Low-intensity focused ultrasound to the insula differentially modulates the heartbeat-evoked potential: A proof-of-concept study
Andrew Strohman, Gabriel Isaac, Brighton Payne, Charles Verdonk, Sahib S. Khalsa, Wynn Legon
Clinical Neurophysiology 2024, 167, 267-281 · 10.1016/j.clinph.2024.09.006
Abstract
Objective The heartbeat evoked potential (HEP) is a brain response time-locked to the heartbeat and a potential marker of interoceptive processing that may be generated in the insula and dorsal anterior cingulate cortex (dACC). Low-intensity focused ultrasound (LIFU) can selectively modulate sub-regions of the insula and dACC to better understand their contributions to the HEP. Methods Healthy participants (n = 16) received stereotaxically targeted LIFU to the anterior insula (AI), posterior insula (PI), dACC, or Sham at rest during continuous electroencephalography (EEG) and electrocardiography (ECG) recording on separate days. Primary outcome was HEP amplitudes. Relationships between LIFU pressure and HEP changes and effects of LIFU on heart rate and heart rate variability (HRV) were also explored. Results Relative to sham, LIFU to the PI, but not AI or dACC, decreased HEP amplitudes; PI effects were partially explained by increased LIFU pressure. LIFU did not affect heart rate or HRV. Conclusions These results demonstrate the ability to modulate HEP amplitudes via non-invasive targeting of key interoceptive brain regions. Significance Our findings have implications for the causal role of these areas in bottom-up heart-brain communication that could guide future work investigating the HEP as a marker of interoceptive processing in healthy and clinical populations.
Abstract via europepmc.
Exposures
Exposure 1: LIFU to anterior insula (AI)
Target: anterior insula — “anterior insula (AI, left dorsal anterior short gyrus)”
Device: Sonic Concepts · Sonic Concepts · H-281 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.36 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 36 | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 380 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 4.2 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 1.51 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 179.8 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | ⚑ |
| In-situ Ispta (W/cm²) | not reported |
100 stimulations (1 s burst duration each) delivered with a fixed inter-stimulus interval of 5 s for a total application time of 10 min, with continuous auditory masking throughout.
Exposure 2: LIFU to posterior insula (PI)
Target: posterior insula — “posterior insula (PI, left dorsal posterior long gyrus)”
Device: Sonic Concepts · Sonic Concepts · H-281 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.36 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 36 | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 380 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 4.2 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 1.51 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 262.8 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
100 stimulations (1 s burst duration each) delivered with a fixed inter-stimulus interval of 5 s for a total application time of 10 min, with continuous auditory masking throughout.
Exposure 3: LIFU to dorsal anterior cingulate cortex (dACC)
Target: dorsal anterior cingulate cortex — “dorsal anterior cingulate cortex (dACC, MNI [0,18,30])”
Device: Sonic Concepts · Sonic Concepts · H-104 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.36 ms (not stated by the paper) | |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 36 | ✓✓✓ |
| Sonication duration (s) | 1 | ✓✓✓ |
| Free-field pressure (kPa) | 400 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 4.5 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 1.62 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | 115.1 | ✓✓✓ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
100 stimulations (1 s burst duration each) delivered with a fixed inter-stimulus interval of 5 s for a total application time of 10 min, with continuous auditory masking throughout.
Flags from extraction
exposures[0].in_situ.isppa_w_cm2— Only in-situ pressure (derated) is reported per subject/target; derated intensity values are not given.direction_of_effect— Effects differ by target (PI inhibitory vs Sham/dACC; AI/dACC no effect vs Sham) so a single top-level direction is an approximation; see direction_notes.