Cerebral gray matter volume losses in essential tremor: A case-control study using high resolution tissue probability maps

Abstract

Introduction: Essential tremor (ET) is increasingly recognized as a multi-dimensional disorder with both motor and non-motor features. For this reason, imaging studies are more broadly examining regions outside the cerebellar motor loop. Reliable detection of cerebral gray matter (GM) atrophy requires optimized processing, adapted to high-resolution magnetic resonance imaging (MRI). We investigated cerebral GM volume loss in ET cases using automated segmentation of MRI T1-weighted images.

Methods: MRI was acquired on 47 ET cases and 36 controls. Automated segmentation and voxel-wise comparisons of volume were performed using Statistical Parametric Mapping (SPM) software. To improve upon standard protocols, the high-resolution International Consortium for Brain Mapping (ICBM) 2009a atlas and tissue probability maps were used to process each subject image. Group comparisons were performed: all ET vs. Controls, ET with head tremor (ETH) vs. Controls, and severe ET vs. Controls. An analysis of variance (ANOVA) was performed between ET with and without head tremor and controls. Age, sex, and Montreal Cognitive Assessment (MoCA) score were regressed out from each comparison.

Results: We were able to consistently identify regions of cerebral GM volume loss in ET and in ET subgroups in the posterior insula, superior temporal gyri, cingulate cortex, inferior frontal gyri and other occipital and parietal regions. There were no significant increases in GM volume in ET in any comparisons with controls.

Conclusion: This study, which uses improved methodologies, provides evidence that GM volume loss in ET is present beyond the cerebellum, and in fact, is widespread throughout the cerebrum as well.

Keywords: Cerebrum; Essential tremor; Gray matter volume; High-resolution MRI; VBM.

Figure 1

Axial slice view of statistically significant clusters (in red). Statistical significance is determined using a peak-voxel p-value < 0.001 and a cluster corrected threshold at the cluster level of p < 0.05. ANOVA was run with three groups: ET with head tremor, ET without head tremor and controls. Abbreviations: “vs” refers to a group comparison between two subject groups. Essential Tremor (ET), Control (C), ET with head tremor (ETH), ET with total tremor score ≥ 23 (ET-ST), Analysis of Variance (ANOVA).