Non-invasive Intermittent Theta Burst Stimulation of the Dorsolateral Prefrontal Cortex in People With Functional Movement Disorders
Condition: Movement Disorders
MeSH terms: Movement Disorders; Conversion Disorder; Hysteria
Study type: Observational

Summary: 
      Background:

      Functional movement disorder (FMD) causes involuntary movements, such as spasms, shaking, or
      jerks. These symptoms are not due to a recognized neurological or medical cause. Researchers
      want to better understand how the brain works to cause these symptoms.

      Objective:

      To test if intermittent theta burst stimulation (iTBS) affects brain areas involved in FMD
      symptoms. Also, to look at the effect of iTBS on mood and motor symptoms.

      Eligibility:

      Right-handed people ages 18-65 who have FMD and participated in protocol 07-N-0190

      Design:

      Participants will have 4 visits.

      In Visit 1, participants will be screened with:

      Medical history

      Physical exam

      Urine test

      Questionnaires

      Visit 1 might also include a brain MRI and functional MRI. The MRI scanner is a cylinder
      surrounded by a strong magnetic field. They will lie on a table that can slide in and out of
      the cylinder. For the functional MRI, they will be asked to perform tasks during the MRI
      scan.

      Visit 2 will be 1-2 weeks after Visit 1. Visits 2, 3, and 4 will be no more than 48 hours
      apart. These include:

      Electromyography: Small electrodes are taped to the skin. Muscle activity is recorded while
      participants receive magnetic stimulation of the brain.

      Transcranial magnetic stimulation and iTBS: A wire coil is held on the scalp. A brief
      electrical current passes through the coil and creates a magnetic pulse to stimulate the
      brain. During iTBS, participants will sit quietly and watch a nature documentary. They will
      wear earplugs and a cap.

      MRI

      Functional MRI

      Questionnaires
    

Detailed description: 
      Objectives:

      The purpose of this protocol is to investigate feasibility and safety of intermittent theta
      burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) in
      patients with functional movement disorders (FMD). We further aim at exploring whether iTBS
      of the DLPFC modulates amygdala activity, by investigating iTBS effects on resting-state
      fronto-amygdala connectivity and on amygdala BOLD response to valenced stimuli.

      Study population:

      FMD patients (N=6), aged 18-65 years, admitted at the Human Motor Control Section (HMCS)
      clinic, who have completed protocol 07-N-0190.

      Design:

      Participants will undergo four outpatient visits. On Visit #1 (baseline), patients will
      undergo a screening session to assess their eligibility to participate in the current study.
      They will undergo neurological and psychiatric assessment, as well as structural and
      functional magnetic resonance imaging. Intermittent TBS will be performed on three separated
      visits (Visit #2, #3 and #4; iTBS1, iTBS 2 and iTBS 3). During each visit, participants will
      receive three iTBS sessions over 1-hour, with a 15-minute interval between sessions. Each
      session will last 190 seconds and a total of 600 pulses will be delivered. Magnetic field
      intensity will be set at 120% of that participants observed daily resting motor threshold.
      The target will be identified using the neuronavigation system Brainsight. Following each
      iTBS visit, behavioral and functional imaging data will be collected.

      Outcome measures:

      Our primary outcomes will be to evaluate the safety and feasibility of different doses of
      iTBS of the left DLPFC in patients with FMD. In addition, in order to investigate amygdala
      engagement by DLPFC iTBS, the following exploratory outcomes will be analyzed: (1) Amygdala
      BOLD signal change in response to valenced stimuli, from baseline to iTBS3; (2) Amygdala BOLD
      signal change in response to valenced stimuli, from baseline to each timepoint (iTBS1-
      iTBS3), for each valence stimuli; (3) Change in fronto-amygdalar resting state functional
      connectivity, from baseline to iTBS3 (z-score); (4) Change in fronto-amygdalar resting state
      functional connectivity from baseline to each time point (iTBS1- iTBS3); (5) Change in the
      valence and arousal subjective levels, using the self-assessment Manikin, from baseline to
      each time point (iTBS1- iTBS3); (6) Correlations of percent amygdala BOLD signal change with
      changes in arousal and valence level; (7) Change in the scores on the simplified version of
      the FMD-RS from pre- to post treatment, for each timepoint.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        FMD subjects will be recruited from patients assessed at the HMCS Clinic of NINDS/NIH, from
        the HMCS database, and from protocol 07-N-0190. Patients who have previously participated
        in protocol 07-N-0190 will be contacted over the telephone and offered participation in the
        study.
      
Keywords: Functional (BOLD) MRI