Stop Success Trials Research Articles

Response inhibition and fronto-striatal-thalamic circuit dysfunction in cocaine addiction

BackgroundMany studies have investigated how cognitive control may be compromised in cocaine addiction. Here, we extend this literature by employing spatial Independent Component Analysis (ICA) to describe circuit dysfunction in relation to impairment in response inhibition in cocaine addiction. MethodsFifty-five cocaine-dependent (CD) and 55 age- and sex-matched non-drug-using healthy control individuals (HC) participated in the study. Task-relatedness of 40 independent components (ICs) was assessed using multiple regression analyses of component time courses with the modeled time courses of hemodynamic activity convolved with go success (GS), stop success (SS) and stop error (SE). This procedure produced beta-weights that represented the degree to which each IC was temporally associated with, or ‘engaged’, by each task event. ResultsBehaviorally, CD participants showed prolonged stop signal reaction times (SSRTs) as compared to HC participants (p < 0.01). ICA identified two networks that showed differences in engagement related to SS between CD and HC (p < 0.05, FDR-corrected). The activity of the fronto-striatal-thalamic network was negatively correlated with SSRTs in HC but not in CD, suggesting a specific role of this network in mediating deficits of response inhibition in CD individuals. In contrast, the engagement of the fronto-parietal-temporal network did not relate to SSRTs, was similarly less engaged for both SS and SE trials, and may reflect attentional dysfunction in cocaine addiction. ConclusionsThis study highlights the utility of ICA in identifying neural circuitry engagement related to SST performance and suggests that specific networks may represent important targets in remedying executive-control impairment in cocaine addiction.

Perigenual anterior cingulate event-related potential precedes stop signal errors

Momentary lapses in attention disrupt goal-directed behavior. Attentional lapse has been associated with increased “default-mode” network (DMN) activity. In our previous fMRI study of a stop signal task (SST), greater activation of the perigenual anterior cingulate cortex (pgACC) – an important node of the DMN – predicts stop signal errors. In event-related potential (ERP) studies, the amplitude of an error-preceding positivity (EPP) also predicts response error. However, it is not clear whether the EPP originates from DMN regions. Here, we combined high-density array EEG and an SST to examine response-locked ERPs of error preceding trials in twenty young adult participants. The results showed an EPP in go trials that preceded stop error than stop success trials. Importantly, source modeling identified the origin of the EPP in the pgACC. By employing a bootstrapping procedure, we further confirmed that pgACC rather than the dorsal ACC as the source provides a better fit to the EPP. Together, these results suggest that attentional lapse in association with EPP in the pgACC anticipates failure in response inhibition.

Error processing and gender-shared and -specific neural predictors of relapse in cocaine dependence

Deficits in cognitive control are implicated in cocaine dependence. Previously, combining functional magnetic resonance imaging and a stop signal task, we demonstrated altered cognitive control in cocaine-dependent individuals. However, the clinical implications of these cross-sectional findings and, in particular, whether the changes were associated with relapse to drug use, were not clear. In a prospective study, we recruited 97 treatment-seeking individuals with cocaine dependence to perform the stop signal task during functional magnetic resonance imaging and participate in follow-up assessments for 3 months, during which time cocaine use was evaluated with timeline follow back and ascertained by urine toxicology tests. Functional magnetic resonance imaging data were analysed using general linear models as implemented in Statistical Parametric Mapping 8, with the contrast 'stop error greater than stop success trials' to index error processing. Using voxelwise analysis with logistic and Cox regressions, we identified brain activations of error processing that predict relapse and time to relapse. In females, decreased error-related activations of the thalamus and dorsal anterior cingulate cortex predicted relapse and an earlier time to relapse. In males, decreased error-related activations of the dorsal anterior cingulate cortex and left insula predicted relapse and an earlier time to relapse. These regional activations were validated with data resampling and predicted relapse with an average area under the curve of 0.849 in receiver operating characteristic analyses. These findings provide direct evidence linking deficits in cognitive control to clinical outcome in a moderate-sized cohort of cocaine-dependent individuals. These results may provide a useful basis for future studies to examine how psychosocial factors interact with cognitive control to determine drug use and to evaluate the efficacy of pharmacological or behavioural treatment in remediating deficits of cognitive control in cocaine addicts.

The influence of risky and conservative mental sets on cerebral activations of cognitive control

Mental set is known to influence cognitive functioning. Risk-seeking and risk-aversive mental sets alter cerebral responses to conflicting events. Here, building on our previous imaging work of the stop signal task, we introduced a “reward uncertainty” condition to elicit changes in participants' mental sets and examined how individual differences altered the neural responses to salient events. Approximately half of 27 adult participants – the Conservatives – became more risk-aversive in the “reward” as compared to the “standard” condition, by slowing down in go reaction time. We hypothesized that stop errors were more salient for these participants, as compared to the other subjects – the Riskys – who speeded up in go reaction time in the reward as compared to standard condition. With statistical parametric mapping, we showed greater activation of the retrosplenial cortex, somatosensory cortex, pre-supplementary motor area, and thalamus during stop error, in contrast to stop success trials, in the Conservatives as compared to Riskys. These results provided evidence that mental set influences cerebral activations during stop signal performance and extended the potential utility of the stop signal task in elucidating the contextual effects on cognitive control.

Deficits in default mode network activity preceding error in cocaine dependent individuals

Background Cocaine dependence is associated with cognitive deficits and altered task-related cerebral activation in cognitive performance (see Li and Sinha, 2008, for a review). Relatively little is known whether these individuals are also impaired in regional brain activation of the default mode network (DMN). We demonstrated previously that greater activation of the default brain regions precedes errors in a stop signal task performed by healthy controls (SST, Li et al., 2007). We seek to determine whether individuals with cocaine dependence are impaired in DMN activity, specifically activity preceding error, as compared to the healthy people. We also examine the relation to years of cocaine use. Methods Individuals with cocaine dependence (CD, n = 23) and demographics-matched healthy controls (HC, n = 27) performed a SST that employed a tracking procedure to adjust the difficulty of stop trials and elicit errors approximately half of the time. Blood oxygenation level dependent (BOLD) signals of go trials preceding stop error as compared to those preceding stop success trials were extracted with generalized linear models using statistical parametric mapping. Results HC showed activation of bilateral precuneus and posterior cingulate cortices and ventromedial prefrontal cortex (vmPFC) preceding errors during the SST. In contrast, despite indistinguishable stop signal performance, CD did not show these error predicting activations. Furthermore, the effect size of error-preceding vmPFC activation was inversely correlated with years of cocaine use. Conclusions These findings indicate DMN deficits and could potentially add to our understanding of the effects of chronic cocaine use on cerebral functions in cocaine dependence. Work to further clarify potential changes in functional connectivity and gray matter volume is warranted to understand the relevance of DMN to the pathology of cocaine misuse.

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.

Error-Related Functional Connectivity of the Habenula in Humans

Error detection is critical to the shaping of goal-oriented behavior. Recent studies in non-human primates delineated a circuit involving the lateral habenula (LH) and ventral tegmental area (VTA) in error detection. Neurons in the LH increased activity, preceding decreased activity in the VTA, to a missing reward, indicating a feedforward signal from the LH to VTA. In the current study we used connectivity analyses to reveal this pathway in humans. In 59 adults performing a stop signal task during functional magnetic resonance imaging, we identified brain regions showing greater psychophysiological interaction with the habenula during stop error as compared to stop success trials. These regions included a cluster in the VTA/substantia nigra (SN), internal segment of globus pallidus, bilateral amygdala, and insula. Furthermore, using Granger causality and mediation analyses, we showed that the habenula Granger caused the VTA/SN, establishing the direction of this interaction, and that the habenula mediated the functional connectivity between the amygdala and VTA/SN during error processing. To our knowledge, these findings are the first to demonstrate a feedforward influence of the habenula on the VTA/SN during error detection in humans.

Dissociable processes of cognitive control during error and non-error conflicts: a study of the stop signal task.

BackgroundConflict detection and subsequent behavioral adjustment are critical to daily life, and how this process is controlled has been increasingly of interest. A medial cortical region which includes the anterior cingulate cortex (ACC) has been theorized to act as a conflict detector that can direct prefrontal activity for behavioral adjustments. This conflict monitoring hypothesis was supported by many imaging studies of the Stroop task, with a focus on non-error processes. Here we sought to examine whether this circuit could be generalized to the stop signal task (SST), another behavioral paradigm widely used to study cognitive control. In particular, with a procedure to elicit errors in the SST, we examined whether error and non-error control were mediated by the same pathways.Methodology/Principal FindingsIn functional magnetic resonance imaging of 60 healthy adults, we demonstrated that the medial cortical activity during stop success (SS) as compared to go success (G) trials is correlated with increased prefrontal activity in post-stop SS as compared to post-go SS trials, though this correlation was not specific to the medial cortical region. Furthermore, thalamic and insular rather than medial cortical activation during stop error (SE) as compared to G trials correlated with increased prefrontal activity in post-stop SS as compared to post-go SS trials.Conclusions/SignificanceTaken together, these new findings challenge a specific role of the ACC and support distinct pathways for error and non-error conflict processing in cognitive control.