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NeuroNetzwerk 17


Projekttitel: Stimulation of the LC-NE system as a personalized therapeutic intervention.

Projektleiter: Dorothea Hämmerer, Matthew Betts, Matthias Prigge, Tino Zähle




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.


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