Department of Psychiatry, University Behavioral Health Care & the Brain Health Institute, Rutgers University-New Brunswick, Piscataway, NJ 08855, USA.
Departments of Psychiatry & Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Neuron. 2023 Dec 20;111(24):4058-4070.e6. doi: 10.1016/j.neuron.2023.09.015. Epub 2023 Oct 25.
Influential accounts of addiction posit alterations in adaptive behavior driven by deficient dopaminergic prediction errors (PEs), signaling the discrepancy between actual and expected reward. Dopamine neurons encode these error signals in subjective terms, calibrated by individual risk preferences, as "utility" PEs. It remains unclear, however, whether people with drug addiction have PE deficits or their computational source. Here, using an analogous task to prior single-unit studies with known expectancies, we show that fMRI-measured PEs similarly reflect utility PEs. Relative to control participants, people with chronic cocaine addiction demonstrate reduced utility PEs in the dopaminoceptive ventral striatum, with similar trends in orbitofrontal cortex. Dissecting this PE signal into its subcomponent terms attributed these reductions to weaker striatal responses to received reward/utility, whereas suppression of activity with reward expectation was unchanged. These findings support that addiction may fundamentally disrupt PE signaling and reveal an underappreciated role for perceived reward value in this mechanism.
成瘾的影响因素假定适应性行为的改变是由多巴胺能预测误差(PE)引起的,这表明了实际奖励和预期奖励之间的差异。多巴胺神经元以主观术语编码这些误差信号,由个体风险偏好校准为“效用”PE。然而,目前尚不清楚吸毒成瘾者是否存在 PE 缺陷或其计算来源。在这里,我们使用与先前具有已知预期的单个单元研究类似的任务,表明 fMRI 测量的 PE 同样反映了效用 PE。与对照组相比,慢性可卡因成瘾者在多巴胺能接受的腹侧纹状体中表现出较低的效用 PE,而在眶额皮质中也有类似的趋势。将该 PE 信号分解为其分量项表明,这些减少归因于对所获得的奖励/效用的纹状体反应较弱,而对奖励预期的活动抑制不变。这些发现支持成瘾可能从根本上破坏 PE 信号,并揭示了感知奖励价值在这种机制中的一个被低估的作用。