A review on eye movement studies in childhood and adolescent psychiatry

The neural substrates of eye movement measures are largely known. Therefore, measurement of eye movements in psychiatric disorders may provide insight into the underlying neuropathology of these disorders. Visually guided saccades, antisaccades, memory guided saccades, and smooth pursuit eye movements will be reviewed in various childhood psychiatric disorders. The four aims of this review are (1) to give a thorough overview of eye movement studies in a wide array of psychiatric disorders occurring during childhood and adolescence (attention-deficit/hyperactivity disorder, oppositional deviant disorder and conduct disorder, autism spectrum disorders, reading disorder, childhood-onset schizophrenia, Tourette’s syndrome, obsessive compulsive disorder, and anxiety and depression), (2) to discuss the specificity and overlap of eye movement findings across disorders and paradigms, (3) to discuss the developmental aspects of eye movement abnormalities in childhood and adolescence psychiatric disorders, and (4) to present suggestions for future research. In order to make this review of interest to a broad audience, attention will be given to the clinical manifestation of the disorders and the theoretical background of the eye movement paradigms.     

Development of eye-movement control

Cognitive control of behavior continues to improve through adolescence in parallel with important brain maturational processes including synaptic pruning and myelination, which allow for efficient neuronal computations and the functional integration of widely distributed circuitries supporting top-down control of behavior. This is also a time when psychiatric disorders, such as schizophrenia and mood disorders, emerge reflecting a particularly vulnerability to impairments in development during adolescence. Oculomotor studies provide a unique neuroscientific approach to make precise associations between cognitive control and brain circuitry during development that can inform us of impaired systems in psychopathology. In this review, we first describe the development of pursuit, fixation, and visually-guided saccadic eye movements, which collectively indicate early maturation of basic sensorimotor processes supporting reflexive, exogenously-driven eye movements. We then describe the literature on the development of the cognitive control of eye movements as reflected in the ability to inhibit a prepotent eye movement in the antisaccade task, as well as making an eye movement guided by on-line spatial information in working memory in the oculomotor delayed response task. Results indicate that the ability to make eye movements in a voluntary fashion driven by endogenous plans shows a protracted development into adolescence. Characterizing the transition through adolescence to adult-level cognitive control of behavior can inform models aimed at understanding the neurodevelopmental basis of psychiatric disorders.     

自主控制眼跳：实验范式、神经机制和应用

自主控制眼跳是眼跳类型之一。自主控制眼跳实验范式为研究各种脑损伤,神经疾病和精神失调提供了一种新的研究手段,为研究眼跳的神经机制以及反应抑制、空间工作记忆等高级认知功能提供了重要的方法。文章介绍了自主控制眼跳的两种实验范式：反向眼跳和记忆导向眼跳,阐述了自主控制眼跳的神经机制及其实验范式的应用,指出自主控制眼跳实验范式为评定精神分裂症等脑功能失调病人的神经功能状态提供了重要的信息,为研究各种脑功能失调和精神疾病提供了重要的研究方法。今后的研究趋势是眼跳研究与神经成像技术和临床观察相结合     

Neurophysiology and neuroanatomy of reflexive and voluntary saccades in non-human primates

A multitude of cognitive functions can easily be tested by a number of relatively simple saccadic eye movement tasks. This approach has been employed extensively with patient populations to investigate the functional deficits associated with psychiatric disorders. Neurophysiological studies in non-human primates performing the same tasks have begun to provide us with insights into the neural mechanisms underlying many cognitive functions. Here, we review studies that have investigated single neuron activity in the superior colliculus (see glossary), frontal eye field, supplementary eye field, dorsolateral prefrontal cortex, anterior cingulate (see glossary) cortex and lateral intraparietal area associated with the performance of visually guided saccades, anti-saccades and memory-guided saccades in awake behaving monkeys.     

Neurophysiology and neuroanatomy of reflexive and voluntary saccades in non-human primates

A multitude of cognitive functions can easily be tested by a number of relatively simple saccadic eye movement tasks. This approach has been employed extensively with patient populations to investigate the functional deficits associated with psychiatric disorders. Neurophysiological studies in non-human primates performing the same tasks have begun to provide us with insights into the neural mechanisms underlying many cognitive functions. Here, we review studies that have investigated single neuron activity in the superior colliculus (see glossary), frontal eye field, supplementary eye field, dorsolateral prefrontal cortex, anterior cingulate (see glossary) cortex and lateral intraparietal area associated with the performance of visually guided saccades, anti-saccades and memory-guided saccades in awake behaving monkeys.     

Pharmacological treatment effects on eye movement control

The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second- generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson’s disease, and Huntington’s disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.     

Pharmacological treatment effects on eye movement control

The increasing use of eye movement paradigms to assess the functional integrity of brain systems involved in sensorimotor and cognitive processing in clinical disorders requires greater attention to effects of pharmacological treatments on these systems. This is needed to better differentiate disease and medication effects in clinical samples, to learn about neurochemical systems relevant for identified disturbances, and to facilitate identification of oculomotor biomarkers of pharmacological effects. In this review, studies of pharmacologic treatment effects on eye movements in healthy individuals are summarized and the sensitivity of eye movements to a variety of pharmacological manipulations is established. Primary findings from these studies of healthy individuals involving mainly acute effects indicate that: (i) the most consistent finding across several classes of drugs, including benzodiazepines, first- and second- generation antipsychotics, anticholinergic agents, and anticonvulsant/mood stabilizing medications is a decrease in saccade and smooth pursuit velocity (or increase in saccades during pursuit); (ii) these oculomotor effects largely reflect the general sedating effects of these medications on central nervous system functioning and are often dose-dependent; (iii) in many cases changes in oculomotor functioning are more sensitive indicators of pharmacological effects than other measures; and (iv) other agents, including the antidepressant class of serotonergic reuptake inhibitors, direct serotonergic agonists, and stimulants including amphetamine and nicotine, do not appear to adversely impact oculomotor functions in healthy individuals and may well enhance aspects of saccade and pursuit performance. Pharmacological treatment effects on eye movements across several clinical disorders including schizophrenia, affective disorders, attention deficit hyperactivity disorder, Parkinson’s disease, and Huntington’s disease are also reviewed. While greater recognition and investigation into pharmacological treatment effects in these disorders is needed, both beneficial and adverse drug effects are identified. This raises the important caveat for oculomotor studies of neuropsychiatric disorders that performance differences from healthy individuals cannot be attributed to illness effects alone. In final sections of this review, studies are presented that illustrate the utility of eye movements for use as potential biomarkers in pharmacodynamic and pharmacogenetic studies. While more systematic studies are needed, we conclude that eye movement measurements hold significant promise as tools to investigate treatment effects on cognitive and sensorimotor processes in clinical populations and that their use may be helpful in speeding the drug development pathway for drugs targeting specific neural systems and in individualizing pharmacological treatments.     

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.     

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.     

Deficits in volitional oculomotor control align with language status in autism spectrum disorders

Eye‐tracking paradigms are increasingly used to investigate higher‐level social and cognitive processing in autism spectrum disorder (ASD). However, the integrity of the oculomotor system within ASD is unclear, with contradictory reports of aberrant eye‐movements on basic oculomotor tasks. The purpose of the current study was to determine whether reducing population heterogeneity and distinguishing neurocognitive phenotypes can clarify discrepancies in oculomotor behaviour evident in previous reports. Reflexive and volitional eye‐movement control was assessed in 73 children aged 8–14 years from four distinct groups: Autism Language Normal (ALN), Autism Language Impaired (ALI), non‐autistic Language Impaired (LI) and Typically Developing (TD). Eye‐movement control was measured using pro‐ and antisaccade tasks and a novel ‘search distracter’ task to measure distractibility. Reflexive eye‐movements were equivalent across groups, but deficits in volitional eye‐movement control were found that aligned with language status, and were not specific to ASD. More than 80% of ALI and LI children presented error rates at least 1.5 SDs below the TD mean in an antisaccade task. In the search distracter task, 35.29% of ALI children and 43.75% of LI children had error rates greater than 1.5 SDs compared with 17.64% of ALN children. A significant proportion of children with neurodevelopmental disorders involving language function have pronounced difficulties suppressing reflexive saccades and maintaining fixations in the presence of competing stimuli. We extend the putative link between ALI and LI populations to non‐language tasks, and highlight the need to account for co‐morbidity in understanding the ontogenesis of ASD.     

平滑追随眼动的神经机制综述

平滑追随眼动作为视觉引导的眼动行为之一,是指为保障对运动目标的精细觉察,眼睛追随慢速运动的目标以使其处于中央凹位置时眼球的运动情况。本文简要归纳介绍了平滑追随眼动的实验范式、测量指标和影响因素,在此基础上重点详述了平滑追随眼动的皮质-脑桥-小脑神经通路,其中皮质区的额眼区、辅眼区、颞中区、内侧上颞区及侧顶区在平滑追随眼动的产生中具有不同作用;而脑桥核和脑桥被盖网状核作为中继站负责将来自顶枕区和额叶区信号传递到小脑中参与眼动的区域;小脑的绒球和副绒球及蚓体负责处理平滑追随的眼动信号,并协调前庭神经反射。对平滑追随眼动的理解不仅可以帮助我们区分眼动的正常与否,发挥其临床诊断和药理学评估的作用,而且有助于确定患者大脑器质性病变或损伤的程度,同时为进一步的实验认知研究和验证提供理论基础。     

The influence of a scene preview on eye movement behavior in natural scenes

Rich contextual and semantic information can be extracted from only a brief presentation of a natural scene. This is presumed to be activated quickly enough to guide initial eye movements into a scene. However, early, short-latency eye movements in natural scenes have been shown to be dependent on the salience distribution across the image (Anderson, Ort, Kruijne, Meeter, & Donk, 2015). In the present work, we manipulated the salience distribution across a natural scene by changing the global contrast. We showed participants a brief real or nonsense preview of the scene and examined the time-course of eye movement guidance. A real preview decreased the latency and increased the amplitude of initial saccades into the image, suggesting that the preview allowed observers to obtain additional contextual information that would otherwise not be available. However, the preview did not completely override the initial tendency for short-latency saccades to be guided by the underlying salience distribution of the image. We discuss these findings in the context of oculomotor selection based on the integration of contextual information and low-level features in a natural scene.     

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.     

Linguistically guided anticipatory eye movements in scene viewing

The present study replicated the well-known demonstration by Altmann and Kamide (1999) that listeners make linguistically guided anticipatory eye movements, but used photographs of scenes rather than clip-art arrays as the visual stimuli. When listeners heard a verb for which a particular object in a visual scene was the likely theme, they made earlier looks to this object (e.g., looks to a cake upon hearing The boy will eat …) than when they heard a control verb (The boy will move …). New data analyses assessed whether these anticipatory effects are due to a linguistic effect on the targeting of saccades (i.e., the where parameter of eye movement control), the duration of fixations (i.e., the when parameter), or both. Participants made fewer fixations before reaching the target object when the verb was selectionally restricting (e.g., will eat). However, verb type had no effect on the duration of individual eye fixations. These results suggest an important constraint on the linkage between spoken language processing and eye movement control: Linguistic input may influence only the decision of where to move the eyes, not the decision of when to move them.     

中文阅读中长距离回视引导机制的眼动研究

从记忆的角度, 探讨中文阅读中长距离回视的引导机制。采用眼动实验, 操纵了回视条件(实验1)、回视可见性(实验2)、目标词位置及词频变量。结果发现:与不阅读组相比, 阅读组的最初回视误差更小, 定位效率更高; 与可见组相比, 不可见组累积回视距离更大, 且难以正确定位目标; 目标词位置主效应显著, 而词频主效应不显著。结果表明, 回视具有空间选择性, 最初的回视由空间记忆引导, 最初回视后的修正眼跳在文本可见情况下才能正常进行, 而词频这一言语属性对回视没有显著影响, 本研究结果支持了空间编码假设。     

Ocular motor indicators of executive dysfunction in fragile X and Turner syndromes

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner syndrome, and 40 females with neither disorder who comprised the comparison group. Group differences emerged for both the fragile X and Turner syndrome groups, each relative to the comparison group: Females with fragile X had deficits in generating memory-guided saccades, predictive saccades, and saccades made in the overlap condition of a gap/overlap task. Females with Turner syndrome showed deficits in generating memory-guided saccades, but not during either the predictive saccade or gap/overlap task. Females with Turner syndrome, but not females with fragile X, showed deficits in visually guided saccades and anti-saccades. These findings indicate that different brain regions are affected in the two disorders, and suggest that different pathways lead to the similar cognitive phenotypes described for fragile X and Turner syndromes.     

Our Eyes Do Not Always Go Where We Want Them to Go: Capture of the Eyes by New Objects

Observers make rapid eye movements to examine the world around them. Before an eye movement is made, attention is covertly shifted to the location of the object of interest. The eyes typically will land at the position at which attention is directed. Here we report that a goal-directed eye movement toward a uniquely colored object is disrupted by the appearance of a new but task-irrelevant object, unless subjects have a sufficient amount of time to focus their attention on the location of the target prior to the appearance of the new object. In many instances, the eyes started moving toward the new object before gaze started to shift to the color-singleton target. The eyes often landed for a very short period of time (25–150 ms) near the new object. The results suggest parallel programming of two saccades: one voluntary, goal-directed eye movement toward the color-singleton target and one stimulus-driven eye movement reflexively elicited by the appearance of the new object. Neuroanatomical structures responsible for parallel programming of saccades are discussed.     

Interdependence of Saccadic and Fixational Fluctuations

Recent research suggests that the different components of eye movements (fixations, saccades) are not strictly separate but are interdependent processes. This argument rests on observations that gaze-step sizes yield unimodal distributions and exhibit power-law scaling, indicative of interdependent processes coordinated across timescales. The studies that produced these findings, however, employed complex tasks (visual search, scene perception). Thus, the question is whether the observed interdependence is a fundamental property of eye movements or emerges in the interplay between cognitive processes and complex visual stimuli. In this study, we used a simple eye movement task where participants moved their eyes in a prescribed sequence at several different paces. We outlined diverging predictions for this task for independence versus interdependence of fixational and saccadic fluctuations and tested these predictions by assessing the spectral properties of eye movements. We found no clear peak in the power spectrum attributable exclusively to saccadic fluctuations. Furthermore, changing the pace of the eye movement sequence yielded a global shift in scaling relations evident in the power spectrum, not just a localized shift for saccadic fluctuations. These results support the conclusion that fixations and saccades are interdependent processes.     

ADHD and delinquency--a developmental perspective

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent psychiatric disorders of childhood and adolescence. Until now, it has been unclear whether ADHD by itself constitutes a risk factor for later delinquency or does so only in combination with other disruptive symptoms. This article seeks to give a comprehensive account of the literature to shed light on the developmental pathway from childhood ADHD to adult criminality. Comorbid ADHD and conduct disorder (CD) are significantly related to a range of biological and environmental risk factors such as neurocognitive impairment, high parental psychopathology, poor social functioning, and other comorbid mental disorders, particularly substance abuse, that are described in this review. In addition, the results of treatment studies are presented, with a special focus on the results of the Multimodal Treatment Study of Children with ADHD (MTA). Although treatment programs, including medication and psychosocial treatment, can be very effective in improving the functioning of children with ADHD in the social and academic domains in the short term, there is no conclusive evidence that such treatments lower the risk for developing delinquency in adulthood.