RT Journal Article SR Electronic T1 How distributed subcortical integration of reward and threat may inform subsequent approach-avoidance decisions JF bioRxiv FD Cold Spring Harbor Laboratory SP 2024.04.22.590530 DO 10.1101/2024.04.22.590530 A1 Hulsman, Anneloes M. A1 Klaassen, Felix H. A1 de Voogd, Lycia D. A1 Roelofs, Karin A1 Klumpers, Floris YR 2024 UL http://biorxiv.org/content/early/2024/04/23/2024.04.22.590530.abstract AB Healthy and successful living involves carefully navigating rewarding and threatening situations by balancing approach and avoidance behaviours. Excessive avoidance to evade potential threats often leads to forfeiting potential rewards. However, little is known about how reward and threat information is integrated neurally to inform either approach or avoidance decisions. In this preregistered study, participants (N=31, 17F) made approach-avoidance decisions under varying reward (monetary gains) and threat (electrical stimulations) prospects during functional MRI scanning. In contrast to theorized parallel subcortical processing of reward and threat information before cortical integration, Bayesian Multivariate Multilevel analyses revealed subcortical reward and threat integration prior to indicating approach-avoidance decisions. This integration occurred in the ventral striatum, thalamus, and bed nucleus of the stria terminalis (BNST). When reward was low, avoidance decisions dominated, reflected in stronger reactivity to threat prior to indicating avoidance decisions across these regions. In addition, the amygdala exhibited dual sensitivity to reward and threat. While anticipating the outcome of approach decisions, characterized by elevated risk of electrical stimulation, increased threat-related activity within the salience network (dorsal anterior cingulate cortex, thalamus, periaqueductal gray, BNST) was observed. Conversely, anticipating the outcome of avoidance decisions, marked by reduced reward potential, was associated with suppression of reward-related activity in the ventromedial prefrontal cortex and ventral striatum. These findings shed light on the temporal dynamics of approach-avoidance decision-making. Importantly, they demonstrate the role of subcortical integration of reward and threat information in balancing approach and avoidance, challenging theories positing predominantly separate subcortical processing before cortical integration.Competing Interest StatementThe authors have declared no competing interest.