Brain Structures Involved in Major Depressive Disorder

There are now over half a dozen sites in the brain which, on electrical stimulation, relieve treatment-resistant depression. This chapter is concerned with how these distributed sites have been identified and to what extent they reveal the brain circuitry involved in depression. The limbic system (cingulate gyrus, hippocampus, hypothalamus, amygdala), together with the medial prefrontal cortex involved in hypothalamic-related functions and specific subcortical nuclei, have been taken since the end of the twentieth century as constituting ‘the emotional brain,’ suggesting that a somewhat distributed network is involved in depression. Deep brain stimulation (DBS) has now evolved to a personalised level of electrode placements in ‘the emotional brain’ as well as of parameter stimulation. The best sites for transcranial magnetic stimulation (TMS) for MDD recovery are in the subgenual area (BA25). When TMS is applied to the dorsolateral PFC, its efficacy is related to the functional connectivity between this site and the subgenual vmPFC (BA25). When TMS is applied to dorsomedial PFC, its efficiency is related to its functional connectivity with vmPFC. Importantly, impulse firing in the amygdala has been shown to track the extent of MDD and that both this firing and the extent of MDD can be modulated by stimulating the VC/VS (ventral capsule/ventral striatum). It has been shown that this functional connectivity between VC/VS and the amygdala provides the optimal subnetwork subserving MDD over those involving the orbitofrontal cortex, hippocampus, and subgenual cingulate cortex (SGC). Deep brain stimulation (DBS) of VC/VS gives similar relief of MDD as does DBS of BA25 so that both VC/VS and BA25 are regarded as the best targets for DBS.