Disentangling common and specific neural subprocesses of response inhibition
Highlights
► A novel task disentangling three subcomponents of response inhibition is introduced. ► All subcomponents share a common fronto-parietal inhibition network. ► Mutual activation in the rIFC and the pre-SMA is present in all subcomponents. ► Interference inhibition is based on a fronto-parietal–pre-motor network. ► Action cancelation relies on the (indirect) prefrontal–striatal pathway.
Introduction
Response inhibition is the ability to suppress inadequate but inadvertently activated, prepotent or ongoing response tendencies (Barkley, 1997, Miyake et al., 2000, Nigg, 2000). In terms of reactive control, response inhibition addresses inhibition in response to external stimuli (for a review see Aron, 2011). Such inhibitory control is ubiquitous in our daily routines like stopping at a traffic light turning red despite being in a hurry. Therefore, it is fundamental to individual and social functioning (Evenden, 1999).
Recently, the need to precisely specify different components and underlying neural substrates of impulse control specifically response inhibition has been increasingly demanded (Aron, 2011, Dalley et al., 2011, Eagle et al., 2008, Nee et al., 2007, Schachar et al., 2007, Swick et al., 2011). Even if different tasks that tap into subprocesses of response inhibition may share common features, inhibition might be required at different time points in the programming and generation of the response output and rely on different neural substrates (Dalley et al., 2011, Nee et al., 2007, Schachar et al., 2007, Swick et al., 2011). At the same time, apparently closely related response inhibition tasks, e.g. Go/no-go- and the Stop-signal tasks, were shown to be modulated by different transmitter systems (Eagle et al. 2008) and, thereby, neurocognitively dissociable. A more precise delineation of common and specific neural subprocesses of response inhibition and related paradigms to capture such subprocesses thus is inevitable to provide a coherent framework to possibly identify disease-related endophenotypes.
A variety of paradigms have been employed to study response inhibition such as Stop-signal-, Go/no-go-, Continuous Performance-, Simon-, Antisaccade-, or Flanker-tasks, all requiring inhibitory control over prepotent response tendencies (Aron, 2011, Nee et al., 2007). Using functional magnetic resonance imaging (fMRI) during such tasks, several neural key regions associated with inhibitory processes have been revealed, especially the right inferior frontal cortex (rIFC), pre-supplementary motor area (pre-SMA), basal ganglia and subthalamic nucleus (STN) (e.g. Aron, 2011, Boehler et al., 2010, Chikazoe, 2010, Jahfari et al., 2011, Levy and Wagner, 2011, Swick et al., 2011).
Although inhibition in the above mentioned tasks is associated with largely overlapping activation patterns, recent research suggests that these patterns are not identical. A recent meta-analysis by Swick et al. (2011) revealed common activation in Go/no-go- and Stop-signal tasks mainly in the right anterior insula and the pre-supplemental motor area (pre-SMA). Inhibition in Stop-signal tasks was, however, more strongly associated with activation in the left anterior insula and the thalamus, while inhibition in Go/no-go tasks relied more on activation in the right middle frontal gyrus (MFG) and parietal regions. Studies employing separate Go/no-go- and Stop-signal tasks in the same subjects revealed common activation in bilateral IFC (McNab et al., 2008, Rubia et al., 2001), right MFG (McNab et al., 2008, Rubia et al., 2001, Zheng et al., 2008), pre-SMA and inferior parietal lobe (Rubia et al., 2001). Activation in the Go/no-go task compared to the Stop-signal task was more pronounced in the left MFG, pre-SMA, and inferior parietal regions while no increased activation was present during Stop-signal tasks (Rubia et al., 2001). Thus, findings regarding common and distinct neural correlates during Go/no-go- and Stop-signal tasks remain divergent.
Behavioral and imaging evidence suggests that inhibition during Simon- and Stop-signal tasks relies on similar mechanisms with common neural correlates (Nee et al., 2007, Verbruggen et al., 2005). Comparing inhibition in the Simon task, which involves a stimulus–response conflict, to tasks involving a stimulus–stimulus conflict (e.g. Stroop task) revealed increased activation mainly in pre-motor, thus more response related regions (Egner et al., 2007, Liu et al., 2004, Wendelken et al., 2009). Other studies have linked parietal activation to both, stimulus–response conflict (Frühholz et al., 2011, Wendelken et al., 2009) and to stimulus–stimulus conflict (Egner et al., 2007, Liu et al., 2004).
Taken together, recent research increasingly suggests that distinguishable components of response inhibition exist, which may be tapped by employing different paradigms (Band and van Boxtel, 1999, Dalley et al., 2011, Eagle et al., 2008, Nee et al., 2007, Schachar et al., 2007, Swick et al., 2011, Verbruggen and Logan, 2008). However, this has yet not been shown in direct comparison of three components within one paradigm. Thus, component-specific neural correlates remain largely unclear. To address this question and thereby meeting the increasing demand for a more precise delineation of mutual and specific neural subprocesses of response inhibition, we introduce a novel task, the Hybrid Response Inhibition (HRI) task, comprising features of Simon-, Go/no-go- and Stop-signal tasks. The Simon task is thought to involve a conflict of response selection by involuntarily co-activating response tendencies due to incongruent stimulus dimensions (‘interference inhibition’; Simon and Berbaum, 1990). The ability to withhold a motor response (‘action withholding’; cf. Schachar et al., 2007) is usually assessed using a Go/no-go task in which rare no-go-stimuli instead of frequent go-stimuli are presented requiring inhibition of a prepotent response tendency. In a Stop-signal task, in contrast, rare stop-signals occur at some delay after the go stimuli, thus requiring an inhibition of an already ongoing motor response (‘action cancelation’; cf. Schachar et al., 2007). By using identical visual stimulus material across conditions within one task, we compare conditions designed to distinguish between different subcomponents of response inhibition, enabling us to study functional and spatial segregation and specialization of underlying neural subprocesses of response inhibition. To assess the validity of the novel task, we additionally assessed interference inhibition, action withholding and action cancelation in separate, commonly employed versions of the Simon-, Go/no-go- and Stop-signal tasks in another sample of participants.
We hypothesized that the subcomponents of response inhibition, i.e. interference inhibition, action withholding and action cancelation share common neural pathways of response inhibition which should be observable as mutual activation in the same key regions of the neural inhibitory network. However, these subcomponents should differ in the extent to which they recruit individual regions of the neural inhibitory network. We further hypothesized based on previous findings that interference inhibition is associated more strongly with activation in pre-motor and parietal regions, action withholding with middle frontal gyrus and parietal regions, whereas action cancelation relies more strongly on bilateral prefrontal and striatal activation.
Section snippets
Participants
Twenty-one healthy subjects were assessed using the novel task (12 males, mean age = 24.24 ± 2.3 years). Twenty-four healthy subjects were assessed using the battery of three separate standard tasks (9 males, mean age = 27.42 ± 5.6 years). All subjects were right handed as determined by the Edinburgh Handedness Inventory (Oldfield, 1971) and had normal or corrected to normal vision. Subjects had no lifetime history of axis I or axis II disorders as thoroughly assessed by a trained psychologist using the
Behavioral performance
Table 1 summarizes behavioral data. Analysis of variance (ANOVA) revealed that in the HRI task, RTs were longer as in the Go/no-go task as were the interference effect and SSRT compared to the separate tasks. This might reflect a higher cognitive load in the HRI task, resulting from the requirements to maintain and apply a more complex set of task rules. However, subjects performed accurately in all tasks with low rates of omission errors in all tasks (< 1.5%), and inhibition scores
Discussion
This study sought to systematically assess functional specialization of the neural inhibitory network during distinguishable subcomponents of response inhibition, i.e. interference inhibition, action withholding, and action cancelation. Therefore, we developed a novel paradigm, the Hybrid Response Inhibition (HRI) task, allowing us to assess these subcomponents and their underlying neural subprocesses within the same individuals and the same task using identical stimulus material. The results
Acknowledgments
This work was supported by the Federal Ministry of Education and Research grant 01GW0730 (AV, CS, CK, KL and OT). We would like to thank the Freiburg Brain Imaging Center, especially Volkmar Glauche, for continuous support, Arian Mobascher for helpful comments on the manuscript, and Birthe Gerdes, Carlos Baldermann, Julian Geißhardt, Lena Schmüser, and Tanja Schmitt for assistance in data collection.
References (66)
From reactive to proactive and selective control: developing a richer model for stopping inappropriate responses
Biol. Psychiatry
(2011)- et al.
Inhibitory motor control in stop paradigms: review and reinterpretation of neural mechanisms
Acta Psychol.
(1999) - et al.
Pinning down response inhibition in the brain — conjunction analyses of the Stop-signal task
Neuroimage
(2010) - et al.
Neural correlates of reaching decisions in dorsal premotor cortex: specification of multiple direction choices and final selection of action
Neuron
(2005) - et al.
Impulsivity, compulsivity, and top–down cognitive control
Neuron
(2011) - et al.
Separate conflict-specific cognitive control mechanisms in the human brain
Neuroimage
(2007) - et al.
Conjunction revisited
Neuroimage
(2005) - et al.
Spatio-temporal brain dynamics in a combined stimulus–stimulus and stimulus–response conflict task
Neuroimage
(2011) - et al.
The dorsal medial frontal cortex is sensitive to time on task, not response conflict or error likelihood
Neuroimage
(2011) - et al.
The role of the right inferior frontal gyrus: inhibition and attentional control
Neuroimage
(2010)
Modulating oscillatory brain activity correlates of behavioral inhibition using transcranial direct current stimulation
Clin. Neurophysiol.
Anterior cingulate and prefrontal cortex activity in an FMRI study of trial-to-trial adjustments on the Simon task
Neuroimage
Common and distinct neural substrates of attentional control in an integrated Simon and spatial Stroop task as assessed by event-related fMRI
Neuroimage
Common and unique components of inhibition and working memory: an fMRI, within-subjects investigation
Neuropsychologia
The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: a latent variable analysis
Cognit. Psychol.
The assessment and analysis of handedness: the Edinburgh inventory
Neuropsychologia
Mapping motor inhibition: conjunctive brain activations across different versions of Go/no-go and stop tasks
Neuroimage
Right inferior prefrontal cortex mediates response inhibition while mesial prefrontal cortex is responsible for error detection
Neuroimage
Action sets and decisions in the medial frontal cortex
Trends Cogn. Sci.
Neural correlates of interference inhibition, action withholding and action cancelation in adult ADHD
Psychiatry Res.
Effect of conflicting cues on information processing: the ‘Stroop effect’ vs. the ‘Simon effect’
Acta Psychol.
Roles for the pre-supplementary motor area and the right inferior frontal gyrus in stopping action: Electrophysiological responses and functional and structural connectivity
Neuroimage
Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain
Neuroimage
Response inhibition in the stop-signal paradigm
Trends Cogn. Sci.
Effects of stimulus–stimulus compatibility and stimulus–response compatibility on response inhibition
Acta Psychol.
Cortical and subcortical contributions to stop signal response inhibition: role of the subthalamic nucleus
J. Neurosci.
Behavioral inhibition, sustained attention, and executive functions: constructing a unifying theory of ADHD
Psychol. Bull.
The role of stimulus salience and attentional capture across the neural hierarchy in a Stop-signal task
PLoS One
Conditional differences in mean reaction time explain effects of response congruency, but not accuracy, on posterior medial frontal cortex activity
Front. Hum. Neurosci.
Activation of the pre-supplementary motor area but not inferior prefrontal cortex in association with short stop signal reaction time — an intra-subject analysis
BMC Neurosci.
Executive ‘‘Brake Failure’’ following deactivation of human frontal lobe
J. Cogn. Neurosci.
Dissociable Mechanisms of Cognitive Control in Prefrontal and Premotor Cortex
J. Neurophysiol.
Dissociation of response inhibition and performance monitoring in the stop signal task using event-related fMRI
Hum. Brain Mapp.
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