在现实世界的决策场景中,负面后果并不总是在选择后立即发生。行动和结果之间的这种延迟导致了低估,或“延迟折扣”,的惩罚。虽然对立即惩罚敏感的神经底物已经得到了充分的研究,对延迟后果的调查很少。这里,我们评估了外侧眶额皮质(LOFC)和基底外侧杏仁核(BLA)的作用,涉及成本/效益决策的两个地区,对延迟惩罚和立即惩罚的敏感性。延迟惩罚决策任务(DPDT)用于衡量啮齿动物的惩罚延迟折扣。DPDT期间,老鼠在一个小的,单个颗粒奖励和一个大的,三粒奖励伴有轻微的脚部电击。随着任务的进展,在冲击之前,延迟会在整个会议期间系统地增加或减少。我们观察到老鼠避免与立即惩罚相关的选择,然后在惩罚延迟时将偏好转向这些选项。LOFC失活不会影响立即惩罚的奖励选择,但减少了延迟惩罚的选择。我们还观察到,BLA失活减少了对上升而不是下降延迟的延迟惩罚的选择。任一大脑区域的失活对男性和女性的决策产生了可比的影响,但是在做出选择的遗漏和潜伏期中观察到性别差异。总之,LOFC和BLA均有助于延迟惩罚,并可作为有希望的治疗目标,以提高决策过程中对延迟惩罚的敏感性.重要性声明延迟后发生的负面后果往往被低估,这可能导致不适应的决策。虽然在寻求奖励过程中对立即惩罚的敏感性已经得到了充分研究,对延迟惩罚敏感的神经基础尚不清楚.这里,我们使用延迟惩罚决策任务来确定外侧眶额皮质和基底外侧杏仁核都调节延迟惩罚的折扣,这表明这些区域可能是改善精神病理学决策的潜在目标。
In real-world decision-making scenarios, negative consequences do not always occur immediately after a choice. This delay between action and outcome drives the underestimation, or \"delay discounting\", of punishment. While the neural substrates underlying sensitivity to immediate punishment have been well-studied, there has been minimal investigation of delayed consequences. Here, we assessed the role of lateral orbitofrontal cortex (LOFC) and basolateral amygdala (BLA), two regions implicated in cost/benefit decision-making, in sensitivity to delayed vs immediate punishment. The delayed punishment decision-making task (DPDT) was used to measure delay discounting of punishment in rodents. During DPDT, rats choose between a small, single pellet reward and a large, three pellet reward accompanied by a mild foot shock. As the task progresses, the shock is preceded by a delay that systematically increases or decreases throughout the session. We observed that rats avoid choices associated with immediate punishment, then shift preference toward these options when punishment is delayed. LOFC inactivation did not influence choice of rewards with immediate punishment, but decreased choice of delayed punishment. We also observed that BLA inactivation reduced choice of delayed punishment for ascending but not descending delays. Inactivation of either brain region produced comparable effects on decision-making in males and females, but there were sex differences observed in omissions and latency to make a choice. In summary, both LOFC and BLA contribute to the delay discounting of punishment and may serve as promising therapeutic targets to improve sensitivity to delayed punishment during decision-making.Significance StatementNegative consequences occurring after a delay are often underestimated, which can lead to maladaptive decision-making. While sensitivity to immediate punishment during reward-seeking has been well-studied, the neural substrates underlying sensitivity to delayed punishment remain unclear. Here, we used the Delayed Punishment Decision-making Task to determine that lateral orbitofrontal cortex and basolateral amygdala both regulate the discounting of delayed punishment, suggesting that these regions may be potential targets to improve decision-making in psychopathology.