Validation of a Bayesian Adaptive Estimation Technique in the Stop-Signal Task.

Event Abstract Back to Event Brain pathways underlying Response Inhibition and Response Caution Renate Thienel1*, Elise Mansfield1, Patrick S. Cooper1, Andrew Heathcote1, Birte Forstmann2, Pat Michie1, Gavin Cooper1 and Frini Karayanidis1 1 School of Psychology, University of Newcastle, Australia 2 University of Amsterdam, Netherlands Background: Our previous findings suggest that the striatum is instrumental in mediating response caution in a task switching paradigm (Mansfield et al., J. Neurosci 2011, 31:14688-92), and that structural integrity in two separate fronto-striatal networks are associated with adopting an overall more risky or more cautious response threshold. In the present study, we examine whether a similar network underlies response inhibition, as operationalized by a stop signal task. Response inhibition has been shown to be mediated by cortical and subcortical structures within the inferior frontal lobe and the subthalamic nucleus, respectively. We investigate whether structural integrity measures in these regions can explain the relationship between stop signal related event related potential (ERP) components and estimates of stop signal reaction time (SSRT). Finally the relationship between, and the differential structural pathways contributing to, response threshold adjustment (task-switching paradigm) and stop signal response time will be examined. Methods: Diffusion weighted Imaging (DWI), ERP and behavioural data has been collected in 16 healthy participants (24.5 years, 5 male). A correlational analysis was performed for the ERPs and the behavioural measures of both tasks (task switching and stop signal task). Tract based spatial statistics (TBSS) of the DWI data was performed to compare the white matter pathways associated with response thresholds adjustment (task-switching task), and response inhibition (stop-signal task) respectively. These regions were then used to explain variation in ERP data. Results/Discussion: The integrity within distinct structural pathways (DWI data) explained the relationship between (1) ERP measures and response threshold adjustment and (2) ERP measures and SSRTs. Distinct fronto-basal ganglia pathways mediated threshold setting and response suppression. Keywords: task-switching, stop signal task, DWI, fronto-striatal circuits, response inhibition Conference: ACNS-2013 Australasian Cognitive Neuroscience Society Conference, Clayton, Melbourne, Australia, 28 Nov - 1 Dec, 2013. Presentation Type: Poster Topic: Executive Processes Citation: Thienel R, Mansfield E, Cooper PS, Heathcote A, Forstmann B, Michie P, Cooper G and Karayanidis F (2013). Brain pathways underlying Response Inhibition and Response Caution. Conference Abstract: ACNS-2013 Australasian Cognitive Neuroscience Society Conference. doi: 10.3389/conf.fnhum.2013.212.00145 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 25 Sep 2013; Published Online: 25 Nov 2013. * Correspondence: Dr. Renate Thienel, School of Psychology, University of Newcastle, Newcastle, Australia, renate.thienel@newcastle.edu.au Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Renate Thienel Elise Mansfield Patrick S Cooper Andrew Heathcote Birte Forstmann Pat Michie Gavin Cooper Frini Karayanidis Google Renate Thienel Elise Mansfield Patrick S Cooper Andrew Heathcote Birte Forstmann Pat Michie Gavin Cooper Frini Karayanidis Google Scholar Renate Thienel Elise Mansfield Patrick S Cooper Andrew Heathcote Birte Forstmann Pat Michie Gavin Cooper Frini Karayanidis PubMed Renate Thienel Elise Mansfield Patrick S Cooper Andrew Heathcote Birte Forstmann Pat Michie Gavin Cooper Frini Karayanidis Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Inhibitory control is a key executive function and has been studied extensively using the stop signal task. By applying a simple race model that posits an independent race between a GO process responsible for initiation of responses and a STOP process responsible for inhibition of responses, one can estimate how long it takes an individual to inhibit an ongoing response, the stop signal reaction time. Here, we examined how stop signal reaction time can be affected by working memory. Participants engaged in a dual task; they completed a stop signal task under low and high working memory load conditions. Working memory capacity was also measured. We found that the STOP process was lengthened in the high, compared to the low, working memory load condition, as evidenced by differences in stop signal reaction time. The GO process was unaffected and working memory capacity could not account for differences across the load conditions. These results indicate that inhibitory control can be influenced by placing demands on working memory.

Roles of the medial frontal cortices in the selection, storage and retrieval of response tactics in a voluntary arm-reaching task

BackgroundA robust feature of sensorimotor synchronization (SMS) performance in finger tapping to an auditory pacing signal is the negative asynchrony of the tap with respect to the pacing signal. The Paillard–Fraisse hypothesis suggests that negative asynchrony is a result of inter-modal integration, in which the brain compares sensory information across two modalities (auditory and tactile). The current study compared the asynchronies of vocalizations and finger tapping in time to an auditory pacing signal. Our first hypothesis was that vocalizations have less negative asynchrony compared to finger tapping due to the requirement for sensory integration within only a single (auditory) modality (intra-modal integration). However, due to the different measurements for vocalizations and finger responses, interpreting the comparison between these two response modalities is problematic. To address this problem, we included stop signals in the synchronization task. The rationale for this manipulation was that stop signals would perturb synchronization more in the inter-modal compared to the intra-modal task. We hypothesized that the inclusion of stop signals induce proactive inhibition, which reduces negative asynchrony. We further hypothesized that any reduction in negative asynchrony occurs to a lesser degree for vocalization than for finger tapping.MethodA total of 30 participants took part in this study. We compared SMS in a single sensory modality (vocalizations (or auditory) to auditory pacing signal) to a dual sensory modality (fingers (or tactile) to auditory pacing signal). The task was combined with a stop signal task in which stop signals were relevant in some blocks and irrelevant in others. Response-to-pacing signal asynchronies and stop signal reaction times were compared across modalities and across the two types of stop signal blocks.ResultsIn the blocks where stopping was irrelevant, we found that vocalization (−61.47 ms) was more synchronous with the auditory pacing signal compared to finger tapping (−128.29 ms). In the blocks where stopping was relevant, stop signals induced proactive inhibition, shifting the response times later. However, proactive inhibition (26.11 ms) was less evident for vocalizations compared to finger tapping (58.06 ms).DiscussionThese results support the interpretation that relatively large negative asynchrony in finger tapping is a consequence of inter-modal integration, whereas smaller asynchrony is associated with intra-modal integration. This study also supports the interpretation that intra-modal integration is more sensitive to synchronization discrepancies compared to inter-modal integration.

Previous studies have shown cultural differences in the behavioral and neural processes of perspective taking and social emotional processing. It is less clear whether culture influences cognitive functions that do not explicitly involve face perception, group membership or social interactions. Here, we addressed this issue by imaging 29 Asians and 168 European Americans while they performed a stop signal task (SST)—a behavioral paradigm widely used to study cognitive control. In the SST participants responded to a frequent go signal and interrupted their response to an infrequent stop signal. Imaging data were processed by published routines implemented in Statistical Parametric Mapping. Behaviorally Asians and European Americans did not differ in SST performance measures, including the go and stop success rates, go and stop signal reaction time, and the sequential effect, an index of performance monitoring and behavioral adjustment. In a Bayesian model of the SST performance, we identified regional responses to stimulus prediction error (expecting go while encountering stop signal or vice versa) and showed that the dorsal anterior cingulate cortex (dACC) responded to Bayesian prediction error, a surprise signal. Importantly, compared to European Americans, Asians showed higher dACC response to prediction error in a voxelwise analysis examined at a corrected threshold. This finding suggested that, although an increased response to surprise did not impact behavioral performance, Asians appeared to exhibit higher arousal to a salient signal than European Americans, a process likely mediated by midbrain catecholaminergic system. This finding supports racial cultural differences in cognitive and affective processes that go beyond the domains of social emotions, and adds to a growing literature of cultural neuroscience.

The ability to inhibit actions inappropriate for the context is essential for meeting the shifting demands of complex environments. The stop signal task (SST) has been used in many previous studies to examine the interactions between go and stop responses in a cognitively demanding task involving attention, conflict resolution, and motor plan selection. The current study uses a variant of the SST, in which the continue signal instructs participants to proceed with the go response they were preparing. Reaction times (RTs) on continue trials were bimodally distributed, suggesting that an aspect of inhibition was involved in at least some of the trials. We investigated whether the cognitive processes delaying the generation of a behavioural response on continue trials are the same as for stop trials. We found improvement of stop signal reaction times (SSRTs) following stop trials, but the decrease in continue signal reaction times (CSRTs) was not significant. No improvement in either SSRT or CSRT was found following continue trials, suggesting that activation of the processes delaying the response on continue trials is insufficient to drive subsequent adjustments in SSRT or CSRT. In addition, go RTs only slowed following stop trials. These effects may suggest the presence of a selective learning process, which requires that the initial inhibition captured by SSRT and CSRT be combined with recognition of the stop signal specifically to affect subsequent performance.

Evidence from animal, clinical, and imaging studies suggests that the basal ganglia and their frontal connections mediate motor inhibition, but the role of dopamine remains unclear. The aim of our study was to investigate, for the first time, whether levodopa medication influences motor inhibition and conflict resolution on the conditional stop-signal reaction time task in patients with Parkinson's disease (PD) tested on or off their medication. Sixteen PD patients and 17 healthy controls performed the conditional stop-signal reaction time (SSRT) task, which requires inhibition of responses when a stop signal is presented on "critical" trials. Additionally, on "non-critical" trials, participants are instructed to ignore the stop signal and respond, thus generating conflict between motor inhibition and initiation; and conflict-induced slowing (CIS) on these "non-critical" trials. Levodopa medication did not significantly influence response initiation, inhibition (SSRT) or the measure of conflict resolution (CIS). Compared to healthy controls, PD patients showed significantly worse response initiation and inhibition both on and off their levodopa medication. Our results suggest that motor inhibition or conflict-induced slowing on the conditional stop-signal RT task are not altered by dopamine replacement in PD. This conclusion is consistent with evidence from animal studies and clinical pharmacological investigations suggesting a role for noradrenaline in motor inhibition and impulsivity.

Conflict anticipation in alcohol dependence — A model-based fMRI study of stop signal task

Cognitive decline is a common feature of Parkinson’s disease, and many of these cognitive deficits fail to respond to dopaminergic therapy. Therefore, targeting other neuromodulatory systems represents an important therapeutic strategy. Among these, the locus coeruleus-noradrenaline system has been extensively implicated in response inhibition deficits. Restoring noradrenaline levels using the noradrenergic reuptake inhibitor atomoxetine can improve response inhibition in some patients with Parkinson’s disease, but there is considerable heterogeneity in treatment response. Accurately predicting the patients who would benefit from therapies targeting this neurotransmitter system remains a critical goal, in order to design the necessary clinical trials with stratified patient selection to establish the therapeutic potential of atomoxetine. Here, we test the hypothesis that integrity of the noradrenergic locus coeruleus explains the variation in improvement of response inhibition following atomoxetine. In a double-blind placebo-controlled randomised crossover design, 19 people with Parkinson’s disease completed an acute psychopharmacological challenge with 40 mg of oral atomoxetine or placebo. A stop-signal task was used to measure response inhibition, with stop-signal reaction times obtained through hierarchical Bayesian estimation of an ex-Gaussian race model. Twenty-six control subjects completed the same task without undergoing the drug manipulation. In a separate session, patients and controls underwent ultra-high field 7T imaging of the locus coeruleus using a neuromelanin-sensitive magnetisation transfer sequence. The principal result was that atomoxetine improved stop-signal reaction times in those patients with lower locus coeruleus integrity. This was in the context of a general impairment in response inhibition, as patients on placebo had longer stop-signal reaction times compared to controls. We also found that the caudal portion of the locus coeruleus showed the largest neuromelanin signal decrease in the patients compared to controls. Our results highlight a link between the integrity of the noradrenergic locus coeruleus and response inhibition in Parkinson’s disease patients. Furthermore, they demonstrate the importance of baseline noradrenergic state in determining the response to atomoxetine. We suggest that locus coeruleus neuromelanin imaging offers a marker of noradrenergic capacity that could be used to stratify patients in trials of noradrenergic therapy and to ultimately inform personalised treatment approaches.

According to the balance model of self-regulation, dysfunction of the inhibitory control and reward processing might be a behavioral marker for addiction and problematic behaviors. Although several studies have separately examined the inhibitory control or reward processing of individuals exhibiting problematic Internet use (PIU), no study has explored these two functions simultaneously to examine the potential imbalance of these functions. This study aimed to investigate whether the self-regulatory failure of PIU individuals results from deficits in both inhibitory control [indexed with the stop signal reaction time (SSRT) in a stop signal task] and risk taking with losses (measured as the acceptance rates of risky gables or the ratio of win/loss in a mixed gambles task). The results revealed that PIU individuals, compared with controls, showed decreased SSRT and increased error rates as well as reduced risk taking with losses. Correlational analyses revealed a significant positive relationship between the SSRT and risk taking with losses. These findings suggest that both the inhibitory control and reward functions are impaired in PIU individuals and reveal an association between these two systems. These results strengthen the balance model of self-regulation theory’s argument that deficits in inhibitory control and risk taking with losses may assist in identifying risk markers for early diagnosis, progression, and prediction of PIU.

The aim of this work is to further understanding into the biological bases of human executive control through an integration of neuropsychology,psychopharmacology and functional imaging. Executive control includes the prototypical executive functions of response inhibition and error awareness. Response inhibition can be further divided into action cancellation and action restraint, which were assayed with the stop signal (SST) and Error Awareness(EAT) tasks, respectively. The EAT, which is a modified go-no go paradigm, was also used to measure error awareness behaviour. Monoamine neurotransmitters, specifically dopamine, noradrenaline and serotonin, were modulated during task performance with acute doses of methylphenidate (a dopamine and noradrenaline reuptake inhibitor), atomoxetine (a noradrenaline reuptake inhibitor), citalopram (a serotonin reuptake inhibitor) and cabergoline (a D2 agonist). The pharmacoimaging correlates of task performance were also examined with functional magnetic resonance imaging (fMRI). All experiments adhered to a randomised, double blind, placebo-controlled, crossover design and were limited to 18-35 year old healthy right-handed male participants. In Chapter 1, twenty-four (24) participants received acute doses of methylphenidate (30mg), atomoxetine (60mg), citalopram (30mg) and placebo and performed the SST. Methylphenidate, but not atomoxetine or citalopram, led to a reduction in response time variability and stop-signal reaction time indicating enhanced action cancellation compared with the other drug conditions. This enhancement occurred without change to overall response speed suggesting that methylphenidate was modulating core response inhibition processes rather than simply augmenting overall processing speed. This result argued for the prominence of dopaminergic, rather than adrenergic or serotonergic, mechanisms in action cancellation. In Chapter 2, the pharmacoimaging correlates of action restraint aspect were explored. Twenty-seven (27) males received acute doses of methylphenidate(30mg), atomoxetine (60mg), citalopram (30mg) and placebo whilst undertaking the EAT during fMRI. No-go related BOLD activations were then correlated for each of the drug conditions. Although Inhibitory performance under methylphenidate was numerically superior to the other drug conditions,this difference did not achieve statistical significance. On fMRI, methylphenidate activated, versus placebo, the anterior cingulate cortex, right inferior frontal, left middle frontal, left angular and right superior temporal gyri and right caudate. Atomoxetine activated a broad network of cortical regions. Both methylphenidate and atomoxetine, but not citalopram, activated superior temporal, right inferior frontal and left middle frontal clusters. Citalopram only activated the left inferior occipital lobe. Taking each condition’s activations as functionally defined regions of interest, the specificity of no-go related activity was compared across the four conditions. Only methylphenidate demonstrated drug specific effects through increased activation of the anterior cingulate and decreased activation of the caudate. A direct comparison of methylphenidate and atomoxetine showed a similar recruitment in prefrontal regions but specific effects of methylphenidate in the anterior cingulate and caudate. This further supported the notion that dopaminergic processes were making a specific and dissociable contribution during response inhibition. In Chapter 3 the pharmacoimaging correlates of error awareness were examined using the EAT. This study examined the fMRI data obtained whilst testing the cohort described in Chapter 2. Methylphenidate, but not atomoxetine or citalopram, significantly improved error awareness behaviour during the EAT. Methylphenidate, versus the other drug conditions, was also associated with specific BOLD activation differences in the dorsal anterior cingulate cortex and inferior parietal lobe for errors made with versus without awareness. These findings suggested that dopaminergic, rather than noradrenergic or serotonergic, mechanisms might also be important during error awareness. Accordingly, the final experiment in this thesis sought to examine specific dopamine receptor mechanisms of executive control. In Chapter 4 the role of the D2 receptor during response inhibition and error awareness was explored. Twenty-five (25) males received acute doses of cabergoline (1.25mg) and placebo before undertaking the SST and EAT. During the SST cabergoline was able to selectively reduce stop signal reaction time without a concomitant effect on reaction time variability or overall response speed. Cabergoline was, however, unable to improve action restraint in the go no-go component of the EAT. This suggested a specific and dissociable role for the D2 receptor in the action cancellation but not action restraint, which was consistent with the findings of Chapters 1 and 2. Cabergoline was also able to enhance the conscious perception of errors during the EAT, suggesting D2 mechanisms during error awareness, which was supportive of the findings in Chapter 3. In summary, this series of experiments showed that dopaminergic, and potentially D2, mechanisms are specifically implicated in the neurobiology of human executive control. Further experiments with more specific D2 agents, combined imaging paradigms and refined task design would extend these findings.

BackgroundAltered brain activity that has been observed in attention deficit hyperactivity disorder (ADHD) while performing cognitive control tasks like the stop signal task (SST) has generally been interpreted as reflecting either weak (under-active) or compensatory (over-active) versions of the same functions as in healthy controls. If so, then regional activities that correlate with the efficiency of inhibitory control (i.e. stop signal reaction time, SSRT) in healthy subjects should also correlate with SSRT in ADHD. Here we test the alternate hypothesis that BOLD (blood-oxygen-level-dependent) differences might instead reflect the redirection of neural processing resources normally used for task-directed inhibitory control, towards actively managing symptomatic behaviour. If so, then activities that correlate with SSRT in TD should instead correlate with inattentive and hyperactive symptoms in ADHD.MethodsWe used fMRI (functional magnetic resonance imaging) in 14 typically developing (TD) and 14 ADHD adolescents performing the SST, and in a replication sample of 14 healthy adults. First, we identified significant group BOLD differences during all phases of activity in the SST (i.e. warning, response, reactive inhibition, error detection and post-error slowing). Next, we correlated these phases of activity with SSRT in TD and with SSRT, inattentive and hyperactive symptom scores in ADHD. We then identified whole brain significant correlations in regions of significant group difference in activity.ResultsOnly three regions of significant group difference were correlated with SSRT in TD and replication groups (left and right inferior frontal gyri (IFG) during error detection and hypothalamus during post-error slowing). Consistent with regions of altered activity managing symptomatic behaviour instead of task-directed behaviour, left IFG correlated with greater inattentive score, right IFG correlated with lower hyperactive score and hypothalamus correlated with greater inattentive score and oppositely correlated with SSRT compared to TD.ConclusionsStimuli that elicit task-directed integration of neural processing in healthy subjects instead appear to be directing integrated function towards managing symptomatic behaviour in ADHD. The ability of the current approach to determine whether altered neural activities reflect comparable functions in ADHD and control groups has broad implications for the development and monitoring of therapeutic interventions.

Inhibitory control is the ability to suppress inappropriate movements and unwanted actions, allowing to regulate impulses and responses. This ability can be measured via the Stop Signal Task, which provides a temporal index of response inhibition, namely the stop signal reaction time (SSRT). At the neural level, Transcranial Magnetic Stimulation (TMS) allows to investigate motor inhibition within the primary motor cortex (M1), such as the cortical silent period (CSP) which is an index of GABAB-mediated intracortical inhibition within M1. Although there is strong evidence that intracortical inhibition varies during action stopping, it is still not clear whether differences in the neurophysiological markers of intracortical inhibition contribute to behavioral differences in actual inhibitory capacities. Hence, here we explored the relationship between intracortical inhibition within M1 and behavioral response inhibition. GABABergic-mediated inhibition in M1 was determined by the duration of CSP, while behavioral inhibition was assessed by the SSRT. We found a significant positive correlation between CSP’s duration and SSRT, namely that individuals with greater levels of GABABergic-mediated inhibition seem to perform overall worse in inhibiting behavioral responses. These results support the assumption that individual differences in intracortical inhibition are mirrored by individual differences in action stopping abilities.

As part of the first randomized double-blind trial of deep brain stimulation (DBS) of the globus pallidus (GPi) in Tourette syndrome, we examined the effect of stimulation on response initiation and inhibition. A total of 14 patients with severe Tourette syndrome were recruited and tested on the stop signal task prior to and after GPi-DBS surgery and compared to eight age-matched healthy controls. Tics were significantly improved following GPi-DBS. The main measure of reactive inhibition, the stop signal reaction time did not change from before to after surgery and did not differ from that of healthy controls either before or after GPi-DBS surgery. This suggests that patients with Tourette syndrome have normal reactive inhibition which is not significantly altered by GPi-DBS.

Response inhibition is a critical cognitive ability underlying executive control over reactions to external cues, or inner requirements. Previous studies suggest that high arousal negative emotions (e.g., anger or fear) could impair response inhibition in implicit emotional stop signal tasks (eSSTs). However, studies exploring how low arousal negative emotions (e.g., sadness) influence response inhibition remain sparse. In the current study, 20 female college students performed an explicit eSST to explore the influence of sadness on response inhibition and its neural mechanism. Participants are instructed to press a button to sad or neutral facial stimuli while inhibiting their response during the presentation of a stop signal. Results showed that compared with neutral stimuli, sad stimuli were related to increased stop signal reaction time (SSRT) (i.e., worse response inhibition). Compared with neutral condition, higher activation during sad condition was found within the right superior frontal gyrus (SFG), right insula, right middle cingulate cortex (MCC), bilateral superior temporal gyrus (STG), left lingual gyrus, and right motor cortex. These findings indicated that sadness, like other negative emotions, may impair response inhibition in an explicit way and highlight the explicit eSST as a new paradigm to investigate the subtle interaction between negative emotion processing and cognitive control.