Transcranial focused ultrasound to human rIFG improves response inhibition through modulation of the P300 onset latency
Justin M Fine, Archana S Mysore, Maria E Fini, William J Tyler, Marco Santello
eLife 2023, 12 · 10.7554/elife.86190
Abstract
Response inhibition in humans is important to avoid undesirable behavioral action consequences. Neuroimaging and lesion studies point to a locus of inhibitory control in the right inferior frontal gyrus (rIFG). Electrophysiology studies have implicated a downstream event-related potential from rIFG, the fronto-central P300, as a putative neural marker of the success and timing of inhibition over behavioral responses. However, it remains to be established whether rIFG effectively drives inhibition and which aspect of P300 activity uniquely indexes inhibitory control-ERP timing or amplitude. Here, we dissect the connection between rIFG and P300 for inhibition by using transcranial-focused ultrasound (tFUS) to target rIFG of human subjects while they performed a Stop-Signal task. By applying tFUS simultaneously with different task events, we found behavioral inhibition was improved, but only when applied to rIFG simultaneously with a 'stop' signal. Improved inhibition through tFUS to rIFG was indexed by faster stopping times that aligned with significantly shorter N200/P300 onset latencies. In contrast, P300 amplitude was modulated during tFUS across all groups without a paired change in behavior. Using tFUS, we provide evidence for a causal connection between anatomy, behavior, and electrophysiology underlying response inhibition.
Abstract via europepmc.
Exposures
Exposure 1: Online tFUS to right inferior frontal gyrus (rIFG, pars opercularis) during a Stop-Signal task
Target: inferior frontal gyrus — “right inferior frontal gyrus (rIFG), pars opercularis”
Device: Blatek · Blatek ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.24 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 24 | ✓✓✓ |
| Sonication duration (s) | 0.5 | ✓✓✓ |
| Free-field pressure (kPa) | 820 | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 22.43 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 5.38 | ✓✓✓ |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 540 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 10.01 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 2.4 | ✓✓✓ |
tFUS was delivered to rIFG for 500 ms, time-locked (t=0 ms) to either the Go signal or the Stop signal on a subset of Go and Stop trials, using a carrier frequency of 0.5 MHz, PRF of 1.0 kHz, and duty cycle of 24%. Each experimental session consisted of 1200 trials across 12 blocks of 100 trials, mixing stimulation and no-stimulation blocks; trial types were randomly distributed to mitigate carry-over effects.
Flags from extraction
n_subjects— The Sham rIFG group (n=15) is excluded from n_subjects because the transducer was pointed away from the head and 'did not want substantial ultrasound energy transmitted'; only the rIFG (n=25) and S1 (n=23) groups received real tFUS to a cortical target, so both group sizes are listed.exposures[0].timing.pulse_duration_ms— The paper reports carrier frequency, PRF and duty cycle but never states the duration of the individual 0.5-MHz bursts triggered by channel 2; not computed from duty cycle/PRF per the no-arithmetic rule.