Editors' ChoiceNeuroscience

Going Deep

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Science Translational Medicine  20 Jun 2012:
Vol. 4, Issue 139, pp. 139ec108
DOI: 10.1126/scitranslmed.3004422

Brain surgery for psychiatric disease originated with the frontal lobotomy, which became notorious after its indiscriminate and unethical use. In the 21st century, functional neurosurgery has progressed beyond permanent lesions with the technique of deep brain stimulation (DBS). For example, Parkinson’s patients refractory to medical therapy can benefit from stimulation of electrodes placed into brain structures that regulate motor control. DBS is also being applied to neuropsychiatric disorders. In a quest to find the optimal electrode targets and the mechanism of therapeutic benefit for DBS treatment of obsessive-compulsive disorder, Rodriguez-Romaguera and colleagues have used an animal model and clarified that DBS can provide symptomatic relief through effects on brain networks.

The authors placed electrodes in different areas of the ventral striatum in rats. The striatum is part of the brain system known as the basal ganglia and is a target for neurons from areas of the frontal cortex; DBS in this region can help patients with obsessive-compulsive disorder. Stimulation of electrodes in the dorsolateral striatum facilitated the extinction of conditioned fear (a good thing for obsessive-compulsive disorder), whereas stimulation in the more ventral and medial portions impaired extinction and led to an inappropriately persistent fear response (a not-so-good thing for the disease). These results are consistent with observations in humans that stimulation of the ventral sites in the basal ganglia can induce fear and panic. Unexpectedly, however, the stimulation did not have a therapeutic effect on local neurons, as it does in Parkinson’s disease. Instead, the effects occurred in the prefrontal cortex and amygdala (a brain structure important for fear processing), which interact with the striatum. This finding is important because it suggests that therapeutic responses to striatal stimulation depend on changes in components of neural circuits outside the striatum. Supporting this hypothesis, phosphorylated extracellular signal–regulated kinase —a marker of neuronal plasticity—was increased in the frontal cortex and amygdala after dorsal (but not ventral) stimulation of the striatum.

The dorsal striatum seems to be the optimal target for DBS that attenuates symptoms related to obsessive-compulsive disorder, but the therapeutic effects actually occur in structures that are part of a larger network that includes the frontal cortex and amygdala. Neural plasticity in these areas distant from the stimulating electrode is the likely therapeutic mediator of DBS for obsessive-compulsive disorder.

J. Rodriguez-Romaguera et al., Deep brain stimulation of the ventral striatum enhances extinction of conditioned fear. Proc. Natl. Acad. Sci. U.S.A. 109, 8764–8769 (2012). [Full Text]

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