Biophysical basis of brain activity: implications for neuroimaging

Area of Science:

• Neuroscience
• Biophysics
• Metabolic Imaging

Background:

• In vivo 13C magnetic resonance spectroscopy (MRS) enables quantitative assessment of brain metabolism.
• Previous in vitro and ex vivo studies suggested different metabolic pathway roles.

Purpose of the Study:

• To quantitatively assess the glutamate-glutamine cycle (Veye) and glucose oxidation (CMRGle(ox)) in vivo.
• To investigate the relationship between brain energy consumption and neurotransmission.
• To re-evaluate functional imaging data interpretation based on resting brain activity.

Main Methods:

• Utilized in vivo 13C-MRS to detect 13C label turnover from glucose.
• Employed functional magnetic resonance imaging (fMRI) with blood oxygen level-dependent (BOLD) contrast.
• Measured changes in cerebral metabolic rate of oxygen use (delta CMRO2%) and neuronal spiking rate (delta v%).

Main Results:

• Demonstrated glutamate recycling as a major metabolic pathway, linked to neurotransmission.
• Found a stoichiometric relationship between Veye and CMRGle(ox) in humans and rats.
• Showed that resting brain exhibits high energy consumption, supporting a significant baseline activity level.
• Corroborated fMRI-derived delta CMRO2% with 13C-MRS findings, showing a stoichiometric relationship with neuronal spiking rate.
• Revealed an inverse relationship between stimulus-induced activity increment and baseline activity.

Conclusions:

• Glutamate neurotransmission is a primary consumer of glucose oxidation energy.
• The resting brain possesses substantial activity, necessitating reinterpretation of functional imaging paradigms.
• Calibrated fMRI can provide high-resolution neuronal activity evaluation by measuring delta CMRO2%.
• Established biophysical relationships between energy consumption and neuronal activity offer new insights into brain function.