Lesion network mapping

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Lesion network mapping is a neuroimaging technique that analyzes the connectivity pattern of brain lesions to identify neuroanatomic correlates of symptoms.[1][2][3] The scientific validity of these methods has been widely disputed.[4][5][6] The technique was developed by Aaron Boes to understand the network anatomy of lesion induced neurologic and psychiatric symptoms that can not be explained by focal anatomic localization.[7][8] Lesion network mapping applies a network-based approach to identify connected brain networks, rather than focal brain regions, that correlate with a specific symptom.

In focal neuroanatomic localization, developed by Paul Broca and others, specific symptoms that occur due to brain lesions can be understood by identifying a specific brain region that is injured by lesions to establish brain-symptom relationships.[2] However, a number of neurologic symptoms, such as peduncular hallucinosis, are not amenable to this approach since the lesions associated with the symptom do not map to one focal brain location.[1] Lesion network mapping helps to explain these lesion-induced syndromes by showing that lesion locations associated with a given symptom all map to a shared brain network even if they do not all map to a focal brain region.[2] The technique maps the location of lesions associated with a specific symptom and analyzes the connectivity pattern of the lesions compared to large, standardized human brain atlases. While initially developed using resting-state fMRIs such as the Human Connectome Project,[1] the technique has been expanded to include large structural network atlases [9] and multimodal-connectome datasets.[10] Software tools for that facilitate lesion network mapping exist within the Lead-DBS framework,[11] which is also used for a related technique, DBS network mapping.

Lesion network mapping has helped map the network anatomy of numerous rare neurologic syndromes (peduncular hallucinosis,[1] delusional misidentification,[12] reduplicative paramensia,[13] akinetic mutism,[14] blindsight,[15] visual anosognosia[16]), common neurologic syndromes (seizures,[17] aphasia,[18] amnesia,[19] parkinsonism,[20] topographical disorientation[21]), psychiatric syndromes[22] (depression,[23][24] mania[25]), as well as complex human behaviors (spirituality,[26] religious fundamentalism,[27] consciousness,[28][29] free will,[14] criminality,[30] addiction[31]). The technique has been successfully applied to a broad range of diseases and lesion types including lesions due to stroke,[1] traumatic brain injury,[26] tuberous sclerosis[32][33] and multiple sclerosis.[34][35] The technique has been broadened to map the connectivity of locations from transcranial magnetic stimulation[24] and deep brain stimulation[36] sites to understand treatment responsiveness.

Research findings based on lesion network mapping have been reported in the New York Times,[37] Scientific American[38] and USA Today[39] and the term has been included in the New England Journal of Medicine's general medical glossary.[3]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 Boes, Aaron D.; Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S.; Fox, Michael D. (October 2015). "Network localization of neurological symptoms from focal brain lesions". Brain: A Journal of Neurology 138 (Pt 10): 3061–3075. doi:10.1093/brain/awv228. ISSN 1460-2156. PMID 26264514. 
  2. ↑ 2.0 2.1 2.2 Fox, Michael D. (2018-12-06). "Mapping Symptoms to Brain Networks with the Human Connectome" (in en). New England Journal of Medicine 379 (23): 2237–2245. doi:10.1056/NEJMra1706158. ISSN 0028-4793. PMID 30575457. http://www.nejm.org/doi/10.1056/NEJMra1706158. 
  3. ↑ 3.0 3.1 NEJM. "Illustrated Glossary - NEJM" (in English). https://illustrated-glossary.nejm.org/term/lesion_network_map. 
  4. ↑ van den Heuvel, Martijn P.; Libedinsky, Ilan; Quiroz Monnens, Sebastian; Repple, Jonathan; Sommer, Iris; Cocchi, Luca (2026-01-15). "Investigating the methodological foundation of lesion network mapping" (in en). Nature Neuroscience. doi:10.1038/s41593-025-02196-7. ISSN 1097-6256. https://www.nature.com/articles/s41593-025-02196-7. 
  5. ↑ Salvalaggio, Alessandro; De Filippo De Grazia, Michele; Zorzi, Marco; Thiebaut de Schotten, Michel; Corbetta, Maurizio (2020-07-01). "Post-stroke deficit prediction from lesion and indirect structural and functional disconnection" (in en). Brain 143 (7): 2173–2188. doi:10.1093/brain/awaa156. ISSN 0006-8950. PMID 32572442. PMC 7363494. https://academic.oup.com/brain/article/143/7/2173/5861020. 
  6. ↑ Sperber, Christoph; Dadashi, Amin (2020-05-01). "The influence of sample size and arbitrary statistical thresholds in lesion-network mapping" (in en). Brain 143 (5): e40–e40. doi:10.1093/brain/awaa094. ISSN 0006-8950. https://academic.oup.com/brain/article/143/5/e40/5829675. 
  7. ↑ Joutsa, Juho; Corp, Daniel T.; Fox, Michael D. (2022-08-01). "Lesion network mapping for symptom localization: recent developments and future directions". Current Opinion in Neurology 35 (4): 453–459. doi:10.1097/WCO.0000000000001085. ISSN 1473-6551. PMID 35788098. 
  8. ↑ Nabizadeh, Fardin; Aarabi, Mohammad Hadi (2023-06-30). "Functional and structural lesion network mapping in neurological and psychiatric disorders: a systematic review". Frontiers in Neurology 14. doi:10.3389/fneur.2023.1100067. ISSN 1664-2295. PMID 37456650. 
  9. ↑ Bowren, Mark; Bruss, Joel; Manzel, Kenneth; Edwards, Dylan; Liu, Charles; Corbetta, Maurizio; Tranel, Daniel; Boes, Aaron D. (2022-05-24). "Post-stroke outcomes predicted from multivariate lesion-behaviour and lesion network mapping". Brain: A Journal of Neurology 145 (4): 1338–1353. doi:10.1093/brain/awac010. ISSN 1460-2156. PMID 35025994. 
  10. ↑ Jimenez-Marin, A.; De Bruyn, N.; Gooijers, J.; Llera, A.; Meyer, S.; Alaerts, K.; Verheyden, G.; Swinnen, S. P. et al. (2022-12-27). "Multimodal and multidomain lesion network mapping enhances prediction of sensorimotor behavior in stroke patients". Scientific Reports 12 (1): 22400. doi:10.1038/s41598-022-26945-x. ISSN 2045-2322. PMID 36575263. Bibcode: 2022NatSR..1222400J. 
  11. ↑ Bowren, Mark; Bruss, Joel; Manzel, Kenneth; Edwards, Dylan; Liu, Charles; Corbetta, Maurizio; Tranel, Daniel; Boes, Aaron D (2022-05-24). "Post-stroke outcomes predicted from multivariate lesion-behaviour and lesion network mapping" (in en). Brain 145 (4): 1338–1353. doi:10.1093/brain/awac010. ISSN 0006-8950. PMID 35025994. PMC 9630711. https://academic.oup.com/brain/article/145/4/1338/6506442. 
  12. ↑ Darby, R. Ryan; Laganiere, Simon; Pascual-Leone, Alvaro; Prasad, Sashank; Fox, Michael D. (February 2017). "Finding the imposter: brain connectivity of lesions causing delusional misidentifications". Brain: A Journal of Neurology 140 (2): 497–507. doi:10.1093/brain/aww288. ISSN 1460-2156. PMID 28082298. 
  13. ↑ Diamantaras, A. A.; Blondiaux, E.; Schumacher, R.; Müri, R. M.; Blanke, O.; Heydrich, L. (2023-07-10). "The neuropsychology and neuroanatomy of reduplicative paramnesia". Cortex; A Journal Devoted to the Study of the Nervous System and Behavior 167: 12–24. doi:10.1016/j.cortex.2023.06.006. ISSN 1973-8102. PMID 37515831. 
  14. ↑ 14.0 14.1 Darby, R. Ryan; Joutsa, Juho; Burke, Matthew J.; Fox, Michael D. (2018-10-16). "Lesion network localization of free will". Proceedings of the National Academy of Sciences of the United States of America 115 (42): 10792–10797. doi:10.1073/pnas.1814117115. ISSN 1091-6490. PMID 30275309. Bibcode: 2018PNAS..11510792D. 
  15. ↑ Kletenik, Isaiah; Ferguson, Michael A.; Bateman, James R.; Cohen, Alexander L.; Lin, Christopher; Tetreault, Aaron; Pelak, Victoria S.; Anderson, Clark Alan et al. (February 2022). "Network Localization of Unconscious Visual Perception in Blindsight". Annals of Neurology 91 (2): 217–224. doi:10.1002/ana.26292. ISSN 1531-8249. PMID 34961965. 
  16. ↑ Kletenik, Isaiah; Gaudet, Kyla; Prasad, Sashank; Cohen, Alexander L.; Fox, Michael D. (2023-06-08). "Network Localization of Awareness in Visual and Motor Anosognosia". Annals of Neurology 94 (3): 434–441. doi:10.1002/ana.26709. ISSN 1531-8249. PMID 37289520. 
  17. ↑ Schaper, Frederic L. W. V. J.; Nordberg, Janne; Cohen, Alexander L.; Lin, Christopher; Hsu, Joey; Horn, Andreas; Ferguson, Michael A.; Siddiqi, Shan H. et al. (2023-07-03). "Mapping Lesion-Related Epilepsy to a Human Brain Network" (in en). JAMA Neurology 80 (9): 891–902. doi:10.1001/jamaneurol.2023.1988. ISSN 2168-6149. PMID 37399040. 
  18. ↑ Wawrzyniak, Max; Schneider, Hans R.; Klingbeil, Julian; Stockert, Anika; Hartwigsen, Gesa; Weiller, Cornelius; Saur, Dorothee (2022-05-01). "Resolution of diaschisis contributes to early recovery from post-stroke aphasia". NeuroImage 251. doi:10.1016/j.neuroimage.2022.119001. ISSN 1095-9572. PMID 35172200. 
  19. ↑ Ferguson, Michael A.; Lim, Chun; Cooke, Danielle; Darby, R. Ryan; Wu, Ona; Rost, Natalia S.; Corbetta, Maurizio; Grafman, Jordan et al. (2019-08-02). "A human memory circuit derived from brain lesions causing amnesia" (in en). Nature Communications 10 (1): 3497. doi:10.1038/s41467-019-11353-z. ISSN 2041-1723. PMID 31375668. Bibcode: 2019NatCo..10.3497F. 
  20. ↑ Joutsa, Juho; Horn, Andreas; Hsu, Joey; Fox, Michael D. (2018-08-01). "Localizing parkinsonism based on focal brain lesions". Brain: A Journal of Neurology 141 (8): 2445–2456. doi:10.1093/brain/awy161. ISSN 1460-2156. PMID 29982424. 
  21. ↑ Roseman, Moshe; Elias, Uri; Kletenik, Isaiah; Ferguson, Michael A.; Fox, Michael D.; Horowitz, Zalman; Marshall, Gad A.; Spiers, Hugo J. et al. (2023-12-13). "A neural circuit for spatial orientation derived from brain lesions". Cerebral Cortex 34 (1). doi:10.1093/cercor/bhad486. ISSN 1460-2199. PMID 38100330. 
  22. ↑ Taylor, Joseph J.; Lin, Christopher; Talmasov, Daniel; Ferguson, Michael A.; Schaper, Frederic L. W. V. J.; Jiang, Jing; Goodkind, Madeleine; Grafman, Jordan et al. (March 2023). "A transdiagnostic network for psychiatric illness derived from atrophy and lesions". Nature Human Behaviour 7 (3): 420–429. doi:10.1038/s41562-022-01501-9. ISSN 2397-3374. PMID 36635585. 
  23. ↑ Padmanabhan, Jaya L.; Cooke, Danielle; Joutsa, Juho; Siddiqi, Shan H.; Ferguson, Michael; Darby, R. Ryan; Soussand, Louis; Horn, Andreas et al. (2019-11-15). "A Human Depression Circuit Derived From Focal Brain Lesions". Biological Psychiatry 86 (10): 749–758. doi:10.1016/j.biopsych.2019.07.023. ISSN 1873-2402. PMID 31561861. 
  24. ↑ 24.0 24.1 Siddiqi, Shan H.; Schaper, Frederic L. W. V. J.; Horn, Andreas; Hsu, Joey; Padmanabhan, Jaya L.; Brodtmann, Amy; Cash, Robin F. H.; Corbetta, Maurizio et al. (2021-07-08). "Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease" (in en). Nature Human Behaviour 5 (12): 1707–1716. doi:10.1038/s41562-021-01161-1. ISSN 2397-3374. PMID 34239076. 
  25. ↑ Cotovio, Gonçalo; Talmasov, Daniel; Barahona-Corrêa, J. Bernardo; Hsu, Joey; Senova, Suhan; Ribeiro, Ricardo; Soussand, Louis; Velosa, Ana et al. (2020-10-01). "Mapping mania symptoms based on focal brain damage". The Journal of Clinical Investigation 130 (10): 5209–5222. doi:10.1172/JCI136096. ISSN 1558-8238. PMID 32831292. 
  26. ↑ 26.0 26.1 Ferguson, Michael A.; Schaper, Frederic L. W. V. J.; Cohen, Alexander; Siddiqi, Shan; Merrill, Sarah M.; Nielsen, Jared A.; Grafman, Jordan; Urgesi, Cosimo et al. (2022-02-15). "A Neural Circuit for Spirituality and Religiosity Derived From Patients With Brain Lesions". Biological Psychiatry 91 (4): 380–388. doi:10.1016/j.biopsych.2021.06.016. ISSN 1873-2402. PMID 34454698. 
  27. ↑ Ferguson, Michael A.; Asp, Erik W.; Kletenik, Isaiah; Tranel, Daniel; Boes, Aaron D.; Nelson, Jenae M.; Schaper, Frederic L. W. V. J.; Siddiqi, Shan et al. (2024-09-03). "A neural network for religious fundamentalism derived from patients with brain lesions" (in en). Proceedings of the National Academy of Sciences 121 (36). doi:10.1073/pnas.2322399121. ISSN 0027-8424. PMID 39190343. Bibcode: 2024PNAS..12122399F. 
  28. ↑ Fischer, David B.; Boes, Aaron D.; Demertzi, Athena; Evrard, Henry C.; Laureys, Steven; Edlow, Brian L.; Liu, Hesheng; Saper, Clifford B. et al. (2016-12-06). "A human brain network derived from coma-causing brainstem lesions". Neurology 87 (23): 2427–2434. doi:10.1212/WNL.0000000000003404. ISSN 1526-632X. PMID 27815400. 
  29. ↑ Snider, Samuel B.; Hsu, Joey; Darby, R. Ryan; Cooke, Danielle; Fischer, David; Cohen, Alexander L.; Grafman, Jordan H.; Fox, Michael D. (2020-04-15). "Cortical lesions causing loss of consciousness are anticorrelated with the dorsal brainstem". Human Brain Mapping 41 (6): 1520–1531. doi:10.1002/hbm.24892. ISSN 1097-0193. PMID 31904898. 
  30. ↑ Darby, R. Ryan; Horn, Andreas; Cushman, Fiery; Fox, Michael D. (2018-01-16). "Lesion network localization of criminal behavior" (in en). Proceedings of the National Academy of Sciences 115 (3): 601–606. doi:10.1073/pnas.1706587115. ISSN 0027-8424. PMID 29255017. Bibcode: 2018PNAS..115..601D. 
  31. ↑ Joutsa, Juho; Moussawi, Khaled; Siddiqi, Shan H.; Abdolahi, Amir; Drew, William; Cohen, Alexander L.; Ross, Thomas J.; Deshpande, Harshawardhan U. et al. (June 2022). "Brain lesions disrupting addiction map to a common human brain circuit" (in en). Nature Medicine 28 (6): 1249–1255. doi:10.1038/s41591-022-01834-y. ISSN 1078-8956. PMID 35697842. 
  32. ↑ Cohen, Alexander L.; Mulder, Brechtje P. F.; Prohl, Anna K.; Soussand, Louis; Davis, Peter; Kroeck, Mallory R.; McManus, Peter; Gholipour, Ali et al. (April 2021). "Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network" (in en). Annals of Neurology 89 (4): 726–739. doi:10.1002/ana.26015. ISSN 0364-5134. PMID 33410532. 
  33. ↑ Cohen, Alexander L.; Kroeck, Mallory R.; Wall, Juliana; McManus, Peter; Ovchinnikova, Arina; Sahin, Mustafa; Krueger, Darcy A.; Bebin, E. Martina et al. (March 2023). "Tubers Affecting the Fusiform Face Area Are Associated with Autism Diagnosis" (in en). Annals of Neurology 93 (3): 577–590. doi:10.1002/ana.26551. ISSN 0364-5134. PMID 36394118. 
  34. ↑ Kletenik, Isaiah; Cohen, Alexander L.; Glanz, Bonnie I.; Ferguson, Michael A.; Tauhid, Shahamat; Li, Jing; Drew, William; Polgar-Turcsanyi, Mariann et al. (2023-08-02). "Multiple sclerosis lesions that impair memory map to a connected memory circuit". Journal of Neurology 270 (11): 5211–5222. doi:10.1007/s00415-023-11907-8. ISSN 1432-1459. PMID 37532802. 
  35. ↑ Siddiqi, Shan H.; Kletenik, Isaiah; Anderson, Mark C.; Cavallari, Michele; Chitnis, Tanuja; Glanz, Bonnie I.; Khalil, Samar; Palotai, Miklos et al. (2023-01-19). "Lesion network localization of depression in multiple sclerosis" (in en). Nature Mental Health 1 (1): 36–44. doi:10.1038/s44220-022-00002-y. ISSN 2731-6076. 
  36. ↑ Horn, Andreas; Reich, Martin M.; Ewert, Siobhan; Li, Ningfei; Al-Fatly, Bassam; Lange, Florian; Roothans, Jonas; Oxenford, Simon et al. (2022-04-05). "Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia" (in en). Proceedings of the National Academy of Sciences 119 (14). doi:10.1073/pnas.2114985119. ISSN 0027-8424. PMID 35357970. Bibcode: 2022PNAS..11914985H. 
  37. ↑ Mueller, Benjamin (2022-06-13). "They Were Cigarette Smokers. Then a Stroke Vanquished Their Addiction." (in en-US). The New York Times. ISSN 0362-4331. https://www.nytimes.com/2022/06/13/health/cigarette-smokers-stroke-addiction.html. 
  38. ↑ Gholipour, Bahar (January 2019). "How Brain Injuries Deprive People of a Sense of Free Will" (in en). https://www.scientificamerican.com/article/how-brain-injuries-deprive-people-of-a-sense-of-free-will/. 
  39. ↑ "Spirituality and sense of awe seem to be hard-wired into our brains, researchers find" (in en-US). https://www.usatoday.com/story/news/health/2021/07/07/brain-circuit-spirituality-identified-harvard-study-shows/7843716002/. 



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