The Role of the Human Brain Neuron-Glia-Synaptic Composition in Forming Resting State Functional Connectivity Networks

ABSTRACT While significant progress has been achieved in studying resting state functional networks in a healthy human brain and in a wide range of clinical conditions, many questions related to their relationship to the brain’s cellular constituents remain open. In this paper we use quantitative Gradient Recalled Echo (qGRE) MRI for in vivo quantitative mapping of human brain cellular composition, and BOLD (blood oxygen level dependent) MRI resting state data from the Human Connectome Project to explore how the brain cellular constituents relate to resting state functional networks. Our results show that the BOLD-signal-defined synchrony of connections between cellular circuits in network-defined individual functional units is mainly associated with the regional neuronal density, while the strength of the functional connectivity between functional units is influenced not only by the neuronal but also glia and synaptic components of brain tissue cellular constituents. Data show that these cellular-functional relationships are most evident in the infra-slow frequency range (0.01–0.16 Hz) of brain activity, which is known to be linked with fluctuations of the BOLD signal. These mechanisms lead to a rather broad distribution of resting state functional network properties. We found that visual networks with the highest neuronal density (but lowest density of glial cells and synapses) exhibit the strongest coherence of BOLD signal in individual functional units, as well as the strongest intra-network connectivity. The Default Mode Network (DMN) is positioned near the opposite part of the spectrum with relatively low coherence of the BOLD signal but a remarkably balanced cellular content enabling DMN prominent role in the overall organization of the brain and the hierarchy of functional networks in health and disease.