Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.
Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.
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DOI：
10.1093/brain/aws273
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发表时间：
2012-12
期刊：
影响因子：
--
通讯作者：
Whone AL
中科院分区：
文献类型：
--
作者：
Coulthard EJ;Bogacz R;Javed S;Mooney LK;Murphy G;Keeley S;Whone AL
即使是简单的行为也需要我们结合多种学到的信息和新信息来做出决策。做出这样的决定需要学习对每个给定刺激的最佳响应，以及在选择响应之前结合多个刺激的概率信息。决策的计算理论预测，学习个体刺激-反应关联以及来自多个刺激的信息的快速组合取决于基底神经节电路的不同组成部分。特别是，最佳反应选择所需的学习和记忆保留很大程度上依赖于多巴胺，而概率性整合信息则严重依赖于谷氨酸能底丘脑核的功能（计算贝叶斯定理中的“标准化项”）。在这里，我们通过调查 22 名帕金森病患者来检验这些理论，这些患者要么接受丘脑底核深部脑刺激并接受多巴胺能治疗，要么单独接受多巴胺能治疗。我们使用计算机化任务来探索三种认知功能：信息获取（学习）、延迟记忆以及必须组合多个顺序呈现的信息时的信息整合。患者执行开启或关闭深部脑刺激和/或开启或关闭多巴胺能治疗的任务。与计算理论一致，我们表明，停止多巴胺能治疗会在一段时间内损害概率信息的记忆，而当必须组合多个获得的信息时，对丘脑底核区域的深部脑刺激会扰乱决策制定。此外，我们发现，当参与者需要根据决策任务中提供的最后一条信息更新他们的决定时，接受丘脑底核区域深部脑刺激的患者并没有适当放慢速度来修改他们的计划，这种行为模式反映了一些接受丘脑底核深部脑刺激的患者临床上描述的冲动性。因此，我们证明了人类决策的两个重要方面的不同机制：首先，多巴胺在记忆巩固中的作用，其次，当必须组合多个信息时，底丘脑核在成功决策中的至关重要性。
Even simple behaviour requires us to make decisions based on combining multiple pieces of learned and new information. Making such decisions requires both learning the optimal response to each given stimulus as well as combining probabilistic information from multiple stimuli before selecting a response. Computational theories of decision making predict that learning individual stimulus–response associations and rapid combination of information from multiple stimuli are dependent on different components of basal ganglia circuitry. In particular, learning and retention of memory, required for optimal response choice, are significantly reliant on dopamine, whereas integrating information probabilistically is critically dependent upon functioning of the glutamatergic subthalamic nucleus (computing the ‘normalization term’ in Bayes’ theorem). Here, we test these theories by investigating 22 patients with Parkinson’s disease either treated with deep brain stimulation to the subthalamic nucleus and dopaminergic therapy or managed with dopaminergic therapy alone. We use computerized tasks that probe three cognitive functions—information acquisition (learning), memory over a delay and information integration when multiple pieces of sequentially presented information have to be combined. Patients performed the tasks ON or OFF deep brain stimulation and/or ON or OFF dopaminergic therapy. Consistent with the computational theories, we show that stopping dopaminergic therapy impairs memory for probabilistic information over a delay, whereas deep brain stimulation to the region of the subthalamic nucleus disrupts decision making when multiple pieces of acquired information must be combined. Furthermore, we found that when participants needed to update their decision on the basis of the last piece of information presented in the decision-making task, patients with deep brain stimulation of the subthalamic nucleus region did not slow down appropriately to revise their plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with subthalamic nucleus deep brain stimulation. Thus, we demonstrate distinct mechanisms for two important facets of human decision making: first, a role for dopamine in memory consolidation, and second, the critical importance of the subthalamic nucleus in successful decision making when multiple pieces of information must be combined.
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影响因子：
158.5
作者：
Follett, Kenneth A.;Weaver, Frances M.;Reda, Domenic J.
通讯作者：
Reda, Domenic J.
影响因子：
5.1
作者：
Halbig, T. D.;Tse, W.;Olanow, C. W.
通讯作者：
Olanow, C. W.
影响因子：
14.5
作者：
Hershey, Tamara;Campbell, Meghan C.;Perlmutter, Joel S.
通讯作者：
Perlmutter, Joel S.
影响因子：
2.6
作者：
Cools, R;Barker, RA;Robbins, TW
通讯作者：
Robbins, TW
影响因子：
5.3
作者：
Isoda, Masaki;Hikosaka, Okihide
通讯作者：
Hikosaka, Okihide