Energetics of Cerebral Cortex: Metabolic Modeling and In Vivo NMR

The energy metabolism of cerebral cortex adapts to the increase in metabolic demand which occurs during enhanced cortical activity (e.g. sensory stimulation). This contributes to the generation of the imaging and spectroscopic signals that are utilized to monitor and appraise the function of the brain in situ. Importantly, the simple paradigm of “neuronal activity” is insufficient to interpret experimental outcomes, as what is observed depends on the balance between (i) activity patterns, whether excitatory or inhibitory; (ii) information processing mechanisms, specifically input/output or synaptic/spiking activity; (iii) stimulation of cell-specific (primarily neuronal and astrocytic) functional and metabolic pathways. Understanding the basis of the metabolic response of the cortical tissue to stimulation (i.e. neurometabolic coupling) is an important goal for neurosciences. In the present work, I studied the coupling between activity and energy metabolism of the human cerebral cortex by combining theoretical and experimental approaches. First, I adapted and used the information about the energy consumed by cortical signaling processes in order to develop a kinetic model of carbohydrate metabolism (Chapters 1 and 2). By encompassing the current knowledge about the regulation of energy supply and demand in cortical tissue, the model predicted that the metabolic response of the cerebral cortex might be strongly dependent on the balance between spiking and synaptic activity. Then, I designed an experiment for the measurement of vascular and metabolic response of the primary visual cortex to specific visual stimulations (Chapter 3). In particular, by acting on the temporal frequency of achromatic luminance and isoluminant chromatic flickering visual stimulations, I aimed at altering the balance between local input processing (synaptic activity) and output firing (spiking activity) through changes in intracortical inhibition. The modeling and experimental results support the hypothesis (discussed in Chapter 4) that spiking activity, which is identified by axonal action potentials propagation, hinges on fast metabolic pathways that do not depend on oxygen (i.e. anaerobic). This suggests that the up-regulation of anaerobic metabolism during enhanced cortical activity is primarily due to the long-range communication between different areas of the cerebral cortex, more than to local processing within an individual cortical area. Identifying the potential significance of this mechanism is the subject of my future research