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 hypothesized 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.

Corticolimbic structural alterations linked to health status and trait anxiety in functional neurological disorder

“…In FND subjects, impaired physical functioning subscale scores also correlated with decreased left anterior insular volume. These inter-related findings are consistent with and extend our prior report of inverse correlations between functional neurological symptom severity and anterior insular volume in FND 33. As a paralimbic, multimodal brain area implicated in the processing and integration of viscerosomatic, interoceptive, affective, cognitive and visceromotor functions and a core region of the salience network, we have postulated an important role for the insula in the pathophysiology of FND 17 45 46.…”

“…Neuroimaging meta-analyses of FND31 and other somatic symptom disorders32 support a neurobiological role for multiple regions within the salience network. Recently, we reported that functional neurological symptom severity was associated with reduced left anterior insular volume in women with FND, while trauma-related hyperarousal correlated with decreased dorsal ACC grey matter 33. These findings demonstrated the utility of within-group designs to dimensionally characterise brain–symptom relationships in FND.…”

“…Considering the literature characterising alterations within the salience network in FND, as well as the recognised relationship between poor health status and affective symptoms, we hypothesised that self-reported measures of health status and affective symptoms would both map onto salience network brain areas. Building on our prior observation that sensorimotor functional neurological symptom severity correlated with reduced insular volume,33 we also hypothesised that reported physical health impairments would be associated with reduced left anterior insular grey matter and that patients with FND compared with controls would show decreased insular volume.…”

Childhood sexual abuse predicts treatment outcome in conversion disorder/functional neurological disorder. An observational longitudinal study

“…In an exploration of immune function in CD/FND, Tilyeki et al found temporarily decreased serum TNF‐α levels in the acute phase of CD/FND, suggesting that stress associated with CD/FND might suppress immune function in the acute phase of CD/FND (Tiyekli, Çalıyurt, & Tiyekli, ). An association between stress‐related neuroplasticity, CD/FND, and reduced insular volume was identified in an MRI study in patients with FND and childhood adversity (Perez et al, ). Childhood physical or sexual abuse has been found in 44% of patients with CD/FND (Roelofs, Spinhoven, Sandijck, Moene, & Hoogduin, ) and is associated with higher symptom loads in patients with nonepileptic seizures (Selkirk, Duncan, Oto, & Pelosi, ).…”

Stress and functional neurological disorders: mechanistic insights

“…Neuroimaging research found that reduced regional volumes including the left hippocampus and left anterior insula (women only) correlated with severity of childhood abuse and lifetime trauma, but not self-reported FND symptoms 45. FND case series indicate that symptoms develop in a proportion after brain injury, including postneurosurgery 46.…”