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.     

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.     

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.     

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.     

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.     

眼跳的研究范式及其主要认知功能

眼跳运动系统为研究者探索行为的认知控制机制提供了有力工具。已有研究发现,很多认知过程会影响不同类型眼跳任务中的眼跳参数。在系统梳理已有研究的基础上,从以下4个方面系统阐述和评价了眼跳运动的研究范式和主要认知功能：（1）视觉导向眼跳的研究范式和变式及其认知功能,包括空白/重叠效应、分心物效应、提示效应、学习效应等;（2）预测性眼跳的研究范式和认知控制,涉及神经生物钟理论、视空间工作记忆、指导语等;（3）记忆导向眼跳的研究范式和变式及其认知控制,包括分心物效应、年龄效应、视空间工作记忆的抑制效应、注意等;（4）反向眼跳的研究范式和变式及其认知控制,包括反向眼跳抑制、眼跳决策信号竞争整合模型、工作记忆容量、注意、错误监控、学习、奖励和年龄效应等。最后,结合已有研究范式对未来眼跳研究的趋势和需解决的问题进行了展望。     

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).     

Saccades elicit obligatory allocation of visual working memory

In daily life, visual working memory (VWM) typically works in contexts in which people make frequent saccades. Here, we investigated whether people can effectively control the allocation of VWM when making a saccade. Subjects were required to make an intervening saccade in the process of a memory task. The saccade target was either a to-be-remembered item or an extra, not-to-be-remembered item. The results showed that memory performance was poorer when a saccade was made to the extra, not-to-be-remembered item, regardless of its similarity to the memory item(s). In contrast, when memorizing the items while remaining fixated, subjects had similar memory performance whether an extra, not-to-be-remembered item was present or not. Taken together, these results demonstrated that volitional control over VWM allocation is greatly impaired when a saccade is made, indicating that VWM contains an automatic part that cooperates with eye movements and is allocated to a saccade target obligatorily.     

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.     

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.     

Saccade landing point selection and the competition account of pro- and antisaccade generation: the involvement of visual attention--a review

This paper presents a review and summary of experimental findings on the role of attention in the preparation of saccadic eye movements. The focus is on experiments where performance of prosaccades (saccades towards a suddenly appearing item) and antisaccades (saccades of equal amplitude in the direction opposite to where the target moved) is compared. Evidence suggests that these two opposite responses to the same stimulus event entail competition between neural pathways that generate reflexive movements to the target and neural mechanisms involved in inhibiting the reflex and generating a voluntary gaze shift in the opposite direction to the target appearance. Evidence for such a competition account is discussed in light of a large amount of experimental findings and the overall picture clearly indicates that this competition account has great explanatory power when data on saccadic reaction times and error rates are compared for the two types of saccade. The role of attention is also discussed in particular in light of the finding that the withdrawal of attention by a secondary task 200 to 500 ms before the saccade target appears, leads to speeded antisaccades (without a similar increase in error rates), showing that the results do not simply reflect a speed-accuracy trade-off. This result indicates that the tendency for "reflexive" prosaccades is diminished when attention is engaged in a different task. Furthermore, experiments are discussed that show that as the tendency for a reflexive prosaccade is weakened, antisaccades are speeded up, further supporting the competition account of pro- and antisaccade generation. In the light of evidence from neurophysiology of monkeys and humans, a tentative model of pro- and antisaccade generation is proposed.     

Working memory capacity and the antisaccade task: individual differences in voluntary saccade control

Performance on antisaccade trials requires the inhibition of a prepotent response (i.e., don't look at the flashing cue) and the generation and execution of a correct saccade in the opposite direction. The authors attempted to further specify the role of working memory (WM) span differences in the antisaccade task. They tested high- and low-span individuals on variants of prosaccade and antisaccade trials in which an eye movement is the sole requirement. In 3 experiments, they demonstrated the importance of WM span differences in both suppression of a reflexive saccade and generation of a volitional eye movement. The results support the contention that individual differences in WM span are not exclusively due to differences in inhibition but also reflect differences in directing the focus of attention.     

The reduction of saccadic latency by prior offset of the fixation point: an analysis of the gap effect

The latency to initiate a saccade (saccadic reaction time) to an eccentric target is reduced by extinguishing the fixation stimulus prior to the target onset. Various accounts have attributed this latency reduction (referred to as the gap effect) to facilitated sensory processing, oculomotor readiness, or attentional processes. Two experiments were performed to explore the relative contributions of these factors to the gap effect. Experiment 1 demonstrates that the reduction in saccadic reaction time (RT) produced by fixation point offset is additive with the effect of target luminance. Experiment 2 indicates that the gap effect is specific for saccades directed toward a peripheral target and does not influence saccades directed away from the target (i.e., antisaccades) or choice-manual RT. The results are consistent with an interpretation of the gap effect in terms of facilitated premotor processing in the superior colliculus.     

Control of fixation duration in visual search and memory search: another look

In visual search a variable delay (up to 150 msec) between the beginning of each fixation and the onset of a search stimulus reduces the time (oculomotor latency) between stimulus onset and the subject's next saccadic eye movement. Two hypotheses for this effect of stimulus onset delay (SOD) were compared: first, process monitoring, that SOD simply serves as a warning interval to facilitate saccadic responses; and second, preprogramming, that saccades are preprogrammed at short SODs. In the first experiment SOD produced a decline in oculomotor latency in search similar to that seen in previous studies. In the second and third experiments, the size of the memory set in a Sternberg memory search paradigm was varied, or a mask flanking some of the search stimuli was used, to vary the processing time of each stimulus. Partial preprogramming of saccades at short delays would predict that increasing the processing time of individual stimuli would increase oculomotor latency at only short SODs. However, oculomotor latency increased equally at all SODs. In this search task, then, the SODs appeared to facilitate saccade initiation.     

Trans-saccadic perception

A basic question in cognition is how visual information obtained in separate glances can produce a stable, continuous percept. Previous explanations have included theories such as integration in a trans-saccadic buffer or storage in visual memory, or even that perception begins anew with each fixation. Converging evidence from primate neurophysiology, human psychophysics and neuroimaging indicate an additional explanation: the intention to make a saccadic eye movement leads to a fundamental alteration in visual processing itself before and after the saccadic eye movement. We outline five principles of 'trans-saccadic perception' that could help to explain how it is possible - despite discrete sensory input and limited memory - that conscious perception across saccades seems smooth and predictable.     

Age-group differences in inhibiting an oculomotor response

Age-group differences were examined in the delayed oculomotor response task, which requires that observers delay the execution of a saccade (eye movement) toward an abrupt-onset visual cue. This task differs from antisaccade and attentional capture in that inhibition causes saccades to be postponed, not redirected. Older adults executed more premature saccades than young adults, but there were no age-group differences in latency or accuracy of saccades executed at the proper time. The results suggest that older adults are less capable of inhibiting a prepotent saccadic response, but that other aspects of visual working memory related to the task are preserved.     

Inhibition of return in single and dual tasks: examining saccadic, keypress, and pointing responses

Two experiments are reported in which inhibition of return (IOR)was examined wit h single-responsetasks (either manual responses alone or saccadic responses alone) and dual-response tasks (simultaneous manual and saccadic responses). The first experiment-using guided limb movements that require considerable spatial information-showed more IOR for saccades than for pointing responses. In addition, saccadic IOR was reduced with concurrent pointing movements, but manual IOR was not affected by concurrent saccades. Importantly, at the time of saccade initiation, the arm movements did not start yet, indicating that the influence on saccade IOR is due to arm-movement preparation. In the second experiment, using localization keypress responses that required only minimal spatial information, greater IOR was again found for saccadic than for manual responses, but no effect of concurrent movements was found. These findings add further support that there is a dissociation between oculomotor and skeletal-motor IOR. Moreover, the results show that the preparation manual responses tend to mediate saccadic behavior-but only when the manual responses require high levels of spatial accuracy-and that the superior colliculus is the likely neural substrate integrating IOR for eye and arm movements.     

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.