Cingulo-insular structural alterations associated with psychogenic symptoms, childhood abuse and PTSD in functional neurological disorders

Abstract

Objective: Adverse early-life events are predisposing factors for functional neurological disorder (FND) and post-traumatic stress disorder (PTSD). Cingulo-insular regions are implicated in the biology of both conditions and are sites of stress-mediated neuroplasticity. We hypothesised that functional neurological symptoms and the magnitude of childhood abuse would be associated with overlapping anterior cingulate cortex (ACC) and insular volumetric reductions, and that FND and PTSD symptoms would map onto distinct cingulo-insular areas.

Methods: This within-group voxel-based morphometry study probes volumetric associations with self-report measures of functional neurological symptoms, adverse life events and PTSD symptoms in 23 mixed-gender FND patients. Separate secondary analyses were also performed in the subset of 18 women with FND to account for gender-specific effects.

Results: Across the entire cohort, there were no statistically significant volumetric associations with self-report measures of functional neurological symptom severity or childhood abuse. In women with FND, however, parallel inverse associations were observed between left anterior insular volume and functional neurological symptoms as measured by the Patient Health Questionnaire-15 and the Screening for Somatoform Symptoms Conversion Disorder subscale. Similar inverse relationships were also appreciated between childhood abuse burden and left anterior insular volume. Across all subjects, PTSD symptom severity was inversely associated with dorsal ACC volume, and the magnitude of lifetime adverse events was inversely associated with left hippocampal volume.

Conclusions: This study reveals distinct cingulo-insular alterations for FND and PTSD symptoms and may advance our understanding of FND. Potential biological convergence between stress-related neuroplasticity, functional neurological symptoms and reduced insular volume was identified.

Keywords: Conversion Disorder; Functional Movement Disorders; Functional Weakness; Psychogenic Nonepileptic Seizures; Voxel-Based Morphometry.

FIGURE 1. Scatter plots of the positive associations between functional neurological symptoms and the magnitude of previously experienced childhood abuse

Also shown, is the scatter plot of the positive correlation between the Conversion Disorder subscale of the Screening for Somatoform Symptoms-7 scale and the Patient Health Questionnaire-15. Spearman correlation coefficients are displayed.

FIGURE 2. Left anterior insula gray matter volume negatively correlated with functional neurological symptoms and previously experienced childhood abuse in women with Functional Neurological Disorder

(A) Patient Health Questionnaire-15 scores were inversely associated with left anterior insular gray matter volume (p_svc=0.032; peak z-score=−3.93). (B) Conversion Disorder subscale of the Screening for Somatoform Symptoms-7 scale scores were also inversely correlated with left anterior insular gray matter volume (p_svc=0.038; peak z-score=−3.87). (C) The magnitude of childhood abuse as measured by the Childhood Trauma Questionnaire showed a parallel negative association with left anterior insular gray matter volume (p_svc=0.021; peak z-score=−4.04). Images are thresholded at a voxel-wise uncorrected p-value of 0.005 for visualization purposes. To display in the scatter plots a measure of gray matter volume for visualization purposes only, the MarsBar toolbox (http://marsbar.sourceforge.net/) was used to extract mean gray matter volumes for each subject at a 5mm sphere centered at the peak coordinate of statistically significant findings.

FIGURE 3. Across individuals with Functional Neurological Disorder (FND), PTSD symptom severity and lifetime trauma burden showed inverse associations with anterior cingulate cortex and hippocampal gray matter volumes respectively

(A) Hyperarousal as measured by the PTSD Checklist for DSM-5 was negatively associated with dorsal anterior cingulate cortex (ACC) gray matter volume (p_svc=0.014, peak z-score=−3.97). (B) In women with FND, avoidance as measured by the PTSD Checklist for DSM-5 was negatively associated with dorsal/perigenual ACC gray matter volume (p_svc=0.046, peak z-score=−3.66). (C) Across all subjects, lifetime adverse events as measured by the “happened to me” item of the Life Events Checklist-5 (LEC) was negatively associated with left hippocampal gray matter volume (p_svc=0.010, peak z-score=−4.01). Images are thresholded at a voxel-wise uncorrected p-value of 0.005 for visualization purposes. To display in the scatter plots a measure of gray matter volume for visualization purposes only, the MarsBar toolbox (http://marsbar.sourceforge.net/) was used to extract mean gray matter volumes for each subject at a 5mm sphere centered at the peak coordinate of statistically significant findings.