NeuroNetzwerk 17

Projekttitel: Stimulation of the LC-NE system as a personalized therapeutic intervention. Projektleiter: Dorothea Hämmerer, Matthew Betts, Matthias Prigge, Tino Zähle (picture: UMMD)

Functional deterioration of the noradrenergic (NE) system, and in particularly the locus coeruleus (LC) in the brainstem, has been shown to occur in a variety of clinical and neurological disorders. A recent approach to non-invasive brain stimulation termed transcutaneous vagus nerve stimulation (tVNS), may provide anatomically and temporally more accurate modulation of the LC-NE system compared to current drug interventions. Whilst animal studies have confirmed that the LC-NE is stimulated by VNS, its effectiveness in clinical trials has been limited. This has been attributed to a) insufficient control of mediating factors such as the current state of the LC-NE system and b) insufficient understanding of how tVNS relates to NE function. The proposed NeuroNetwork will use a multidisciplinary translational approach to develop novel tVNS interventions that take into account interindividual differences in the integrity of the LC-NE system using state-of-the-art methodologies. We will investigate across four subprojects how interindividual differences in the 'physiological fitness' of the LC-NE system (LC structure, connectivity, vascularization, receptor/transporter density and cognition) modulate tVNS effects. Inter-individual effects following tVNS intervention will also be investigated in LC target regions (temporal memory structures and frontal executive control structures) using optogenetic tVNS studies in mice and simultaneous tVNS-EEG, tVNS-fMRI, and MRI-PET in humans. These measures will be used to collectively determine the efficacy of personalised short, long-term and inhibitory tVNS interventions. It is hoped this network in collaboration with tVNS Technologies (Erlangen) will contribute towards the development of more personalised non-invasive interventions to target the LC-NE system.