Concurrent neurochemical and neurophysiological investigation of fMRI signals

Abstract

Functional magnetic resonance imaging (fMRI) is a frequently-used non-invasive technique to investigate the operational organization of the brain. In particular, blood-oxygen-level-dependent (BOLD) fMRI has become a mainstay of basic and clinical neuroscience. However, the colorful images that fMRI produces often mask the immense complexity of the underlying neurobiological processes generating them. While previous studies conducted in non-human primates suggest a notable correlation between BOLD and neocortical local field potentials (LFP). LFP itself is the result of neural microcircuits, the so-called excitation-inhibition networks (EIN), that integrate signals from glutamatergic and GABAergic neurons in a complex dynamical manner. Thus, to understand the neural basis of BOLD signals, it is inevitable to characterize its causal relationship with dynamical states of EIN. Methods for simultaneous electrophysiological, neurochemical and imaging experiments are therefore essential to unveil the mystery of the neuronal origin of fMRI and may lead to answers unlikely to be obtained by using either technique alone. In particular, it would allow us to decompose the BOLD response into its excitatory and inhibitory components, which is of outmost importance for identifying brain states in animals and humans. In this thesis, the development of a novel MRI-based microelectrode-based technology is introduced that allows simultaneous recording of glutamate, GABA, neural activity and BOLD in consistent time-scales in several brain regions. Measurements were conducted in two brain pathways, namely the somatosensory and visual systems. The results suggest that BOLD signal is related to a complex and often opposite interplay of glutamatergic and GABAergic neuronal populations. The overall findings not only improve our understanding of the neurobiological processes that underly functional imaging of the brain, but will ultimately support efforts for development of new therapeutic strategies for neuropsychiatric diseases.