The aim of this thesis is to determine the changes in BOLD signal of the human brain during various stages of reinforcement learning. In order to accomplish that goal two probabilistic reinforcement-learning tasks were developed and assessed with healthy participants by using functional magnetic resonance imaging (fMRI). For both experiments the brain imaging data of the participants were analysed by using a combination of univariate and model–based techniques. In Experiment 1 there were three types of stimulus-response pairs where they predict either a reward, a neutral or a monetary loss outcome with a certain probability. The Experiment 1 tested the following research questions: Where does the activity occur in the brain for expecting and receiving a monetary reward and a punishment ? Does avoiding a loss outcome activate similar brain regions as gain outcomes and vice a verse does avoiding a reward outcome activate similar brain regions as loss outcomes? Where in the brain prediction errors, and predictions for rewards and losses are calculated? What are the neural correlates of reward and loss predictions for reward and loss during early and late phases in learning? The results of the Experiment 1 have shown that expectation for reward and losses activate overlapping brain areas mainly in the anterior cingulate cortex and basal ganglia but outcomes of rewards and losses activate separate brain regions, outcomes of losses mainly activate insula and amygdala whereas reward activate bilateral medial frontal gyrus. The model-based analysis also revealed early versus late learning related changes. It was found that predicted-value in early trials is coded in the ventro-medial orbito frontal cortex but later in learning the activation for the predicted value was found in the putamen. The second experiment was designed to find out the differences in processing novel versus familiar reward-predictive stimuli. The results revealed that dorso-lateral prefrontal cortex and several regions in the parietal cortex showed greater activation for novel stimuli than for familiar stimuli. As an extension to the fourth research question of Experiment 1, reward predictedvalues of the conditional stimuli and prediction errors of unconditional stimuli were also assessed in Experiment 2. The results revealed that during learning there is a significant activation of the prediction error mainly in the ventral striatum with extension to various cortical regions but for familiar stimuli no prediction error activity was observed. Moreover, predicted values for novel stimuli activate mainly ventro-medial orbito frontal cortex and precuneus whereas the predicted value of familiar stimuli activates putamen. The results of Experiment 2 for the predictedvalues reviewed together with the early versus later predicted values in Experiment 1 suggest that during learning of CS-US pairs activation in the brain shifts from ventro-medial orbito frontal structures to sensori-motor parts of the striatum.

Action control arises from the interaction of two anatomically distinct decision-making systems, namely goal-directed and habitual behaviour. Goal-directed behaviour is characterized by the consideration of future choices and respective outcomes whereas habitual responding is driven by stimulus-response associations. Response inhibition is essential for goal-directed behaviour and deficits are shown in impulsivity. We administered an acute clinically relevant dosage of the commonly used serotonin reuptake inhibitor escitalopram to sixty-six healthy volunteers in a double-blind, randomized, placebo-controlled design. We administered a large task battery in order to study the effect of escitalopram in several cognitive functions including response inhibition, learning and affective processing. We found dissociate effects on cognitive aspects possibly mediated by distinct cortico-striatal loops. Acute escitalopram administration had a beneficial effect on action cancellation, one aspect of inhibitory control, without any effect on action restraint or waiting impulsivity. The treatment resulted in impaired performance in a probabilistic reversal-learning task and increased sensitivity to misleading feedback thus leading to maladaptive performance. An extra-dimensional set shift impairment during an attention set shift task and a tendency towards impaired instrumental learning discrimination were also observed in the escitalopram group. Our results are discussed in the context of well-documented effects of the dopaminergic system and suggestions of opponent interaction of serotonin and dopamine.

Articulate rationale for early assessment Describe process of assessment and feedback sessions List benefits of process based on: Objective data Opinion of interns over past 2 years