Schizophrenia is a chronic and disabling psychiatric illness that is often refractory to treatment. Psychotic symptoms (e.g. hallucinations and delusions) in schizophrenia are reliably correlated with excess dopamine levels in the striatum, and have more recently been related to excess metabolic activity in the hippocampus. Multiple lines of evidence suggest that aberrantly high hippocampal activity may, via hippocampal connections with the limbic basal ganglia, drive excessive dopamine release into the striatum. In the present paper, we hypothesize that inhibition or stabilization of neural activity with high-frequency electrical stimulation of the hippocampus or nucleus accumbens, through different mechanisms, would treat the positive symptoms of schizophrenia. Thus, we suggest a direction for further experimentation aimed at developing neurosurgical therapeutic approaches for this devastating disease.
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