Inhibition of midfrontal theta with transcranial ultrasound explains greater approach versus withdrawal behavior in humans
Philipp Ziebell, Johannes Rodrigues, André Forster, Joseph L. Sanguinetti, John JB. Allen, Johannes Hewig
Brain Stimulation 2023, 16, 1278-1288 · 10.1016/j.brs.2023.08.011
Abstract
Recent reviews highlighted low-intensity transcranial focused ultrasound (TUS) as a promising new tool for non-invasive neuromodulation in basic and applied sciences. Our preregistered double-blind within-subjects study (N = 152) utilized TUS targeting the right prefrontal cortex, which, in earlier work, was found to positively enhance self-reported global mood, decrease negative states of self-reported emotional conflict (anxiety/worrying), and modulate related midfrontal functional magnetic resonance imaging activity in affect regulation brain networks. To further explore TUS effects on objective physiological and behavioral variables, we used a virtual T-maze task that has been established in prior studies to measure motivational conflicts regarding whether participants execute approach versus withdrawal behavior (with free-choice responses via continuous joystick movements) while allowing to record related electroencephalographic data such as midfrontal theta activity (MFT). MFT, a reliable marker of conflict representation on a neuronal level, was of particular interest to us since it has repeatedly been shown to explain related behavior, with relatively low MFT typically preceding approach-like risky behavior and relatively high MFT typically preceding withdrawal-like risk aversion. Our central hypothesis is that TUS decreases MFT in T-maze conflict situations and thereby increases approach and reduces withdrawal. Results indicate that TUS led to significant MFT decreases, which significantly explained increases in approach behavior and decreases in withdrawal behavior. This study expands TUS evidence on a physiological and behavioral level with a large sample size of human subjects, suggesting the promise of further research based on this distinct TUS-MFT-behavior link to influence conflict monitoring and its behavioral consequences. Ultimately, this can serve as a foundation for future clinical work to establish TUS interventions for emotional and motivational mental health.
Abstract via europepmc.
Exposures
Exposure 1: Right prefrontal cortex TUS vs Sham (virtual T-maze task)
Target: prefrontal cortex — “right prefrontal cortex (PFC), targeted via EEG electrode position F8”
Device: other named manufacturer · Thync (device prototype; product name Neurotrek U+) · Neurotrek U+ ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 0.125 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 40 | ✓✓✓⚑ |
| Duty cycle (%) | 0.5pulse duration × PRF gives 0.5% | ✓✓✓⚑ |
| Sonication duration (s) | 120 | ✓✓✓ |
| Free-field pressure (kPa) | 1,090 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 40 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 0.199 | ✓✓✓ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Single-element transducer focused at 30 mm via a two-part lens, applied via EEG electrode position F8 to target the right PFC; TUS or Sham (transducer flipped so the beam emanated away from the skull) was delivered double-blind, order randomly counterbalanced within subjects across two sessions separated by exactly 7 days; the virtual T-maze task (100 trials) began about 50 min and ended about 100 min after TUS/Sham.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— Table 1 row labels are shifted by one row in text extraction (MinerU); PRF=40 Hz value read from the row visually labelled 'PL' which, cross-checked against the referenced Sanguinetti/Reznik studies with identical device and known published parameters, is actually the PRF row.exposures[0].timing.duty_cycle_pct— Table 1 row labels are shifted by one row; the 0.50% value read from the row visually labelled '$PRF$' is, by cross-check with the known device parameters, the duty-cycle row.exposures[0].timing.pulse_duration_ms— Table 1 row labels are shifted by one row; 125 µs read from the row visually labelled '$I_{SPTA}$' is, by cross-check, the pulse-length (PL) row.auditory_control— Both TUS and Sham conditions produced the same audible 40 Hz PRF humming from the device, so auditory experience was matched between conditions; this does not map cleanly onto the closed vocabulary (not masking, ramping, or a dedicated sound-only sham).sham_type— Sham was delivered by flipping the transducer so the beam emanated away from the skull (device still powered), matching the 'aimed away' variant of inactive_transducer.