Investigating Transcranial Ultrasound as a Potential Intervention for Depression

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* Beck Depression Inventory score between 10 and 25

Exclusion Criteria:

* left-handedness
* prior serious head-related injury
* any medical condition that would impact EEG profiles
* chronic migraines or other severe headaches
* pregnancy
* lack of proficiency in English
* lack of secure housing
* current confounding treatment (including any psychotropic medication or psychotherapy)
* current active suicidal potential necessitating immediate treatment, as such participants will be referred for immediate treatment.