Parsing Mechanistic Relationships Between Circuits and Negative Valence System Behaviors in Treatment-Resistant Depression With Ultrasound Neuromodulation
Laureate Institute for Brain Research, Inc.
Summary
Approximately one third of individuals with Major Depressive Disorder (MDD) are considered treatment-resistant, subject to severe disability and risk of suicide, and exhibit symptoms anchored in abnormalities of Research Domain Criteria (RDoC) Negative Valence Systems behavioral processes. In the present study we plan to use low-intensity focused ultrasound in 120 persons with treatment-resistant MDD to modulate deep white matter tracts connecting the thalamus and different regions of the prefrontal cortex reversibly and non-invasively, with the aim of assigning a causal, mechanistic role to large scale brain circuits in the production of those critical behavioral abnormalities. A successful study will help to attain the precise definition of neuromodulation targets for this clinical population in utter need of help.
Description
Approximately one third of individuals with depression are considered treatment-resistant (TRD) and exhibit symptoms anchored in abnormalities of RDoC Negative Valence Systems behavioral processes. For example, anhedonia and rumination contribute to significant impairment in daily functioning, high relapse rates, and a staggering global toll of over 700,000 annual suicides. One reason for inadequate treatment response is our limited understanding of causal mechanisms linking brain circuit function to Negative Valence behavior abnormalities, which impedes the development of precision neuromodul…
Eligibility
- Age range
- 18–65 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Persons 18-65 years old, with sex and ethnicity recruitment targets including a M:F proportion of 1:2 and White:Black:Hispanic:Native American proportion as close as possible to 8:2:2:1 to reflect the regional epidemiology of TRD (63% White American; 16% African American; 14% Hispanic of any race; 5% Native American), 2. DSM-5-TR diagnosis of MDD as confirmed by MINI structured interview followed by consultation with a board-certified psychiatrist, 3. Evidence of treatment resistance defined as continued MDD symptoms despite any of the following: 1. two or more adeq…
Interventions
- OtherLow-intensity focused ultrasound
80-second stimulus with an estimated tissue ISSPA=2.26 W/cm2, with (sham) or without (verum) interposition of Sorbothane film
Location
- Laureate Institute for Brain ResearchTulsa, Oklahoma