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Transcranial Focused Ultrasound Targeting the Amygdala May Increase Psychophysiological and Subjective Negative Emotional Reactivity in Healthy Older Adults.

Authors: Hoang-Dang B, Halavi SE, Rotstein NM, Spivak NM, Dang NH, Cvijanovic L, Hiller SH, Vallejo-Martelo M, Rosenberg BM, Swenson A, Becerra S, Sun M, Revett ME, Kronemyer D, Berlow R, Craske MG, Suthana N, Monti MM, Zbozinek TD, Bookheimer SY, Kuhn TP

The amygdala is highly implicated in an array of psychiatric disorders but is not accessible using currently available noninvasive neuromodulatory techniques. Low-intensity transcranial focused ultrasound (TFUS) is a neuromodulatory technique that has the capability of reaching subcortical regions noninvasively. We studied healthy older adult participants (<i>N</i> = 21, ages 48-79 years) who received TFUS targeting the right amygdala and left entorhinal cortex (active control region) using a 2-visit within-participant crossover design. Before and after TFUS, behavioral measures were collected via the State-Trait Anxiety Inventory and an emotional reactivity and regulation task utilizing neutral and negatively valenced images from the International Affective Picture System. Heart rate and self-reported emotional valence and arousal were measured during the emotional reactivity and regulation task to investigate subjective and physiological responses to the task. Significant increases in both self-reported arousal in response to negative images and heart rate during emotional reactivity and regulation task intertrial intervals were observed when TFUS targeted the amygdala; these changes were not evident when the entorhinal cortex was targeted. No significant changes were found for state anxiety, self-reported valence to the negative images, cardiac response to the negative images, or emotion regulation. The results of this study provide preliminary evidence that a single session of TFUS targeting the amygdala may alter psychophysiological and subjective emotional responses, indicating some potential for future neuropsychiatric applications. However, more work on TFUS parameters and targeting optimization is necessary to determine how to elicit changes in a more clinically advantageous way.

Introduction

Purpose Transcranial ultrasound stimulation
Study Objective To determine whether MRI-guided transcranial focused ultrasound (TFUS) targeting the right amygdala can noninvasively modulate emotional and psychophysiological responses in healthy older adults.
Animal model / Human subject Homo sapiens (human); strain: N/A; age: 48–79 years (mean 60.67 ± 8.52); sex: 11 female, 10 male
Disease model Healthy
MRI or image guidance method MRI-guided neuronavigation: MRI-console-guided targeting using structural localizer images and transducer fiducial markers to visualize and adjust transducer trajectory (Siemens MRI console)
Targeted brain region(s) Amygdala

Outcomes and Safety

Summary of Outcomes TFUS targeting the right amygdala (vs. an entorhinal cortex control) increased self-reported arousal to negative images and increased heart rate during task intertrial intervals, with no changes in state anxiety, valence ratings, cardiac responses to the images, or emotion regulation. The study used a single sonication protocol and only the amygdala target produced effects—no different TFUS parameter variants were tested or found successful.
Safety-related matter No serious adverse events were reported; one participant experienced a brief period of irritability and tearfulness shortly after amygdala TFUS that largely resolved by the end of the session and fully resolved within 3 days (causality unclear), and no other adverse events were reported.

Brain Region

Ultrasound Parameters

Ultrasound instrument BrainSonix Corp. BX Pulsar 1002 (MRI-compatible); transducers: 65-mm and 55-mm
FUS Frequency 0.65 MHz
FUS Intensity 0.72 W/cm2 (Ispta.3 = 720 mW/cm2)
FUS Mode pulsed
Pulse duration 5 ms (amygdala); 0.5 ms (entorhinal cortex)
Focal Characteristics Focal depth: None; Focal length: 65 mm, 55 mm; Aperture size: None
Treatment frequency Multiple sessions

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