Multilayer MEG source modelling enables depth-resolved laminar inference in humans.

Neural dynamics at the laminar level are critical for cortical computation. However, in humans, non-invasive methods to probe such dynamics have been limited to coarse distinctions between deep and superficial layers. Here, we present a multilayer magnetoencephalography source reconstruction framework and evaluate the conditions under which depth-resolved laminar inference may be feasible. Using simulations, we systematically assess the limits of magnetoencephalography depth resolution, showing that laminar discrimination depends on sufficiently high signal-to-noise ratio, precise co-registration, and accurate specification of cortical column orientation. We demonstrate that regional variations in cortical anatomy influence reconstruction fidelity, with lead-field separability emerging as a key determinant. We then apply this framework to empirical data from three independent datasets and find laminar activation patterns that align with canonical feedforward and feedback motifs in visual and sensorimotor circuits, supporting the plausibility of laminar inference under favorable conditions and offering opportunities to bridge invasive electrophysiology and human neuroimaging.