Predictive and reactive behaviors represent two mutually exclusive strategies in a sensorimotor task. Predictive behavior consists in internally estimating timing and features of a target stimulus and relies on a cortical medial frontal system (superior frontal gyrus - SFG). Reactive behavior consists in waiting for actual perception of the target stimulus and relies on the lateral frontal cortex (inferior frontal gyrus - IFG). We investigated whether SFG-IFG connections by the frontal aslant tract (FAT) can mediate predictive/reactive interactions. In 19 healthy human volunteers, we applied online transcranial magnetic stimulation (TMS) to 6 spots along the medial and lateral terminations of the FAT, during the set period of a delayed reaction task. Such scenario can be solved using either predictive or reactive strategies. TMS increased the propensity towards reactive behavior if applied to a specific portion of the SFG and increased predictive behavior when applied to a specific IFG spot. The two active spots in the SFG and IFG were directly connected by a sub-bundle of FAT fibers as indicated by DWI-tractography. Since FAT connectivity identifies two distant cortical nodes with opposite functions, we propose that the FAT mediates mutually inhibitory interactions between SFG and IFG to implement a "winner takes all" decisional process. We hypothesize such role of the FAT to be domain-general, whenever competition occurs between internal predictive and external reactive behaviors. Finally, we also show that anatomical connectivity is a powerful factor to explain and predict the spatial distribution of brain stimulation effects.Significance StatementWe interact with sensory cues adopting two main mutually-exclusive strategies: a) trying to anticipate the occurrence of the cue or b) waiting for the GO-signal to be manifest and react to it. Here we showed, by using non-invasive brain stimulation (TMS), that two specific cortical regions in the superior frontal gyrus (SFG) and the inferior frontal gyrus (IFG) have opposite roles in facilitating a predictive or a reactive strategy. Importantly these two very distant regions but with highly interconnected functions are specifically connected by a small white matter bundle, which mediates the direct competition and exclusiveness between predictive and reactive strategies. More generally, implementing anatomical connectivity in TMS studies strongly reduces spatial noise.
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