Morphometric features of drug-resistant essential tremor and recovery after stereotactic radiosurgical thalamotomy

Abstract

Essential tremor (ET) is the most common movement disorder. Its neural underpinnings remain unclear. Here, we quantified structural covariance between cortical thickness (CT), surface area (SA), and mean curvature (MC) estimates in patients with ET before and 1 year after ventro-intermediate nucleus stereotactic radiosurgical thalamotomy, and contrasted the observed patterns with those from matched healthy controls. For SA, complex rearrangements within a network of motion-related brain areas characterized patients with ET. This was complemented by MC alterations revolving around the left middle temporal cortex and the disappearance of positive-valued covariance across both modalities in the right fusiform gyrus. Recovery following thalamotomy involved MC readjustments in frontal brain centers, the amygdala, and the insula, capturing nonmotor characteristics of the disease. The appearance of negative-valued CT covariance between the left parahippocampal gyrus and hippocampus was another recovery mechanism involving high-level visual areas. This was complemented by the appearance of negative-valued CT/MC covariance, and positive-valued SA/MC covariance, in the right inferior temporal cortex and bilateral fusiform gyrus. Our results demonstrate that different morphometric properties provide complementary information to understand ET, and that their statistical cross-dependences are also valuable. They pinpoint several anatomical features of the disease and highlight routes of recovery following thalamotomy.

Keywords: Cortical thickness; Essential tremor; Mean curvature; Morphometry; Radiosurgery; Structural covariance analysis; Surface area; Thalamotomy; Ventro-intermediate nucleus.

Figure 1.

Structural covariance patterns across groups and modalities. For cortical thickness (A), surface area (B), and mean curvature (C), structural covariance matrices for the HC, ET_pre, and ET_post groups (top row, from left to right), associated HC-ET_pre and ET_post-ET_pre group differences (bottom row, left and middle panels), and summarizing histogram (bottom row, right panel). Discarded connections are depicted in gray.

Figure 2.

Graphical overview of significant findings. Significant structural covariance edges for cortical thickness and the ET_post-ET_pre contrast (A), surface area and the HC-ET_pre contrast (B), and mean curvature and the ET_post-ET_pre (C), and HC-ET_pre (D) contrasts. Positive-valued group differences are represented by yellow connections, and negative-values ones by pink connections. Nodal size and color are proportional to the number of emanating significant connections. For the cortical thickness/surface area (E), cortical thickness/mean curvature (F), and surface area/mean curvature (G) cross-measure analyses, overview of significance for the HC-ET_pre (left) and ET_post-ET_pre (right) group differences. Nodal size and color are proportional to −log(p value), with black nodes the ones found significant in our analyses. P, posterior; R, right; A, anterior; L, left.

Figure 3.

Cross-property covariance relationships. For the relationship between cortical thickness and mean curvature for the ET_post-ET_pre contrast (A), and for the relationship between surface area and mean curvature for the HC-ET_pre (B), and ET_post-ET_pre (C) group differences, cross-property covariance differences between groups (black squares) and associated null distributions (box plots) for all 68 cortical regions from the Desikan-Killiany atlas. Color coding of the box plots denotes brain lobes. Significant cases are highlighted by a light gray box in the background.