| For much of the past 150 years the main paradigm in brain research has been one of localisation -- the mapping of processes to particular regions. More recently, a shift towards a more network-based approach has taken place. One of the factors supporting this shift has been an appreciation of the importance of ongoing, stimulus-independent, activity to mental processes. Such ongoing activity has been productively studied at the functional and anatomical network level, as well as within isolated regions. However, to date, less has been established regarding the biochemical underpinnings of such activity and the links between the different levels of investigation (structural, functional, process). In order to investigate these points, multiple magnetic resonance imaging (MRI) techniques were combined with GABAA receptor positron emission tomography and electroencephalography in a set of studies in healthy humans. Using magnetic resonance spectroscopy, diffusion tensor imaging, and functional MRI, it was shown firstly that medial prefrontal cortex (mPFC) glutamate levels correlate with structural and functional connectivity to multiple cortical and subcortical regions during both rest and task. It was further shown that glutamate in this region is correlated with the signal dynamics of the ongoing activity. Secondly, it was shown that cortical GABAA receptor distribution follows similar topologies to structural and functional connectivity, fitting the description of "small-worldness". It was further shown that the distribution can be decomposed into distinct networks that correspond to known functional and structural ones. Thirdly, using fMRI and DTI, it was shown that the structural network profile of the insula predicts its activity during a specific task and that the different structural networks identified corresponded well with previously established ones. Finally, it was shown that ongoing activity dynamics in adulthood are related to early-life stress, and that the dynamical differences seen across individuals were related to mPFC glutamate levels. It was further shown that these early-life stress related changes are correlated with altered neural responses to aversive stimuli. Taken together, the results presented provide initial biochemical links between structural and functional networks and that these can be related to individual differences in psychological processes. |
