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 technique was developed by Michael D. Fox and Aaron Boes to understand the network anatomy of lesion induced neurologic and psychiatric symptoms that can not be explained by focal anatomic localization.[4][5] 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.[6]

Lesion network mapping has helped map the network anatomy of numerous rare neurologic syndromes (peduncular hallucinosis,[1] delusional misidentification,[7] reduplicative paramensia,[8] akinetic mutism,[9] blindsight,[10] visual anosognosia[11]), common neurologic syndromes (seizures,[12] aphasia,[13] amnesia,[14] parkinsonism,[15] topographical disorientation[16]), psychiatric syndromes[17] (depression,[18][19] mania[20]), as well as complex human behaviors (religiosity,[21] consciousness,[22][23] free will,[9] criminality,[24] addiction[25]). The technique has been successfully applied to a broad range of diseases and lesion types including lesions due to stroke,[1] traumatic brain injury,[21] tuberous sclerosis[26][27] and multiple sclerosis.[28][29] The technique has been broadened to map the connectivity of locations from transcranial magnetic stimulation[19] and deep brain stimulation[30] sites to understand treatment responsiveness.

Research findings based on lesion network mapping have been reported in the New York Times,[31] Scientific American[32] and USA Today[33] and the term has been included in the New England Journal of Medicine's general medical glossary.[3]

References

  1. 1 2 3 4 5 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. PMC 4671478. PMID 26264514.
  2. 1 2 3 Fox, Michael D. (2018-12-06). "Mapping Symptoms to Brain Networks with the Human Connectome". New England Journal of Medicine. 379 (23): 2237–2245. doi:10.1056/NEJMra1706158. ISSN 0028-4793. PMID 30575457. S2CID 58666837.
  3. 1 2 NEJM. "Illustrated Glossary - NEJM". New England Journal of Medicine. Retrieved 2023-08-18.
  4. ↑ 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. PMC 9724189. PMID 35788098.
  5. ↑ 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. PMC 10349201. PMID 37456650.
  6. ↑ 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. PMC 9630711. PMID 35025994.
  7. ↑ 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. PMC 5278302. PMID 28082298.
  8. ↑ 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.
  9. 1 2 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. Bibcode:2018PNAS..11510792D. doi:10.1073/pnas.1814117115. ISSN 1091-6490. PMC 6196503. PMID 30275309.
  10. ↑ Kletenik, Isaiah; Ferguson, Michael A.; Bateman, James R.; Cohen, Alexander L.; Lin, Christopher; Tetreault, Aaron; Pelak, Victoria S.; Anderson, Clark Alan; Prasad, Sashank; Darby, Richard Ryan; Fox, Michael D. (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. PMC 10013845. PMID 34961965.
  11. ↑ 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. doi:10.1002/ana.26709. ISSN 1531-8249. PMID 37289520. S2CID 259119253.
  12. ↑ Schaper, Frederic L. W. V. J.; Nordberg, Janne; Cohen, Alexander L.; Lin, Christopher; Hsu, Joey; Horn, Andreas; Ferguson, Michael A.; Siddiqi, Shan H.; Drew, William; Soussand, Louis; Winkler, Anderson M.; Simó, Marta; Bruna, Jordi; Rheims, Sylvain; Guenot, Marc (2023-07-03). "Mapping Lesion-Related Epilepsy to a Human Brain Network". JAMA Neurology. doi:10.1001/jamaneurol.2023.1988. ISSN 2168-6149. PMC 10318550. PMID 37399040.
  13. ↑ 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: 119001. doi:10.1016/j.neuroimage.2022.119001. ISSN 1095-9572. PMID 35172200.
  14. ↑ Ferguson, Michael A.; Lim, Chun; Cooke, Danielle; Darby, R. Ryan; Wu, Ona; Rost, Natalia S.; Corbetta, Maurizio; Grafman, Jordan; Fox, Michael D. (2019-08-02). "A human memory circuit derived from brain lesions causing amnesia". Nature Communications. 10 (1): 3497. Bibcode:2019NatCo..10.3497F. doi:10.1038/s41467-019-11353-z. ISSN 2041-1723. PMC 6677746. PMID 31375668.
  15. ↑ 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. PMC 6061866. PMID 29982424.
  16. ↑ Roseman, Moshe; Elias, Uri; Kletenik, Isaiah; Ferguson, Michael A.; Fox, Michael D.; Horowitz, Zalman; Marshall, Gad A.; Spiers, Hugo J.; Arzy, Shahar (2023-12-13). "A neural circuit for spatial orientation derived from brain lesions". Cerebral Cortex (New York, N.Y.: 1991): bhad486. doi:10.1093/cercor/bhad486. ISSN 1460-2199. PMID 38100330.
  17. ↑ Taylor, Joseph J.; Lin, Christopher; Talmasov, Daniel; Ferguson, Michael A.; Schaper, Frederic L. W. V. J.; Jiang, Jing; Goodkind, Madeleine; Grafman, Jordan; Etkin, Amit; Siddiqi, Shan H.; Fox, Michael D. (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. PMC 10236501. PMID 36635585.
  18. ↑ Padmanabhan, Jaya L.; Cooke, Danielle; Joutsa, Juho; Siddiqi, Shan H.; Ferguson, Michael; Darby, R. Ryan; Soussand, Louis; Horn, Andreas; Kim, Na Young; Voss, Joel L.; Naidech, Andrew M.; Brodtmann, Amy; Egorova, Natalia; Gozzi, Sophia; Phan, Thanh G. (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. PMC 7531583. PMID 31561861.
  19. 1 2 Siddiqi, Shan H.; Schaper, Frederic L. W. V. J.; Horn, Andreas; Hsu, Joey; Padmanabhan, Jaya L.; Brodtmann, Amy; Cash, Robin F. H.; Corbetta, Maurizio; Choi, Ki Sueng; Dougherty, Darin D.; Egorova, Natalia; Fitzgerald, Paul B.; George, Mark S.; Gozzi, Sophia A.; Irmen, Frederike (2021-07-08). "Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease". Nature Human Behaviour. 5 (12): 1707–1716. doi:10.1038/s41562-021-01161-1. hdl:11577/3398294. ISSN 2397-3374. PMC 8688172. PMID 34239076.
  20. ↑ Cotovio, Gonçalo; Talmasov, Daniel; Barahona-Corrêa, J. Bernardo; Hsu, Joey; Senova, Suhan; Ribeiro, Ricardo; Soussand, Louis; Velosa, Ana; Silva, Vera Cruz E.; Rost, Natalia; Wu, Ona; Cohen, Alexander L.; Oliveira-Maia, Albino J.; Fox, Michael D. (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. PMC 7524493. PMID 32831292.
  21. 1 2 Ferguson, Michael A.; Schaper, Frederic L. W. V. J.; Cohen, Alexander; Siddiqi, Shan; Merrill, Sarah M.; Nielsen, Jared A.; Grafman, Jordan; Urgesi, Cosimo; Fabbro, Franco; Fox, Michael D. (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. PMC 8714871. PMID 34454698.
  22. ↑ Fischer, David B.; Boes, Aaron D.; Demertzi, Athena; Evrard, Henry C.; Laureys, Steven; Edlow, Brian L.; Liu, Hesheng; Saper, Clifford B.; Pascual-Leone, Alvaro; Fox, Michael D.; Geerling, Joel C. (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. PMC 5177681. PMID 27815400.
  23. ↑ 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. PMC 7268053. PMID 31904898.
  24. ↑ Darby, R. Ryan; Horn, Andreas; Cushman, Fiery; Fox, Michael D. (2018-01-16). "Lesion network localization of criminal behavior". Proceedings of the National Academy of Sciences. 115 (3): 601–606. Bibcode:2018PNAS..115..601D. doi:10.1073/pnas.1706587115. ISSN 0027-8424. PMC 5776958. PMID 29255017.
  25. ↑ Joutsa, Juho; Moussawi, Khaled; Siddiqi, Shan H.; Abdolahi, Amir; Drew, William; Cohen, Alexander L.; Ross, Thomas J.; Deshpande, Harshawardhan U.; Wang, Henry Z.; Bruss, Joel; Stein, Elliot A.; Volkow, Nora D.; Grafman, Jordan H.; van Wijngaarden, Edwin; Boes, Aaron D. (June 2022). "Brain lesions disrupting addiction map to a common human brain circuit". Nature Medicine. 28 (6): 1249–1255. doi:10.1038/s41591-022-01834-y. ISSN 1078-8956. PMC 9205767. PMID 35697842.
  26. ↑ Cohen, Alexander L.; Mulder, Brechtje P. F.; Prohl, Anna K.; Soussand, Louis; Davis, Peter; Kroeck, Mallory R.; McManus, Peter; Gholipour, Ali; Scherrer, Benoit; Bebin, E. Martina; Wu, Joyce Y.; Northrup, Hope; Krueger, Darcy A.; Sahin, Mustafa; Warfield, Simon K. (April 2021). "Tuber Locations Associated with Infantile Spasms Map to a Common Brain Network". Annals of Neurology. 89 (4): 726–739. doi:10.1002/ana.26015. ISSN 0364-5134. PMC 7969435. PMID 33410532.
  27. ↑ Cohen, Alexander L.; Kroeck, Mallory R.; Wall, Juliana; McManus, Peter; Ovchinnikova, Arina; Sahin, Mustafa; Krueger, Darcy A.; Bebin, E. Martina; Northrup, Hope; Wu, Joyce Y.; Warfield, Simon K.; Peters, Jurriaan M.; Fox, Michael D.; the Tuberous Sclerosis Complex Autism Center of Excellence Network Study Group (March 2023). "Tubers Affecting the Fusiform Face Area Are Associated with Autism Diagnosis". Annals of Neurology. 93 (3): 577–590. doi:10.1002/ana.26551. ISSN 0364-5134. PMC 9974824. PMID 36394118.
  28. ↑ Kletenik, Isaiah; Cohen, Alexander L.; Glanz, Bonnie I.; Ferguson, Michael A.; Tauhid, Shahamat; Li, Jing; Drew, William; Polgar-Turcsanyi, Mariann; Palotai, Miklos; Siddiqi, Shan H.; Marshall, Gad A.; Chitnis, Tanuja; Guttmann, Charles R. G.; Bakshi, Rohit; Fox, Michael D. (2023-08-02). "Multiple sclerosis lesions that impair memory map to a connected memory circuit". Journal of Neurology. doi:10.1007/s00415-023-11907-8. ISSN 1432-1459. PMID 37532802. S2CID 260433348.
  29. ↑ Siddiqi, Shan H.; Kletenik, Isaiah; Anderson, Mark C.; Cavallari, Michele; Chitnis, Tanuja; Glanz, Bonnie I.; Khalil, Samar; Palotai, Miklos; Bakshi, Rohit; Guttmann, Charles R. G.; Fox, Michael D. (2023-01-19). "Lesion network localization of depression in multiple sclerosis". Nature Mental Health. 1 (1): 36–44. doi:10.1038/s44220-022-00002-y. ISSN 2731-6076.
  30. ↑ Horn, Andreas; Reich, Martin M.; Ewert, Siobhan; Li, Ningfei; Al-Fatly, Bassam; Lange, Florian; Roothans, Jonas; Oxenford, Simon; Horn, Isabel; Paschen, Steffen; Runge, Joachim; Wodarg, Fritz; Witt, Karsten; Nickl, Robert C.; Wittstock, Matthias (2022-04-05). "Optimal deep brain stimulation sites and networks for cervical vs. generalized dystonia". Proceedings of the National Academy of Sciences. 119 (14): e2114985119. Bibcode:2022PNAS..11914985H. doi:10.1073/pnas.2114985119. ISSN 0027-8424. PMC 9168456. PMID 35357970.
  31. ↑ Mueller, Benjamin (2022-06-13). "They Were Cigarette Smokers. Then a Stroke Vanquished Their Addiction". The New York Times. ISSN 0362-4331. Retrieved 2023-08-18.
  32. ↑ Gholipour, Bahar. "How Brain Injuries Deprive People of a Sense of Free Will". Scientific American. Retrieved 2023-08-18.
  33. ↑ "Spirituality and sense of awe seem to be hard-wired into our brains, researchers find". USA TODAY. Retrieved 2023-08-18.
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