Dormegny-Jeanjean Ludovic C, de Crespin de Billy Clément, Pierrat Camille, Mainberger Olivier, Schorr Benoit, Obrecht Alexandre, Arcay Hippolyte, Moreau Augustin, Humbert Ilia, Scarlatti Francesco, Bertschy Gilles, de Sousa Paulo Loureiro, Lamy Julien, Weibel Sebastien, Landré Lionel, Foucher Jack R
ICube Laboratory, UMR 7357, University of Strasbourg, CNRS, Strasbourg, France.
Non-invasive Neuromodulation Center of Strasbourg (CEMNIS), Department of Psychiatry of the Elderly and Neurostimulation, University Hospitals of Strasbourg, Strasbourg, France.
Eur Arch Psychiatry Clin Neurosci. 2025 Jun 14. doi: 10.1007/s00406-025-02027-7.
Studies examining treatment-resistant depression (TRD) as a group implicitly assume that these conditions share similar pathophysiological features, like left prefrontal hypoactivity, and should respond to standardized treatments like repetitive transcranial magnetic stimulation (S-rTMS) or transcranial direct current stimulation (tDCS). Recent advances in arterial spin labeling functional MRI (ASL-fMRI) revealed that subject-specific perfusion abnormalities may be more heterogeneous than expected. Individualized rTMS protocols (I-rTMS) could alleviate such abnormalities and establish their relevance.
iADAPT was a randomized, cross-over trial comparing I-rTMS with active comparators (S-rTMS and tDCS) on brain perfusion, assessed with ASL-fMRI, and single blind clinical evaluation. Patient-specific abnormalities were determined from three ASL-fMRI sessions. I-rTMS multi-target interventions targeted all reachable bi-frontal abnormalities, upregulating hypoperfusions and downregulating hyperperfusions. S-rTMS and tDCS were placed on F3. rTMS interventions used neuronavigation and a robotic targeting device. Each arm included 20 sessions over two weeks.
Twenty-two patients with TRD were included and analyzed. While at the group level they presented subgenual cingulate hyperperfusion, they presented heterogeneous prefrontal perfusion abnormalities individually. I-rTMS was the only intervention to have specific effects on brain perfusion, showing perfusion reductions compatible with the disengagement of negative emotional systems, e.g. subgenual cingulate, anterior insula.
Paradoxically, I-rTMS induced more reproducible remote effects on cerebral perfusion than S-rTMS, while the I-rTMS protocol differed considerably between participants. These results suggest that the heterogeneities observed in ASL-MRI at the individual level are significant and may have the potential to inform individualized treatment.
gov no NCT02863380, registered on 2016-08-05.
将难治性抑郁症（TRD）作为一个群体进行研究时，隐含地假设这些病症具有相似的病理生理特征，如左前额叶低活性，并且应该对标准化治疗有反应，如重复经颅磁刺激（S-rTMS）或经颅直流电刺激（tDCS）。动脉自旋标记功能磁共振成像（ASL-fMRI）的最新进展表明，个体特异性灌注异常可能比预期的更加异质性。个体化重复经颅磁刺激方案（I-rTMS）可以缓解此类异常并确定其相关性。
iADAPT是一项随机交叉试验，比较I-rTMS与活性对照（S-rTMS和tDCS）对脑灌注的影响，通过ASL-fMRI评估以及单盲临床评估。根据三次ASL-fMRI检查确定患者特异性异常。I-rTMS多靶点干预针对所有可触及的双侧额叶异常，上调灌注不足区域并下调灌注过度区域。S-rTMS和tDCS置于F3位置。重复经颅磁刺激干预使用神经导航和机器人靶向装置。每组在两周内进行20次治疗。
纳入并分析了22例难治性抑郁症患者。虽然在群体水平上他们表现出膝下扣带回灌注过度，但个体表现出异质性的前额叶灌注异常。I-rTMS是唯一对脑灌注有特定影响的干预措施，显示出与负性情绪系统脱离相关的灌注减少，例如膝下扣带回、前岛叶。
矛盾的是，I-rTMS对脑灌注产生的远程效应比S-rTMS更具可重复性，而参与者之间的I-rTMS方案差异很大。这些结果表明，在个体水平上ASL-MRI观察到的异质性很显著，可能有潜力为个体化治疗提供依据。
美国国立医学图书馆临床试验注册中心编号NCT02863380，于2016年8月5日注册。
