Neuroimage-Clinical最新文献

{"title":"Exploring the effect of multi-modal intervention against cognitive decline on atrophy and small vessel disease imaging markers in the AgeWell.de imaging study","authors":"Frauke Beyer , Lukas Kleine , Andrea Zülke , Melanie Luppa , Toralf Mildner , Jochen Gensichen , Thomas Frese , David Czock , Birgitt Wiese , Hans-Helmut König , Hanna Kaduszkiewicz , Wolfgang Hoffmann , Jochen René Thyrian , Arno Villringer , Steffi Riedel-Heller , A.Veronica Witte","doi":"10.1016/j.nicl.2025.103796","DOIUrl":"10.1016/j.nicl.2025.103796","url":null,"abstract":"<div><h3>Background</h3><div>Multimodal lifestyle interventions might help to maintain healthy cognition in older age and to delay onset of dementia. Here, we studied the effects of a multi-modal lifestyle-based intervention, based on the FINGER trial, on magnetic resonance imaging (MRI) markers of hippocampal-limbic atrophy and cerebral small vessel disease in older adults at increased risk for dementia in Germany.</div></div><div><h3>Methods</h3><div>Leipzig participants of the multicenter AgeWell.de randomized controlled trial underwent neuroimaging before and after a two year intervention at 3 Tesla MRI. We extracted hippocampal volume and entorhinal cortex thickness (ECT), free water fraction (FW), peak width of skeletonized mean diffusivity (PSMD), white matter hyperintensity volume and mean gray matter cerebral blood flow and assessed the effect of the intervention on these imaging markers using linear mixed models. We also tested the effect of the intervention on the hippocampus-dependent Mnemonic Similarity Test and fixel-based white matter microstructure.</div></div><div><h3>Results</h3><div>56 individuals (mean (sd) age: 68.8 (4.2) years, 26 females, 24/32 intervention/control group) were included at baseline and 41 returned after an average of 28 months for the second assessment. ECT and FW exhibited stronger decline in the intervention compared to the control group in preregistered models but not when adjusted for baseline differences. All other markers progressed similarly across groups, however sample size was smaller than expected. In exploratory analyses, cerebral blood flow increased more in the intervention group and this change was associated with decreases in systolic blood pressure.</div></div><div><h3>Conclusions</h3><div>In this group of older adults at risk for dementia, we find no conclusive evidence whether a multi-modal lifestyle intervention improves brain imaging markers of neurodegeneration and small vessel disease. Preliminary evidence suggested an association of the intervention, increased cerebral blood flow and systolic blood pressure reductions.</div><div>Abbreviations: ECT, entorhinal cortex thickness; FW, free water fraction; WHO, world health organization; AD, Alzheimer’s disease; VCI, vascular cognitive impairment; FINGER, Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability; MTL, medial temporal lobe; MIND, Mediterranean-DASH Intervention for Neurodegenerative Delay diet; cSVD, cerebral small vessel disease; WMH, white matter hyperintensities of presumed vascular origin; PSMD, peak width of the mean diffusivity distribution; WW-FINGERS, world wide FINGER studies; CAIDE, Cardiovascular Risk Factors, Aging, and Incidence of Dementia; GPP, general practitioner praxis; MRI, magnetic resonance imaging; MST, Mnemonic Similarity Test; TE, echo time; TR, repetition time; FA, flip angle; FOV, field of view; GRAPPA, GeneRalized Autocalibrating Partial Parallel Acquisition; CMRR, Center","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"46 ","pages":"Article 103796"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143946816","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}

{"title":"Corrigendum to “Association between clinical features and decreased degree centrality and variability in dynamic functional connectivity in the obsessive-compulsive disorder” [Neuroimage: Clinical 44 (2024) 1–9/103665]","authors":"Changjun Teng , Wei Zhang , Da Zhang , Xiaomeng Shi , Xin Wu , Huifen Qiao , Ning Zhang , Xiao Hu , Chengbin Guan","doi":"10.1016/j.nicl.2024.103675","DOIUrl":"10.1016/j.nicl.2024.103675","url":null,"abstract":"","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"45 ","pages":"Article 103675"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142332387","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}

{"title":"Disturbed hierarchy and mediation in reward-related circuits in depression","authors":"Ruikun Yang ,&nbsp;Junxia Chen ,&nbsp;Suping Yue ,&nbsp;Yue Yu ,&nbsp;Jiamin Fan ,&nbsp;Yuling Luo ,&nbsp;Hui He ,&nbsp;Mingjun Duan ,&nbsp;Sisi Jiang ,&nbsp;Dezhong Yao ,&nbsp;Cheng Luo","doi":"10.1016/j.nicl.2025.103739","DOIUrl":"10.1016/j.nicl.2025.103739","url":null,"abstract":"<div><h3>Backgrounds/Objective</h3><div>Deep brain stimulation (DBS) has proved the viability of alleviating depression symptoms by stimulating deep reward-related nuclei. This study aims to investigate the abnormal connectivity profiles among superficial, intermediate, and deep brain regions within the reward circuit in major depressive disorder (MDD) and therefore provides references for identifying potential superficial cortical targets for non-invasive neuromodulation.</div></div><div><h3>Methods</h3><div>Resting-state functional magnetic resonance imaging data were collected from a cohort of depression patients (N = 52) and demographically matched healthy controls (N = 60). Utilizing existing DBS targets as seeds, we conducted step-wise functional connectivity (sFC) analyses to delineate hierarchical pathways linking to cerebral cortices. Subsequently, the mediation effects of cortical regions on the interaction within reward-related circuits were further explored by constructing mediation models.</div></div><div><h3>Results</h3><div>In both cohorts, sFC analysis revealed two reward-related pathways from the deepest DBS targets to intermediate regions including the thalamus, insula, and anterior cingulate cortex (ACC), then to the superficial cortical cortex including medial frontal cortex, posterior default mode network (pDMN), and right dorsolateral prefrontal cortex (DLPFC). Patients exhibited reduced sFC in bilateral thalamus and medial frontal cortex in short and long steps respectively compared to healthy controls. We also discovered the disappearance of the mediation effects of superficial cortical regions on the interaction between DBS targets and intermediate regions in reward-related pathways in patients with MDD.</div></div><div><h3>Conclusion</h3><div>Our findings support abnormal hierarchical connectivity and mediation effects in reward-related brain regions at different depth levels in MDD, which might elucidate the underlying pathophysiological mechanisms and inspire novel targets for non-invasive interventions.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"45 ","pages":"Article 103739"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048585","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}

{"title":"Differential patterns of axonal loss associated with threat-related adversity in atypical depression and non-atypical depression","authors":"Huifeng Zhang ,&nbsp;Lei Ding ,&nbsp;Lanxiang He ,&nbsp;Rubai Zhou ,&nbsp;Wenxian Lu ,&nbsp;Tenghuan Xu ,&nbsp;Ye Wu ,&nbsp;Daihui Peng","doi":"10.1016/j.nicl.2025.103786","DOIUrl":"10.1016/j.nicl.2025.103786","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) encompasses a broad spectrum of heterogeneous symptoms arising from distinct etiological mechanisms. Phenotypic markers of psychopathology are most likely influenced by exposure to childhood maltreatment, yielding distinct subtypes within conventional diagnostic boundaries. However, the biological interactions between MDD subtypes and types of childhood trauma remain unclear.</div></div><div><h3>Methods</h3><div>50 atypical depression (AD) patients, 97 non-AD patients and 50 healthy controls were included to complete multi-shell diffusion MRI scans and clinical assessments. Differential tractography was performed to clarify the axonal injury between the AD and non-AD groups. Moreover, correlational tractography was employed to individually assess the relationship between quantitative anisotropy (QA) and all types of childhood trauma in each depressed subgroup.</div></div><div><h3>Results</h3><div>Our study found that AD and non-AD patients had differential axonal loss primarily involving the bilateral superior longitudinal fasciculus, arcuate fasciculus, inferior longitudinal fasciculus, parietal aslant tract, and corpus callosum. Furthermore, AD patients showed significantly negative associations between QA values, childhood trauma total scores, and threat-related adversity, while significantly positive associations were observed in non-AD patients. However, similar phenomena were not observed for deprivation-related adversities.</div></div><div><h3>Discussion</h3><div>Our findings indicate differential spatial patterns of axonal alterations associated with threat-related adversity in atypical depression and non-atypical depression. Efforts to attenuate the consequences of childhood maltreatment for MDD should consider the associations between specific patterns of adversity and specific clinical manifestations.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"46 ","pages":"Article 103786"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143833359","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}

{"title":"Structural brain network in relation to language in school-aged extremely preterm children: A diffusion tensor imaging study","authors":"M. Boumeester ,&nbsp;E. Blom ,&nbsp;T. Boerma ,&nbsp;F. Lammertink ,&nbsp;M.P. van den Heuvel ,&nbsp;J. Dudink ,&nbsp;M.J.N.L. Benders ,&nbsp;E. Roze","doi":"10.1016/j.nicl.2025.103782","DOIUrl":"10.1016/j.nicl.2025.103782","url":null,"abstract":"<div><div>Between 22 and 45 % of children born preterm experience difficulties with expressive and receptive language when they reach school age. Little is currently known about the neural mechanisms behind their linguistic performance. This study investigates the brain areas and white matter connections that form the structural language network in extremely preterm-born children who have reached school age. Structural brain connectivity was quantified using diffusion-weighted imaging (DWI) and tractography in <em>n</em> = 58 (62 % female) extremely preterm-born children aged 8–12 years. Language outcomes were assessed using the CELF-4-NL Recalling Sentences subtest. Language scores were below average in <em>n</em> = 13 (22 %) children. Language outcomes related significantly to a subnetwork of 16 brain regions (<em>p</em> = 0.012). The network comprised brain regions from the left hemisphere including the pars orbitalis, middle and superior frontal gyrus, frontal pole, pre- and postcentral gyrus, superior temporal gyrus, insula, caudate nucleus, thalamus, and putamen. In the right hemisphere, the anterior cingulate was part of the network. These findings suggest that extremely preterm children rely mostly on their left hemisphere during language processing, which is similar to typically developing children. However, they seem to use compensatory neural pathways that include brain areas right next to the areas typically involved in language processing. These areas include the pars orbitalis (adjacent to Broca’s area) and the putamen and caudate nucleus (adjacent to the limbic system). It is important to note that language difficulties were not necessarily related to brain injury around birth.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"46 ","pages":"Article 103782"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860528","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}

{"title":"Diminished reward circuit response underlies pain avoidance learning deficits in problem drinkers","authors":"Thang M. Le ,&nbsp;Takeyuki Oba ,&nbsp;Chiang-Shan R. Li","doi":"10.1016/j.nicl.2025.103762","DOIUrl":"10.1016/j.nicl.2025.103762","url":null,"abstract":"<div><div>Individuals engaging in problem drinking show impaired proactive pain avoidance. As successful pain avoidance is intrinsically rewarding, this impairment suggests reward deficiency, as hypothesized for those with alcohol and substance misuse. Nevertheless, how reward circuit dysfunctions impact avoidance learning and contribute to drinking behavior remains poorly understood. Here, we combined functional imaging and a probabilistic learning go/nogo task to examine the neural processes underlying proactive pain avoidance learning in 103 adult drinkers. We hypothesized that greater drinking severity would be associated with poorer avoidance learning and that the deficits would be accompanied by weakened activity and connectivity of the reward circuit. Our behavioral findings indeed showed a negative relationship between drinking severity and learning from successful pain avoidance. We identified hypoactivation of the posterior cingulate cortex (PCC), a brain region important in avoidance, as the neural correlate of lower learning rate in association with problem drinking. The reward circuit, including the medial orbitofrontal cortex, ventral tegmental area, and substantia nigra, also exhibited diminished activation and connectivity with the PCC with greater drinking severity and learning deficits. Finally, path modeling suggested a pathway in which problem drinking disengaged the reward circuit. The weakened circuit subsequently induced PCC hypoactivation, resulting in poorer pain avoidance learning. As the learning dysfunction worsened alcohol use, the pathway represents a self-perpetuating cycle of drinking and distress. Together, these findings substantiate a role of reward deficiency in problem drinkers’ compromised proactive avoidance, thus identifying a potential target for intervention aimed at mitigating harmful alcohol use.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"45 ","pages":"Article 103762"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479824","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}

{"title":"Abnormal structural covariance network in major depressive disorder: Evidence from the REST-meta-MDD project","authors":"Changmin Chen ,&nbsp;Yuhan Liu ,&nbsp;Yu Sun ,&nbsp;Wenhao Jiang ,&nbsp;Yonggui Yuan ,&nbsp;Zhao Qing ,&nbsp;DIRECT Consortium","doi":"10.1016/j.nicl.2025.103794","DOIUrl":"10.1016/j.nicl.2025.103794","url":null,"abstract":"<div><h3>Background</h3><div>Major depressive disorder (MDD) is a common mental illness associated with brain morphological abnormalities. Although extensive studies have examined gray matter volume (GMV) changes in MDD, inconsistencies persist in reported findings. In the current study, we employed source-based morphometry (SBM) and structural covariance network (SCN) analyses to a large multi-center sample from the REST-meta-MDD database, aiming to characterize robust results of structural abnormalities in MDD.</div></div><div><h3>Methods</h3><div>We analyzed 798 MDD patients and 974 healthy controls (HCs) from the REST-meta-MDD consortium. Voxel-based morphometry was applied to generate GMV maps. SBM was used to adaptively parcellate brain into different components, and SCN was constructed based on SBM components. Volume scores in each component and SCNs between the components were both compared between MDD and HC groups, as well as between first-episode drug-naive (FEDN) and recurrent MDD subgroups.</div></div><div><h3>Results</h3><div>SBM identified 20 stable components. Three components encompassing the middle temporal gyrus, middle orbitofrontal gyrus and superior frontal gyrus exhibited volumetric differences between the MDD and HC groups. Volume differences were observed in the cingulate cortex and medial frontal gyrus between the FEDN and recurrent groups. SCN analysis revealed 9 aberrant pairs in MDD vs. HCs, and 7 pairs in FEDN vs. recurrent groups. All aberrant component pairs in the SCN implicated the prefrontal cortex.</div></div><div><h3>Conclusions</h3><div>These findings demonstrated brain structural deficits in MDD, and highlighted the prefrontal cortex as a central hub of SCN alterations. Our findings advance the understanding of MDD’s neural mechanisms and suggest directions for diagnostic research.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"46 ","pages":"Article 103794"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907042","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}

{"title":"Neural processing of social reciprocity in autism","authors":"Afton M. Bierlich ,&nbsp;Irene Sophia Plank ,&nbsp;Nanja T. Scheel ,&nbsp;Daniel Keeser ,&nbsp;Christine M. Falter-Wagner","doi":"10.1016/j.nicl.2025.103793","DOIUrl":"10.1016/j.nicl.2025.103793","url":null,"abstract":"<div><div>Social reciprocity and interpersonal synchrony implicitly mediate social interactions to facilitate natural exchanges. These processes are altered in autism, but it is unclear how such alterations manifest at the neural level during social interaction processing. Using task-based fMRI, we investigated the neural correlates of interpersonal synchrony during basic reciprocal interactions in a preregistered study. Participants communicated with a virtual partner by sending visual signals. Analyses showed comparable activation patterns and experienced synchrony ratings between autistic and non-autistic participants, as well as between interactions with virtual partners who had high or low synchronous responses. An exploratory whole brain analysis for the effect of task revealed significant activation of the inferior frontal gyrus, insular cortex, and anterior inferior parietal lobe; areas associated with cognitive control, rhythmic temporal coordination, and action observation. This activation was independent of the virtual partner’s response synchrony and was similar for autistic and non-autistic participants. These results provide an initial look into the neural basis of processing social reciprocity in autism, particularly when individuals are part of an interaction, and hint that the neural processing of social reciprocity may be spared in autism when their partners’ behavior is predictable.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"46 ","pages":"Article 103793"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143891924","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}

{"title":"Medulla oblongata dominated synaptic density network degeneration in amyotrophic lateral sclerosis","authors":"Ting Zou ,&nbsp;Manliu Hou ,&nbsp;Honghao Han ,&nbsp;Xuyang Wang ,&nbsp;Huafu Chen ,&nbsp;Yongxiang Tang ,&nbsp;Rong Li ,&nbsp;Shuo Hu","doi":"10.1016/j.nicl.2025.103814","DOIUrl":"10.1016/j.nicl.2025.103814","url":null,"abstract":"<div><h3>Background</h3><div>Amyotrophic lateral sclerosis (ALS) is a brain network disorder closely associated with synaptic loss in the upper and lower motor neurons. However, the <em>in vivo</em> synaptic network changes and their progressive processes remain unclear. Here, we aim to investigate the synaptic density network connectivity and the likely sequences of synaptic loss in patients with ALS.</div></div><div><h3>Methods</h3><div>We examined data from 21 patients diagnosed with ALS and 25 sex- and age-matched healthy controls (HCs) who underwent PET imaging with the SV2A radioligand [¹⁸F]SynVesT-1. The individual synaptic density similarity network was constructed for each patient by calculating the similarity between interregional synaptic density distributions. The synaptic network connectivity changes were investigated, followed by an examination of the local synaptic density in regions that showed significant network alterations. Finally, we constructed the voxel-wise and ROI-wise causal synaptic covariance network (cSCN) by applying Granger causality analysis. This allowed us to identify the sequence of synaptic loss in these brain regions.</div></div><div><h3>Results</h3><div>We observed an overall decrease in synaptic density network connectivity in ALS patients compared to controls, with the highest nodal degree in the right medulla oblongata. Specifically, the reduced connections were dominantly between the medulla oblongata and the striatum, frontal lobe, occipital lobe, as well as between the striatum and the frontal lobe, occipital lobe. Furthermore, patients with ALS displayed significantly synaptic loss in those brain regions. The cSCN analyses showed that as the disease progresses, the cortical synaptic loss sequences of ALS extend from the medulla oblongata to the regions including the striatum, frontal lobe, occipital lobe, and parietal lobe.</div></div><div><h3>Conclusions</h3><div>These findings suggest that synaptic density network degeneration in ALS may follow a bottom-up transmission pattern, primarily involving in the medulla oblongata-striatum-neocortex network, which have the potential to capture new network-based targets for clinical therapy in the progression of ALS.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"47 ","pages":"Article 103814"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330066","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}

{"title":"Neuroimaging correlates of domain-specific cognitive deficits in amyotrophic lateral sclerosis","authors":"Harold H.G. Tan ,&nbsp;Abram D. Nitert ,&nbsp;Kevin van Veenhuijzen ,&nbsp;Stefan Dukic ,&nbsp;Martine J.E. van Zandvoort ,&nbsp;Jeroen Hendrikse ,&nbsp;Michael A. van Es ,&nbsp;Jan H. Veldink ,&nbsp;Henk-Jan Westeneng ,&nbsp;Leonard H. van den Berg","doi":"10.1016/j.nicl.2025.103749","DOIUrl":"10.1016/j.nicl.2025.103749","url":null,"abstract":"<div><h3>Background</h3><div>Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with frequent extra-motor involvement. In the present study, we investigated whether specific cognitive and behavioral deficits in ALS correlate with distinct extra-motor neurodegeneration patterns on brain MRI.</div></div><div><h3>Methods</h3><div>We performed multimodal brain MRI and Edinburgh cognitive and behavioral ALS screen (ECAS) in 293 patients and 237 controls. Follow-up data were acquired from 171 patients with a median duration of 7.9 months. Domain-level cognitive scores from the ECAS were compared with grey and white matter MRI parameters. Interaction analyses between patients and controls were performed to explore whether correlates were specific to ALS, rather than related to normal aging. Follow-up data were used to assess changes of domain-associated brain structures over time.</div></div><div><h3>Results</h3><div>Language impairment was significantly associated with (left predominant) frontal, temporal, parietal and subcortical grey matter neurodegeneration. Letter fluency with widespread cortical and subcortical grey matter involvement. Memory dysfunction with hippocampal and medial-temporal atrophy. Executive impairment was exclusively correlated with widespread white matter impairment. Visuospatial scores did not correlate with MRI parameters. Interaction analyses between patients and controls showed that most ECAS-MRI correlations were stronger in ALS than in controls (75.7% significant in grey matter, 52.7% in white matter). Longitudinal analyses showed that all grey matter structures associated with cognitive domains worsened over time while, for this study population, ECAS domain scores did not decline significantly.</div></div><div><h3>Conclusions</h3><div>MRI can capture the heterogeneity of cognitive and behavioral involvement in ALS and provides a useful longitudinal biomarker for progression of extra-motor neurodegeneration.</div></div>","PeriodicalId":54359,"journal":{"name":"Neuroimage-Clinical","volume":"45 ","pages":"Article 103749"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143395222","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}