Analysis of intersubject variability in activation: an application to the incidental episodic retrieval during recognition test.

Since the brain may engage different neuronal systems for a single behavioral goal, activation may show intersubject variability expressed in the systematic recruitment of multiple distinct networks. We apply a principal component analysis (PCA) to activation over task conditions and subjects to reveal cortical networks that may underlie this intersubject variability. Normal subjects were presented with novel meaningless objects, which appeared in personally familiar or unfamiliar places. During a subsequent, event-related functional MRI (fMRI) experiment, each subject was presented with learned or novel objects in isolation and performed a learned/novel judgment. Recollection of places was not essential for the task, and may exhibit large intersubject variations. The right posterodorsal posterior cingulate cortex (pPCC) and left retrosplenial cortex, whose involvement in place-recognition has been previously established, were selected as regions of interest for the PCA. Neural responses to objects associated with familiar relative to unfamiliar places in pPCC, but not in the retrosplenial cortex, were negatively correlated with task-related activation (common over all objects) in the right anterolateral prefrontal cortex and the left intraparietal sulcus. The latter areas have been implicated previously in cognitive control and object recognition, respectively. These results suggest right prefrontal control over neural processes both in the left parietal cortex, related to object-recognition (enhancement), and pPCC, related to nonessential recollection of place-memory (suppression), but not in the retrosplenial cortex, related to the sense of familiarity. This analysis revealed an important aspect of functional anatomy that was not detectable using a conventional analysis of average activations.