Causal Contributions of Left Inferior and Medial Frontal Cortex to Semantic and Executive Control

Abstract

Semantic control guides the targeted and context-based retrieval from semantic memory. The overlap with and dissociation from domain-general executive control in the frontal lobe remains contentious. Here, we used transcranial magnetic stimulation (TMS) to probe the functional relevance of the left inferior frontal gyrus (IFG) and pre-supplementary motor area (pre-SMA) for semantic and executive control. Across four sessions, 24 participants received 1 Hz repetitive TMS to each region individually, dual-site TMS targeting both regions sequentially (IFG followed by pre-SMA), and sham TMS. Participants then completed semantic fluency, figural fluency, and picture-naming tasks. Stimulation of either region broadly disrupted both semantic and figural fluency, suggesting shared functionality. However, electric field modeling of the induced stimulation strength revealed distinct specializations: The left IFG was primarily associated with semantic control, as evidenced by verbal fluency deficits, while the pre-SMA played a domain-general role in executive functions, affecting non-verbal fluency and cognitive flexibility (e.g., clustering and switching during semantic fluency). Notably, only dual-site TMS impaired accuracy in figural fluency, providing unique evidence for successful compensation of executive functions through either the left IFG or pre-SMA following single-site perturbation. These findings underscore the multidimensionality of cognitive control and suggest a flexible task-dependent contribution of the IFG to control processes, either as semantic-specific or general executive resource. Furthermore, they highlight the tightly interconnected network of executive control subserved by the left IFG and pre-SMA, advancing our understanding of the neural basis of semantic and executive functions.