Exploring the Limits of MEG Spatial Resolution with Multipolar Expansions

The advent of scalp magnetoencephalography (MEG) based on optically pumped magnetometers (OPMs) may represent a step change in the field of human electrophysiology. Compared to cryogenic MEG based on superconducting quantum interference devices (SQUIDs, placed 2-4 cm above scalp), scalp MEG promises significantly higher spatial resolution imaging but it also comes with numerous challenges regarding how to optimally design OPM arrays. In this context, we sought to provide a systematic description of MEG spatial resolution as a function of the number of sensors (allowing comparison of low- vs. high-density MEG), sensor-to-brain distance (cryogenic SQUIDs vs. scalp OPM), sensor type (magnetometers vs. gradiometers; single- vs. multi-component sensors), and signal-to-noise ratio. To that aim, we present an analytical theory based on MEG multipolar expansions that enables, once supplemented with experimental input and simulations, quantitative assessment of the limits of MEG spatial resolution in terms of two qualitatively distinct regimes. In the regime of asymptotically high-density MEG, we provide a mathematically rigorous description of how magnetic field smoothness constraints spatial resolution to a slow, logarithmic divergence. In the opposite regime of low-density MEG, it is sensor density that constraints spatial resolution to a faster increase following a square-root law. The transition between these two regimes controls how MEG spatial resolution saturates as sensors approach sources of neural activity. This two-regime model of MEG spatial resolution integrates known observations (e.g., the difficulty of improving spatial resolution by increasing sensor density, the gain brought by moving sensors on scalp, or the usefulness of multi-component sensors) and gathers them under a unifying theoretical framework that highlights the underlying physics and reveals properties inaccessible to simulations. We propose that this framework may find useful applications to benchmark the design of future OPM-based scalp MEG systems.