Figure 5.

Possible mechanisms involved in the relationship between dTMS, rebalancing of the gut microbiota composition and norepinephrine variation. Deep TMS by stimulating the PFC at high frequency could acutely induce activation of the dopaminergic reward system (striatum, VTA, nucleus accumbens), promoting dopamine release. Norepinehrine mainly derives from dopamine manipulation by dopamine B-hydroxylase; norepinephrine could be locally released in the gut through postganglionic sympathetic nerve fibers. At the same time, dTMS could induce a HPA axis-mediated systemic response, promoting norepinephrine synthetization from chromaffin cells of the adrenal medulla; norepinephrine achieves the gut through the bloodstream. Chronic treatment with dTMS has been suggested to induce a NET modulation, with a consequent central decrease in norepinephrine outflow. We hypothesized that the decreased systemic norepinephrine results in a reduced gut luminal norepinephrine, with consequent beneficial effects on gut microbiota composition. Legend: dTMS = deep transcranial magnetic stimulation; PFC= prefrontal cortex; VTA= ventral tegmental area; HPA = hypothalamic-pituitary-adrenal; NET = norepinephrine transporter.