Discovering networks altered by potential threat (“anxiety”) using quadratic discriminant analysis

Researchers have only recently begun using functional neuroimaging to explore the human response to periods of sustained anxious anticipation, namely potential threat. Here, we investigated brain responses acquired with functional MRI during an instructed threat of shock paradigm used to create sustained periods of aversive anticipation. In this re-analysis of previously published data, we employed quadratic discriminant analysis to classify the multivariate pattern of whole-brain functional connectivity and to identify connectivity changes during periods of potential threat. Our method identifies clusters with altered connectivity on a voxelwise basis, thus eschewing the need to define regions a priori. Classifier generalization was evaluated by testing on data from participants not used during training. Robust classification between threat and safe contexts was possible, and inspection of “diagnostic features” revealed altered functional connectivity involving the intraparietal sulcus, task-negative regions, striatum, and anterior cingulate cortex. We anticipate that the proposed method will prove useful to experimenters wishing to identify large-scale functional networks that distinguish between experimental conditions or groups.