The Prefrontal Cortex Achieves Inhibitory Control by Facilitating Subcortical Motor Pathway Connectivity

Abstract

Communication between the prefrontal cortex and subcortical nuclei underpins the control and inhibition of behavior. However, the interactions in such pathways remain controversial. Using a stop-signal response inhibition task and functional imaging with analysis of effective connectivity, we show that the lateral prefrontal cortex influences the strength of communication between regions in the frontostriatal motor system. We compared 20 generative models that represented alternative interactions between the inferior frontal gyrus, presupplementary motor area (preSMA), subthalamic nucleus (STN), and primary motor cortex during response inhibition. Bayesian model selection revealed that during successful response inhibition, the inferior frontal gyrus modulates an excitatory influence of the preSMA on the STN, thereby amplifying the downstream polysynaptic inhibition from the STN to the motor cortex. Critically, the strength of the interaction between preSMA and STN, and the degree of modulation by the inferior frontal gyrus, predicted individual differences in participants' stopping performance (stop-signal reaction time). We then used diffusion-weighted imaging with tractography to assess white matter structure in the pathways connecting these three regions. The mean diffusivity in tracts between preSMA and the STN, and between the inferior frontal gyrus and STN, also predicted individual differences in stopping efficiency. Finally, we found that white matter structure in the tract between preSMA and STN correlated with effective connectivity of the same pathway, providing important cross-modal validation of the effective connectivity measures. Together, the results demonstrate the network dynamics and modulatory role of the prefrontal cortex that underpin individual differences in inhibitory control.

Complementary roles of cortical oscillations in automatic and controlled processing during rapid serial tasks

“…In fact, a recent study demonstrated that the prefrontal cortex may achieve inhibitory control by influencing frontostriatal circuits (Rae et al, 2015), which are known to participate in action selection (Seo et al, 2012). We suggest theta oscillations may be a mechanism through which this is achieved.…”

Memory-reliant Post-error Slowing Is Associated with Successful Learning and Fronto-occipital Activity

“…A recent effective connectivity study showed that rIFG modulates the excitatory influence between the pre-SMA and subthalamic nucleus (Rae, Hughes, Anderson, & Rowe, 2015). Consistent with the idea that response inhibition requires online maintenance of relevant information, rIFG has also been implicated in storing behaviorally relevant information in memory (Spitzer, Goltz, Wacker, Auksztulewicz, & Blankenburg, 2014;Marklund & Persson, 2012;Clark et al, 2007).…”

Response inhibition rapidly increases single-neuron responses in the subthalamic nucleus of patients with Parkinson's disease

“…These inter-species differences might reflect distinct electrophysiological recording context (e.g., the spatial sampling of STN during extracellular recordings is generally weak in humans), inter-species differences regarding STN connectivity with the prefrontal cortex (Astafiev et al, 2003) or a different implementation of inhibitory control signals in the human prefrontal cortex that would impact basal ganglia activities (Wessel & Aron, 2015). On a related note, thalamic and pedunculopontine nucleus projections to the STN could be the substrate for the very quick STN response observed in rat (Schmidt et al, 2013), while STN activity in humans could be driven by a slower prefrontalsubthalamic pathway (originating in the pre-SMA or in the inferior frontal gyrus, see Rae, Hughes, Anderson, Rowe, & Rowe, 2015).…”