The micro-architecture of the cerebral cortex: functional neuroimaging models and metabolism.

In order to interpret/integrate data obtained with different functional neuroimaging modalities (e.g. fMRI, EEG/MEG, PET/SPECT, fNIRS), forward-generative models of a diversity of brain mechanisms at the mesoscopic level are considered necessary. For the cerebral cortex, the brain structure with possibly the most relevance for functional neuroimaging, a variety of such biophysical models has been proposed over the last decade. The development of technological tools to investigate in vitro the physiological, anatomical and biochemical principles at the microscopic scale in comparative studies formed the basis for such theoretical progresses. However, with the most recent introduction of systems to record electrical (e.g. miniaturized probes chronically/acutely implantable in the brain), optical (e.g. two-photon laser scanning microscopy) and atomic nuclear spectral (e.g. nuclear magnetic resonance spectroscopy) signals using living laboratory animals, the field is receiving even greater attention. Major advances have been achieved by combining such sophisticated recording systems with new experimental strategies (e.g. transgenic/knock-out animals, high resolution stereotaxic manipulation systems for probe-guidance and cellular-scale chemical-delivery). Theoreticians may now be encouraged to re-consider previously formulated mesoscopic level models in order to incorporate important findings recently made at the microscopic scale. In this series of reviews, we summarize the background at the microscopic scale, which we suggest will constitute the foundations for upcoming representations at the mesoscopic level. In this first part, we focus our attention on the nerve ending particles in order to summarize basic principles and mechanisms underlying cellular metabolism in the cerebral cortex. It will be followed by two parts highlighting major features in its organization/working-principles to regulate both cerebral blood circulation and neuronal activity, respectively. Contemporary theoretical models for functional neuroimaging will be revised in the fourth part, with particular emphasis in their applications, advantages/limitations and future prospects.