Computational Dissociation of Dopaminergic and Cholinergic Effects on Action Selection and Inhibitory Control
Computational Dissociation of Dopaminergic and Cholinergic Effects on Action Selection and Inhibitory Control
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DOI：
10.1016/j.bpsc.2019.10.011
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发表时间：
2020-03-01
影响因子：
5.9
通讯作者：
Heinzle, Jakob
中科院分区：
文献类型：
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作者：
Aponte, Eduardo A.;Schobi, Dario;Heinzle, Jakob
背景：精神分裂症患者在反跳任务中比健康人犯更多的错误。在这个范例中，要求参与者抑制对目标的反射性扫视，并选择正确的动作（相反方向的扫视）。虽然这种赤字的确切起源尚不清楚，它已连接到异常的多巴胺能和胆碱能neuromodulation.METHODS：研究多巴胺和乙酰胆碱对抑制控制和动作选择的影响，我们管理两个选择性药物（左旋多巴200 mg/加兰他敏8 mg）健康志愿者（N = 100）进行antisaccade任务。计算模型SERIA（随机早期反应，抑制，和后期行动）被用来分离的贡献抑制控制和行动选择经验的反应时间和错误率。结果：建模表明，左旋多巴改善行动选择（在成本增加的反应时间），但抑制控制没有显着的效果。相比之下，根据我们的模型，加兰他敏以剂量依赖性方式影响抑制控制，在低剂量下减少抑制失败，在较高水平下增加抑制失败。这些影响是足够具体的计算分析允许识别的药物给一个人与70%的accuracy.CONCLUSIONS：我们的研究结果不支持这一假设，即升高的紧张性多巴胺强烈损害抑制控制。相反，左旋多巴提高了选择正确行动的能力。然而，抑制控制调制胆碱能药物。这种方法可能为未来的计算分析提供一个起点，以区分异质性疾病（如精神分裂症）中的神经调节异常。
BACKGROUND: Patients with schizophrenia make more errors than healthy subjects in the antisaccade task. In this paradigm, participants are required to inhibit a reflexive saccade to a target and to select the correct action (a saccade in the opposite direction). While the precise origin of this deficit is not clear, it has been connected to aberrant dopaminergic and cholinergic neuromodulation.METHODS: To study the impact of dopamine and acetylcholine on inhibitory control and action selection, we administered two selective drugs (levodopa 200 mg/galantamine 8 mg) to healthy volunteers (N = 100) performing the antisaccade task. The computational model SERIA (stochastic early reaction, inhibition, and late action) was employed to separate the contribution of inhibitory control and action selection to empirical reaction times and error rates.RESULTS: Modeling suggested that levodopa improved action selection (at the cost of increased reaction times) but did not have a significant effect on inhibitory control. By contrast, according to our model, galantamine affected inhibitory control in a dose-dependent fashion, reducing inhibition failures at low doses and increasing them at higher levels. These effects were sufficiently specific that the computational analysis allowed for identifying the drug administered to an individual with 70% accuracy.CONCLUSIONS: Our results do not support the hypothesis that elevated tonic dopamine strongly impairs inhibitory control. Rather, levodopa improved the ability to select correct actions. However, inhibitory control was modulated by cholinergic drugs. This approach may provide a starting point for future computational assays that differentiate neuromodulatory abnormalities in heterogeneous diseases like schizophrenia.