Depression, Depressionen

Vagus Nerve Anatomy:

The PB/LC sends direct connections to every level of the forebrain, including the hypothalamus, and several thalamic regions that control the insula and orbitofrontal and prefrontal cortices. Perhaps important for mood regulation, the PB/LC has direct connections to the amygdala and the bed nucleus of the stria terminalis-structures that are implicated in emotion recognition and mood regulation (Van Bockstaele et al 1999; for review of the functional neuroanatomy of depression, see George et al 1997; Ketter et al 1997).

These brainstem and limbic anatomie connections have functional consequences. The oncogen C-fos is a general marker for cellular activity. C-fos studies in rats during VNS reveal increased activity in the amygdala, cingulate, LC, and hypothalamus (Naritoku et al 1995). Recently, Walker and colleagues (1999) outlined a possible role of the NTS in how VNS reduces seizures. By microinjecting the NTS with either y-aminobutyric acid (GABA) agonists or glutamate antagonists, they found that increased GABA or decreased glutamate in the NTS blocked seizures. These findings suggest that VNS may change NTS GABA and glutamate concentrations, with secondary changes in the function of specific limbic structures noted above.

Some have suggested that because of the rotation of the body during embryonic development the left and right vagus nerves carry different information. This theory implies that the right vagus is closely associated with the cardiac atria and the left vagus with cardiac ventricular function, perhaps explaining the lack of cardiac effects of left VNS. Additionally, the NeuroCybernetic Prosthesis (NCP) System stimulating electrode is intended to be positioned below the cardiac branch of the vagus nerve. However, this line of thinking is not totally supported by early animal VNS research. There is even one patient who has been treated on the right side without complication (G.L. Morris, personal communication, October 1999). An alternative theory holds that the cardiac functional response is more a function of stimulation parameters than whether the right or left nerve is stimulated.

In sum, incoming sensory (afferent) connections of the vagus nerve provide direct projections to many of the brain regions implicated in neuropsychiatric disorders. These connections reveal how vagus nerve stimulation might be a portal to the brainstem and connected regions. These circuits likely account for the neuropsychiatric effects of VNS. and they invite additional theoretical considerations for potential research and clinical applications.