Altered Control of Visual Fixation and Saccadic Eye Movements in Attention-Deficit Hyperactivity Disorder

Abstract

Attention-deficit hyperactivity disorder (ADHD) is characterized by the overt symptoms of impulsiveness, hyperactivity, and inattention. A frontostriatal pathophysiology has been hypothesized to produce these symptoms and lead to reduced ability to inhibit unnecessary or inappropriate behavioral responses. Oculomotor tasks can be designed to probe the ability of subjects to generate or inhibit reflexive and voluntary responses. Because regions of the frontal cortex and basal ganglia have been identified in the control of voluntary responses and saccadic suppression, we hypothesized that children and adults diagnosed with ADHD may have specific difficulties in oculomotor tasks requiring the suppression of reflexive or unwanted saccadic eye movements. To test this hypothesis, we measured eye movement performance in pro- and anti-saccade tasks of 114 ADHD and 180 control participants ranging in age from 6 to 59 yr. In the pro-saccade task, participants were instructed to look from a central fixation point toward an eccentric visual target. In the anti-saccade task, stimulus presentation was identical, but participants were instructed to suppress the saccade to the stimulus and instead look from the central fixation point to the side opposite the target. The state of fixation was manipulated by presenting the target either when the central fixation point was illuminated (overlap condition) or at some time after it disappeared (gap condition). In the pro-saccade task, ADHD participants had longer reaction times, greater intra-subject variance, and their saccades had reduced peak velocities and increased durations. In the anti-saccade task, ADHD participants had greater difficulty suppressing reflexive pro-saccades toward the eccentric target, increased reaction times for correct anti-saccades, and greater intra-subject variance. In a third task requiring prolonged fixation, ADHD participants generated more intrusive saccades during periods when they were required to maintain steady fixation. The results suggest that ADHD participants have reduced ability to suppress unwanted saccades and control their fixation behavior voluntarily, a finding that is consistent with a fronto-striatal pathophysiology. The findings are discussed in the context of recent neurophysiological data from nonhuman primates that have identified important control signals for saccade suppression that emanate from frontostriatal circuits.

Deficits in visuo-spatial working memory, inhibition and oculomotor control in boys with ADHD and their non-affected brothers

“…However, because the tendency to undershoot in healthy controls is used as baseline, a tendency to overshoot is present both in children with ADHD and siblings, which may be familial and a putative endophenotype. Since the saccades of children with ADHD had a substantially longer trajectory than those of controls but there were no group differences for velocity, the total duration of saccades was longer in ADHD boys than in controls, a finding consistent with a previous study (Munoz et al 2003).…”

“…These anticipatory and intrusive saccades are present irrespective of the paradigm used to study saccades and are also present in adults with ADHD (Munoz et al 2003;Feifel et al 2004), despite an age dependent decline in anticipatory and intrusive saccades (Ross et al 1994b). This may suggest that these abnormal saccades form an important, characteristic sign of pathology in ADHD.…”

“…Besides more frequent anticipatory saccades, there has also been reported an elevated number of intrusive saccades in ADHD patients (Gould et al 2001;Klein et al 2003;Munoz et al 2003). Intrusive saccades are defined as inappropriate saccades during the fixation period and may also be regarded as tapping into response inhibition, since a significant correlation has been found between intrusive saccades and inhibition errors on an antisaccade paradigm (Munoz et al 2003).…”

Behavioral response inhibition and maturation of goal representation in prefrontal cortex after puberty

“…We relied on the antisaccade task, used widely in the human literature for its simplicity, as performance of the task does not require mastery of complex rules requiring extensive instruction but rather the ability to resist a prepotent stimulus and plan a movement away from it (3,4,(35)(36)(37). Our longitudinal study was designed to track the same individuals at different stages to minimize interindividual variability, which is considerable around puberty (38).…”

“…Performance on the antisaccade task exhibits significant improvements in adolescence in humans (3,4) and is impaired in childhood conditions such as attention deficit/hyperactivity disorder (35) and mental illnesses such as schizophrenia, which typically manifest in early adulthood (36,37). Young monkeys are able to master tasks that require response inhibition, such as the stop signal task and the object retrieval detour, and performance has been shown to improve with age around the time of puberty (38).…”