An Investigation of the Neurobiology of Psychogenic Non-Epileptic Seizures

Background: Psychogenic non-epileptic seizures (PNES) are paroxysmal episodes of seizure-like behaviour that superficially resemble epileptic events, but lack EEG correlates of epilepsy. Diagnosis is often delayed and the condition is associated with significant impairments of general functioning. At the time that this project was commenced, there were few neuropsychological studies of PNES and the neural correlates of this condition were unknown. Aims: This project aimed to firstly, examine the prevalence and management of PNES in an Irish epilepsy monitoring unit (EMU) and secondly to examine neuropsychiatric, neuropsychological, structural and functional neuroimaging correlates of adults with PNES. Methods: Standardised assessments and cognitive test batteries were used to assess the psychiatric and neuropsychological functioning of patients with PNES and a matched healthy control group. All participants underwent structural neuroimaging, diffusion tensor imaging and a functional neuroimaging task involving implicit face processing. Only those who passed a test of effort were included. Data analysis controlled for known potential confounders, including differences in intelligence. Results: Patients with PNES were found to score significantly higher on measures of stress, alexithymia and multiple dissociative-conversion indices. In addition, they demonstrated abnormal spatial working memory performance, even after controlling for between-group differences in FSIQ. ROI analyses of the sMRI and DTI data showed that patients had reduced grey matter in a region comprising left middle and inferior temporal gyrus, and abnormal integrity of white matter tracts involving forceps major (FM), thalamus, and especially the superior longitudinal fasciculus (SLF), but these findings did not survive statistical correction for group differences in FSIQ (which was not taken into account in the previous studies). Analysis of the fMRI data demonstrated that patients with PNES exhibited an abnormally reduced functional response to the implicit face-processing task, in regions known to be involved in face-processing, socio-emotional processing and movement. Conclusions: The fMRI findings demonstrated that patients with PNES have abnormal functioning of brain regions that subserve cognitive, emotional, face-processing and movement processes. Patients with PNES had relatively reduced grey matter volumes in an area of the left temporal lobe known to be involved in semantic memory and language (MTG), face-processing (ITG), and multimodal sensory-integration (MTG and ITG). In addition, patients had relatively increased fractional anisotropy in white matter tracts involving the left frontotemporal region [comprising left superior longitudinal fasciculus (SLF) forceps major (FM)] and thalamus, tracts that are involved in the integration of motor, sensory and visual functioning, interhemispheric connectivity, and regulation of consciousness, transmission of sensory and motor output and intentional movement, respectively. The changes observed may represent an abnormal maturation process of white matter. However, both sMRI and DTI findings were not statistically significant between groups after controlling for the effects of differences in FSIQ. Some of the neuroimaging findings were related to clinical indices associated with PNES, with a focus on physical and sensory symptoms related to conversion disorder being a particularly prominent association. These findings have important implications for our current understanding of the neurobiology of PNES. Future studies are necessary to replicate these findings with larger sample sizes and to delineate the processes underlying abnormal emotional processing in PNES.