{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T22:15:56Z","timestamp":1791065756702,"version":"4.1.0"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T00:00:00Z","timestamp":1714953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["202106380078"],"award-info":[{"award-number":["202106380078"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Dutch Brain Foundation","award":["H04-12; F2009(1)-16"],"award-info":[{"award-number":["H04-12; F2009(1)-16"]}]},{"name":"VIDI innovational"},{"DOI":"10.13039\/501100001826","name":"The Netherlands Organization for Health Research and Development","doi-asserted-by":"publisher","award":["016.126.351"],"award-info":[{"award-number":["016.126.351"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Netherlands Cardiovascular Research Initiative"},{"DOI":"10.13039\/501100002996","name":"The Dutch Heart Foundation","doi-asserted-by":"publisher","award":["CVON 2018-28"],"award-info":[{"award-number":["CVON 2018-28"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002996","name":"The Dutch Heart Foundation","doi-asserted-by":"publisher","award":["2012-06"],"award-info":[{"award-number":["2012-06"]}],"id":[{"id":"10.13039\/501100002996","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Heart Brain Connection","award":["2016T044"],"award-info":[{"award-number":["2016T044"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,11,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Cerebral small vessel disease (SVD) is known to contribute to cognitive impairment, apathy and gait dysfunction. Although associations between cognitive impairment and either apathy or gait dysfunction have been shown in SVD, the inter-relations among these three clinical features and their potential common neural basis remain unexplored. The dopaminergic meso-cortical and meso-limbic pathways have been known as the important brain circuits for both cognitive control, emotion regulation and motor function. Here, we investigated the potential inter-relations between cognitive impairment, apathy and gait dysfunction, with a specific focus on determining whether these clinical features are associated with damage to the meso-cortical and meso-limbic pathways in SVD.<\/jats:p>\n               <jats:p>In this cross-sectional study, we included 213 participants with SVD for whom MRI and comprehensive neurobehavioural assessments were performed. These assessments comprised six clinical measures: processing speed, executive function, memory, apathy (based on the Apathy Evaluation Scale) and gait function (based on the time and steps in the Timed Up and Go Test). We reconstructed five tracts connecting the ventral tegmental area (VTA) and dorsolateral prefrontal cortex (PFC), ventral lateral PFC, medial orbitofrontal cortex, anterior cingulate cortex (ACC) and nucleus accumbens within meso-cortical and meso-limbic pathways using diffusion weighted imaging. The damage along the five tracts was quantified using the free water (FW) and FW-corrected mean diffusivity indices. Furthermore, we explored the inter-correlations among the six clinical measures and identified their common components using principal component analysis (PCA).<\/jats:p>\n               <jats:p>Linear regression analyses showed that higher FW values of tracts within meso-cortical pathways were related to these clinical measures in cognition, apathy, and gait (all P-corrected values &amp;lt; 0.05). The PCA showed strong inter-associations among these clinical measures and identified a common component wherein all six clinical measures loaded on. Higher FW values of tracts within meso-cortical pathways were related to the PCA-derived common component (all P-corrected values &amp;lt; 0.05). Moreover, FW values of the VTA-ACC tract showed the strongest contribution to the PCA-derived common component over all other neuroimaging features.<\/jats:p>\n               <jats:p>In conclusion, our study showed that the three clinical features (cognitive impairment, apathy, and gait dysfunction) of SVD are strongly inter-related and that the damage in meso-cortical pathway could be the common neural basis underlying the three features in SVD. These findings advance our understanding of the mechanisms behind these clinical features of SVD and have the potential to inform novel management and intervention strategies for SVD.<\/jats:p>","DOI":"10.1093\/brain\/awae145","type":"journal-article","created":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T18:11:55Z","timestamp":1715019115000},"page":"3804-3816","source":"Crossref","is-referenced-by-count":26,"title":["Meso-cortical pathway damage in cognition, apathy and gait in cerebral small vessel disease"],"prefix":"10.1093","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2125-9092","authenticated-orcid":false,"given":"Hao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurology, Radboud Institute for Medical research and Innovation and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , 6525 GA Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mina A","family":"Jacob","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboud Institute for Medical research and Innovation and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , 6525 GA Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengfei","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboud Institute for Medical research and Innovation and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , 6525 GA Nijmegen ,","place":["The Netherlands"]},{"name":"Department of Neurology, Guangdong Neuroscience Institute, Guangdong Provincial People\u2019s Hospital, Guangdong Academy of Medical Sciences, Southern Medical University , 510000 Guangzhou ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roy P C","family":"Kessels","sequence":"additional","affiliation":[{"name":"Radboud University, Donders Institute for Brain, Cognition and Behaviour, Centre for Cognition, Radboud University , 6525 GD Nijmegen ,","place":["The Netherlands"]},{"name":"Department of Medical Psychology and Radboudumc Alzheimer Center, Radboud University Medical Center , 6525 GA Nijmegen ,","place":["The Netherlands"]},{"name":"Centre of Excellence for Korsakoff and Alcohol-Related Cognitive Disorders, Vincent van Gogh Institute for Psychiatry , 5804 AV Venray ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G","family":"Norris","sequence":"additional","affiliation":[{"name":"Donders Institute for Brain, Cognition and Behaviour, Centre for Cognitive Neuroimaging, Radboud University , 6525 GD Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2302-3136","authenticated-orcid":false,"given":"Marco","family":"Duering","sequence":"additional","affiliation":[{"name":"Medical Image Analysis Center (MIAC AG) and Department of Biomedical Engineering, University of Basel , 4051 Basel ,","place":["Switzerland"]},{"name":"Institute for Stroke and Dementia Research (ISD), LMU University Hospital , 81377 LMU Munich ,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank-Erik","family":"de Leeuw","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboud Institute for Medical research and Innovation and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , 6525 GA Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil M","family":"Tuladhar","sequence":"additional","affiliation":[{"name":"Department of Neurology, Radboud Institute for Medical research and Innovation and Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center , 6525 GA Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,5,6]]},"reference":[{"key":"2024110323580197500_awae145-B1","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/S1474-4422(23)00131-X","article-title":"Neuroimaging standards for research into small vessel disease-advances since 2013","volume":"22","author":"Duering","year":"2023","journal-title":"Lancet Neurol"},{"key":"2024110323580197500_awae145-B2","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/S1474-4422(19)30079-1","article-title":"Small vessel disease: Mechanisms and clinical 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