Hierarchical Organization of Bilateral Prefrontal-Basal Ganglia Circuits for Response Inhibition Control

Abstract

Response inhibition control is primarily supported by the right inferior frontal gyrus (IFG) and the prefrontal-basal ganglia network, though the mechanisms behind right lateralization and regional interplay remain unclear. In this fMRI study, we explore the neural substrates supporting efficient inhibition control and examine whether the typical right lateralization of IFG activation can be modulated by stimulus properties (semantic features) and inhibitory demand (reaction times, RT). We chose a Go/No-Go lexical decision task, utilizing concrete and abstract words as Go stimuli and pseudo-word as No-Go stimuli. Behavioral results reveal that inhibition is more effective during concrete word sessions compared to abstract word sessions, suggesting a modulation of cognitive inhibition by semantic features. Neuroimaging results further demonstrate that successful inhibition activates bilateral IFG, indicating a flexible right lateralization pattern of IFG activation that varies with stimulus properties. To examine how varying inhibitory demands modulate neural activation patterns, we reclassified concrete and abstract sessions into fast and slow sessions based on RT, followed by within-group comparisons. Our study highlights the crucial role of the bilateral subthalamic nucleus (STN) in efficient inhibition, with increased activation associated with rapid response inhibition. Furthermore, we report enhanced neural coupling between the right IFG and multiple functionally connected regions, including bilateral insula, putamen, and pallidum, as well as between the right middle frontal gyrus and other prefrontal regions during rapid inhibitory responses, whereas no engagement of the left IFG was observed in efficient inhibition. These findings imply a hierarchical functional organization of the bilateral fronto-basal ganglia circuits, in which the right prefrontal regions play a dominant role in inhibition control, supported by basal ganglia regions, while the left IFG may serve a supplementary function. Stimulus properties can modulate right lateralization, underscoring the dynamic and flexible nature of the prefrontal-basal ganglia network in inhibition control.