The neural substrates of the warning effect: A functional magnetic resonance imaging study

•The warning effect is mediated by the parieto-frontal attentional network.•It modulates the motor system, including the pre-SMA and the M1.•Thus the warning effect is an interaction of attentional and motor systems. To test the hypothesis the warning effect is mediated by the top-down attentional modulation of the motor system, we conducted functional MRI using a Go/No-Go task with visual and auditory warning stimuli. For aurally-warned, visually-prompted trials, the auditory warning stimulus was presented for 1500ms, during which visual cues were presented that prompted either Go or No-Go responses. The same format was used for visually-warned, aurally-prompted trials. Both auditory and visual warning cues shortened the reaction time for the Go trials. The warning cues activated the right-lateralized parieto-frontal top-down attentional network, and motor cortical areas including the pre-supplementary motor area (pre-SMA), the bilateral dorsal premotor cortex, and the left primary motor cortex (M1). The warning-related activation of the pre-SMA matched the difference between its activation by Go-with-warning and by Go-without-warning. Thus, the pre-SMA was primed by the warning cue. The same pre-SMA priming effect was observed for the No-Go cue-related activation, consistent with its role in movement preparation and selection. Similar but less prominent Go cue-related priming was observed in the M1. Thus, the warning effect represents the pre-potentiation of the motor control pathway by the top-down attentional system, from the selection and preparation of the movement to its execution.