Am J Psychiatry. 2013 Nov;170(11):1326-34. doi: 10.1176/appi.ajp.2013.12070978.
Frontostriatal circuitry is critical to learning processes, and its disruption may underlie maladaptive decision making and the generation of psychotic symptoms in schizophrenia. However, there is a paucity of evidence directly examining the role of modulatory neurotransmitters on frontostriatal function in humans. In order to probe the effects of modulation on frontostriatal circuitry during learning and to test whether disruptions in learning processes may be related to the pathogenesis of psychosis, the authors explored the brain representations of reward prediction error and incentive value, two key reinforcement learning parameters, before and after methamphetamine challenge.
Healthy volunteers (N=18) underwent functional MRI (fMRI) scanning while performing a reward learning task on three occasions: after placebo, after methamphetamine infusion (0.3 mg/kg body weight), and after pretreatment with 400 mg of amisulpride and then methamphetamine infusion. Brain fMRI representations of learning signals, calculated using a reinforcement Q-learning algorithm, were compared across drug conditions.
In the placebo condition, reward prediction error was coded in the ventral striatum bilaterally and incentive value in the ventromedial prefrontal cortex bilaterally. Reward prediction error and incentive value signals were disrupted by methamphetamine in the left nucleus accumbens and left ventromedial prefrontal cortex, respectively. Psychotic symptoms were significantly correlated with incentive value disruption in the ventromedial prefrontal and posterior cingulate cortex. Amisulpride pretreatment did not significantly alter methamphetamine-induced effects.
The results demonstrate that methamphetamine impairs brain representations of computational parameters that underpin learning. They also demonstrate a significant link between psychosis and abnormal monoamine-regulated learning signals in the prefrontal and cingulate cortices.
额-纹状体神经回路对学习过程至关重要，其功能障碍可能是精神分裂症患者产生适应不良决策和精神病症状的基础。然而，目前直接研究调节性神经递质在人类额-纹状体功能中的作用的证据很少。为了探究调节对学习过程中额-纹状体回路的影响，并检验学习过程的中断是否与精神病的发病机制有关，作者在健康志愿者接受安非他命（0.3 毫克/千克体重）和预先给予 400 毫克氨磺必利后接受安非他命输注之前和之后，使用功能磁共振成像（fMRI）扫描来探索奖励预测误差和激励价值的大脑代表，这是两个关键的强化学习参数。
健康志愿者（N=18）在三次试验中进行 fMRI 扫描：安慰剂后、安非他命输注后（0.3 毫克/千克体重）和预先给予 400 毫克氨磺必利后再给予安非他命输注后。使用强化 Q 学习算法比较了不同药物条件下学习信号的大脑 fMRI 代表。
在安慰剂条件下，双侧腹侧纹状体编码奖励预测误差，双侧腹内侧前额叶皮层编码激励价值。安非他命分别在左侧伏隔核和左侧腹内侧前额叶皮层破坏了奖励预测误差和激励价值信号。精神病症状与腹内侧前额叶和后扣带回皮层的激励价值破坏显著相关。氨磺必利预先给药并没有显著改变安非他命引起的影响。
结果表明，安非他命损害了学习基础的计算参数的大脑代表。它们还表明，前额叶和扣带回皮层中异常的单胺调节学习信号与精神病之间存在显著联系。
