Abstract Body: Background: Occurrence of post-stroke apathy (PSA) is associated with worse outcomes and poorer quality of life. Particularly, post-thalamic stroke apathy was repeatedly reported. In this study, we performed disconnection-based analyses to reveal the neural basis of post-thalamic stroke apathy from both focal and network perspectives.

Method: This study recruited first-ever unilateral thalamic ischemic stroke patients. The Lille Apathy Rating Scale was used to characterize the appearance and severity of apathy. Patient’s lesion masks were embedded into normative connectome to generate functional or structural disconnection maps. Support Vector Regression-based Multivariate Lesion-Symptom Mapping and Disconnection-Symptom Mapping were employed to explore associations between lesion locations, structural and functional disconnections, and PSA.

Results: A total of 92 patients with thalamic infarction were included. No significant associations were found between thalamic lesion locations and PSA. However, structural disconnection in the anterior thalamic radiation and functional disconnection in the bilateral medial prefrontal cortex, bilateral inferior frontal gyrus, bilateral anterior insular cortex, right inferior parietal lobule, and right superior temporal gyrus were significantly associated with PSA.

Conclusion: The study revealed that apathy following thalamic ischemic stroke is associated with disruptions in thalamocortical networks rather than specific lesion locations. These findings suggest that post-thalamic stroke apathy is a network disorder, driven by functional diaschisis and secondary neurodegeneration. Understanding these mechanisms may inform treatment targets and improve post-stroke rehabilitation strategies.