Structural connectivity differences in motor network between tremor-dominant and nontremor Parkinson's disease

Abstract

Motor phenotypes of Parkinson's disease (PD) are recognized to have different prognosis and therapeutic response, but the neural basis for this clinical heterogeneity remains largely unknown. The main aim of this study was to compare differences in structural connectivity metrics of the main motor network between tremor-dominant and nontremor PD phenotypes (TD-PD and NT-PD, respectively) using probabilistic tractography-based network analysis. A total of 63 PD patients (35 TD-PD patients and 28 NT-PD patients) and 30 healthy controls underwent a 3 T MRI. Next, probabilistic tractography-based network analysis was performed to assess structural connectivity in cerebello-thalamo-basal ganglia-cortical circuits, by measuring the connectivity indices of each tract and the efficiency of each node. Furthermore, dopamine transporter single-photon emission computed tomography (DAT-SPECT) with ¹²³ I-ioflupane was used to assess dopaminergic striatal depletion in all PD patients. Both PD phenotypes showed nodal abnormalities in the substantia nigra, in agreement with DAT-SPECT evaluation. In addition, NT-PD patients displayed connectivity alterations in nigro-pallidal and fronto-striatal pathways, compared with both controls and TD-PD patients, in which the same motor connections seemed to be relatively spared. Of note, in NT-PD group, rigidity-bradykinesia score correlated with fronto-striatal connectivity abnormalities. These findings demonstrate that structural connectivity alterations occur in the cortico-basal ganglia circuit of NT-PD patients, but not in TD-PD patients, suggesting that these anatomical differences may underlie different motor phenotypes of PD. Hum Brain Mapp 38:4716-4729, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: Parkinson's disease; dopamine transporter single-photon emission computed tomography; motor phenotypes of Parkinson's disease; nontremor Parkinson's disease; probabilistic tractography; structural network analysis; tremor-dominant Parkinson's disease.

Figure 1

MRI processing workflow. AAL, automated anatomical labeling; MRI, magnetic resonance imaging; FIRST, Bayesian segmentation of subcortical structures. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Group differences in MRI network metrics (i.e., connectivity index and weighted nodal efficiency). Spheres and lines represent brain nodes and edges, with red spheres and red lines indicating respectively the nodes and the edges showing significance between groups (top). Anatomical connectivity index and weighted nodal efficiency mean values for each brain edges and nodes, respectively (bottom). Regarding the MRI network metrics in the figure, we considered the more affected side for patients with Parkinson's disease, and the average of right and left side for control subjects. NT‐PD, patients with nontremor Parkinson's disease; TD‐PD, patients with tremor‐dominant Parkinson's disease; *P value <0.05 after false discovery rate correction. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

Correlation analysis. Correlation scatterplots of the clinical variables [disease duration (A–C), nontremor subscore (D–F), and tremor subscore (G–I)] with the functional and structural neuroimaging metrics of more affeceted side, in all PD patients (A–C, D, G), in NT‐PD patients (E, F), and in TD‐PD patients (H, I). UPDRS‐ME subscores in PD subgroups (panels E, F and panels H, I) are, respectively, the nontremor and tremor subscores of more severely affected limbs. ¹²³I‐ioflupane uptake ratios and MRI network metrics (i.e., anatomical connectivity indices and weighted nodal efficiency values) are reported on the x axis; clinical data are reported on the y axis; blue = patients with TD‐PD; green = patients with NT‐PD; r = Spearman's correlation coefficient; P = P value corrected according to false discovery rate. [Color figure can be viewed at http://wileyonlinelibrary.com]