The antisaccade task as a research tool in psychopathology: A critical review

The antisaccade task is a measure of volitional control of behavior sensitive to fronto-striatal dysfunction. Here we outline important issues concerning antisaccade methodology, consider recent evidence of the cognitive processes and neural mechanisms involved in task performance, and review how the task has been applied to study psychopathology. We conclude that the task yields reliable and sensitive measures of the processes involved in resolving the conflict between volitional and reflexive behavioral responses, a key cognitive deficit relevant to a number of neuropsychiatric conditions. Additionally, antisaccade deficits may reflect genetic liability for schizophrenia. Finally, the ease and accuracy with which the task can be administered, combined with its sensitivity to fronto-striatal dysfunction and the availability of suitable control conditions, may make it a useful benchmark tool for studies of potential cognitive enhancers

Transcranial direct current stimulation of the frontal eye fields during pro- and antisaccade tasks

Transcranial direct current stimulation (tDCS) has been successfully applied to cortical areas such as the motor cortex and visual cortex. In the present study, we examined whether tDCS can reach and selectively modulate the excitability of the frontal eye field (FEF). In order to assess potential effects of tDCS, we measured saccade latency, landing point, and its variability in a simple prosaccade task and in an antisaccade task. In the prosaccade task, we found that anodal tDCS shortened the latency of saccades to a contralateral visual cue. However, cathodal tDCS did not show a significant modulation of saccade latency. In the antisaccade task, on the other hand, we found that the latency for ipisilateral antisaccades was prolonged during the stimulation, whereas anodal stimulation did not modulate the latency of antisaccades. In addition, anodal tDCS reduced the erroneous saccades toward the contralateral visual cue. These results in the antisaccade task suggest that tDCS modulates the function of FEF to suppress reflexive saccades to the contralateral visual cue. Both in the prosaccade and antisaccade tasks, we did not find any effect of tDCS on saccade landing point or its variability. Our present study is the first to show effects of tDCS over FEF and opens the possibility of applying tDCS for studying the functions of FEF in oculomotor and attentional performance

Neural networks related to pro-saccades and anti-saccades revealed by independent component analysis

The saccadic eye movement system provides an excellent model for investigating basic cognitive processes and flexible control over behaviour. While the mechanism of pro-saccades (PS) is well known, in the case of the anti-saccade task (AS) it is still not clear which brain regions play a role in the inhibition of reflexive saccade to the target, nor what is the exact mechanism of vector inversion (i.e. orienting in the opposite direction). Independent component analysis (ICA) is one of the methods being used to establish temporally coherent brain regions, i.e. neural networks related to the task. In the present study ICA was applied to fMRI data from PS and AS experiments. The study revealed separate networks responsible for saccade generation into the desired direction, the inhibition of automatic responses, as well as vector inversion. The first function is accomplished by the eye fields network. The inhibition of automatic responses is associated with the executive control network. Vector inversion seems to be accomplished by the network comprising a large set of areas, including intraparietal sulcus, precuneus/posterior cingulate cortices, retrosplenial and parahippocampal. Those regions are associated with the parieto-medial temporal pathway, so far linked only to navigation. These results provide a new insight into understanding of the processes of the inhibition and vector inversion

An Investigation of the Neural Mechanism by which the Prefrontal Cortex Facilitates Anti-saccade Task Performance

Cognitive control enables us to guide our behaviour in an appropriate manner, such as rapid eye movements (saccades) toward a location or object of interest. A well-established test of cognitive control is the anti-saccade task, which instructs subjects to look away from a suddenly-appearing stimulus. The dorsolateral prefrontal cortex (dlPFC) and anterior cingulate cortex (ACC) are part of a cortical saccade control network that influences the superior colliculus (SC), which sends saccade commands to the brainstem saccade generator. To compare and contrast the roles of the dlPFC and ACC in saccade control, the cryoloop method of reversible cryogenic deactivation was used to identify the effects of dlPFC and ACC deactivation on pro-saccades and anti-saccades. Both dlPFC and ACC deactivation increased the incidence of ipsilateral saccades, but only dlPFC deactivation impaired contralateral saccades. An inhibitory model of prefrontal function has been proposed by which the prefrontal cortex suppresses the activity of SC saccade neurons on anti-saccade trials, to inhibit an unwanted saccade toward the stimulus. A direct test of this inhibitory model was performed by deactivating the dlPFC and recording the activity of SC saccade neurons. Unilateral dlPFC deactivation delayed the onset of saccade-related activity in the SC ipsilateral to deactivation, which suggests that the dlPFC has an excitatory influence on SC saccade neurons. There was also an increase of activity in the contralateral SC, which suggests that unilateral dlPFC deactivation caused a neural imbalance at the SC. Bilateral dlPFC deactivation, on the other hand, should not cause a neural imbalance, and thus was used to identify the effects of dlPFC deactivation that were caused by cognitive control impairments. Bilateral dlPFC deactivation increased the stimulus-related activity, and decreased the saccade-related activity, of SC saccade neurons. An increase of anti-saccade errors was more substantial in a “rule memorized” condition, which suggests that the dlPFC plays an important role in rule maintenance. Given an excitatory influence of the dlPFC on SC saccade neurons, I propose that the dlPFC facilitates anti-saccade task performance by first maintaining the relevant rule in working memory, then implementing the rule by enhancing the saccade-generating signal at the SC

Contextual control of orienting eye-head gaze shifts in the monkey

Vision is one of the principal methods used by primates to acquire information about the surrounding environment. As a result, both humans and monkeys have a highly evolved oculomotor system that functions to rapidly relocate the line of sight to areas of interest. These orienting movements are called gaze shifts. Gaze shifts commonly include the coordinated movement of the eyes-in-head and the head-in-space. This thesis examines the muscular and neural control of orienting head movements. The contextual control of behavior is important as it allows one to act appropriately in response to different situations. A common task used to examine the contextual control of behavior is the pro- and anti-saccade task. Pro-saccades simply require a subject to look towards a stimulus. Anti-saccades require a subject to inhibit a movement towards a stimulus in favor of a volitional movement to the diametrically opposite position. This task is can reveal capabilities of the oculomotor system and its response to varying behavioral states. To understand the neuromuscular control of orienting head movements during various tasks, we recorded the electromyographic (EMG) activity in ten turner and extensor neck muscles. Recording neck EMGs provides an objective and precise measurement of the neural signals received at the neck muscles, circumventing some of the structural and biomechanical complexities of head motion. Chapter two examines neck muscle activity in a pro- and anti-saccade task. Many neural areas and certain neck muscles become active in response to the presentation of a visual stimulus. This visual response on the neck muscles can result in a head turning synergy that orients the head towards the stimulus. By dissociating the typical stimulus-response paradigm, we can analyze if and how the bottom-up visual activity changes in relation to different contexts. A number of cortical and subcortical areas are involved in the generation of correct anti-saccades. By combining EMG recordings while subjects perform this task, we can examine whether top-down task-related activity is present in the neck muscles. This experiment could reveal flexibility in the eye-head gaze shift system that has previously gone unreported. Chapter three will elucidate the supplementary eye fields (SEF) role in the control of orienting eye-head gaze shifts. Neck EMG activity was recorded while providing electrical microstimulation to the SEF in a pro-saccade task The combination of EMGs and SEF stimulation is the first to systematically study the cephalomotor command during head-restrained and head-unrestrained orienting eye-head gaze shifts. The evoked activity of EMGs could reveal functional properties of the neural circuitry between the SEF and the motor related neurons responsible for eye and head movements. The timing and metrics of evoked EMG activity and eye-head gaze shifts are consistent with other frontal areas suggesting a functional role of the frontal cortex in influencing eye-head gaze shifts. Chapter four will combine EMG recordings with SEF stimulation during a pro- and anti-saccade task. The SEF is thought to serve as an interface between high-level cognitive control of gaze shifts and low-level activity associated with the production of saccades. As will be described later in the thesis, neck muscles demonstrate top-down task related activity during anti-saccades. The SEF is a likely candidate for the generation of task-dependent signals observed during anti-saccades. By combining SEF stimulation and neck EMGs in an anti-saccade task, we can reveal if neck muscle activity is consistent with a role for the SEF in the contextual control of eye-head gaze shifts. In summary, this thesis identifies three central point’s concerning orienting eye-head gaze shifts. First, chapter two emphasizes the complex interaction of sensori-motor processes in orienting head movements. Second, chapter three attests to the consistent nature of certain areas in frontal cortex and their impact on eye-head gaze shifts. Finally, chapter four demonstrates a potential candidate for influencing the contextual control of cephalomotor commands. Combined, these results highlight the complex interactions of sensori-motor transformations in the motor periphery and emphasize the parallel nature of information processing during the contextual control of eye-head gaze shifts

Studies on eye movements in Parkinson's disease

Heterogeneity in Parkinson’s Disease (PD) phenotype and genotype is probably the main reason why, despite the abundance of biomarkers, we still lack a robust method for diagnosis and prognosis, besides clinical evaluation. Subjective changes in vision and objective measures in eye movements have been extensively studied, but the results are mainly used to better understand the pathophysiology of PD and are not integrated into the clinical praxis. The aim of this doctoral project was to examine if eye movements could serve as useful biomarkers for PD diagnosis and prognosis, and investigate their association with motor function, cognition, and medication effect. In addition, we aimed to examine cognition in a group of patients with a rare metabolic disorder and prominent eye-movement difficulties, the Norrbottnian Gaucher Disease 3 (GD3). Saccades, reading, and sustained fixation were examined in PD patients and healthy controls (HC) in the first three studies. Recruitment took place at Karolinska University Hospital Huddinge for the first two studies, and for the third study at Academic Specialist Center in Stockholm. Three different eye trackers were used, a head-mounted and two screen based, and the assessments were performed in a clinical setting. In the first two studies patients were examined in ON and OFF medication status, in order to evaluate the role of levodopa. In study 1, we examined saccadic parameters in 20 HC and 40 PD patients; study 2 involved reading assessments for 13 HC and 19 PD patients; in study 3 we examined sustained fixation in 43 HC and 50 PD patients. Recruitment for study 4 took place at Sunderby Regional Hospital, in Luleå, and we examined 10 patients with the Norrbottnian type of GD3. Cognitive evaluation was done with the Repeatable Battery for Assessment of Neuropsychological Status (RBANS). PD participants had worse saccadic performance, a slower reading speed, and deficient fixation control. Saccadic gain was associated with motor performance, while latency was related to cognition. Levodopa had no effect on saccadic gain, it worsened latency for the horizontal visually guided saccades and ameliorated the latency of antisaccades, but not the error rate or reading performance. We assumed that reading difficulties were attributed to cognitive, rather than oculomotor deficits. Fixation was more easily interrupted in PD compared to HC, and PD participants’ pupils did not dilate to the same extent as HC, in response to the cognitive effort put during sustained fixation. In study 4 we found that patients with the Norrbottnian type of GD3 have an overall worse cognitive performance compared to that of healthy population, scoring worse in memory and attention tests, present however with preserved language and visuospatial skills. The eye-tracking studies led to the conclusion that this method could be integrated into the clinical praxis as part of the clinical evaluation. It is easy to perform and provides reliable results that enable the understanding of motor, cognitive, and behavioral changes in PD. In order to do so, we would need a common protocol of assessment, so that the results would be comparable between different populations. The last study identified RBANS as a useful and easy-to-use tool for the cognitive examination of Norrbottnian GD3 patients

Children and older adults exhibit distinct sub-optimal cost-benefit functions when preparing to move their eyes and hands

"© 2015 Gonzalez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited"Numerous activities require an individual to respond quickly to the correct stimulus. The provision of advance information allows response priming but heightened responses can cause errors (responding too early or reacting to the wrong stimulus). Thus, a balance is required between the online cognitive mechanisms (inhibitory and anticipatory) used to prepare and execute a motor response at the appropriate time. We investigated the use of advance information in 71 participants across four different age groups: (i) children, (ii) young adults, (iii) middle-aged adults, and (iv) older adults. We implemented 'cued' and 'non-cued' conditions to assess age-related changes in saccadic and touch responses to targets in three movement conditions: (a) Eyes only; (b) Hands only; (c) Eyes and Hand. Children made less saccade errors compared to young adults, but they also exhibited longer response times in cued versus non-cued conditions. In contrast, older adults showed faster responses in cued conditions but exhibited more errors. The results indicate that young adults (18 -25 years) achieve an optimal balance between anticipation and execution. In contrast, children show benefits (few errors) and costs (slow responses) of good inhibition when preparing a motor response based on advance information; whilst older adults show the benefits and costs associated with a prospective response strategy (i.e., good anticipation)

Reflexive and volitional saccadic eye movements and their changes in age and progressive supranuclear palsy

BACKGROUND AND OBJECTIVES: Saccades, rapid movements of the eyes towards a visual or remembered target, are useful in understanding the healthy brain and the pathology of neurological conditions such as progressive supranuclear palsy (PSP). We set out to investigate the parameters of horizontal reflexive and volitional saccades, both visually guided and memory-guided, over a 1 min epoch in healthy individuals and PSP patients. METHODS: An experimental paradigm tested reflexive, volitional visually guided, and volitional memory-guided saccades in young healthy controls (n = 14; 20-31 years), PSP patients (n = 11; 46-75 years) and older age-matched healthy controls (n = 6; 56-71 years). The accuracy and velocity of saccades was recorded using an EyeBrain T2® video eye tracker and analyses performed using the MyEyeAnalysis® software. Two-way analysis of variance (ANOVA) was used to identify significant effects (p < 0.01) between young and older controls to investigate the effects of ageing upon saccades, and between PSP patients and age-matched controls to study the effects of PSP upon saccades. RESULTS: In both healthy individuals and PSP patients, volitional saccades are slower and less accurate than reflexive saccades. In PSP patients, accuracy is lower across all saccade types compared to age-matched controls, but velocity is lower only for reflexive saccades. Crucially, there is no change in accuracy or velocity of consecutive saccades over short (one-minute) timescales in controls or PSP patients. CONCLUSIONS: Velocity and accuracy of saccades in PSP does not decrease over one-minute timescales, contrary to that previously observed in Parkinson's Disease (PD), suggesting a potential clinical biomarker for the distinction of PSP from PD