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| Hauptseite > Publikationsdatenbank > Local synchronicity in dopamine-rich caudate nucleus influences Huntington’s disease motor phenotype > print |
| Hauptseite > Publikationsdatenbank > Local synchronicity in dopamine-rich caudate nucleus influences Huntington’s disease motor phenotype > print |
| 001 | 1002271 | ||
| 005 | 20231027114355.0 | ||
| 024 | 7 | _ | |a 10.1093/brain/awad043 |2 doi |
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| 100 | 1 | _ | |a Kasper, Jan |0 P:(DE-Juel1)184653 |b 0 |u fzj |
| 245 | _ | _ | |a Local synchronicity in dopamine-rich caudate nucleus influences Huntington’s disease motor phenotype |
| 260 | _ | _ | |a Oxford |c 2023 |b Oxford Univ. Press |
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| 520 | _ | _ | |a Structural grey and white matter changes precede the manifestation of clinical signs of Huntington's disease by many years. Conversion to clinically manifest disease therefore likely reflects not merely atrophy but a more wide-spread breakdown of brain function. Here, we investigated the structure - function relationship close to and after the clinical onset testing for its co-localization with specific neurotransmitter/receptor systems and important regional brain hubs, in particular caudate nucleus and putamen that are central to maintain normal motor behavior. In two independent cohorts of patients with premanifest Huntington's disease close to onset and very early manifest Huntington's disease (total n = 84; n = 88 matched controls) we used structural and resting state functional MRI. We show that measures of functional activity and local synchronicity within cortical and subcortical regions remain normal in the premanifest Huntington's disease phase despite clear evidence of brain atrophy. In manifest Huntington's disease, homeostasis of synchronicity was disrupted in subcortical hub regions such as caudate nucleus and putamen, but also in cortical hub regions, for instance the parietal lobe. Cross-modal spatial correlations of functional MRI data with receptor/neurotransmitter distribution maps showed that Huntington's disease specific alterations co-localize with dopamine receptors D1, D2, as well as dopamine and serotonin transporters. Caudate nucleus synchronicity significantly improved models predicting the severity of the motor phenotype or predicting the classification into premanifest Huntington's disease or motor manifest Huntington's disease. Our data suggest that the functional integrity of the dopamine receptor rich caudate nucleus is key to maintain network function. The loss of caudate nucleus functional integrity affects network function to a degree that causes a clinical phenotype. These insights into what happens in Huntington's disease could serve as a model for what might be a more general relationship between brain structure and function in neurodegenerative diseases in which other brain regions are vulnerable. |
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| 773 | _ | _ | |a 10.1093/brain/awad043 |g p. awad043 |0 PERI:(DE-600)1474117-9 |n 8 |p 3319–3330 |t Brain |v 146 |y 2023 |x 0006-8950 |
| 856 | 4 | _ | |u https://juser.fz-juelich.de/record/1002271/files/awad043.pdf |
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