# Thalamic Structural Connectivity Alterations in Essential Tremor Associated with REM Sleep Behaviour Disorder

## TL;DR

This study shows that Essential Tremor patients with REM Sleep Behavior Disorder have altered thalamic connectivity, suggesting a role for the thalamus in the disorder's development.

## Contribution

First demonstration of thalamic structural connectivity changes in Essential Tremor patients with RBD.

## Key findings

- ET-RBD patients showed increased local strength and clustering in the Geniculate Body and Pulvinar Nucleus.
- ET-RBD patients had increased strength and clustering in the Left Lateral and Right Medial Geniculate Body compared to controls.
- Thalamic volume loss and altered connectivity were observed in ET-RBD patients, particularly in geniculate and pulvinar nuclei.

## Abstract

REM sleep behavior disorder (RBD) is a rare REM-parasomnia, now considered a non-motor symptom of Essential Tremor (ET). Distinct structural alterations in the thalamus, as a key region modulating REM sleep, have been reported in patients with idiopathic and Parkinson’s disease-related forms. In this work, we investigated thalamic regions in ET patients with and without RBD, using a graph theoretical analysis.

MRI data were acquired from 96 participants (41 ET, 10 ET with polysomnographic-confirmed RBD, ET-RBD, 45 controls). T1-weighted scans were obtained, and grey matter volumes were estimated across 28 thalamic regions of the AAL3 template (Cat12 toolbox). An adjacency matrix for each group was calculated using Pearson correlation. Group-specific matrices were extracted and nodal measures such as centrality measures and clustering coefficient were calculated. Differences between ET groups were computed using a set of 10000 random networks.

Interestingly, among analyzed thalamic regions, ET-RBD patients showed increased local strength and weighted clustering coefficient in Geniculate Body and increased Betweenness centrality in Right Pulvinar Inferior Nucleus (p = 0.05 FDR-corrected). Moreover, ET-RBD patients showed an increased strength and weighted clustering coefficient in Left Lateral Geniculate Body and Right Medial Geniculate Body, compared to controls (p = 0.05 FDR-corrected).

Our study demonstrates, for the first time, that the presence of RBD in ET is associated with an altered structural connectivity in thalamic regions. Our findings support the pathophysiologic role of the thalamus in the complex circuit causing RBD, in this particular ET phenotype.

ET-RBD phenotype is associated with thalamic volume loss and altered structural connectivity, particularly in the medial and lateral geniculate and pulvinar nuclei.

Our findings support the pathophysiologic role of the thalamus in the complex RBD pathophysiology in this particular ET phenotype.