The subthalamic nucleus and inhibitory control: impact of subthalamotomy in Parkinson’s disease

Abstract

The subthalamic nucleus (STN) is hypothesized to play a central role in the rapid stopping of movement in reaction to a stop signal. Single-unit recording evidence for such a role is sparse, however, and it remains uncertain how that role relates to the disparate functions described for anatomic subdivisions of the STN. Here we address that gap in knowledge using non-human primates and a task that distinguishes reactive and proactive action inhibition, switching and skeletomotor functions. We found that specific subsets of STN neurons have activity consistent with causal roles in reactive action stopping or switching. Importantly, these neurons were strictly segregated to a ventromedial region of STN. Neurons in other subdivisions encoded task dimensions such as movement per se and proactive control. We propose that the involvement of STN in reactive control is restricted to its ventromedial portion, further implicating this STN subdivision in impulse control disorders.

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

“…PD is characterized by over-synchrony between basal ganglia and cortex (Brown, 2003; George et al, 2013; Swann et al, 2015); and it is thought that this ‘locking’ prevents cortico-basal-ganglia circuits from operating properly. Indeed, multiple studies show PD patients off treatment are impaired at stopping (George et al, 2013; Obeso et al, 2014; Obeso et al, 2011; Swann et al, 2011). We hypothesize that the mental inflexibility in PD is at least partly explained by a system that is not properly interruptible by new information (because the STN-mediated interrupt is ineffective due to oversynchrony).…”

“…Nonetheless, there is converging evidence for the role of the STN from several other methods. Clinically-induced lesions to the STN in patients (subthalomotomies) affected stopping (Obeso et al, 2014) and several studies have shown the impact of STN deep brain stimulation (DBS) on stopping. Three of these studies found a speeding of stopping (i.e., SSRT) when stimulation was bilateral (Mirabella et al, 2011; Swann et al, 2011; van den Wildenberg et al, 2006) while one did not (Obeso et al, 2013).…”

Association of Protein Phosphatase PPM1G With Alcohol Use Disorder and Brain Activity During Behavioral Control in a Genome-Wide Methylation Analysis

“…Several studies have suggested that the right subthalamic nucleus and right inferior frontal gyrus are correlated with response inhibition, suggesting that they form a frontal-subcortical pathway of control inhibition (40, 45, 46). The right-lateralized subthalamic nucleus and inferior frontal gyrus have been used as regions of interest for response inhibition tasks (i.e., the stop signal task and go/no-go task) in studies reporting compromised impulse control in alcohol-dependent individuals (37, 38) and reduced ability to cancel prepotent responses (47), as well as in lesion studies (48), deep brain stimulation studies (49), and fMRI studies (50) of response inhibition in individuals with Parkinson's disease. Studies of in vivo deep brain stimulation of the sub-thalamic nucleus in Parkinson's patients (51) and in animal models (52) have shown a decrease in craving and regulation of substance preference, indicating the involvement of this brain region in neural processes that underlie addictive behavior.…”

Neuropsychological Effects of Deep Brain Stimulation in Subjects with Early Stage Parkinson's Disease in a Randomized Clinical Trial

“…Verbal fluency may be particularly vulnerable to dis-393 ruption, as deficits are often seen in PD and become 394 increasingly common in later stages of the illness [16]. trol, reward learning, and risk decision-making [18].…”