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

“These results suggest that the function of the IFC may extend beyond signal monitoring and mediate other aspects of attention function such as detection of behaviorally relevant, salient stimuli (Corbetta and Shulman, 2002; Yamasaki et al., 2002).”

“Activation in the anterior cingulate did not correlate with SSRT, EM effect, or frustrating rating, suggesting that this brain region probably plays a more complicated role that would require additional studies to understand (Bush et al., 2000; Rushworth et al., 2004).”

“With the staircase procedure, a “critical” SSD could be computed that represented the time delay required for the subject to succeed in withholding a response in the stop trials half of the time (Levitt, 1970).”

“05, corrected for false discovery rate (FDR) (Genovese et al., 2002) and an extent threshold of 10 voxels, successful inhibition was associated with greater bihemispheric activation of multiple cortical areas (Fig.”

“One would thus expect the anterior cingulate cortex to participate in a wide variety of cognitive and affective tasks in which inhibitory control assumes an integral position (Schall et al., 2002; Phillips et al., 2003; Dalley et al., 2004; Isomura and Takada, 2004; Nieuwenhuis et al., 2004; Ridderinkhof et al., 2004;…”

“One would thus expect the anterior cingulate cortex to participate in a wide variety of cognitive and affective tasks in which inhibitory control assumes an integral position (Schall et al., 2002; Phillips et al., 2003; Dalley et al., 2004; Isomura and Takada, 2004; Nieuwenhuis et al., 2004; Ridderinkhof et al., 2004;…”

“But perhaps most relevant to the current study is the hypothesis that the IFC mediates outcome monitoring of behavior (Kringelbach and Rolls, 2004).”

“Although signal monitoring can explain the activation of the IFC in these previous neuroimaging studies and the work of Aron et al. (2003) found that patients with right inferior frontal lesions were impaired in stop-signal inhibitions, a general attention mechanism could also be at play in causing…”

“One would thus expect the anterior cingulate cortex to participate in a wide variety of cognitive and affective tasks in which inhibitory control assumes an integral position (Schall et al., 2002; Phillips et al., 2003; Dalley et al., 2004; Isomura and Takada, 2004; Nieuwenhuis et al., 2004; Ridderinkhof et al., 2004;…”

“However, the exact locale of the activated IFC area varied from one study to another (Konishi et al., 1998, 1999; Garavan et al., 1999, 2001; Rubia et al., 2001, 2003, 2005; Watanabe et al., 2002; Fassbender et al., 2004), including activation of the left IFC in some studies (Rubia et al., 2001,…”

“One would thus expect the anterior cingulate cortex to participate in a wide variety of cognitive and affective tasks in which inhibitory control assumes an integral position (Schall et al., 2002; Phillips et al., 2003; Dalley et al., 2004; Isomura and Takada, 2004; Nieuwenhuis et al., 2004; Ridderinkhof et al., 2004;…”

“Conversion of the MNI to the Talairach coordinates (Talairach and Tournoux, 1988) was accomplished using a linear algorithm (Brett et al., 2002a) (http://www.mrc-cbu.cam.ac.uk/Imaging/Common/mnispace.shtml), and Brodmann’s areas (BA) were identified using the Talairach Daemon (Lancaster et al.,…”

“Activation in the anterior cingulate did not correlate with SSRT, EM effect, or frustrating rating, suggesting that this brain region probably plays a more complicated role that would require additional studies to understand (Bush et al., 2000; Rushworth et al., 2004).”

“However, the exact locale of the activated IFC area varied from one study to another (Konishi et al., 1998, 1999; Garavan et al., 1999, 2001; Rubia et al., 2001, 2003, 2005; Watanabe et al., 2002; Fassbender et al., 2004), including activation of the left IFC in some studies (Rubia et al., 2001,…”

“These findings speak broadly to a role of the frontal cortex in the temporal organization of motor sets and inhibitions (Fuster, 2002).”

“However, the exact locale of the activated IFC area varied from one study to another (Konishi et al., 1998, 1999; Garavan et al., 1999, 2001; Rubia et al., 2001, 2003, 2005; Watanabe et al., 2002; Fassbender et al., 2004), including activation of the left IFC in some studies (Rubia et al., 2001,…”

“However, the exact locale of the activated IFC area varied from one study to another (Konishi et al., 1998, 1999; Garavan et al., 1999, 2001; Rubia et al., 2001, 2003, 2005; Watanabe et al., 2002; Fassbender et al., 2004), including activation of the left IFC in some studies (Rubia et al., 2001,…”

“Lesions of the IFC could thus result in indiscriminating responses to unexpected sudden onsets that mimic behavioral perseveration, as demonstrated by these monkeys in the go/nogo task (Iversen and Mishkin, 1970).”

“Previous imaging studies have shown that attention modulates visual cortical activation and allocation of attention to central vision can lead to concurrent deactivation of peripheral visual cortices (Brefczynski and DeYoe, 1999; Smith et al., 2000; Slotnick et al., 2003).”

“Previous studies have shown that patients with a variety of psychiatric and neurological conditions, including attention deficit hyperactivity disorder, have impaired response inhibition during such tasks (Aron and Poldrack, 2005).”

“…to participate in a wide variety of cognitive and affective tasks in which inhibitory control assumes an integral position (Schall et al., 2002; Phillips et al., 2003; Dalley et al., 2004; Isomura and Takada, 2004; Nieuwenhuis et al., 2004; Ridderinkhof et al., 2004; Ochsner and Gross, 2005).”

“However, the exact locale of the activated IFC area varied from one study to another (Konishi et al., 1998, 1999; Garavan et al., 1999, 2001; Rubia et al., 2001, 2003, 2005; Watanabe et al., 2002; Fassbender et al., 2004), including activation of the left IFC in some studies (Rubia et al., 2001,…”

“These results suggest that the function of the IFC may extend beyond signal monitoring and mediate other aspects of attention function such as detection of behaviorally relevant, salient stimuli (Corbetta and Shulman, 2002; Yamasaki et al., 2002).”

“Related to this hypothesis, a recent fMRI study showed greater activation in the IFC when subjects had to select an externally guided response and monitor its outcome compared with when they selected an instructed response and had already known the outcome of their selection (Walton et al., 2004).”

“However, the exact locale of the activated IFC area varied from one study to another (Konishi et al., 1998, 1999; Garavan et al., 1999, 2001; Rubia et al., 2001, 2003, 2005; Watanabe et al., 2002; Fassbender et al., 2004), including activation of the left IFC in some studies (Rubia et al., 2001,…”

“…to another (Konishi et al., 1998, 1999; Garavan et al., 1999, 2001; Rubia et al., 2001, 2003, 2005; Watanabe et al., 2002; Fassbender et al., 2004), including activation of the left IFC in some studies (Rubia et al., 2001, 2005; Durston et al., 2002; Watanabe et al., 2002; Fassbender et al., 2004).”

“Pre-SMA decreased activity concurrent with activation of the primary motor cortex before voluntary movements (Ball et al., 1999).”

“Indeed, the IFC has been implicated in affective processing (Fulbright et al., 2001; Nomura et al., 2003; Hennenlotter et al., 2005; Kuchinke et al., 2005; Wood et al., 2005).”

“Moreover, a recent study using an oculomotor paradigm found greater activation in the rostral pre-SMA in trials requiring a change in motor plan compared with those trials not requiring such a change (Nachev et al., 2005).”

“…cingulate cortex to participate in a wide variety of cognitive and affective tasks in which inhibitory control assumes an integral position (Schall et al., 2002; Phillips et al., 2003; Dalley et al., 2004; Isomura and Takada, 2004; Nieuwenhuis et al., 2004; Ridderinkhof et al., 2004;…”

“Electrophysiological studies in awake monkeys and humans have long shown neural activities in the medial frontal and premotor cortices during changes in motor plans and execution of movement sequences (Amador and Fried, 2004; Leuthold and Jentzsch, 2002; Shima et al., 1996; Wise and Mauritz, 1985).”

“Indeed, the IFC has been implicated in affective processing (Fulbright et al., 2001; Nomura et al., 2003; Hennenlotter et al., 2005; Kuchinke et al., 2005; Wood et al., 2005).”

“Previous imaging studies have shown that attention modulates visual cortical activation and allocation of attention to central vision can lead to concurrent deactivation of peripheral visual cortices (Brefczynski and DeYoe, 1999; Smith et al., 2000; Slotnick et al., 2003).”

“Previous imaging studies have shown that attention modulates visual cortical activation and allocation of attention to central vision can lead to concurrent deactivation of peripheral visual cortices (Brefczynski and DeYoe, 1999; Smith et al., 2000; Slotnick et al., 2003).”

“Consistent with the current results, a previous imaging study implicated pre-SMA in mediating the motor inhibition required for voluntary muscle relaxation (Toma et al., 1999).”

“These “negative motor areas,” including a medial frontal region that has been identified as a presupplementary motor area (pre-SMA) and a lateral frontal region located anterior to the face motor cortex, appeared to correspond to the IMA identified in the current study (Ikeda et al., 2000; Yazawa et al., 2000).”

“The middle/inferior frontal cortices have also been implicated in EM and feedback processing (O’Doherty et al., 2001; Jimura et al., 2004; Kemmotsu et al., 2005; Paulus et al., 2005).”

“Indeed, the IFC has been implicated in affective processing (Fulbright et al., 2001; Nomura et al., 2003; Hennenlotter et al., 2005; Kuchinke et al., 2005; Wood et al., 2005).”

“…motor areas,” including a medial frontal region that has been identified as a presupplementary motor area (pre-SMA) and a lateral frontal region located anterior to the face motor cortex, appeared to correspond to the IMA identified in the current study (Ikeda et al., 2000; Yazawa et al., 2000).”

“Indeed, the IFC has been implicated in affective processing (Fulbright et al., 2001; Nomura et al., 2003; Hennenlotter et al., 2005; Kuchinke et al., 2005; Wood et al., 2005).”

“The middle/inferior frontal cortices have also been implicated in EM and feedback processing (O’Doherty et al., 2001; Jimura et al., 2004; Kemmotsu et al., 2005; Paulus et al., 2005).”

“Electrophysiological studies in awake monkeys and humans have long shown neural activities in the medial frontal and premotor cortices during changes in motor plans and execution of movement sequences (Amador and Fried, 2004; Leuthold and Jentzsch, 2002; Shima et al., 1996; Wise and Mauritz, 1985).”

“One would thus expect the anterior cingulate cortex to participate in a wide variety of cognitive and affective tasks in which inhibitory control assumes an integral position (Schall et al., 2002; Phillips et al., 2003; Dalley et al., 2004; Isomura and Takada, 2004; Nieuwenhuis et al., 2004; Ridderinkhof et al., 2004;…”

“Indeed, the IFC has been implicated in affective processing (Fulbright et al., 2001; Nomura et al., 2003; Hennenlotter et al., 2005; Kuchinke et al., 2005; Wood et al., 2005).”

“The middle/inferior frontal cortices have also been implicated in EM and feedback processing (O’Doherty et al., 2001; Jimura et al., 2004; Kemmotsu et al., 2005; Paulus et al., 2005).”

“Electrophysiological studies in awake monkeys and humans have long shown neural activities in the medial frontal and premotor cortices during changes in motor plans and execution of movement sequences (Amador and Fried, 2004; Leuthold and Jentzsch, 2002; Shima et al., 1996; Wise and Mauritz, 1985).”

“Both change-of-plan and stop tasks for hand and eye movements have demonstrated pre-SMA and/or SEF activity that is related specifically to altering movement plan”

“In particular, suppression produced significant responses in areas of right ventrolateral PFC previously related to inhibitory motor control (24-31).”

“, 2007), increased stop signal reaction time on the Stop Signal task (Fillmore and Rush, 2002; Li et al., 2006), and increased interference scores on the Stroop (Bolla et al.”

“Event-related fMRI studies showed that (mainly) parietal and frontal brain regions are more activated when inhibition is unsuccessful [15,16,18,19].”

“A recent fMRI study associated greater activation in left superior frontal gyrus (BA 8) with more efficient response inhibition [58].”

“Other reported contrasts have included Successful Stop vs. Unsuccessful Stop trials (Li et al., 2006b; Padmala and Pessoa, 2010), groups of subjects with a short vs. long stop signal RT (Li et al., 2006a,b), and hard vs. easy to inhibit trials (Matthews et al., 2005).”

“fMRI studies of stop-signal tasks reveal inhibitory-associated activation in the pre-SMA (Aron & Poldrack, 2006; Ramataur, Slagter, Kok, & Ridderinkhof, 2006; Rubia, Russell, et al., 2001), and one study demonstrated that individuals with better inhibitory performance activated the pre-SMA to a greater degree than ind…”

“…(IFG) are critical regions for stopping (Aron et al., 2003; Chambers et al., 2006, 2007; Floden and Stuss, 2006; Chen et al., 2008), and functional MRI affirms this (Rubia et al., 2003; Aron and Poldrack, 2006; Li et al., 2006; Aron et al., 2007; Chevrier et al., 2007; Chamberlain et al., 2008).”

“We used a simple reaction time (RT) task in this stop signal paradigm (Logan and Cowan, 1984; Li et al., 2006a, 2008a,b).”

“does lesion overlap in patients with Broca’s aphasia indicates the cerebral source for fluency or syntax? As pointed out by Rorden and Karnath (2004), another problem is that the overlap is confounded by how often different regions of the brain are Figure 1.”

“detected that both simple and complex GO/NOGO tasks were involved in the SMA and they revealed the important role of the SMA in mediating cognitive control [46,60].”

“Prior neuropsychology (Aron et al., 2003) and neuroimaging (Rubia et al., 2001; Aron and Poldrack, 2006; Li et al., 2006a; Leung and Cai, 2007) studies have revealed the neural basis of this function in brain regions including the inferior frontal gyrus (IFG), dorsolateral prefrontal cortex…”

“19,20,115 Based on the postulated model it can be expected that improvement of dACC functioning, either through direct neuromodulation or indirect behavioural therapies would result in increased control over addictive behaviours.”

“Recent evidence from human functional imaging studies shows that medial frontal areas are selectively activated when responses to external stimuli must be inhibited in stop-signal reaction-time tasks (Li et al., 2006).”

“Isolating the neural correlates of response inhibition during the SST Previous neuroimaging studies employing the SST have examined the cortical processes of response inhibition (Aron and Poldrack, 2006; Li et al., 2006a; Liddle et al., 2001; Rubia et al., 2003, 2005).”

“…PFC (Chambers et al., 2009; Leung and Cai, 2007; Swann et al., 2009), presupplementary motor areas (Chen et al., 2009; Floden and Stuss, 2006; Li et al., 2006), as well as posterior parietal cortices, subthalamic nuclei, and cerebellar regions (see Chambers et al., 2009; Chikazoe, 2010 for…”

“Cerebral Cortex January 2009;19:146--152 doi:10.1093/cercor/bhn065 Advance Access publication April 28, 2008”

“org as supplemental material) as well as in many previous experiments (Durston et al., 2002; Wager et al., 2005; Aron and Poldrack, 2006; Li et al., 2006; Aron et al., 2007; Boehler et al., 2008; Braet et al., 2009).”

“…(Kawashima et al. 1996; Garavan et al. 1999; Konishi et al. 1999; Menon et al. 2001; Rubia et al. 2001; Aron et al. 2003; Kelly et al. 2004; Aron and Poldrack 2006; Li et al. 2006; Hodgson et al. 2007; Leung and Cai 2007), suggesting that this region plays a specialized role in response inhibition.”

“Other studies on this same cohort of subjects indicate the important modulatory effect of personality traits and the synergistic effect of multiple substance use on stress-related brain activation (Li et al., 2005c; Li et al., 2006b; Li and Sinha, 2006).”

“Modulation of neural activity using tDCS Although elevated SSRTs and increased error rates were observed as a consequence of TMS stimulation of Pre-SMA, it is unclear whether the underlying neurons were facilitated or inhibited by TMS (Chen et al., 2009).”

“Neural correlates of more circumscribed measures of impulsivity overlap only partially with those of ADHD, and effect sizes linking such measures to neurobiological function tend to be smaller (e.g., Aron & Poldrack 2006, C.R. Li et al. 2006).”

“By contrasting stop and go trials or stop success and error trials, previous studies have implicated a wide array of cortical and subcortical regions in mediating intersubject variation in the SSRT (Li et al., 2006; Li et al., 2008c; Chao et al., 2009; Duann et al., 2009; Zhang et al., 2015), highlighting a role of re…”

“…correlated with neurophysiological variables such as anterior cingulate activity (Danielmeier, Eichele, Forstmann, Tittgemeyer, & Ullsperger, 2011; Li, Huang, Constable, & Sinha, 2006), error-related negativity (ERN) and positivity (Pe; Hajcak, McDonald, & Simons, 2003b), and cortisol levels…”

“This is not to say that the rIFG is exclusively involved in response inhibition; it is part of a wider network of regions, for example, ACC (Garavan, Ross, Murphy, Roche, & Stein, 2002; Kiehl et al., 2000), and other cortical as well as subcortical regions (Aron & Poldrack, 2006; Li et al., 2006).”

“…study found such correlations in the right IFG and STN (Aron and Poldrack, 2006), another in superior frontal cortex and the left pre-central gyrus (Li et al., 2006, 2008), and a study investigating development of inhibitory function across different ages found a relationship between SSRT and…”

“…of an anterior preSMA region (x = –4, y = 36, z = 56) in individuals with better inhibitory control as indexed by shorter stop signal reaction time (Li et al. 2006; Duann et al. 2009) and activation of a caudal locale (x = –4, y = 16, z = 44 and x = 4, y = 8, z = 54) during error processing in…”

“Some authors have, thus, argued that the pre-SMA rather than the rIFC might be critical for response inhibition (Chao et al., 2009; Duann et al., 2009; Floden and Stuss, 2006; Li et al., 2006; Sharp et al., 2010).”

“Forty healthy adults (20 males, 22–42 years of age, all righthanded and using their right hand to respond, including the 24 subjects we reported in Li et al., 2006) were paid to participate in the study.”

“…a median split for all of the behavioral parameters [GO%, SS%, median GO RT, stop signal RT (SSRT), posterror slowing, and FP effect] as in a previous study [Li et al., 2006] and did not observe any significant differences in any of the beta weights of the six components (all Ps >0.1, uncorrected).”

“Both of these measures are indices of inhibitory control, and so the results are related to a pattern of disruption consistent with the findings of Li et al. (2006b).”

“This hypothesis is in good agreement with neuroimaging studies that demonstrate robust activation of the medial frontal cortex, in particular of the pre-SMA, SMA, supplementary eye field, and anterior cingulate cortex in the countermanding paradigm (Curtis et al., 2005; Aron and Poldrack, 2006; Li et al., 2006; Aron e…”

“This view is in line with our assumption that the SECPT affected primarily participants’ ability to inhibit learned responses since the PFC is also of central importance for cognitive control and response inhibition (Aron et al., 2004; Li et al., 2006).”

“, 2006), fMRI data showed that VLPFC in both hemispheres as well as other frontal and parietal regions are involved in inhibition of manual responses (Garavan et al., 1999, Rubia et al., 2003; Li et al., 2006).”

“Also of note is that this area of SMAdid not overlap amore anterior region,which we labeled as anterior pre-SMA (MNI coordinate: x=−4; y=36; z=56) that our previous studies showed to mediate response inhibition in the stop signal task (Li et al., 2006, 2008a; Chao et al., 2009).”

“The Figure 2 (a) The dorsal medial frontal cortex (dmFC) as an ROI (Talairach coordinate: x¼ 4, y¼ 32, z¼ 51; Li et al, 2006a).”

“…relation between activation and stopping ability) have been observed in a number of regions including the right IFC and right STN (Aron and Poldrack, 2006), the left superior frontal gyrus (SFG) and left precentral gyrus (Li et al., 2006), as well as the pre-SMA and caudate (Li et al., 2008).”

“Functional imaging studies indicate that the right inferior frontal cortex is active during successful response inhibition, with increased activation associated with faster stop-signal reaction times (87).”

“The joint results of these studies might indicate hat inferior frontal gyrus/ventrolateral prefrontal cortex activation ound during response inhibition tasks is associated to affective rocesses rather than response inhibition per se (for a similar sugestion, see Li et al., 2006).”

“D 2008 Massachusetts Institute of Technology Journal of Cognitive Neuroscience 20:6, pp. 1021–1029 ( Li, Huang, Constable, & Sinha, 2006; Li, Milivojevic, Kemp, Hong, & Sinha, 2006; Aron & Poldrack, 2005; Liotti, Pliszka, Perez, Kothmann, & Woldorff, 2005; Schachar et al., 2004; Logan & Cowan, 1984).,D 2008 Massachuse…”

“Publish : +81 75 751 3202. a). regions, especially the pre-supplementary motor area (pre-SMA) (Floden and Stuss, 2006; Li et al., 2006; Mostofsky and Schafer, 2003 Suskauer et al., 2008) in voluntary suppression.”

“, 2008), and studies linking inter-individual differences in SSRT and fMRI activation levels (Congdon et al., 2010; Li et al., 2006) also endorse the idea that frontal regions in both the left and right hemisphere are critical for successful inhibitory control.”

“The present study used a modified version of the stopsignal task described by Li et al. (2006).”

“Results are presented in Figure 1A.”

“Given recent studies showing gender diVerences for EBR and for SSRT (Dreisbach et al. 2005; Li et al. 2006; Müller et al. 2007; Mulvihill et al. 1997), independent samples t tests were performed for analysis of EBR and SSRT diVerences between men and women.”

“Also in this case, effect sizes were determined by using the ƞ2p method.”

“1) based on the work of Li et al. (2006, 2008, 2009).”

“We employed a simple reaction time task in this stop-signal paradigm [9,13] (Figure 1).”

“Our observation that estrogen modulates inhibitory control may explain why Li et al. (2006) found gender differences in a stop-signal task with respect to some but not other measures.”

“For impulsive action, existing studies have implicated distributed cortical and subcortical areas for response inhibition, including the right inferior frontal gyrus (IFG) and adjacent anterior insula (AI), anterior cingulate cortex (ACC), pre-SMA, and striatum (Aron et al., 2007b; Aron and Poldrack, 2005; Aron et al.…”

“It has been shown that medial frontal cortices are implicated in proactive control mechanisms (Brown and Braver 2005; Li et al. 2006; Forstmann et al. 2008; Chen et al. 2010; Domenech and Dreher 2010) and it is known that these regions project to the ventral portion of STN (Krack et al.”

“These studies have revealed a large fronto-parietal network involved in response inhibition, including middle, inferior, and superior frontal cortices, pre-supplementary motor areas, and anterior cingulate cortex (Zheng, Oka, Bokura, & Yamaguchi, 2008; Aron & Poldrack, 2006; Chambers et al., 2006; Li, Huang, Constable…”

“2013) as was faster reaction time (Li et al. 2006; Sakai et al. 2013).”

“While a range of studies on response inhibition point toward a single inhibitory module within the IFC that directly initiates stopping (Aron et al., 2003), other studies assign this role to pre-SMA (Li et al., 2006; Nachev et al., 2007).”

“Part of the right posterior IFG implements the control of response inhibition, which comprises cognitive and motor inhibition (Aron and Poldrack, 2006; Chambers et al., 2006; Li et al., 2006, 2008; Aron et al., 2014; Cai et al., 2014b).”

“Figure 4 (red and blue areas) shows that reactive inhibition elicited activation and deactivation in a widespread network of brain regions commonly reported in stop-signal tasks at baseline (Boehler et al., 2010; Zandbelt & Vink, 2010; Aron & Poldrack, 2006; Li et al., 2006), including activation in a mainly right-lat…”

“Li et al. (2006), however, found more superior frontal areas to be correlated with SSRT. Vink et al. (2005) manipulated the likelihood of having to inhibit a response quasi-parametrically by varying the number of go trials (2–6) that immediately preceded a stop trial.”