Rapid self-paced event-related functional MRI: feasibility and implications of stimulus- versus response-locked timing.

Many cognitive paradigms require self-paced responses or examine events that occur at unpredictable times. To explore whether functional MRI (fMRI) can accommodate such paradigms, a method allowing rapid, unpredictable trial pacing was developed and tested on 17 subjects using activation of the motor network as a model. Trial onset was determined solely by the subjects' self-paced responses and trials occurred, on average, less than 2 s apart. The hemodynamic response was estimated both in relation to stimulus onset (stimulus-locked) and in relation to behavioral response time (response-locked). Results yielded robust activation maps and hemodynamic response estimates. Specifically, significant activation in motor cortex, supplementary motor area (SMA), and cerebellum was observed both at the group and at the individual-subject level, confirming predicted patterns of brain activity. Moreover, the self-paced design resulted in even temporal sampling of the hemodynamic response across the image acquisition, allowing estimation of response parameters. Stimulus-locked analysis demonstrated strong correlation between hemodynamic- and behavioral-response timing both within and across subjects. Conversely, response-locked analysis showed minimal correlation with behavioral timing, suggesting effective resynchronization of the timing parameters. These results demonstrate fMRI procedures that can accommodate rapid, arbitrarily timed events and, in doing so, provide precise temporal estimates of the hemodynamic response.