Taulu, SamuMcPherson, Alexandria Nicole2026-02-052026-02-052026-02-052025McPherson_washington_0250E_28985.pdfhttps://hdl.handle.net/1773/55287Thesis (Ph.D.)--University of Washington, 2025The recent implementation of novel on-scalp magnetoencephalography (MEG) sensors, specifically optically pumped magnetometers (OPM), has brought about exciting prospects for more precise measurements of natural human brain activity. In order to leverage the full potential of on-scalp systems, certain challenges must be overcome, requiring improvements in both the methodology and instrumentation of these MEG systems. First, traditional signal space separation (SSS) methods for isolating the nano-Tesla (nT) magnetic fields generated form neuronal activity fail when the MEG sensors are on the scalp, as opposed to elevated above the head in a liquid helium Dewar as with traditional, cryogenic MEG systems made of Superconducting Quantum Interference Devices (SQUID). Next, due to the increased proximity of sensors to the brain, on-scalp systems can in principle capture higher spatial frequencies of magnetic signal topology, but current inverse methods may fail with the increased noise that comes with higher frequency components. Finally, the OPM sensors themselves are more sensitive to low-frequency and DC fields than SQUID MEG systems, so new hardware and magnetic field compensation techniques are needed to reduce the remnant magnetic field around the sensor systems. In this dissertation, we first present the novel multi-SSS (mSSS) method, a straightforward mathematical adaptation to the SSS method to account for the on-scalp sensor geometry with various OPM systems. Next, we explore the applications of a matrix regularization method, Foster's Inverse, on SSS to reduce the detrimental impacts of sensor noise on the reconstruction of the internal brain activity, specifically when focusing on higher order components of the magnetic field. Finally, we discuss challenges and current solutions for reducing the remnant magnetic field in the presence of OPM sensors low enough for desired operation and present the coil compensation system designed for use at the Institute for Learning and Brain Sciences (I-LABS) MEG Center, University of Washington. All three of these projects culminate to an advancement of the methodology and instrumentation needed for successful studies of human brain activity with on-scalp MEG systems.application/pdfen-USCC BYBiophysicsMagnetoencephalographyon-scalp MEGoptically pumped magnetometerPhysicsPhysicsBiophysicsPhysicsThesis