<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03042962</url>
  </required_header>
  <id_info>
    <org_study_id>2019P001183</org_study_id>
    <secondary_id>R01NS088160</secondary_id>
    <nct_id>NCT03042962</nct_id>
  </id_info>
  <brief_title>Brain Networks in Dystonia</brief_title>
  <official_title>Brain Networks in Dystonia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kristina Simonyan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts Eye and Ear Infirmary</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Task-specific focal dystonias are characterized by selective activation of dystonic movements&#xD;
      during performance of highly learned motor tasks, such as writing or playing a musical&#xD;
      instrument. To date, there is only limited knowledge about the distinct neural abnormalities&#xD;
      that lead to the development of task-specificity in focal dystonias, which affect similar&#xD;
      muscle groups but result in different clinical manifestations, such as writer's cramp vs.&#xD;
      pianist's dystonia or spasmodic dysphonia vs. singer's dystonia. Our goal is to dissect the&#xD;
      pathophysiological mechanisms underlying the phenomenon of task specificity in isolated focal&#xD;
      dystonias using multi-level brain network analysis in conjunction with neuropathological&#xD;
      examination of postmortem brain tissue from patients with dystonia. Rather than viewing these&#xD;
      disorders as interesting curiosities, understanding the biology of task-specific activation&#xD;
      of motor programs is central to understanding dystonia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Task-specific primary focal dystonias (tsPFDs) are characterized by selective activation of&#xD;
      dystonic movements during performance of highly learned motor tasks, such as writing, playing&#xD;
      a musical instrument, speaking, or singing. Despite the recent advances in describing the&#xD;
      clinical features of dystonia, there is a fundamental gap in understanding the neural&#xD;
      abnormalities underlying the development of tsPFDs, which affect the same muscles but result&#xD;
      in different clinical manifestations as in writer's cramp vs. pianist's dystonia or spasmodic&#xD;
      dysphonia vs. singer's dystonia. Continued existence of this gap is an important problem&#xD;
      because it renders us unable to differentiate between primary and secondary brain changes&#xD;
      contributing to the tsPFD pathophysiology and to develop novel treatment options targeting&#xD;
      disorder-specific brain alterations. The objective of this application is to identify the&#xD;
      brain mechanisms underlying the phenomenon of task specificity in two representative groups&#xD;
      of patients with writer's cramp vs. musician's hand dystonia and spasmodic dysphonia vs.&#xD;
      singer's laryngeal dystonia using a novel approach of combined clinico-behavioral&#xD;
      examination, brain network analysis and quantitative neuropathology of postmortem brain&#xD;
      tissue. Our central hypothesis is that each tsPFD is characterized by distinct brain&#xD;
      abnormalities, which selectively affect the focal segments of brain networks responsible for&#xD;
      the performance of the respective motor task. The rationale for the proposed research is that&#xD;
      identification of tsPFD-specific brain changes and associated neuropathology will clarify the&#xD;
      neural mechanisms (primary vs. secondary) contributing to the clinical manifestation of these&#xD;
      disorders and thus explain the phenomenon of tsPFDs. The obtained results are expected to&#xD;
      provide strong scientific bases for the next series of studies directed towards&#xD;
      identification and validation of novel pharmacological and/or surgical therapies for these&#xD;
      patients. The researchers will pursue the following two specific aims: (1) determine distinct&#xD;
      features of brain functional network abnormalities underlying task-specificity in different&#xD;
      tsPFDs, and (2) establish structural correlates of functional neuroimaging abnormalities in&#xD;
      tsPFDs. The proposed research is significant because it is expected to establish scientific&#xD;
      evidence that tsPFD is a network disorder with abnormalities following distinct patterns in&#xD;
      different tsPFDs and certain abnormalities showing structure-function correlations are&#xD;
      associated with underlying neuropathology. By converging the results from multimodal&#xD;
      cross-disciplinary studies to a coherent and pathophysiologically meaningful picture, the&#xD;
      researchers will be well positioned to identify primary vs. secondary changes in tsPFDs and&#xD;
      establish a scientific framework for the development of diagnostic biomarkers and novel&#xD;
      treatment options for these disorders.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2015</start_date>
  <completion_date type="Actual">May 31, 2022</completion_date>
  <primary_completion_date type="Actual">May 31, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of brain structural and functional changes</measure>
    <time_frame>5 years</time_frame>
    <description>Identify imaging alterations responsible for task specificity in dystonia. Identify changes in brain activity and gray and white matter in patients with task-specific dystonia</description>
  </primary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">141</enrollment>
  <condition>Spasmodic Dysphonia</condition>
  <condition>Singer's Dystonia</condition>
  <condition>Writer's Cramp</condition>
  <condition>Musician's Focal Hand Dystonia</condition>
  <arm_group>
    <arm_group_label>Patients with dystonia</arm_group_label>
    <description>Patients with dystonia (spasmodic dysphonia, singer's dystonia, writer's cramp, musician's focal hand dystonia) will undergo MRI of the brain and blood draw.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <description>Healthy subjects without any neurological, psychiatric or otolaryngological problems will undergo MRI of the brain and blood draw.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>MRI</intervention_name>
    <description>Functional and structural MRI of the brain will be conducted to identify disorder specific neural markers</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>Patients with dystonia</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood draw</intervention_name>
    <description>Blood samples will be collected, the DNA will be extracted and banked for genetic studies</description>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <arm_group_label>Patients with dystonia</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Blood samples will be collected, the DNA will be extracted and banked for genetic studies&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Patients with writer's cramp, musician's focal hand dystonia, spasmodic dysphonia, singer's&#xD;
        dystonia, and healthy volunteers&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients will have clinically documented focal dystonia (including spasmodic&#xD;
             dysphonia, singer's dystonia, writer's cramp, musician's focal hand dystonia)&#xD;
&#xD;
          -  Healthy controls will be healthy volunteers with a negative history of neurological,&#xD;
             laryngeal or psychiatric problems&#xD;
&#xD;
          -  Age from 21 to 80 years.&#xD;
&#xD;
          -  Native English speakers.&#xD;
&#xD;
          -  Right-handedness (based on Edinburgh Handedness Inventory).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who are incapable of giving an informed consent.&#xD;
&#xD;
          -  Pregnant or breastfeeding women until a time when they are no longer pregnant or&#xD;
             breastfeeding. All women of childbearing potential will have a urine pregnancy test&#xD;
             performed, which must be negative for participation in the imaging studies.&#xD;
&#xD;
          -  Subjects with past or present medical history of (a) neurological problems, such as&#xD;
             stroke, movement disorders (other than dystonia in the patient groups), brain tumors,&#xD;
             traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia&#xD;
             gravis, demyelinating diseases, alcoholism, drug depend-ence; (b) psychiatric&#xD;
             problems, such as schizophrenia, major and/or bipolar depression, obsessive-compulsive&#xD;
             disorder; (c) laryngeal problems, such as vocal fold paralysis, paresis, vocal fold&#xD;
             nodules and polyps, carcinoma, chronic laryngitis.&#xD;
&#xD;
          -  Patients who are not symptomatic due to treatment with botulinum toxin injections into&#xD;
             the laryngeal muscles. The duration of positive effects of botulinum toxin vary from&#xD;
             patient to patient but lasts on average for 3-4 months. All patients will be evaluated&#xD;
             to ensure that they are fully symptomatic prior to entering the study.&#xD;
&#xD;
          -  Patients with other forms of dystonia.&#xD;
&#xD;
          -  Patients with hereditary forms of dystonia (e.g., DYT1, DYT6, GNAL). If ARSG gene is&#xD;
             identified in musician's dystonia patients, it will be used as a nuisance covariate in&#xD;
             imaging analysis.&#xD;
&#xD;
          -  Patients who have dystonia symptoms at rest in order to avoid the potential confound&#xD;
             of dystonic spasms occurring during the scanning.&#xD;
&#xD;
          -  To avoid the possibility of confounding effects of drugs acting upon the central&#xD;
             nervous system, all study participants will be questioned about any prescribed or&#xD;
             over-the-counter medications as part of their initial intake screening. Those patients&#xD;
             who receive medication(s) affecting the central nervous system will be excluded from&#xD;
             the study.&#xD;
&#xD;
          -  The patients will be asked whether they have undergone any head, neck, or hand&#xD;
             surgeries, which resulted in changes in regional anatomy or innervation. Because&#xD;
             brain, hand and laryngeal surgery may potentially lead to the brain structure and&#xD;
             function re-organization, all patients with history of brain, hand and/or laryngeal&#xD;
             surgery will be excluded from the study.&#xD;
&#xD;
          -  Subjects who have tattoos, ferromagnetic objects in their bodies (e.g., implanted&#xD;
             stimulators, surgical clips, prosthesis, artificial heart valve, etc.) that cannot be&#xD;
             removed for the purpose of study participation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Kristina Simonyan, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Massachusetts Eye and Ear Infirmary</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts Eye and Ear Infirmary</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://projectreporter.nih.gov/project_info_description.cfm?aid=9117647&amp;icde=32825760&amp;ddparam=&amp;ddvalue=&amp;ddsub=&amp;cr=3&amp;csb=default&amp;cs=ASC&amp;pball=</url>
    <description>NIH grant description</description>
  </link>
  <reference>
    <citation>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.</citation>
    <PMID>33858994</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>32098856</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>30755797</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>30473192</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>29219190</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>28543038</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>29076564</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>27911747</PMID>
  </reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>26679193</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27575646</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>27939583</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>28674168</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>33504639</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>33004625</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>32311207</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>31930574</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30582159</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30840778</PMID>
  </results_reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>30264427</PMID>
  </results_reference>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>February 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 3, 2017</study_first_posted>
  <last_update_submitted>August 26, 2022</last_update_submitted>
  <last_update_submitted_qc>August 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts Eye and Ear Infirmary</investigator_affiliation>
    <investigator_full_name>Kristina Simonyan</investigator_full_name>
    <investigator_title>Associate Professor of Otolaryngology - Head and Neck Surgery</investigator_title>
  </responsible_party>
  <keyword>dystonia</keyword>
  <keyword>imaging</keyword>
  <keyword>genetics</keyword>
  <keyword>neuropathology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dysphonia</mesh_term>
    <mesh_term>Dystonia</mesh_term>
    <mesh_term>Dystonic Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03042962
org study id: 2019P001183
secondary id: R01NS088160
nct id: NCT03042962
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Task-specific focal dystonias are characterized by selective activation of dystonic movements
      during performance of highly learned motor tasks, such as writing or playing a musical
      instrument. To date, there is only limited knowledge about the distinct neural abnormalities
      that lead to the development of task-specificity in focal dystonias, which affect similar
      muscle groups but result in different clinical manifestations, such as writer's cramp vs.
      pianist's dystonia or spasmodic dysphonia vs. singer's dystonia. Our goal is to dissect the
      pathophysiological mechanisms underlying the phenomenon of task specificity in isolated focal
      dystonias using multi-level brain network analysis in conjunction with neuropathological
      examination of postmortem brain tissue from patients with dystonia. Rather than viewing these
      disorders as interesting curiosities, understanding the biology of task-specific activation
      of motor programs is central to understanding dystonia.
Task-specific primary focal dystonias (tsPFDs) are characterized by selective activation of
      dystonic movements during performance of highly learned motor tasks, such as writing, playing
      a musical instrument, speaking, or singing. Despite the recent advances in describing the
      clinical features of dystonia, there is a fundamental gap in understanding the neural
      abnormalities underlying the development of tsPFDs, which affect the same muscles but result
      in different clinical manifestations as in writer's cramp vs. pianist's dystonia or spasmodic
      dysphonia vs. singer's dystonia. Continued existence of this gap is an important problem
      because it renders us unable to differentiate between primary and secondary brain changes
      contributing to the tsPFD pathophysiology and to develop novel treatment options targeting
      disorder-specific brain alterations. The objective of this application is to identify the
      brain mechanisms underlying the phenomenon of task specificity in two representative groups
      of patients with writer's cramp vs. musician's hand dystonia and spasmodic dysphonia vs.
      singer's laryngeal dystonia using a novel approach of combined clinico-behavioral
      examination, brain network analysis and quantitative neuropathology of postmortem brain
      tissue. Our central hypothesis is that each tsPFD is characterized by distinct brain
      abnormalities, which selectively affect the focal segments of brain networks responsible for
      the performance of the respective motor task. The rationale for the proposed research is that
      identification of tsPFD-specific brain changes and associated neuropathology will clarify the
      neural mechanisms (primary vs. secondary) contributing to the clinical manifestation of these
      disorders and thus explain the phenomenon of tsPFDs. The obtained results are expected to
      provide strong scientific bases for the next series of studies directed towards
      identification and validation of novel pharmacological and/or surgical therapies for these
      patients. The researchers will pursue the following two specific aims: (1) determine distinct
      features of brain functional network abnormalities underlying task-specificity in different
      tsPFDs, and (2) establish structural correlates of functional neuroimaging abnormalities in
      tsPFDs. The proposed research is significant because it is expected to establish scientific
      evidence that tsPFD is a network disorder with abnormalities following distinct patterns in
      different tsPFDs and certain abnormalities showing structure-function correlations are
      associated with underlying neuropathology. By converging the results from multimodal
      cross-disciplinary studies to a coherent and pathophysiologically meaningful picture, the
      researchers will be well positioned to identify primary vs. secondary changes in tsPFDs and
      establish a scientific framework for the development of diagnostic biomarkers and novel
      treatment options for these disorders.
observational model: Cohort
time perspective: Cross-Sectional
measure: Incidence of brain structural and functional changes
time frame: 5 years
description: Identify imaging alterations responsible for task specificity in dystonia. Identify changes in brain activity and gray and white matter in patients with task-specific dystonia
arm group label: Patients with dystonia
description: Patients with dystonia (spasmodic dysphonia, singer's dystonia, writer's cramp, musician's focal hand dystonia) will undergo MRI of the brain and blood draw.
arm group label: Healthy volunteers
description: Healthy subjects without any neurological, psychiatric or otolaryngological problems will undergo MRI of the brain and blood draw.
intervention type: Other
intervention name: MRI
description: Functional and structural MRI of the brain will be conducted to identify disorder specific neural markers
arm group label: Healthy volunteers
arm group label: Patients with dystonia
intervention type: Procedure
intervention name: Blood draw
description: Blood samples will be collected, the DNA will be extracted and banked for genetic studies
arm group label: Healthy volunteers
arm group label: Patients with dystonia
Blood samples will be collected, the DNA will be extracted and banked for genetic studies
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Kristina Simonyan, MD, PhD
role: Principal Investigator
affiliation: Massachusetts Eye and Ear Infirmary
facility: 
country: United States
url: https://projectreporter.nih.gov/project_info_description.cfm?aid=9117647&icde=32825760&ddparam=&ddvalue=&ddsub=&cr=3&csb=default&cs=ASC&pball=
description: NIH grant description
citation: 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.
PMID: 33858994
citation: 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.
PMID: 32098856
citation: 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.
PMID: 30755797
citation: 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.
PMID: 30473192
citation: 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.
PMID: 29219190
citation: 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.
PMID: 28543038
citation: 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.
PMID: 29076564
citation: 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.
PMID: 27911747
citation: 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.
PMID: 26679193
citation: 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.
PMID: 27575646
citation: 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.
PMID: 27939583
citation: 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.
PMID: 28674168
citation: 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.
PMID: 33504639
citation: 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.
PMID: 33004625
citation: 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.
PMID: 32311207
citation: 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.
PMID: 31930574
citation: 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.
PMID: 30582159
citation: 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.
PMID: 30840778
citation: 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.
PMID: 30264427
responsible party type: Sponsor-Investigator
investigator affiliation: Massachusetts Eye and Ear Infirmary
investigator full name: Kristina Simonyan
investigator title: Associate Professor of Otolaryngology - Head and Neck Surgery
mesh term: Dysphonia
mesh term: Dystonia
mesh term: Dystonic Disorders
sharing ipd: No