Ocular motor indicators of executive dysfunction in fragile X and Turner syndromes

doi:10.1016/j.bandc.2006.08.002

Brain and Cognition

Volume 63, Issue 3, April 2007, Pages 203-220

https://doi.org/10.1016/j.bandc.2006.08.002 Get rights and content

Abstract

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with executive function and visual spatial deficits. In the present study, we used ocular motor paradigms to examine evidence that disruption to different neurological pathways underlies these deficits. We tested 17 females with fragile X, 19 females with Turner syndrome, and 40 females with neither disorder who comprised the comparison group. Group differences emerged for both the fragile X and Turner syndrome groups, each relative to the comparison group: Females with fragile X had deficits in generating memory-guided saccades, predictive saccades, and saccades made in the overlap condition of a gap/overlap task. Females with Turner syndrome showed deficits in generating memory-guided saccades, but not during either the predictive saccade or gap/overlap task. Females with Turner syndrome, but not females with fragile X, showed deficits in visually guided saccades and anti-saccades. These findings indicate that different brain regions are affected in the two disorders, and suggest that different pathways lead to the similar cognitive phenotypes described for fragile X and Turner syndromes.

Introduction

Fragile X and Turner syndromes are two X-chromosome-related disorders associated with neuropsychological deficits. Despite reports of deficits in memory, spatial, and executive function skills for persons with either disorder (as reviewed by Mazzocco & McCloskey, 2005), it remains unclear what primary neurobiological mechanisms underlie these corresponding cognitive phenotypes. The present study of ocular motor behavior was designed to investigate possible mechanisms underlying the impairments associated with fragile X and Turner syndromes. Following a brief introduction to each disorder, we describe how ocular motor studies help to delineate neurological pathways that underlie cognitive deficits.

Section snippets

Fragile X syndrome

Fragile X syndrome is the most common known hereditary cause of mental retardation, occurring in approximately 1 per 4000 to 9000 individuals (Crawford, Acuna, & Sherman, 2001). In most individuals with fragile X, the disorder results from a mutation of a single gene on the X-chromosome (Verkerk et al., 1991). As an X-linked disorder, fragile X affects males more severely than it affects females. Nearly all males with fragile X (Bailey, Hatton, & Skinner, 1998), and approximately half of

Contribution of ocular motor assessment to neuropsychological theory

Eye movement studies can be a useful complement to other diagnostic and exploratory methods, because ocular motor assessments afford a degree of quantification about signal processing and timing (i.e., latencies) that is not found in methods such as MRI and neuropsychological testing alone. Consequently, with judicious use of specific ocular motor paradigms, it is possible to assess involvement of areas known to be associated with ocular motor control. For example, in a study of the cognitive

The present study

In the present study, we used five eye movement testing paradigms based on the model of the ocular motor system described above, in order to measure neuropsychological performance implicated by ocular motor behavior. These paradigms were used to test the ability to generate reflexive saccades (visually guided saccade paradigm), disengage fixation (gap/overlap paradigm), inhibit reflexive saccades and generate a volitional saccades (anti-saccade paradigm), inhibit and initiate volitional

Methods

Informed consent for this study was obtained according to procedures approved by an institutional review board, prior to carrying out any of the procedures. Participants 18 years of age or older signed consent forms, whereas children below 18 years of age signed an assent form in the presence of the examiner. Parents of children under 18 years of age signed consent forms. All consent and assent forms indicated that participation was voluntary.

Preliminary analyses

There was no group difference in age at testing across the three participant groups, p = 0.498. As expected, there was an inverse correlation between age and the other variables measured. Therefore, age was included as a covariate in the subsequent parametric analyses.

Primary analyses using three group comparisons

The results of the three-group MANCOVA were significant for the majority of dependent variables. These are summarized in Table 2. Results of the subsequent planned pairwise comparisons are summarized in Table 3, Table 4, and are

Discussion

The aim of the present study was to use eye movement paradigms to infer differences in the underlying neurobiological mechanisms in children with fragile X or Turner syndrome, two developmental disorders with globally similar cognitive phenotypes. Based upon previous neuropsychological and neuroimaging studies, we hypothesized that girls with Turner syndrome would have difficulty in generating visually guided saccades, but that girls with either syndrome would show deficits in latencies during

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^☆: This work was supported by Grants NS 35356 awarded to Dr. M.B. Denckla and Grant RO1 HD 34061 awarded to Dr. Mazzocco. The authors thank the children who participated in this study and the children’s parents; and acknowledge Research Assistants D. Lanham, J. Teisl, and G.F. Myers.

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Ocular motor indicators of executive dysfunction in fragile X and Turner syndromes☆

Abstract

Introduction

Section snippets

Fragile X syndrome

Contribution of ocular motor assessment to neuropsychological theory

The present study

Methods

Preliminary analyses

Primary analyses using three group comparisons

Discussion

Psychiatry Research

Genetics in Medicine

Vision Research

Neuropsychologia

Journal of Adolescent Health Care

Journal of the American Academy of Child and Adolescent Psychiatry

Cortex

NeuroImage

Lancet

Cortex

Vision Research

Brain Research Molecular Brain Research

Biological Psychiatry

Neuropsychologia

Cortex

Cell

Molecular-neurobehavioral associations in females with the fragile X full mutation

American Journal of Medical Genetics

Defective figure drawing, geometric and human, in Turner’s syndrome

Journal of Nervous and Mental Disease

Early developmental trajectories of males with fragile X syndrome

American Journal of Mental Retardation

Cognitive functions in Turner’s syndrome

Minerva Pediatrica

Neuropsychological impairment in 42 adolescents with sex chromosome abnormalities

American Journal of Medical Genetics

Profile of cognitive functioning in women with the fragile X mutation

Neuropsychology

The dorsomedial frontal cortex of the macaca monkey: fixation and saccade-related activity

Experimental Brain Research

Predictive ocular motor control in Parkinson’s disease

Brain

A re-examination of the visuospatial deficit in Turner syndrome: contributions of working memory

Developmental Neuropsychology

Neural substrate of antisaccades: role of subcortical structures

Neurology

Differential impact of the FMR-1 full mutation on memory and attention functioning: a neuropsychological perspective

Journal of Cognitive Neuroscience

Electrical microstimulation of primate posterior parietal cortex initiates orienting and alerting components of covert attention

Experimental Brain Research

The effect of electromagnetic stimulation of the posterior parietal cortex on eye movements

Eye

Positron emission tomography and neuropsychological correlates in children with Turner’s syndrome

Developmental Neuropsychology

Health supervision for children with Turner syndrome

Pediatrics

Dorsolateral prefrontal lesions and oculomotor delayed-response performance: evidence for mnemonic “scotomas”

Journal of Neuroscience

A direct prefrontotectal tract against distractibility in the human brain

Annals of Neurology

The frontal eye field is involved in spatial short-term memory but not in reflexive saccade inhibition

Experimental Brain Research

Cortical control of saccades

Experimental Brain Research

Effects of anterior cingulate cortex lesions on ocular saccades in humans

Experimental Brain Research

Evidence of normal cerebellar control of the vestibulo-ocular reflex (VOR) in children with high-functioning autism

Journal of Autism and Developmental Disorders

Role of the basal ganglia in the control of purposive saccadic eye movements

Physiological Reviews

Cognitive control of predictive eye tracking: influence of instructions

Experimental Brain Research

Cortical control of vestibular-guided saccades in man

Brain

Fragile-X: neuropsychological test performance, CGG triplet repeat lengths, and hippocampal volumes

Journal of Clinical Investigation

Differentiating aspects of executive dysfunction in girls with fragile X or Turner syndrome using the Contingency Naming Test

Developmental Neuropsychology

Ocular motor behavior of children with neurofibromatosis 1