Deep Brain Stimulation for Depression: Is It a Gray or White “Matter”?

Abstract

Deep brain stimulation (DBS) within the subcallosal cingulate gyrus was shown to impressively improve depressive symptoms in patients with refractory depression ( 1 Mayberg H.S. Lozano A.M. Voon V. McNeely H.E. Seminowicz D. Hamani C. et al. Deep brain stimulation for treatment-resistant depression. Neuron. 2005; 45: 651-660 Abstract Full Text Full Text PDF PubMed Scopus (2883) Google Scholar ). Despite these exciting results, the neurobiological bases underlying the therapeutic action of DBS remain largely unknown. Based on its anatomic connections and cytoarchitectural features, the rodent ventromedial prefrontal cortex (vmPFC) is considered as the equivalent of the subcallosal cingulate gyrus in humans. Hence, in their article in Biological Psychiatry, Hamani et al. ( 2 Hamani C. Diwan M. Macedo C.E. Brandao M.L. Shumake J. Gonzalez-Lima F. et al. Antidepressant-like effects of medial prefrontal cortex deep brain stimulation in rats. Biol Psychiatry. 2010; 67: 117-124 Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar ) reported that the stimulation of the vmPFC in rats induces antidepressant-like behavior in the forced swim test, a test frequently used to screen potential antidepressant treatments. Moreover, this group presented evidence that, similar to most currently used pharmacologic antidepressants, the antidepressant-like effects of vmPFC DBS are serotoninergic dependent. First, vmPFC stimulation was correlated with a sustained increase in hippocampal 5-hydroxytryptamine release. Second, antidepressant-like behaviors induced by vmPFC DBS were prevented by a lesion of the 5-hydroxytryptamine system with 5,7-dihydroxytryptamine. The authors showed that the antidepressant-like behavioral response of DBS in the forced swim test was blocked by vmPFC radiofrequency lesions or by injections of the gamma-aminobutyric acid A receptor agonist muscimol, but was unchanged after a neuronal lesion of vmPFC induced by ibotenic acid. How can such differences in inactivation outcomes be clarified? This is a crucial issue regarding the role and involvement of the gray matter versus white matter in mechanisms of action of subcallosal cingulate gyrus DBS. Although Hamani et al. ( 2 Hamani C. Diwan M. Macedo C.E. Brandao M.L. Shumake J. Gonzalez-Lima F. et al. Antidepressant-like effects of medial prefrontal cortex deep brain stimulation in rats. Biol Psychiatry. 2010; 67: 117-124 Abstract Full Text Full Text PDF PubMed Scopus (260) Google Scholar ) did not provide a full explanation for this discrepancy in their article, they have speculated on the possible involvement of passing fibers or of glial cells in the antidepressant effect of vmPFC DBS. Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in RatsBiological PsychiatryVol. 67Issue 2PreviewSubcallosal cingulate gyrus (SCG) deep brain stimulation (DBS) is being investigated as a treatment for major depression. We report on the effects of ventromedial prefrontal cortex (vmPFC) DBS in rats, focusing on possible mechanisms involved in an antidepressant-like response in the forced swim test (FST). Full-Text PDF Reply to: Deep Brain Stimulation for Depression: Is It a Gray or White “Matter”?Biological PsychiatryVol. 80Issue 6PreviewWe thank Etiévant et al. (1) for their comments and the opportunity to discuss our data. In response, we should first consider some of the concepts involving deep brain stimulation (DBS) at high frequencies (e.g., >100 Hz). One of the mechanisms commonly described is a depolarization block. This mechanism is characterized by a state in which cells undergo depolarization with an almost complete abolishment of spontaneous action potentials (functional inactivation) (2). In addition, DBS excites fiber pathways in the vicinity of the electrodes (efferent and afferent projections from and to the targeted region as well as fibers en passant) (2,3); this is important, as the anterograde and retrograde propagation of action potentials may influence the functioning of brain regions projecting to or receiving projections from the stimulated site. Full-Text PDF