Table 2

Possible DBS targets and effects on schizophrenia symptoms

DBS targetSubterritoryModels of aberrant circuitryHypothetical effects of DBS
VSNAc1) Hippocampal disinhibition of striatum leads to ↑DA in VS.17*
2) ↑Striatal DA inhibits GLU signalling in VS.25
3) ↑Striatal DA, but ↓DA to reward circuit within VS (NAc) and frontal cortex27
1) Block ↑ DA signalling in VS normalises striatal DA.28 29 31 35
2) Restore GLU signalling in VS.25
3) May ↑DA overall in striatum9
Investigational target for depression5 28 29 31
1) Block ↑ DA signalling in VS* restoring reward response
2) Restore GLU signalling in VS.
3) ↑DA signalling needed for reward pathway9
Normalise reward-based learning.30
Normalise DA to frontal cortex.9 27
mPFCSGCWM4) Default network deactivation failure, possible overactivation33 34 Investigational target for depression. Modulation of the default network33 34
SNrBelow STN5) MD inhibition36–42 MD disinhibitionMD disinhibition
VTAAscending3) ↓DA in NAc and PFC contributes to cognitive deficits.16 27 Normalising striatal dopaminergic tone through ↑DA NAc and feedforward DA spiral regulation of SN and AS35 or ↑striatal DA may contribute to psychosis.↑DA NAc effects on reward/motivation pathways5 77 ↑DA in PFC
ASRegion connecting to DLPFC6) Cognitive deficits related to dysregulation of circuitry to prefrontal cortex16 48 Possible modulation DA signalling involved in psychosis48 Modulation DA signalling to PFC48
MSN1) Excess extracellular GLU in hippocampus17 Prevent hippocampal disinhibition of striatum, normalise striatal DA.30 Normalise reward/motivation pathway DA.5 Normalise DA signalling to PFC.
GPiPosteroventrolateral10 7) Antidyskinetic treatment of tardive dyskinesia10
HCA11) Striatal disinhibition17 32 Normalise striatal DA.32 Normalise reward/motivation pathway DA.5 Normalise DA signalling to PFC.32
  • *High levels of dopamine make NAc cells less responsive to reward-based dopamine changes leading to negative symptoms in some patients with schizophrenia (SZ) (this is also consistent with patients being more susceptible to cigarette addiction where addition occurs in subjects with smaller responses requiring more of the addictive substance).

  • AS, associative striatum; CA1, cornu ammonis 1; DA, dopamine; DBS, deep brain stimulation; DLPFC, dorsolateral prefrontal cortex; GLU, glutamate; GPi, globus pallidus internal; H, hippocampus; MD, medial dorsal; mPFC, medial prefrontal cortex; MSN, medial septal nucleus; NAc, nucleus accumbens; PFC, prefrontal cortex; SGCWM, subgenual cingulate white matter; SN, substantia nigra; SNr, substantia nigra pars reticulata; STN, subthalamic nucleus; VS, ventral striatum; VTA, ventral tegmental area.