Amsterdam UMC location University of Amsterdam, Department of Psychiatry, Meibergdreef 9, Amsterdam, The Netherlands.
Amsterdam Neuroscience, Amsterdam, The Netherlands.
Mol Psychiatry. 2023 Jun;28(6):2500-2507. doi: 10.1038/s41380-023-02030-1. Epub 2023 Mar 29.
Deep brain stimulation (DBS) of the ventral anterior limb of the internal capsule (vALIC) is a promising intervention for treatment-resistant depression (TRD). However, the working mechanisms of vALIC DBS in TRD remain largely unexplored. As major depressive disorder has been associated with aberrant amygdala functioning, we investigated whether vALIC DBS affects amygdala responsivity and functional connectivity. To investigate the long-term effects of DBS, eleven patients with TRD performed an implicit emotional face-viewing paradigm during functional magnetic resonance imaging (fMRI) before DBS surgery and after DBS parameter optimization. Sixteen matched healthy controls performed the fMRI paradigm at two-time points to control for test-retest effects. To investigate the short-term effects of DBS de-activation after parameter optimization, thirteen patients additionally performed the fMRI paradigm after double-blind periods of active and sham stimulation. Results showed that TRD patients had decreased right amygdala responsivity compared to healthy controls at baseline. Long-term vALIC DBS normalized right amygdala responsivity, which was associated with faster reaction times. This effect was not dependent on emotional valence. Furthermore, active compared to sham DBS increased amygdala connectivity with sensorimotor and cingulate cortices, which was not significantly different between responders and non-responders. These results suggest that vALIC DBS restores amygdala responsivity and behavioral vigilance in TRD, which may contribute to the DBS-induced antidepressant effect.
深部脑刺激（DBS）的腹侧前肢的内囊（vALIC）是一种有前途的干预治疗抵抗性抑郁症（TRD）。然而，vALIC DBS 在 TRD 中的工作机制在很大程度上仍未得到探索。由于重度抑郁症与杏仁核功能异常有关，我们研究了 vALIC DBS 是否影响杏仁核反应性和功能连接。为了研究 DBS 的长期效果，11 名 TRD 患者在 DBS 手术前和 DBS 参数优化后进行了功能磁共振成像（fMRI）的隐性情绪面孔观察范式。16 名匹配的健康对照组在两个时间点进行 fMRI 范式，以控制测试-再测试效应。为了研究 DBS 参数优化后去激活的短期效果，13 名患者在主动和假刺激的双盲期后额外进行了 fMRI 范式。结果表明，TRD 患者在基线时右杏仁核反应性低于健康对照组。长期 vALIC DBS 使右杏仁核反应性正常化，与更快的反应时间相关。这种效果不依赖于情绪效价。此外，与假刺激相比，主动刺激增加了杏仁核与感觉运动和扣带回皮质的连接，而在应答者和非应答者之间没有显著差异。这些结果表明，vALIC DBS 恢复了 TRD 中的杏仁核反应性和行为警觉性，这可能有助于 DBS 诱导的抗抑郁作用。
