Elsevier

Neuroscience

Volume 177, 17 March 2011, Pages 230-239
Neuroscience

Neurodegeneration, Neuroprotection, and Disease-Oriented Neuroscience
Research Paper
Differential involvement of striato- and cerebello-thalamo-cortical pathways in tremor- and akinetic/rigid-predominant Parkinson's disease

https://doi.org/10.1016/j.neuroscience.2010.12.060Get rights and content

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 (PDT) and eight akinetic-rigidity predominant (PDAR)] 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 (CHTC) and vermis-thalamo-cortical (CVTC)] circuits was calculated. Multivariate analysis of variance compared the activation patterns of these circuits between study groups. Compared to controls, both PDAR and PDT 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 PDT subjects, and in contralateral CTC pathways for PDAR subjects. Comparison of PDAR and PDT subjects revealed significant differences in ipsilateral STC (P=0.005) and CTC (P=0.043 for CHTC and P=0.003 for CVTC) 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.

Research highlights

▶PDAR and PDT subjects show more activity in STC and CTC circuits compared to controls. ▶PDT subjects show significant changes from controls in contralateral STC and CTC. ▶PDAR subjects only show significance in contralateral CTC compared to controls. ▶Comparing PDT and PDAR subjects shows significant differences in ipsilateral STC and CTC.

Section snippets

Subjects

Seventeen PD subjects (nine PDT and eight PDAR) were recruited for this study from a tertiary movement disorders clinic (see Table 1 for demographic information). Each PD subject was diagnosed by a movement disorders specialist (XH) based on previously published criteria (Gibb and Lees, 1988). Twelve PD subjects (six PDAR and six PDT) had right side predominant symptoms. Most subjects were early in their disease course (see Table 1), with a mean (±SD) disease duration for PDAR subjects of

Demographic data

Although PDT subjects appeared on average to be slightly older than control and PDAR subjects, there were no significant differences in age among the groups (Table 1). For PD subtypes, there were no significant differences in disease duration, total UPRDS, or Hoehn and Yahr scores. PDAR subjects had a higher LED compared to PDT subjects. As expected, the two subtypes showed significant differences in the tremor/AR ratio (Table 1).

PDAR versus control subjects

In all ROIs comprising the bilateral STC and CTC circuits, PDAR

Discussion

In doing the first fMRI study that has compared control, PDAR, and PDT subjects, we have shown that there is differential involvement of STC and CTC pathways for the two different PD clinical presentations (or subtypes). The results indicate first, that PDAR and PDT subjects both display overall increased recruitment of STC and CTC neurocircuitry compared to controls during this internally guided motor task. Second, the pattern of the recruitment of STC and CTC circuits was different for PDAR

Acknowledgments

We thank all those who participated in the study and support of the UNC MRI center. This work was supported in part by NIH grants AG21491 (XH), NS060722 (XH, MML, and GD), and the UNC GCRC (RR00046).

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    Present address: Biostatistics Center, Kurume University, Kurume 830-0011, Japan.

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