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Human claustrum neurons encode uncertainty and prediction errors during aversive learning

damisah, e. c.; Hu, M.; Dalvit, R.; Medina, M.; dougherty, m.; Zhou, Y.; barretonieves, j.; obaid, s.; Afrasiyabi, A.; Krishnaswamy, S.; Kaye, A. P.; Gunel, M.; krystal, j.; Sheth, K. N.; Gu, X.; Pittenger, C.; wise, t.

2026-03-15 neuroscience
10.64898/2026.03.13.711590 bioRxiv
Show abstract

Flexible behavior depends on continuous updating of internal models, yet the neural circuits coordinating this process remain poorly understood [1]. The claustrum -- reciprocally connected to nearly the entire neocortex -- is uniquely positioned to influence cortical processing. Here we report single-neuron recordings from the human claustrum during aversive learning [2], with anterior cingulate cortex and amygdala recordings for comparison. Claustrum and anterior cingulate neurons displayed structured, task-related responses. Distinct subpopulations encoded stimulus onset and action-contingent outcomes, with outcome representations diverging between regions. Critically, both regions encoded model-derived latent variables -- uncertainty and prediction error -- but with different temporal profiles: only the anterior cingulate carried uncertainty signals during the intertrial period, while both regions encoded uncertainty and prediction error during the active-avoidance period. The amygdala, by contrast, showed minimal latent-variable modulation. These findings provide evidence that human claustrum neurons track higher-order cognitive variables not directly observable from sensory input, and reveal dissociable roles for the claustrum and anterior cingulate cortex in tracking latent task states.

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