Mental fatigue in stress-related exhaustion disorder: Structural brain correlates, clinical characteristics and relations with cognitive functioning

Emerging evidence suggests that mental fatigue is a central component of the cognitive and clinical characteristics of stress-related exhaustion disorder (ED). Yet, the underlying mechanisms of mental fatigue in this patient group are poorly understood. The aim of this study was to investigate cortical and subcortical structural neural correlates of mental fatigue in patients with ED, and to explore the association between mental fatigue and cognitive functioning. Fifty-five patients with clinical ED diagnosis underwent magnetic resonance imaging. Mental fatigue was assessed using the Concentration subscale from the Checklist Individual Strength. Patients with high levels of mental fatigue (n = 30) had smaller caudate and putamen volumes compared to patients with low-moderate levels of mental fatigue (n = 25). No statistically significant differences in cortical thickness were observed between the groups. Mediation analysis showed that mental fatigue mediated the relationship between caudate volume and working memory; specifically, smaller caudate volume was associated with higher level of mental fatigue and mental fatigue was positively associated with working memory performance. Our findings demonstrate that the structural integrity of the striatum is of relevance for the subjective perception of mental fatigue in ED, while also highlighting the complex relationship between mental fatigue, cognitive performance and its neural underpinnings.