Subcortical processes of motor response inhibition during a stop signal task.
ABSTRACT: 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:People make decisions by evaluating existing evidence against a threshold or level of confidence. Individuals vary widely in response times even when they perform a simple task in the laboratory. We examine the neural bases of this individual variation by combining computational modeling and brain imaging of 64 healthy adults performing a stop signal task. Behavioral performance was modeled by an accumulator model that describes the process of information growth to reach a threshold to respond. In this model, go trial reaction time (goRT) is jointly determined by the information growth rate, threshold, and movement time (MT). In a linear regression of activations in successful go and all stop (Go+Stop) trials against goRT across participants, the insula, supplementary motor area (SMA), pre-SMA, thalamus including the subthalamic nucleus (STN), and caudate head respond to increasing goRT. Among these areas, the insula, SMA, and thalamus including the STN respond to a slower growth rate, the caudate head responds to an elevated threshold, and the pre-SMA responds to a longer MT. In the regression of Go+Stop trials against the stop signal reaction time (SSRT), the pre-SMA shows a negative correlation with SSRT. These results characterize the component processes of decision making and elucidate the neural bases of a critical aspect of inter-subject variation in human behavior. These findings also suggest that the pre-SMA may play a broader role in response selection and cognitive control rather than simply response inhibition in the stop signal task.
Project description:Successful behavioral inhibition involves both proactive and reactive inhibition, allowing people to prepare for restraining actions, and cancel their actions if the response becomes inappropriate. In the present study, we utilized the stop-signal paradigm to examine whole-brain contrasts and functional connectivity for proactive and reactive inhibition. The results of our functional magnetic resonance imaging (fMRI) data analysis show that the inferior frontal gyrus (IFG), the supplementary motor area (SMA), the subthalamic nucleus (STN), and the primary motor cortex (M1) were activated by both proactive and reactive inhibition. We then created 70 dynamic causal models (DCMs) representing the alternative hypotheses of modulatory effects from proactive and reactive inhibition in the IFG-SMA-STN-M1 network. Bayesian model selection (BMS) showed that causal connectivity from the IFG to the SMA was modulated by both proactive and reactive inhibition. To further investigate the possible brain circuits involved in behavioral control, including proactive inhibitory processes, we compared 13 DCMs representing the alternative hypotheses of proactive modulation in the dorsolateral prefrontal cortex (DLPFC)-caudate-IFG-SMA neural circuits. BMS revealed that the effective connectivity from the caudate to the IFG is modulated only in the proactive inhibition condition but not in the reactive inhibition. Together, our results demonstrate how fronto-basal ganglia pathways are commonly involved in proactive and reactive inhibitory control, with a "longer" pathway (DLPFC-caudate-IFG-SMA-STN-M1) playing a modulatory role in proactive inhibitory control, and a "shorter" pathway (IFG-SMA-STN-M1) involved in reactive inhibition. These results provide causal evidence for the roles of indirect and hyperdirect pathways in mediating proactive and reactive inhibitory control.
Project description:Mean stop-signal reaction time (SSRT) is frequently employed as a measure of response inhibition in cognitive neuroscience research on ADHD. However, this measurement model is limited by two factors which may bias SSRT estimation in this population: 1) excessive skew in "go" RT distributions, and 2) trigger failures, or instances in which individuals fail to trigger an inhibition process in response to the "stop" signal. We use a Bayesian parametric approach, which allows unbiased estimation of the shape of entire SSRT distributions and the probability of trigger failures, to clarify mechanisms of stop-signal task deficits in ADHD. Children with ADHD displayed greater positive skew than their peers in both "go" RT and SSRT distributions. However, they also displayed more frequent trigger failures, which appeared to drive ADHD-related stopping difficulties. Results suggest that stop-signal task performance in ADHD reflects impairments in early attentional processes, rather than inefficiency in the stop process.
Project description:Cognitive control is a critical executive function. Many studies have combined general linear modeling and the stop signal task (SST) to delineate the component processes of cognitive control. For instance, by contrasting stop success (SS) and stop error (SE) trials in the SST, investigators examined regional responses to stop signal inhibition. In contrast to this parameterized approach, independent component analysis (ICA) elucidates brain networks subserving cognitive control. In our earlier work of 59 adults performing the SST during fMRI, we characterized six independent components (ICs). However, none of these ICs correlated with stop signal performance, raising questions about their behavioral validity. Here, in a larger sample (n?=?100), we identified and explored 23 ICs for correlation with the stop signal reaction time (SSRT), a measure of the efficiency of response inhibition. At a corrected threshold (P?<?0.0005), a paracentral lobule-midcingulate network and a left inferior parietal-supplementary motor-somatomotor network showed a positive correlation between SE beta weight and SSRT. In contrast, a midline cerebellum-thalamus-pallidum network showed a negative correlation between SE beta weight and SSRT. These findings suggest that motor preparation and execution prolongs the SSRT, likely via an interaction between the go and stop processes as suggested by the race model. Behaviorally, consistent with this hypothesis, the difference in G and SE reaction times is positively correlated with SSRT across subjects. These new results highlight the importance of cognitive motor regions in response inhibition and support the utility of ICA in uncovering functional networks for cognitive control in the SST.
Project description:Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons exhibited low-latency responses to 'Stop' cues, irrespective of whether actions were canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) only responded to Stop cues in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral 'core' subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with stopping requiring Stop-cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return.
Project description:This study investigated the preparatory control of motor inhibition and motor execution using a stop signal task (SST) and functional magnetic resonance imaging (fMRI). In the SST, a frequent "go" signal triggered a prepotent response and a less frequent "stop" signal prompted the inhibition of this response. Preparatory control of motor inhibition and execution in the stop signal trials were examined by contrasting brain activation between stop success and stop error trials during the fore-period, in which participants prepared to respond to go or to stop. Results from 91 healthy adults showed greater activation in the right prefrontal cortex and inferior parietal lobule during preparatory motor inhibition. Preparatory motor execution activated bilateral putamen, primary motor cortices, posterior cingulate cortex, ventromedial prefrontal cortex, and superior temporal/intraparietal sulci. Furthermore, the extents of these inhibition and execution activities were inversely correlated across subjects. On the basis of a median split of the stop signal reaction time (SSRT), subjects with short SSRT showed greater activity in the right orbital frontal cortex during preparatory inhibition. These new findings suggest that the go and stop processes interact prior to target presentation in the SST, in accord with recent computational models of stop signal inhibition.
Project description:Impaired response inhibition has been consistently reported in patients diagnosed with obsessive-compulsive disorder (OCD). This clinically heterogeneous disorder is characterized by several symptom dimensions that may have distinct, but partially overlapping, neural correlates. The present study examined whether alterations in response inhibition may be related to symptom severity and symptom dimensions. Event-related potentials (ERPs) were recorded in a group of 42 medication-free OCD patients as well as 42 healthy controls during a stop-signal task. Symptom dimension scores were obtained using the Yale-Brown Obsessive Compulsive Scale symptom checklist. OCD patients showed longer stop-signal reaction times (SSRT, p < 0.01) and larger stop-N2 amplitudes (p < 0.01) compared to healthy controls. Neither the longer SSRT nor the larger stop-N2 scores were significantly correlated with symptom severity or present or lifetime OCD symptoms in OCD patients. These results indicate that deficient response inhibition is a common occurrence in OCD patients that is independent of global symptom severity and symptom dimensions. These data support the notion that impaired response inhibition may be a general attribute of patients with OCD.
Project description: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.
Project description:Prior research points to the importance of psychostimulants in improving self-control. However, the neural substrates underlying such improvement remain unclear. Here, in a pharmacological functional MRI study of the stop signal task, we show that methylphenidate (as compared with placebo) robustly decreased stop signal reaction time (SSRT), an index of improved control, in cocaine-dependent patients (a population in which inhibitory control is impaired). Methylphenidate-induced decreases in SSRT were positively correlated with inhibition-related activation of left middle frontal cortex (MFC) and negatively with activation of the ventromedial prefrontal cortex (vmPFC) in whole brain linear regressions. Inhibition-related MFC but not vmPFC activation distinguished individuals with short and long SSRT in 36 demographically matched healthy individuals, whereas vmPFC but not MFC activation, along with improvement in SSRT, was correlated with a previously implicated biomarker of methylphenidate response (systolic blood pressure). These results implicate a specific neural (i.e., vmPFC) mechanism whereby stimulants improve inhibitory control. Altered ventromedial prefrontal activation and increased blood pressure may represent useful CNS and peripheral biomarkers in individualized treatment with methylphenidate for patients with cocaine dependence.