Collins Anne G E, Brown Jaime K, Gold James M, Waltz James A, Frank Michael J
Department of Cognitive, Linguistics, and Psychological Sciences, Brown University, Providence, Rhode Island 02912, and
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, Maryland 21201.
J Neurosci. 2014 Oct 8;34(41):13747-56. doi: 10.1523/JNEUROSCI.0989-14.2014.
Previous research has shown that patients with schizophrenia are impaired in reinforcement learning tasks. However, behavioral learning curves in such tasks originate from the interaction of multiple neural processes, including the basal ganglia- and dopamine-dependent reinforcement learning (RL) system, but also prefrontal cortex-dependent cognitive strategies involving working memory (WM). Thus, it is unclear which specific system induces impairments in schizophrenia. We recently developed a task and computational model allowing us to separately assess the roles of RL (slow, cumulative learning) mechanisms versus WM (fast but capacity-limited) mechanisms in healthy adult human subjects. Here, we used this task to assess patients' specific sources of impairments in learning. In 15 separate blocks, subjects learned to pick one of three actions for stimuli. The number of stimuli to learn in each block varied from two to six, allowing us to separate influences of capacity-limited WM from the incremental RL system. As expected, both patients (n = 49) and healthy controls (n = 36) showed effects of set size and delay between stimulus repetitions, confirming the presence of working memory effects. Patients performed significantly worse than controls overall, but computational model fits and behavioral analyses indicate that these deficits could be entirely accounted for by changes in WM parameters (capacity and reliability), whereas RL processes were spared. These results suggest that the working memory system contributes strongly to learning impairments in schizophrenia.
先前的研究表明，精神分裂症患者在强化学习任务中存在障碍。然而，此类任务中的行为学习曲线源自多种神经过程的相互作用，包括基底神经节和多巴胺依赖的强化学习（RL）系统，以及涉及工作记忆（WM）的前额叶皮质依赖的认知策略。因此，尚不清楚精神分裂症中是哪个特定系统导致了障碍。我们最近开发了一项任务和计算模型，使我们能够在健康成年人类受试者中分别评估RL（缓慢的累积学习）机制与WM（快速但容量有限）机制的作用。在此，我们使用这项任务来评估患者在学习中障碍的具体来源。在15个单独的模块中，受试者学习为刺激选择三种动作之一。每个模块中要学习的刺激数量从两个到六个不等，这使我们能够将容量有限的WM的影响与增量RL系统区分开来。正如预期的那样，患者（n = 49）和健康对照组（n = 36）均表现出集合大小和刺激重复之间延迟的影响，证实了工作记忆效应的存在。总体而言，患者的表现明显比对照组差，但计算模型拟合和行为分析表明，这些缺陷完全可以由WM参数（容量和可靠性）的变化来解释，而RL过程则未受影响。这些结果表明，工作记忆系统对精神分裂症的学习障碍有很大影响。
