Transcranial magnetic stimulation (TMS) is a technique whereby a pulsed magnetic field created by a small coil in contact with the head is used to induce neuron depolarization in the brain. TMS has been used as a neuroscience tool and has potential clinical applications, especially in treating depression, but progress has been slowed by incomplete understanding of TMS' effects, especially in treating depression, but progress has been slowed by incomplete understanding of TMS' effects, especially in areas other than motor cortex. Functional magnetic resonance imaging (fMRI) is an MRI technique which uses blood flow dependent changes in the brain to image the sites of neuronal activity. We propose to develop a combination of TMS and fMRI that will greatly accelerate the use of TMS as a research and perhaps therapeutic tool. Though TMS has been combined with positron emission tomography (PET), fMRI is potentially superior to PET and other modalities for imaging TMS' effects because of: the lack of ionizing radiation, MRI's superior temporal and spatial resolution, and the ability to merge functional data as well as the TMS coil's magnetic field onto structural scans. Combined TMS/fMRI has the potential for adding a new dimension to fMRI, namely, a non-invasive means for non-cognition stimulation or inhibition of neuronal circuits to complement the repertoire of cognitive tasks now used. In addition to significantly enhancing fMRI's ability to map neuronal circuitry, this new methodology makes it possible to use fMRI to objectively and systematically explore the effects of TMS, i.e exactly where stimulation occurs, and how much, accelerating development of this exciting new tool and its anticipated therapeutic application. Having already demonstrated the feasibility of combining TMS and fMRI, something many thought impossible, we propose to refine and characterize our technique, and then apply it in human studies aimed at the accumulation of essential normative data.
Specific Aim #1 to demonstrate that our TMS/fMRI technique can produce repeatable results with signal- to-noise ratios (SNR) comparable to standard fMRI studies.
Specific Aim #2 To merge 3D in-vivo maps of the TMS coil's magnetic field with BOLD- fMRI images to obtain actual TMS stimulation intensities at fMRI response sites for better understanding of observed images to obtain actual TMS stimulation intensities at fMRI response sites for better understanding of observed effects and estimates of absolute cortical sensitivity.
Specific Aim #3 To gather overall normative data on TMS/fMRI repeatability and sensitivity in paired studies of the differences between TMS-induced and volitional movement for TMS over sites determined by image-based (3a) and functional-based (3b) localization, and (3c) compare the two localization for relative spatial consistency, repeatability and levels of response.
