Abstracts

Rationale: Increased fronto-parietal resting state functional connectivity whose severity is associated with dissociation and seizure severity is one of the most consistently observed findings in PNES. A potential mechanism is a disturbance of the neuromodulatory brainstem system whose widespread projections shape the intrinsic activity across the cortex. The ventral tegmental area (VTA) and brainstem structures connected to it (VTAplus), i.e., locus coeruleus (LC), periaqueductal gray (PAG), dorsal raphe (DR), parabrachial (Pb) and pedunculopontine nuclei (PP) are of particular interest because not only projects the VTA heavily to the motor cortices but the VTAplus also plays a crucial role in mood regulation. The aims of this project were therefore to use volumetric and functional resting state MRI to investigate if (1) PNES is associated with volume loss in the VTAplus and the motor cortex (precentral (Pre), postcentral gyrus (Post), supplementary motor area (SMA)), and (2) PNES is associated with increased functional connectivity within the VTAplus- motor network.

Methods: A total of 22 participants (12 PNES, mean age 44.6 (29-60) and 10 controls (Con), mean age 39.0 (23-60) underwent volumetric and task-free functional MRI at 3T and a psychological assessment. The T1 and T2 images were used to segment internal brainstem structures using a modification of a previously developed cluster-based segmentation approach. Deformation-based morphometry (DBM) restricted to the brainstem was used to identify volume losses in VTA, PAG, DR, LC, PB, PP and whole brain DBM to identify volume loss in Pre, Post and SMA. Connectivity within the VTAplus-motor network as well as motor-amygdala, motor-anterior cingulate and motor-orbitofrontal networks was characterized by graph analysis (mean positive strength of all nodes in network)

Results: PNES was characterized by volume loss (p< 0.05) in the VTA (0.87(0.12) vs. 0.99(0.10), p=0.01), DR (0.83(0.16) vs. 0.94(0.11), p=0.031), right PP (0.78(0.07) vs. 0.85(0.11) p=0.046 and left PB (0.75(0.10) vs. 0.85(0.07), p=0.004), left SMA (1.0(0.04) vs. 1.03(0.06) p=0.04, left Post (1.01(0.07) vs. 1.07(0.06) p=0.02) and right Post (0.98(0.06) vs. 1.05(0.08) p=0.02). VTAplus-motor strength was increased in PNES compared to CON (1.13(0.14) vs 0.91(0.20) p=0.02) and correlated with dissociation severity (Kendall’s tau=0.32,p=0.02). Connectivity strength within the motor-amygdala, motor-anterior cingulate or motor-orbitofrontal network was not different between the groups.