A principal component network analysis of prefrontal-limbic functional magnetic resonance imaging time series in schizophrenia patients and healthy controls.

We investigated neural regulation of emotional arousal. We hypothesized that the interactions between the components of the prefrontal-limbic system determine the global trajectories of the individual's brain activation, with the strengths and modulations of these interactions being potentially key components underlying the differences between healthy individuals and those with schizophrenia. Using affect-valent facial stimuli presented to 11 medicated schizophrenia patients and 65 healthy controls, we activated neural regions associated with the emotional arousal response during functional magnetic resonance imaging (fMRI). Performing first a random effects analysis of the fMRI data to identify activated regions, we obtained 352 data-point time series for six brain regions: bilateral amygdala, hippocampus and two prefrontal regions (Brodmann Areas 9 and 45). Since standard statistical methods are not designed to capture system features and evolution, we used principal component analyses on two types of pre-processed data: contrasts and group averages. We captured an important characteristic of the evolution of our six-dimensional brain network: all subject trajectories are almost embedded in a two-dimensional plane. Moreover, the direction of the largest principal component was a significant differentiator between the control and patient populations: the left and right amygdala coefficients were substantially higher in the case of patients, and the coefficients of Brodmann Area 9 were, to a lesser extent, higher in controls. These results are evidence that modulations between the regions of interest are the important determinant factors for the system's dynamical behavior. We place our results within the context of other principal component analyses used in neuroimaging, as well as of our existing theoretical model of prefrontal-limbic dysregulation.