Connectivity by the Frontal Aslant Tract (FAT) Explains Local Functional Specialization of the Superior and Inferior Frontal Gyri in Humans When Choosing Predictive over Reactive Strategies: A Tractography-Guided TMS Study.

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 six 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 toward reactive behavior if applied to a specific portion of the IFG and increased predictive behavior when applied to a specific SFG spot. The two active spots in the SFG and IFG were directly connected by a sub-bundle of FAT fibers as indicated by diffusion-weighted imaging (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 anatomic connectivity is a powerful factor to explain and predict the spatial distribution of brain stimulation effects.