Interaction and functional specialization across a distributed neural circuit for flexible task control in macaques
K. Marche, N. Trudel, U. Schüffelgen, S. Smart, C. M. Harbison, J. Scholl, J. Sallet, F-X Neubert, J. Algermissen, N. Khalighinejad, JX O’Reilly, MC Klein-Flügge, MFS Rushworth
Nature Communications 2026 · 10.1038/s41467-025-65766-0
Abstract
Reversal tasks have been regarded as probes of behavioural inhibition and linked to prefrontal and specifically orbitofrontal cortex. The centrality of behavioural inhibition to reversal task performance and the task's dependence on particular prefrontal sub-regions have, however, been questioned in primates. Using a combination of whole brain recording, transient ultrasonic disruption, two types of reversal task, and a task model emphasizing identification of transitions between latent states, we show that male macaques track latent state transitions in addition to choice values in reversal tasks. Activity reflecting both these features is prominent in dorsomedial frontal cortex, and anterior and dorsomedial thalamus when, and just before, animals select choices. By contrast, hippocampal activity continually tracks the probability of a reversal between latent states. We identify patterns of activity interaction spanning the three nodes of this circuit and demonstrate that disruption of each leads to reversal task impairment albeit in different ways.
Abstract via europepmc.
Exposures
Exposure 1: dmPFC TUS
Target: dorsomedial prefrontal cortex — “dmPFC”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-250 ✓
| 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) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 60 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 16 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
TUS was delivered bilaterally (40 s to the left hemisphere, 40 s to the right hemisphere) using a duty cycle of 30%, pulse length of 30 ms, and pulse repetition interval of 100 ms. This was an offline protocol: monkeys began the behavioural task 5-10 minutes after stimulation ended. Each stimulation condition (dmPFC, hippocampus, thalamus, or sham) was repeated 5-8 times per animal on separate days, at least 24 hours apart, with a sham day scheduled at the start and end of the series.
Exposure 2: Hippocampus TUS
Target: hippocampus — “hippocampus”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-250 ✓
| 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) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 60 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 18.5 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
TUS was delivered bilaterally (40 s to the left hemisphere, 40 s to the right hemisphere) using a duty cycle of 30%, pulse length of 30 ms, and pulse repetition interval of 100 ms. This was an offline protocol: monkeys began the behavioural task 5-10 minutes after stimulation ended. Each stimulation condition (dmPFC, hippocampus, thalamus, or sham) was repeated 5-8 times per animal on separate days, at least 24 hours apart, with a sham day scheduled at the start and end of the series.
Exposure 3: Thalamus TUS
Target: anterior thalamic nucleus, mediodorsal nucleus — “anterior and dorsomedial thalamus”
Device: NeuroFUS · Sonic Concepts (sold by Brainbox) · NeuroFUS CTX-250 ✓
| 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) | 40 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 60 | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | simulationsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 17 | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
TUS was delivered bilaterally (40 s to the left hemisphere, 40 s to the right hemisphere) using a duty cycle of 30%, pulse length of 30 ms, and pulse repetition interval of 100 ms. This was an offline protocol: monkeys began the behavioural task 5-10 minutes after stimulation ended. Each stimulation condition (dmPFC, hippocampus, thalamus, or sham) was repeated 5-8 times per animal on separate days, at least 24 hours apart, with a sham day scheduled at the start and end of the series.
Flags from extraction
n_sessions_per_subject— Paper states 'each stimulation condition was repeated 5-8 times for each animal' (per target/sham condition, not a single total-sessions count); recorded as the stated range.randomised— Paper describes the order of TUS targets as 'pseudo-randomized' rather than fully randomised; recorded as true.auditory_control— Sham TUS matched the real procedure except that 'sonication was not triggered although the TUS sound was simulated'; classified as sound_only_sham.exposures[2].target.terms— Paper refers to the thalamic target variably as 'anterior medial thalamus' and 'anterior and dorsomedial thalamus'; both anterior_thalamic_nucleus and mediodorsal_nucleus terms are given.direction_of_effect— TUS effects differed qualitatively across the three targets (loss of influence vs. reversal of influence direction), so classified as mixed_or_unclear.