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.     

The tell-tale tasks: a review of saccadic research in psychiatric patient populations

This review focuses on saccade research with adult psychiatric patients. It begins with an introduction of the various types of saccades and the tasks used to evoke them. The functional significance of the different types of eye movements is briefly discussed. Research findings regarding the saccadic performance of different adult psychiatric patient populations are discussed in detail, with particular emphasis on findings regarding error rates, response latencies, and any specific task parameters that might affect those variables. Findings regarding the symptom, neurocognitive, and neural correlates of saccadic performance and the functional significance of patients’ saccadic deficits are also discussed. We also discuss the saccadic deficits displayed by various patient groups in terms of circuitry (e.g. cortical/basal ganglia circuits) that may be implicated in the underlying pathophysiology of several of these disorders. Future directions for research in this growing area are offered.     

Differential roles of the frontal and parietal cortices in the control of saccades

Although externally as well as internally-guided eye movements allow us to flexibly explore the visual environment, their differential neural mechanisms remain elusive. A better understanding of these neural mechanisms will help us to understand the control of action and to elucidate the nature of cognitive deficits in certain psychiatric populations (e.g. schizophrenia) that show increased latencies in volitional but not visually-guided saccades. Both the superior precentral sulcus (sPCS) and the intraparietal sulcus (IPS) are implicated in the control of eye movements. However, it remains unknown what differential contributions the two areas make to the programming of visually-guided and internally-guided saccades. In this study we tested the hypotheses that sPCS and IPS distinctly encode internally-guided saccades and visually-guided saccades. We scanned subjects with fMRI while they generated visually-guided and internally-guided delayed saccades. We used multi-voxel pattern analysis to test whether patterns of cue related, preparatory and saccade related activation could be used to predict the direction of the planned eye movement. Results indicate that patterns in the human sPCS predicted internally-guided saccades but not visually-guided saccades in all trial periods and patterns in the IPS predicted internally-guided saccades and visually-guided saccades equally well. The results support the hypothesis that the human sPCS and IPS make distinct contributions to the control of volitional eye movements.     

Neurophysiology and neuroanatomy of reflexive and volitional saccades as revealed by lesion studies with neurological patients and transcranial magnetic stimulation (TMS)

This review discusses the neurophysiology and neuroanatomy of the cortical control of reflexive and volitional saccades in humans. The main focus is on classical lesion studies and studies using the interference method of transcranial magnetic stimulation (TMS). To understand the behavioural function of a region, it is essential to assess oculomotor deficits after a focal lesion using a variety of oculomotor paradigms, and to study the oculomotor consequences of the lesion in the chronic phase. Saccades are controlled by different cortical regions, which could be partially specialised in the triggering of a specific type of saccade. The division of saccades into reflexive visually guided saccades and intentional or volitional saccades corresponds to distinct regions of the neuronal network, which are involved in the control of such saccades.TMS allows to specifically interfere with the functioning of a region within an intact oculomotor network. TMS provides advantages in terms of temporal resolution, allowing to interfere with brain functioning in the order of milliseconds, thereby allowing to define the time course of saccade planning and execution.In the first part of the paper, we present an overview of the cortical structures important for saccade control, and discuss the pro’s and con’s of the different methodological approaches to study the cortical oculomotor network. In the second part, the functional network involved in reflexive and volitional saccades is presented. Finally, studies concerning recovery mechanisms after a lesion of the oculomotor cortex are discussed.     

Neurophysiology and neuroanatomy of reflexive and volitional saccades as revealed by lesion studies with neurological patients and transcranial magnetic stimulation (TMS)

This review discusses the neurophysiology and neuroanatomy of the cortical control of reflexive and volitional saccades in humans. The main focus is on classical lesion studies and studies using the interference method of transcranial magnetic stimulation (TMS). To understand the behavioural function of a region, it is essential to assess oculomotor deficits after a focal lesion using a variety of oculomotor paradigms, and to study the oculomotor consequences of the lesion in the chronic phase. Saccades are controlled by different cortical regions, which could be partially specialised in the triggering of a specific type of saccade. The division of saccades into reflexive visually guided saccades and intentional or volitional saccades corresponds to distinct regions of the neuronal network, which are involved in the control of such saccades.TMS allows to specifically interfere with the functioning of a region within an intact oculomotor network. TMS provides advantages in terms of temporal resolution, allowing to interfere with brain functioning in the order of milliseconds, thereby allowing to define the time course of saccade planning and execution.In the first part of the paper, we present an overview of the cortical structures important for saccade control, and discuss the pro’s and con’s of the different methodological approaches to study the cortical oculomotor network. In the second part, the functional network involved in reflexive and volitional saccades is presented. Finally, studies concerning recovery mechanisms after a lesion of the oculomotor cortex are discussed.     

Action effects in saccade control

According to the ideomotor principle, action preparation involves the activation of associations between actions and their effects. However, there is only sparse research on the role of action effects in saccade control. Here, participants responded to lateralized auditory stimuli with spatially compatible saccades toward peripheral targets (e.g., a rhombus in the left hemifield and a square in the right hemifield). Prior to the imperative auditory stimulus (e.g., a left tone), an irrelevant central visual stimulus was presented that was congruent (e.g., a rhombus), incongruent (e.g., a square), or unrelated (e.g., a circle) to the peripheral saccade target (i.e., the visual effect of the saccade). Saccade targets were present throughout a trial (Experiment 1) or appeared after saccade initiation (Experiment 2). Results showed shorter response times and fewer errors in congruent (vs. incongruent) conditions, suggesting that associations between oculomotor actions and their visual effects play an important role in saccade control.     

A model of saccadic landing positions in reading under the influence of sensory noise

During reading, saccadic eye movements are produced to move the high acuity foveal region of the eye to words of interest for efficient word processing. Distributions of saccadic landing positions peak close to a word's centre but are relatively broad compared to simple oculomotor tasks. Moreover, landing-position distributions are modulated both by distance of the launch site and by saccade type (e.g., one-step saccade, word skipping, refixation). Here we present a mathematical model for the computation of a saccade intended for a given target word. Two fundamental assumptions are related to (1) the sensory computation of the word centre from inter-word spaces and (2) the integration of sensory information and a priori knowledge using Bayesian estimation. Our model was developed for data from a large corpus of eye movements from normal reading. We demonstrate that the model is able simultaneously to account for a systematic shift of saccadic mean landing position with increasing launch-site distance and for qualitative differences between one-step saccades (i.e., from a given word to the next word) and word-skipping saccades.     

Quantifying the performance limits of human saccadic targeting during visual search.

In previous studies of saccadic targeting, the issue how visually guided saccades to unambiguous targets are programmed and executed has been examined. These studies have found different degrees of guidance for saccades depending on the task and task difficulty. In this study, we use ideal-observer analysis to estimate the visual information used for the first saccade during a search for a target disk in noise. We quantitatively compare the performance of the first saccadic decision to that of the ideal observer (ie absolute efficiency of the first saccade) and to that of the associated final perceptual decision at the end of the search (ie relative efficiency of the first saccade). Our results show, first, that at all levels of salience tested, the first saccade is based on visual information from the stimulus display, and its highest absolute efficiency is approximately 20%. Second, the efficiency of the first saccade is lower than that of the final perceptual decision after active search (with eye movements) and has a minimum relative efficiency of 19% at the lowest level of saliency investigated. Third, we found that requiring observers to maintain central fixation (no saccades allowed) decreased the absolute efficiency of their perceptual decision by up to a factor of two, but that the magnitude of this effect depended on target salience. Our results demonstrate that ideal-observer analysis can be extended to measure the visual information mediating saccadic target-selection decisions during visual search, which enables direct comparison of saccadic and perceptual efficiencies.     

Visual and oculomotor selection: links, causes and implications for spatial attention

Natural scenes contain far more information than can be processed simultaneously. Thus, our visually guided behavior depends crucially on the capacity to attend to relevant stimuli. Past studies have provided compelling evidence of functional overlap of the neural mechanisms that control spatial attention and saccadic eye movements. Recent neurophysiological work demonstrates that the neural circuits involved in the preparation of saccades also play a causal role in directing covert spatial attention. At the same time, other studies have identified separable neural populations that contribute uniquely to visual and oculomotor selection. Taken together, all of the recent work suggests how visual and oculomotor signals are integrated to simultaneously select the visual attributes of targets and the saccades needed to fixate them.     

Syntactic processing in the human brain: what we know, what we don't know, and a suggestion for how to proceed

For every claim in the neuroimaging literature about a particular brain region supporting syntactic processing, there exist other claims implicating the target region in different linguistic processes, and, in many cases, in non-linguistic cognitive processes (e.g., Blumstein, 2009). We argue that traditional group analysis methods in neuroimaging may obscure functional specificity because of inter-subject anatomical variability (Fedorenko & Kanwisher, 2009). In Fedorenko, Hsieh, Nieto-Castanon, Whitfield-Gabrieli, and Kanwisher (2010) we presented a functional localizer that allows quick and reliable identification of key language-sensitive regions in each individual brain. This approach enables pooling data from corresponding functional regions across subjects rather than from the same locations in stereotaxic space that may differ functionally due to inter-subject anatomical variability. In the current paper we demonstrate that the individual-subjects functional localization approach is superior to the traditional methods in its ability to distinguish among conditions in a brain region’s response. This ability is at the core of all neuroimaging research and is critical for answering questions of functional specialization (e.g., does a brain region specialize for processing syntactic aspects of the linguistic signal), which is in turn essential for making inferences about the precise computations conducted in each brain region. Based on our results, we argue that supplementing existing methods with an individual-subjects functional localization approach may lead to a clearer picture of the neural basis of syntactic processing, as it has in some other domains, such as high-level vision (e.g., Kanwisher, 2010) and social cognition (e.g., Saxe & Kanwisher, 2003).     

Suppressing where but not what: the effect of saccades on dorsal- and ventral-stream visual processing

Some cognitive processes are suppressed during saccadic eye movements, whereas others are not. In two experiments, we investigated the locus of this interference effect. In one experiment, subjects decided whether pictured items were objects or nonobjects while making saccades of different lengths. Saccade distance had no effect on response time, indicating that saccades do not interfere with object recognition. However, in a second experiment, in which subjects decided whether pictured items faced to the left or to the right, response time increased with saccade distance, indicating that processing was suppressed during the saccade. These results (along with others) suggest that dorsal-stream (where) processes are suppressed during saccades, whereas ventral-stream (what) processes are not. Because the dorsal stream is instrumental in generating saccades, we propose that cognitive saccadic suppression results from dual-task interference within this visual subsystem.     

The Role of Emotional Content and Perceptual Saliency During the Programming of Saccades Toward Faces

Previous studies have shown that the human visual system can detect a face and elicit a saccadic eye movement toward it very efficiently compared to other categories of visual stimuli. In the first experiment, we tested the influence of facial expressions on fast face detection using a saccadic choice task. Face-vehicle pairs were simultaneously presented and participants were asked to saccade toward the target (the face or the vehicle). We observed that saccades toward faces were initiated faster, and more often in the correct direction, than saccades toward vehicles, regardless of the facial expressions (happy, fearful, or neutral). We also observed that saccade endpoints on face images were lower when the face was happy and higher when it was neutral. In the second experiment, we explicitly tested the detection of facial expressions. We used a saccadic choice task with emotional-neutral pairs of faces and participants were asked to saccade toward the emotional (happy or fearful) or the neutral face. Participants were faster when they were asked to saccade toward the emotional face. They also made fewer errors, especially when the emotional face was happy. Using computational modeling, we showed that this happy face advantage can, at least partly, be explained by perceptual factors. Also, saccade endpoints were lower when the target was happy than when it was fearful. Overall, we suggest that there is no automatic prioritization of emotional faces, at least for saccades with short latencies, but that salient local face features can automatically attract attention.     

Strategic control over saccadic eye movements: studies of the fixation offset effect

We studied the strategic (presumably cortical) control of ocular fixation in experiments that measured the fixation offset effect (FOE) while manipulating readiness to make reflexive or voluntary eye movements. The visual grasp reflex, which generates reflexive saccades to peripheral visual signals, reflects an opponent process in the superior colliculus (SC) between fixation cells at the rostral pole, whose activity helps maintain ocular position and increases when a stimulus is present at fixation, and movement cells, which generate saccades and are inhibited by rostral fixation neurons. Voluntary eye movements are controlled by movement and fixation cells in the frontal eye field (FEF). The FOE--a decrease in saccade latency when the fixation stimulus is extinguished--has been shown to reflect activity in the collicular eye movement circuitry and also to have an activity correlate in the FEF. Our manipulation of preparatory set to make reflexive or voluntary eye movements showed that when reflexive saccades were frequent and voluntary saccades were infrequent, the FOE was attenuated only for reflexive saccades. When voluntary saccades were frequent and reflexive saccades were infrequent, the FOE was attenuated only for voluntary saccades. We conclude that cortical processes related to task strategy are able to decrease fixation neuron activity even in the presence of a fixation stimulus, resulting in a smaller FOE. The dissociation in the effects of a fixation stimulus on reflexive and voluntary saccade latencies under the same strategic set suggests that the FOEs for these two types of eye movements may reflect a change in cellular activity in different neural structures, perhaps in the SC for reflexive saccades and in the FEF for voluntary saccades.     

Hearing others’ pain: neural activity related to empathy

The human voice is one of the principal conveyers of social and affective communication. Recent neuroimaging studies have suggested that observing pain in others activates neural representations similar to those from the first-hand experience of pain; however, studies on pain expressions in the auditory channel are lacking. We conducted a functional magnetic resonance imaging study to examine brain responses to emotional exclamations of others’ pain. The control condition comprised positive (e.g., laughing) or negative (e.g., snoring) stimuli of the human voice that were not associated with pain and suffering. Compared to these control stimuli, pain-related exclamations elicited increased activation in the superior and middle temporal gyri, left insula, secondary somatosensory cortices, thalamus, and right cerebellum, as well as deactivation in the anterior cingulate cortex. The left anterior insular and thalamic activations correlated significantly with the Empathic Concern subscale of the Interpersonal Reactivity Index. Thus, the brain regions involved in hearing others’ pain are similar to those activated in the empathic processing of visual stimuli. Additionally, the findings emphasise the modulating role of interindividual differences in affective empathy.     

Aging and the strategic control of the fixation offset effect

A study was conducted to examine potential age-related differences in the strategic control of exogenous and endogenous saccades within the context of the fixation offset effect (FOE; i.e., faster saccades when a fixation point is removed than when it is left on throughout a trial). Subjects were instructed to make rapid saccades either on the basis of a suddenly appearing peripheral visual stimulus (exogenous saccade) or in response to a tone (endogenous saccade). On half of the trials the fixation point was removed simultaneously with the occurrence of the cue stimulus. Subjects' preparatory set was varied by manipulating the proportion of saccades generated to a visual and auditory stimulus within a trial block. Young and old adults both produced FOEs, and the FOEs were strategically modulated by preparatory set. The data are discussed in terms of aging and oculomotor control.     

Long-lasting modifications of saccadic eye movements following adaptation induced in the double-step target paradigm

The adaptation of saccadic eye movements to environmental changes occurring throughout life is a good model of motor learning and motor memory. Numerous studies have analyzed the behavioral properties and neural substrate of oculomotor learning in short-term saccadic adaptation protocols, but to our knowledge, none have tested the persistence of the oculomotor memory. In the present study, the double-step target protocol was used in five human subjects to adaptively decrease the amplitude of reactive saccades triggered by a horizontally-stepping visual target. We tested the amplitude of visually guided saccades just before and at different times (up to 19 days) after the adaptation session. The results revealed that immediately after the adaptation session, saccade amplitude was significantly reduced by 22% on average. Although progressively recovering over days, this change in saccade gain was still statistically significant on days 1 and 5, with an average retention rate of 36% and 19%, respectively. On day 11, saccade amplitude no longer differed from the pre-adaptation value. Adaptation was more effective and more resistant to recovery for leftward saccades than for rightward ones. Lastly, modifications of saccade gain related to adaptation were accompanied by a decrease of both saccade duration and peak velocity. A control experiment indicated that all these findings were specifically related to the adaptation protocol, and further revealed that no change in the main sequence relationships could be specifically related to adaptation. We conclude that in humans, the modifications of saccade amplitude that quickly develop during a double-step target adaptation protocol can remain in memory for a much longer period of time, reflecting enduring plastic changes in the brain.     

Effects of direct and averted gaze on the subsequent saccadic response

The saccadic latency to visual targets is susceptible to the properties of the currently fixated objects. For example, the disappearance of a fixation stimulus prior to presentation of a peripheral target shortens saccadic latencies (the gap effect). In the present study, we investigated the influences of a social signal from a facial fixation stimulus (i.e., gaze direction) on subsequent saccadic responses in the gap paradigm. In Experiment 1, a cartoon face with a direct or averted gaze was used as a fixation stimulus. The pupils of the face were unchanged (overlap), disappeared (gap), or were translated vertically to make or break eye contact (gaze shift). Participants were required to make a saccade toward a target to the left or the right of the fixation stimulus as quickly as possible. The results showed that the gaze direction influenced saccadic latencies only in the gaze shift condition, but not in the gap or overlap condition; the direct-to-averted gaze shift (i.e., breaking eye contact) yielded shorter saccadic latencies than did the averted-to-direct gaze shift (i.e., making eye contact). Further experiments revealed that this effect was eye contact specific (Exp. 2) and that the appearance of an eye gaze immediately before the saccade initiation also influenced the saccadic latency, depending on the gaze direction (Exp. 3). These results suggest that the latency of target-elicited saccades can be modulated not only by physical changes of the fixation stimulus, as has been seen in the conventional gap effect, but also by a social signal from the attended fixation stimulus.     

Having to identify a target reduces latencies in prosaccades but not in antisaccades

In a princeps study, Trottier and Pratt (2005) showed that saccadic latencies were dramatically reduced when subjects were instructed to not simply look at a peripheral target (reflexive saccade) but to identify some of its properties. According to the authors, the shortening of saccadic reactions times may arise from a top-down disinhibition of the superior colliculus (SC), potentially mediated by the direct pathway connecting frontal/prefrontal cortex structures to the SC. Using a “cue paradigm” (a cue preceded the appearance of the target), the present study tests if the task instruction (Identify vs. Glance) also reduces the latencies of antisaccades (AS), which involve prefrontal structures. We show that instruction reduces latencies for prosaccade but not for AS. An AS requires two processes: the inhibition of a reflexive saccade and the generation of a voluntary saccade. To separate these processes and to better understand the task effect we also test the effect of the task instruction only on voluntary saccades. The effect still exists but it is much weaker than for reflexive saccades. The instruction effect closely depends on task demands in executive resources.     

EGOCENTRIC ACTION IN EARLY INFANCY:

Abstract— The extent to which infants combine visual (i e, retinal position) and nonvisual (eye or head position) spatial information in planning saccades relates to the issue of what spatial frame or frames of reference influence early visually guided action. We explored this question by testing infants from 4 to 6 months of age on the double-step saccade paradigm, which has shown that adults combine visual and eye position information into an egocentric (head- or trunk-centered) representation of saccade target locations. In contrast, our results imply that infants depend on a simple retinocentric representation at age 4 months, but by 6 months use egocentric representations more often to control saccade planning. Shifts in the representation of visual space for this simple sensorimotor behavior may index maturation in cortical circuitry devoted to visual spatial processing in general.     

Attention and saccadic eye movements

Four threshold detection experiments addressed three issues concerning the relationship between movements of spatial attention and saccadic eye movements: (a) the time course of attention shifts wit saccades, (b) the response of the two systems to changes in stimulus parameters, and (c) the relationship of attention to saccadic suppression. These issues bear on the more general question of the degree of independence between the saccadic and attentional movement systems. The results of these experiments support the contention that the mechanisms that shift attention are separate from those that control saccadic eye movements. Relevant events in the visual field periphery, however, will trigger both a saccade and attention shift. The attentional response to such events does not appear to be under subjects' control. The implication of these results for theories of saccadic suppression is discussed.