Reduced mind-wandering and fewer depressive symptoms associated with damage to the medial prefrontal cortex and default mode network

Neuropsychologia. 2025 May 9:109168. doi: 10.1016/j.neuropsychologia.2025.109168. Online ahead of print.

ABSTRACT

Depressive disorders have been consistently associated with elevated levels of mind-wandering and self-focused negative rumination. Separate tracks of research have implicated brain structures within the default mode network (DMN) in both mind-wandering and depression. In this study, we hypothesized that diminished mind-wandering and fewer depressive symptoms would co-occur in individuals with damage to the DMN. To test this hypothesis, we used a k-means clustering algorithm to identify a target group of patients with reduced mind-wandering and fewer depressive symptoms relative to brain-damaged comparison subjects (n = 37 of 68; ps < 0.001). The anatomical localization of lesions for this target group was predominantly within the medial prefrontal cortex (mPFC). Structural and functional lesion network mapping results revealed that lesions of the target group had significantly greater connectivity with DMN and limbic regions. Taken together, these results suggest that brain injury affecting the mPFC and DMN is associated with both reduced mind-wandering and fewer depressive symptoms. Further investigation of neuroanatomical substrates that mediate a causal relationship between mind-wandering and mood may facilitate the identification of new therapeutic targets for neuromodulation in patients with disorders characterized by maladaptive mind-wandering, such as rumination.

PMID:40350145 | DOI:10.1016/j.neuropsychologia.2025.109168