Ensuring anatomical specificity in lesion network mapping: a multicentre study of 2,950 stroke patients

Case-control lesion network mapping in 2,950 stroke patients across 12 cohorts yields distinct, domain-specific lesion network maps, whereas one-sample analyses converge on nonspecific connectome properties.

• Why it matters: Anatomically diverse lesions can produce similar deficits, and prior critiques suggested LNM procedures may reflect nonspecific normative connectome features rather than symptom-specific networks.
• What they did: The study compared lesion-derived connectivity maps between impaired and unimpaired groups across six cognitive domains using permutation of symptom labels, parametric two-sample inference, and a one-sample approach; simulations across 10,000 null studies tested type I error.
• The result: Two-sample approaches showed limited correspondence to nonspecific connectome properties with valid type I error control, while one-sample analyses reproduced convergence and domain similarity, implying design choice is critical for anatomical specificity.

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