Low-intensity focused ultrasound to the human dorsal anterior cingulate attenuates acute pain perception and autonomic responses.

Abstract

The dorsal anterior cingulate cortex (dACC) is a critical brain area for pain and autonomic processing, making it a promising non-invasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to non-invasively modulate the dACC for effects on behavioral and cardiac autonomic responses using transient heat pain stimuli. N = 16 healthy human volunteers (6M/10F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included pain ratings, heart-rate variability, EDR response, blood pressure, and the amplitude of the contact heat-evoked potential (CHEP).LIFU reduced pain ratings by 1.09 ± 0.20 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on blood pressure or EDR. LIFU resulted in a 38.1% reduction in the P2 CHEP amplitude. Results demonstrate LIFU to the dACC reduces pain and alters autonomic responses to acute heat pain stimuli. This has implications for the causal understanding of human pain and autonomic processing in the dACC and potential future therapeutic options for pain relief and modulation of homeostatic signals.Significance StatementNew lines of inquiry demonstrate autonomic signals like heart rate variability (HRV) are aberrant in chronic pain and mental health disorders, which may contribute to their underlying etiology. The dorsal anterior cingulate cortex (dACC) is a key center in pain processing with direct influences on autonomic function, but its depth precludes direct access without invasive surgery. For the first time in humans, we demonstrate low-intensity focused ultrasound (LIFU) can non-invasively and selectively modulate the dACC to reduce acute pain perception, autonomic responses, and pain processing signals. This work further establishes a causal role of the dACC in pain and autonomic processing with potential future clinical applications in chronic pain and neuropsychological populations.