Probabilistic Tractography-Based Tremor Network Connectivity in Tremor Dominant Parkinson's Disease and Essential Tremor plus

Background: The basal ganglia-thalamocortical (BGTC) and cerebello-thalamocortical (CTC) networks are implicated in tremor genesis; however, exact contributions across disorders have not been studied.Objective: Evaluate the structural connectivity of BGTC and CTC in tremor-dominant Parkinson's disease (TDPD) and essential tremor plus (ETP) with the aid of probabilistic tractography and graph theory analysis.Methods: Structural connectomes of the BGTC and CTC were generated by probabilistic tractography for TDPD (n = 25), ETP (ET with rest tremor, n = 25), and healthy control (HC, n = 22). The Brain Connectivity Toolbox was used for computing standard topological graph measures of segregation, integration, and centrality. Tremor severity was ascertained using the Fahn-Tolosa-Marin tremor rating scale (FTMRS).Results: There was no difference in total FTMRS scores. Compared with HC, TDPD had a lower global efficiency and characteristic path length. Abnormality in segregation, integration, and centrality of bilateral putamen, globus pallidus externa (GPe), and GP interna (GPi), with reduction of centrality of right caudate and cerebellar lobule 8, was observed. ETP showed reduction in segregation and integration of right GPe and GPi, ventrolateral posterior nucleus, and centrality of right putamen, compared with HC. Differences between TDPD and ETP were a reduction of strength of the right putamen, and lower clustering coefficient, local efficiency, and strength of the left GPi in TDPD.Conclusions: Contrary to expectations, TDPD and ETP may not be significantly different with regard to tremor pathogenesis, with definite overlaps. There may be fundamental similarities in network disruption across different tremor disorders with the same tremor activation patterns, along with disease-specific changes. Impact Statement Tremor-dominant Parkinson's disease and essential tremor plus have definite similarities in pathogenesis, and this observation may explain the similar response to thalamic lesioning or deep brain stimulation. Furthermore, different disorders with common tremor phenotypes may have similar underlying abnormalities in the tremor network. This observation is highly relevant from a therapeutic perspective especially for functional surgeries such as deep brain stimulation or lesioning, as it may explain the basis for therapeutic response across different tremor disorders.