Prefrontal-Subthalamic Hyperdirect Pathway Modulates Movement Inhibition in Humans

• Published in: Neuron (Cambridge, Mass.) Vol. 106; no. 4; pp. 579 - 588.e3
• Main Authors: Chen, Witney, de Hemptinne, Coralie, Miller, Andrew M., Leibbrand, Michael, Little, Simon J., Lim, Daniel A., Larson, Paul S., Starr, Philip A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 20.05.2020; Elsevier Limited
• Subjects: Aged; Electrocorticography; Electroencephalography; Experiments; Female; Frontal gyrus; Humans; hyperdirect pathway; Inhibition, Psychological; Latency; Male; Middle Aged; Movement - physiology; movement inhibition; Neural Pathways - physiology; Parkinson Disease - physiopathology; Parkinson's disease; prefrontal cortex; Prefrontal Cortex - physiology; Reaction time task; Subthalamic nucleus; Subthalamic Nucleus - physiology; Synchronization; Temporal cortex; Topography; hyperdirect pathway; electrocorticography; prefrontal cortex; Parkinson’s disease; movement inhibition
• ISSN: 0896-6273; 1097-4199; 1097-4199
• DOI: 10.1016/j.neuron.2020.02.012

The ability to dynamically change motor outputs, such as stopping an initiated response, is an important aspect of human behavior. A hyperdirect pathway between the inferior frontal gyrus and subthalamic nucleus is hypothesized to mediate movement inhibition, but there is limited evidence for this in humans. We recorded high spatial and temporal resolution field potentials from both the inferior frontal gyrus and subthalamic nucleus in 21 subjects. Cortical potentials evoked by subthalamic stimulation revealed short latency events indicative of monosynaptic connectivity between the inferior frontal gyrus and ventral subthalamic nucleus. During a stop signal task, stopping-related potentials in the cortex preceded stopping-related activity in the subthalamic nucleus, and synchronization between these task-evoked potentials predicted the stop signal reaction time. Thus, we show that a prefrontal-subthalamic hyperdirect pathway is present in humans and mediates rapid stopping. These findings may inform therapies to treat disorders featuring perturbed movement inhibition. •Demonstration of a monosynaptic, prefrontal hyperdirect pathway in humans•Fastest fibers between the inferior frontal gyrus and ventral subthalamic nucleus•Stopping elicits co-activation of the origin and target of this pathway•Degree of co-activation predicts stopping speed Chen et al. identify a fast, non-stop pathway between the prefrontal cortex and subthalamic nucleus in humans using multisite invasive brain recordings. This pathway is critically involved in the stopping of ongoing actions. Modulation of this pathway may be a means of treating disorders of inhibitory control, such as impulsivity.