Background: The left dorsolateral prefrontal cortex (DLPFC) is the most commonly used target for transcranial magnetic stimulation (TMS) in the treatment of depression. The "5-cm rule" is an empiric method used for probabilistic targeting of the DLPFC in most clinical trials. This rule may be suboptimal, as it does not account for differences in skull size or variations in prefrontal anatomy relative to motor cortex location. This study is a post hoc analysis of data from a large repetitive TMS (rTMS) trial in which we examined the variability of coil placement and how it affects antidepressant efficacy. Methods: Fifty-four depressed subjects enrolled in a randomized, single-site trial received either active rTMS or sham for 3 weeks. Prior to treatment initiation, investigators placed vitamin E capsules at the point of stimulation and used a high-resolution magnetic resonance imaging (MRI) scan to image these fiducials relative to anatomy. We employed a semiautomated imaging-processing algorithm to localize the cortical region stimulated. Results: Active TMS significantly reduced Hamilton Depression Rating Scale (HDRS) scores. A linear model for this improvement involving the coordinates of the stimulated cortex location, age, and treatment condition was highly significant. Specifically, individuals with more anterior and lateral stimulation sites were more likely to respond. Conclusions: These results suggest that within the general anatomical area targeted by the 5-cm rule, placing the TMS coil more laterally and anteriorly is associated with improved response rates in TMS depression studies. Controlled studies testing this anatomical hypothesis are needed.
Bibliographical noteFunding Information:
Dr. Nahas reports having received consulting fees from Neuronetics, Inc., and research funding from NIMH, National Alliance of Research for Schizophrenia And Depression, Hope for Depression Research, Neuronetics, Inc., Cyberonics, Inc., and Medtronic, Inc. Dr. Avery disclosed consulting fees from North Star Neuroscience, Neuronetics, Inc., and Performance Plus; research funding from NIMH, National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); honoraria for speaking and being on advisory boards from Eli Lilly and Takeda; and received private gift from Bipolar Illness Fund. Dr. George reported consulting for Bristol-Meyers-Squibb, DarPharma, GlaxoSmithKline, Jazz Pharmaceuticals, Parke Davis, Aspect Medical, Brainsway, Brainsonix (unpaid), Cephos (unpaid), Cyberonics, Inc., Dantex, Mediphysics/Amersham, Neuronetics, Inc. (unpaid), and Neuropace. Dr. George also reported that the Medical University of South Carolina (MUSC) has filed eight patents or invention disclosures under his name regarding brain imaging and brain stimulation. Dr. Holtzheimer received honoraria from Abbot Laboratories, Cyberonics, Inc., Boerhinger-Ingelheim, Bristol-Meyers-Squibb, and Forest; received consulting fees from Advanced Neuromodulation Systems, Inc. Tetragenex, Inc., Shaw Science and AstraZeneca, Inc., American Federation for Aging Research (AFAR), Dana Foundation, Neuronetics, Inc., NARSAD, National Center for Research Resources, NIMH, National Institutes of Health Loan Repayment Program, Northstar, Inc., Stanley Medical Research Institute, and Woodruff Foundation. Drs. Herbsman and Haynor along with Mr. Ramsey, Ms. Wadjik, and Ms. Hardaway reported no biomedical financial interests or potential conflicts of interest.
This study was funded by National Institute of Mental Health (NIMH) RO1 MH62154 (DA), NIMH 1K08MH70615-01A1 (ZN), and NIMH Optimization of TMS for the Treatment of Depression (OPT-TMS) 5 R01 MH069887-04 (MSG). The study was also made possible with general funds from the Brain Stimulation Laboratory (BSL), the Center for Advanced Imaging Research (CAIR), and the South Carolina Research Authority (DR).
- frontal lobes