Assessing the effects of transcutaneous vagus nerve stimulation on noradrenaline related cognitive function: the effects on alerting and its possible implication for Tourette syndrome

Objective. Tourette syndrome (TS) is a neurodevelopmental disorder characterized by vocal and motor tics. Even though the central neural mechanisms of tic generation are still debated, impaired cortico-striato-thalamo-cortical activity and a general elevation of the sympathetic (over the parasympathetic) tone are important signatures of TS. To increase tic control, the use of pharmacological treatments targeting the dopaminergic system, but also the GABA and Noradrenergic systems has been proposed. Previous studies have suggested that the invasive stimulation of the vagus nerve may trigger the Noradrenergic system activity and modulate noradrenaline NE transmission. As a preliminary investigation on the effectiveness of transcutaneous vagus nerve stimulation (tVNS) in TS, here we investigated the effects of tVNS in modulating alerting, which is known to be a proxy of NE concentration. Material. We applied active and sham tVNS during the execution of the Attentional Network Test (ANT). This test allows measuring the effectiveness of three cognitive and attentive components, namely the alerting, the orienting, the executive control components, which are thought to rely, respectively, over the noradrenergic, cholinergic and dopaminergic systems. Methods. 40 healthy participants underwent a two-sessions, sham-controlled, within-subjects single-blind design in which active or sham tVNS was applied during the execution of the ANT. Results. The results showed that active tVNS, with respect to sham, selectively boosted the alerting, but not the orienting and the executive control components. Discussion. Our data provides evidence for the effects of tVNS on alerting response, and this facilitation could be related to the regulation of noradrenergic activity. Conclusions. By considering the wide spectrum of effects induced by tVNS, encompassing also an infliuence on GABA neurotransmission and autonomic regulation, this finding encourages the development of future clinical studies using tVNS for addressing TS symptomatology.