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

  • Clement Hamani
    Correspondence
    Address correspondence to Clement Hamani, M.D., Ph.D., Neuroimaging Research Section, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
    Affiliations
    Neuroimaging Research Section, Toronto, Ontario, Canada

    Division of Neurosurgery, Toronto Western Hospital, Toronto, Ontario, Canada
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  • José N. Nobrega
    Affiliations
    Biopsychology Section, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
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      We thank Etiévant et al. (
      • Etiévant A.
      • Lucas G.
      • Haddjeri N.
      Deep brain stimulation for depression: Is it a gray or white “matter”?.
      ) 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) (
      • Florence G.
      • Sameshima K.
      • Fonoff E.T.
      • Hamani C.
      Deep brain stimulation: More complex than the inhibition of cells and excitation of fibers.
      ). 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) (
      • Florence G.
      • Sameshima K.
      • Fonoff E.T.
      • Hamani C.
      Deep brain stimulation: More complex than the inhibition of cells and excitation of fibers.
      ,
      • Hamani C.
      • Temel Y.
      Deep brain stimulation for psychiatric disease: Contributions and validity of animal models.
      ); 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. Finally, DBS has been shown to modulate activity of glial cells and induce plastic changes, such as long-term potentiation, increases in neurotrophin levels, and neurogenesis (
      • Hamani C.
      • Temel Y.
      Deep brain stimulation for psychiatric disease: Contributions and validity of animal models.
      ,
      • Bambico F.R.
      • Bregman T.
      • Diwan M.
      • Li J.
      • Darvish-Ghane S.
      • Li Z.
      • et al.
      Neuroplasticity-dependent and -independent mechanisms of chronic deep brain stimulation in stressed rats.
      ,
      • Hamani C.
      • Machado D.C.
      • Hipolide D.C.
      • Dubiela F.P.
      • Suchecki D.
      • Macedo C.E.
      • et al.
      Deep brain stimulation reverses anhedonic-like behavior in a chronic model of depression: Role of serotonin and brain derived neurotrophic factor.
      ,
      • Hamani C.
      • Nobrega J.N.
      Preclinical studies modeling deep brain stimulation for depression.
      ). In contrast to the complexity of the above-described mechanisms, optogenetics, which is often delivered for short periods of time at much lower frequencies, is a very clean technique that allows the precise distinction of the neural elements involved in mechanisms of behavioral and physiologic processes.
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      References

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        • Lucas G.
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        Deep brain stimulation for depression: Is it a gray or white “matter”?.
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        Deep brain stimulation: More complex than the inhibition of cells and excitation of fibers.
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        Deep brain stimulation for psychiatric disease: Contributions and validity of animal models.
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      Linked Article

      • Deep Brain Stimulation for Depression: Is It a Gray or White “Matter”?
        Biological PsychiatryVol. 80Issue 6
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          Deep brain stimulation (DBS) within the subcallosal cingulate gyrus was shown to impressively improve depressive symptoms in patients with refractory depression (1). 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.
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      • Erratum
        Biological PsychiatryVol. 80Issue 6
        • Preview
          Erratum to: “Reply to: Deep Brain Stimulation for Depression: Is It a Gray or White “Matter”?” by Clement Hamani and José N. Nobrega (Biol Psychiatry corrected article-in-press, available online Jan 26, 2016). This article is being corrected between the corrected proof and final print version stages of publication. It came to the authors’ attention that the last four sentences of the article needed to be altered to correct a misunderstanding of the prior literature. The original text and corrected text are both provided here for clarity.
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