Reduction of Pavlovian Bias in Schizophrenia: Enhanced Effects in Clozapine-Administered Patients

The negative symptoms of schizophrenia (SZ) are associated with a pattern of reinforcement learning (RL) deficits likely related to degraded representations of reward values. However, the RL tasks used to date have required active responses to both reward and punishing stimuli. Pavlovian biases have been shown to affect performance on these tasks through invigoration of action to reward and inhibition of action to punishment, and may be partially responsible for the effects found in patients. Forty-five patients with schizophrenia and 30 demographically-matched controls completed a four-stimulus reinforcement learning task that crossed action (“Go” or “NoGo”) and the valence of the optimal outcome (reward or punishment-avoidance), such that all combinations of action and outcome valence were tested. Behaviour was modelled using a six-parameter RL model and EEG was simultaneously recorded. Patients demonstrated a reduction in Pavlovian performance bias that was evident in a reduced Go bias across the full group. In a subset of patients administered clozapine, the reduction in Pavlovian bias was enhanced. The reduction in Pavlovian bias in SZ patients was accompanied by feedback processing differences at the time of the P3a component. The reduced Pavlovian bias in patients is suggested to be due to reduced fidelity in the communication between striatal regions and frontal cortex. It may also partially account for previous findings of poorer “Go-learning” in schizophrenia where “Go” responses or Pavlovian consistent responses are required for optimal performance. An attenuated P3a component dynamic in patients is consistent with a view that deficits in operant learning are due to impairments in adaptively using feedback to update representations of stimulus value.

精神分裂症（schizophrenia, SZ）的阴性症状与一类强化学习（reinforcement learning, RL）缺陷模式相关，该缺陷大概率与奖赏价值表征受损有关。然而，迄今已有的强化学习任务均要求对奖赏与惩罚性刺激做出主动反应。已有研究表明，巴甫洛夫偏差（Pavlovian biases）可通过增强对奖赏的行动激活、抑制对惩罚的行动，影响受试者在这类任务中的表现，且可能部分解释了患者群体中观测到的相关效应。本研究纳入45名精神分裂症患者与30名人口统计学特征匹配的健康对照，所有受试者完成一项四刺激强化学习任务。该任务交叉设置行动类型（"Go"或"NoGo"）与最优结果效价（奖赏或回避惩罚），覆盖了行动类型与结果效价的全部组合。研究采用六参数强化学习模型对行为数据进行建模，并同步采集脑电图（electroencephalogram, EEG）信号。患者群体表现出巴甫洛夫行为偏差的减弱，该现象在全组受试者中均体现为"Go"偏差的降低。在接受氯氮平（clozapine）治疗的患者亚组中，巴甫洛夫偏差的减弱程度更为显著。精神分裂症患者的巴甫洛夫偏差减弱，同时伴随P3a成分（P3a component）出现时段的反馈加工差异。研究推测，患者的巴甫洛夫偏差减弱源于纹状体区域（striatal regions）与前额叶皮层（frontal cortex）之间的信息传递保真度下降。该现象也可部分解释此前在精神分裂症中观测到的"Go学习"能力受损的结果——这类任务要求"Go"反应或与巴甫洛夫机制一致的反应，才能达成最优表现。患者群体中P3a成分的动态过程减弱，与“操作性学习缺陷源于适应性利用反馈更新刺激价值表征的能力受损”这一学术观点相符。