Dysfunctome

thumb|Fiber bundles that are dysfunctional and when suppressed associated with symptom improvement following deep brain stimulation in Parkinson's disease (green), dystonia (yellow), Tourette's syndrome (blue), and obsessive-compulsive disorder (red).<ref>{{Cite journal |last1=Hollunder |first1=Barbara |last2=Ostrem |first2=Jill L. |last3=Sahin |first3=Ilkem Aysu |last4=Rajamani |first4=Nanditha |last5=Oxenford |first5=Simón |last6=Butenko |first6=Konstantin |last7=Neudorfer |first7=Clemens |last8=Reinhardt |first8=Pablo |last9=Zvarova |first9=Patricia |last10=Polosan |first10=Mircea |last11=Akram |first11=Harith |last12=Vissani |first12=Matteo |last13=Zhang |first13=Chencheng |last14=Sun |first14=Bomin |last15=Navratil |first15=Pavel |date=March 2024 |title=Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation |journal=Nature Neuroscience |language=en |volume=27 |issue=3 |pages=573–586 |doi=10.1038/s41593-024-01570-1 |issn=1097-6256 |pmc=10917675 |pmid=38388734}}</ref> The '''dysfunctome''' is a proposed conceptual framework<ref>{{Cite journal |last1=Hollunder |first1=Barbara |last2=Ostrem |first2=Jill L. |last3=Sahin |first3=Ilkem Aysu |last4=Rajamani |first4=Nanditha |last5=Oxenford |first5=Simón |last6=Butenko |first6=Konstantin |last7=Neudorfer |first7=Clemens |last8=Reinhardt |first8=Pablo |last9=Zvarova |first9=Patricia |last10=Polosan |first10=Mircea |last11=Akram |first11=Harith |last12=Vissani |first12=Matteo |last13=Zhang |first13=Chencheng |last14=Sun |first14=Bomin |last15=Navratil |first15=Pavel |date=March 2024 |title=Mapping dysfunctional circuits in the frontal cortex using deep brain stimulation |journal=Nature Neuroscience |language=en |volume=27 |issue=3 |pages=573–586 |doi=10.1038/s41593-024-01570-1 |issn=1097-6256 |pmc=10917675 |pmid=38388734}}</ref> that describes a library of circuits that may become dysfunctional in the human brain as a consequence of various brain disorders.<ref>{{Cite web |last=Cho |first=SungJun |date=2024-04-27 |title=How scientists are building a library of the brain's dysfunctional pathways |url=https://oxsci.org/how-scientists-are-building-a-library-of-the-brains-dysfunctional-pathways/ |access-date=2025-01-11 |website=The Oxford Scientist |language=en-GB}}</ref><ref>{{Cite web |title=Unveiling the True Colors of the 'Dysfunctome' |url=https://brain.harvard.edu/hbi_news/unveiling-the-true-colors-of-the-dysfunctome/ |access-date=2025-01-11 |website=Harvard Brain Science Initiative |language=en-US}}</ref><ref>{{Cite web |date=2024-04-16 |title=Drafting a 'dysfunctome': Faulty connections to subthalamic nucleus characterize disparate brain disorders |url=https://www.thetransmitter.org/connectivity/drafting-a-dysfunctome-faulty-connections-to-subthalamic-nucleus-characterize-disparate-brain-disorders/ |access-date=2025-01-11 |website=The Transmitter: Neuroscience News and Perspectives |language=en-US}}</ref> 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'<ref>{{Cite journal |last1=Vedam-Mai |first1=Vinata |last2=Deisseroth |first2=Karl |last3=Giordano |first3=James |last4=Lazaro-Munoz |first4=Gabriel |last5=Chiong |first5=Winston |last6=Suthana |first6=Nanthia |last7=Langevin |first7=Jean-Philippe |last8=Gill |first8=Jay |last9=Goodman |first9=Wayne |last10=Provenza |first10=Nicole R. |last11=Halpern |first11=Casey H. |last12=Shivacharan |first12=Rajat S. |last13=Cunningham |first13=Tricia N. |last14=Sheth |first14=Sameer A. |last15=Pouratian |first15=Nader |date=2021-04-19 |title=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 |journal=Frontiers in Human Neuroscience |volume=15 |doi=10.3389/fnhum.2021.644593 |doi-access=free |issn=1662-5161 |pmc=8092047 |pmid=33953663}}</ref> or 'disorders of the connectome'.<ref>{{Cite journal |last1=van den Heuvel |first1=Martijn P. |last2=Sporns |first2=Olaf |date=July 2019 |title=A cross-disorder connectome landscape of brain dysconnectivity |journal=Nature Reviews Neuroscience |language=en |volume=20 |issue=7 |pages=435–446 |doi=10.1038/s41583-019-0177-6 |issn=1471-003X |pmc=8864539 |pmid=31127193}}</ref> 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.<ref>{{Cite journal |last1=Coenen |first1=Volker Arnd |last2=Sajonz |first2=Bastian |last3=Prokop |first3=Thomas |last4=Reisert |first4=Marco |last5=Piroth |first5=Tobias |last6=Urbach |first6=Horst |last7=Jenkner |first7=Carolin |last8=Reinacher |first8=Peter Christoph |date=May 2020 |title=The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: an observational case series |journal=Acta Neurochirurgica |language=en |volume=162 |issue=5 |pages=1053–1066 |doi=10.1007/s00701-020-04248-2 |issn=0001-6268 |pmc=7156360 |pmid=31997069}}</ref> Similarly, a common circuit involved in obsessive compulsive behavior has been identified to play a role in OCD and Tourette's Syndrome.<ref>{{Cite journal |last1=Johnson |first1=Kara A. |last2=Duffley |first2=Gordon |last3=Foltynie |first3=Thomas |last4=Hariz |first4=Marwan |last5=Zrinzo |first5=Ludvic |last6=Joyce |first6=Eileen M. |last7=Akram |first7=Harith |last8=Servello |first8=Domenico |last9=Galbiati |first9=Tommaso F. |last10=Bona |first10=Alberto |last11=Porta |first11=Mauro |last12=Meng |first12=Fan-Gang |last13=Leentjens |first13=Albert F.G. |last14=Gunduz |first14=Aysegul |last15=Hu |first15=Wei |date=October 2021 |title=Basal Ganglia Pathways Associated With Therapeutic Pallidal Deep Brain Stimulation for Tourette Syndrome |journal=Biological Psychiatry: Cognitive Neuroscience and Neuroimaging |language=en |volume=6 |issue=10 |pages=961–972 |doi=10.1016/j.bpsc.2020.11.005 |pmc=8864935 |pmid=33536144}}</ref>

Finally, a shared polysynaptic brain network has been associated with the occurrence of depression in Major depression, epilepsy and Parkinson's Disease.<ref>{{Cite journal |last1=Siddiqi |first1=Shan H. |last2=Schaper |first2=Frederic L. W. V. J. |last3=Horn |first3=Andreas |last4=Hsu |first4=Joey |last5=Padmanabhan |first5=Jaya L. |last6=Brodtmann |first6=Amy |last7=Cash |first7=Robin F. H. |last8=Corbetta |first8=Maurizio |last9=Choi |first9=Ki Sueng |last10=Dougherty |first10=Darin D. |last11=Egorova |first11=Natalia |last12=Fitzgerald |first12=Paul B. |last13=George |first13=Mark S. |last14=Gozzi |first14=Sophia A. |last15=Irmen |first15=Frederike |date=2021-07-08 |title=Brain stimulation and brain lesions converge on common causal circuits in neuropsychiatric disease |journal=Nature Human Behaviour |language=en |volume=5 |issue=12 |pages=1707–1716 |doi=10.1038/s41562-021-01161-1 |issn=2397-3374 |pmc=8688172 |pmid=34239076|hdl=11577/3398294 }}</ref> 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.<ref>{{Cite journal |last1=Tozzi |first1=Leonardo |last2=Staveland |first2=Brooke |last3=Holt-Gosselin |first3=Bailey |last4=Chesnut |first4=Megan |last5=Chang |first5=Sarah E. |last6=Choi |first6=David |last7=Shiner |first7=Melissa |last8=Wu |first8=Hua |last9=Lerma-Usabiaga |first9=Garikoitz |last10=Sporns |first10=Olaf |last11=Barch |first11=Deanna M. |last12=Gotlib |first12=Ian H. |last13=Hastie |first13=Trevor J. |last14=Kerr |first14=Adam B. |last15=Poldrack |first15=Russell A. |date=July 2020 |title=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 |journal=NeuroImage |language=en |volume=214 |article-number=116715 |doi=10.1016/j.neuroimage.2020.116715 |pmc=8597395 |pmid=32147367}}</ref><ref>{{Cite journal |last1=Van Essen |first1=David C. |last2=Barch |first2=Deanna M. |date=June 2015 |title=The human connectome in health and psychopathology |journal=World Psychiatry |language=en |volume=14 |issue=2 |pages=154–157 |doi=10.1002/wps.20228 |pmc=4471963 |pmid=26043324}}</ref>

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.<ref>{{Cite journal |date=March 2024 |title=Mapping the dysfunctome provides an avenue for targeted brain circuit therapy |url=https://www.nature.com/articles/s41593-024-01572-z |journal=Nature Neuroscience |language=en |volume=27 |issue=3 |pages=401–402 |doi=10.1038/s41593-024-01572-z |pmid=38388735 |issn=1097-6256|url-access=subscription }}</ref>

== 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).<ref>{{Cite web |title=Unveiling the True Colors of the 'Dysfunctome' |url=https://brain.harvard.edu/hbi_news/unveiling-the-true-colors-of-the-dysfunctome/ |access-date=2025-01-11 |website=Harvard Brain Science Initiative |language=en-US}}</ref> 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.<ref>{{Cite journal |date=March 2024 |title=Mapping the dysfunctome provides an avenue for targeted brain circuit therapy |url=https://www.nature.com/articles/s41593-024-01572-z |journal=Nature Neuroscience |language=en |volume=27 |issue=3 |pages=401–402 |doi=10.1038/s41593-024-01572-z |pmid=38388735 |issn=1097-6256|url-access=subscription }}</ref>

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Category:Brain anatomy Category:Omics Category:Neuroscience Category:Neurology Category:Psychiatry