Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making

Elizabeth J Coulthard, Rafal Bogacz, Shazia Javed, Lucy K Mooney, Gillian Murphy, Sophie Keeley, Alan L Whone, Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making. Brain, in press, . November 2012. No electronic version available.


Even simple behavior requires us to take 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 prior to 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 a??normalization terma?? in Bayesa?? theorem). Here, we test these theories by investigating twenty-two patients with Parkinsona??s disease either treated with both deep brain stimulation (DBS) to the subthalamic nucleus (STN) and dopaminergic therapy or managed with dopaminergic therapy alone. We employ computerised tasks that probe three cognitive functions a?? 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 DBS 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, while DBS to the region of the STN 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 STN region DBS ON did not slow down appropriately to revise their plan, a pattern of behaviour that mirrors the impulsivity described clinically in some patients with STN DBS. Thus, we demonstrate distinct mechanisms for two important facets of human decision making a?? first, a role for dopamine in memory consolidation and, second, the critical importance of STN in successful decision making when multiple pieces of information must be combined.

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