| Summary: | Summary: Learning to seek rewards and avoid punishments, based on positive and negative choice outcomes, is essential for human survival. Yet, the neural underpinnings of outcome valence in the human brainstem and the extent to which they differ in reward and punishment learning contexts remain largely elusive. Here, using simultaneously acquired electroencephalography and functional magnetic resonance imaging data, we show that during reward learning the substantia nigra (SN)/ventral tegmental area (VTA) and locus coeruleus are initially activated following negative outcomes, while the VTA subsequently re-engages exhibiting greater responses for positive than negative outcomes, consistent with an early arousal/avoidance response and a later value-updating process, respectively. During punishment learning, we show that distinct raphe nucleus and SN subregions are activated only by negative outcomes with a sustained post-outcome activity across time, supporting the involvement of these brainstem subregions in avoidance behavior. Finally, we demonstrate that the coupling of these brainstem structures with other subcortical and cortical areas helps to shape participants’ serial choice behavior in each context.
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