Multiple insular-prefrontal pathways underlie perception to execution during response inhibition in humans
Takahiro Osada, Koji Nakajima, Tomohiko Shirokoshi, Akitoshi Ogawa, Satoshi Oka, Koji Kamagata, Shigeki Aoki, Yasushi Oshima, Sakae Tanaka, Seiki Konishi
Nature Communications 2024, 15 · 10.1038/s41467-024-54564-9
Abstract
Inhibiting prepotent responses in the face of external stop signals requires complex information processing, from perceptual to control processing. However, the cerebral circuits underlying these processes remain elusive. In this study, we used neuroimaging and brain stimulation to investigate the interplay between human brain regions during response inhibition at the whole-brain level. Magnetic resonance imaging suggested a sequential four-step processing pathway: initiating from the primary visual cortex (V1), progressing to the dorsal anterior insula (daINS), then involving two essential regions in the inferior frontal cortex (IFC), namely the ventral posterior IFC (vpIFC) and anterior IFC (aIFC), and reaching the basal ganglia (BG)/primary motor cortex (M1). A combination of ultrasound stimulation and time-resolved magnetic stimulation elucidated the causal influence of daINS on vpIFC and the unidirectional dependence of aIFC on vpIFC. These results unveil asymmetric pathways in the insular-prefrontal cortex and outline the macroscopic cerebral circuits for response inhibition: V1→daINS→vpIFC/aIFC→BG/M1.
Abstract via europepmc.
Exposures
Exposure 1: TUS to dorsal anterior insula (daINS) for sustained suppression
Target: anterior insula — “dorsal anterior insula (daINS)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-500 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓⚑ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 30% | |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 30 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 10 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 15.2, 13.5swept | ✓✓✓⚑ |
| In-situ Ispta (W/cm²) | 4.5, 4.1swept | ✓✓✓ |
The ultrasound stimulation consisted of 30 ms pulse repeated every 100 ms, and the total sonication lasted for 40 s, which is known to induce sustained suppression of the target region. TUS was applied once to induce sustained suppression, and the stop-signal task (or spTMS-combined stop-signal task) was performed before and after TUS (e.g., three runs before and five runs after TUS in the daINS/vaINS experiment) to assess behavioral disruption.
Exposure 2: TUS to ventral anterior insula (vaINS) as control target
Target: anterior insula — “ventral anterior insula (vaINS)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-500 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 30% | |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 30 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 10 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 14.3 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 4.3 | ✓✓✓ |
The ultrasound stimulation consisted of 30 ms pulse repeated every 100 ms, and the total sonication lasted for 40 s, which is known to induce sustained suppression of the target region. TUS was applied once to induce sustained suppression, and the stop-signal task (or spTMS-combined stop-signal task) was performed before and after TUS (e.g., three runs before and five runs after TUS in the daINS/vaINS experiment) to assess behavioral disruption.
Exposure 3: TUS to ventral posterior inferior frontal cortex (vpIFC) for sustained suppression
Target: inferior frontal gyrus — “ventral posterior inferior frontal cortex (vpIFC)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-500 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 30% | |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 30 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 10 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 12.1 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 3.6 | ✓✓✓ |
The ultrasound stimulation consisted of 30 ms pulse repeated every 100 ms, and the total sonication lasted for 40 s, which is known to induce sustained suppression of the target region. TUS was applied once to induce sustained suppression, and the stop-signal task (or spTMS-combined stop-signal task) was performed before and after TUS (e.g., three runs before and five runs after TUS in the daINS/vaINS experiment) to assess behavioral disruption.
Exposure 4: TUS to anterior inferior frontal cortex (aIFC) for sustained suppression
Target: inferior frontal gyrus — “anterior inferior frontal cortex (aIFC)”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-500 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 500 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | not reportedpulse duration × PRF gives 30% | |
| Sonication duration (s) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 30 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 10 | ✓✓✓ |
| In-situ estimate | simulationmean or range across subjects | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 13.7 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 4.1 | ✓✓✓ |
The ultrasound stimulation consisted of 30 ms pulse repeated every 100 ms, and the total sonication lasted for 40 s, which is known to induce sustained suppression of the target region. TUS was applied once to induce sustained suppression, and the stop-signal task (or spTMS-combined stop-signal task) was performed before and after TUS (e.g., three runs before and five runs after TUS in the daINS/vaINS experiment) to assess behavioral disruption.
Flags from extraction
exposures[0].timing.pulse_repetition_frequency_hz— PRF (10 Hz) was derived from the stated inter-pulse period ('repeated every 100 ms'), a unit conversion rather than a directly stated PRF value.exposures[*].timing.duty_cycle_pct— Duty cycle is not explicitly stated; computing it from the 30 ms pulse / 100 ms period would require arithmetic the paper does not perform, so left not_reported.exposures[0].in_situ.isppa_w_cm2— Two different simulated intracranial intensity estimates for TUS to the daINS are given in different sub-experiments (15.2±1.7 W/cm2 in the daINS/vaINS behavioral experiment; 13.5±1.8 W/cm2 in the combined TUS-daINS+spTMS experiment); both are listed.n_subjects— Paper reports separate cohorts of 20 subjects for the daINS/vaINS TUS experiment, the TUS-daINS+spTMS-vpIFC/aIFC experiment, and the TUS-vpIFC/aIFC+spTMS experiment; it does not state whether these cohorts overlap or a total unique subject count exposed to TUS, so the three group sizes are listed rather than summed.n_sessions_per_subject— Paper does not explicitly state how many separate sessions (e.g., whether daINS and vaINS, or vpIFC and aIFC, TUS conditions were delivered on the same day or different sessions) each subject underwent.exposures[0].target.terms— The dorsal anterior insula (daINS) has no distinct id in the vocabulary (only 'anterior_insula' and 'posterior_insula' are listed); classified as anterior_insula.exposures[1].target.terms— The ventral anterior insula (vaINS) has no distinct id in the vocabulary; classified as anterior_insula, distinguished by label.