The imprint of dissociative seizures on the brain.

Background: Increased resting state functional connectivity between regions involved in emotion control with regions with other specializations, e.g. motor control (emotional hyperconnectivity) is one of the most consistent imaging findings in persons suffering from dissociative seizures (DS). The overall goal of this study was to better characterize DS-related emotional hyperconnectivity using dynamic resting state analysis combined with brainstem volumetry to investigate 1. If emotional hyperconnectivity is restricted to a single state. 2. How volume losses within the modulatory and emotional motor subnetworks of the neuromodulatory system influence the expression of the emotional hyperconnectivity.

Methods: 13 persons with dissociative seizures (PDS) (f/m:10/3, mean age (SD) 44.6 (11.5)) and 15 controls (CON) (f/m:10/5, mean age (SD) 41.7 (13.0)) underwent a mental health test battery and structural and functional imaging at 3 T. Deformation based morphometry was used to assess brain volume loss by extracting the mean Jacobian determinants from 457 brain, forebrain and brainstem structures. The bold signals from 445 brainstem and brain rois were extracted with CONN and a dynamic fMRI analysis combined with graph and hierarchical analysis was used to identify and characterize 9 different brain states. Welch's t tests and Kendall tau tests were used for group comparisons and correlation analyses.

Results: The duration of Brain state 6 was longer in PDS than in CON (93.1(88.3) vs. 23.4(31.2), p = 0.01) and positively correlated with higher degrees of somatization, depression, PTSD severity and dissociation. Its global connectivity was higher in PDS than CON (90.4(3.2) vs 86.5(4.2) p = 0.01) which was caused by an increased connectivity between regions involved in emotion control and regions involved in sense of agency/body control. The brainstem and brainstem-forebrain modulatory and emotional motor subnetworks of the neuromodulatory system were atrophied in PDS. Atrophy severity within the brainstem-forebrain subnetworks was correlated with state 6 dwell time (modulatory: tau = -0.295, p = 0.03; emotional motor: tau = -0.343, p = 0.015) and atrophy severity within the brainstem subnetwork with somatization severity (modulatory: tau = -0.25, p = 0.036; emotional motor: tau = -0.256, p = 0.033).

Conclusion: DS-related emotional hyperconnectivity was restricted to state 6 episodes. The remaining states were not different between PDS and CON. The modulatory subnetwork synchronizes brain activity across brain regions. Atrophy and dysfunction within that subnetwork could facilitate the abnormal interaction between regions involved in emotion control with those controlling sense of agency/body ownership during state 6 and contribute to the tendency for somatization in PDS. The emotional motor subnetwork controls the activity of spinal motoneurons. Atrophy and dysfunction within this subnetwork could impair that control resulting in motor symptoms during DS. Taken together, these findings indicate that DS have a neurophysiological underpinning.