Investigating Low Intensity Focused Ultrasound Pulsation in Anhedonic Depression - A Randomized Controlled Trial

Natalie M. Rotstein ^1* Zachary D. Cohen ² Amelia Welborn ¹ Tomislav D. Zbozinek ¹ Samir Akre ³ Keith G. Jones ¹ Kaylee E. Null ⁴ Jillian Pontanares ¹ Katy L. Sanchez ⁵ Demarko C. Flanagan ⁵ Sabrina E. Halavi ¹ Evan Kittle ¹ Mason G. McClay ⁴ Alex A. T. Bui ³ Katherine L. Narr ^1,5 Robert C Welsh ¹ Michelle G. Craske ^1,4 Taylor P. Kuhn ¹

• ¹ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, United States
• ² Department of Psychology, University of Arizona, Tuscon, United States
• ³ Medical Informatics Home Area, University of California, Los Angeles, Los Angeles, United States
• ⁴ Department of Psychology, University of California, Los Angeles, Los Angeles, United States
• ⁵ Department of Neurology, University of California, Los Angeles, Los Angeles, United States

Introduction: Anhedonic depression is a subtype of depression characterized by deficits in reward processing. This subtype of depression is associated with higher suicide risk and longer depressive episodes, underscoring the importance of effective treatments. Anhedonia has also been found to correlate with alterations in activity in several subcortical regions, including the caudate head and nucleus accumbens. Low intensity focused ultrasound pulsation (LIFUP) is an emerging technology that enables non-invasive stimulation of these subcortical regions, which were previously only accessible with surgically-implanted electrodes. Methods: This double-blinded, sham-controlled study aims to investigate the effects of LIFUP to the left caudate head and right nucleus accumbens in participants with anhedonic depression. Participants in this protocol will undergo 3 sessions of LIFUP over the span of 5-9 days. To investigate LIFUP-related changes, this seven-week protocol collects continuous digital phenotyping data, an array of self-report measures of depression, anhedonia, and other psychopathology, and magnetic resonance imaging (MRI) before and after the LIFUP intervention. Primary self-report outcome measures include Ecological Momentary Assessment, the Positive Valence Systems Scale, and the Patient Health Questionnaire. Primary imaging measures include magnetic resonance spectroscopy and functional MRI during reward-based tasks and at rest. Digital phenotyping data is collected with an Apple Watch and participants’ personal iPhones throughout the study, and includes information about sleep, heart rate, and physical activity.Discussion: This study is the first to investigate the effects of LIFUP to the caudate head or nucleus accumbens in depressed subjects. Furthermore, the data collected for this protocol covers a wide array of potentially affected modalities. As a result, this protocol will help to elucidate potential impacts of LIFUP in individuals with anhedonic depression.