Neural and BOLD responses across the brain

Functional Magnetic Resonance Imaging (fMRI) has quickly grown into one of the most important tools for studying brain function, especially in humans. Despite its prevalence, we still do not have a clear picture of what exactly the blood oxygenation level dependent (BOLD) signal represents or how it compares to the signals obtained with other methods (e.g., electrophysiology). We particularly refer to single neuron recordings and electroencephalography when we mention 'electrophysiological methods', given that these methods have been used for more than 50 years, and have formed the basis of much of our current understanding of brain function. Brain function involves the coordinated activity of many different areas and many different cell types that can participate in an enormous variety of processes (neural firing, inhibitory and excitatory synaptic activity, neuromodulation, oscillatory activity, etc.). Of these cells and processes, only a subset is sampled with electrophysiological techniques, and their contribution to the recorded signals is not exactly known. Functional imaging signals are driven by the metabolic needs of the active cells, and are most likely also biased toward certain cell types and certain neural processes, although we know even less about which processes actually drive the hemodynamic response. This article discusses the current status on the interpretation of the BOLD signal and how it relates to neural activity measured with electrophysiological techniques.