Nature Neuroscience, Published online: 20 May 2026; doi:10.1038/s41593-026-02319-8Lesion network mapping (LNM), or atrophy network mapping, has become a widely adopted tool for linking focal brain lesions or neurodegenerative brain clusters, respectively, to distributed functional networks associated with cognitive or clinical deficits. Recent insights, however, suggest that LNM primarily captures elementary topological properties of the normative connectome rather than disorder-specific circuits. Independent clinical evidence supports these methodological concerns, reflecting a deeper biological issue. LNM is inherently unable to capture the higher-order disconnection effects and non-linear connectivity changes that characterize the brain response to a broad range of neurological conditions. Brain injuries can induce widespread changes in distal regions not directly affected by the damage, as well as complex patterns of pathological hyperconnectivity and hypoconnectivity that evolve over time and whose functional significance remains uncertain. These phenomena represent a central challenge in clinical neuroscience. LNM is intrinsically limited in capturing these dynamics, with important implications for clinical translation and neuromodulation.
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This post is Copyright: | May 20, 2026
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