Chiang-shan R. Li

Imaging Response Inhibition in a Stop-Signal Task: Neural Correlates Independent of Signal Monitoring and Post-Response Processing

Execution of higher cortical functions requires inhibitory control to restrain habitual responses and meet changing task demands. We used functional magnetic resonance imaging to show the neural correlates of response inhibition during a stop-signal task. The task has a frequent “go” stimulus to set up a pre-potent response tendency and a less frequent “stop” signal for subjects to withhold their response. We contrasted brain activation between successful and failed inhibition for individual subjects and compared groups of subjects with short and long stop-signal reaction times. The two groups of subjects did not differ in their inhibition failure rates or the extent of signal monitoring, error monitoring, or task-associated frustration ratings. The results showed that short stop-signal reaction time or more efficient response inhibition was associated with greater activation in the superior medial and precentral frontal cortices. Moreover, activation of these inhibitory motor areas correlated negatively with stop-signal reaction time. These brain regions may represent the neural substrata of response inhibition independent of other cognitive and affective functions.

Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications

Stress- and drug-related cues are major factors contributing to high rates of relapse in addictive disorders. Brain imaging studies have begun to identify neural correlates of stress and drug cue-induced craving states. Findings indicate considerable overlap in neural circuits involved in processing stress and drug cues with activity in the corticostriatal limbic circuitry underlying both affective and reward processing. More recent efforts have begun to identify the relationships between neural activity during stress and drug cue exposure and drug relapse outcomes. Findings suggest medial prefrontal, anterior and posterior cingulate, striatal and posterior insula regions to be associated with relapse outcomes. Altered function in these brain regions is associated with stress-induced and drug cue-induced craving states and an increased susceptibility to relapse. Such alterations can serve as markers to identify relapse propensity and a more severe course of addiction. Efficacy of pharmacological and behavioral treatments that specifically target stress and cue-induced craving and arousal responses may also be assessed via alterations in these brain correlates.

Functional Connectivity Delineates Distinct Roles of the Inferior Frontal Cortex and Presupplementary Motor Area in Stop Signal Inhibition

The neural basis of motor response inhibition has drawn considerable attention in recent imaging literature. Many studies have used the go/no-go or stop signal task to examine the neural processes underlying motor response inhibition. In particular, showing greater activity during no-go (stop) compared with go trials and during stop success compared with stop error trials, the right inferior prefrontal cortex (IFC) has been suggested by numerous studies as the cortical area mediating response inhibition. Many of these same studies as well as others have also implicated the presupplementary motor area (preSMA) in this process, in accord with a function of the medial prefrontal cortex in goal-directed action. Here we used connectivity analyses to delineate the roles of IFC and preSMA during stop signal inhibition. Specifically, we hypothesized that, as an integral part of the ventral attention system, the IFC responds to a stop signal and expedites the stop process in the preSMA, the primary site of motor response inhibition. This hypothesis predicted that preSMA and primary motor cortex would show functional interconnectivity via the basal ganglia circuitry to mediate response execution or inhibition, whereas the IFC would influence the basal ganglia circuitry via connectivity with preSMA. The results of Granger causality analyses in 57 participants confirmed this hypothesis. Furthermore, psychophysiological interaction showed that, compared with stop errors, stop successes evoked greater effective connectivity between the IFC and preSMA, providing additional support for this hypothesis. These new findings provided evidence critically differentiating the roles of IFC and preSMA during stop signal inhibition and have important implications for our understanding of the component processes of inhibitory control.

Subcortical processes of motor response inhibition during a stop signal task

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.

Inhibitory Control and Emotional Stress Regulation: Neuroimaging Evidence for Frontal-Limbic Dysfunction in Psycho-stimulant Addiction

This review focuses on neuroimaging studies that examined stress processing and regulation and cognitive inhibitory control in patients with psycho-stimulant addiction. We provide an overview of these studies, summarizing converging evidence and discrepancies as they occur in the literature. We also adopt an analytic perspective and dissect these psychological processes into their sub-components, to identify the neural pathways specific to each component process and those that are more specifically involved in psycho-stimulant addiction. To this aim we refer frequently to studies conducted in healthy individuals. Despite the separate treatment of stress/affect regulation, stress-related craving or compulsive drug seeking, and inhibitory control, neural underpinnings of these processes overlap significantly. In particular, the ventromedial prefrontal regions including the anterior cingulate cortex, amygdala and the striatum are implicated in psychostimulant dependence. Our overarching thesis is that prefrontal activity ensures intact emotional stress regulation and inhibitory control. Altered prefrontal activity along with heightened striatal responses to addicted drug and drug-related salient stimuli perpetuates habitual drug seeking. Further studies that examine the functional relationships of these neural systems will likely provide the key to understanding the mechanisms underlying compulsive drug use behaviors in psycho-stimulant dependence.

Altered Impulse Control in Alcohol Dependence: Neural Measures of Stop Signal Performance

BACKGROUND Altered impulse control has been implicated in the shaping of habitual alcohol use and eventual alcohol dependence. We sought to identify the neural correlates of altered impulse control in 24 abstinent patients with alcohol dependence (PAD), as compared to 24 demographics matched healthy control subjects (HC). In particular, we examined the processes of risk taking and cognitive control as the neural endophenotypes of alcohol dependence. METHODS To this end, functional magnetic resonance imaging (fMRI) was conducted during a stop signal task (SST), in which a procedure was used to elicit errors in the participants. The paradigm allowed trial-by-trial evaluation of response inhibition, error processing, and post-error behavioral adjustment. Furthermore, by imposing on the subjects to be both fast and accurate, the SST also introduced a distinct element of risk, which participants may or may not avert during the task. Brain imaging data were analyzed with Statistical Parametric Mapping in covariance analyses accounting for group disparity in general performance. RESULTS The results showed that, compared to HC, PAD demonstrated longer go trial reaction time (RT) and higher stop success rate (SS%). HC and PAD were indistinguishable in stop signal reaction time (SSRT) and post-error slowing (PES). In a covariance analysis accounting for go trial RT and SS%, HC showed greater activity in the left dorsolateral prefrontal cortex than PAD, when subjects with short and long SSRT were contrasted. By comparing PAD and HC directly during stop errors (SE), as contrasted with SS, we observed greater activity in PAD in bilateral visual and frontal cortices. Compared to HC, PAD showed less activation of the right dorsolateral prefrontal cortex during PES, an index of post-error behavioral adjustment. Furthermore, PAD who showed higher alcohol urge at the time of the fMRI were particularly impaired in dorsolateral prefrontal activation, as compared to those with lower alcohol urge. Finally, compared to HC subjects, PAD showed less activity in cortical and subcortical structures including putamen, insula, and amygdala during risk-taking decisions in the SST. CONCLUSION These preliminary results provided evidence for altered neural processing during impulse control in PAD. These findings may provide a useful neural signature in the evaluation of treatment outcomes and development of novel pharmacotherapy for alcohol dependence.

Greater activation of the "default" brain regions predicts stop signal errors.

Previous studies have provided evidence for a role of the medial cortical brain regions in error processing and post-error behavioral adjustment. However, little is known about the neural processes that precede errors. Here in an fMRI study we employ a stop signal task to elicit errors approximately half of the time despite constant behavioral adjustment of the observers (n=40). By comparing go trials preceding a stop error and those preceding a stop success, we showed that (at p<0.05, corrected for multiple comparisons) the activation of midline brain regions including bilateral precuneus and posterior cingulate cortices, perigenual anterior cingulate cortices and transverse frontopolar gyri precedes errors during the stop signal task. Receiver operating characteristic (ROC) analysis based on the signal detection theory showed that the activity in these three regions predicts errors with an accuracy between 0.81 and 0.85 (area under the ROC curve). Broadly supporting the hypothesis that deactivation of the default mode circuitry is associated with mental effort in a cognitive task, the current results further indicate that greater activity of these brain regions can precede performance errors.

Neural Correlates of Impulse Control During Stop Signal Inhibition in Cocaine-Dependent Men

Altered impulse control is associated with substance use disorders, including cocaine dependence. We sought to identify the neural correlates of impulse control in abstinent male patients with cocaine dependence (PCD). Functional magnetic resonance imaging (fMRI) was conducted during a stop signal task that allowed trial-by-trial evaluation of response inhibition. Fifteen male PCD and 15 healthy control (HC) subjects, matched in age and years of education, were compared. Stop signal reaction time (SSRT) was derived on the basis of a horse race model. By comparing PCD and HC co-varied for stop success rate, task-related frustration rating, and post-error slowing, we isolated the neural substrates of response inhibition, independent of attentional monitoring (of the stop signal) and post-response processes including affective responses and error monitoring. Using region of interest analysis, we found no differences between HC and PCD who were matched in stop signal performance in the pre-supplementary motor area (pre-SMA) previously shown to be associated with SSRT. However, compared with HC, PCD demonstrated less activation of the rostral anterior cingulate cortex (rACC), an area thought to be involved in the control of stop signal inhibition. The magnitude of rACC activation also correlated negatively with the total score and the impulse control subscore of the Difficulty in Emotion Regulation Scale in PCD. The current study thus identified the neural correlates of altered impulse control in PCD independent of other cognitive processes that may influence stop signal performance. Relative hypoactivation of the rACC during response inhibition may represent a useful neural marker of difficulties in impulse control in abstinent cocaine-dependent men who are at risk of relapse.

Functional networks for cognitive control in a stop signal task: independent component analysis.

Cognitive control is a critical executive function of the human brain. 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 the neural processes underlying stop signal inhibition (SS > SE) and error processing (SE > SS). To complement this parameterized approach, here, we employed a data‐driven method—independent component analysis (ICA)—to elucidate neural networks and the relationship between neural networks subserving cognitive control. In 59 adults performing the SST during fMRI, we characterized six independent components with ICA. These functional networks, temporally sorted for go success, SS, and SE trials as the events of interest, included a motor cortical network for motor preparation and execution; a right fronto‐parietal network for attentional monitoring; a left fronto‐parietal network for response inhibition; a midline cortico‐subcortical network for error processing; a cuneus–precuneus network for behavioral engagement; and a “default” network for self‐referential processing. Across subjects the event‐associated weights of these functional networks showed a distinct pattern of correlation. These results provide new insight into the component processes of cognitive control. Hum Brain Mapp, 2012.

Neural correlates of post-error slowing during a stop signal task: A functional magnetic resonance imaging study

The ability to detect errors and adjust behavior accordingly is essential for maneuvering in an uncertain environment. Errors are particularly prone to occur when multiple, conflicting responses are registered in a situation that requires flexible behavioral outputs; for instance, when a go signal requires a response and a stop signal requires inhibition of the response during a stop signal task (SST). Previous studies employing the SST have provided ample evidence indicating the importance of the medial cortical brain regions in conflict/error processing. Other studies have also related these regional activations to postconflict/error behavioral adjustment. However, very few studies have directly explored the neural correlates of postconflict/error behavioral adjustment. Here we employed an SST to elicit errors in approximately half of the stop trials despite constant behavioral adjustment of the observers. Using functional magnetic resonance imaging, we showed that prefrontal loci including the ventrolateral prefrontal cortex are involved in post-error slowing in reaction time. These results delineate the neural circuitry specifically involved in error-associated behavioral modifications.