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

Abstract

ElectrophysiologyStop-signal task a b s t r a c tThe subthalamic nucleus (STN) plays a critical role during action inhibition, perhaps by acting like a fast brake on the motor system when inappropriate responses have to be rapidly suppressed. However, the mechanisms involving the STN during motor inhibition are still unclear, particularly because of a relative lack of single-cell responses reported in this structure in humans. In this study, we used extracellular microelectrode recordings during deep brain stimulation surgery in patients with Parkinson's disease (PD) to study STN neurophysiological correlates of inhibitory control during a stop signal task. We found two neuronal subpopulations responding either during motor execution (GO units) or during motor inhibition (STOP units). GO units fired selectively before patients' motor responses whereas STOP units fired selectively when patients successfully withheld their move at a latency preceding the duration of the inhibition process. These results provide electrophysiological evidence for the hypothesized role of the STN in current models of response inhibition.© 2016 Published by Elsevier Ltd. IntroductionNeuroimaging studies have shown that response-stopping processes activate a frontal-subcortical network (Aron, 2006;Chikazoe et al., 2009;Li, Yan, Sinha, & Lee, 2008). The dynamics of this network has been conceptualized in several computational models of response inhibition (Frank, 2006;Ratcliff & Frank, 2012;Wiecki & Frank, 2013) Available online at www.sciencedirect.com ScienceDirectJournal homepage: www.elsevier.com/locate/cortex c o r t e x 8 4 ( 2 0 1 6 ) 1 1 1 e1 2 3http://dx

Movement context modulates neuronal activity in motor and limbic-associative domains of the human subthalamic nucleus

“…Surprisingly, we found that the STN evoked responses to the frequent tone in the Go-NoGo task are lower than the evoked responses in the All-Go task. Previous studies that examined inhibitory paradigms detected a stronger evoked response to an inhibitory signal and thus suggested a mechanism of an increased activation of the STN to the inhibitory signal (Aron and Poldrack, 2006, Isoda et al, 2008, Benis et al, 2016, Wessel et al, 2016a. Our results suggest that the response to the inhibitory cue does not increase, but rather the response to the go cue decreases.…”

“…Many studies have examined STN-mediated motor inhibition using classical versions of stop signal tasks (Kuhn et al, 2004, Aron and Poldrack, 2006, Alegre et al, 2013, Schmidt et al, 2013, Benis et al, 2016. These studies compared no-go and go trials or successful and unsuccessful stop trials.…”

On the Globality of Motor Suppression: Unexpected Events and Their Influence on Behavior and Cognition

“…Further evidence, however, comes from STN local field potentials (LFPs) in Parkinson’s patients. Such studies generally show an increase in the power of oscillations in the beta band (13–30 Hz), before SSRT, that is greater for successful vs. failed stop trials (Bastin et al, 2014; Kuhn et al, 2004; Ray et al, 2009; Wessel et al, In press) (also see for single unit evidence Bastin et al, 2014; Benis et al, 2016)}. Note though, that while the STN beta-power increase is a well-established marker of stopping, it may not be specific to the STN itself (Leventhal et al, 2012).…”

Causal role for the subthalamic nucleus in interrupting behavior

“…For example, the STN is activated by signals to stop an initiated response as shown by human fMRI (Aron and Poldrack, 2006), local field potential recording (Ray et al, 2012; Wessel et al, 2016a), and single-unit recordings in humans (Bastin et al, 2014; Benis et al, 2016), non-human primates (Isoda and Hikosaka, 2008), and rodents (Schmidt et al, 2013). The STN is also activated by the need to delay responding during conflict (reviewed by Zavala et al, 2015) or in response to surprising events (Wessel et al, 2016b).…”