Decoupling of neurophysiological activity from structure mirrors global microarchitectural and neuromodulatory trends

The brain’s functional activity is shaped by the complex architecture of its fibers. Yet, the lack of a direct one-to-one mapping between functional and structural connections makes this relationship elusive. To date, most studies on structure–function coupling (SFC) have conceptualized function in terms of resting-state functional Magnetic Resonance Imaging (fMRI) connectivity. Here, we extend this framework to neurophysiological data by examining how magnetoencephalography (MEG) activity relates to the structural connectome, leveraging its rich spectral content and direct sensitivity to neuronal population dynamics. We show that the decoupling of MEG activity from structure is strongly associated with the expression levels of synaptic plasticity markers, pointing to a link between flexible functional reconfiguration and the molecular mechanisms of plasticity. Moreover, regions with greater decoupling exhibit higher neurotransmitter receptor diversity, underscoring neuromodulatory heterogeneity as a substrate for functional flexibility. This association is especially pronounced for slow-acting metabotropic receptors, whose diffuse and prolonged signaling may facilitate functional reorganization atop the structural connectome. Analysis of neurophysiological (MEG) structure–function coupling sheds light on its association with molecular plasticity markers and diversity of neuromodulatory receptors in the human brain.