EXPERIMENTAL STUDIES A High Resolution Assessment of the Repeatability of Relative Location and Intensity of Transcranial Magnetic Stimulation–induced and Volitionally Induced Blood Oxygen Level–dependent Response in the Motor Cortex Stewart Denslow, PhD,* Mikhail Lomarev, MD, PhD,*¶ Daryl E. Bohning, PhD,* Qiwen Mu, MD, PhD,* and Mark S. George, MD*†‡§ Objective: Using functional magnetic resonance imaging, we as- sessed variation in location and intensity of blood oxygen level– dependent contrast associated with movements induced by transcra- nial magnetic stimulation or volition. Background: Anatomic location and within-subject repeatability of blood oxygen level–dependent responses induced by transcranial magnetic stimulation comprise critical information to the use of in- terleaved transcranial magnetic stimulation/functional magnetic reso- nance imaging as a neuroscience tool. Methods: Eleven healthy adults were scanned 3 times each at 1.5 T. Interleaved with functional magnetic resonance imaging, 1-Hz trans- cranial magnetic stimulation was applied over motor cortex. VOL was alternated with transcranial magnetic stimulation over the scans. Results: Intra-subject standard deviations in blood oxygen level– dependent locations ranged between 3 and 6 millimeters, allowing localization to subregions of the motor strip. Coil placement relative to blood oxygen level–dependent location varied more than blood oxygen level–dependent location (sd x = 9.5mm, sd y = 8.7mm, sd z = 9.0mm) with consistent anterior displacement (dy = 21.8 mm, P = <0.025). Analysis of variance did not detect significant differences between transcranial magnetic stimulation and VOL blood oxygen level–dependent locations or intensities, in contrast to significant inten- sity differences detected in auditory blood oxygen level dependence. Conclusion: The high repeatability of location of transcranial mag- netic stimulation–induced blood oxygen level–dependent activation suggests that transcranial magnetic stimulation/functional magnetic resonance imaging stimulation can be used as a precise tool in inves- tigation of cortical mechanisms. The similarity between VOL and transcranial magnetic stimulation suggests that transcranial magnetic stimulation may act through natural brain movement circuits. Key Words: functional magnetic resonance imaging, human motor cortex, volitional movement, blood flow (Cog Behav Neurol 2004;17:163–173) T he capacity of transcranial magnetic stimulation (TMS) to directly stimulate cortical neurons 1 has made TMS attrac- tive as a probe of basic neural interconnections. 2,3 The nonin- vasive nature of TMS has also generated great interest in its use for investigation and treatment of depression. 2,4,5 These fac- tors have led to growing interest in combining TMS with func- tional imaging methods to explore brain circuitry. 6–12 Both positron emission tomography and functional magnetic reso- nance imaging (fMRI) observations have shown similarity in the brain’s responses to TMS and cognitive tasks. 6,7,9,10,13 However, the relations among cortical response locations, TMS coil locations, and specific cortical anatomy are not yet precisely described. Additionally, recent fMRI results have demonstrated the large variability in volume of blood oxygen level dependent (BOLD) activation that is encountered be- tween repeated scans. 14,15 It is consequently unclear what magnitude of variation in location indices can be expected for BOLD responses both from physiological tasks and from TMS stimulation. TMS depolarization of axons displays a complex depen- dence upon configuration between the induced electric field and axonal axis. Models have shown greater likelihood of de- polarization for axons parallel rather than perpendicular to the Received for publication June 2, 2003; revised October 10, 2003; accepted November 16, 2003. From the *Center for Advanced Imaging Research and Brain Stimulation Laboratories, Department of Radiology, Medical University of South Carolina, Charleston, South Carolina; †Center for Advanced Imaging Re- search and Brain Stimulation Laboratories, Department of Psychiatry, Medical University of South Carolina, Charleston, South Carolina; ‡Cen- ter for Advanced Imaging Research and Brain Stimulation Laboratories, Department of Neurology, Medical University of South Carolina, Charles- ton, South Carolina; §Ralph H. Johnson Veterans Hospital, Charleston, South Carolina; and ¶Institute of the Human Brain, St. Petersburg, Russia. Supported in part by research grants from the Dana Foundation (Bohning), from the National Institute of Neurological Disorders and Stroke (RO1 RR14080-02), and from the Defense Advanced Research Projects Agency Defense Sciences Office. None of the authors have equity or significant financial conflicts. Reprints: Dr. Stewart Denslow, Radiology Department, 171 Ashley Avenue, Medical University of South Carolina, Charleston, SC 29425 (e-mail: denslows@musc.edu). Copyright © 2004 by Lippincott Williams & Wilkins Cog Behav Neurol • Volume 17, Number 3, September 2004 163