Functional Connectivity in Primary Focal Dystonia
Condition: Dystonia
MeSH terms: Dystonia; Dystonic Disorders
Study type: Observational

Summary: 
      In this study we are looking at primary focal dystonias, including dystonias of the limbs,
      eyes, jaw or face, neck, and vocal chords. This study will use magnet resonance imaging (MRI)
      to see how the brain reacts while resting and doing a finger-tapping task.

      The investigators will test the hypothesis that disturbances in functional connectivity
      within the motor, affective and cognitive basal ganglia networks in primary focal dystonia
      (PFD) underlie the motor and non-motor symptoms in this disorder.
    

Detailed description: 
      After written consent is obtained, all subjects undergo a neurological examination by a board
      certified neurologist and complete a Montreal Cognitive Assessment and Edinburgh Handedness
      Inventory. Primary focal dystonia (PFD) patients will have their dystonia assessed with
      commonly used clinical rating scales for dystonia using Unified Dystonia Rating
      Scale,Fahn-Marsden Scale, Global Dystonia Rating Scale, Toronto Western Spasmodic Torticollis
      Rating Scale-TWSTRS,and the Jankovic Rating Scale for blepharospasm. Patients and controls
      will have affective symptoms assessed using the Liebowitz Social Anxiety Scale, Hospital
      Anxiety and Depression Scale,Yale-Brown Obsessive Compulsive Scale,and Beck Depression
      Inventory. Clinical evaluations will be performed at the University of Colorado Denver and
      Denver Veterans Affairs (VA) Hospital Brain Imaging Center on the Anschutz Medical Campus,
      prior to Magnetic Resonance Imaging (MRI) scanning. Consenting, exam, and clinical scale
      assessments are estimated to take 30-40 minutes to complete.

      MRI scanning protocol

      MRI scanning will be performed using an 8-channel head coil and a 3 Tesla General Electric
      (GE) Signa MR scanner system that is FDA-approved for clinical MR scanning. The principal
      investigator and/or a co-investigator will be present for every scanning session. Head motion
      will be minimized using cushions and passive restraints. The total MRI scanning session will
      take approximately 50-60 minutes, including set-up time and scan time, and includes the
      following MRI runs:

        1. Anatomic scans: A high-resolution 3D spoiled gradient echo T1-weighted image (~8
           minutes) will be collected for image registration and normalization. The subject simply
           rests while the sequence is run. A diffusion tensor imaging (DTI) scan (~10 minutes)
           will be acquired using a double spin-echo diffusion echo-planar imaging (EPI) sequence
           and 32 diffusion directions.

        2. Resting-state task (~6 min): Subject remains motionless with eyes closed and tries not
           to sleep or think of anything in particular.

        3. Motor tapping task (~6 min): Subject performs a sequential five-finger finger-tapping
           sequence in 30 sec blocks that alternate with 30 sec of rest. The tapping task was
           designed to minimize variance in performance between and within individuals and so is
           paced with an audible cue. During the rest condition the subject is to remain motionless
           and not think of anything in particular. A similar motor task has been shown to be
           feasible in primary dystonia (PD) patients and lead to striatal dopamine release.

        4. Repeat of motor task functional Magnetic Resonance Imagine (fMRI) scan (~6 minutes) -
           subject uses opposite hand to perform sequential finger tapping task, but otherwise scan
           is identical to above.

      Behavioral assessments

        1. Button presses during finger-tapping task scanning will be recorded using an
           MRI-compatible five-button response unit.

        2. Surface electromyographic (EMG) recordings will be obtained during resting-state and
           motor task fMRI scans to assess spontaneous dystonic motor activity, movement during
           rest, and muscle activity during tapping. Simultaneous EMG monitoring will be performed
           using a EMG Amplifier designed for fMRI acquisition and small adhesive pad EMG
           electrodes taped to the skin.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        Adult-onset primary focal dystonia patients 18 years old and older with symptoms affecting
        muscles of the eye (blepharospasm), jaw or face (cranial), neck (cervical), limbs
        (arm/leg), or vocal chords.