Brain activity, disruption and connectivity comparisons identify origins of human metacognition in other primates
Kentaro Miyamoto, Simone D’Ambrogio, Caroline Harbison, Nicole Eichert, Urs Schüffelgen, Andrew Emberton, Jerome Sallet, Rogier B. Mars, Nima Khalighinejad, Matthew FS Rushworth
Nature Human Behaviour 2026 · 10.1038/s41562-026-02473-w
Abstract
Planning requires anticipating the environmental contingencies that we will encounter and also our own future behaviour in those scenarios. The evolutionary origins of such prospective decision simulations have, however, been difficult to investigate. Moreover, in humans, these metacognitive processes are associated with a distinctively human brain region in the anterior lateral prefrontal cortex. Here we demonstrate these capacities in macaques and their neural bases in two complementary patterns of brain activity in different ventrolateral prefrontal areas: areas 45a and 47/12o. We also examine the impact of ultrasonic disruption of each area. We compare behavioural, brain activity and disruption patterns in humans and macaques. Finally, comparative connectional analysis revealed similarities between the conjunction of the two circuits associated with areas 45a and 47/12o in macaques and the human anterior lateral prefrontal area. In combination, the results suggest behavioural and anatomical origins of metacognitive processes that have become especially sophisticated in humans.
Abstract via europepmc.
Exposures
Exposure 1: TUS of macaque area 45a (bilateral)
Target: inferior frontal gyrus — “area 45a”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-250 four-element annular array, driven by TPO-105 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓⚑ |
| Duty cycle (%) | 30pulse duration × PRF gives 30% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 80 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 900, 1,090swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 27.3, 40.3swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | 8.2, 12.1swept | ✓✓✓ |
Duty cycle 30%; pulse length 30 ms; pulse repetition interval 100 ms; total stimulation duration 40 s. All targets were sonicated bilaterally for 60 s in total, with 30 s of stimulation applied to a target from each hemisphere, immediately followed by the homologous contralateral target in pseudo-random order; behaviour was tested straight after sonication, with 24 h between sessions.
Exposure 2: TUS of macaque area 47/12o (bilateral)
Target: inferior frontal gyrus — “area 47/12o”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-250 four-element annular array, driven by TPO-105 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | 30 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 30pulse duration × PRF gives 30% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 80 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | 1,130, 1,170swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 43.2, 45.7swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | 12.3, 13.7swept | ✓✓✓ |
Duty cycle 30%; pulse length 30 ms; pulse repetition interval 100 ms; total stimulation duration 40 s. All targets were sonicated bilaterally for 60 s in total, with 30 s of stimulation applied to a target from each hemisphere, immediately followed by the homologous contralateral target in pseudo-random order; behaviour was tested straight after sonication, with 24 h between sessions.
Flags from extraction
exposures[0].timing.sonication_duration_s— Protocol states total stimulation duration 40 s, but the design paragraph says 60 s in total with 30 s per hemisphere; recorded the protocol statement.exposures[0].in_situ.pressure_kpa— Simulated values are given separately for left and right hemisphere (k-Plan); recorded as a two-element list [min, max] in kPa converted from MPa, not a range of subjects.exposures[1].in_situ.pressure_kpa— Simulated values are given separately for left and right hemisphere (k-Plan); recorded as a two-element list [min, max] in kPa converted from MPa.n_subjects— Three monkeys in the behavioural TUS experiment; the resting-state fMRI after TUS used two animals, one of which (M5) is not among the listed behavioural animals, so the total exposed may be four.anaesthesia— Behavioural testing after TUS was awake; anaesthesia state during the TUS rs-fMRI scans is not stated.exposures[0].timing.pulse_repetition_frequency_hz— PRF 10 Hz is the conversion of the stated 100 ms pulse repetition interval.n_sessions_per_subject— Five to seven sessions per condition per animal are stated; the total per animal is not, so left not_reported.exposures[0].label— The parietal opercular control stimulation (real ultrasound, 0.89-1.17 MPa simulated) is treated as a control condition, not an exposure.