Effects of unilateral deactivations of dorsolateral prefrontal cortex and anterior cingulate cortex on saccadic eye movements

Abstract

Koval MJ, Hutchison RM, Lomber SG, Everling S. Effects of unilateral deactivations of dorsolateral prefrontal cortex and anterior cingulate cortex on saccadic eye movements. J Neurophysiol 111: 787-803, 2014. First published November 27, 2013 doi:10.1152/jn.00626.2013.-The dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) have both been implicated in the cognitive control of saccadic eye movements by single neuron recording studies in nonhuman primates and functional imaging studies in humans, but their relative roles remain unclear. Here, we reversibly deactivated either dlPFC or ACC subregions in macaque monkeys while the animals performed randomly interleaved pro-and antisaccades. In addition, we explored the wholebrain functional connectivity of these two regions by applying a seed-based resting-state functional MRI analysis in a separate cohort of monkeys. We found that unilateral dlPFC deactivation had stronger behavioral effects on saccades than unilateral ACC deactivation, and that the dlPFC displayed stronger functional connectivity with frontoparietal areas than the ACC. We suggest that the dlPFC plays a more prominent role in the preparation of pro-and antisaccades than the ACC.saccades; monkeys; cortical cooling; functional connectivity RESEARCH OVER THE PAST 40 yr has demonstrated that a number of cortical areas participate in the generation of saccadic eye movements in primates. Of particular importance are the frontal eye field (FEF; Bruce et al. 1985), supplementary eye field (SEF; Schlag and Schlag-Rey 1987), and lateral intraparietal area (LIP; Shibutani et al. 1984), from which saccades can be directly evoked by electrical microstimulation. Two additional regions that are frequently activated in human functional neuroimaging studies lie in the dorsolateral prefrontal cortex (dlPFC), and the presupplementary motor area/anterior cingulate cortex (ACC). In monkeys, these areas correspond to the dlPFC in and around the principal sulcus (areas 46 and 9/46; Petrides and Pandya 1999), and the ACC in the rostral cingulate sulcus (area 24c;Picard and Strick 1996).Activations in the dlPFC and ACC are typically not seen in neuroimaging experiments when simple visually-guided saccades are compared with fixation (Luna et al. 1998;Sweeney et al. 1996), but instead when a more complex saccade task is compared with a simple saccade task (Brown et al. 2004; DeSouza et al. 2003;McDowell et al. 2008;Sweeney et al. 1996). A well-studied example is the comparison of the performance of antisaccades, which requires subjects to look away from a suddenly appearing stimulus (Hallett 1978;Munoz and Everling 2004), with the performance of prosaccades, which requires subjects simply to look toward the stimulus. Event-related functional magnetic resonance imaging (fMRI) studies using long instruction periods (DeSouza et al. 2003; Ford et al. 2005) or rapid designs with catch trials (Brown et al. 2007) have shown that the dlPFC and ACC are more active for anti-than prosaccades during the instruct...

Unilateral deactivation of macaque dorsolateral prefrontal cortex induces biases in stimulus selection

“…Interestingly, in that study, both selection biases and RT changes were less pro-nounced following lesions of the SEF, similar to the differences in magnitude of both RT and selection biases between the DPC and cPS loops we observed here. Although our laboratory has previously reported decreases in saccade peak velocity and increases in saccade duration during unilateral dorsolateral PFC deactivation (Koval et al 2014), these changes are generally small, and we do not believe they contributed to the selection biases we observed here, since they reflect changes in motor output occurring after the initial selection process.…”

Alterations in intrinsic fronto‐thalamo‐parietal connectivity are associated with cognitive control deficits in psychotic disorders

“…The DLPFC has been frequently implicated in antisaccade execution although its specific role is still not fully understood (Johnston, Koval, Lomber, & Everling, 2014; Sweeney et al, 1996). It shows strong functional connectivity within the fronto-parietal network in resting state studies (Koval, Hutchison, Lomber, & Everling, 2014) projecting directly and indirectly to SC to mediate top-down resting and excitatory control over SC neurons (Johnston et al, 2014). Others have shown that components of the default mode network including the middle temporal gyrus and the inferior parietal cortex, as well as the parahippocampus, are also involved in active antisaccade generation (Domagalik et al, 2012; Talanow et al, 2016).…”

Isoflurane induces dose-dependent alterations in the cortical connectivity profiles and dynamic properties of the brain's functional architecture

“…5, Column 1]. A custom seed drawn to encompass the posterior end of the principal sulcus including area 46 and parts of 9/46 of the dorsal lateral PFC [Koval et al, 2014] showed a network of regions that resemble the macaque default-mode network [Hutchison and Everling, 2012;Hutchison et al, 2011;Mantini et al, 2011;Fig. 5, Column 2].…”