2023 Junior Research award

Network-based statistics of the tremor network in tremor-dominant Parkinson’s disease and essential tremor plus syndrome

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Receiving the 2023 Junior Award at the 8th Asian and Oceanian Parkinson’s Disease and Movement Disorders Congress has been a definite highlight of my career so far. I am grateful for the recognition and motivated for the future. This work was a part of my PhD thesis, and I am indebted to the support I received from my PhD supervisors through this journey.

This work was conceptualised with the fundamental principle of attempting to unravel the mechanisms of tremorogenesis across tremor disorders. The dimmer switch theory is perhaps the most prolific concept of tremorogenesis in the recent past, and implicates the role of the basal ganglia-thalamocortical (BGTC) network, and the cerebello-thalamocortical (CTC) network for a parkinsonian tremor  [1,2].  Specifically, it suggests that the BGTC, particularly, the globus pallidus internus, triggers the rest tremor, while the CTC modulates the amplitude of tremor. Although this explains what probably happens in PD, the mechanisms for other disorders with similar combinations of tremor activation patterns is uncertain. Tremor-dominant Parkinson’s disease (TDPD) and essential tremor plus (ETP) syndrome are highly prevalent movement disorders wherein a tremor is the most significant symptom. A rest tremor and an action tremor are critical components in both disorders, albeit in varying severity and order of onset. Owing to the similarity in the type of tremor in TDPD and ETP, studying these two groups may yield information pertaining to the unique patterns of network disruption and aid in ascertaining the extent of overlap in abnormalities contributing to the genesis of rest and action tremor.   

In order to evaluate these changes, we attempted to evaluate alterations in white matter (WM) connectivity of the tremor network by estimating network-based statistics of the tremor network. Multi-shell diffusion-weighted images were acquired for 25 patients with TDPD, 25 with ETP, and 25 healthy controls (HC). Following this, the structural connectomes of the BGTC and CTC were generated by probabilistic tractography, and network-based statistics was utilised to perform edge-wise analysis. Both groups of patients had a similar severity of tremor as measured by the Fahn Tolosa Marin tremor rating scale. Analysis of connectivity using network-based statistics revealed a single abnormal edge between the right thalamus and right precentral gyrus with reduction in connectivity seen in TDPD when compared to ETP. These results are of importance, since contrary to the expectation of numerous differneces between two seeingly different diseases, there were barely any differences. This suggests that a similar phenotype of tremor may have similar abnormalities in the tremor network in addition to disease-specific changes. Furthermore, this could explain the improvement in both disorders following lesioning surgery involving the VIM.  

Future studies utilising simultaneous EMG-fMRI will be necessary to further valiadate the identified regions. Furthermore, inclusion of non-TDPD and ET in the study design will help clearly elucidate findings specific to TDPD and ETP. Finally, it is imperative to evaluate other groups with similar combinations of tremor activation states to better understand tremorogenesis across disorders.

References

[1] Helmich RC. The cerebral basis of Parkinsonian tremor: A network perspective. Mov Disord. 2017. 

[2] Helmich RC, Hallett M, Deuschl G, Toni I, Bloem BR. Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits? Brain. 2012;135(Pt 11):3206-3226. 

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