Interaction and functional specialization across a distributed neural circuit for flexible task control in macaques

Journal article

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.

Authors: Marche, K; Trudel, N; Schüffelgen, U; Smart, S; Harbison, CM

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 17
• Issue: 1
• Article number: 1063
• Publication date: 2026-01-24
• Acceptance date: 2025-10-23
• DOI: 10.1038/s41467-025-65766-0
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Task (project management); Hippocampal formation; Macaque; Thalamus; Prefrontal cortex; Nerve net; Centrality; Neural activity; Control (management); Ventral tegmental area