Functional and Structural Imaging and Motor Control in Spinocerebellar Ataxia
Condition: Spinocerebellar Ataxia
MeSH terms: Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations
Study type: Interventional

Summary: 
      The purpose of this research study is to investigate how the brain and motor behavior changes
      both in individuals with spinocerebellar ataxia and healthy individuals, and to assess
      whether a therapeutic intervention reduces levels of uncoordinated movement and improves
      motor function in spinocerebellar ataxia (SCA).
    

Detailed description: 
      Thirty individuals who have been diagnosed with either Spinocerebellar Ataxia - 1 (SCA1),
      Spinocerebellar Ataxia - 3 (SCA3), or Spinocerebellar Ataxia - 6 (SCA6) will be recruited for
      this study. Participants will be randomly assigned to a best medical management (BMM /
      control) group and an error-reduction group. All participants will visit the lab twice for
      testing one month apart. Participants in the control group will not train between the pre-
      and post-test time.

      The error-reduction intervention will be a 4-week home-based program. Investigators will use
      a novel, custom designed computer interface. Participants will perform goal-directed
      movements with each leg to targets in a 3D virtual environment designed to emphasize accurate
      movements. The goal-directed leg movements (similar to leg press) will be performed seated
      and require hip, knee, and ankle joint control. Leg movement will be detected using the
      LeapMotion sensor (Leap Motion Inc. San Francisco, CA), a device that supports hand, and
      finger / tool motions as input, similar to a mouse, but requiring no contact. Spatial
      endpoint errors will be quantified in 3D space by comparing the endpoint location of the foot
      trajectory (extending from the big toe) and the virtual location of the target. Time endpoint
      errors will be quantified by comparing the timing of the foot trajectory and the required
      time to target.

      The length of the intervention will be 4 weeks. Each participant will train 4 days a week for
      ~1 hour per day. Within a week the task difficulty will increase by changing the presentation
      of the target from a predictable to an unpredictable location, by increasing movement speed
      requirements and by changing target size. Targets will be made predictable by identifying
      them prior to the cue for movement onset (target turning green). Specifically, there will be
      a flashing dotted line around the target prior to the target turning green. Targets will be
      made unpredictable by not providing any indication of the target location prior to the target
      turning green. Movement speed will be quantified from the voluntary movement onset of the leg
      (no reaction time) to the movement end.The movement speed requirements will be increased
      within a week and participants will learn to execute faster movements from the feedback after
      each trial. The size of the target will be progressively reduced during the 4 weeks.

      All individuals in the study will receive a pre- and post-test assessment using the
      International Cooperative Ataxia Rating Scale (ICARS) and the Scale for the Assessment and
      Rating of Ataxia (SARA). The individual sections of the ICARS (e.g. Kinetic section) and SARA
      will be quantified.

      In addition, leg dysmetria will be quantified using a custom-made goal-directed movement
      protocol. Specifically, participants will perform unloaded ankle dorsiflexion movements and
      attempt to reach a space-time target. The primary outcomes will be position and time errors.

      Biomechanics of overground walking in SCA will be monitored using the APDM mobility lab
      (APDM, Inc. Mobility Lab, Oregon, USA). Participants will wear APDM's wireless sensors on the
      hands, legs, trunk and forehead and walk overground a distance of 7 meters for 2 minutes.
      APDM quantifies 80 common biomechanical outcomes of gait (e.g. stride length variability).

      The neurophysiology of SCA will be quantified with functional Magnetic Resonance Imaging
      (fMRI) and motor unit pool activity. Brain activity will be quantified with task-based fMRI
      using a 32-channel head coil. During fMRI force tasks, ankle dorsiflexion will be measured
      from the most affected lower limb using customized fiber optic sensors, as has been done in
      the past. Real-time feedback of force performance will be provided to the subject. During the
      rest blocks, subjects will fixate on a stationary target but do not produce force. During
      task blocks, subjects will complete 2 second pulse-hold contractions to 15% maximum voluntary
      contraction(MVC) of ankle dorsiflexion followed by 1 second of rest. There will be 10 pulses
      per block. The knee will be supported by a pillow to flex the knee so that the forces applied
      by the ankle do not cause head movement.
    

Intervention name(s): Error-reduction; International Cooperative Ataxia Rating Scale; Scale for the Assessment and Rating of Ataxia; Beck Depression Inventory, 2nd Ed; Stroop; Purdue Pegboard; Brief Test of Attention; 6-minute Walk; Hand Grip Dynamometer; Montreal Cognitive Assessment; Physical Performance Function; Biomechanical Assessments of Dysmetria; Neurophysiological assessment of brain activity; Biomechanical gait analysis
Intervention type(s): Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral; Behavioral
Intervention description(s): During this time participants will use a novel, custom designed computer interface to perform goal-directed movements with each leg in a 3D virtual environment designed to emphasize accurate movements. Leg movement will be detected using the LeapMotion sensor and we will quantify time endpoint errors by comparing the timing of the foot trajectory and the required time to target.
The error-reduction intervention will be a 4-week home-based program. Each participant will train 4 days a week for approximately 1 hours per day. Within a week, the task difficulty will increase by changing the presentation of the targets to be more unpredictable and by increasing movement speed.; The ICARS is an assessment of the ataxia severity. The ICARS score is the total sum of the sub scores on specific movements and ranges from 0 to 100, with a score of 100 being indicative of the most severely affected outcome.; The SARA is an assessment of the ataxia severity. The SARA score is the total sum of the sub scores on specific movements and ranges from 0 to 100, with a score of 100 being indicative of the most severely affected outcome.; This is a 21 question self-report inventory for measuring severity of depression.; This test measures selective attention and cognitive flexibility through reading aloud of color names or color of the print.; This test consists of a series of timed hand coordination and dexterity tasks.; A cognitive test assessing focus and attention.; This test consists on a timed 6-minute walk test to evaluate how much distance is covered.; This tests measures hand grip strength.; This test is used to assess cognitive abilities.; This test consists of a series of physical activities used to evaluate speed, coordination, and ease of movement.; Dysmetria will be assessed using a custom-made goal-directed movement protocol where participant perform unloaded limb movement tasks and attempt to reach a space-time target. During these task muscle activity is monitored using Electromyography (EMG) recording.; Neurophysiology will be assessed by monitoring brain activity using Task-based fMRI and motor unit pool activity using a specialized EMG system.; Participants will wear APDM's wireless sensors on the hands, legs, trunk and forehead and walk overground a distance of 7 m for 2 minutes. APDM quantifies 80 common biomechanical outcomes of gait (e.g. stride length variability).
Other intervention name(s): SARA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: SCA, dysmetria