Massive Modulation of Brain Areas After Mechanical Pain Stimulation: A Time-Resolved fMRI Study

To date, relatively little is known about the spatiotemporal aspects of whole-brain blood oxygenation level-dependent (BOLD) responses to brief nociceptive stimuli. It is known that the majority of brain areas show a stimulus-locked response, whereas only some are characterized by a canonical hemodynamic response function. Here, we investigated the time course of brain activations in response to mechanical pain stimulation applied to participants' hands while they were undergoing functional magnetic resonance imaging (fMRI) scanning. To avoid any assumption about the shape of BOLD response, we used an unsupervised data-driven method to group voxels sharing a time course similar to the BOLD response to the stimulus and found that whole-brain BOLD responses to painful mechanical stimuli elicit massive activation of stimulus-locked brain areas. This pattern of activations can be segregated into 5 clusters, each with a typical temporal profile. In conclusion, we show that an extensive activity of multiple networks is engaged at different time latencies after presentation of a noxious stimulus. These findings aim to motivate research on a controversial topic, such as the temporal profile of BOLD responses, the variability of these response profiles, and the interaction between the stimulus-related BOLD response and ongoing fluctuations in large-scale brain networks.