Schedule of Events | Symposia

Mapping the Neural Basis of Cotard Syndrome: Insights from Lesion Network Analysis

Poster Session D - Monday, March 31, 2025, 8:00 – 10:00 am EDT, Back Bay Ballroom/Republic Ballroom

Mengyuan Ding^1,2 (jessy@neurospirituality.io), Morgan Healey¹, Yaser Sánchez Gama^1,2, Michael A. Ferguson^1,2; ¹Neurospirituality Lab, Center for Brain Circuit Therapeutics, ²Brigham and Women's Hospital, Harvard Medical School

Background: Cotard syndrome (CS), characterized by nihilistic delusions such as believing one is dead or non-existent, remains poorly understood due to its rarity and subjective presentation. Using lesion network mapping, we sought to identify brain network disruptions underlying CS to advance the understanding of its neuroanatomical basis. Methods: A systematic review identified 19 lesion-induced CS cases. Lesions were mapped onto a standard brain template, and functional connectivity was analyzed using a resting-state fMRI connectome from 1,000 healthy subjects. Sensitivity was tested by overlapping lesion network maps (threshold: t > 4.7) to identify regions connected to >70% of CS lesion sites. Specificity was assessed by comparing CS lesion networks to a stroke lesion dataset not associated with CS (n = 135). A CS conjunction map was derived from regions meeting both sensitivity and specificity criteria. Results: A CS-specific functional network was identified, with key nodes in the right inferior frontal lobe, anterior temporal pole, anterior insula, and temporoparietal junction. These regions are implicated in neuroimaging tests of CS cases, highlighting structural and metabolic disruptions in the right frontal, temporal, and parietal lobes. Their roles in self-awareness, emotional regulation, and bodily perception align with the symptoms of CS, providing a cohesive neural explanation for its characteristic delusions. Conclusions: This study identifies a functional network underlying Cotard syndrome, implicating disrupted connectivity in self-perception and body ownership. These results provide a framework for understanding CS and suggest potential targets for neuromodulation, paving the way for future research into this enigmatic condition.

Topic Area: METHODS: Neuroimaging