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Related Experiment Video

Updated: Jun 17, 2026

Lesion Explorer: A Video-guided, Standardized Protocol for Accurate and Reliable MRI-derived Volumetrics in Alzheimer's Disease and Normal Elderly
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Investigating the methodological foundation of lesion network mapping.

Martijn P van den Heuvel1,2, Ilan Libedinsky3, Sebastian Quiroz Monnens3

  • 1Department of Neurosciences, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. martijn.vanden.heuvel@vu.nl.

Nature Neuroscience
|January 16, 2026
PubMed
Summary
This summary is machine-generated.

Lesion network mapping (LNM) may not accurately identify distinct brain networks in neurological disorders. This neuroimaging method repeatedly samples the same data, leading to similar network findings across different conditions.

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Area of Science:

  • Neuroimaging
  • Network Neuroscience
  • Computational Psychiatry

Background:

  • Lesion network mapping (LNM) links brain lesions to functional alterations using functional connectivity (FC) data.
  • LNM is applied across various neurological and psychiatric conditions, including addiction, depression, psychosis, and epilepsy.
  • Observed similarities in identified networks across diverse conditions prompted a re-examination of LNM methodology.

Purpose of the Study:

  • To investigate the methodological underpinnings of observed similarities in lesion network mapping (LNM) results.
  • To identify potential limitations in the LNM framework regarding the specificity of identified brain networks.

Main Methods:

  • Re-analysis of data from multiple LNM studies.
  • Assessment of the methodological foundations of the LNM framework.
  • Examination of the repetitive sampling of functional connectivity (FC) matrices within LNM.

Main Results:

  • Lesion network mapping (LNM) fundamentally involves repetitive sampling of a single functional connectivity (FC) matrix.
  • This repetitive sampling leads to the mapping of diverse brain alterations onto nonspecific FC properties.
  • Consequently, LNM produces highly similar network findings across different neurological and psychiatric conditions.

Conclusions:

  • A foundational limitation exists in LNM due to its reliance on repetitive sampling of the same FC matrix.
  • This limitation results in nonspecific network identification, cautioning against its use for studying distinct biological networks in brain disorders.
  • The findings advocate for the development of novel network-mapping methodologies based on first principles.