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. Author manuscript; available in PMC: 2017 May 24.
Published in final edited form as: Nat Neurosci. 2016 Mar;19(3):404–413. doi: 10.1038/nn.4238

Figure 5.

Figure 5

Theory-driven biophysical and RL approaches. (a) Insights into working-memory disturbances in schizophrenia. Reducing NMDA currents on inhibitory interneurons leads to overall disinhibition and broadens the bump representation of a stimulus in working memory (compare top versus bottom), making it more susceptible to distractors, especially those that activate neighboring neurons. Adapted with permission from ref. 90. (b) Insights into obsessive-compulsive disorder. Both lowering serotonin levels and increasing glutamatergic levels renders activity patterns excessively stable, such that when a new cluster of neurons is stimulated, activity does not shift to the new location, as would be expected (top, normal response), but rather remains ‘stuck’ in the previous location (bottom). Adapted with permission from ref. 2. (c) Negative symptoms in schizophrenia are related to a failure to represent expected values. In an instrumental-learning task, healthy controls and patients with schizophrenia with low levels of negative symptoms learned according to a reinforcement-learning algorithm that explicitly represents the expected value of each state-action pair (Q-learning), whereas patients with schizophrenia with high levels of negative symptoms learned according to an algorithm that learns preferences without such explicit representations (actor-critic). Adapted with permission from ref. 101. (d) Examining the processes that guide goal-directed evaluations. Shown is a decision tree corresponding to a sequence of three binary choices, where each choice leads to a gain or loss indicated by the numbers. A RL model was fitted to choices and contained two key parameters, representing the probability of continuing thinking when encountering a large salient loss (red arrow, −X) or when encountering other outcomes (blue arrows). (e) Subjects were far less likely to continue evaluating a branch after encountering a salient loss (red bars) than after other outcomes, for a variety of salient loss sizes. Adapted with permission from ref. 132.