The main objectives of this review were to provide an update on the progress made in understanding specific circuit abnormalities leading to psychotic symptoms in schizophrenia and to propose rational targets for therapeutic deep brain stimulation (DBS). Refractory schizophrenia remains a major unsolved clinical problem, with 10%-30% of patients not responding to standard treatment options. Progress made over the last decade was analyzed through reviewing structural and functional neuroimaging studies in humans, along with studies of animal models of schizophrenia. The authors reviewed theories implicating dysfunction in dopaminergic and glutamatergic signaling in the pathophysiology of the disorder, paying particular attention to neurosurgically relevant nodes in the circuit. In this context, the authors focused on an important pathological circuit involving the associative striatum, anterior hippocampus, and ventral striatum, and discuss the possibility of targeting these nodes for therapeutic neuromodulation with DBS. Finally, the authors examined ethical considerations in the treatment of these vulnerable patients. The functional anatomy of neural circuits relevant to schizophrenia remains of great interest to neurosurgeons and psychiatrists and lends itself to the development of specific targets for neuromodulation. Ongoing progress in the understanding of these structures will be critical to the development of potential neurosurgical treatments of schizophrenia.
Keywords: AST = associative striatum; BOLD = blood oxygen level-dependent; DBS = deep brain stimulation; DLPFC = dorsolateral prefrontal cortex; GABA = gamma-aminobutyric acid; HDE = humanitarian device exemption; MDD = major depressive disorder; NMDA = N-methyl-d-aspartate; OCD = obsessive-compulsive disorder; SICI = short-interval intracortical inhibition; TMS = transcranial magnetic stimulation; VBM = voxel-based morphometry; VS = ventral striatum; VTA = ventral tegmental area; cSP = cortical silent period; deep brain stimulation; fMRI; fMRI = functional MRI; functional neurosurgery; neuroimaging; rCBF = regional cerebral blood flow; rTMS = repetitive TMS; schizophrenia.