Patient-Reported Outcome Severity and Emotional Salience Network Disruption in Multiple Sclerosis

Background Overall burden of white matter damage is associated with increased self-report fatigue severity in people with multiple sclerosis. However, a paradoxically opposite association was reported for white matter damage to tracts in specific subnetworks including the amygdala, temporal pole, and insula. Based on neuroanatomical principles and other data from the literature, we hypothesized that these results might be indicative of a broader relationship between damage to these subnetworks and impaired recognition of negative emotional salience central to patient-reported outcomes. Objective We examined whether damage in the same previously-identified subnetworks is also associated with lower self-report depressive symptoms, something which may be decreased in individuals with impaired recognition of negative emotional salience. Other patient characteristics were also explored. Methods In a cohort of 137 people with multiple sclerosis, we measured location-specific network white matter tract damage in the proposed negative emotional salience network, along with self-report severity of depressive symptoms and cognitive problems, personality characteristics, objective cognitive performance, and physical disability. We applied regression analyses, accounting for lesion burden, to explore the relationship between damage in the proposed negative emotional salience network and these factors. Results We found disruption within the negative emotional salience network is associated with lower self-report depressive symptoms (beta = -0.277, p = 0.036), cognitive complaints (r = -0.196, p = 0.024) and personality trait Neuroticism (r = -0.179, p = 0.042). In contrast, damage within this network was not significantly associated with objective cognitive processing speed, personality trait Openness, or physical disability. Conclusion The identified network may be a generalizable network which corresponds to the recognition of negative emotional salience, but not to objective factors such as processing speed and physical disability. Damage to this network may paradoxically buffer against negative emotional perception of symptom severity, central to patient-reported outcomes.