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1.  The effect of linguistic and visual salience in visual world studies 
Research using the visual world paradigm has demonstrated that visual input has a rapid effect on language interpretation tasks such as reference resolution and, conversely, that linguistic material—including verbs, prepositions and adjectives—can influence fixations to potential referents. More recent research has started to explore how this effect of linguistic input on fixations is mediated by properties of the visual stimulus, in particular by visual salience. In the present study we further explored the role of salience in the visual world paradigm manipulating language-driven salience and visual salience. Specifically, we tested how linguistic salience (i.e., the greater accessibility of linguistically introduced entities) and visual salience (bottom-up attention grabbing visual aspects) interact. We recorded participants' eye-movements during a MapTask, asking them to look from landmark to landmark displayed upon a map while hearing direction-giving instructions. The landmarks were of comparable size and color, except in the Visual Salience condition, in which one landmark had been made more visually salient. In the Linguistic Salience conditions, the instructions included references to an object not on the map. Response times and fixations were recorded. Visual Salience influenced the time course of fixations at both the beginning and the end of the trial but did not show a significant effect on response times. Linguistic Salience reduced response times and increased fixations to landmarks when they were associated to a Linguistic Salient entity not present itself on the map. When the target landmark was both visually and linguistically salient, it was fixated longer, but fixations were quicker when the target item was linguistically salient only. Our results suggest that the two types of salience work in parallel and that linguistic salience affects fixations even when the entity is not visually present.
PMCID: PMC3941304  PMID: 24624108
linguistic salience; visual salience; visual world paradigm; centering theory; saliency map
2.  Saccadic Momentum and Facilitation of Return Saccades Contribute to an Optimal Foraging Strategy 
PLoS Computational Biology  2013;9(1):e1002871.
The interest in saccadic IOR is funneled by the hypothesis that it serves a clear functional purpose in the selection of fixation points: the facilitation of foraging. In this study, we arrive at a different interpretation of saccadic IOR. First, we find that return saccades are performed much more often than expected from the statistical properties of saccades and saccade pairs. Second, we find that fixation durations before a saccade are modulated by the relative angle of the saccade, but return saccades show no sign of an additional temporal inhibition. Thus, we do not find temporal saccadic inhibition of return. Interestingly, we find that return locations are more salient, according to empirically measured saliency (locations that are fixated by many observers) as well as stimulus dependent saliency (defined by image features), than regular fixation locations. These results and the finding that return saccades increase the match of individual trajectories with a grand total priority map evidences the return saccades being part of a fixation selection strategy that trades off exploration and exploitation.
Author Summary
Sometimes humans look at the same location twice. To appreciate the importance of this inconspicuous statement you have to consider that we move our eyes several billion (109) times during our lives and that looking at something is a necessary condition to enable conscious visual awareness. Thus, understanding why and how we move our eyes provides a window into our mental life. Here we investigate one heavily discussed aspect of human's fixation selection strategy: whether it inhibits returning to previously fixated locations. We analyze a large data set (more than 550,000 fixations from 235 subjects) and find that, returning to previously fixated locations happens much more often than expected from the statistical properties of eye-movement trajectories. Furthermore, those locations that we return to are not ordinary – they are more salient than locations that we do not return to. Thus, the inconspicuous statement that we look at the same locations twice reveals an important aspect of our strategy to select fixation points: That we trade off exploring our environment against making sure that we have fully comprehended the relevant parts of our environment.
PMCID: PMC3547797  PMID: 23341766
3.  Oculomotor Evidence for Top-Down Control following the Initial Saccade 
PLoS ONE  2011;6(9):e23552.
The goal of the current study was to investigate how salience-driven and goal-driven processes unfold during visual search over multiple eye movements. Eye movements were recorded while observers searched for a target, which was located on (Experiment 1) or defined as (Experiment 2) a specific orientation singleton. This singleton could either be the most, medium, or least salient element in the display. Results were analyzed as a function of response time separately for initial and second eye movements. Irrespective of the search task, initial saccades elicited shortly after the onset of the search display were primarily salience-driven whereas initial saccades elicited after approximately 250 ms were completely unaffected by salience. Initial saccades were increasingly guided in line with task requirements with increasing response times. Second saccades were completely unaffected by salience and were consistently goal-driven, irrespective of response time. These results suggest that stimulus-salience affects the visual system only briefly after a visual image enters the brain and has no effect thereafter.
PMCID: PMC3169564  PMID: 21931603
4.  Psychophysical Tests of the Hypothesis of a Bottom-Up Saliency Map in Primary Visual Cortex 
PLoS Computational Biology  2007;3(4):e62.
A unique vertical bar among horizontal bars is salient and pops out perceptually. Physiological data have suggested that mechanisms in the primary visual cortex (V1) contribute to the high saliency of such a unique basic feature, but indicated little regarding whether V1 plays an essential or peripheral role in input-driven or bottom-up saliency. Meanwhile, a biologically based V1 model has suggested that V1 mechanisms can also explain bottom-up saliencies beyond the pop-out of basic features, such as the low saliency of a unique conjunction feature such as a red vertical bar among red horizontal and green vertical bars, under the hypothesis that the bottom-up saliency at any location is signaled by the activity of the most active cell responding to it regardless of the cell's preferred features such as color and orientation. The model can account for phenomena such as the difficulties in conjunction feature search, asymmetries in visual search, and how background irregularities affect ease of search. In this paper, we report nontrivial predictions from the V1 saliency hypothesis, and their psychophysical tests and confirmations. The prediction that most clearly distinguishes the V1 saliency hypothesis from other models is that task-irrelevant features could interfere in visual search or segmentation tasks which rely significantly on bottom-up saliency. For instance, irrelevant colors can interfere in an orientation-based task, and the presence of horizontal and vertical bars can impair performance in a task based on oblique bars. Furthermore, properties of the intracortical interactions and neural selectivities in V1 predict specific emergent phenomena associated with visual grouping. Our findings support the idea that a bottom-up saliency map can be at a lower visual area than traditionally expected, with implications for top-down selection mechanisms.
Author Summary
Only a fraction of visual input can be selected for attentional scrutiny, often by focusing on a limited extent of the visual space. The selected location is often determined by the bottom-up visual inputs rather than the top-down intentions. For example, a red dot among green ones automatically attracts attention and is said to be salient. Physiological data have suggested that the primary visual cortex (V1) in the brain contributes to creating such bottom-up saliencies from visual inputs, but indicated little on whether V1 plays an essential or peripheral role in creating a saliency map of the input space to guide attention. Traditional psychological frameworks, based mainly on behavioral data, have implicated higher-level brain areas for the saliency map. Recently, it has been hypothesized that V1 creates this saliency map, such that the image location whose visual input evokes the highest response among all V1 output neurons is most likely selected from a visual scene for attentional processing. This paper derives nontrivial predictions from this hypothesis and presents their psychophysical tests and confirmations. Our findings suggest that bottom-up saliency is computed at a lower brain area than previously expected, and have implications on top-down attentional mechanisms.
PMCID: PMC1847698  PMID: 17411335
5.  Sensory Processing of Motor Inaccuracy Depends on Previously Performed Movement and on Subsequent Motor Corrections: A Study of the Saccadic System 
PLoS ONE  2011;6(2):e17329.
When goal-directed movements are inaccurate, two responses are generated by the brain: a fast motor correction toward the target and an adaptive motor recalibration developing progressively across subsequent trials. For the saccadic system, there is a clear dissociation between the fast motor correction (corrective saccade production) and the adaptive motor recalibration (primary saccade modification). Error signals used to trigger corrective saccades and to induce adaptation are based on post-saccadic visual feedback. The goal of this study was to determine if similar or different error signals are involved in saccadic adaptation and in corrective saccade generation. Saccadic accuracy was experimentally altered by systematically displacing the visual target during motor execution. Post-saccadic error signals were studied by manipulating visual information in two ways. First, the duration of the displaced target after primary saccade termination was set at 15, 50, 100 or 800 ms in different adaptation sessions. Second, in some sessions, the displaced target was followed by a visual mask that interfered with visual processing. Because they rely on different mechanisms, the adaptation of reactive saccades and the adaptation of voluntary saccades were both evaluated. We found that saccadic adaptation and corrective saccade production were both affected by the manipulations of post-saccadic visual information, but in different ways. This first finding suggests that different types of error signal processing are involved in the induction of these two motor corrections. Interestingly, voluntary saccades required a longer duration of post-saccadic target presentation to reach the same amount of adaptation as reactive saccades. Finally, the visual mask interfered with the production of corrective saccades only during the voluntary saccades adaptation task. These last observations suggest that post-saccadic perception depends on the previously performed action and that the differences between saccade categories of motor correction and adaptation occur at an early level of visual processing.
PMCID: PMC3044175  PMID: 21383849
6.  Anticipatory remapping of attentional priority across the entire visual field 
It has been suggested that one way we may create a stable percept of the visual world across multiple eye movements is to pass information from one set of neurons to another around the time of each eye movement. Previous studies have shown that some neurons in the lateral intraparietal area (LIP) exhibit anticipatory remapping: these neurons produce a visual response to a stimulus that will enter their receptive field after a saccade, but before it actually does so. LIP responses during fixation are thought to represent attentional priority, behavioral relevance or value. In this study, we test whether the remapped response represents this attentional priority, by examining the activity of LIP neurons while animals perform a visual foraging task. We find that the population responds more to a target than to a distractor before the saccade even begins to bring the stimulus into the receptive field. Within 20 ms of the saccade ending, the responses in almost a third of LIP neurons closely resemble the responses that will emerge during stable fixation. Finally, we show that in these neurons and in the population as a whole, this remapping occurs for all stimuli in all locations across the visual field and for both long and short saccades. We conclude that this complete remapping of attentional priority across the visual field could underlie spatial stability across saccades.
PMCID: PMC3508767  PMID: 23152627
7.  Understanding the Function of Visual Short-Term Memory: Transsaccadic Memory, Object Correspondence, and Gaze Correction 
Visual short-term memory (VSTM) has received intensive study over the past decade, with research focused on VSTM capacity and representational format. Yet, the function of VSTM in human cognition is not well understood. Here we demonstrate that VSTM plays an important role in the control of saccadic eye movements. Intelligent human behavior depends on directing the eyes to goal-relevant objects in the world, yet saccades are very often inaccurate and require correction. We hypothesized that VSTM is used to remember the features of the current saccade target so that it can be rapidly reacquired after an errant saccade, a fundamental task faced by the visual system thousands of times each day. In four experiments, memory-based gaze correction was found to be accurate, fast, automatic, and largely unconscious. In addition, a concurrent VSTM load was found to interfere with memory-based gaze correction, but a verbal short-term memory load did not. These findings demonstrate VSTM plays a direct role in a fundamentally important aspect of visually guided behavior, and they suggest the existence of previously unknown links between VSTM representations and the occulomotor system.
PMCID: PMC2784885  PMID: 18248135
8.  Remapping in Human Visual Cortex 
Journal of neurophysiology  2006;97(2):1738-1755.
With each eye movement, stationary objects in the world change position on the retina, yet we perceive the world as stable. Spatial updating, or remapping, is one neural mechanism by which the brain compensates for shifts in the retinal image caused by voluntary eye movements. Remapping of a visual representation is believed to arise from a widespread neural circuit including parietal and frontal cortex. The current experiment tests the hypothesis that extrastriate visual areas in human cortex have access to remapped spatial information. We tested this hypothesis using functional magnetic resonance imaging (fMRI). We first identified the borders of several occipital lobe visual areas using standard retinotopic techniques. We then tested subjects while they performed a single-step saccade task analogous to the task used in neurophysiological studies in monkeys, and two conditions that control for visual and motor effects. We analyzed the fMRI time series data with a nonlinear, fully Bayesian hierarchical statistical model. We identified remapping as activity in the single-step task that could not be attributed to purely visual or oculomotor effects. The strength of remapping was roughly monotonic with position in the visual hierarchy: remapped responses were largest in areas V3A and hV4 and smallest in V1 and V2. These results demonstrate that updated visual representations are present in cortical areas that are directly linked to visual perception.
PMCID: PMC2292409  PMID: 17093130
9.  Changes in Timing and kinematics of goal directed eye-hand movements in early-stage Parkinson’s disease 
Many daily activities involve intrinsic or extrinsic goal-directed eye and hand movements. An extensive visuomotor coordination network including nigro-striatal pathways is required for efficient timing and positioning of eyes and hands. The aim of this study was to investigate how Parkinson’s disease (PD) affects eye-hand coordination in tasks with different cognitive complexity.
We used a touch screen, an eye-tracking device and a motion capturing system to quantify changes in eye-hand coordination in early-stage PD patients (H&Y < 2.5) and age-matched controls. Timing and kinematics of eye and hand were quantified in four eye-hand coordination tasks (pro-tapping, dual planning, anti-tapping and spatial memory task).
In the pro-tapping task, saccade initiation towards extrinsic goals was not impaired. However, in the dual planning and anti-tapping task initiation of saccades towards intrinsic goals was faster in PD patients. Hand movements were differently affected: initiation of the hand movement was only delayed in the pro-tapping and dual planning task. Overall, hand movements in PD patients were slower executed compared to controls.
Whereas initiation of saccades in an extrinsic goal-directed task (pro-tapping task) is not affected, early stage PD patients have difficulty in suppressing reflexive saccades towards extrinsic goals in tasks where the endpoint is an intrinsic goal (e.g. dual planning and anti-tapping task). This is specific for eye movements, as hand movements have delayed responses in the pro-tapping and dual planning task. This suggests that reported impairment of the dorsolateral prefrontal cortex in early-stage PD patients affects only inhibition of eye movements. We conclude that timing and kinematics of eye and hand movements in visuomotor tasks are affected in PD patients. This result may have clinical significance by providing a behavioral marker for the early diagnosis of PD.
PMCID: PMC3563471  PMID: 23298720
10.  Experiences of Living and Dying With COPD 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at:
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at:
For more information on the economic analysis, please visit the PATH website:
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website:
Objective of Analysis
The objective of this analysis was to review empirical qualitative research on the experiences of patients with chronic obstructive pulmonary disease (COPD), informal caregivers (“carers”), and health care providers—from the point of diagnosis, through daily living and exacerbation episodes, to the end of life.
Clinical Need and Target Population
Qualitative empirical studies (from social sciences, clinical, and related fields) can offer important information about how patients experience their condition. This exploration of the qualitative literature offers insights into patients’ perspectives on COPD, their needs, and how interventions might affect their experiences. The experiences of caregivers are also explored.
Research Question
What do patients with COPD, their informal caregivers (“carers”), and health care providers experience over the course of COPD?
Research Methods
Literature Search
Search Strategy
Literature searches for studies published from January 1, 2000, to November 2010 were performed on November 29, 2010, using OVID MEDLINE; on November 26, 2010, using ISI Web of Science; and on November 28, 2010, using EBSCO Cumulative Index to Nursing and Allied Health Literature (CINAHL). Titles and abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. One additional report, highly relevant to the synthesis, appeared in early 2011 during the drafting of this analysis and was included post hoc.
Inclusion Criteria
English-language full reports
studies published between January 1, 2000, and November 2010
primary qualitative empirical research (using any descriptive or interpretive qualitative methodology, including the qualitative component of mixed-methods studies) and secondary syntheses of primary qualitative empirical research
studies addressing any aspect of the experiences of living or dying with COPD from the perspective of persons at risk, patients, health care providers, or informal carers; studies addressing multiple conditions were included if COPD was addressed explicitly
Exclusion Criteria
studies addressing topics other than the experiences of living or dying with COPD from the perspective of persons at risk, patients, health care providers, or informal carers
studies labelled “qualitative” but not using a qualitative descriptive or interpretive methodology (e.g., case studies, experiments, or observational analysis using qualitative categorical variables)
quantitative research (i.e., using statistical hypothesis testing, using primarily quantitative data or analyses, or expressing results in quantitative or statistical terms)
studies that did not pose an empirical research objective or question, or involve the primary or secondary analysis of empirical data
Outcomes of Interest
qualitative descriptions and interpretations (narrative or theoretical) of personal and social experiences of COPD
Summary of Findings
Experiences at Diagnosis
Patients typically seek initial treatment for an acute episode rather than for chronic early symptoms of COPD.
Many patients initially misunderstand terms such as COPD, chronic obstructive pulmonary disease, or exacerbation.
Patients may not realize that COPD is incurable and fatal; some physicians themselves do not consider early COPD to be a fatal disease.
Smokers may not readily understand or agree with the idea that smoking caused or worsens their COPD. Those who believe there is a causal link may feel regret or shame.
Experiences of Living Day to Day
COPD patients experience alternating good days and bad days. A roller-coaster pattern of ups and downs becomes apparent, and COPD becomes a way of life.
Patients use many means (social, psychological, medical, organizational) to control what they can, and to cope with what they cannot. Economic hardship, comorbidities, language barriers, and low health literacy can make coping more difficult.
Increasing vulnerability and unpredictable setbacks make patients dependent on others for practical assistance, but functional limitations, institutional living or self-consciousness can isolate patients from the people they need.
For smokers, medical advice to quit can conflict with increased desire to smoke as a coping strategy.
Many of the factors that isolate COPD patients from social contact also isolate them from health care.
Experiences of Exacerbations
Patients may not always attribute repeated exacerbations to advancing disease, instead seeing them as temporary setbacks caused by activities, environmental factors, faltering self-management, or infection.
Lack of confidence in community-based services leads some patients to seek hospital admission, but patients also feel vulnerable when hospitalized. They may feel dependent on others for care or traumatized by hospital care routines.
Upon hospital discharge following an exacerbation, patients may face new levels of uncertainty about their illness, prognosis, care providers, and supports.
Experiences of the End of Life
Patients tend to be poorly informed about the long-term prognosis of COPD and what to expect toward the end of life; this lack of understanding impairs quality of life as the disease progresses.
As the end of life approaches, COPD patients face the usual challenges of daily living, but in a context of increasing exacerbations and deepening dependency. Activities and mobility decrease, and life may become confined.
Some clinicians have difficulty identifying the beginning of “the end of life,” given the unpredictable course of COPD. Long-term physician-patient relationships, familiarity and understanding, trust, good communication skills, sensitivity, and secure discussion settings can help facilitate end-of-life discussions.
Divergent meanings and goals of palliative care in COPD lead to confusion about whether such services are the responsibility of home care, primary care, specialty care, or even critical care. Palliative end-of-life care may not be anticipated prior to referral for such care. A palliative care referral can convey the demoralizing message that providers have “given up.”
Experiences of Carers
Carers’ challenges often echo patients’ challenges, and include anxiety, uncertainty about the future, helplessness, powerlessness, depression, difficulties maintaining employment, loss of mobility and freedoms, strained relationships, and growing social isolation.
Carers feel pressured by their many roles, struggling to maintain patience when they feel overwhelmed, and often feeling guilty about not doing enough.
Carers often face their own health problems and may have difficulty sustaining employment.
Synthesis: A Disease Trajectory Reflecting Patient Experiences
The flux of needs in COPD calls for service continuity and flexibility to allow both health care providers and patients to respond to the unpredictable yet increasing demands of the disease over time.
PMCID: PMC3384365  PMID: 23074423
11.  A Case-Control Study to Assess the Relationship between Poverty and Visual Impairment from Cataract in Kenya, the Philippines, and Bangladesh 
PLoS Medicine  2008;5(12):e244.
The link between poverty and health is central to the Millennium Development Goals (MDGs). Poverty can be both a cause and consequence of poor health, but there are few epidemiological studies exploring this complex relationship. The aim of this study was to examine the association between visual impairment from cataract and poverty in adults in Kenya, Bangladesh, and the Philippines.
Methods and Findings
A population-based case–control study was conducted in three countries during 2005–2006. Cases were persons aged 50 y or older and visually impaired due to cataract (visual acuity < 6/24 in the better eye). Controls were persons age- and sex-matched to the case participants with normal vision selected from the same cluster. Household expenditure was assessed through the collection of detailed consumption data, and asset ownership and self-rated wealth were also measured. In total, 596 cases and 535 controls were included in these analyses (Kenya 142 cases, 75 controls; Bangladesh 216 cases, 279 controls; Philippines 238 cases, 180 controls). Case participants were more likely to be in the lowest quartile of per capita expenditure (PCE) compared to controls in Kenya (odds ratio = 2.3, 95% confidence interval 0.9–5.5), Bangladesh (1.9, 1.1–3.2), and the Philippines (3.1, 1.7–5.7), and there was significant dose–response relationship across quartiles of PCE. These associations persisted after adjustment for self-rated health and social support indicators. A similar pattern was observed for the relationship between cataract visual impairment with asset ownership and self-rated wealth. There was no consistent pattern of association between PCE and level of visual impairment due to cataract, sex, or age among the three countries.
Our data show that people with visual impairment due to cataract were poorer than those with normal sight in all three low-income countries studied. The MDGs are committed to the eradication of extreme poverty and provision of health care to poor people, and this study highlights the need for increased provision of cataract surgery to poor people, as they are particularly vulnerable to visual impairment from cataract.
Hannah Kuper and colleagues report a population-based case-control study conducted in three countries that found an association between poverty and visual impairment from cataract.
Editors' Summary
Globally, about 45 million people are blind. As with many other conditions, avoidable blindness (preventable or curable blindness) is a particular problem for people in developing countries—90% of blind people live in poor regions of the world. Although various infections and disorders can cause blindness, cataract is the most common cause. In cataract, which is responsible for half of all cases of blindness in the world, the lens of the eye gradually becomes cloudy. Because the lens focuses light to produce clear, sharp images, as cataract develops, vision becomes increasingly foggy or fuzzy, colors become less intense, and the ability to see shapes against a background declines. Eventually, vision may be lost completely. Cataract can be treated with an inexpensive, simple operation in which the cloudy lens is surgically removed and an artificial lens is inserted into the eye to restore vision. In developed countries, this operation is common and easily accessible but many poor countries lack the resources to provide the operation to everyone who needs it. In addition, blind people often cannot afford to travel to the hospitals where the operation, which also may come with a fee, is done.
Why Was This Study Done?
Because blindness may reduce earning potential, many experts believe that poverty and blindness (and, more generally, poor health) are inextricably linked. People become ill more often in poor countries than in wealthy countries because they have insufficient food, live in substandard housing, and have limited access to health care, education, water, and sanitation. Once they are ill, their ability to earn money may be reduced, which increases their personal poverty and slows the economic development of the whole country. Because of this potential link between health and poverty, improvements in health are at the heart of the United Nations Millennium Development Goals, a set of eight goals established in 2000 with the primary aim of reducing world poverty. However, few studies have actually investigated the complex relationship between poverty and health. Here, the researchers investigate the association between visual impairment from cataract and poverty among adults living in three low-income countries.
What Did the Researchers Do and Find?
The researchers identified nearly 600 people aged 50 y or more with severe cataract-induced visual impairment (“cases”) primarily through a survey of the population in Kenya, Bangladesh, and the Philippines. They matched each case to a normally sighted (“control”) person of similar age and sex living nearby. They then assessed a proxy for the income level, measured as “per capita expenditure” (PCE), of all the study participants (people with cataracts and controls) by collecting information about what their households consumed. The participants' housing conditions and other assets and their self-rated wealth were also measured. In all three countries, cases were more likely to be in the lowest quarter (quartile) of the range of PCEs for that country than controls. In the Philippines, for example, people with cataract-affected vision were three times more likely than normally sighted controls to have a PCE in the lowest quartile than in the highest quartile. The risk of cataract-related visual impairment increased as PCE decreased in all three countries. Similarly, severe cataract-induced visual impairment was more common in those who owned fewer assets and those with lower self-rated wealth. However, there was no consistent association between PCE and the level of cataract-induced visual impairment.
What Do These Findings Mean?
These findings show that there is an association between visual impairment caused by cataract and poverty in Kenya, Bangladesh, and the Philippines. However, because the financial circumstances of the people in this study were assessed after cataracts had impaired their sight, this study does not prove that poverty is a cause of visual impairment. A causal connection between poverty and cataract can only be shown by determining the PCEs of normally sighted people and following them for several years to see who develops cataract. Nevertheless, by confirming an association between poverty and blindness, these findings highlight the need for increased provision of cataract surgery to poor people, particularly since cataract surgery has the potential to improve the quality of life for many people in developing countries at a relatively low cost.
Additional Information.
Please access these Web sites via the online version of this summary at
This study is further discussed in a PLoS Medicine Perspective by Susan Lewallen
The MedlinePlus encyclopedia contains a page on cataract, and MedlinePlus also provides a list of links to further information about cataract (in English and Spanish)
VISION 2020, a global initiative for the elimination of avoidable blindness launched by the World Health Organization and the International Agency for the Prevention of Blindness, provides information in several languages about many causes of blindness, including cataract. It also has an article available for download on blindness, poverty, and development
Information is available from the World Health Organization on health and the Millennium Development Goals (in English, French, and Spanish)
The International Centre for Eye Health carries out research and education activities to improve eye health and eliminate avoidable blindness with a focus on populations with low incomes
PMCID: PMC2602716  PMID: 19090614
12.  Eye movements and attention: The role of pre-saccadic shifts of attention in perception, memory and the control of saccades 
Vision research  2012;74:40-60.
Saccadic eye movements and perceptual attention work in a coordinated fashion to allow selection of the objects, features or regions with the greatest momentary need for limited visual processing resources. This study investigates perceptual characteristics of pre-saccadic shifts of attention during a sequence of saccades using the visual manipulations employed to study mechanisms of attention during maintained fixation. The first part of this paper reviews studies of the connections between saccades and attention, and their significance for both saccadic control and perception. The second part presents three experiments that examine the effects of pre-saccadic shifts of attention on vision during sequences of saccades. Perceptual enhancements at the saccadic goal location relative to non-goal locations were found across a range of stimulus contrasts, with either perceptual discrimination or detection tasks, with either single or multiple perceptual targets, and regardless of the presence of external noise. The results show that the preparation of saccades can evoke a variety of attentional effects, including attentionally-mediated changes in the strength of perceptual representations, selection of targets for encoding in visual memory, exclusion of external noise, or changes in the levels of internal visual noise. The visual changes evoked by saccadic planning make it possible for the visual system to effectively use saccadic eye movements to explore the visual environment.
PMCID: PMC3623695  PMID: 22809798
Eye movements; Saccadic eye movements; Saccades; Vision; Attention; Orientation identification; Detection; Visual memory; Motor planning; Dual-task performance
13.  Human Visual Search Does Not Maximize the Post-Saccadic Probability of Identifying Targets 
PLoS Computational Biology  2012;8(2):e1002342.
Researchers have conjectured that eye movements during visual search are selected to minimize the number of saccades. The optimal Bayesian eye movement strategy minimizing saccades does not simply direct the eye to whichever location is judged most likely to contain the target but makes use of the entire retina as an information gathering device during each fixation. Here we show that human observers do not minimize the expected number of saccades in planning saccades in a simple visual search task composed of three tokens. In this task, the optimal eye movement strategy varied, depending on the spacing between tokens (in the first experiment) or the size of tokens (in the second experiment), and changed abruptly once the separation or size surpassed a critical value. None of our observers changed strategy as a function of separation or size. Human performance fell far short of ideal, both qualitatively and quantitatively.
Author Summary
Vision is most sensitive to fine detail at the center of gaze (the fovea). We typically move our eyes several times a second to build up an accurate picture of the world around us and find objects of interest. Very recently, researchers have developed models of how a visual system like ours could search a scene for a specific target with the smallest possible number of eye fixations. In two experiments, we tested the assumptions underlying such models. We set up visual “games” in which observers were rewarded for their performance in moving their eyes once to recognize simple targets. To do well (earn the maximum possible reward), observers had to move their eyes according to the predictions of recent models of eye movement. We found that our observers failed to choose optimal eye movement strategies and failed to maximize their potential winnings. Our results suggest a simpler picture of eye movement selection, driven by a few simple heuristic rules that lead to good but not optimal performance in everyday tasks.
PMCID: PMC3271024  PMID: 22319428
14.  Gaze is driven by an internal goal trajectory in a visuomotor task 
The European journal of neuroscience  2012;37(7):1112-1119.
When we make hand movements to visual targets, gaze usually leads hand position by a series of saccades to task-relevant locations. Recent research suggests that the slow smooth pursuit eye movement system may interact with the saccadic system in complex tasks, suggesting that the smooth pursuit system can receive non-retinal input. We hypothesize that a combination of saccades and smooth pursuit guides the hand movements toward a goal in a complex environment, using an internal representation of future trajectories as input to the visuomotor system. This would imply that smooth pursuit leads hand position, which is remarkable since the general idea is that smooth pursuit is driven by retinal slip. To test this hypothesis, we designed a video-game task in which human subjects used their thumbs to move two cursors to a common goal position while avoiding stationary obstacles. We found that gaze led the cursors by a series of saccades interleaved with ocular fixation or pursuit. Smooth pursuit was neither correlated with cursor position nor cursor velocity. We conclude that a combination of fast and slow eye-movements, driven by an internal goal instead of a retinal goal, led the cursor movements and that both saccades and pursuit are driven by an internal representation of future trajectories of the hand. The lead distance of gaze relative to the hand may reflect a compromise between exploring future hand (cursor) paths and verifying that the cursors move along the desired paths.
PMCID: PMC3618614  PMID: 23279153
eye-hand coordination; smooth pursuit; saccades; oculomotor neurophysiology; human
15.  How Sensitive Is the Human Visual System to the Local Statistics of Natural Images? 
PLoS Computational Biology  2013;9(1):e1002873.
A key hypothesis in sensory system neuroscience is that sensory representations are adapted to the statistical regularities in sensory signals and thereby incorporate knowledge about the outside world. Supporting this hypothesis, several probabilistic models of local natural image regularities have been proposed that reproduce neural response properties. Although many such physiological links have been made, these models have not been linked directly to visual sensitivity. Previous psychophysical studies of sensitivity to natural image regularities focus on global perception of large images, but much less is known about sensitivity to local natural image regularities. We present a new paradigm for controlled psychophysical studies of local natural image regularities and compare how well such models capture perceptually relevant image content. To produce stimuli with precise statistics, we start with a set of patches cut from natural images and alter their content to generate a matched set whose joint statistics are equally likely under a probabilistic natural image model. The task is forced choice to discriminate natural patches from model patches. The results show that human observers can learn to discriminate the higher-order regularities in natural images from those of model samples after very few exposures and that no current model is perfect for patches as small as 5 by 5 pixels or larger. Discrimination performance was accurately predicted by model likelihood, an information theoretic measure of model efficacy, indicating that the visual system possesses a surprisingly detailed knowledge of natural image higher-order correlations, much more so than current image models. We also perform three cue identification experiments to interpret how model features correspond to perceptually relevant image features.
Author Summary
Several aspects of primate visual physiology have been identified as adaptations to local regularities of natural images. However, much less work has measured visual sensitivity to local natural image regularities. Most previous work focuses on global perception of large images and shows that observers are more sensitive to visual information when image properties resemble those of natural images. In this work we measure human sensitivity to local natural image regularities using stimuli generated by patch-based probabilistic natural image models that have been related to primate visual physiology. We find that human observers can learn to discriminate the statistical regularities of natural image patches from those represented by current natural image models after very few exposures and that discriminability depends on the degree of regularities captured by the model. The quick learning we observed suggests that the human visual system is biased for processing natural images, even at very fine spatial scales, and that it has a surprisingly large knowledge of the regularities in natural images, at least in comparison to the state-of-the-art statistical models of natural images.
PMCID: PMC3554546  PMID: 23358106
16.  The influence of onsets and offsets on saccade programming 
i-Perception  2010;1(2):83-94.
When making a saccadic eye movement to a peripheral target, a simultaneous stimulus onset at central fixation generally increases saccadic latency, while offsets reduce latency (‘gap effect’). Visual onsets remote from fixation also increase latency (‘remote distractor effect’); however, the influence of remote visual offsets is less clear. Previous studies, which used a search task, found that remote offsets either facilitated, inhibited, or did nothing to saccade latencies towards a peripheral target. It cannot be excluded, however, that the target selection process in such search tasks influenced the results. We therefore simplified the task and asked participants to make eye movements to a predictable target. Simultaneously with target onset, either one or multiple remote stimulus onsets and offsets were presented. It was found that peripheral onsets increased saccade latencies, but offsets did not influence the initiation of a saccade to the target. Moreover, the number of onsets and offsets did not affect the results. These results suggest that earlier effects of remote stimulus offsets and of the number of remote distractor onsets reside in the target identification process of the visual search task rather than the competition between possible saccade goals. The results are discussed in the context of models of saccade target selection.
PMCID: PMC3563056  PMID: 23397028
eye movements; remote distractor effect; saccadic response times
17.  Saccadic performance characteristics and the behavioural neurology of Tourette's syndrome 
OBJECTIVE—To better understand the neuropathological correlates of Tourette's syndrome (TS), measures of saccadic eye movement performance were examined among patients with TS.
METHODS—A case-control design was used. Twenty one patients with DSM-IV TS (mean age 40.6 years (SD 11.0); 38% female) mainly recruited from UCSD Psychiatry Services, and a community based sample of 21 normal subjects (mean age 34.6 years (SD 13.4); 43% women) participated in this study. Participants were administered ocular motor tasks assessing visual fixation, and the generation of prosaccades, predictive saccades, and antisaccades. Saccadic reaction time, amplitude, duration, and mean and peak velocity were computed. Intrusive saccades during visual fixation and the proportion of correct antisaccade responses were also evaluated.
RESULTS—The groups had similar visual fixation performance. Whereas patients with TS generated prosaccades with normal reaction times and amplitudes, their saccade durations were shorter and their mean velocities were higher than in normal subjects. During a prosaccade gap task, patients with TS exhibited an increased proportion of anticipatory saccades (RTs<90). The proportion of "express" saccades (90
PMCID: PMC1736262  PMID: 10084528
BMC Bioinformatics  2011;12(Suppl 8):S1.
The overall goal of the BioCreative Workshops is to promote the development of text mining and text processing tools which are useful to the communities of researchers and database curators in the biological sciences. To this end BioCreative I was held in 2004, BioCreative II in 2007, and BioCreative II.5 in 2009. Each of these workshops involved humanly annotated test data for several basic tasks in text mining applied to the biomedical literature. Participants in the workshops were invited to compete in the tasks by constructing software systems to perform the tasks automatically and were given scores based on their performance. The results of these workshops have benefited the community in several ways. They have 1) provided evidence for the most effective methods currently available to solve specific problems; 2) revealed the current state of the art for performance on those problems; 3) and provided gold standard data and results on that data by which future advances can be gauged. This special issue contains overview papers for the three tasks of BioCreative III.
The BioCreative III Workshop was held in September of 2010 and continued the tradition of a challenge evaluation on several tasks judged basic to effective text mining in biology, including a gene normalization (GN) task and two protein-protein interaction (PPI) tasks. In total the Workshop involved the work of twenty-three teams. Thirteen teams participated in the GN task which required the assignment of EntrezGene IDs to all named genes in full text papers without any species information being provided to a system. Ten teams participated in the PPI article classification task (ACT) requiring a system to classify and rank a PubMed® record as belonging to an article either having or not having “PPI relevant” information. Eight teams participated in the PPI interaction method task (IMT) where systems were given full text documents and were required to extract the experimental methods used to establish PPIs and a text segment supporting each such method. Gold standard data was compiled for each of these tasks and participants competed in developing systems to perform the tasks automatically.
BioCreative III also introduced a new interactive task (IAT), run as a demonstration task. The goal was to develop an interactive system to facilitate a user’s annotation of the unique database identifiers for all the genes appearing in an article. This task included ranking genes by importance (based preferably on the amount of described experimental information regarding genes). There was also an optional task to assist the user in finding the most relevant articles about a given gene. For BioCreative III, a user advisory group (UAG) was assembled and played an important role 1) in producing some of the gold standard annotations for the GN task, 2) in critiquing IAT systems, and 3) in providing guidance for a future more rigorous evaluation of IAT systems. Six teams participated in the IAT demonstration task and received feedback on their systems from the UAG group. Besides innovations in the GN and PPI tasks making them more realistic and practical and the introduction of the IAT task, discussions were begun on community data standards to promote interoperability and on user requirements and evaluation metrics to address utility and usability of systems.
In this paper we give a brief history of the BioCreative Workshops and how they relate to other text mining competitions in biology. This is followed by a synopsis of the three tasks GN, PPI, and IAT in BioCreative III with figures for best participant performance on the GN and PPI tasks. These results are discussed and compared with results from previous BioCreative Workshops and we conclude that the best performing systems for GN, PPI-ACT and PPI-IMT in realistic settings are not sufficient for fully automatic use. This provides evidence for the importance of interactive systems and we present our vision of how best to construct an interactive system for a GN or PPI like task in the remainder of the paper.
PMCID: PMC3269932  PMID: 22151647
PeerJ  2013;1:e9.
A large amount of classic and contemporary vision studies require subjects to fixate a target. Target fixation serves as a normalizing factor across studies, promoting the field’s ability to compare and contrast experiments. Yet, fixation target parameters, including luminance, contrast, size, shape and color, vary across studies, potentially affecting the interpretation of results. Previous research on the effects of fixation target size and luminance on the control of fixation position rendered conflicting results, and no study has examined the effects of fixation target characteristics on square-wave jerks, the most common type of saccadic intrusion. Here we set out to determine the effects of fixation target size and luminance on the characteristics of microsaccades and square-wave jerks, over a large range of stimulus parameters. Human subjects fixated a circular target with varying luminance and size while we recorded their eye movements with an infrared video tracker (EyeLink 1000, SR Research). We detected microsaccades and SWJs automatically with objective algorithms developed previously. Microsaccade rates decreased linearly and microsaccade magnitudes increased linearly with target size. The percent of microsaccades forming part of SWJs decreased, and the time from the end of the initial SWJ saccade to the beginning of the second SWJ saccade (SWJ inter-saccadic interval; ISI) increased with target size. The microsaccadic preference for horizontal direction also decreased moderately with target size . Target luminance did not affect significantly microsaccades or SWJs, however. In the absence of a fixation target, microsaccades became scarcer and larger, while SWJ prevalence decreased and SWJ ISIs increased. Thus, the choice of fixation target can affect experimental outcomes, especially in human factors and in visual and oculomotor studies. These results have implications for previous and future research conducted under fixation conditions, and should encourage forthcoming studies to report the size of fixation targets to aid the interpretation and replication of their results.
PMCID: PMC3628898  PMID: 23638403
Saccadic intrusions; Fixation control; Fixation error
The primate superior colliculus (SC) has long been known to be involved in saccade generation. However, SC neurons also exhibit fixation-related and smooth-pursuit-related activity. A parsimonious explanation for these seemingly disparate findings is that the SC contains a map of behaviorally relevant goal locations, rather than just a motor map for saccades and fixation. This explanation predicts that SC activity should reflect the behavioral goal, even when the behavioral response is not fixation or saccades, and even if the goal does not correspond to a visual stimulus. We tested this prediction by employing a tracking task that dissociates the stimulus and goal locations. In this task, monkeys tracked the invisible midpoint between two peripheral bars, such that the visual stimuli were peripheral but the goal was foveal/parafoveal. We recorded from SC neurons representing peripheral locations associated with the stimulus or central locations associated with the goal. Most neurons with peripheral response fields did not respond differently during tracking than during passive viewing of the stimulus under fixation; most neurons with central response fields responded more during tracking than during fixation, despite the lack of a visual stimulus. Moreover, the spatial distribution of activity during tracking was larger than that during fixation or tracking of a foveal stimulus, suggesting that the greater spatial uncertainty about the invisible goal corresponded to more widespread SC activity. These results demonstrate the flexibility with which activity across the SC represents the location - and also the spatial precision - of behaviorally relevant goals for multiple eye movements.
PMCID: PMC2698013  PMID: 18799675
Superior Colliculus; Pursuit; Voluntary Eye Movement; Stimulus-Response; Behavioral Goal; Population Coding
Journal of vision  2008;8(16):15.1-1518.
Selective attention is closely linked to eye movements. Prior to a saccade, attention shifts to the saccadic goal at the expense of surrounding locations. Such a constricted attentional field, while useful to ensure accurate saccades, constrains the spatial range of high-quality perceptual analysis. The present study showed that the attention could be allocated to locations other than the saccadic goal without disrupting the ongoing pattern of saccades. Saccades were made sequentially along a color-cued path. Attention was assessed by a visual memory task presented during a random pause between successive saccades. Saccadic planning had several effects on memory: (1) fewer letters were remembered during intersaccadic pauses than during maintained fixation; (2) letters appearing on the saccadic path, including locations previously examined, could be remembered; off-path performance was near chance; (3) memory was better at the saccadic target than all other locations, including the currently fixated location. These results show that the distribution of attention during intersaccadic pauses results from a combination of top-down enhancement at the saccadic target coupled with a more automatic allocation of attention to selected display locations. This suggests that the visual system has mechanisms to control the distribution of attention without interfering with ongoing saccadic programming.
PMCID: PMC2629352  PMID: 19146281
PLoS ONE  2013;8(9):e74845.
Eye-movement abnormalities in schizophrenia are a well-established phenomenon that has been observed in many studies. In such studies, visual targets are usually presented in the center of the visual field, and the subject's head remains fixed. However, in every-day life, targets may also appear in the periphery. This study is among the first to investigate eye and head movements in schizophrenia by presenting targets in the periphery of the visual field.
Methodology/Principal Findings
Two different visual recognition tasks, color recognition and Landolt orientation tasks, were presented at the periphery (at a visual angle of 55° from the center of the field of view). Each subject viewed 96 trials, and all eye and head movements were simultaneously recorded using video-based oculography and magnetic motion tracking of the head. Data from 14 patients with schizophrenia and 14 controls were considered. The patients had similar saccadic latencies in both tasks, whereas controls had shorter saccadic latencies in the Landolt task. Patients performed more head movements, and had increased eye-head offsets during combined eye-head shifts than controls.
Patients with schizophrenia may not be able to adapt to the two different tasks to the same extent as controls, as seen by the former's task-specific saccadic latency pattern. This can be interpreted as a specific oculomotoric attentional dysfunction and may support the hypothesis that schizophrenia patients have difficulties determining the relevance of stimuli. Patients may also show an uneconomic over-performance of head-movements, which is possibly caused by alterations in frontal executive function that impair the inhibition of head shifts. In addition, a model was created explaining 93% of the variance of the response times as a function of eye and head amplitude, which was only observed in the controls, indicating abnormal eye-head coordination in patients with schizophrenia.
PMCID: PMC3769305  PMID: 24040351
In scrutinizing a scene, the eyes alternate between fixations and saccades. During a fixation, two component processes can be distinguished: visual encoding and selection of the next fixation target. We aimed to distinguish the neural correlates of these processes in the electrical brain activity prior to a saccade onset. Participants viewed color photographs of natural scenes, in preparation for a change detection task. Then, for each participant and each scene we computed an image heat map, with temperature representing the duration and density of fixations. The temperature difference between the start and end points of saccades was taken as a measure of the expected task-relevance of the information concentrated in specific regions of a scene. Visual encoding was evaluated according to whether subsequent change was correctly detected. Saccades with larger temperature difference were more likely to be followed by correct detection than ones with smaller temperature differences. The amplitude of presaccadic activity over anterior brain areas was larger for correct detection than for detection failure. This difference was observed for short “scrutinizing” but not for long “explorative” saccades, suggesting that presaccadic activity reflects top-down saccade guidance. Thus, successful encoding requires local scanning of scene regions which are expected to be task-relevant. Next, we evaluated fixation target selection. Saccades “moving up” in temperature were preceded by presaccadic activity of higher amplitude than those “moving down”. This finding suggests that presaccadic activity reflects attention deployed to the following fixation location. Our findings illustrate how presaccadic activity can elucidate concurrent brain processes related to the immediate goal of planning the next saccade and the larger-scale goal of constructing a robust representation of the visual scene.
PMCID: PMC3694272  PMID: 23818877
saccades; EEG; presaccadic interval; attention; visual encoding; saccade guidance; change detection; heat maps
The general research question of the present study was to assess the impact of visually salient online adverts on children's task-oriented internet use. In order to answer this question, an experimental study was constructed in which 9- and 12-year-old Swedish children were asked to solve a number of tasks while interacting with a mockup website. In each trial, web adverts in several saliency conditions were presented. By both measuring children's task accuracy, as well as the visual processing involved in solving these tasks, this study allows us to infer how two types of visual saliency affect children's attentional behavior, and whether such behavioral effects also impacts their task performance. Analyses show that low-level visual features and task relevance in online adverts have different effects on performance measures and process measures respectively. Whereas task performance is stable with regard to several advert saliency conditions, a marked effect is seen on children's gaze behavior. On the other hand, task performance is shown to be more sensitive to individual differences such as age, gender and level of gaze control. The results provide evidence about cognitive and behavioral distraction effects in children's task-oriented internet use caused by visual saliency in online adverts. The experiment suggests that children to some extent are able to compensate for behavioral effects caused by distracting visual stimuli when solving prospective memory tasks. Suggestions are given for further research into the interdiciplinary area between media research and cognitive science.
PMCID: PMC3921552  PMID: 24575057
online advertising; children; internet use; distraction; visual saliency; visual attention
The Journal of Neuroscience  2013;33(41):16394-16408.
Neuronal activity in the frontal eye field (FEF) ranges from purely motor (related to saccade production) to purely visual (related to stimulus presence). According to numerous studies, visual responses correlate strongly with early perceptual analysis of the visual scene, including the deployment of spatial attention, whereas motor responses do not. Thus, functionally, the consensus is that visually responsive FEF neurons select a target among visible objects, whereas motor-related neurons plan specific eye movements based on such earlier target selection. However, these conclusions are based on behavioral tasks that themselves promote a serial arrangement of perceptual analysis followed by motor planning. So, is the presumed functional hierarchy in FEF an intrinsic property of its circuitry or does it reflect just one possible mode of operation? We investigate this in monkeys performing a rapid-choice task in which, crucially, motor planning always starts ahead of task-critical perceptual analysis, and the two relevant spatial locations are equally informative and equally likely to be target or distracter. We find that the choice is instantiated in FEF as a competition between oculomotor plans, in agreement with model predictions. Notably, although perception strongly influences the motor neurons, it has little if any measurable impact on the visual cells; more generally, the more dominant the visual response, the weaker the perceptual modulation. The results indicate that, contrary to expectations, during rapid saccadic choices perceptual information may directly modulate ongoing saccadic plans, and this process is not contingent on prior selection of the saccadic goal by visually driven FEF responses.
PMCID: PMC3792470  PMID: 24107969

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