title: Neural correlates underlying micrographia in Parkinson's disease.
abstract: Micrographia is a common symptom in Parkinson's disease, which manifests as either a consistent or progressive reduction in the size of handwriting or both. Neural correlates underlying micrographia remain unclear. We used functional magnetic resonance imaging to investigate micrographia-related neural activity and connectivity modulations. In addition, the effect of attention and dopaminergic administration on micrographia was examined. We found that consistent micrographia was associated with decreased activity and connectivity in the basal ganglia motor circuit; while progressive micrographia was related to the dysfunction of basal ganglia motor circuit together with disconnections between the rostral supplementary motor area, rostral cingulate motor area and cerebellum. Attention significantly improved both consistent and progressive micrographia, accompanied by recruitment of anterior putamen and dorsolateral prefrontal cortex. Levodopa improved consistent micrographia accompanied by increased activity and connectivity in the basal ganglia motor circuit, but had no effect on progressive micrographia. Our findings suggest that consistent micrographia is related to dysfunction of the basal ganglia motor circuit; while dysfunction of the basal ganglia motor circuit and disconnection between the rostral supplementary motor area, rostral cingulate motor area and cerebellum likely contributes to progressive micrographia. Attention improves both types of micrographia by recruiting additional brain networks. Levodopa improves consistent micrographia by restoring the function of the basal ganglia motor circuit, but does not improve progressive micrographia, probably because of failure to repair the disconnected networks.
authors.affiliation: 1 Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China 2 Beijing Key Laboratory on Parkinson's Disease, Parkinson Disease Centre of Beijing Institute for Brain Disorders, Beijing, China wutao69@gmail.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: 1 Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China 2 Beijing Key Laboratory on Parkinson's Disease, Parkinson Disease Centre of Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Jiarong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: 3 Human Motor Control Section, Medical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hallett
authors.affiliation: 2 Beijing Key Laboratory on Parkinson's Disease, Parkinson Disease Centre of Beijing Institute for Brain Disorders, Beijing, China 4 China National Clinical Research Centre for Neurological Diseases, Beijing, China 5 Department of Neurology, Centre for Neurodegenerative Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.affiliation: 1 Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China 2 Beijing Key Laboratory on Parkinson's Disease, Parkinson Disease Centre of Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Hou
authors.affiliation: 1 Department of Neurobiology, Key Laboratory on Neurodegenerative Disorders of Ministry of Education, Beijing Institute of Geriatrics, Xuanwu Hospital, Capital Medical University, Beijing, China 2 Beijing Key Laboratory on Parkinson's Disease, Parkinson Disease Centre of Beijing Institute for Brain Disorders, Beijing, China.
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
mesh_terms: D000368:Aged; D001288:Attention / Q000502:physiology; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology*; D001545:Benserazide / Q000494:pharmacology; D001931:Brain Mapping; D016022:Case-Control Studies; D002531:Cerebellum / Q000503:physiopathology*; D004338:Drug Combinations; D005260:Female; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006236:Handwriting; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000503:physiopathology*; D009434:Neural Pathways / Q000473:pathology* / Q000503:physiopathology; D010300:Parkinson Disease / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D004338:Drug Combinations; C005177:benserazide, levodopa drug combination; D007980:Levodopa; D001545:Benserazide
keywords: Parkinson’s disease; attention; dopaminergic intervention; micrographia; sequence effect