title: 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.
authors.affiliation: MRC Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, United Kingdom, and Department of Clinical Neurosciences and c.rae@bsms.ac.uk.
authors.forename: Charlotte L
authors.identifier: http://orcid.org/0000-0002-4503-4971
authors.initials: CL
authors.lastname: Rae
authors.affiliation: MRC Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, United Kingdom, and Department of Clinical Neurosciences and.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Hughes
authors.affiliation: MRC Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, United Kingdom, and Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, United Kingdom.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Anderson
authors.affiliation: MRC Cognition and Brain Sciences Unit, Cambridge, CB2 7EF, United Kingdom, and Department of Clinical Neurosciences and Behavioral and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, United Kingdom.
authors.forename: James B
authors.identifier: http://orcid.org/0000-0001-7216-8679
authors.initials: JB
authors.lastname: Rowe
mesh_terms: D000328:Adult; D063132:Connectome; D004525:Efferent Pathways / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D009044:Motor Cortex / Q000502:physiology*; D009433:Neural Inhibition; D017397:Prefrontal Cortex / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000502:physiology*
keywords: diffusion MRI tractography; dynamic causal modelling; inferior frontal gyrus; presupplementary motor area; response inhibition; stop-signal task