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

Area of Science:

• Neuroscience
• Computational Neuroscience
• Systems Neuroscience

Background:

• Brain function relies on neuronal activity patterns influenced by synaptic neurotransmission.
• Significant regional variability exists in neurotransmitter receptor expression and neuronal population dynamics across the human cortex.

Purpose of the Study:

• To characterize the relationship between regional neurotransmitter receptor architectonics and electrophysiological signals in the human cortex.
• To investigate if regional receptor density variations explain differences in synaptic connectivity and cortical population dynamics.

Main Methods:

• Utilized dynamic causal modelling (DCM) to fit neural mass models to intracranial electroencephalography (EEG) data.
• Employed Bayesian model comparison to assess the impact of incorporating regional neurotransmitter receptor density data as constraints on synaptic connectivity.
• Generated a cortical atlas of neurobiologically informed intracortical synaptic connectivity parameters.

Main Results:

• Dynamic causal models accurately predicted region-specific intracranial EEG spectra.
• Incorporating normative receptor distributions as prior information significantly improved model evidence.
• Demonstrated that regional receptor density variations are key determinants of synaptic connectivity and population dynamics.

Conclusions:

• Molecular characteristics, specifically receptor densities, enhance and inform generative, biophysically plausible models of neuronal populations.
• This research explains regional variations in human electrophysiology and provides a foundation for integrating multimodal data.
• The developed cortical atlas serves as a normative resource for future patient-specific dynamic causal modelling studies.