Transcranial Focused Ultrasound Targeting the Amygdala May Increase Psychophysiological and Subjective Negative Emotional Reactivity in Healthy Older Adults
Bianca Hoang-Dang, Sabrina E. Halavi, Natalie M. Rotstein, Norman M. Spivak, Nolan H. Dang, Luka Cvijanovic, Sonja H. Hiller, Mauricio Vallejo-Martelo, Benjamin M. Rosenberg, Andrew Swenson, Sergio Becerra, Michael Sun, Malina E. Revett, David Kronemyer, Rustin Berlow, Michelle G. Craske, Nanthia Suthana, Martin M. Monti, Tomislav D. Zbozinek, Susan Y. Bookheimer, Taylor P. Kuhn
Biological Psychiatry Global Open Science 2024, 4, 100342 · 10.1016/j.bpsgos.2024.100342
Abstract
Background 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. Methods We studied healthy older adult participants ( N = 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. Results 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. Conclusions 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.
Abstract via europepmc.
Exposures
Exposure 1: TFUS targeting the right amygdala
Target: amygdala — “right amygdala”
Device: BrainSonix · BrainSonix Corp. · BX Pulsar 1002 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | not reported |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓⚑ |
For TFUS targeting the amygdala, a pulse repetition frequency of 10 Hz and a pulse width of 5 ms were used because these parameters were hypothesized to inhibit activity, and disruption of amygdala activity is hypothesized to be beneficial in treating anxiety disorders.
Exposure 2: TFUS targeting the left entorhinal cortex (active control)
Target: entorhinal cortex — “left entorhinal cortex”
Device: BrainSonix · BrainSonix Corp. · BX Pulsar 1002 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | not reported |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓ |
Conversely, TFUS of the entorhinal cortex used a pulse repetition frequency of 100 Hz and a pulse width of 0.5 ms, parameters that have been hypothesized to increase activity because it has been hypothesized that excitation of the entorhinal cortex improves learning and memory.
Flags from extraction
exposures[0].in_situ.ispta_w_cm2— Paper describes Ispta.3 as derated using a 0.3 dB/cm-MHz derating factor but does not state whether the underlying (non-derated) value was measured in water or estimated; classified here as in_situ (derating) per the paper's own description of Ispta.3 as a derated value.randomised— Paper states the study used a randomized, double-blinded crossover design for order of target site, not randomization to treatment arm per se (all participants received both conditions).sham_type— There is no inactive/sham condition; the entorhinal cortex TFUS served as an active control site rather than a sham.