Low-intensity focused ultrasound to the human insular cortex differentially modulates the heartbeat-evoked potential: a proof-of-concept study.

Background: The heartbeat evoked potential (HEP) is a brain response time-locked to the heartbeat and a potential marker of interoceptive processing. The insula and dorsal anterior cingulate cortex (dACC) are brain regions that may be involved in generating the HEP. Low-intensity focused ultrasound (LIFU) is a non-invasive neuromodulation technique that can selectively target sub-regions of the insula and dACC to better understand their contributions to the HEP. Objective: Proof-of-concept study to determine whether LIFU modulation of the anterior insula (AI), posterior insula (PI), and dACC influences the HEP. Methods: In a within-subject, repeated-measures design, healthy human participants (n=16) received 10 minutes of stereotaxically targeted LIFU to the AI, PI, dACC or Sham at rest during continuous electroencephalography (EEG) and electrocardiography (ECG) recording on separate days. Primary outcome was change in HEP amplitudes. Relationships between LIFU pressure and HEP changes were examined using linear mixed modelling. Peripheral indices of visceromotor output including heart rate and heart rate variability (HRV) were explored between conditions. Results: Relative to sham, LIFU to the PI, but not AI or dACC, decreased HEP amplitudes; this was partially explained by increased LIFU pressure. LIFU did not affect time or frequency dependent measures of HRV. Conclusions: These results demonstrate the ability to modulate HEP amplitudes via non-invasive targeting of key interoceptive brain regions. 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.