| Transcranial magnetic stimulation (TMS) was first described in 1985 as a non-invasive, painless way to stimulate the human motor cortex. In the past three decades, TMS has been administered to individuals with various neurological and psychiatric pathologies to investigate the neurophysiology of these disorders and test the feasibility of developing TMS-based diagnostics and treatments. Focal TMS of the hand area of the primary motor cortex (M1hand) during bimanual volitional muscular contraction can elicit extremely recognizable phenomena in the electromyography (EMG) from both hands. Specifically, TMS can elicit a motor evoked potential (MEP) followed by a contralateral cortical silent period (CSP) in contralateral hand musculature. At low stimulation intensities an isolated contralateral cortical silent period (iCSP) can be recorded. Additionally, TMS of M1hand can also suppress volitional activity in ipsilateral hand musculature, termed the ipsilateral silent period (ISP). Timing, amplitude, and threshold measures specific to each of these phenomena have been used to quantify neuronal dysfunction, disease progression, and drug treatment responsiveness in various neurological and psychiatric disorders. However, the exact mechanism under which TMS causes these phenomena is unknown. In this dissertation, we suggest that these phenomena have distinct neuronal populations and circuits that contribute to their formation. Furthermore, we argue that these distinct neuronal populations differ in their response characteristics following changes in TMS intensity, force production, and task. In our first study, we describe the variety of calculation techniques and criteria used to define and measure stimulus-response characteristics from these phenomena, emphasizing the need for standardization. We introduce a computer-based, automated-parameterization program (APP) we developed which provides a comprehensive set of EMG magnitude and temporal measures. The APP was tested using MEP, CSP, and iCSP TMS stimulus--response data from a healthy adult population (N = 13). The APP had the highest internal reliability (Cronbach's alpha = .98) for CSP offset time compared with two prominent automated methods. The immediate post-CSP EMG recovery level was 49% higher than the pre-TMS EMG level. MEP size (peak amplitude, mean amplitude, peak-to-peak amplitude, and area) correlated higher with effective electric-field (Eeff) than other intensity measures (r ≈ 0.5 vs. r ≈ 0.3) suggesting that Eeff is better suited for standardizing MEP stimulus.response relationships. The APP successfully characterized individual and mean epochs containing MEP, CSP, and iCSP responses. The APP provided common signal and temporal measures consistent with previous studies and novel additional parameters. In our second study, we used uni- and bi-manual tasks to simultaneously measure MEPs, iCSPs, CSPs, and ISPs during TMS to M1hand. We aimed to better understand the neuronal populations contributing to these phenomena during uni- and bi- manual tasks. Healthy adult subjects (N = 14) performed uni- and bi-manual isometric contractions of the first dorsal interosseous (FDI) muscles at two isotonic loads. TMS was applied to the hand area of the left primary motor cortex to elicit MEPs, CSPs, iCSPs, and ISPs across a range of stimulus intensities. We found that a symmetric bimanual task requiring low (12 - 25% MVC) force production was the most efficient at eliciting these phenomena across a range of TMS intensities. The time courses of these phenomena appear to be distinctive and indicate separate origins. Response characteristics to intensity, force, and task manipulation further support diverse contributions from inter- and intra-hemispheric excitatory and inhibitory elements. A symmetric bimanual task provides a means to simultaneously stimulate multiple cortical excitatory and inhibitory elements synchronized to a single TMS pulse. Thus, TMS studies using a symmetric bimanual task support efficient acquisition of MEP, iCSP, CSP, ISP, and IHCT measures in populations whose attention or endurance may be limited (i.e. children, elderly, or patients). |
