使用基于fMRI的靶向方法对抑郁症进行个体化的rTMS治疗
Summary
本方案描述了重复经颅磁刺激（rTMS）的应用，其中背外侧前额叶皮层（DLPFC）的一个子区域与亚属前扣带皮层（sgACC）具有最强的功能反相关，位于基于fMRI的神经导航系统的辅助下作为刺激靶标。
Abstract
为了获得更大的临床疗效，重度抑郁症（MDD）的治疗革命备受期待。重复性经颅磁刺激（rTMS）是一种非侵入性和安全的神经调节技术，可立即改变大脑活动。尽管在MDD的治疗中应用广泛，但治疗反应在个体之间仍然不同，这可能是由于刺激靶点的定位不准确。我们的研究旨在研究功能性磁共振成像（fMRI）辅助定位是否能提高rTMS治疗抑郁症的疗效。我们打算鉴定和刺激MDD中背外侧前额叶皮层（DLPFC）的分区域，该分区域与亚属前扣带皮层（sgACC）具有最强的抗相关性，并对这种新方法和传统的5-cm规则进行比较研究。为了实现更精确的刺激，在神经导航系统的指导下应用了这两种方法。我们预计，基于静息状态功能连接的个体化定位TMS治疗可能比5-cm方法显示出更好的临床疗效。
Introduction
重性抑郁障碍（MDD）的特征是显着和持续的抑郁症，在更严重的情况下，患者可能会遇到幻觉和/或妄想1，2。与一般人群相比，MDD患者的自杀风险高出约20倍3。虽然药物是目前最常用的MDD治疗方法，但30%-50%的患者缺乏对抗抑郁药的充分反应4。对于应答者来说，症状改善往往在相对较长的潜伏期后出现，并伴有副作用。心理治疗虽然对某些患者有效，但成本高昂且耗时。因此，迫切需要更安全、更有效的MDD治疗。
重复经颅磁刺激（rTMS）是一种非侵入性和安全的技术，已被批准用于治疗各种精神障碍5，6，7。尽管其治疗机制尚不清楚，但据推测，rTMS通过调节受刺激大脑区域的活动和神经可塑性8，9，10起作用，从而使特定的功能网络10，11，12正常化。rTMS还引起网络效应，其通过连接途径唤起远程大脑区域的变化，导致放大的治疗效果13。虽然rTMS可以立即而有力地改变大脑活动，但其在MDD治疗中的反应率仅为18%左右14。主要原因可能是刺激目标15的位置不准确。
亚属前扣带皮层（sgACC）主要负责情绪处理，并在调节对压力事件的反应，对内部和外部刺激的情绪反应以及情绪表达中发挥作用16，17，18。ACC的这个次区域与大脑皮层和边缘系统共享大量的结构和功能连接19，20。有趣的是，研究表明，该区域的刺激后活动与TMS的临床疗效密切相关。例如，在针对右背外侧前额叶皮层（DLPFC）的TMS疗程后，sgACC的血流量减少，这与缓解抑郁症状有关21。Vink等人发现靶 向DLPFC的刺激被传播到sgACC，并提出sgACC活性可以是TMS治疗反应的生物标志物。根据之前的研究，Fox及其同事22提出，靶向DLPFC的一个次区域，该次区域与sgACC（MNI坐标：6，16，-10）显示出最强的功能抗连通性，可以增强抗抑郁作用。在这里，我们展示了一个旨在检验这一假设的研究方案。
Protocol
告知所有参与者有关研究的信息，并要求他们在研究开始前签署知情同意书。本方案经广州医科大学附属脑医院研究伦理委员会批准。 注意：在这项双盲研究中，抑郁症患者被随机分为两组。在实验组中，刺激目标通过基于DLPFC-sgACC的个性化定位方法定位（详见3.3）。对照组的目标通过平均5-cm方法获得（即（-41，16，54））22。 1. 参与者?…
Representative Results
ROI方面的FC分析应该表明，sgACC与DLPFC具有显着的反相关性，其中最强的负相关是要选择的刺激目标。sgACC-DLPFC功能连接性与治疗反应之间的显著反相关性应在相关性分析33中找到。 目前的方案基于一种创新的TMS靶向方法，以前没有研究应用过。在这里，我们介绍一项应用传统5厘米方法的fMRI指导TMS试验的结果。该研究34 提出了一种新的治疗?…
Discussion
sgACC负责情绪处理，并在压力调节16，17，18中发挥重要作用。一项研究表明，靶向与sgACC（6，16，-10）表现出最强功能抗连通性的DLPFC次区域可以增强抗抑郁作用25。因此，精确定位此目标是该协议的关键步骤。在刺激之前，应在神经导航的帮助下准确标出大脑的边界，并仔细记录头部以确保头部模型的准确性?…
Offenlegungen
The authors have nothing to disclose.
Acknowledgements
本研究由中国博士后科学基金资助项目（2019M652854）和中国广东省自然科学基金（批准号：2020A1515010077）资助。
Materials
| 3T Philips Achieva MRI scanner | Philips | ||
| Harvard/Oxford cortical template | http://www.cma.mgh.harva rd.edu/ | ||
| MATLAB | MathWorks | ||
| SPM12 | http://www.fil.ion.ucl.ac.uk/spm | ||
| The Visor2 system | ANT Neuro | The Visor2 software, the optical tracking system, tracking tools and calibration board are part of the visor2 system. | |
| TMS device | Magstim, Carmarthenshire, UK |
Referenzen
- Schramm, E., Klein, D. N., Elsaesser, M., Furukawa, T. A., Domschke, K. Review of dysthymia and persistent depressive disorder: History, correlates, and clinical implications. Lancet Psychiatry. 7 (9), 801-812 (2020).
- Knight, M. J., Baune, B. T. Cognitive dysfunction in major depressive disorder. Current Opinion in Psychiatry. 31 (1), 26-31 (2018).
- Otte, C., et al. Major depressive disorder. Nature Reviews Disease Primers. 2 (1), 1-20 (2016).
- Rafeyan, R., Papakostas, G. I., Jackson, W. C., Trivedi, M. H. Inadequate response to treatment in major depressive disorder: Augmentation and adjunctive strategies. Journal of Clinical Psychiatry. 81 (3), (2020).
- Zhang, J. J., Fong, K. N., Ouyang, R. g., Siu, A. M., Kranz, G. S. J. A. Effects of repetitive transcranial magnetic stimulation (rTMS) on craving and substance consumption in patients with substance dependence: A systematic review and meta-analysis. Addiction. 114 (12), 2137-2149 (2019).
- Enokibara, M., Trevizol, A., Shiozawa, P., Cordeiro, Q. Establishing an effective TMS protocol for craving in substance addiction: Is it possible. American Journal on Addictions. 25 (1), 28-30 (2016).
- Diana, M., et al. Rehabilitating the addicted brain with transcranial magnetic stimulation. Nature Reviews Neuroscience. 18 (11), 685 (2017).
- Vink, J. J. T., et al. A novel concurrent TMS-fMRI method to reveal propagation patterns of prefrontal magnetic brain stimulation. Human Brain Mapping. 39 (11), 4580-4592 (2018).
- Baeken, C., De Raedt, R. Neurobiological mechanisms of repetitive transcranial magnetic stimulation on the underlying neurocircuitry in unipolar depression. Dialogues in Clinical Neuroscience. 13 (1), 139-145 (2011).
- Tik, M., et al. Towards understanding rTMS mechanism of action: Stimulation of the DLPFC causes network-specific increase in functional connectivity. Neuroimage. 162, 289-296 (2017).
- Castrén, E. Neuronal network plasticity and recovery from depression. JAMA Psychiatry. 70 (9), 983-989 (2013).
- Cantone, M., et al. Cortical plasticity in depression. ASN Neuro. 9 (3), 1759091417711512 (2017).
- Valero-Cabré, A., Amengual, J. L., Stengel, C., Pascual-Leone, A., Coubard, O. A. Transcranial magnetic stimulation: A comprehensive review of fundamental principles and novel insights. Neuroscience & Biobehavioral Reviews. 83, 381-404 (2017).
- Luber, B. M., et al. Using neuroimaging to individualize TMS treatment for depression: Toward a new paradigm for imaging-guided intervention. Neuroimage. 151, 65-71 (2017).
- Wassermann, E. M., Zimmermann, T. J. P. Transcranial magnetic brain stimulation: Therapeutic promises and scientific gaps. Pharmacology & Therapeutics. 133 (1), 98-107 (2012).
- Kim, H., et al. Hypometabolism and altered metabolic connectivity in patients with internet gaming disorder and alcohol use disorder. Progress in Neuro-Psychopharmacology & Biological Psychiatry. 95, 109680 (2019).
- Kim, J. Y., et al. The correlation between the frontostriatal network and impulsivity in internet gaming disorder. Scientific Reports. 9 (1), 1191 (2019).
- Wang, Y., et al. Impaired decision-making and impulse control in Internet gaming addicts: evidence from the comparison with recreational Internet game users. Addiction Biology. 22 (6), 1610-1621 (2017).
- Mayberg, H. S. Limbic-cortical dysregulation: A proposed model of depression. Journal of Neuropsychiatry and Clinical Neurosciences. 9 (3), 471-481 (1997).
- Rolls, E. T. The cingulate cortex and limbic systems for emotion, action, and memory. Brain Structure and Function. 224 (9), 3001-3018 (2019).
- Philip, N. S., et al. Network mechanisms of clinical response to transcranial magnetic stimulation in posttraumatic stress disorder and major depressive disorder. Biological Psychiatry. 83 (3), 263-272 (2018).
- Fox, M. D., Buckner, R. L., White, M. P., Greicius, M. D., Pascual-Leone, A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biological Psychiatry. 72 (7), 595-603 (2012).
- Sheehan, D. V., et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry. 59, 22-33 (1998).
- Montgomery, S. A., Asberg, M. A new depression scale designed to be sensitive to change. British Journal of Psychiatry. 134, 382-389 (1979).
- Fox, M. D., Buckner, R. L., White, M. P., Greicius, M. D., Pascual-Leone, A. J. B. p. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biological Psychiatry. 72 (7), 595-603 (2012).
- Cash, R. F. H., et al. Personalized connectivity-guided DLPFC-TMS for depression: Advancing computational feasibility, precision and reproducibility. Human Brain Mapping. , (2021).
- Hamilton, M. A rating scale for depression. Journal of Neurology, Neurosurgery, and Psychiatry. 23 (1), 56-62 (1960).
- Beck, A. T., Steer, R. A., Brown, G. K. . Manual for the Beck depression inventory-II. , 1-82 (1996).
- Hamilton, M. The assessment of anxiety states by rating. British Journal of Medical Psychology. 32 (1), 50-55 (1959).
- Guy, W. ECDEU assessment manual for psychopharmacology, revised. U.S. Dept. of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs. , (1976).
- Kern, R. S., et al. The MATRICS consensus cognitive battery, part 2: Co-norming and standardization. American Journal of Psychiatry. 165 (2), 214-220 (2008).
- Nuechterlein, K. H., et al. The MATRICS consensus cognitive battery, part 1: Test selection, reliability, and validity. American Journal of Psychiatry. 165 (2), 203-213 (2008).
- Jing, Y., et al. Pregenual or subgenual anterior cingulate cortex as potential effective region for brain stimulation of depression. Brain and Behavior. 10 (4), 01591 (2020).
- Cole, E. J., et al. Stanford accelerated intelligent neuromodulation therapy for treatment-resistant depression. American Journal of Psychiatry. 177 (8), 716-726 (2020).
- Cash, R. F. H., et al. Subgenual functional connectivity predicts antidepressant treatment response to transcranial magnetic stimulation: Independent validation and evaluation of personalization. Biological Psychiatry. 86 (2), 5-7 (2019).
- Ge, R., Downar, J., Blumberger, D. M., Daskalakis, Z. J., Vila-Rodriguez, F. Functional connectivity of the anterior cingulate cortex predicts treatment outcome for rTMS in treatment-resistant depression at 3-month follow-up. Brain Stimulation. 13 (1), 206-214 (2020).
- Ojemann, J. G., et al. Anatomic localization and quantitative analysis of gradient refocused echo-planar fMRI susceptibility artifacts. Neuroimage. 6 (3), 156-167 (1997).
- Schonfeldt-Lecuona, C., et al. The value of neuronavigated rTMS for the treatment of depression. Clinical Neurophysiology. 40 (1), 37-43 (2010).
- Krieg, S. M., et al. Protocol for motor and language mapping by navigated TMS in patients and healthy volunteers; workshop report. Acta Neurochir (Wien). 159 (7), 1187-1195 (2017).
- Haddad, A. F., Young, J. S., Berger, M. S., Tarapore, P. E. Preoperative applications of navigated transcranial magnetic stimulation. Frontiers in Neurology. 11, 628903 (2020).
- Baeken, C., Duprat, R., Wu, G. R., De Raedt, R., van Heeringen, K. Subgenual anterior cingulate-medial orbitofrontal functional connectivity in medication-resistant major depression: A neurobiological marker for accelerated intermittent theta burst stimulation treatment. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. 2 (7), 556-565 (2017).
- Wu, G. R., De Raedt, R., Van Schuerbeek, P., Baeken, C. Opposite subgenual cingulate cortical functional connectivity and metabolic activity patterns in refractory melancholic major depression. Brain Imaging and Behavior. 14 (2), 426-435 (2020).
- Salomons, T. V., et al. Resting-state cortico-thalamic-striatal connectivity predicts response to dorsomedial prefrontal rTMS in major depressive disorder. Neuropsychopharmacology. 39 (2), 488-498 (2014).
- Iseger, T. A., van Bueren, N. E. R., Kenemans, J. L., Gevirtz, R., Arns, M. A frontal-vagal network theory for major depressive disorder: Implications for optimizing neuromodulation techniques. Brain Stimulation. 13 (1), 1-9 (2020).
Diesen Artikel zitieren
Luo, X., Hu, Y., Wang, R., Zhang, M., Zhong, X., Zhang, B. Individualized rTMS Treatment for Depression using an fMRI-Based Targeting Method. J. Vis. Exp. (174), e62687, doi:10.3791/62687 (2021).