The LC-NE system as a potential target for neuromodulation to ameliorate non-motor symptoms in Parkinson's disease

Parkinson's disease (PD) is associated with severe motor symptoms but also with several non-motor symptoms (NMS). A substantial reduction of norepinephrine (NE) levels in various brain regions reflecting an extensive loss of innervation from the LC has been assumed as causal for the development of NMS and specifically of attentional impairments in PD. Transcutaneous auricular vagus nerve stimulation (taVNS) is a new, non-invasive neurostimulation method supposed to modulate the LC-NE system in humans. In the current opinion paper, we introduce taVNS as a systemic approach to directly affect NE neurotransmission in healthy as well as clinical populations and discuss its potential as therapeutic option for the treatment of NMS, specifically attentional deficits, in patients with PD. Here, we first describe the LC-NE system and discuss how LC-NE dysfunction might affects cognition in PD before detailing the mode of action of taVNS and proposing its use to modulate cognitive deficits in these patients.