Electrical Brain Stimulation in Depression: Which Target(s)?

Abstract

In a recent publication in Biological Psychiatry, Hamani and coworkers ( 1 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 (256) Google Scholar ) reported on the mechanism responsible for the therapeutic effect of electrical brain stimulation in depression. Although clinical studies have shown that electrical stimulation of the subgenual cingulate gyrus induces a striking and sustained remission of depressive symptoms in patients with refractory depression ( 2 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 (2782) Google Scholar , 3 Lozano A.M. Mayberg H.S. Giacobbe P. Hamani C. Craddock R.C. Kennedy S.H. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2008; 64: 461-467 Abstract Full Text Full Text PDF PubMed Scopus (712) Google Scholar ), the underlying mechanisms are still unknown. Using a rat model, Hamani and coworkers performed electrical stimulation of the ventromedial part of the prefrontal cortex, which is, according to the authors, the potential correlate of the human subgenual cingulate gyrus. Their anatomic illustrations reveal that the vast majority of the electrodes were placed specifically in the infralimbic cortex. Electrical stimulation produced profound antidepressant effects in the forced swim test, indicated by substantial reduction in immobility time. Central 5-HT depletion by injection of the neurotoxin 5,7-dihydroxytryptamine into the dorsal raphe nucleus and median raphe nucleus completely abolished the therapeutic effect of electrical stimulation. The authors concluded that the antidepressant effect of electrical stimulation of the infralimbic cortex was linked to the 5-HT system. Interestingly, a link among electrical brain stimulation, the 5-HT system, and mood has been described previously ( 4 Temel Y. Boothman L.J. Blokland A. Magill P.J. Steinbusch H.W. Visser-Vandewalle V. et al. Inhibition of 5-HT neuron activity and induction of depressive-like behavior by high-frequency stimulation of the subthalamic nucleus. Proc Natl Acad Sci U S A. 2007; 104: 17087-17092 Crossref PubMed Scopus (151) Google Scholar ). 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: Electrical Brain Stimulation in Depression: Which Target(s)?Biological PsychiatryVol. 69Issue 4PreviewWe thank Lim and colleagues for their comments and for the opportunity to discuss our results further. In our initial article (1), we purposefully avoided using the term “infralimbic cortex (IL) stimulation” and referred to our target as ventromedial prefrontal cortex (vmPFC). This area, including the IL and ventral prelimbic cortex (vPL), has been defined as a functional entity based on physiologic features as well as afferent and efferent projections (2,3). Although there is debate and controversy regarding the homology of prefrontal cortical structures across phylogeny, the vmPFC in rodents (particularly the IL) has been suggested as being homologous to the primate subcallosal cingulate gyrus (3–5). Full-Text PDF