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| ID | Type | Description | Link |
|---|---|---|---|
| R01DE030464 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute of Dental and Craniofacial Research (NIDCR) | NIH |
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To date, there is only limited knowledge about the distinct neural abnormalities that lead to the development of different forms of focal dystonia. The goal of this study is to dissect the pathophysiological mechanisms underlying this clinical phenomenon using multi-level brain network analysis in patients with focal dystonia.
Among the many causes of craniofacial disease are focal dystonias such as blepharospasm (BSP) and oromandibular dystonia (OMD), affecting the eyes and jaw, respectively, as well as Meige Syndrome, which combines features of both. Craniofacial dystonias are poorly understood and have limited treatment options. The investigators hypothesize that craniofacial dystonia (CFD) may be caused by both rare and common genetic variants. To identify neural correlates of different genetic causes of CFD, the investigators will perform structural and functional whole-brain imaging and examine the organization of the neural network in these patients compared to healthy individuals and their unaffected blood relatives.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patients with dystonia and their unaffected relatives | Patients with dystonia and their unaffected blood relatives will undergo MRI of the brain and blood draw. |
| |
| Healthy volunteers | Healthy subjects without any neurological, psychiatric or otolaryngological problems will undergo MRI of the brain and blood draw. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MRI | Other | Functional and structural MRI of the brain will be conducted to identify disorder specific neural markers |
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| Measure | Description | Time Frame |
|---|---|---|
| Incidence of brain structural and functional changes | Identify changes in brain activity and gray and white matter in patients with dystonia vs. unaffected relatives vs. healthy controls | 5 years |
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Inclusion Criteria:
Exclusion Criteria:
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Patients with focal dystonia, thier unaffected blood relatives, and healthy volunteers
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Kristina Simonyan, MD, PhD | Contact | 617-573-6016 | Simonyan_Lab@MEEI.HARVARD.EDU |
| Name | Affiliation | Role |
|---|---|---|
| Kristina Simonyan, MD, PhD | Massachusetts Eye and Ear Infirmary | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts Eye and Ear | Recruiting | Boston | Massachusetts | 02114 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 26679193 | Result | Battistella G, Termsarasab P, Ramdhani RA, Fuertinger S, Simonyan K. Isolated Focal Dystonia as a Disorder of Large-Scale Functional Networks. Cereb Cortex. 2017 Feb 1;27(2):1203-1215. doi: 10.1093/cercor/bhv313. | |
| 27575646 | Result | Fuertinger S, Simonyan K. Stability of Network Communities as a Function of Task Complexity. J Cogn Neurosci. 2016 Dec;28(12):2030-2043. doi: 10.1162/jocn_a_01026. Epub 2016 Aug 30. |
| Label | URL |
|---|---|
| NIH grant description | View source |
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| ID | Term |
|---|---|
| D055154 | Dysphonia |
| D020821 | Dystonic Disorders |
| D008538 | Meige Syndrome |
| D004421 | Dystonia |
| ID | Term |
|---|---|
| D014832 | Voice Disorders |
| D007818 | Laryngeal Diseases |
| D012140 | Respiratory Tract Diseases |
| D010038 | Otorhinolaryngologic Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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Blood samples will be collected, the DNA will be extracted and banked for genetic studies
| Blood draw | Procedure | Blood samples will be collected, the DNA will be extracted and banked for genetic studies |
|
| 27939583 | Result | Rittiner JE, Caffall ZF, Hernandez-Martinez R, Sanderson SM, Pearson JL, Tsukayama KK, Liu AY, Xiao C, Tracy S, Shipman MK, Hickey P, Johnson J, Scott B, Stacy M, Saunders-Pullman R, Bressman S, Simonyan K, Sharma N, Ozelius LJ, Cirulli ET, Calakos N. Functional Genomic Analyses of Mendelian and Sporadic Disease Identify Impaired eIF2alpha Signaling as a Generalizable Mechanism for Dystonia. Neuron. 2016 Dec 21;92(6):1238-1251. doi: 10.1016/j.neuron.2016.11.012. Epub 2016 Dec 8. |
| 28674168 | Result | Fuertinger S, Simonyan K. Connectome-Wide Phenotypical and Genotypical Associations in Focal Dystonia. J Neurosci. 2017 Aug 2;37(31):7438-7449. doi: 10.1523/JNEUROSCI.0384-17.2017. Epub 2017 Jul 3. |
| 33858994 | Result | Simonyan K, Barkmeier-Kraemer J, Blitzer A, Hallett M, Houde JF, Jacobson Kimberley T, Ozelius LJ, Pitman MJ, Richardson RM, Sharma N, Tanner K; The NIH/NIDCD Workshop on Research Priorities in Spasmodic Dysphonia/Laryngeal Dystonia. Laryngeal Dystonia: Multidisciplinary Update on Terminology, Pathophysiology, and Research Priorities. Neurology. 2021 May 25;96(21):989-1001. doi: 10.1212/WNL.0000000000011922. Epub 2021 Apr 15. |
| 33504639 | Result | Worthley A, Simonyan K. Suicidal Ideations and Attempts in Patients With Isolated Dystonia. Neurology. 2021 Mar 16;96(11):e1551-e1560. doi: 10.1212/WNL.0000000000011596. Epub 2021 Jan 27. |
| 33004625 | Result | Valeriani D, Simonyan K. A microstructural neural network biomarker for dystonia diagnosis identified by a DystoniaNet deep learning platform. Proc Natl Acad Sci U S A. 2020 Oct 20;117(42):26398-26405. doi: 10.1073/pnas.2009165117. Epub 2020 Oct 1. |
| 32311207 | Result | Hanekamp S, Simonyan K. The large-scale structural connectome of task-specific focal dystonia. Hum Brain Mapp. 2020 Aug 15;41(12):3253-3265. doi: 10.1002/hbm.25012. Epub 2020 Apr 20. |
| 31930574 | Result | Maguire F, Reilly RB, Simonyan K. Normal Temporal Discrimination in Musician's Dystonia Is Linked to Aberrant Sensorimotor Processing. Mov Disord. 2020 May;35(5):800-807. doi: 10.1002/mds.27984. Epub 2020 Jan 13. |
| 32098856 | Result | Lungu C, Ozelius L, Standaert D, Hallett M, Sieber BA, Swanson-Fisher C, Berman BD, Calakos N, Moore JC, Perlmutter JS, Pirio Richardson SE, Saunders-Pullman R, Scheinfeldt L, Sharma N, Sillitoe R, Simonyan K, Starr PA, Taylor A, Vitek J; participants and organizers of the NINDS Workshop on Research Priorities in Dystonia. Defining research priorities in dystonia. Neurology. 2020 Mar 24;94(12):526-537. doi: 10.1212/WNL.0000000000009140. Epub 2020 Feb 25. |
| 30582159 | Result | Guiry S, Worthley A, Simonyan K. A separation of innate and learned vocal behaviors defines the symptomatology of spasmodic dysphonia. Laryngoscope. 2019 Jul;129(7):1627-1633. doi: 10.1002/lary.27617. Epub 2018 Dec 24. |
| 30840778 | Result | Bianchi S, Fuertinger S, Huddleston H, Frucht SJ, Simonyan K. Functional and structural neural bases of task specificity in isolated focal dystonia. Mov Disord. 2019 Apr;34(4):555-563. doi: 10.1002/mds.27649. Epub 2019 Mar 6. |
| 30755797 | Result | Simonyan K. Recent advances in understanding the role of the basal ganglia. F1000Res. 2019 Jan 30;8:F1000 Faculty Rev-122. doi: 10.12688/f1000research.16524.1. eCollection 2019. |
| 30264427 | Result | Fuertinger S, Simonyan K. Task-specificity in focal dystonia is shaped by aberrant diversity of a functional network kernel. Mov Disord. 2018 Dec;33(12):1918-1927. doi: 10.1002/mds.97. Epub 2018 Sep 27. |
| 30473192 | Result | Simonyan K. Neuroimaging Applications in Dystonia. Int Rev Neurobiol. 2018;143:1-30. doi: 10.1016/bs.irn.2018.09.007. Epub 2018 Oct 23. |
| 29219190 | Result | Blitzer A, Brin MF, Simonyan K, Ozelius LJ, Frucht SJ. Phenomenology, genetics, and CNS network abnormalities in laryngeal dystonia: A 30-year experience. Laryngoscope. 2018 Jan;128 Suppl 1(Suppl 1):S1-S9. doi: 10.1002/lary.27003. Epub 2017 Dec 8. |
| 28543038 | Result | Mor N, Simonyan K, Blitzer A. Central voice production and pathophysiology of spasmodic dysphonia. Laryngoscope. 2018 Jan;128(1):177-183. doi: 10.1002/lary.26655. Epub 2017 May 23. |
| 29076564 | Result | Killian O, McGovern EM, Beck R, Beiser I, Narasimham S, Quinlivan B, O'Riordan S, Simonyan K, Hutchinson M, Reilly RB. Practice does not make perfect: Temporal discrimination in musicians with and without dystonia. Mov Disord. 2017 Dec;32(12):1791-1792. doi: 10.1002/mds.27185. Epub 2017 Oct 27. No abstract available. |
| 27911747 | Result | Simonyan K, Ackermann H, Chang EF, Greenlee JD. New Developments in Understanding the Complexity of Human Speech Production. J Neurosci. 2016 Nov 9;36(45):11440-11448. doi: 10.1523/JNEUROSCI.2424-16.2016. |
| 39287592 | Result | Laabs BH, Lohmann K, Vollstedt EJ, Reinberger T, Nuxoll LM, Kilic-Berkmen G, Perlmutter JS, Loens S, Cruchaga C, Franke A, Dobricic V, Hinrichs F, Grozinger A, Altenmuller E, Bellows S, Boesch S, Bressman SB, Duque KR, Espay AJ, Ferbert A, Feuerstein JS, Frank S, Gasser T, Haslinger B, Jech R, Kaiser F, Kamm C, Kollewe K, Kuhn AA, LeDoux MS, Lohmann E, Mahajan A, Munchau A, Multhaupt-Buell T, Pantelyat A, Pirio Richardson SE, Raymond D, Reich SG, Saunders Pullman R, Schormair B, Sharma N, Sichani AH, Simonyan K, Volkmann J, Wagle Shukla A, Winkelmann J, Wright LJ, Zech M, Zeuner KE, Zittel S, Kasten M, Sun YV, Baumer T, Bruggemann N, Ozelius LJ, Jinnah HA, Klein C, Konig IR. Genetic Risk Factors in Isolated Dystonia Escape Genome-Wide Association Studies. Mov Disord. 2024 Nov;39(11):2110-2116. doi: 10.1002/mds.29968. Epub 2024 Sep 17. |
| 35584784 | Result | Schill J, Simonyan K, Corsten M, Mathys C, Thiel C, Witt K. Graph-theoretical insights into the effects of aging on the speech production network. Cereb Cortex. 2023 Feb 20;33(5):2162-2173. doi: 10.1093/cercor/bhac198. |
| 34887826 | Result | Schill J, Zeuner KE, Knutzen A, Todt I, Simonyan K, Witt K. Functional Neural Networks in Writer's Cramp as Determined by Graph-Theoretical Analysis. Front Neurol. 2021 Nov 23;12:744503. doi: 10.3389/fneur.2021.744503. eCollection 2021. |
| 36440757 | Result | Yao D, O'Flynn LC, Simonyan K. DystoniaBoTXNet: Novel Neural Network Biomarker of Botulinum Toxin Efficacy in Isolated Dystonia. Ann Neurol. 2023 Mar;93(3):460-471. doi: 10.1002/ana.26558. Epub 2022 Dec 14. |
| 36640203 | Result | Frankford SA, O'Flynn LC, Simonyan K. Sensory processing in the auditory and olfactory domains is normal in laryngeal dystonia. J Neurol. 2023 Apr;270(4):2184-2190. doi: 10.1007/s00415-023-11562-z. Epub 2023 Jan 14. |
| 37338705 | Result | Battistella G, Simonyan K. Clinical Implications of Dystonia as a Neural Network Disorder. Adv Neurobiol. 2023;31:223-240. doi: 10.1007/978-3-031-26220-3_13. Epub 2023 Jun 21. |
| 37397896 | Result | Schill J, Simonyan K, Lang S, Mathys C, Thiel C, Witt K. Parkinson's disease speech production network as determined by graph-theoretical network analysis. Netw Neurosci. 2023 Jun 30;7(2):712-730. doi: 10.1162/netn_a_00310. eCollection 2023. |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009069 | Movement Disorders |
| D002493 | Central Nervous System Diseases |
| D001480 | Basal Ganglia Diseases |
| D001927 | Brain Diseases |
| D020820 | Dyskinesias |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |