Differential involvement of striato- and cerebello-thalamo-cortical pathways in tremor- and akinetic/rigid-predominant Parkinson's disease

Mechelle Lewis, Guangwei Du, S. Sen, A. Kawaguchi, Y. Truong, S. Lee, Richard Mailman, Xuemei Huang

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Abstract

Parkinson's disease (PD) presents clinically with varying degrees of resting tremor, rigidity, and bradykinesia. For decades, striatal-thalamo-cortical (STC) dysfunction has been implied in bradykinesia and rigidity, but does not explain resting tremor in PD. To understand the roles of cerebello-thalamo-cortical (CTC) and STC circuits in the pathophysiology of the heterogeneous clinical presentation of PD, we collected functional magnetic resonance imaging (fMRI) data from 17 right-handed PD patients [nine tremor predominant (PD T) and eight akinetic-rigidity predominant (PD AR)] and 14 right-handed controls while they performed internally-guided (IG) sequential finger tapping tasks. The percentage of voxels activated in regions constituting the STC and CTC [divided as cerebellar hemisphere-thalamo-cortical (C HTC) and vermis-thalamo-cortical (C VTC)] circuits was calculated. Multivariate analysis of variance compared the activation patterns of these circuits between study groups. Compared to controls, both PD AR and PD T subjects displayed an overall increase in the percentage of voxels activated in both STC and CTC circuits. These increases reached statistical significance in contralateral STC and CTC circuits for PD T subjects, and in contralateral CTC pathways for PD AR subjects. Comparison of PD AR and PD T subjects revealed significant differences in ipsilateral STC (P=0.005) and CTC (P=0.043 for C HTC and P=0.003 for C VTC) circuits. These data support the differential involvement of STC and CTC circuits in PD subtypes, and help explain the heterogeneous presentation of PD symptoms. These findings underscore the importance of integrating CTC circuits in understanding PD and other disorders of the basal ganglia.

Original languageEnglish (US)
Pages (from-to)230-239
Number of pages10
JournalNeuroscience
Volume177
DOIs
StatePublished - Mar 17 2011

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Tremor
Parkinson Disease
Corpus Striatum
Hypokinesia
Basal Ganglia Diseases
Fingers
Analysis of Variance
Multivariate Analysis

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

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title = "Differential involvement of striato- and cerebello-thalamo-cortical pathways in tremor- and akinetic/rigid-predominant Parkinson's disease",
abstract = "Parkinson's disease (PD) presents clinically with varying degrees of resting tremor, rigidity, and bradykinesia. For decades, striatal-thalamo-cortical (STC) dysfunction has been implied in bradykinesia and rigidity, but does not explain resting tremor in PD. To understand the roles of cerebello-thalamo-cortical (CTC) and STC circuits in the pathophysiology of the heterogeneous clinical presentation of PD, we collected functional magnetic resonance imaging (fMRI) data from 17 right-handed PD patients [nine tremor predominant (PD T) and eight akinetic-rigidity predominant (PD AR)] and 14 right-handed controls while they performed internally-guided (IG) sequential finger tapping tasks. The percentage of voxels activated in regions constituting the STC and CTC [divided as cerebellar hemisphere-thalamo-cortical (C HTC) and vermis-thalamo-cortical (C VTC)] circuits was calculated. Multivariate analysis of variance compared the activation patterns of these circuits between study groups. Compared to controls, both PD AR and PD T subjects displayed an overall increase in the percentage of voxels activated in both STC and CTC circuits. These increases reached statistical significance in contralateral STC and CTC circuits for PD T subjects, and in contralateral CTC pathways for PD AR subjects. Comparison of PD AR and PD T subjects revealed significant differences in ipsilateral STC (P=0.005) and CTC (P=0.043 for C HTC and P=0.003 for C VTC) circuits. These data support the differential involvement of STC and CTC circuits in PD subtypes, and help explain the heterogeneous presentation of PD symptoms. These findings underscore the importance of integrating CTC circuits in understanding PD and other disorders of the basal ganglia.",
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T1 - Differential involvement of striato- and cerebello-thalamo-cortical pathways in tremor- and akinetic/rigid-predominant Parkinson's disease

AU - Lewis, Mechelle

AU - Du, Guangwei

AU - Sen, S.

AU - Kawaguchi, A.

AU - Truong, Y.

AU - Lee, S.

AU - Mailman, Richard

AU - Huang, Xuemei

PY - 2011/3/17

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N2 - Parkinson's disease (PD) presents clinically with varying degrees of resting tremor, rigidity, and bradykinesia. For decades, striatal-thalamo-cortical (STC) dysfunction has been implied in bradykinesia and rigidity, but does not explain resting tremor in PD. To understand the roles of cerebello-thalamo-cortical (CTC) and STC circuits in the pathophysiology of the heterogeneous clinical presentation of PD, we collected functional magnetic resonance imaging (fMRI) data from 17 right-handed PD patients [nine tremor predominant (PD T) and eight akinetic-rigidity predominant (PD AR)] and 14 right-handed controls while they performed internally-guided (IG) sequential finger tapping tasks. The percentage of voxels activated in regions constituting the STC and CTC [divided as cerebellar hemisphere-thalamo-cortical (C HTC) and vermis-thalamo-cortical (C VTC)] circuits was calculated. Multivariate analysis of variance compared the activation patterns of these circuits between study groups. Compared to controls, both PD AR and PD T subjects displayed an overall increase in the percentage of voxels activated in both STC and CTC circuits. These increases reached statistical significance in contralateral STC and CTC circuits for PD T subjects, and in contralateral CTC pathways for PD AR subjects. Comparison of PD AR and PD T subjects revealed significant differences in ipsilateral STC (P=0.005) and CTC (P=0.043 for C HTC and P=0.003 for C VTC) circuits. These data support the differential involvement of STC and CTC circuits in PD subtypes, and help explain the heterogeneous presentation of PD symptoms. These findings underscore the importance of integrating CTC circuits in understanding PD and other disorders of the basal ganglia.

AB - Parkinson's disease (PD) presents clinically with varying degrees of resting tremor, rigidity, and bradykinesia. For decades, striatal-thalamo-cortical (STC) dysfunction has been implied in bradykinesia and rigidity, but does not explain resting tremor in PD. To understand the roles of cerebello-thalamo-cortical (CTC) and STC circuits in the pathophysiology of the heterogeneous clinical presentation of PD, we collected functional magnetic resonance imaging (fMRI) data from 17 right-handed PD patients [nine tremor predominant (PD T) and eight akinetic-rigidity predominant (PD AR)] and 14 right-handed controls while they performed internally-guided (IG) sequential finger tapping tasks. The percentage of voxels activated in regions constituting the STC and CTC [divided as cerebellar hemisphere-thalamo-cortical (C HTC) and vermis-thalamo-cortical (C VTC)] circuits was calculated. Multivariate analysis of variance compared the activation patterns of these circuits between study groups. Compared to controls, both PD AR and PD T subjects displayed an overall increase in the percentage of voxels activated in both STC and CTC circuits. These increases reached statistical significance in contralateral STC and CTC circuits for PD T subjects, and in contralateral CTC pathways for PD AR subjects. Comparison of PD AR and PD T subjects revealed significant differences in ipsilateral STC (P=0.005) and CTC (P=0.043 for C HTC and P=0.003 for C VTC) circuits. These data support the differential involvement of STC and CTC circuits in PD subtypes, and help explain the heterogeneous presentation of PD symptoms. These findings underscore the importance of integrating CTC circuits in understanding PD and other disorders of the basal ganglia.

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