Increased thalamic centrality and putamen–thalamic connectivity in patients with parkinsonian resting tremor

INTRODUCTION: Evidence has indicated a strong association between hyperactivity in the cerebello‐thalamo‐motor cortical loop and resting tremor in Parkinson's disease (PD). Within this loop, the thalamus serves as a central hub based on its structural centrality in the generation of resting tremor. To study whether this thalamic abnormality leads to an alteration at the whole‐brain level, our study investigated the role of the thalamus in patients with parkinsonian resting tremor in a large‐scale brain network context. METHODS: Forty‐one patients with PD (22 with resting tremor, TP and 19 without resting tremor, NTP) and 45 healthy controls (HC) were included in this resting‐state functional MRI study. Graph theory‐based network analysis was performed to examine the centrality measures of bilateral thalami across the three groups. To further provide evidence to the central role of the thalamus in parkinsonian resting tremor, the seed‐based functional connectivity analysis was then used to quantify the functional interactions between the basal ganglia and the thalamus. RESULTS: Compared with the HC group, patients with the TP group exhibited increased degree centrality (p < .04), betweenness centrality (p < .01), and participation coefficient (p < .01) in the bilateral thalami. Two of these alterations (degree centrality and participation coefficient) were significantly correlated with tremor severity, especially in the left hemisphere (p < .02). The modular analysis showed that the TP group had more intermodular connections between the thalamus and the regions within the cerebello‐thalamo‐motor cortical loop. Furthermore, the data revealed significantly enhanced functional connectivity between the putamen and the thalamus in the TP group (p = .027 corrected for family‐wise error). CONCLUSIONS: These findings suggest increased thalamic centrality as a potential tremor‐specific imaging measure for PD, and provide evidence for the altered putamen–thalamic interaction in patients with resting tremor.