Development of eye-movement control

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Brain Cogn. Author manuscript; available in PMC 2009 December 1.
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Published in final edited form as:
Brain Cogn. 2008 December ; 68(3): 293-308. doi:10.1016/j.bandc.2008.08.019.
Development of eye-movement control
Beatriz Luna*, Katerina Velanova, and Charles F. Geier
Laboratory of Neurocognitive Development, Department of Psychology and the Center for the
Neural Basis of Cognition, University of Pittsburgh, 121 Meyran Avenue, Loeffler Building Room
111, Pittsburgh, PA 15213, USA
Abstract
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
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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.
Keywords
Oculomotor; Working memory; Inhibition; Saccades; Cognition; DLPFC; FEF
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1. Introduction
The neurodevelopmental basis of psychopathology is not widely recognized. Disorders such
as schizophrenia, bipolar disorder, anxiety disorder, and anorexia nervosa often emerge during
adolescence from systems that appeared to have been developing within normative ranges.
Disorders such as autism, attention deficit hyperactivity disorder (ADHD), and Tourette's
syndrome, while present early in development, show unique developmental progressions. Each
of these disorders is now understood as having a neurobiological basis in which development
plays a significant role. While most of the work on the neurobiological basis of
psychopathology has focused on the mature system, investigation of the developmental
trajectories of such disorders can provide crucial information regarding their etiology and,
importantly, insight on appropriate windows for intervention and the effects of treatment.
(c) 2008 Published by Elsevier Inc.
* Corresponding author. Fax: +1 412 383 8179. E-mail address: lunab@upmc.edu (B. Luna)..

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Eye-movement tasks are a unique neuroscientific tool that allows us to examine the relationship
between brain and behavior and its development, critically important to our understanding of
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the neurobiological basis of psychiatric illnesses. Oculomotor methods have proven to be
sensitive to impaired executive function in a wide range of psychopathologies that are believed
to have a neurodevelopmental basis, such as schizophrenia, ADHD, autism, and others
(Everling & Fischer, 1998; Sweeney, Takarae, Macmillan, Luna, & Minshew, 2004) (see
Section by Rommelse et al., in this volume). Specifically, voluntary control of saccades is
particularly sensitive to psychopathology (Sweeney et al., 2004). These impairments are
believed to reflect abnormalities in circuitry supporting executive control of responses that is
also core to psychopathology.
This review will focus on the developmental transition from adolescence to adulthood of eye-
movement performance on tasks of sensorimotor and cognitive control. During this period,
performance on various eye-movement tasks begins to reach stabilization, paralleling
developmental changes in the brain. Specific brain maturational processes will be described
first because they provide the bases for developmental improvements in behavior. We then
review the literature on the development of basic eye-movement processes as well as those
that require cognitive control, including response inhibition, working memory, and reward
processing. We conclude with a summary of which processes are mature and which have a
protracted development which support the transition to adult-level eye-movement control.
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2. The oculomotor system: A Model for characterizing cognitive development
The oculomotor system is an ideal system for investigating the neural basis of reflexive and
voluntary behavior and for characterizing developmental improvements in behavior that are
linked to brain maturational processes. Oculomotor tasks have been used extensively in
investigations of the brain bases of higher cognitive processes such as memory, planning,
expectation, and reading (Basso, 1998; Evarts, Shinoda, & Wise, 1984; Hutton & Ettinger,
2006; Land & Furneaux, 1997) in healthy populations. Given that such processes are also often
disrupted in psychiatric illness, oculomotor tasks have been used to investigate the biological
basis of clinical impairments (Everling & Fischer, 1998; Luna & Sweeney, 1999; Luna &
Sweeney, 2001). By adding cognitive demands to a task, voluntary eye movements require the
use of high-level cognitive processes as they generate neuronal activity throughout the brain
in anticipation of a planned response, allowing brain regions involved in cognitive processes
to be identified (Basso, 1998). Delineating the emergence of this brain circuitry through
development can thus provide us with valuable information about the brain/behavior
interaction underlying cognitive maturation.
Eye-movement studies also have a good fit with pediatric populations. Oculomotor tasks are
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simple and can readily be performed successfully by children (Cohen & Ross, 1978; Ross,
Radant, & Hommer, 1993). Performance on these tasks is less likely to be aided by verbal or
learning strategies which often overestimate developmental progression in neuropsychological
tests. Moreover, the stimulus-response relationship of a saccade to a visual stimulus is direct,
in contrast to paper and pencil or manual responses where transformations to adapt to different
input/output modalities are applied. Additionally, eye-movement responses can be measured
with extreme precision and are unusually rich in terms of derivable parameters compared to
other modes of responses (e.g., manual responses) (see Smyrnis review, in this volume).
Furthermore, the oculomotor system is well suited to investigate brain/behavior relationships
because single-cell studies in non-human primates have delineated its neurophysiology,
neuroanatomy, and neurochemistry to a greater degree than other systems (Bon & Lucchetti,
1990; Bruce & Goldberg, 1985; Robinson, Goldberg, & Stanton, 1978). As such, the
oculomotor system provides a unique model for making links between brain and behavior.
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Performance on these tasks has also been well documented in normal adults (Leigh & Zee,
1991) and brain lesion patients (Guitton, Buchtel, & Douglas, 1985; Henik, Rafal, & Rhodes,
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1994; Paus et al., 1991; Pierrot-Deseilligny, Rivaud, Gaymard, Muri, & Vermersch, 1995) (see
Mueri & Nyffeler review, in this volume). Additionally, oculomotor tasks are known to result
in robust brain activation in adult subjects, engaging a distributed network including the frontal
eye field (FEF), posterior parietal cortex (PPC), the supplementary eye fields (SEF),
dorsolateral prefrontal cortex (DLPFC; see glossary) basal ganglia, thalamus, superior
colliculus (see glossary), and cerebellum (see glossary) (Luna et al., 1998; Muri et al., 1996;
Petit, Clark, Ingeholm, & Haxby, 1997; Sweeney et al., 1996). The oculomotor system is thus
particularly well suited for functional neuroimaging studies and to test hypotheses about
changes in brain systems during development.
Additionally, oculomotor tasks are exquisitely adaptable. Different oculomotor paradigms
have been developed that tap into discrete behavioral and cognitive processes. Pursuit tasks
require the tracking of a visual stimulus which allows prediction (see glossary) and adjustment
processes to be assessed (see Barnes et al. review in this issue). Fixation tasks test the ability
to voluntarily retain gaze on a visual stimulus, thereby reflecting cognitive control. Visually
guided saccade tasks require the simple, reflexive foveation of a visual stimulus, which allows
basic aspects of attention and sensorimotor control to be assessed (see Hutton review in this
Issue). A cognitive load can also be added to eye-movement tasks allowing higher-order
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cognitive processes to be investigated (see Hutton review in this issue). The antisaccade
task (Hallett, 1978) requires the suppression of a prepotent saccadic response and the generation
of an endogenous response, modulated by the integration of preparatory activity (see glossary)
in frontal and brain stem regions (Everling & Munoz, 2000). The oculomotor delayed response
(ODR) task, the prototypical spatial working-memory task used in single-cell studies with non-
human primates (Funahashi, Bruce, & Goldman-Rakic, 1989; Hikosaka & Wurtz, 1983),
requires the execution of a saccade guided only by the memory of a previously presented target
location and is also subserved by a widely distributed fronto-parieto-striatal network
(Funahashi et al., 1989; Sweeney et al., 1996). Given that the regional neurophysiology
subserving performance on these oculomotor tests has been well studied, changes in
performance due to cognitive development can be interpreted within the context of a well-
developed neuroscience and neurological framework.
3. Brain maturation
Concurrent with the influences of the environment and learning on age-related improvements
in cognitive control, brain maturation processes provide the mechanisms for these processes
to affect behavior. During adolescence, the brain undergoes significant specialization that
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enables the individual to be adaptable to their particular environment. Understanding these
changes in brain structure and periods of plasticity can provide insight on the possible
neurodevelopmental underpinnings of psychopathology.
Although the skull thickens throughout childhood and is often interpreted as reflecting change
in brain size, the gross morphology of the brain is actually in place early in development. The
degree of cortical folding (Armstrong, Schleicher, Omran, Curtis, & Zilles, 1995), overall size,
weight, and regional functional specialization is adult-like by early childhood (Caviness,
Kennedy, Bates, & Makris, 1996; Giedd Snell, et al., 1996; Reiss, Abrams, Singer, Ross, &
Denckla, 1996). While the basic aspects of brain development are in place early, key processes
which refine the basic structure persist, sculpting the brain to fit the biological and external
environments. These processes include synaptic pruning and myelination (Huttenlocher,
1990; Pfefferbaum et al., 1994; Yakovlev & Lecours, 1967) which enhance neuronal
processing and support mature cognitive control of behavior.
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Synaptic pruning refers to the programmed loss of excessive neuronal connections of which
experience is thought to be a primary contributor (Rauschecker & Marler, 1987). The loss of
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non-essential connections results in neural systems that support complex computations within
regional circuitry, as well as enhancing the capacity and speed of information processing
(Huttenlocher, 1990; Huttenlocher & Dabholkar, 1997). Structural neuroimaging studies have
indicated reductions in gray matter throughout cortical association areas, notably the frontal
and temporal regions (Giedd et al., 1999; Gogtay et al., 2004; Paus et al., 1999; Toga,
Thompson, & Sowell, 2006), as well as the basal ganglia (Sowell, Thompson, Holmes,
Jernigan, & Toga, 1999), thought in part to reflect loss of synaptic connections. Notably, the
last parts of the brain to show persistent decreases in gray matter volume are association areas
in each brain lobe and not a hierarchical protracted development of frontal regions as had been
traditionally thought (see Fig. 1). These results indicate that the transition to adult-level control
of behavior is supported by the ability to efficiently integrate information throughout the brain,
which would support the complex computations needed for executive control of responses.
Myelination refers to the process of electrically insulating nerve tracts, which has the effect of
significantly increasing the speed of neuronal transmission (Drobyshevsky et al., 2005).
Increased speed of neuronal transmission allows for distant regions to integrate function more
efficiently. Importantly, this supports the integration of widely distributed circuitry needed for
complex behavior (Goldman-Rakic, Chafee, & Friedman, 1993). Specifically, these structural
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changes are believed to underlie the functional integration of frontal regions with the rest of
the brain supporting top-down control of behavior (Chugani, 1998; Luna & Sweeney, 2004;
Thatcher, Walker, & Giudice, 1987). While some subcortical areas such as the brain stem
myelinate early (Sano, Kaga, Kuan, Ino, & Mima, 2007), neocortical areas continue to
myelinate past adolescence and may reflect both reduced synaptic connections and increased
myelination. Diffusion Tensor Imaging (DTI; see glossary) is an MRI method that images the
coherence of the trajectory of water molecules. Given that there is higher coherence of water
molecule trajectories within tracts, this method can identify white matter tracts and provide a
measure of white matter integrity of which myelination is a primary factor (Conturo,
McKinstry, Akbudak, & Robinson, 1996; Moseley et al., 1990). DTI studies indicate a
continued increase in frontal white matter integrity throughout childhood, providing evidence
for continued myelination with age (Klingberg, Vaidya, Gabrieli, Moseley, & Hedehus,
1999). Similar to findings regarding gray matter thinning, myelination also does not occur last
in frontal regions but throughout the brain. These findings suggest that the functional
integration of widely distributed circuitry characterizes late development into adulthood (Luna
& Sweeney, 2004).
Taken together, these studies indicate that the brain systems crucial for exerting cognitive
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control over behavior are still maturing during adolescence. An immature system is able to
exert cognitive control, but fails to do so in a consistent manner and with limited flexibility
and motivational control. In other words, although the basic elements are established,
refinements persist, which support the necessary efficiency in circuit processing to establish
reliable executive control evident in adulthood.
4. Development of the pursuit system
The smooth pursuit system is distinct from the saccadic system (described below) in that it
supports voluntarily foveation of a stimulus that is moving. This is the system that allows us,
for example, to catch a ball speeding toward us, or to cross the street without getting run over
by a moving vehicle. Different from the rapid eye movements in the saccade system, pursuit
involves slow eye movements (as well as small compensatory saccades) that approximate the
velocity of a moving target in order to focus the visual image on the fovea. Single-cell and
human neuroimaging studies have found that smooth pursuit is supported by regions adjacent
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to the saccade system (Berman et al., 1999; MacAvoy, Gottlieb, & Bruce, 1991) and overlaps
with regions supporting the vestibular system, which is integral to pursuit processes
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(Fukushima, Akao, Kurkin, Kaneko, & Fukushima, 2006). Areas related to pursuit include the
cerebellar floccular region, dorsal vermis, caudal fastigial nucleus, medial superior temporal
cortical area, caudal FEF, SEF, dorsolateral pontine nucleus, and nucleus reticularis tegmenti
pontis (see glossary; for review see Fukushima et al., 2006). Additionally, pursuit also recruits
regions of visual cortex (V5; see glossary, a.k.a. area MT) known to support motion processing
(Newsome, Wurtz, & Komatsu, 1988), also see reviews by Lencer & Trillenberg; Ilg & Their;
Sharpe; and Barnes, in this volume).
While the pursuit system is immature at birth, it undergoes significant improvements in the
first year of life. In the first two weeks after birth, there is evidence for the ability to track a
moving object using optokinetic nystagmus (see glossary) but not yet smooth pursuit (Haishi
& Kokubun, 1998; Rosander, 2007; Shea & Aslin, 1990). In the first 2 months of life, tracking
of moving objects is accomplished by a series of saccadic movements (Rosander & von
Hofsten, 2002; Roucoux, Culee, & Roucoux, 1983; Shea & Aslin, 1990). The ability to track
a moving object with slow, controlled smooth eye movements that are distinct from saccades
comes on-line after the first few months of life, but it is slow and inaccurate (Rosander & von
Hofsten, 2002; Shea & Aslin, 1990). Increases in pursuit speed show great improvements
through infancy supporting the ability to track faster moving stimuli (Roucoux et al., 1983).
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During the first few months of life, there are also significant improvements in the ability to
coordinate head movements with gaze shifts, becoming mature by approximately 7 months of
age (Daniel & Lee, 1990). Saccadic aspects of pursuit tracking, which are needed to make
adjustments, are present by 6 months (Gredeback, von Hofsten, Karlsson, & Aus, 2005) and
continue to appear adult-like through childhood and adolescence (Ross et al., 1993). Important
for pursuit processes is the ability to predict movement in repetitive tracking enhancing pursuit
accuracy. Consistent predictive gaze tracking is not present until 8 months of age (Gredeback
et al., 2005) and continues to improve through childhood (Salman, Sharpe, Lillakas, Dennis,
& Steinbach, 2006).
The ability to tightly match pursuit eye movements with a moving stimulus (i.e., pursuit
accuracy) continues to be immature throughout infancy (Gronqvist, Gredeback, & Hofsten,
2006; Jacobs, Harris, Shawkat, & Taylor, 1997; Shea & Aslin, 1990; von Hofsten & Rosander,
1997). Pursuit accuracy is achieved by smooth tracking movements that rely on the ability to
predict the motion of the stimuli, but small corrections are also used in the form of catch-up
saccades (Leigh & Zee, 1999). Pursuit gain (see glossary) is used to assess accuracy
independent of catch-up saccades (see glossary) hence reflecting the integrity of the pursuit
system independent from that of the saccade system (Leigh & Zee, 1999). While saccadic
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mechanisms are present since infancy, pursuit accuracy, determined by the gain of smooth eye
tracking, continues to improve through childhood into adolescence, especially at higher speeds
of pursuit tracking (Haishi & Kokubun, 1995; Katsanis, Iacono, & Harris, 1998; Ross et al.,
1993; Rutsche, Baumann, Jiang, & Mojon, 2006) and some studies show continued
improvements into mid-adolescence (Salman et al., 2006). Pursuit accuracy requires the
prediction of movement and performance monitoring requiring an efficient distributed system
that may not reach maturity until adulthood. Young human children (9-11 years old) and
monkeys (3-4 years old) have been found to have asymmetric eye movements when
performing upward pursuit eye movements, suggesting immaturities in the organization of the
floccular-vestibular system as well as compensatory mechanisms supported by the SEF that
allow for the cancellation of the downward vestibular ocular reflex (Fukushima, Akao,
Takeichi, Kaneko, & Fukushima, 2003; Takeichi et al., 2003). The establishment of mature,
adult-level pursuit tracking is believed to reflect the integration of cortical and cerebellar
circuitries supporting the predictive processes underlying pursuit accuracy (Rosander, 2007).
As such, accuracy of pursuit eye movements reflects the integrity of long-range brain circuits
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that also underlie complex behavior impaired in psychopathology. There is a large literature
that describes pursuit abnormalities in psychopathology, especially schizophrenia and their
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first degree relatives (Sweeney et al., 1998) (also see review by O'Driscoll).
5. Development of the fixation system
Visual fixation, the ability to resist eye movements in order to retain a stationary visual stimulus
in the fovea, is often considered part of the pursuit system because of the need to detect and
correct drifts in fixation (threading a needle), although there is also evidence to support that
they are distinct systems (Leigh & Zee, 1999). Visual fixation is not a resting or passive process
but in fact an active process that plays an important role in both maintaining focused attention
and inhibiting inappropriate eye movements. Visual fixation is the process that drives the
shifting of attention, including the engagement or locking of attention. Subsequent saccades
to new visual targets require that visual fixation be actively inhibited. The retention of fixation,
however, does not exclude the presence of microsaccades around the visual target (Engbert,
2006). Non-human primate single-cell studies have demonstrated that active visual fixation
also recruits a distributed circuitry including frontal eye field (see glossary; Goldberg,
Bushnell, & Bruce, 1986), posterior parietal cortex (Mountcastle, Andersen, & Motter, 1981;
Shibutani, Sakata, & Hyvarinen, 1984), and brain stem (Munoz & Wurtz, 1992).
The ability to fixate is present early in life, but the stability and control of fixation continues
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to improve through adolescence. Results indicate that the distance of fixations around the
"center of gravity" and number of intruding saccades decreases while the duration of fixation
increases from 4 to 15 years of age, indicating developmental improvement in the stability of
fixations (Aring, Gronlund, Hellstrom, & Ygge, 2007; Ygge, Aring, Han, Bolzani, &
Hellstrom, 2005). Interestingly, the degree of attention engaged in the test stimulus appears to
affect age-related differences in fixation. A clear decrease in number of breaks of fixation has
been found in 8-10 year olds to distracting peripheral stimuli when the stimulus was
meaningless and subjects were verbally instructed to maintain fixation. However, when the
central stimulus was engaging (name the animal and press a button), age-related differences
disappeared (Paus, 1989; Paus, Babenko, & Radil, 1990). These results suggest that
developmental limitations in visual fixation are related to higher order, cognitive control
processes such as the ability to inhibit eye-movement responses to distracting peripheral
stimuli.
6. Development of the reflexive saccade system
Saccades are rapid eye movements (the fastest movement the human body can make) that allow
visual stimuli to be foveated and become the target of attention. Saccades are therefore essential
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to our interaction with the world. Saccades can be automatic in nature, as when reflexively
gazing to a suddenly appearing visual stimulus (e.g., a person walks into your office and you
promptly turn to look at him/her). Saccades can also be controlled in a more endogenous and
voluntary fashion, and in this manner tap into executive control (e.g., a person walks into your
office but you stop the reflexive gazing because you "choose" to continue writing a paper). In
this section, we will describe the development of the reflexive system which requires minimal
cognitive control. The next section will review the development of voluntary saccades in detail.
Saccade performance is assessed by measuring peak velocity, latency, and accuracy. In general,
the saccade system is known to be supported by a widely distributed circuitry of which
cerebellar, brain stem, and cortical eye fields in frontal and parietal regions are involved (Bruce
& Goldberg, 1985; Goldberg & Bruce, 1990; Keating & Gooley, 1988; Leigh & Zee, 1999;
Schlag & Schlag-Rey, 1987). Saccade velocity is determined by burst neurons (see glossary)
and omni-pause neurons in the brainstem (Leigh & Zee, 1999) and is considered a basic aspect
of sensorimotor function. In infancy, saccade velocity is slower compared to adults (Hainline,
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Turkel, Abramov, Lemerise, & Harris, 1984). Developmental changes from childhood have
not been consistent, however. Some studies have found no age-related effects from childhood
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to adulthood in saccade velocity (Luna, Garver, Urban, Lazar, & Sweeney, 2004; Munoz,
Broughton, Goldring, & Armstrong, 1998), whereas other studies have found that children
make faster saccades than adults (Fioravanti, Inchingolo, Pensiero, & Spanio, 1995; Funk &
Anderson, 1977; Irving, Steinbach, Lillakas, Babu, & Hutchings, 2006). Across studies,
however, age ranges varied and given the modest difference found between ages (typically less
than 100 deg/s) there may have been differences in the sensitivity to capture developmental
changes. The studies that have not found age differences in peak velocity considered age as a
continuous variable (Luna et al., 2004) or used small age bins of 2-3 years (Munoz et al.,
1998). The ones that have found faster saccades in children have used large age bins (5 years)
(Fioravanti et al., 1995; Irving et al., 2006). One study with a large age range (3-86 years of
age) found that saccade velocity increased throughout childhood peaking in a group of 10-15
year olds followed by a decrease with age (Irving et al., 2006). Thus, age appears to have an
effect, if minimal, on saccade velocity which may be due to a peak in physical health during
adolescence or to a slowing down of basic process due to voluntary control of even basic aspects
of behavior evident in adulthood.
Saccade accuracy, the process of stopping a saccade in a location to optimally foveate a visual
stimulus, is primarily determined by cerebellar circuits. Hypometria (see glossary), making a
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saccade short of the optimal location for foveation, is evident in infancy (Aslin & Salapatek,
1975; Harris, Jacobs, Shawkat, & Taylor, 1993; Regal, Ashmead, & Salapatek, 1983) and
appears to continue into childhood (Fioravanti et al., 1995; Munoz et al., 1998) when it
stabilizes and age effects are no longer predominant (Irving et al., 2006). The fact that adults
generate saccades with slower velocities but similar or improved accuracy suggests that
increased velocity may not always be a gain.
Saccade latency refers to the reaction time to initiate an eye movement. Studies have agreed
that latency to initiate reflexive and voluntary eye movements decreases exponentially from
birth to approximately 14-15 years of age when it stabilizes throughout adulthood (Fischer,
Biscaldi, & Gezeck, 1997; Fukushima, Hatta, & Fukushima, 2000; Irving et al., 2006; Klein
& Foerster, 2001; Munoz et al., 1998). Our results in 245 8-30 year old subjects confirm this
finding (Luna et al., 2004) (see Fig. 2). These results are similar to developmental studies of
saccade latency to cognitively driven saccade responses, such as in the antisaccade task and
the memory-guided saccade task (described below), in that while voluntary saccades show
much longer latencies, they are similar to reflexive saccades (see glossary) in their protracted
development into adolescence. It is important to note that the similarity in development across
these tasks is only in the shape of the trajectory, as cognitively driven responses are longer,
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and only for latency. Accuracy of responses matures early for visually guided saccades (see
glossary) in comparison to the protracted development of accuracy of voluntary saccades which
continues into adolescence. Studies using manual responses to a range of cognitive tasks also
show decreases in reaction time into adolescence (Hale, 1990; Kail & Park, 1992). It is
surprising that the reaction time to an automatic/reflexive response such as a visually guided
response would parallel those of harder tasks that involve overall longer reaction times and
that they would show such delays of development into adolescence. These results indicate that
age-related decreases in saccade latency are driven by processes that generalize beyond the
oculomotor system and may reflect the speed of information processing supported by enhanced
neuronal processing afforded by continued myelination throughout this age period. Circuits
crucial to response planning and preparation that support response latency may show specific
maturation that becomes adult-like in adolescence, including neocortical to subcortical
pathways that allow for top-down control of behavior. As such, developmental studies on
saccade latency can be used to probe the integrity of information processing especially in
populations with impaired development such as in psychiatric disorders.
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Saccades with a latency of 80 to approximately 140 ms are defined as express saccades (see
glossary) and believed to be primarily guided by subcortical systems (Dorris, Martin, & Munoz,
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1997; Dorris & Munoz, 1995; Guitton et al., 1985; Klein, Foerster, Hartnegg, & Fischer,
2005). Express saccades are considered to be the most reflexive type of eye movement toward
a visual stimulus. A large number of express saccades has been found to be associated with a
higher tendency to make inhibitory errors in the antisaccade task (see below), suggesting
immaturities in the fixation system. However, the number of inhibitory errors is not associated
with number of express saccades, indicating that immaturities in the voluntary production of
saccades are distinct from the fixation system (Fischer et al., 1997). Unlike with visually guided
saccades, which have a longer latency that decreases significantly with age, there is a weak
relationship with age and express saccades, showing only modest decreases of their occurrence
with age (Fischer et al., 1997; Klein et al., 2005) that can persist past adulthood (Munoz et al.,
1998). The lack of developmental changes in the express saccade system suggests that the
fixation system supported by subcortical systems matures earlier than the cognitive processes
that support voluntary eye-movement responses.
Taken together, the development of pursuit, fixation, and reflexive saccades appear by infancy
or childhood, yet show continued refinement into adolescence of cognitive components. The
peaking of saccade velocity in adolescence and the stabilizing of saccade accuracy by
childhood indicates that subcortical processes may still have some specialization into childhood
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affecting basic mechanisms, albeit having relatively minimal effects on behavior. The
protracted development of the latency to make a reflexive saccade may reflect the age-related
enhancement of more generalized systems across the brain such as myelination. The continued
improvements in pursuit accuracy and prediction and the ability to suppress distraction to
maintain fixation all reflect improvements of more complex systems that integrate larger
networks across neocortex, which are known to support cognitive control in general. These we
will describe in more detail next.
7. Development of voluntary control of eye movements
Eye movements can also be voluntarily generated by a goal-directed plan, thereby providing
a model to study executive/cognitive control of behavior in a direct manner. Cognitive control
is exerted in all planned behavior and it is particularly vulnerable to psychopathology where
executive dysfunction is a common feature. Fundamental to executive function is the ability
to voluntarily suppress prepotent or reflexive/automatic responses in order to make a planned
response (response inhibition), working memory, the ability to retain and manipulate
information on-line in order to make a plan to direct a response, and attention switching, the
ability to change attentional focus in a controlled fashion (Miyake et al., 2000). These processes
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work in unison to support cognitive control, but can be characterized independently (Asato,
Sweeney, & Luna, 2006; Miyake et al., 2000). Response inhibition and working memory have
been described as aspects of the same mental process (Miller & Cohen, 2001). While the
circuitry that underlies inhibitory and workingmemory tasks overlap, the neuronal
computations are distinct. Primary to working memory is the reliance on reverberating circuits
that can maintain activity across prolonged periods of time (Funahashi et al., 1989). Primary
to inhibition is top-down modulation that permits the shutting down of a reflexive response.
Voluntary movements, including inhibitory control, require that a planned response be on-line,
while working memory, as defined by (Baddeley, 1992), includes the ability to manipulate
information on-line, which would require inhibitory components,. Developmental studies
indicate that even in childhood these two processes work closely together to affect performance
(Eenshuistra, Ridderinkhof, Weidema, & van der Molen, 2007), as in adulthood (Kane,
Bleckley, Conway, & Engle, 2001; Van der Stigchel, Merten, Meeter, & Theeuwes, 2007).
Although these processes cannot be completely separated, they are unique computational
processes. When considering development and psychopathology, the relative integrity of these
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two systems can be assessed. Aspects of response inhibition and working memory have been
found to develop on different time tables and influence performance in complex executive
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tasks differently (Asato et al., 2006; Luna et al., 2004; Miyake et al., 2000). As described below,
while latency and accuracy of initial responses to working memory and inhibitory oculomotor
tasks appear to mature around mid-adolescence, the ability to enhance precision of mnemonic
responses continues into adulthood (Luna et al., 2004). There is also evidence that these two
processes may be affected differentially in psychopathology such as in ADHD, where the
ability to inhibit an eye movement is impaired while the ability to make a memory-guided
saccade has been found to be preserved, suggesting that ADHD is associated more with a
specific impairment in inhibitory control and less so with working memory, when there are
minimal working memory requirements (Ross, Hommer, Breiger, Varley, & Radant, 1994).
Schizophrenia, on the other hand, appears to show impairment in both inhibitory eye
movements and memory-guided saccades indicating a different vulnerability in cognitive
control (Ross, Harris, Olincy, & Radant, 2000). The ability to test these two aspects of cognitive
control by manipulating the reliance on each process could potentially be of great use in
dissociating impairments in specific circuitry in psychopathology especially in the context of
development. Most neuropsychological tasks, however, have both response inhibition and
working memory processes tightly associated in the demands of the task (e.g., the Wisconsin
Card Sort involves both keeping on-line previous stimulus arrangements and inhibiting the
perseveration of responses that are inadequate). This is another area where oculomotor studies
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are particularly well suited to characterize inhibitory control with minimal working memory
demands except for remembering the general instruction (the antisaccade task, below), as well
as tasks with minimal inhibitory demands and driven primarily by working memory (the
memory-guided saccade task, below). We will now describe the developmental trajectories of
performance in these tasks that are able to reveal the basic aspects of the development of
cognitive control.
7.1. Development of antisaccades
7.1.1. Development of the ability to suppress a prepotent saccade--The
antisaccade (AS; see glossary) task is an oculomotor task that probes the ability to exert
cognitive control of behavior by exerting voluntary response inhibition. In this task, subjects
must voluntarily inhibit a reflexive eye movement towards a visual stimulus (prosaccade-PS;
see glossary) and instead make a planned movement to its mirror location (Hallett, 1978). An
antisaccade error (often referred to as response "accuracy") refers to the inability to suppress
the reflexive eye-movement response to the peripheral stimulus. These errors are usually
followed by a corrective response to the appropriate location, indicating that the instruction
was understood but that the reflexive response was not able to be suppressed (Luna et al.,
2004). Investigators studying the development of AS performance have typically compared
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AS and PS performance in an effort to distinguish developmental change in systems implicated
in response suppression (and maintenance of fixation) from systems supporting basic
sensorimotor function (Fischer et al., 1997). As we will detail, the bulk of evidence indicates
that age-related improvements in AS performance are largely attributable to changes in the
ability to consistently exert inhibitory control.
Many studies have used the AS task in large samples of healthy controls and have found
strikingly similar results (Fischer et al., 1997; Fukushima et al., 2000; Klein & Foerster,
2001; Luna et al., 2004; Mayfrank, Mobashery, Kimmig, & Fischer, 1986; Munoz et al.,
1998; Nelson et al., 2000). From childhood to adolescence there is a reduction in the latency
to initiate both prosaccades and antisaccades and in correcting inhibitory errors, supporting
developmental increases in speed of processing (see Fig. 2). Importantly, these studies have
also found that from childhood to approximately 15 years of age there is a significant reduction
in inhibitory errors, which indicates important improvements in cognitive control.
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Additionally, when a short gap separates fixation offset and target onset, antisaccade errors are
increased compared to the case when an overlap in fixation and target exists, which allows the
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fixation system to support the inhibition of reflexive saccades (Fischer, Gezeck, & Hartnegg,
1997). The relative gain in performance from the overlap compared to the gap condition is
called the gap-effect. This gap-effect decreases from childhood to adulthood indicating that
children rely more on the protective effect of fixation than mature individuals (Klein, 2001;
Klein & Foerster, 2001; Klein et al., 2005).
Fischer et al. (1997) performed the original study where the above findings were evident in
300 8-65 year old subjects (as well as demonstrating a moderate deterioration of performance
from 40 to 65 years of age). The strong developmental effects observed in AS performance
were subsequently replicated and extended in other studies examining developmental change
(Fukushima et al., 2000; Klein & Foerster, 2001; Luna et al., 2004; Mayfrank et al., 1986;
Munoz et al., 1998; Nelson et al., 2000). For example, Munoz and colleagues (1998) showed
dramatic age-dependence from 8 to 20 years of AS error rates and response times, but little
variation with age in PS metrics and dynamics. Additionally, these authors noted that all
subjects corrected at least some of their errors, indicating that all subjects, independent of age,
were capable of generating post-inhibition voluntary saccades. Their results indicated that
children have greater difficulty suppressing short-latency reflexive prosaccades. Fukushima et
al. (2000) reached similar conclusions in their study of children (aged 8-12 years) versus adults,
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reporting stabilization of AS error rates at 10-12 years of age, but continued decreases to
adulthood coupled with decreasing saccade latencies. In contrast, PS latencies reached adult
levels by 12 years, with their peak velocities showing no change. Fukushima et al. echoed the
conclusions reached by prior investigators, arguing that brain systems supporting the inhibition
of reflexive prosaccades are still immature at age 12. As in prior studies, Klein (2001) and
colleagues observed dramatic developmental change in AS error rates in 6-26 year old
participants. However, they added a novel approach by fitting regression models across the
age range as a continuous variable. Their findings indicated that a curvilinear model that shows
rapid changes through childhood and slower rate of change later in development provided the
best fit.
Our own study of 245 8-30 year old sought specifically to characterize the transition to adult-
level performance and to better determine the age of adult-level performance (Luna et al.,
2004). Similar to Klein et al. (2001), we chose to also use curvilinear regressions in order to
investigate the shape of developmental maturation. "Maturation" in this context is used to
highlight the specific stage of development of adolescence when development is reaching
stabilization of adult levels. Our results indicated that similar to Klein et al., 2001, an inverse
regression [Y = b0 + (b1/t)] best represented the age-related changes in saccade latency and
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proportion of inhibitory errors (see Figs. 2 and 3), indicating that from childhood to adolescence
there is a steep improvement in performance which stabilizes through adulthood. In order to
determine the age of maturation, we applied change-point analyses, which can be performed
only on cross-sectional data, to determine the age at which the distribution of responses ceases
to change (see also Klein, Foerster, & Hartnegg, 2007; Klein et al., 2005). Our results indicated
that maturity was reached by 14-15 years of age for prosaccade and antisaccade latency, as
well as inhibitory control (see Fig. 2). The exact age of maturity, however, varies across studies
including those indicating development into the twenties (Klein et al., 2005; Munoz et al.,
1998), which may be linked to sample variability.
Thus, studies have consistently demonstrated that improvements in AS performance continue
into adolescence. Nevertheless, it is important to note that across all studies the ability to
successfully suppress a prepotent saccade was present early (that is, by age 8 children could
perform at least one correct AS trial in each of the studies reviewed above). Indeed, the ability
to suppress a response toward a suddenly presented stimulus has been documented even in
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