Heritability and molecular genetic basis of antisaccade eye tracking error rate: A genome-wide association study

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Abstract

Antisaccade deficits reflect abnormalities in executive function linked to various disorders including schizophrenia, externalizing psychopathology, and neurological conditions. We examined the genetic bases of antisaccade error in a sample of community-based twins and parents (N = 4,469). Biometric models showed that about half of the variance in the antisaccade response was due to genetic factors and half due to nonshared environmental factors. Molecular genetic analyses supported these results, showing that the heritability accounted for by common molecular genetic variants approximated biometric estimates. Genome-wide analyses revealed several SNPs as well as two genes-B3GNT7 and NCL-on Chromosome 2 associated with antisaccade error. SNPs and genes hypothesized to be associated with antisaccade error based on prior work, although generating some suggestive findings for MIR137, GRM8, and CACNG2, could not be confirmed.

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The Nature and Organization of Individual Differences in Executive Functions: Four General Conclusions.

Akira Miyake, Naomi Friedman (2012)

Executive functions (EFs)-a set of general-purpose control processes that regulate one's thoughts and behaviors-have become a popular research topic lately and have been studied in many subdisciplines of psychological science. This article summarizes the EF research that our group has conducted to understand the nature of individual differences in EFs and their cognitive and biological underpinnings. In the context of a new theoretical framework that we have been developing (the unity/diversity framework), we describe four general conclusions that have emerged from our research. Specifically, we argue that individual differences in EFs, as measured with simple laboratory tasks, (1) show both unity and diversity (different EFs are correlated yet separable); (2) reflect substantial genetic contributions; (3) are related to various clinically and societally important phenomena; and (4) show some developmental stability.

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Altered control of visual fixation and saccadic eye movements in attention-deficit hyperactivity disorder.

Douglas Munoz, Irene T. Armstrong, Karen Hampton … (2003)

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.

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Maturation of executive function in autism.

S Döll, Beatriz Barrón, Eric Hegedus … (2007)

Executive dysfunction has been reported at different ages in autism. It is not clear however, when this impairment emerges or how its expression is affected by development. 61 non-mentally retarded autism participants (AUT) and 61 age, gender, and IQ matched typically developing participants (CON) were assessed with two oculomotor executive function tasks, the oculomotor delayed response task (ODR) and the antisaccade task (AS), as well as a visually-guided saccade sensorimotor task (VGS). The AUT group demonstrated impairments in response inhibition and spatial working memory at all ages tested. Developmental improvements in speed of sensorimotor processing and voluntary response inhibition were similar in both groups indicating sparing of some attentional control of behavior. Developmental progression in the speed of initiating a cognitive plan and maintaining information on line over time, however, was impaired in the AUT group indicating abnormal development of working memory. These results indicate that while executive dysfunction is present throughout development, there is evidence for both typical and atypical developmental progression of executive functions in autism. The plasticity suggested by the developmental improvements may have implications regarding appropriate developmental epochs and types of interventions aimed at enhancing cognitive capacities in individuals with autism.