Investigating the causal role of the locus coeruleus norepinephrine system in decision-making using transcutaneous vagus nerve stimulation

Details

Supervisors

Duque, Julie ; Su, Shiyong

Faculty

Faculté de pharmacie et des sciences biomédicales

Degree label

Master [120] en sciences biomédicales, à finalité approfondie

Abstract

Previous research suggests a strong contribution of the locus coeruleus (LC) system to various behaviors via its noradrenaline norepinephrine (NE) neuron projections throughout the forebrain. However, the exact role of LC in behavioral control remains unclear. Previous human studies have found that pupil size, used as a non-invasive index of LC-NE activity, is larger when decisions are made quickly under urgent deadlines compared to when more time is provided for accuracy, leading to the proposal that LC may generate urgency, speeding up decisions at the cost of accuracy. However, this contrasts with the perspective from animal studies that LC serves to enhance information processing, implying that the involvement of the LC-NE system should primarily improve accuracy. During my Master’s thesis, I conducted a study using transcutaneous vagus nerve stimulation (tVNS) to modulate LC-NE activity and investigate its causal role in regulating speed and accuracy during decision-making. The study involved three experiments. In the first experiment, conducted on 22 subjects, we evaluated the effect of a new tVNS protocol, consisting of a 4-second stimulation train, on pupil size at rest. The results indicate significant pupil dilation under tVNS compared to SHAM stimulation, suggesting the effectiveness of this tVNS protocol in modulating LC-NE activity. In the second experiment, conducted on 62 participants, we explored the impact of this tVNS protocol on decision-making performance in the Random Dot Motion (RDM) task. Participants were asked to make decisions based on the coherent direction of dot motion while undergoing either tVNS or SHAM stimulation. The results demonstrate that a tVNS-induced increase in LC-NE activity can enhance decision accuracy, particularly in challenging trials at a risk of accuracy decline. The third experiment, currently ongoing, investigates whether the effect of tVNS on accuracy varies with task difficulty. With 11 participants tested so far (out of a target of 20), preliminary analyses suggest that tVNS leads to greater accuracy improvement with higher task difficulty, consistent with the second experiment. Additional data are needed to get more comprehensive results. Altogether, our findings indicate that the LC-NE system enhances information processing, reflected by improved accuracy in our decision-making tasks, and this influence becomes especially beneficial in challenging contexts.