Biology:Dysfunctome

From HandWiki

The dysfunctome is a proposed conceptual framework[1] that describes a library of circuits that may become dysfunctional in the human brain as a consequence of various brain disorders.[2][3][4] Analogous to terms like the genome (the total genetic information of an organism), the proteome (the entire set of proteins expressed) and the connectome (the parts of the entire brain and their interconnections) the dysfunctome aims to map out how disruptions—of whichever nature—contribute to disease states and pathological signs or symptoms if specific brain circuits become dysfunctional.

Description

An increasingly adopted view is that many symptoms of neurological or psychiatric diseases originate from brain circuit dysfunctions, which have also been termed 'oscillopathies'[5] or 'disorders of the connectome'.[6] Indeed, evidence accumulates, that the same circuit may be responsible for the same symptom as expressed by patients with different diseases. Examples include a dysfunctional circuit between cerebellar nuclei, the cerebellar receiving thalamus and primary motor cortex, which has been associated with various forms of tremor in disorders such as Parkinson's Disease, Essential Tremor, Multiple Sclerosis and other disorders.[7] Similarly, a common circuit involved in obsessive compulsive behavior has been identified to play a role in OCD and Tourette's Syndrome.[8]

Finally, a shared polysynaptic brain network has been associated with the occurrence of depression in Major depression, epilepsy and Parkinson's Disease.[9] This transnosologic view, which associates brain circuit disruption with symptoms, rather with disorders, is also reflected by the Research Domain Criteria (RDoC) concept by the National Institutes of Mental Health.[10][11]

In this light, the hypothetical concept of the dysfunctome aims at constructing an exhaustive library that maps circuits, which, when dysfunctional, will lead to a given neurological or psychiatric symptom. Critically, the concept does not specify the nature of the dysfunction, which could include hyper-/hypoactivity, loss of sensible information processing, microseizures or other disruptions that could unfold along brain circuits.[12]

Etymology

The term "dysfunctome" combines "dysfunction," referring to the impaired or abnormal functioning of processes, with the suffix "-ome," commonly used to denote a totality or complete set (e.g., genome, metabolome, microbiome).[13] The concept underscores the importance of comprehensive, system-wide approaches to understanding diseases, moving beyond the study of individual brain circuits or individual pathological symptoms.[14]

See also

References

  1. ↑ Hollunder, Barbara; Ostrem, Jill L.; Sahin, Ilkem Aysu; Rajamani, Nanditha; Oxenford, Simón; Butenko, Konstantin; Neudorfer, Clemens; Reinhardt, Pablo et al. (March 2024). "Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation" (in en). Nature Neuroscience 27 (3): 573–586. doi:10.1038/s41593-024-01570-1. ISSN 1097-6256. PMID 38388734. 
  2. ↑ Cho, SungJun (2024-04-27). "How scientists are building a library of the brain's dysfunctional pathways" (in en-GB). https://oxsci.org/how-scientists-are-building-a-library-of-the-brains-dysfunctional-pathways/. 
  3. ↑ "Unveiling the True Colors of the 'Dysfunctome'" (in en-US). https://brain.harvard.edu/hbi_news/unveiling-the-true-colors-of-the-dysfunctome/. 
  4. ↑ "Drafting a 'dysfunctome': Faulty connections to subthalamic nucleus characterize disparate brain disorders" (in en-US). 2024-04-16. https://www.thetransmitter.org/connectivity/drafting-a-dysfunctome-faulty-connections-to-subthalamic-nucleus-characterize-disparate-brain-disorders/. 
  5. ↑ Vedam-Mai, Vinata; Deisseroth, Karl; Giordano, James; Lazaro-Munoz, Gabriel; Chiong, Winston; Suthana, Nanthia; Langevin, Jean-Philippe; Gill, Jay et al. (2021-04-19). "Proceedings of the Eighth Annual Deep Brain Stimulation Think Tank: Advances in Optogenetics, Ethical Issues Affecting DBS Research, Neuromodulatory Approaches for Depression, Adaptive Neurostimulation, and Emerging DBS Technologies". Frontiers in Human Neuroscience 15. doi:10.3389/fnhum.2021.644593. ISSN 1662-5161. PMID 33953663. 
  6. ↑ van den Heuvel, Martijn P.; Sporns, Olaf (July 2019). "A cross-disorder connectome landscape of brain dysconnectivity" (in en). Nature Reviews Neuroscience 20 (7): 435–446. doi:10.1038/s41583-019-0177-6. ISSN 1471-003X. PMID 31127193. 
  7. ↑ Coenen, Volker Arnd; Sajonz, Bastian; Prokop, Thomas; Reisert, Marco; Piroth, Tobias; Urbach, Horst; Jenkner, Carolin; Reinacher, Peter Christoph (May 2020). "The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: an observational case series" (in en). Acta Neurochirurgica 162 (5): 1053–1066. doi:10.1007/s00701-020-04248-2. ISSN 0001-6268. PMID 31997069. 
  8. ↑ Johnson, Kara A.; Duffley, Gordon; Foltynie, Thomas; Hariz, Marwan; Zrinzo, Ludvic; Joyce, Eileen M.; Akram, Harith; Servello, Domenico et al. (October 2021). "Basal Ganglia Pathways Associated With Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome" (in en). Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 6 (10): 961–972. doi:10.1016/j.bpsc.2020.11.005. PMID 33536144. 
  9. ↑ 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. 
  10. ↑ Tozzi, Leonardo; Staveland, Brooke; Holt-Gosselin, Bailey; Chesnut, Megan; Chang, Sarah E.; Choi, David; Shiner, Melissa; Wu, Hua et al. (July 2020). "The human connectome project for disordered emotional states: Protocol and rationale for a research domain criteria study of brain connectivity in young adult anxiety and depression" (in en). NeuroImage 214. doi:10.1016/j.neuroimage.2020.116715. PMID 32147367. 
  11. ↑ Van Essen, David C.; Barch, Deanna M. (June 2015). "The human connectome in health and psychopathology" (in en). World Psychiatry 14 (2): 154–157. doi:10.1002/wps.20228. PMID 26043324. 
  12. ↑ "Mapping the dysfunctome provides an avenue for targeted brain circuit therapy" (in en). Nature Neuroscience 27 (3): 401–402. March 2024. doi:10.1038/s41593-024-01572-z. ISSN 1097-6256. PMID 38388735. https://www.nature.com/articles/s41593-024-01572-z. 
  13. ↑ "Unveiling the True Colors of the 'Dysfunctome'" (in en-US). https://brain.harvard.edu/hbi_news/unveiling-the-true-colors-of-the-dysfunctome/. 
  14. ↑ "Mapping the dysfunctome provides an avenue for targeted brain circuit therapy" (in en). Nature Neuroscience 27 (3): 401–402. March 2024. doi:10.1038/s41593-024-01572-z. ISSN 1097-6256. PMID 38388735. https://www.nature.com/articles/s41593-024-01572-z. 



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