Investigating Transcranial Ultrasound as a Potential Intervention for Depression
Condition: Depression; Anxiety Disorders
MeSH terms: Depression; Depressive Disorder; Anxiety Disorders
Study type: Interventional

Summary: 
      Depression is the leading cause of disability worldwide. Because a significant number of
      people with depression do not respond to medication or therapy, alternative treatment options
      are greatly needed. Recent research has focused on brain stimulation methods due to their
      therapeutic utility for treating depression. Yet, current brain stimulation methods have
      drawbacks, including invasive surgery and limited precision in targeting specific areas. A
      novel brain stimulation method, transcranial ultrasound (TUS), is noninvasive, has greater
      spatial precision than most existing methods, and is proven safe for humans. TUS has been
      found to increase positive mood in chronic pain patients. In a double blind study, TUS
      increased positive mood in over 140 healthy undergraduates at the University of Arizona.

      Despite evidence that TUS can increase positive mood in humans, it has yet to be investigated
      whether TUS can increase positive mood in humans who are experiencing chronic low mood or
      depression. The present study will, for the first time, examine whether TUS can improve
      depressive symptoms. Twenty to thirty participants with mild to moderate depressive symptoms
      (Beck Depression Inventory Score between 10 and 25) will be randomly assigned to a TUS sham
      or TUS activation condition. In the TUS activation condition, TUS will be used to stimulate
      the right fronto-temporal area, which has previously been shown to increase positive mood.
      Participants in the TUS sham condition will not receive any brain stimulation. Participants
      will attend five sessions within seven days or ten sessions within fourteen days. At each
      session, in addition to brain stimulation, self-reported mood and depressive symptoms will be
      recorded. Furthermore, the investigators will use electroencephalogram (EEG) to record
      changes in brain electrical signals during TUS stimulation. Based on prior research, the
      investigators predict that mood will increase and depressive symptoms will decrease with TUS
      stimulation.
    

Detailed description: 
      Participants will first complete the online screening and those who qualify to complete the
      study will be contacted via telephone (see above for telephone recruitment and consent
      procedure). After providing informed consent, on the first day, participants will be randomly
      assigned to either a TUS treatment or a TUS sham condition (placebo), and the study will be
      double blind. Participants in the TUS treatment condition (with sham or treatment unknown to
      both participant and experimenter) will have TUS stimulation at the right fronto-temporal
      area five times within seven days or ten times within fourteen days.

      Participants will sign up for the first five sessions first but will be reminded participants
      may withdraw from the study at any time. Should participants choose to continue with the
      second week of treatment, participants will be scheduled for another five sessions. In other
      words, participants will have the option of completing 10 days of the procedure. The
      procedure does not differ between week 1 and week 2. However, participants will be
      compensated less for week 2. Participants will have the option to continue into week 2, as
      participants may find that the treatment is benefiting them. The first, fifth, and tenth days
      of the study will take approximately 2 hours and the second, third, fourth, sixth, seventh,
      eighth, and ninth will take only one hour.

      In the sham condition, the ultrasound probe will be placed at the right fronto-temporal area
      five times over the course of seven days or ten times over the course of fourteen days
      without the stimulation. Prior research has shown that stimulation at this area induces
      positive mood change and is implicated in positive mood. On the first, middle, and last day
      of the procedure (day 1, 5, 10), EEG data will be collected. On the second, third, and fourth
      day as well as sixth through ninth days of the procedure EEG data will not be collected and
      only TUS stimulation will occur. Collecting EEG data at these points will allow for
      comparison of resting electrical brain profiles from the beginning of the study to the end of
      the study. Additionally, the investigators will assess state mood and rumination before and
      after TUS, as well as depressive and anxiety symptoms at the end of each day. The state mood
      and rumination will allow us to examine the mood effects of TUS, whereas the depressive and
      anxiety symptoms questionnaires will allow us to examine any changes in these important
      profiles over the course of the study.
    

Intervention name(s): Transcranial Ultrasound Power; Transcranial Ultrasound Sham
Intervention type(s): Device; Device
Intervention description(s): Transcranial ultrasound will be to stimulate at the right fronto-temporal cortex. 30 seconds of stimulation at 500 kHZ with duty cycle 0.24% and pulse rate frequency at 40 Hz.; Transcranial ultrasound will be used without power for a "sham" condition.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment