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Arkypallidal Cells Send a Stop Signal to Striatum.

ABSTRACT: The suppression of inappropriate actions is critical for flexible behavior. Cortical-basal ganglia networks provide key gating mechanisms for action suppression, yet the specific roles of neuronal subpopulations are poorly understood. Here, we examine Arkypallidal (‘‘Arky’’) and Prototypical (‘‘Proto’’) globus pallidus neurons during a Stop task, which requires abrupt cancellation of an imminent action. We first establish that Arky neurons can be identified by their firing properties across the natural sleep/wake cycle. We then show that Stop responses are earlier and stronger in the Arky compared to the Proto subpopulation. In contrast to other basal ganglia neurons, pallidal Stop responses are selective to Stop, rather than Go, cues. Furthermore, the timing of these Stop responses matches the suppression of developing striatal Go-related activity. Our results support a two-step model of action suppression: actions-inpreparation are first paused via a subthalamic-nigral pathway, then cancelled via Arky GABAergic projections to striatum.

SUBMITTER: Mallet N

PROVIDER: S-EPMC4871723 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Arkypallidal Cells Send a Stop Signal to Striatum.

Mallet Nicolas N Schmidt Robert R Leventhal Daniel D Chen Fujun F Amer Nada N Boraud Thomas T Berke Joshua D JD

Neuron 20160101 2

The suppression of inappropriate actions is critical for flexible behavior. Cortical-basal ganglia networks provide key gating mechanisms for action suppression, yet the specific roles of neuronal subpopulations are poorly understood. Here, we examine Arkypallidal (‘‘Arky’’) and Prototypical (‘‘Proto’’) globus pallidus neurons during a Stop task, which requires abrupt cancellation of an imminent action. We first establish that Arky neurons can be identified by their firing properties across the ...[more]

PMID: 26777273

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Project description:Previous studies have delineated the neural processes of motor response inhibition during a stop signal task, with most reports focusing on the cortical mechanisms. A recent study highlighted the importance of subcortical processes during stop signal inhibition in 13 individuals and suggested that the subthalamic nucleus (STN) may play a role in blocking response execution (Aron and Poldrack, 2006. Cortical and subcortical contributions to Stop signal response inhibition: role of the subthalamic nucleus. J Neurosci 26, 2424-2433). Here in a functional magnetic resonance imaging (fMRI) study we replicated the finding of greater activation in the STN during stop (success or error) trials, compared to go trials, in a larger sample of subjects (n=30). However, since a contrast between stop and go trials involved processes that could be distinguished from response inhibition, the role of subthalamic activity during stop signal inhibition remained to be specified. To this end we followed an alternative strategy to isolate the neural correlates of response inhibition (Li et al., 2006a. Imaging response inhibition in a stop signal task--neural correlates independent of signal monitoring and post-response processing. J Neurosci 26, 186-192). We compared individuals with short and long stop signal reaction time (SSRT) as computed by the horse race model. The two groups of subjects did not differ in any other aspects of stop signal performance. We showed greater activity in the short than the long SSRT group in the caudate head during stop successes, as compared to stop errors. Caudate activity was positively correlated with medial prefrontal activity previously shown to mediate stop signal inhibition. Conversely, bilateral thalamic nuclei and other parts of the basal ganglia, including the STN, showed greater activation in subjects with long than short SSRT. Thus, fMRI delineated contrasting roles of the prefrontal-caudate and striato-thalamic activities in mediating motor response inhibition.

Project description:BackgroundA lack of ability to inhibit prepotent responses, or more generally a lack of impulse control, is associated with several disorders such as attention-deficit/hyperactivity disorder and schizophrenia as well as general damage to the prefrontal cortex. A stop-signal task (SST) is a reliable and established measure of response inhibition. However, using the SST as an objective assessment in diagnostic or research-focused settings places significant stress on participants as the task itself requires concentration and cognitive effort and is not particularly engaging. This can lead to decreased motivation to follow task instructions and poor data quality, which can affect assessment efficacy and might increase drop-out rates. Gamification-the application of game-based elements in nongame settings-has shown to improve engaged attention to a cognitive task, thus increasing participant motivation and data quality.ObjectiveThis study aims to design a gamified SST that improves participants' engagement and validate this gamified SST against a standard SST.MethodsWe described the design of our gamified SST and reported on 2 separate studies that aim to validate the gamified SST relative to a standard SST. In study 1, a within-subject design was used to compare the performance of the SST and a stop-signal game (SSG). In study 2, we added eye tracking to the procedure to determine if overt attention was affected and aimed to replicate the findings from study 1 in a between-subjects design. Furthermore, in both studies, flow and motivational experiences were measured.ResultsIn contrast, the behavioral performance was comparable between the tasks (P<.87; BF01=2.87), and the experience of flow and intrinsic motivation were rated higher in the SSG group, although this difference was not significant.ConclusionsOverall, our findings provide evidence that the gamification of SST is possible and that the SSG is enjoyed more. Thus, when participant engagement is critical, we recommend using the SSG instead of the SST.

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Arkypallidal Cells Send a Stop Signal to Striatum.

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Arkypallidal Cells Send a Stop Signal to Striatum.

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