Effect of Transcranial Magnetic Stimulation to the Frontoparietal Attention Network on Anxiety Potentiated Startle
Condition: Healthy Volunteers
Study type: Interventional

Summary: 
      Background:

      Researchers want to better understand brain processes related to fear and anxiety. They want
      to find out if transcranial magnetic stimulation (TMS), a type of brain stimulation, can
      reduce anxiety.

      Objective:

      To see how TMS affects fear and anxiety through memory and attention tasks.

      Eligibility:

      Healthy people ages 18-50 who are right-handed

      Design:

      Participants will be screened through another protocol.

      Participants in the pilot study will have 1 visit. This includes:

      Urine tests

      Questionnaires about mood and thinking

      Shock and startle workup: Electrodes are taped to the wrists or fingers. Participants will be
      shocked to find out what level of shock is uncomfortable but tolerable. They will hear loud,
      sudden noises through headphones.

      TMS: A coil is held on the scalp. A magnetic field stimulates the brain. Sometimes they might
      receive fake TMS. This feels the same as real TMS. They will perform simple tasks.
      Participants in the main study will have 2 visits within 2 weeks.

      The first visit includes:

      Urine tests

      Questionnaires about mood and thinking

      MRI: Participants lie on a table that slides into a scanner. They will be in the scanner
      about 1 hour. A computer screen in the scanner will tell them to perform simple tasks.

      The second visit includes:

      Shock and startle workup

      TMS
    

Detailed description: 
      Objective: To determine the effect of non-invasive brain stimulation on anxiety and
      anxiety-cognition interactions in healthy subjects. Toward this aim we will test the effect
      of transcranial magnetic stimulation (TMS) on two outcome measures: 1) Fear and anxiety
      during the threat of predictable and unpredictable shock (NPU threat test; Substudies 1 and
      3), and 2) Working memory (WM) related anxiety downregulation while performing the Sternberg
      WM task under threat of shock (Substudy 2).

      Study population: The study population will consist of up to 184 healthy volunteers between
      the ages of 18-50.

      Design: This study will consists of two (sub-studies 1 and 2) or three (sub-study 3)
      outpatient visits (1 MRI, 1 or 2 TMS visits [2 for sub-study 3]). In this protocol we will
      explore the effect of TMS in three sub-studies in the TMS study visit. The sub-studies will
      contain either the NPU or the Sternberg task during the TMS visits. The first visit (MRI)
      will consist of the same procedures for all sub-studies. Each subject will be assigned to
      only one of the sub-studies.

      Sternberg Task: Expose subjects to active or sham TMS to a region of the frontoparietal
      attention network during the Sternberg WM task. Subjects will have to maintain a series of
      letters in WM for a brief interval during blocks of safety and threat of shock.

      NPU Task: Expose subjects to active or sham TMS to a region of the frontoparietal attention
      network during the NPU threat test. Subjects will be exposed to blocks in which they are
      either 1) safe from shock (neutral), 2) at risk of shock delivered only during a cue
      (predictable), or 3) at risk of shock presented randomly (unpredictable).

      Outcome measures: In both studies the primary outcome measure will be anxiety-potentiated
      startle (APS), which is the increase in startle magnitude during periods of threat compared
      to periods of safety. We expect active, but not sham TMS to increase activity in the dlPFC,
      and therefore reduce APS in both studies
    

Intervention name(s): Transcranial Magnetic Stimulation Sham; Transcranial Magnetic Stimulation
Intervention type(s): Drug; Device
Intervention description(s): TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.; TMS device is used to determine the effect of non-invasive brain stimulation on anxiety and anxiety-cognition interactions in healthy subjects.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: Anxiety; Startle; Dorsolateral Prefrontal Cortex; Transcranial Magnetic Stimulation (TMS); Working Memory