Topographic Variation in Human Neurotransmitter Receptor Densities Explains Differences in Intracranial EEG Spectra.

Brain function and its failures arise from dynamical patterns of neuronal activity shaped by synaptic neurotransmission. Both neurotransmitter receptor expression and neuronal population dynamics show a remarkable regional variability across the human cortex. We leverage this functional specialisation to characterise the relationship between receptor architectonics and electrophysiological signals. Using dynamic causal modelling (DCM), we fitted neural mass models to a normative set of intracranial EEG data. Subsequently, Bayesian model comparison helped to evaluate whether models improved when equipped with constraints on synaptic connectivity, based on regional neurotransmitter receptor densities. The results show that dynamic causal models generated region-specific intracranial EEG spectra accurately. Incorporating prior information on normative receptor distributions further improved model evidence, indicating that regional variation in receptor density explains variations in synaptic connectivity and ensuing cortical population dynamics. The output is a cortical atlas of neurobiologically informed intracortical synaptic connectivity parameters. These can serve as empirical priors in future, patient-specific models. In summary, we show that molecular cortical characteristics-that is, receptor densities-enrich and inform generative, biophysically plausible models of coupled neuronal populations. This work helps to explain regional variations in human electrophysiology, provides a methodological foundation to integrate multimodal data, and serves as a normative resource for future DCM studies of electrophysiology.