When humans are faced with multiple options, they must decide whether to choose a novel or less certain option (explore) or stick with what they know (exploit). Exploration is a fundamental cognitive process. Importantly, when humans attempt to solve the explore-exploit dilemma, they must effectively incorporate both feedback and uncertainty to guide their actions. While prior work has shown that both acute (short-term) and chronic (long-term) stress can disrupt how humans solve the explore-exploit dilemma, the mechanisms of how this occurs are unclear. For example, does stress disrupt how people integrate feedback to guide their decisions to explore or exploit, or does stress disrupt computations of uncertainty regarding their choices? Importantly, the use of electroencephalography as a tool can help reveal the impact of stress on explore-exploit decision making by measuring neural signals sensitive to feedback learning and uncertainty. In the present dissertation, I provide evidence from a series of experiments where I examined the impact of both acute and chronic stress on the explore-exploit dilemma while electroencephalographic data was collected. In experiment 1, I exposed participants to an acute stressor and then examined their decisions to switch or stay – as a proxy for explore and exploit decisions – in a multi-arm bandit paradigm. I found tentative evidence that the acute stress response disrupted both the feedback learning signal (the reward positivity) and the uncertainty signal (the switch P300). In experiment 2 I adopted a computational neuroscience approach and directly classified participants decisions as explorations or exploitations using reinforcement learning models. There was only an effect of the acute stress response on feedback signals, in this case, the feedback P300. In experiments 1 and 2, I used contextual bandit tasks where the reward probabilities of the options shifted throughout, and there was no behavioural effect of acute stress on task performance or exploration rate. However, in experiment 3, I examined a learnable bandit where one option was preferred. Again, using computational modelling and electroencephalography, I found tentative evidence that the acute stress response disrupted the feedback learning signals (the feedback P300) and stronger evidence that acute stress disrupted the uncertainty signal (the exploration P300). As well, I observed that the acute stress response reduced task performance and increased exploration rate. Lastly, in experiment 4, I examined the impact of chronic stress exposure on explore-exploit decision making and electrophysiology – while I found no effects of chronic stress, I believe future research is necessary. Taken together, these findings provide novel evidence for the neural mechanisms of how the acute stress response impacts the explore-exploit dilemma through disruptions to feedback learning and assessments of uncertainty. These findings also highlight how theories of the P300 signal may not be properly capturing the varied role of the P300 in cognition. / Graduate

The basal ganglia (BG) is known for its function not only in motor modulation but also in action selection and reward learning. There are two major anatomical pathways through the BG, the direct and the indirect pathways. The direct pathway starts from the striatum and then directly projects to the globus pallidus, pars interna (GPi) and the substantia nigra, pars reticulata (SNr) respectively, while the indirect pathway starts from the striatum but then indirectly projects to GPi and SNr through the globus pallidus, pars externa and then to the subthalamic nucleus. In addition, the output from GPi not only projects to the thalamus where it has been proposed to function in motor control, but also to the lateral habenula (LHb) where it has been proposed to function in outcome evaluation. Previous studies have found that there are three major genetically distinct neuron groups in the entopeduncular nucleus (EP) (rodent homologue of the primate GPi): 1) purely glutamatergic neurons projecting to LHb neurons expressing parvalbumin (PVLHb); 2) purely GABAergic neurons projecting to motor thalamic neurons expressing parvalbumin (PVThal); 3) GABA/glutamate co-releasing neurons projecting to LHb neurons expressing somatostatin (SstLHb). In this study, we knocked out the vesicular glutamate transporter 2 in SstLHb neurons through an adeno-associated virus in mice to test for the impact on goal-directed behavior using a probabilistic switching, two-armed bandit task (2ABT). Results obtained from the freely moving, water-restricted somatostatin-cre mice with the vesicular glutamate transporter 2 ablated in SstLHb neurons showed that: 1) there was neither improvement nor decline in their performance on the task; 2) they might be more distracted between trials while more concentrated within a trial; 3) they had an increase in the probability of switching between ports on consecutive trials when uncertainty in the location of the highly rewarded port was maximum compared to the control animals with intact glutamate release from SstLHb neurons to LHb. The success of the viral expression was then confirmed through whole-cell voltage-clamp recordings of postsynaptic neurons of the LHb, receiving projections from SstLHb neurons. In conclusion, our study has suggested that the glutamate release from the GABA/glutamate co-releasing neurons of EP projecting to LHb may play a role in reinforcement learning and motivation to obtain rewards, and the loss of glutamate in the GABA/glutamate co-releasing vesicles results in increasing uptake of GABA into these vesicles, leading to possible rebound burst firing of SstLHb neurons that eventually increases the sensitivity towards low rate of reward-delivery dramatically. / 2026-03-13T00:00:00Z