Familiarity enhances functional connectivity between visual and nonvisual regions of the brain during natural viewing.

We explored the neural correlates of familiarity with people and places using a naturalistic viewing paradigm. Neural responses were measured using functional magnetic resonance imaging, while participants viewed a movie taken from Game of Thrones. We compared inter-subject correlations and functional connectivity in participants who were either familiar or unfamiliar with the TV series. Higher inter-subject correlations were found between familiar participants in regions, beyond the visual brain, that are typically associated with the processing of semantic, episodic, and affective information. However, familiarity also increased functional connectivity between face and scene regions in the visual brain and the nonvisual regions of the familiarity network. To determine whether these regions play an important role in face recognition, we measured responses in participants with developmental prosopagnosia (DP). Consistent with a deficit in face recognition, the effect of familiarity was significantly attenuated across the familiarity network in DP. The effect of familiarity on functional connectivity between face regions and the familiarity network was also attenuated in DP. These results show that the neural response to familiarity involves an extended network of brain regions and that functional connectivity between visual and nonvisual regions of the brain plays an important role in the recognition of people and places during natural viewing.