Abstract

The relationship between cortical excitability and hemodynamic activity has been demonstrated in animal studies. However, it is poorly reproduced and understood in humans, limited by the requirement of simultaneous measurements of excitability and hemodynamic activity. Transcranial Magnetic Stimulation (TMS) is a non-invasive technique that induces human cortical plasticity and allows the assessment of modulated cortical excitability. Functional Near Infra-Red Spectroscopy (fNIRS) is a non-invasive neuroimaging modality, which allows monitoring changes in oxy- and deoxy-hemoglobin (i.e., HbO/HbR) in the cerebral cortex. Taking advantage of the fNIRS technique being insensitive to electromagnetic artifacts and wearable, the combination with TMS provides a unique and promising way to assess the relationship between cortical excitability and hemodynamic responses in humans.
This Ph.D. thesis consists of four original studies combining personalized Near Infra-Red Optical Tomography (NIROT) and TMS to investigate the hemodynamic correlates of fluctuations in neuronal excitability, each including key methodological developments. In the first manuscript, we proposed and evaluated a new NIROT reconstruction method – the Maximum Entropy on the Mean (MEM), by adapting and improving its original version proposed for Electro-/Magneto-encephalography source imaging. After detailed evaluations of MEM NIROT on realistic simulated data, we introduced in the second manuscript the original concept of personalized NIROT workflow combining MEM reconstruction and personalized optimal montage. Using functional magnetic resonance imaging as the reference, the evaluation of finger tapping data demonstrated that our proposed workflow allowed better spatial accuracy and reliability than other widely used NIROT methods. The third manuscript applied this workflow on a simultaneous TMS and fNIRS study and demonstrated a positive relationship between motor task-related hemodynamic activity and cortical excitability. The last manuscript applied advanced Bayesian data analysis and hierarchical models to the same data set, which improved the accuracy and reliability of the results when dealing with relatively high variability and small sample size data. Our results showed a significant positive correlation between the effects of TMS modulated cortical excitability and its effects on task-related hemodynamic activity. Therefore, our studies contribute to further expand the application of brain stimulation to the treatment of neuronal disorders that may require modulations of the hemodynamic response.