Functional Connectivity in Primary Focal Dystonia

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.

Inclusion Criteria:

- English as their primary language

- Volunteers with PFD and healthy controls

- PFD volunteers must be on a stable dose of all dystonia and neuroactive drugs (e.g.
antidepressants) for one month prior to enrollment

- PFD volunteers must not have been injected with botulinum toxin within the prior 2
months

Exclusion Criteria:

- Any contraindication to MRI scanning

- Any untreated neurological or psychiatric condition

- Evidence on neurological exam of any potentially confounding neurological disorder
(e.g., Parkinson disease, Essential Tremor, etc.)

- Evidence of significant cognitive impairment (all subjects assessed using the Montreal
Cognitive Assessment