Figure 1.

Postulated bottom-up effect influence of transcutaneous auricular vagal nerve stimulation on the mesocircuit in a severely damaged brain. The model suggests that the reduction of thalamocortical and thalamostriatal outflow following deafferentation and loss of neurons from the central thalamus withdraws important afferent drive to the medium spiny neurons of the striatum (green lines). Loss of active inhibition from the striatum (dashed red line) allows neurons of the globus pallidus interna (GPi) to tonically fire and provide active inhibition (red line) to their synaptic targets, including relay neurons of the already understimulated central thalamus, thus reducing thalamic activity and consequent thalamo-cortical connectivity. taVNS may hypothetically supply for the missing thalamic excitatory inputs by stimulating the lower and upper brainstem nuclei and thus promote the reinstatement of the thalamo-cortical connectivity. Adapted fromGiacino et al., 2014.