Inhibition and generation of saccades: Rapid event-related fMRI of prosaccades, antisaccades, and nogo trials

“This is a quantitatively validated approach to estimating components within a trial (Ollinger, Corbetta, and Shulman 2001; Ollinger, Shulman, and Corbetta 2001; Goghari and MacDonald 2008), and it has been previously reported in the literature (Shulman et al. 1999; Corbetta et al. 2000; Wheeler et al. 2005; Brown et a…”

“…to FEF, increased saccade-related activity in SEF has been observed in a number of functional neuroimaging studies (e.g. Berman et al., 1999; Brown et al., 2006; DeSouza et al., 2003; Dyckman et al., 2007; Gagnon et al., 2002; Kimmig et al., 2001; Matsuda et al., 2004; McDowell et al.,…”

“, 2002], visual search and detection [Brown et al., 2006; Hufner et al., 2008; Patel and Sathian, 2000], and the maintenance of visual information in working memory [Owen, 2004; Suchan et al.”

“In particular, previous studies have indicated that saccadic eye-movements are controlled by a cortical network that includes FEF, SMA/ preSMA, (lateral) PPC and striatum (Pierrot-Deseilligny et al. 1995; Pierrot-Deseilligny et al. 2004; Brown et al. 2006; Ettinger et al. 2007).”

“…cortex, basal ganglia, superior colliculus, and thalamus, among others, as indicated by non-human primate electrophysiology (Munoz and Everling, 2004; Funahashi et al., 1993) and functional imaging work in human (Brown et al., 2006; Luna et al., 2001; Connolly et al., 2002; Ford et al., 2005).”

“Like the FEF, the ACC consistently shows greater activation for antisaccades vs. prosaccades in neuroimaging studies (e.g., Brown et al 2006; Doricchi et al 1997; Ford et al 2005; Manoach et al 2007; Matsuda et al 2004; Paus et al 1993).”

“The precuneus is involved in networks responsible for maintaining and updating visuospatial information in working memory, visual detection and attention, mental rotation and visual imagery [Brown et al., 2006; Cavanna and Trimble, 2006; Hufner et al., 2008; Owen, 2004; Suchan et al., 2006; Yeh et al., 2007].”

“…of voluntary saccadic eye movements as well as the processing of rewards are well-delineated (Apicella et al., 1991; Breiter et al., 2001; Brown et al., 2006; Delgado et al., 2000; Delgado et al., 2003; Elliott et al., 2003; Hikosaka & Watanabe, 2000; Knutson et al., 2000; Luna &…”

“(2006) concluded that the activation observed during antisaccades may thus not be uniquely attributed to simply triggering a saccade but might reflect visual attention and visuospatial remapping of the target into an oculomotor response (Brown et al. 2006).”

“For instance, both anti-saccade and ‘no-go’ activated these brain regions to a greater extent then pro-saccade in an oculomotor countermanding task (”

“Both FEF and the posterior IPS have been associated with spatial attention, spatial working memory and spatial updating across saccadic eye movement”

“For details of the mixed-effects analysis, see APPENDIX B of Brown et al. (2006) and Worsley et al. (2002).”

“Event-related fMRI studies report that AS performance elicits activation in these brain regions (Connolly et al., 2000; Polli et al., 2005; Brown et al., 2006; Curtis and Connolly, 2008), and, in the present study, recruitment of analogous regions was readily evident across age groups (Velanova et al.”

“Higher field strengths may be required to detect more robust activation in both individual and group-wise results for the contrast between antisaccades and prosaccades, as is observed in other studies (Brown et al., 2006; Connolly et al., 2002; Curtis and D’Esposito, 2003; Desouza et al., 2003; Ford et al., 2005).”

“The dorsal anterior cingulate and the dorsolateral prefrontal cortex were active during this BOLD contrast, suggesting their involvement in saccade inhibition (Brown et al. 2006; Curtis et al. 2005).”

“2003, 2005a; b; Brown et al., 2004, 2006; Prado et al., 2005; Fernandez-Ruiz et al., 2007; Beurze et al., 2009; Cavina-Pratesi et al., 2010; Fabbri et al., 2012; Konen et al., 2013).”

“The SEF also shows increased fMRI activity for antisaccade versus prosaccade trials in this and other studies (Brown et al., 2006).”

“The ACC shows increased activation during prosaccades compared to fixation (Brown et al., 2006), greater activation for antisaccades than prosaccades (e.g., Brown et al., 2006; Doricchi et al., 1997; Ford et al., 2005; Manoach et al., 2007; Paus et al., 1993), and reduced activity in association…”

“…parietal cortex, basal ganglia and thalamus (O’Driscoll et al., 1995; Kimmig et al., 2001; Connolly et al., 2002; Curtis & D’Esposito, 2003; DeSouza et al., 2003; Matsuda et al., 2004; Ford et al., 2005; Miller et al., 2005; Polli et al., 2005; Brown et al., 2006, 2007; Cameron et al., 2009).”

“3A) in order to identify regions previously shown with fMRI to display greater activation for antisaccades compared to prosaccades: DLPFC, FEF, SEF, PEF and caudate nucleus (CN) (Brown et al., 2006; Connolly et al., 2002, 2005; Curtis and D'Esposito, 2003; DeSouza et al., 2003; Luna et al., 1998; Luna et al., 1998; Sw…”

“There is some inconsistency; however, whether frontal eye fields (FEF) or intraparietal sulcus (IPS) is more active during anti-saccades compared with prosaccades (Connolly et al., 2002; Cornelissen et al., 2002; Curtis et al., 2004; Brown et al., 2006; Ettinger et al., 2008).”

“When the pro- and antisaccade paradigms are interleaved, CN activation is stronger for antisaccades than prosaccades in normal subjects (Sweeney et al., 1996; Brown et al., 2006; Dyckman et al., 2007; Ettinger et al., 2008; Cameron et al., 2009).”

“Human imaging studies on the cancellation of preplanned motor responses confirm a contribution of parietal and premotor cortex to response inhibition (Garavan et al., 1999; Watanabe et al., 2002; Curtis et al., 2005; Brown et al., 2006; Cavina-Pratesi et al., 2006).”

“The higher degree of difficulty of antisaccades has been documented in the fMRI literature as evidence of hyperactivation in NV studies.(7) The presence of increased activation at 30 days postinjury in the visual cortices may point to an inefficiency, and hence increased effort, to resolve directional selectivity.”

“Alternatively, the selection process could reflect motor inhibition of the alternative effectors (Brown et al., 2006).”

“Some of these regions (SMG, DLPFC) probably take a key position in inhibitory phase of antisaccade tasks [4, 15, 33].”

“…with pro-saccade trials (Everling and Munoz, 2000) while BOLD fMRI in humans has shown increased activation in the FEF for anti-saccade trials (Brown et al., 2006, 2007; Connolly et al., 2000, 2002, 2005; Curtis and D'Esposito, 2003; Desouza et al., 2003; Ford et al., 2005; Kimmig et al.,…”

“…on previous functional imaging studies that showed consistent activation in these areas during prosaccade and antisaccade execution and preparation (Brown et al., 2006; Cameron et al., 2012; Connolly et al., 2005; DeSouza et al., 2003; Ford et al., 2006; Hakvoort Schwerdtfeger et al., 2013;…”

“…in these areas during prosaccade and antisaccade execution and preparation (Luna et al., 1998; DeSouza et al., 2003; Connolly et al., 2005; Ford et al., 2005; Brown et al., 2006, 2007; Raemaekers et al., 2007; Cameron et al., 2012; Hakvoort Schwerdtfeger et al., 2012; Jamadar et al., 2013).”

“…findings in the ACC, an area that has been shown consistently to be involved in monitoring antisaccade performance (Polli et al., 2005) and signaling the likelihood and actual occurrence of antisaccade errors (Nieuwenhuis et al., 2001; Ford et al., 2005; Brown et al., 2006; Endrass et al., 2007).”

“FEF and SEF activity has also been found during antisaccade performance (e.g. Brown et al., 2006; O'Driscoll et al., 1995; Sweeney et al., 1996), and antisaccade deficits have been reported for patients with lesions to these areas (Guitton et al., 1985; Machado and Rafal, 2004a; Parton et al.,…”

“For details of how the mixed effects analysis works, see Appendix B of Brown et al. (2006) and Worsley et al. (2002).”

“3 Typically, interstimulus intervals are longer than the intervals that we employed here, although similarly short intervals have been used previously n event-related fMRI experiments (e.g., Brown et al., 2006; Rubia et al., 2005).”

“The right DLPFC and ACC, in addition to other regions, are commonly implicated in performing the AS task (Brown et al., 2006; Ettinger et al., 2008).”

“It is relatively well understood that the FEF is involved in both execution and inhibition of saccadic eye movements [Brown et al., 2006, 2008; Cornelissen et al., 2002; Curtis et al., 2005; Ettinger et al., 2008; Heinen, et al., 2006].”

“[23]: antisaccade cue> no-go cue, antisaccade cue> prosaccade cue, prosaccade cue> no-go cue, antisaccade response> no-go response, antisaccade response> prosaccade response, and prosaccade response> no-go response.”

“Concerning prosaccades, Brown et al. (2006) report that prosaccades and their no-go counterparts exhibit comparable activity in cortical saccade regions (e.g., frontal eye Welds, intraparietal sulcus) and suggest that such a result reXects the importance of high-level saccade networks for discriminating task-speciWc v…”

“…previous imaging studies have shown greater activation in the FEF for antisaccades relative to prosaccades (O’Driscoll et al., 1995; Sweeney et al., 1996; Curtis & D’Esposito, 2003; DeSouza et al., 2003; Connolly et al., 2005; Ford et al., 2005; Miller et al., 2005; Brown et al., 2006, 2007).”

“This finding is generally consistentwith previous PET and fMRI studies (Brown et al., 2006; DeSouza et al., 2003; Ettinger et al., 2008; Ford et al., 2005; O'Driscoll et al., 1995; Sweeney et al., 1996).”

“…is involved in the top-down biasing of the oculomotor system in the service of task goals (PierrotDeseilligny et al., 2003, 2004; Ford et al., 2005; Brown et al., 2006; Ettinger et al., 2008; Hwang et al., 2010) and the anterior cingulate is involved in signaling the requirement for increased…”

“respond to inhibition of saccadic eye movements in an oculomotor go/ nogo task (Brown et al., 2006; Brown et al., 2008; Ettinger et al., 2008).”

“Alternatively, some studies using pro- and anti- saccade tasks have observed that right IFG and/or MFG are activated during those tasks, suggesting that these regions are associated with inhibition of responses such as reflexive eye movements during the anti-saccade task (Aichert et al., 2012; Brown et al., 2006; for…”

“For completeness, we also implemented the reverse contrast (of no-go minus go trials), since saccade inhibition or cancellation on the no-go trials might arguably involve some additional neural processes (e.g. Pare and Hanes, 2003;Brown et al., 2006;Brown et al., 2008).”

“Fitting this design matrix to the resampled data automatically deconvolves the time series of each RS condition (Brown et al. 2006), without making any assumption about the shape of the activation profile, other than its length (15 s in this case).”

“The cortical network includes primary visual cortex, parietal eye fields, putatively located in medial intraparietal sulcus in humans, and supplementary and frontal eye fields (SEF and FEF; Clementz et al., 2001; Brown et al., 2006; Manoach et al., 2007; McDowell et al., 2008).”

“…underlying typical saccade production has been thoroughly described in humans using the blood oxygenation level-dependent (BOLD) signal in functional magnetic resonance imaging (fMRI; e.g., Brown et al. 2006; Curtis and Connolly 2008; Dyckman et al. 2007; Matsuda et al. 2004; Reuter et al. 2010).”

“cue are suppressed and directed towards the mirrored cue location in the opposite hemifield (Brown et al., 2006; Brown et al., 2007; Dyckman et al., 2007; Kimmig et al., 2001).”

“Other studies using fMRI showed a higher activity during antisaccade tasks than during prosaccade tasks, not only in the PPC, but also in the FEF [11–12].”

“The interaction also revealed a cluster in the left PCG, close to but inferior (z = 36, MNI) to previously reported FEF coordinates (zP 39, Talairach) (Brown et al., 2006; Desmurget et al., 2000; O’Driscoll et al., 2000).”

“In the antisaccade task, the IPS is thought to be involved in the process of vector inversion [Brown et al., 2006; Medendorp et al., 2005] that spatially transforms the target for the saccade from the visually presented stimulus location to the mirror opposite location [Domagalik et al., 2012;…”

“In a slightly different view Brown et al. (2006) proposed that both the insula and IFG are needed to keep attention captured while inhibiting any shift of attention towards the distracting location.”

“The overall very low error rate ( 2.6%, compare 10% in Brown et al., 2006) is also consistent with the paradigm being less demanding than other tasks.”

“However, an event-related fMRI study suggested that the stronger activation during anti-saccades might also reXect visuospatial remapping or increased attention levels (Brown et al. 2006).”

“…fields (FEFs) and intraparietal sulcus (IPS) are more selectively involved in the preparation and generation of voluntary antisaccades (Pierrot-Deseilligny et al. 2002; Connolly et al. 2002; Cornelissen et al. 2002; DeSouza et al. 2003; Ploner et al. 2005; Brown et al. 2006; Ettinger et al. 2008).”