Node centrality in MEG resting-state networks covaries with neurotransmitter receptor and transporter density

Abstract

Neuronal oscillations are central mechanisms in the regulation of neuronal processing and communication (Deco et al., 2011; Fries, 2015; S. Palva & Palva, 2012; Siegel et al., 2012; Singer, 1999), but the relationship between the emergent inter-areal synchronization of oscillations and their underlying synaptic and neuromodulatory mechanisms - the dynome - has remained poorly understood (Kopell et al., 2014). While oscillations are largely generated by fast synaptic neurotransmission among pyramidal cells and interneurons (Traub et al., 2004), these microcircuits are subject to slower neuromodulation in a frequency- and region-specific manner (Batista-Brito et al., 2018; Roopun et al., 2010). While the efferent connections, receptor densities, and neurotransmitter reuptake regulation of neuromodulatory systems are highly heterogeneous across the cortical mantle (Avery & Krichmar, 2017; Deco et al., 2017; Hansen et al., 2022), it has remained unresolved how this variability shapes inter-areal connectivity of neuronal oscillations. Here, we used source-reconstructed human magnetoencephalography (MEG) data to assess how the centrality of brain areas (nodes) in large-scale networks of phase synchrony and amplitude correlations covaries with neurotransmitter receptor and transporter densities. Node centrality strongly covaried with receptor and transporter densities in a coupling- and frequency-specific manner both at the level of individual receptors and transporters and that of principal components. In delta, theta, and gamma frequencies, node centrality in phase-synchronization networks covaried positively, and in high-alpha and beta bands negatively, with dopaminergic, GABA, NMDA, muscarinic, and most serotonergic receptor densities. In amplitude-correlation networks, node centrality in delta and gamma bands covaried positively, and in theta to beta bands negatively, with most receptor and transporter densities. These results establish the contribution of neurotransmitter receptor and transporter densities for shaping connectivity of neuronal oscillations in the human brain and demonstrate a link between coupling of neuronal oscillations with the underlying biological details.