Locus coeruleus co-activation patterns at rest show higher state persistence in patients with dissociative seizures: A Pilot Study

Objective: Dissociative seizures are paroxysmal disruptions of awareness and behavioral control in the context of affective arousal. Alterations in stress-related endocrine function have been demonstrated, but the timescale of dissociation suggests that the central locus coeruleus (LC) noradrenergic system is likely pivotal. Here, we investigate whether LC activation at rest is associated with altered brain network dynamics. Methods: A preliminary co-activation pattern (CAP) analysis of resting-state functional magnetic resonance imaging (fMRI) in 14 patients with dissociative seizures and 14 healthy controls was performed by using the LC as a seeding region. The red nucleus served as a control condition. Entry rates, durations, and state transition probabilities of identified CAPs were calculated. Analyses were corrected for demographic, technical, and clinical confounders including depression and anxiety. Results: Three LC-related CAPs were identified, with the dominant two showing inverse activations and deactivations of the default mode network and the attention networks, respectively. Analysis of transition probabilities between and within the three CAPs revealed higher state persistence in patients compared to healthy controls for both CAP2LC (Cohen's d = -0.55; p = 0.01) and CAP3LC (Cohen's d = -0.57; p = 0.01). The control analysis using the red nucleus as a seed yielded similar CAPs, but no significant between-group differences in transition probabilities. Significance: Higher state persistence of LC-CAPs in patients with dissociative seizures generates the novel hypothesis that arousal-related impairments of network switching might be a candidate neural mechanism of dissociation. Plain language summary: Dissociative seizures often arise during high affective arousal. The locus coeruleus is a brain structure involved in managing such acute arousal states. We investigated whether the activity of the locus coeruleus correlates with activity in other regions of the brain (which we refer to as "brain states"), and whether those brain states were different between patients with dissociative seizures and healthy controls. We found that patients tended to stay in certain locus coeruleus-dependent brain states instead of switching between them. This might be related to the loss of awareness and disruptions of brain functions ("dissociation") that patients experience during seizures.