MRI引导dmPFC-rTMS治疗作为治疗难治性抑郁症
Summary
Here we outline the procedure for MRI-guided repetitive transcranial magnetic stimulation to the dorsomedial prefrontal cortex as an experimental treatment for major depressive disorder.
Abstract
Here we outline the protocol for magnetic resonance imaging (MRI) guided repetitive transcranial magnetic stimulation (rTMS) to the dorsal medial prefrontal cortex (dmPFC) in patients with major depressive disorder (MDD). Technicians used a neuronavigation system to process patient MRIs to generate a 3-dimensional head model. The head model was subsequently used to identify patient-specific stimulatory targets. The dmPFC was stimulated daily for 20 sessions. Stimulation intensity was titrated to address scalp pain associated with rTMS. Weekly assessments were conducted on the patients using the Hamilton Rating Scale for Depression (HamD17) and Beck Depression Index II (BDI-II). Treatment-resistant MDD patients achieved significant improvements on both HAMD and BDI-II. Of note, angled, double-cone coil rTMS at 120% resting motor threshold allows for optimal stimulation of deeper midline prefrontal regions, which results in a possible therapeutic application for MDD. One major limitation of the rTMS field is the heterogeneity of treatment parameters across studies, including duty cycle, number of pulses per session and intensity. Further work should be done to clarify the effect of stimulation parameters on outcome. Future dmPFC-rTMS work should include sham-controlled studies to confirm its clinical efficacy in MDD.
Introduction
重复经颅磁刺激（rTMS治疗）是间接的局灶性皮质刺激的一种形式。颅磁刺激员工短暂，焦电磁场脉冲穿透颅骨刺激目标的大脑区域。磁刺激被认为是啮合的突触长期增强，长期抑郁的机制，从而增加或减少区域的皮层的兴奋性刺激的1。一般地，磁刺激脉冲的频率决定其效应：较高频率刺激趋向于兴奋性，而较低的频率是抑制性的。非侵入性的刺激程序也被广泛使用作为因果探针以诱导临时“皮质性病变”，并且通过暂时禁用期望皮层区2的功能建立神经行为关系或功能区域– 4。
颅磁刺激治疗涉及多个刺激会话，通常施一次ðaily在几个星期，治疗各种疾病，包括重度抑郁症（MDD）5，进食障碍6，和强迫症7。磁刺激MDD的是难治的患者潜在的选择，并且允许临床医生能够无创靶向并改变直接参与与抑郁病因或病理生理学皮质区的兴奋性。对于MDD-rTMS治疗常规皮质目标是背外侧前额叶皮层（DLPFC）8。然而，从神经影像学，病变组织，刺激研究的证据，确定背内侧前额皮层（dmPFC）作为MDD 9潜在的重要治疗靶标和各种在自我调节的思想，行为特征在于赤字其它精神障碍和情感规定10。该dmPFC是一致的活化在情绪调节11，行为监管12,13的区域。该dmPFC也与神经化学相关的14，15的结构和功能异常16在MDD
此处所描述的程序是用于磁共振成像（MRI）引导的磁刺激的dmPFC双边的20届（4周），作为用于抑郁症的治疗。除了 施加在30分钟的常规10赫兹协议，间歇THETA突发刺激方案（TBS）进行了讨论，其在6分钟会话17施加50赫兹三峰脉冲串在5赫兹。这两个协议都被认为是兴奋性的，与具有实现使用短得多的会话18可比效 应的可能性的TBS协议。在这两个协议，解剖核磁共振成像以及临床评估之前将磁刺激获得的。神经导航使用解剖扫描占dmPFC的解剖变化和优化磁刺激的位置。一个相对较新的120°-angled流体冷却磁刺激线圈也是我们ED为了刺激更深中线皮质结构。最后，磁刺激强度滴定，使用过的rTMS会话的第一个星期，以确保病人能，观察者与dmPFC刺激相关的更高的疼痛水平相对于传统DLPFC刺激。
Protocol
Representative Results
Discussion
这里，MRI引导dmPFC-磁刺激涂敷了用于治疗难治性抑郁症。在一般情况下，的rTMS在这个网站的耐受性良好，轻度头皮不适和疼痛刺激时的网站使用自适应滴定充分的管理。在开放性试验和图审查，既10赫兹和theta爆裂刺激导致抑郁症的严重程度显著的改善为由HAMD 17和BDI-II测量。
有两个值得注意的rTMS治疗过程中进行优化dmPFC刺激的关键步骤。首先，有角度的，双锥形…
Divulgations
The authors have nothing to disclose.
Acknowledgements
The authors wish to thank Aisha Dar, Vanathy Niranjan, and Dr. Umar Dar for technical assistance with rTMS delivery and data collection. The authors also wish to acknowledge the generous support of the Toronto General and Western Hospital Foundation, the Buchan Family Foundation, and the Ontario Brain Institute in funding this work.
Materials
| 3T GE Signa HDx Scanner | GE | n/a | |
| Visor 2.0 Neuronavigation System | ANT Neuro | n/a | |
| MagPro R30 Stimulator | MagVenture | n/a | |
| Cool-DB80 Coil | MagVenture | n/a |
References
- Fitzgerald, P. B., Fountain, S., Daskalakis, Z. J. A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition. Clinical Neurophysiology. 117, 2584-2596 (2006).
- Pascual-Leone, A., Gates, J. R., Dhuna, A. Induction of speech arrest and counting errors with rapid-rate transcranial magnetic stimulation. Neurology. 41, 697-702 (1991).
- Young, L., Camprodon, J. A., Hauser, M., Pascual-Leone, A., Saxe, R. Disruption of the right temporoparietal junction with transcranial magnetic stimulation reduces the role of beliefs in moral judgments. Proceedings of the National Academy of Sciences of the United States of America. 107, 6753-6758 (2010).
- Hilgetag, C. C., Théoret, H., Pascual-Leone, A. Enhanced visual spatial attention ipsilateral to rTMS-induced “virtual lesions” of human parietal cortex. Nature neuroscience. 4, 953-957 (2001).
- Berman, R. M., et al. A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Biological psychiatry. 47, 332-337 (2000).
- Van den Eynde, F., et al. Repetitive transcranial magnetic stimulation reduces cue-induced food craving in bulimic disorders. Biological psychiatry. 67 (8), 793-795 (2010).
- Berlim, M. T., Neufeld, N. H., Vanden Eynde, F. Repetitive transcranial magnetic stimulation (rTMS) for obsessive-compulsive disorder (OCD): an exploratory meta-analysis of randomized and sham-controlled trials. Journal of psychiatric research. 47 (8), 999-1006 (2013).
- Fitzgerald, P. B., et al. A randomized trial of unilateral and bilateral prefrontal cortex transcranial magnetic stimulation in treatment-resistant major depression. Psychological Medicine. 41, 1187-1196 (2011).
- Downar, J., Daskalakis, Z. J. New targets for rTMS in depression: A review of convergent evidence. Brain Stimulation. 6, 231-240 (2013).
- Downar, J., Sankar, A., Giacobbe, P., Woodside, B., Colton, P. Unanticipated Rapid Remission of Refractory Bulimia Nervosa, during High-Dose Repetitive Transcranial Magnetic Stimulation of the Dorsomedial Prefrontal Cortex: A Case Report. Frontiers in psychiatry. 3 (30), 1-5 (2012).
- Gallinat, J., Brass, M. Keep Calm and Carry On”: Structural Correlates of expressive suppression of emotions. PLoS ONE. 6, e1-e4 (2011).
- Langner, R., Cieslik, E. C., Rottschy, C., Eickhoff, S. B. Interindividual differences in cognitive flexibility: influence of gray matter volume, functional connectivity and trait impulsivity. Brain structure, & function. , (2014).
- Jung, Y. -. C., et al. Synchrony of anterior cingulate cortex and insular-striatal activation predicts ambiguity aversion in individuals with low impulsivity. Cerebral cortex. 24 (5), 1397-1408 (2014).
- Auer, D. P., Pütz, B., Kraft, E., Lipinski, B., Schill, J., Holsboer, F. Reduced glutamate in the anterior cingulate cortex in depression: An in vivo proton magnetic resonance spectroscopy study. Biological Psychiatry. 47, 305-313 (2000).
- Bora, E., Fornito, A., Pantelis, C., Yucel, M. Gray matter volume in major depressive disorder: a meta-analysis of voxel-based morphometry studies. Psychiatry research. 211 (1), 37-46 (2013).
- Sheline, Y. I., Price, J. L., Yan, Z., Mintun, M. A. Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences of the United States of America. 107, 11020-11025 (2010).
- Huang, Y. -. Z., Edwards, M. J., Rounis, E., Bhatia, K. P., Rothwell, J. C. Theta burst stimulation of the human motor cortex. Neuron. 45, 201-206 (2005).
- Bakker, N., et al. rTMS of the dorsomedial prefrontal cortex for major depression: safety, tolerability, effectiveness, and outcome predictors for 10 Hz versus intermittent theta-burst stimulation. Brain Stimulation. In Press, 1-22 (2014).
- Talairach, J., Tournoux, P. Co-planar stereotaxic atlas of the human brain: 3-dimensional proportional system: an approach to cerebral imaging. Neuropsychologia. 39, 145 (1988).
- Terao, Y., et al. A single motor unit recording technique for studying the differential activation of corticospinal volleys by transcranial magnetic stimulation. Brain Research Protocols. 7, 61-67 (2001).
- Schutter, D. J. L. G., van Honk, J. A standardized motor threshold estimation procedure for transcranial magnetic stimulation research. The journal of ECT. 22, 176-178 (2006).
- Downar, J., Geraci, J., et al. Anhedonia and Reward-Circuit Connectivity Distinguish Nonresponders from Responders to Dorsomedial Prefrontal Repetitive Transcranial Magnetic Stimulation in Major Depression. Biological psychiatry. , 1-26 (2013).
- Downar, J., Geraci, J., et al. Anhedonia and Reward-Circuit Connectivity Distinguish Nonresponders from Responders to Dorsomedial Prefrontal Repetitive Transcranial Magnetic Stimulation in Major Depression. Biological Psychiatry. 76 (3), 176-185 (2014).
- Beck, A. T., Steer, R. A., Brown, G. K. . Manual for the Beck depression inventory-II. , 1-82 (1996).
- Beck, A. T., Epstein, N., Brown, G., Steer, R. A. An inventory for measuring clinical anxiety: psychometric properties. Journal of consulting and clinical psychology. 56, 893-897 (1988).
- Hamilton, M. C. Hamilton Depression Rating Scale (HAM-D). REDLOC. 23, 56-62 (1960).
- Salomons, T. V., et al. Resting-State Cortico-Thalamic-Striatal Connectivity Predicts Response to Dorsomedial Prefrontal rTMS in Major Depressive Disorder. Neuropsychopharmacology official publication of the American College of Neuropsychopharmacology. 39, 488-498 (2014).
- Hayward, G., et al. Exploring the physiological effects of double-cone coil TMS over the medial frontal cortex on the anterior cingulate cortex: an H2(15)O PET study. The European journal of neuroscience. 25, 2224-2233 (2007).
- Vanneste, S., Ost, J., Langguth, B., De Ridder, D. TMS by double-cone coil prefrontal stimulation for medication resistant chronic depression: a case report. Neurocase. 20 (1), 61-68 (2014).
- Mueller, S., et al. Individual Variability in Functional Connectivity Architecture of the Human Brain. Neuron. 77, 586-595 (2013).
- 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, 595-603 (2012).
- Fox, M. D., Liu, H., Pascual-Leone, A. Identification of reproducible individualized targets for treatment of depression with TMS based on intrinsic connectivity. NeuroImage. 66, 151-160 (2013).
- Kedzior, K., Azorina, V., Reitz, S. More female patients and fewer stimuli per session are associated with the short-term antidepressant properties of repetitive transcranial magnetic stimulation (rTMS): a meta-analysis of 54 sham-controlled studies published between 1997-2013. Neuropsychiatric disease and treatment. 10, 727-756 (2014).
- Lee, J. C., Blumberger, D. M., Fitzgerald, P. B., Daskalakis, Z. J., Levinson, A. J. The Role of Transcranial Magnetic Stimulation in Treatment-Resistant Depression: A Review. Current Pharmaceutical Design. 18, 5846-5852 (2012).
- Maeda, F., Keenan, J. P., Tormos, J. M., Topka, H., Pascual-Leone, A. Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability. Experimental Brain Research. 133, 425-430 (2000).
- Brunoni, A. R., Ferrucci, R., Fregni, F., Boggio, P. S., Priori, A. Transcranial direct current stimulation for the treatment of major depressive disorder: a summary of preclinical, clinical and translational findings. Progress in neuro-psychopharmacology, & biological psychiatry. 39, 9-16 (2012).
- Mantovani, A., Simpson, H. B., Fallon, B. A., Rossi, S., Lisanby, S. H. Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP. 13, 217-227 (2010).
- Watts, B. V., Landon, B., Groft, A., Young-Xu, Y. A sham controlled study of repetitive transcranial magnetic stimulation for posttraumatic stress disorder). Brain Stimulation. 5, 38-43 (2012).
- Berlim, M. T., Broadbent, H. J., Van den Eynde, F. Blinding integrity in randomized sham-controlled trials of repetitive transcranial magnetic stimulation for major depression: a systematic review and meta-analysis. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 16, 1173-1181 (2013).
- Brunoni, A. R., Lopes, M., Kaptchuk, T. J., Fregni, F. Placebo response of non-pharmacological and pharmacological trials in major depression: a systematic review and meta-analysis. PLoS One. 4, e4824 (2009).
- Chistyakov, A. V., Rubicsek, O., Kaplan, B., Zaaroor, M., Klein, E. Safety tolerability and preliminary evidence for antidepressant efficacy of theta-burst transcranial magnetic stimulation in patients with major depression. The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP). 13, 387-393 (2010).
- Iyer, M. B., Schleper, N., Wassermann, E. M. Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation). The Journal of neuroscience the official journal of the Society for Neuroscience. 23, 10867-10872 (2003).
- Vedeniapin, A., Cheng, L., George, M. S. Feasibility of simultaneous cognitive behavioral therapy and left prefrontal RTMS for treatment resistant depression. Brain Stimulation. 3, 207-210 (2010).
- Rumi, D. O., et al. Transcranial magnetic stimulation accelerates the antidepressant effect of amitriptyline in severe depression: A double-blind placebo-controlled study. Biological Psychiatry. 57, 162-166 (2005).
- Platz, T., Rothwell, J. C. Brain stimulation and brain repair–rTMS: from animal experiment to clinical trials–what do we know. Restorative neurology and neuroscience. 28, 387-398 (2010).
