Neurophysiology and neuroanatomy of reflexive and volitional saccades: evidence from studies of humans

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually guided saccades (redirections of gaze to a visual stimulus or pro-saccades) and more complex volitional saccades require similar basic neural circuitry with additional neural regions supporting requisite higher level processes. The saccadic system has been studied extensively in non-human (e.g., single-unit recordings) and human (e.g., lesions and neuroimaging) primates. Considerable knowledge of this system’s functional neuroanatomy makes it useful for investigating models of cognitive control. The network involved in pro-saccade generation (by definition largely exogenously-driven) includes subcortical (striatum, thalamus, superior colliculus, and cerebellar vermis) and cortical (primary visual, extrastriate, and parietal cortices, and frontal and supplementary eye fields) structures. Activation in these regions is also observed during endogenously-driven voluntary saccades (e.g., anti-saccades, ocular motor delayed response or memory saccades, predictive tracking tasks and anticipatory saccades, and saccade sequencing), all of which require complex cognitive processes like inhibition and working memory. These additional requirements are supported by changes in neural activity in basic saccade circuitry and by recruitment of additional neural regions (such as prefrontal and anterior cingulate cortices). Activity in visual cortex is modulated as a function of task demands and may predict the type of saccade to be generated, perhaps via top-down control mechanisms. Neuroimaging studies suggest two foci of activation within FEF - medial and lateral - which may correspond to volitional and reflexive demands, respectively. Future research on saccade control could usefully (i) delineate important anatomical subdivisions that underlie functional differences, (ii) evaluate functional connectivity of anatomical regions supporting saccade generation using methods such as ICA and structural equation modeling, (iii) investigate how context affects behavior and brain activity, and (iv) use multi-modal neuroimaging to maximize spatial and temporal resolution.     

Neurophysiology and neuroanatomy of reflexive and volitional saccades: Evidence from studies of humans

This review provides a summary of the contributions made by human functional neuroimaging studies to the understanding of neural correlates of saccadic control. The generation of simple visually guided saccades (redirections of gaze to a visual stimulus or pro-saccades) and more complex volitional saccades require similar basic neural circuitry with additional neural regions supporting requisite higher level processes. The saccadic system has been studied extensively in non-human (e.g., single-unit recordings) and human (e.g., lesions and neuroimaging) primates. Considerable knowledge of this system’s functional neuroanatomy makes it useful for investigating models of cognitive control. The network involved in pro-saccade generation (by definition largely exogenously-driven) includes subcortical (striatum, thalamus, superior colliculus, and cerebellar vermis) and cortical (primary visual, extrastriate, and parietal cortices, and frontal and supplementary eye fields) structures. Activation in these regions is also observed during endogenously-driven voluntary saccades (e.g., anti-saccades, ocular motor delayed response or memory saccades, predictive tracking tasks and anticipatory saccades, and saccade sequencing), all of which require complex cognitive processes like inhibition and working memory. These additional requirements are supported by changes in neural activity in basic saccade circuitry and by recruitment of additional neural regions (such as prefrontal and anterior cingulate cortices). Activity in visual cortex is modulated as a function of task demands and may predict the type of saccade to be generated, perhaps via top-down control mechanisms. Neuroimaging studies suggest two foci of activation within FEF - medial and lateral - which may correspond to volitional and reflexive demands, respectively. Future research on saccade control could usefully (i) delineate important anatomical subdivisions that underlie functional differences, (ii) evaluate functional connectivity of anatomical regions supporting saccade generation using methods such as ICA and structural equation modeling, (iii) investigate how context affects behavior and brain activity, and (iv) use multi-modal neuroimaging to maximize spatial and temporal resolution.     

Self-bias modulates saccadic control

We present novel data on the role of attention in eliciting enhanced processing of stimuli associated with self. Participants were required to make pro- or anti-saccades according to whether learned shape–label pairings matched or mismatched. When stimuli matched participants were required to make an anti-saccade, and when the stimuli mismatched a pro-saccade was required. We found that anti-saccades were difficult to make to stimuli associated with self when compared to stimuli associated with a friend and a stranger. In contrast, anti-saccades to friend-stimuli were easier to make than anti-saccades to stranger-stimuli. In addition, a correct anti-saccade to a self-associated stimulus disrupted subsequent pro-saccade trials, relative to when the preceding anti-saccade was made to other stimuli. The data indicate that self-associated stimuli provide a strong cue for explicit shifts of attention to them, and that correct anti-saccades to such stimuli demand high levels of inhibition (which carries over to subsequent pro-saccade trials). The self exerts an automatic draw on attention.     

The effects of eye and limb movements on working memory

Three experiments examined the role of eye and limb movements in the maintenance of information in spatial working memory. In Experiment 1, reflexive saccades interfered with memory span for spatial locations but did not interfere with memory span for letters. In Experiment 2, three different types of eye movements (reflexive saccades, pro-saccades, and anti-saccades) interfered with working memory to the same extent. In all three cases, spatial working memory was much more affected than verbal working memory. The results of these two experiments suggest that eye movements interfere with spatial working memory primarily by disrupting processes localised in the visuospatial sketchpad. In Experiment 3, limb movements performed while maintaining fixation produced as much interference with spatial working memory as reflexive saccades. These results suggest that the interference produced by eye movements is not the result of their visual consequences. Rather, all spatially directed movements appear to have similar effects on visuospatial working memory.     

The control of stimulus-driven saccades is subject not to central, but to visual attention limitations

In three experiments, we investigated whether the control of reflexive saccades is subject to central attention limitations. In a dual-task procedure, Task 1 required either unspeeded reporting or ignoring of briefly presented masked stimuli, whereas Task 2 required a speeded saccade toward a visual target. The stimulus onset asynchrony (SOA) between the two tasks was varied. In Experiments 1 and 2, the Task 1 stimulus was one or three letters, and we asked how saccade target selection is influenced by the number of items. We found (1) longer saccade latencies at short than at long SOAs in the report condition, (2) a substantially larger latency increase for three letters than for one letter, and (3) a latency difference between SOAs in the ignore condition. Broadly, these results match the central interference theory. However, in Experiment 3, an auditory stimulus was used as the Task 1 stimulus, to test whether the interference effects in Experiments 1 and 2 were due to visual instead of central interference. Although there was a small saccade latency increase from short to long SOAs, this difference did not increase from the ignore to the report condition. To explain visual interference effects between letter encoding and stimulus-driven saccade control, we propose an extended theory of visual attention.     

Probing the attentional control theory in social anxiety: An emotional saccade task

Volitional attentional control has been found to rely on prefrontal neuronal circuits. According to the attentional control theory of anxiety, impairment in the volitional control of attention is a prominent feature in anxiety disorders. The present study investigated this assumption in socially anxious individuals using an emotional saccade task with facial expressions (happy, angry, fearful, sad, neutral). The gaze behavior of participants was recorded during the emotional saccade task, in which participants performed either pro- or antisaccades in response to peripherally presented facial expressions. The results show that socially anxious persons have difficulties in inhibiting themselves to reflexively attend to facial expressions: They made more erratic prosaccades to all facial expressions when an antisaccade was required. Thus, these findings indicate impaired attentional control in social anxiety. Overall, the present study shows a deficit of socially anxious individuals in attentional control—for example, in inhibiting the reflexive orienting to neutral as well as to emotional facial expressions. This result may be due to a dysfunction in the prefrontal areas being involved in attentional control.     

Looming Threats and Animacy: Reduced Responsiveness in Youth with Disrupted Behavior Disorders

Theoretical models have implicated amygdala dysfunction in the development of Disruptive Behavior Disorders (DBDs; Conduct Disorder/Oppositional Defiant Disorder). Amygdala dysfunction impacts valence evaluation/response selection and emotion attention in youth with DBDs, particularly in those with elevated callous-unemotional (CU) traits. However, amygdala responsiveness during social cognition and the responsiveness of the acute threat circuitry (amygdala/periaqueductal gray) in youth with DBDs have been less well-examined, particularly with reference to CU traits. 31 youth with DBDs and 27 typically developing youth (IQ, age and gender-matched) completed a threat paradigm during fMRI where animate and inanimate, threatening and neutral stimuli appeared to loom towards or recede from participants. Reduced responsiveness to threat variables, including visual threats and encroaching stimuli, was observed within acute threat circuitry and temporal, lateral frontal and parietal cortices in youth with DBDs. This reduced responsiveness, at least with respect to the looming variable, was modulated by CU traits. Reduced responsiveness to animacy information was also observed within temporal, lateral frontal and parietal cortices, but not within amygdala. Reduced responsiveness to animacy information as a function of CU traits was observed in PCC, though not within the amygdala. Reduced threat responsiveness may contribute to risk taking and impulsivity in youth with DBDs, particularly those with high levels of CU traits. Future work will need to examine the degree to which this reduced response to animacy is independent of amygdala dysfunction in youth with DBDs and what role PCC might play in the dysfunctional social cognition observed in youth with high levels of CU traits.     

Giving subjects the eye and showing them the finger: socio-biological cues and saccade generation in the anti-saccade task

Pointing with the eyes or the finger occurs frequently in social interaction to indicate direction of attention and one's intentions. Research with a voluntary saccade task (where saccade direction is instructed by the colour of a fixation point) suggested that gaze cues automatically activate the oculomotor system, but non-biological cues, like arrows, do not. However, other work has failed to support the claim that gaze cues are special. In the current research we introduced biological and non-biological cues into the anti-saccade task, using a range of stimulus onset asynchronies (SOAs). The anti-saccade task recruits both top-down and bottom-up attentional mechanisms, as occurs in naturalistic saccadic behaviour. In experiment 1 gaze, but not arrows, facilitated saccadic reaction times (SRTs) in the opposite direction to the cues over all SOAs, whereas in experiment 2 directional word cues had no effect on saccades. In experiment 3 finger pointing cues caused reduced SRTs in the opposite direction to the cues at short SOAs. These findings suggest that biological cues automatically recruit the oculomotor system whereas non-biological cues do not. Furthermore, the anti-saccade task set appears to facilitate saccadic responses in the opposite direction to the cues.     

Spider fearful individuals attend to threat, then quickly avoid it: evidence from eye movements

According to cognitive models of anxiety, anxiety patients exhibit an early reflexive attentional bias toward threat stimuli, which may be followed by intentional avoidance of these stimuli. To determine the time course of attentional vigilance and avoidance, the authors conducted an eye-tracking study in which 22 highly spider fearful participants (SFs) and 23 nonanxious control participants (NACs) studied groups of 4 pictures (spider, butterfly, dog, and cat). The authors found that the very first fixation was on a spider picture more often in SFs than in NACs. However, SFs quickly moved their eyes away from the spider they had fixated first, yielding shorter gaze durations than NACs. Afterward, SFs exhibited shorter gaze durations on spiders than NACs for the rest of the 1-min presentation time. This early reflexive attentional bias toward threat followed by avoidance of threat may explain earlier failures to find attentional biases in anxiety.     

Toward neuroanatomical models of analogy: a positron emission tomography study of analogical mapping

Several brain regions associated with analogical mapping were identified using (15)O-positron emission tomography with 12 normal, high intelligence adults. Each trial presented during scanning consisted of a source picture of colored geometric shapes, a brief delay, and a target picture of colored geometric shapes. Analogous pictures did not share similar geometric shapes but did share the same system of abstract visuospatial relations. Participants judged whether each source-target pairing was analogous (analogy condition) or identical (literal condition). The results of the analogy-literal comparison showed activation in the dorsomedial frontal cortex and in the left hemisphere; the inferior, middle, and medial frontal cortices; the parietal cortex; and the superior occipital cortex. Based on these results as well as evidence from relevant cognitive neuroscience studies of reasoning and of executive working memory, we hypothesize that analogical mapping is mediated by the left prefrontal and inferior parietal cortices.     

Frontal and parietal EEG asymmetries interact to predict attentional bias to threat

Frontal and parietal electroencephalographic (EEG) asymmetries mark vulnerability to depression and anxiety. Drawing on cognitive theories of vulnerability, we hypothesise that cortical asymmetries predict attention to threat. Participants completed a dot-probe task in which bilateral face displays were followed by lateralised targets at either short (300 ms) or long (1050 ms) SOA. We also measured N2pc to face onset as an index of early attentional capture. At long SOA only, frontal and parietal asymmetry interacted to predict attentional bias to angry faces. Those with leftward frontal asymmetry showed no attentional bias. Among those with rightward frontal asymmetry those with low right parietal activity showed vigilance for threat, and those with high right parietal activity showed avoidance. Asymmetry was not related to the N2pc or to attentional bias at the short SOA. Findings suggest that trait asymmetries reflect function in a fronto-parietal network that controls attention to threat.     

Anxiety selectively disrupts visuospatial working memory

On the basis of a review of the extant literature describing emotion-cognition interactions, the authors propose 4 methodological desiderata for studying how task-irrelevant affect modulates cognition and present data from an experiment satisfying them. Consistent with accounts of the hemispheric asymmetries characterizing withdrawal-related negative affect and visuospatial working memory (WM) in prefrontal and parietal cortices, threat-induced anxiety selectively disrupted accuracy of spatial but not verbal WM performance. Furthermore, individual differences in physiological measures of anxiety statistically mediated the degree of disruption. A second experiment revealed that individuals characterized by high levels of behavioral inhibition exhibited more intense anxiety and relatively worse spatial WM performance in the absence of threat, solidifying the authors' inference that anxiety causally mediates disruption. These observations suggest a revision of extant models of how anxiety sculpts cognition and underscore the utility of the desiderata.     

Attention training improves aberrant neural dynamics during working memory processing in veterans with PTSD

Posttraumatic stress disorder (PTSD) is associated with executive functioning deficits, including disruptions in working memory (WM). Recent studies suggest that attention training reduces PTSD symptomatology, but the underlying neural mechanisms are unknown. We used high-density magnetoencephalography (MEG) to evaluate whether attention training modulates brain regions serving WM processing in PTSD. Fourteen veterans with PTSD completed a WM task during a 306-sensor MEG recording before and after 8 sessions of attention training treatment. A matched comparison sample of 12 combat-exposed veterans without PTSD completed the same WM task during a single MEG session. To identify the spatiotemporal dynamics, each group’s data were transformed into the time-frequency domain, and significant oscillatory brain responses were imaged using a beamforming approach. All participants exhibited activity in left hemispheric language areas consistent with a verbal WM task. Additionally, veterans with PTSD and combat-exposed healthy controls each exhibited oscillatory responses in right hemispheric homologue regions (e.g., right Broca’s area); however, these responses were in opposite directions. Group differences in oscillatory activity emerged in the theta band (4–8 Hz) during encoding and in the alpha band (9–12 Hz) during maintenance and were significant in right prefrontal and right supramarginal and inferior parietal regions. Importantly, following attention training, these significant group differences were reduced or eliminated. This study provides initial evidence that attention training improves aberrant neural activity in brain networks serving WM processing.     

A Cognitive-Behavioral Model of Persistent Postural-Perceptual Dizziness

Persistent postural-perceptual dizziness (PPPD; previously termed “chronic subjective dizziness”) is a frequently observed disorder in patients who present with dizziness to audiology; ear, nose, and throat; or neurology clinics. The primary symptoms are persistent nonvertiginous dizziness, and hypersensitivity to motion and visual stimuli. These occur either in the absence of any active neuro-otologic illness or, where an episodic vestibular disorder exists, symptoms cannot be fully explained by the disorder alone. Diagnosis is necessarily multidisciplinary and proceeds by identification of primary symptoms and exclusion of other neurological or active medical disorders requiring treatment. Psychological processes are implicated in the development and maintenance of PPPD, with similarities to cognitive models of health anxiety and panic disorder, and there is evidence that cognitive-behavioral therapy is an effective treatment. A cognitive-behavioral model of PPPD is presented along with a case example. It is suggested that dizziness becomes persistent when it is processed as a threat, and that it is maintained by (a) unhelpful appraisals, (b) avoidance and safety behaviors, and (c) attentional strategies including selective attention to body sensations associated with dizziness. Once PPPD is identified techniques for its effective treatment fall within the skills mix of qualified cognitive-behavioral therapists or vestibular clinical scientists who have received additional training in cognitive and behavioral treatment.     

ERPs associated with visual duration discriminations in prefrontal and parietal cortex

An event-related potentials (ERP) study was undertaken to examine the role of prefrontal and parietal association cortices on selective attention and short-term memory functions in a duration discrimination task. Subjects performed better when discriminating the first stimulus relative to the second and not the reverse. Two contingent negative variations (CNV) were obtained for each stimulus duration at prefrontal regions, as well as two P300s at parietal regions. The CNV(S1) component recorded during the first stimulus (S1) appeared to be involved in selective attention at bilateral sites, while the P300(S1) component in the left hemisphere may be implicated in retaining it. The CNV(S2) wave, displayed during the second stimulus (S2), at bilateral sites and the right-sided P300(S2) wave seem to be implicated in working memory. The results indicate that recorded activity at prefrontal and parietal association cortices is tightly linked to task parameters and behavioral performances.     

Amygdala activation to sad pictures during high-field (4 tesla) functional magnetic resonance imaging

Fear-related processing in the amygdala has been well documented, but its role in signaling other emotions remains controversial. The authors recovered signal loss in the amygdala at high-field strength using an inward spiral pulse sequence and probed its response to pictures varying in their degree of portrayed sadness. These pictures were presented as intermittent task-irrelevant distractors during a concurrent visual oddball task. Relative to neutral distractors, sad distractors elicited greater activation along ventral brain regions, including the amygdala, fusiform gyrus, and inferior frontal gyrus. In contrast, oddball targets engaged dorsal sectors of frontal, parietal, and cingulate cortices. The amygdala's role in emotional evaluation thus extends to images of grief and despair as well as to those depicting violence and threat.     

Updating the premotor theory: The allocation of attention is not always accompanied by saccade preparation

There is an ongoing controversy regarding the relationship between covert attention and saccadic eye movements. While there is quite some evidence that the preparation of a saccade is obligatory preceded by a shift of covert attention, the reverse is not clear: Is allocation of attention always accompanied by saccade preparation? Recently, a shifting and maintenance account was proposed suggesting that shifting and maintenance components of covert attention differ in their relation to the oculomotor system. Specifically, it was argued that a shift of covert attention is always accompanied by activation of the oculomotor program, while maintaining covert attention at a location can be accompanied either by activation or suppression of oculomotor program, depending on the probability of executing an eye movement to the attended location. In the present study we tested whether there is such an obligatory coupling between shifting of attention and saccade preparation and how quickly saccade preparation gets suppressed. The results showed that attention shifting was always accompanied by saccade preparation whenever covert attention had to be shifted during visual search, as well as in response to exogenous or endogenous cues. However, for the endogenous cues the saccade program to the attended location was suppressed very soon after the attention shift was completed. The current findings support the shifting and maintenance account and indicate that the premotor theory needs to be updated to include a shifting and maintenance component for the cases in which covert shifts of attention are made without the intention to execute a saccade. (PsycINFO Database Record (c) 2012 APA, all rights reserved).     

Suppression of reflexive saccades in younger and older adults: Age comparisons on an antisaccade task

Inhibitory control of prepotent responses has been examined by using the antisaccade task, during which a reflexive saccade toward a peripheral onset must be suppressed before an eye movement in the opposite direction from the onset can be executed. In the present experiments, we sought to determine whether older and younger adults would perform similarly on this task. Older adults had a harder time suppressing their reflexive responses, as measured by an increase in the proportion of saccade direction errors. Despite an age-related decline in saccade direction accuracy, the increase in saccade latency associated with the antisaccade condition was the same for both younger and older adults. These results support the view that the effectiveness of inhibitory control declines with age (Hasher & Zacks, 1988; Hasher, Zacks, & May, 1999).     

Neuronal correlates of full and partial visual conscious perception

Stimuli may induce only partial consciousness—an intermediate between null and full consciousness—where the presence but not identity of an object can be reported. The differences in the neuronal basis of full and partial consciousness are poorly understood. We investigated if evoked and oscillatory activity could dissociate full from partial conscious perception. We recorded human cortical activity with magnetoencephalography (MEG) during a visual perception task in which stimulus could be either partially or fully perceived. Partial consciousness was associated with an early increase in evoked activity and theta/low-alpha-band oscillations while full consciousness was also associated with late evoked activity and beta-band oscillations. Full from partial consciousness was dissociated by stronger evoked activity and late increase in theta oscillations that were localized to higher-order visual regions and posterior parietal and prefrontal cortices. Our results reveal both evoked activity and theta oscillations dissociate partial and full consciousness.     

The time-course of threat processing in children: a temporal dissociation between selective attention and behavioral interference

Although selective attention to threatening information is an adaptive mechanism, exaggerated attention to threat may be related to anxiety disorders. However, studies examining threat processing in children have obtained mixed findings. In the present study, the time-course of attentional bias for threat and behavioral interference was analyzed in a community sample of 8-18-year-old children (N=33) using a pictorial dot probe task. Threatening and neutral stimuli were shown during 17 ms (masked), 500 ms, and 1250 ms. Results provide preliminary evidence of an automatic attentional bias for threat at 17 ms that persists during later, more controlled stages of information processing (500 and 1250 ms). Furthermore, participants showed a delayed response to threat-containing trials relative to neutral trials in the 500 and 1250 ms condition, which may indicate interference by threat. Together, these results suggest that an attentional bias for threat precedes behavioral interference in children. Furthermore, results indicate that performance in daily life can be temporarily interrupted by the processing of threatening information. In addition, results of earlier studies into selective attention in children using tasks based on behavioral responses may have been confounded by interference effects of threat. For future studies, we recommend to take behavioral interference into account.