Brain Networks in Dystonia
Condition: Spasmodic Dysphonia; Singer's Dystonia; Writer's Cramp; Musician's Focal Hand Dystonia
MeSH terms: Dysphonia; Dystonia; Dystonic Disorders
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): MRI; Blood draw
Intervention type(s): Other; Procedure
Intervention description(s): Functional and structural MRI of the brain will be conducted to identify disorder specific neural markers; Blood samples will be collected, the DNA will be extracted and banked for genetic studies
Observational model: Cohort
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients with writer's cramp, musician's focal hand dystonia, spasmodic dysphonia, singer's
        dystonia, and healthy volunteers
      
Biospecimen description: 
      Blood samples will be collected, the DNA will be extracted and banked for genetic studies
    
Keywords: dystonia; imaging; genetics; neuropathology