DIFFERENTIAL POSTERIOR CINGULATE CORTEX ENGAGEMENT IN DISEASE-RELATED VERSUS GENERAL SELF-JUDGEMENT IN FIBROMYALGIA AND DEPRESSION VS. HEALTHY WOMEN

Patients with chronic pain and major depressive disorder often show a poor self-concept. However, the neural mechanisms underlying illness-related self-judgement remain poorly understood. In this study, we combined behavioral measures, machine-learning classification, and voxel-wise stability analyses to characterize the neural signature of illness-related (vs. general) self-judgement in fibromyalgia, depressive patients, and healthy controls.
Behaviorally, patients endorsed significantly more negative and fewer positive traits when judging illness-related attributes, compared to general ones (F=108.01, p<0.001). At the neural level, multivoxel pattern analysis revealed highly accurate brain signatures discriminating illness-related from general self-judgement (T=75.93, p<0.001); however,voxel-wise stability analyses revealed differences between groups in the underlying neural substrates.
In patients, stable positive contributions were predominantly localized within posterior nodes of the default mode network (DMN) -posterior cingulate cortex and precuneus- (390 voxels, p-value=0.00000016), and negative contributions for the medial prefrontal cortex. In contrast, controls showed minimal stability in such regions, but greater involvement of dorsolateral prefrontal and temporo-parietal areas, associated with task-driven and linguistic processing (148 voxels, p-value=0.00000207). Meta-analytic semantic decoding further supported this dissociation, linking patients’ signature to memory retrieval and self-related neural systems, whereas the healthy controls’ to comprehension-demanding perceptual processes.
Together, these results suggest a functional differentiation within anterior–posterior DMN nodes in shaping disease-related cognition and behavior in a disease context. Illness-related self-judgement seems to preferably engage posterior DMN hubs, thus relying more heavily on memory-based internal mentation systems, highlighting a neurobiological mechanism by which the self-referential network would contribute to the formation and maintenance of ruminative maladaptive illness-related self-beliefs.