TY - JOUR
T1 - Disordered network structure and function in dystonia
T2 - pathological connectivity vs. adaptive responses
AU - Vo, An
AU - Nguyen, Nha
AU - Fujita, Koji
AU - Schindlbeck, Katharina A.
AU - Rommal, Andrea
AU - Bressman, Susan B.
AU - Niethammer, Martin
AU - Eidelberg, David
N1 - Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press. All rights reserved.
PY - 2023/6/1
Y1 - 2023/6/1
N2 - Primary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is readily implemented on conventional MRI scanners, we identified similar disease topographies in hereditary dystonia associated with the DYT1 or DYT6 mutations and in sporadic patients lacking these mutations. Both networks were characterized by contributions from the basal ganglia, cerebellum, thalamus, sensorimotor areas, as well as cortical association regions. Expression levels for the two networks were elevated in hereditary and sporadic dystonia, and in non-manifesting carriers of dystonia mutations. Nonetheless, the distribution of abnormal functional connections differed across groups, as did metrics of network organization and efficiency in key modules. Despite these differences, network expression correlated with dystonia motor ratings, significantly improving the accuracy of predictions based on thalamocortical tract integrity obtained with diffusion tensor MRI (DTI). Thus, in addition to providing unique information regarding the anatomy of abnormal brain circuits, rs-fMRI functional networks may provide a widely accessible method to help in the objective evaluation of new treatments for this disorder.
AB - Primary dystonia is thought to emerge through abnormal functional relationships between basal ganglia and cerebellar motor circuits. These interactions may differ across disease subtypes and provide a novel biomarker for diagnosis and treatment. Using a network mapping algorithm based on resting-state functional MRI (rs-fMRI), a method that is readily implemented on conventional MRI scanners, we identified similar disease topographies in hereditary dystonia associated with the DYT1 or DYT6 mutations and in sporadic patients lacking these mutations. Both networks were characterized by contributions from the basal ganglia, cerebellum, thalamus, sensorimotor areas, as well as cortical association regions. Expression levels for the two networks were elevated in hereditary and sporadic dystonia, and in non-manifesting carriers of dystonia mutations. Nonetheless, the distribution of abnormal functional connections differed across groups, as did metrics of network organization and efficiency in key modules. Despite these differences, network expression correlated with dystonia motor ratings, significantly improving the accuracy of predictions based on thalamocortical tract integrity obtained with diffusion tensor MRI (DTI). Thus, in addition to providing unique information regarding the anatomy of abnormal brain circuits, rs-fMRI functional networks may provide a widely accessible method to help in the objective evaluation of new treatments for this disorder.
KW - connectivity patterns
KW - graph metrics
KW - network development
KW - primary dystonia
KW - resting-state fMRI
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U2 - 10.1093/cercor/bhad012
DO - 10.1093/cercor/bhad012
M3 - Article
C2 - 36749014
AN - SCOPUS:85160965696
SN - 1047-3211
VL - 33
SP - 6943
EP - 6958
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 11
ER -