anterior TPJ (laTPJ), right posterior TPJ (rpTPJ), left posterior TPJ (lpTPJ)]. Post-hoc graph theoretical analyses were performed for raTPJ connectivity in PTSD + DS and healthy controls.
Results
As compared to healthy controls, PTSD + DS showed decreased raTPJ functional connectivity with critical anterior frontal lobe nodes involved in the ventral attention and social cognition networks (i.e., left ventrolateral and dorsomedial prefrontal cortices). PTSD showed decreased lpTPJ functional connectivity with the left superior parietal lobule as compared to healthy controls. When comparing PTSD to PTSD + DS, we observed increased bilateral TPJ functional connectivity with the cerebellum. Lastly, compared to healthy controls, both PTSD and PTSD + DS displayed decreased bilateral TPJ functional connectivity with the occipital lobe. Graph theoretical analyses revealed that PTSD + DS showed limited raTPJ involvement and instead more efficient neural communication between occipital lobe and frontal lobe structures as compared to healthy controls, suggesting a possible compensatory neural network in PTSD + DS.
Conclusions
These findings reveal disruptions in TPJ neural circuitry in PTSD and PTSD + DS, which may carry cascading effects on intersecting neural networks involving the TPJ. Implications for psychotherapeutic treatments targeting disembodiment and social cognition are discussed.
{"title":"Bridging the self to the world: resting-state functional connectivity of the temporoparietal junction in post-traumatic stress disorder and its dissociative subtype","authors":"Sandhya Narikuzhy , Sherain Harricharan , Daniela Rabellino , Maria Densmore , Jean Théberge , Jonathan Lieberman , Margaret C. McKinnon , Andrew A. Nicholson , Ruth A. Lanius","doi":"10.1016/j.nicl.2025.103920","DOIUrl":"10.1016/j.nicl.2025.103920","url":null,"abstract":"<div><h3>Background</h3><div>The temporoparietal junction (TPJ) is a cross-network hub involved in social cognition and attention, processes which are directly impacted by symptoms observed in clinical profiles of post-traumatic stress disorder (PTSD) and its dissociative subtype (PTSD + DS).</div></div><div><h3>Methods</h3><div>Using SPM12 and CONN, seed-based TPJ resting-state functional connectivity patterns were analyzed in individuals with PTSD (<em>n</em> = 81), PTSD + DS (<em>n</em> = 49), and healthy controls (<em>n</em> = 54) using four seeds [right anterior TPJ (raTPJ), left anterior TPJ (laTPJ), right posterior TPJ (rpTPJ), left posterior TPJ (lpTPJ)]. Post-hoc graph theoretical analyses were performed for raTPJ connectivity in PTSD + DS and healthy controls.</div></div><div><h3>Results</h3><div>As compared to healthy controls, PTSD + DS showed decreased raTPJ functional connectivity with critical anterior frontal lobe nodes involved in the ventral attention and social cognition networks (i.e., left ventrolateral and dorsomedial prefrontal cortices). PTSD showed decreased lpTPJ functional connectivity with the left superior parietal lobule as compared to healthy controls. When comparing PTSD to PTSD + DS, we observed increased bilateral TPJ functional connectivity with the cerebellum. Lastly, compared to healthy controls, both PTSD and PTSD + DS displayed decreased bilateral TPJ functional connectivity with the occipital lobe. Graph theoretical analyses revealed that PTSD + DS showed limited raTPJ involvement and instead more efficient neural communication between occipital lobe and frontal lobe structures as compared to healthy controls, suggesting a possible compensatory neural network in PTSD + DS.</div></div><div><h3>Conclusions</h3><div>These findings reveal disruptions in TPJ neural circuitry in PTSD and PTSD + DS, which may carry cascading effects on intersecting neural networks involving the TPJ. Implications for psychotherapeutic treatments targeting disembodiment and social cognition are discussed.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103920"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913943","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.2025.103933
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.2025.103935
Jacob Chernicky , Ally Dworetsky , Sarah Grossen , Emma Carr , Abdulmunaim Eid , Meghan C. Campbell , Caterina Gratton
Background
Parkinson’s disease (PD) is a complex neurodegenerative condition that leads to widespread disruption of large-scale brain networks and is further complicated by substantial individual variability in symptomology, progression rates, and treatment response. Consequently, the investigation of individual differences in networks measured via resting state functional connectivity (RSFC) may provide insight. However, most RSFC studies are unable to identify interindividual differences due to poor reliability and group average network definitions. “Precision” RSFC addresses these shortcomings through extended data collection, strict denoising, and individual network definition, but remains untested in PD.
Objectives
To evaluate the feasibility and reliability of precision RSFC studies in PD.
Methods
We collected > 100 min of RSFC data from 20 PD and 10 healthy control participants. We evaluated the level of motion, reliability and stability of RSFC measures in each participant, as well as compared to a conventional 5 min of RSFC data. These measures were benchmarked against HC to evaluate comparability. In addition, we created individualized brain network measures in PD participants to establish feasibility in this population.
Results
Using precision RSFC methods, the PD group produced reliable and stable measures of brain networks that were comparable in quality to healthy controls and substantially exceeded those derived from conventional approaches (whole-brain reliability: 5 min. r = 0.60 ± 0.06, 40 min. r = 0.88 ± 0.04; within-person stability: 5 min. r = 0.40 ± 0.08, 25 min. r = 0.68 ± 0.07; ps < 0.001). Individualized network maps in people with PD captured variation both from group-averaged templates and between individuals, including within motor-related networks.
Conclusion
Precision RSFC is feasible and reliable in individuals with PD. This approach holds promise for advancing personalized diagnostics and identifying brain-based biomarkers underlying clinical variability in PD.
{"title":"Towards precision functional brain network mapping in Parkinson’s disease","authors":"Jacob Chernicky , Ally Dworetsky , Sarah Grossen , Emma Carr , Abdulmunaim Eid , Meghan C. Campbell , Caterina Gratton","doi":"10.1016/j.nicl.2025.103935","DOIUrl":"10.1016/j.nicl.2025.103935","url":null,"abstract":"<div><h3>Background</h3><div>Parkinson’s disease (PD) is a complex neurodegenerative condition that leads to widespread disruption of large-scale brain networks and is further complicated by substantial individual variability in symptomology, progression rates, and treatment response. Consequently, the investigation of individual differences in networks measured via resting state functional connectivity (RSFC) may provide insight. However, most RSFC studies are unable to identify interindividual differences due to poor reliability and group average network definitions. “Precision” RSFC addresses these shortcomings through extended data collection, strict denoising, and individual network definition, but remains untested in PD.</div></div><div><h3>Objectives</h3><div>To evaluate the feasibility and reliability of precision RSFC studies in PD.</div></div><div><h3>Methods</h3><div>We collected > 100 min of RSFC data from 20 PD and 10 healthy control participants. We evaluated the level of motion, reliability and stability of RSFC measures in each participant, as well as compared to a conventional 5 min of RSFC data. These measures were benchmarked against HC to evaluate comparability. In addition, we created individualized brain network measures in PD participants to establish feasibility in this population.</div></div><div><h3>Results</h3><div>Using precision RSFC methods, the PD group produced reliable and stable measures of brain networks that were comparable in quality to healthy controls and substantially exceeded those derived from conventional approaches (whole-brain reliability: 5 min. r = 0.60 ± 0.06, 40 min. r = 0.88 ± 0.04; within-person stability: 5 min. r = 0.40 ± 0.08, 25 min. r = 0.68 ± 0.07; ps < 0.001). Individualized network maps in people with PD captured variation both from group-averaged templates and between individuals, including within motor-related networks.</div></div><div><h3>Conclusion</h3><div>Precision RSFC is feasible and reliable in individuals with PD. This approach holds promise for advancing personalized diagnostics and identifying brain-based biomarkers underlying clinical variability in PD.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103935"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913664","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.2025.103910
Joshua P. McGeown , Mangor Pedersen , Remika Mito , Alice Theadom , Jerome J. Maller , Paul Condron , Samantha J. Holdsworth
Background
Mild traumatic brain injury (mTBI) represents 95% of all traumatic brain injuries. Despite being classified as “mild,” mTBI can lead to persistent symptoms that impact quality of life. Diagnostic and management strategies rely heavily on subjective symptom reporting due to a lack of validated biomarkers. Identifying neuroimaging biomarkers to characterise the pathophysiological features underlying symptom burden and poor recovery is critical for improving mTBI management.
Objective
To synthesise evidence on cross-sectional, longitudinal, and prognostic links between Magnetic Resonance Imaging (MRI) features and mTBI symptom burden and functional recovery.
Methods
The review followed PRISMA guidelines. Systematic searches of MEDLINE, SCOPUS, and Cochrane Library identified mTBI studies with acute MRI data, measures of symptom burden or functional recovery, and at least one follow-up clinical timepoint, covering publications to July 18, 2025. Risk of bias was evaluated using the Quality in Prognostic Studies tool, and findings were synthesised narratively.
Results
Sixty-two of 7,232 articles were included. The review identified heterogeneous evidence across MRI modalities. Structural MRI findings showed limited correlation with clinical outcomes, while changes in white matter and functional connectivity were more strongly associated with symptom burden and recovery. Disruptions of integrative regions and association pathways such as the thalamus, superior longitudinal fasciculus, and cingulate cortex were linked to worse symptom burden and recovery outcomes.
Conclusions
Acute MRI, when contextualised with clinical data, helps delineate correlates of mTBI symptom burden and functional recovery. To strengthen inference, future neuroimaging studies should prespecify and report symptom burden and functional recovery as core endpoints.
{"title":"Neuroimaging correlates of symptom burden and functional recovery following mild traumatic brain injury: A systematic review","authors":"Joshua P. McGeown , Mangor Pedersen , Remika Mito , Alice Theadom , Jerome J. Maller , Paul Condron , Samantha J. Holdsworth","doi":"10.1016/j.nicl.2025.103910","DOIUrl":"10.1016/j.nicl.2025.103910","url":null,"abstract":"<div><h3>Background</h3><div>Mild traumatic brain injury (mTBI) represents 95% of all traumatic brain injuries. Despite being classified as “mild,” mTBI can lead to persistent symptoms that impact quality of life. Diagnostic and management strategies rely heavily on subjective symptom reporting due to a lack of validated biomarkers. Identifying neuroimaging biomarkers to characterise the pathophysiological features underlying symptom burden and poor recovery is critical for improving mTBI management.</div></div><div><h3>Objective</h3><div>To synthesise evidence on cross-sectional, longitudinal, and prognostic links between Magnetic Resonance Imaging (MRI) features and mTBI symptom burden and functional recovery.</div></div><div><h3>Methods</h3><div>The review followed PRISMA guidelines. Systematic searches of MEDLINE, SCOPUS, and Cochrane Library identified mTBI studies with acute MRI data, measures of symptom burden or functional recovery, and at least one follow-up clinical timepoint, covering publications to July 18, 2025. Risk of bias was evaluated using the Quality in Prognostic Studies tool, and findings were synthesised narratively.</div></div><div><h3>Results</h3><div>Sixty-two of 7,232 articles were included. The review identified heterogeneous evidence across MRI modalities. Structural MRI findings showed limited correlation with clinical outcomes, while changes in white matter and functional connectivity were more strongly associated with symptom burden and recovery. Disruptions of integrative regions and association pathways such as the thalamus, superior longitudinal fasciculus, and cingulate cortex were linked to worse symptom burden and recovery outcomes.</div></div><div><h3>Conclusions</h3><div>Acute MRI, when contextualised with clinical data, helps delineate correlates of mTBI symptom burden and functional recovery. To strengthen inference, future neuroimaging studies should prespecify and report symptom burden and functional recovery as core endpoints.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103910"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913925","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.2026.103950
Lara Keller , Leon D. Lotter , Claudia R. Eickhoff , Simon B. Eickhoff , Katharina Otten , Beate Herpertz-Dahlmann , Jochen Seitz
Substantial brain volume loss is well-documented during acute anorexia nervosa (AN); however, longitudinal outcomes are unclear. Our comprehensive meta-analysis investigated global and regional structural brain alterations in adult and adolescent individuals with AN by extracting reported brain volume scores and neuroimaging coordinates from the literature. Results showed significant global brain volume reductions in gray matter (GM), white matter (WM), and increases in cerebrospinal fluid (CSF) in acute AN (N = 1130 patients; N = 40 papers), gradually improving upon weight rehabilitation. However, even after 1.5 years of recovery, significantly lower global GM volume compared to healthy controls was found (N = 232 patients; N = 12 papers). Regarding potential regional changes, our search identified 35 eligible papers with neuroimaging coordinates for 412 foci as input for our anatomical likelihood estimation (ALE) analyses. The results revealed widespread reductions of GM volume and cortical thickness, but notably also identified consistently affected brain regions including the cingulate gyrus, precentral gyrus, and precuneus. Spatial colocalization analyses using the Neurosynth data base indicated brain areas associated with eating, food, threat, and reinforcement to be relatively preserved. The findings of our meta-analysis contribute to a better understanding of the underlying pathophysiology of AN, the time course and residuals of brain structural alterations during recovery and clinical implications potentially relevant for more-targeted treatment options.
{"title":"Structural brain alterations in anorexia nervosa: a global brain volume and anatomical likelihood estimation (ALE) meta-analysis combined with a functional decoding approach","authors":"Lara Keller , Leon D. Lotter , Claudia R. Eickhoff , Simon B. Eickhoff , Katharina Otten , Beate Herpertz-Dahlmann , Jochen Seitz","doi":"10.1016/j.nicl.2026.103950","DOIUrl":"10.1016/j.nicl.2026.103950","url":null,"abstract":"<div><div>Substantial brain volume loss is well-documented during acute anorexia nervosa (AN); however, longitudinal outcomes are unclear. Our comprehensive meta-analysis investigated global and regional structural brain alterations in adult and adolescent individuals with AN by extracting reported brain volume scores and neuroimaging coordinates from the literature. Results showed significant global brain volume reductions in gray matter (GM), white matter (WM), and increases in cerebrospinal fluid (CSF) in acute AN (N = 1130 patients; N = 40 papers), gradually improving upon weight rehabilitation. However, even after 1.5 years of recovery, significantly lower global GM volume compared to healthy controls was found (N = 232 patients; N = 12 papers). Regarding potential regional changes, our search identified 35 eligible papers with neuroimaging coordinates for 412 foci as input for our anatomical likelihood estimation (ALE) analyses. The results revealed widespread reductions of GM volume and cortical thickness, but notably also identified consistently affected brain regions including the cingulate gyrus, precentral gyrus, and precuneus. Spatial colocalization analyses using the Neurosynth data base indicated brain areas associated with eating, food, threat, and reinforcement to be relatively preserved. The findings of our meta-analysis contribute to a better understanding of the underlying pathophysiology of AN, the time course and residuals of brain structural alterations during recovery and clinical implications potentially relevant for more-targeted treatment options.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"49 ","pages":"Article 103950"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146077834","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}