Faraz Farzin

Fragile-X–Associated Tremor/Ataxia Syndrome (FXTAS) in Females with the FMR1 Premutation

We describe five female carriers of the FMR1 premutation who presented with symptoms of tremor and ataxia and who received a diagnosis of definite or probable fragile-X-associated tremor/ataxia syndrome (FXTAS). Unlike their male counterparts with FXTAS, none of the women had dementia. Females had not been reported in previous studies of FXTAS, suggesting that they may be relatively protected from this disorder. Brain tissue was available from one of the five subjects, a women who died at age 85 years; microscopic examination revealed intranuclear neuronal and astrocytic inclusions, in accord with the findings previously reported in males with FXTAS. The work-up of families with the FMR1 mutation should include questions regarding neurological symptoms in both older male and female carriers, with the expectation that females may also manifest the symptoms of FXTAS, although more subtly and less often than their male counterparts.

Aging in Individuals With the FMR1 Mutation

Individuals with fragile X mental retardation 1 (FMR1) premutation (55 to 200 CGG repeats) are typically unaffected by fragile X syndrome. However, a subgroup of older males with the premutation have developed a neurological syndrome, which usually begins between 50 and 70 years and is associated with a progressive intention tremor and/or ataxia manifested by balance problems, frequent falling, and Parkinsonian symptoms, such as masked facies, intermittent resting tremor, and mild rigidity. This finding has been termed the fragile X-associated tremor/ataxia syndrome (FXTAS) and has brought focus to the aging process in individuals with the FMR1 mutation. The premutation is associated with elevated messenger RNA levels leading to the formation of intranuclear inclusions in neurons and astrocytes associated with FXTAS. This review is a summary of our experience with FXTAS in male carriers of the premutation.

Holistic crowding of Mooney faces

An object or feature is generally more difficult to identify when other objects are presented nearby, an effect referred to as crowding. Here, we used Mooney faces to examine whether crowding can also occur within and between holistic face representations (C. M. Mooney, 1957). Mooney faces are ideal stimuli for this test because no cues exist to distinguish facial features in a Mooney face; to find any facial feature, such as an eye or a nose, one must first holistically perceive the image as a face. Through a series of six experiments we tested the effect of crowding on Mooney face recognition. Our results demonstrate crowding between and within Mooney faces and fulfill the diagnostic criteria for crowding, including eccentricity dependence and lack of crowding in the fovea, critical flanker spacing consistent with less than half the eccentricity of the target, and inner-outer flanker asymmetry. Further, our results show that recognition of an upright Mooney face is more strongly impaired by upright Mooney face flankers than inverted ones. Taken together, these results suggest crowding can occur selectively between high-level representations of faces and that crowding must occur at multiple levels in the visual system.

Brief Report: Visual Processing of Faces in Individuals with Fragile X Syndrome: An Eye Tracking Study

Gaze avoidance is a hallmark behavioral feature of fragile X syndrome (FXS), but little is known about whether abnormalities in the visual processing of faces, including disrupted autonomic reactivity, may underlie this behavior. Eye tracking was used to record fixations and pupil diameter while adolescents and young adults with FXS and sex- and age-matched typically developing controls passively viewed photographs of faces containing either a calm, happy, or fearful expression, preceded by a scrambled face matched on luminance. Results provide quantitative evidence for significant differences in gaze patterns and increased pupillary reactivity when individuals with FXS passively view static faces. Such abnormalities have significant implications in terms of understanding causes of gaze avoidance observed in individuals with FXS.

Contrast detection in infants with fragile X syndrome.

Studies have reported that a selective deficit in visual motion processing is present in certain developmental disorders, including Williams syndrome and autism. More recent evidence suggests a visual motion impairment is also present in adults with fragile X syndrome (FXS), the most common form of inherited mental retardation. The goal of the current study was to examine low-level cortical visual processing in infants diagnosed with FXS in order to explore the developmental origin of this putative deficit. We measured contrast detection of first-order (luminance-defined) and second-order (contrast-defined) gratings at two levels of temporal frequency, 0 Hz (static) and 4 Hz (moving). Results indicate that infants with FXS display significantly higher detection thresholds only for the second-order, moving stimuli compared to mental age-matched typically developing controls.

Reliability of Eye Tracking and Pupillometry Measures in Individuals with Fragile X Syndrome

Recent insight into the underlying molecular and cellular mechanisms of fragile X syndrome (FXS) has led to the proposal and development of new pharmaceutical treatment strategies, and the initiation of clinical trials aimed at correcting core symptoms of the developmental disorder. Consequently, there is an urgent and critical need for outcome measures that are valid for quantifying specific symptoms of FXS and that are consistent across time. We used eye tracking to evaluate test–retest reliability of gaze and pupillometry measures in individuals with FXS and we demonstrate that these measures are viable options for assessing treatment-specific outcomes related to a core behavioral feature of the disorder.

Dynamic object representations in infants with and without fragile X syndrome

Our visual world is dynamic in nature. The ability to encode, mentally represent, and track an objects identity as it moves across time and space is critical for integrating and maintaining a complete and coherent view of the world. Here we investigated dynamic object processing in typically developing (TD) infants and infants with fragile X syndrome (FXS), a single-gene disorder associated with deficits in dorsal stream functioning. We used the violation of expectation method to assess infants’ visual response to expected versus unexpected outcomes following a brief dynamic (dorsal stream) or static (ventral stream) occlusion event. Consistent with previous reports of deficits in dorsal stream-mediated functioning in individuals with this disorder, these results reveal that, compared to mental age-matched TD infants, infants with FXS could maintain the identity of static, but not dynamic, object information during occlusion. These findings are the first to experimentally evaluate visual object processing skills in infants with FXS, and further support the hypothesis of dorsal stream difficulties in infants with this developmental disorder.

Impaired visual decision-making in individuals with amblyopia

This study examined the effects of amblyopia on perceptual decision-making processes to determine the consequences of visual deprivation on the development of higher level cortical networks outside of the visual cortex. A variant of the Eriksen flanker task was used to measure response time and accuracy for decisions made in the presence of response-selection conflict. Performance of adults with amblyopia was compared to that of neurotypical participants of the same age. Additionally, simple and choice reaction time tasks presented in the visual and the auditory modality were used to control for factors such as feature visibility, crowding, and motor execution speed. A selective deficit in response time for visual decisions was found when individuals with amblyopia used either the amblyopic or non-amblyopic (dominant) eye, and this deficit was independent of visual acuity, motor time, and performance accuracy. In trial conditions that provoked response-selection conflict, responses were significantly delayed in amblyopic relative to neurotypical participants and were not subject to standard trial sequence effects. Our results indicate that, beyond the known effects of abnormal visual experience on visual cortex, suboptimal binocular input during a developmental critical period may also impact cortical connections to downstream areas of the brain, including parietal and frontal cortices, that are believed to underlie decision and response-selection processes.

Piecing it together: Infants' neural responses to face and object structure

Integration of local elements into a coherent global form is a fundamental aspect of visual object recognition. How the different hierarchically organized stages of visual analysis develop in order to support object representation in infants remains unknown. The aim of this study was to investigate structural encoding of natural images in 4- to 6-month-old infants and adults. We used the steady-state visual evoked potential (ssVEP) technique to measure cortical responses specific to the global structure present in object and face images, and assessed whether differential responses were present for these image categories. This study is the first to apply the ssVEP method to high-level vision in infants. Infants and adults responded to the structural relations present in both image categories, and topographies of the responses differed based on image category. However, while adult responses to face and object structure were localized over occipitotemporal scalp areas, only infant face responses were distributed over temporal regions. Therefore, both infants and adults show object category specificity in their neural responses. The topography of the infant response distributions indicates that between 4 and 6 months of age, structure encoding of faces occurs at a higher level of processing than that of objects.

Time Crawls: The Temporal Resolution of Infants’ Visual Attention

Conscious visual perception of the constantly changing environment is one of the brain’s most critical functions. In virtually every moment of every daily activity, the visual system is confronted with the task of accurately representing and interpreting scenes that change rapidly over time. Adults can judge the identity and order of changing images presented at a rate of up to 10 Hz (~50 ms per image); this limit reflects a finite temporal resolution of attention. In the research reported here, although 6- to 15-month-old infants could detect the presence of rapid flicker without difficulty, their ability to segment individual alternating states within the flicker was severely limited: Fifteen-month-old infants had a temporal resolution of attention approximately one order of magnitude lower than that of adults (~1 Hz). Coarse temporal resolution constrains how infants perceive and utilize dynamic visual information and may play a role in the visual processing deficits found in individuals with neurodevelopmental disorders.