title: Distinct roles of dopamine and subthalamic nucleus in learning and probabilistic decision making.
abstract: 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.
authors.affiliation: Consultant Senior Lecturer, Department of Neurology, Institute of Clinical Neurosciences, University of Bristol and North Bristol NHS Trust, Frenchay Hospital, BS16 1LE, Bristol, UK. elizabeth.coulthard@bristol.ac.uk
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Coulthard
authors.forename: Rafal
authors.initials: R
authors.lastname: Bogacz
authors.forename: Shazia
authors.initials: S
authors.lastname: Javed
authors.forename: Lucy K
authors.initials: LK
authors.lastname: Mooney
authors.forename: Gillian
authors.initials: G
authors.lastname: Murphy
authors.forename: Sophie
authors.initials: S
authors.lastname: Keeley
authors.forename: Alan L
authors.initials: AL
authors.lastname: Whone
mesh_terms: D000704:Analysis of Variance; D003657:Decision Making / Q000187:drug effects / Q000502:physiology*; D046690:Deep Brain Stimulation / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D010775:Photic Stimulation; D011336:Probability; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D020531:Subthalamic Nucleus / Q000502:physiology*; D013997:Time Factors
chemical_list: D015259:Dopamine Agents; D004298:Dopamine