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Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

ABSTRACT: Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions remain about the elementary cognitive processes that account for the deficit.Using the Designer Receptors Exclusively Activated by Designer Drugs system, we reversibly decreased MD activity during behavioral tasks assessing elementary cognitive processes inherent to flexible goal-directed behaviors, including extinction, contingency degradation, outcome devaluation, and Pavlovian-to-instrumental transfer (n = 134 mice).While MD hypofunction impaired reversal learning, it did not affect the ability to learn about nonrewarded cues or the ability to modulate action selection based on the outcome value. In contrast, decreasing MD activity delayed the ability to adapt to changes in the contingency between actions and their outcomes. In addition, while Pavlovian learning was not affected by MD hypofunction, decreasing MD activity during Pavlovian learning impaired the ability of conditioned stimuli to modulate instrumental behavior.Mediodorsal thalamus hypofunction causes cognitive inflexibility reflected by an impaired ability to adapt actions when their consequences change. Furthermore, it alters the encoding of environmental stimuli so that they cannot be properly utilized to guide behavior. Modulating MD activity could be a potential therapeutic strategy for promoting adaptive behavior in human subjects with cognitive inflexibility.

SUBMITTER: Parnaudeau S

PROVIDER: S-EPMC4177020 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

Parnaudeau Sébastien S Taylor Kathleen K Bolkan Scott S SS Ward Ryan D RD Balsam Peter D PD Kellendonk Christoph C

Biological psychiatry 20140326 5

<h4>Background</h4>Cognitive inflexibility is a core symptom of several mental disorders including schizophrenia. Brain imaging studies in schizophrenia patients performing cognitive tasks have reported decreased activation of the mediodorsal thalamus (MD). Using a pharmacogenetic approach to model MD hypofunction, we recently showed that decreasing MD activity impairs reversal learning in mice. While this demonstrates causality between MD hypofunction and cognitive inflexibility, questions rema ...[more]

PMID: 24813335

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Project description:Humans have the ability to craft abstract, temporally extended and hierarchically organized plans. For instance, when considering how to make spaghetti for dinner, we typically concern ourselves with useful "subgoals" in the task, such as cutting onions, boiling pasta, and cooking a sauce, rather than particulars such as how many cuts to make to the onion, or exactly which muscles to contract. A core question is how such decomposition of a more abstract task into logical subtasks happens in the first place. Previous research has shown that humans are sensitive to a form of higher-order statistical learning named "community structure". Community structure is a common feature of abstract tasks characterized by a logical ordering of subtasks. This structure can be captured by a model where humans learn predictions of upcoming events multiple steps into the future, discounting predictions of events further away in time. One such model is the "successor representation", which has been argued to be useful for hierarchical abstraction. As of yet, no study has convincingly shown that this hierarchical abstraction can be put to use for goal-directed behavior. Here, we investigate whether participants utilize learned community structure to craft hierarchically informed action plans for goal-directed behavior. Participants were asked to search for paintings in a virtual museum, where the paintings were grouped together in "wings" representing community structure in the museum. We find that participants' choices accord with the hierarchical structure of the museum and that their response times are best predicted by a successor representation. The degree to which the response times reflect the community structure of the museum correlates with several measures of performance, including the ability to craft temporally abstract action plans. These results suggest that successor representation learning subserves hierarchical abstractions relevant for goal-directed behavior.

Dataset Information

Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

Publications

Mediodorsal thalamus hypofunction impairs flexible goal-directed behavior.

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