Rett Syndrome: Basic Features of Visual Processing—A Pilot Study of Eye-Tracking

doi:10.1016/j.pediatrneurol.2012.04.009

Pediatric Neurology

Volume 47, Issue 1, July 2012, Pages 25-29

https://doi.org/10.1016/j.pediatrneurol.2012.04.009 Get rights and content

Abstract

Consistently observed “strong eye gaze” has not been validated as a means of communication in girls with Rett syndrome, ubiquitously affected by apraxia, unable to reply either verbally or manually to questions during formal psychologic assessment. We examined nonverbal cognitive abilities and basic features of visual processing (visual discrimination attention/memory) by analyzing patterns of visual fixation in 44 girls with Rett syndrome, compared with typical control subjects. To determine features of visual fixation patterns, multiple pictures (with the location of the salient and presence/absence of novel stimuli as variables) were presented on the screen of a TS120 eye-tracker. Of the 44, 35 (80%) calibrated and exhibited meaningful patterns of visual fixation. They looked longer at salient stimuli (cartoon, 2.8 ± 2 seconds S.D., vs shape, 0.9 ± 1.2 seconds S.D.; P = 0.02), regardless of their position on the screen. They recognized novel stimuli, decreasing the fixation time on the central image when another image appeared on the periphery of the slide (2.7 ± 1 seconds S.D. vs 1.8 ± 1 seconds S.D., P = 0.002). Eye-tracking provides a feasible method for cognitive assessment and new insights into the “hidden” abilities of individuals with Rett syndrome.

Introduction

Rett syndrome is a severe, X-linked disorder of neurodevelopment, caused by mutations in the methyl-cytosine-phosphate-guanine binding protein 2 (MECP2) gene located on Xq28, first described in 1966 [1], [2]. Profound impairments in the ability to speak, walk, and use hands, caused by apraxia and movement disorder, severely limit the abilities of girls with Rett syndrome to reply to questions during standardized neuropsychologic testing, and thus may have led to underestimations of their cognitive abilities [3], [4].

Vision and gaze are considered the most important ways in which girls with Rett syndrome relate to the world [5], [6]. Numerous observations in the literature contend that these girls demonstrate strong eye gaze, eye contact, and visual tracking [7], [8], [9], and almost uniform reports by parents and caretakers state that these girls use eye gaze to greet, point, request, and refuse. However, the approach best suited for the assessment of cognitive function in girls with Rett syndrome remains unclear [10], [11].

The specific aims of this pilot study were:

(1)
To determine the basic features of nonverbal cognitive processes in girls with Rett syndrome, such as characteristics of their visual fixation pattern (meaningful vs random) and visual attention (in response to novelty); and
(2)
To determine the feasibility of eye-tracking as a method for cognitive assessment in girls with Rett syndrome.

Section snippets

Study Design and Methods

This study was performed in 44 consecutive female patients with the typical form of Rett syndrome (which was also genetically confirmed; mean age, 10 ± 6 years S.D.) [12]. Good eye contact was present in 34 (78%) girls with Rett syndrome, and nonverbal communication (intentional eye or hand pointing) was present in 32 (74%) girls with Rett syndrome. Only eight (18%) girls were able to execute some purposeful movements with their hands (such as manipulating switches or toys, or eating with

Results

Girls with typical Rett syndrome who were able to complete testing exhibited meaningful patterns of visual fixation when multiple stimuli were presented simultaneously. Salience of the visual stimuli was the single most important determinant of the pattern of their visual fixation. They looked at the same location within the slide significantly more often (4.8 ± 4 times S.D. vs 2.5 ± 3 times S.D., P = 0.06) and longer (2.8 ± 2 seconds S.D. vs 0.9 ± 1.2 seconds S.D., P = 0.024) when a cartoon

Discussion

Girls with Rett syndrome demonstrated a preference for novel and salient stimuli in a way that normally developing children do. These results, together with the results reported in our previous study (that girls with Rett syndrome exhibit exquisite visual preference for socially weighted stimuli, i.e., a preference for looking at people vs objects, regardless of their position on the screen, and a preference for looking into people’s eyes), open up new insights about their neurodevelopmental

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Cited by (42)

Sleep and the Social Profiles of Individuals With Rett Syndrome
2024, Pediatric Neurology
This study investigates the distinctive social behaviors observed in individuals with Rett syndrome (RTT), characterized by the loss of spoken language, impaired eye gaze communication, gait abnormalities, and sleep issues. The research aims to identify social profiles in RTT and explore their correlation with sleep, sleep-disordered breathing (SDB), and daytime sleepiness.
Standard overnight sleep macrostructure and respiratory parameters were assessed. Extracting 25 social-related items and one for daytime sleepiness from the Rett Syndrome Behavioral Questionnaire, factor analysis was applied to establish latent social profiles. These profiles were then correlated with sleep parameters. The nonparametric Mann-Whitney U test compared social profiles based on the presence of SDB (defined by an apnea-hypopnea index greater than one per hour) and daytime sleepiness.
The study involved 12 female subjects with confirmed RTT diagnoses and MECP2 mutations, aged 8.54 ± 5.30 years. The Rett Syndrome Behavioral Questionnaire revealed a total average score of 25.83 ± 12.34, indicating varying degrees of social impairments. Comprising 25 social-related items, factor analysis yielded four social profiles: “interactive motricity,” “mood change,” “anxiety/agitation,” and “gazing.” Longer sleep onset latency correlated with increased socio-behavioral impairments, particularly in interactive motricity reduction. Conversely, higher rapid eye movement sleep was associated with fewer interactive socio-motor behaviors. No significant differences in social profiles were found concerning the presence of SDB or daytime sleepiness.
The findings suggest four distinct social profiles in RTT individuals, hinting at shared disrupted circuits between sensorimotor functioning and sleep-related neuronal pathways. Despite the absence of differences in SDB or daytime sleepiness, the study highlights the relationship between sleep parameters, such as sleep onset latency and rapid eye movement sleep, and socio-behavioral outcomes in RTT with MECP2 mutations.
A comparison of formal and informal methods for assessing language and cognition in children with Rett syndrome
2021, Research in Developmental Disabilities
Citation Excerpt :
Thus, a combination of assessment approaches – direct and indirect, formal and informal – is recommended by the Guidelines in order to gain a holistic picture of an individual’s underlying skills and potential. Some studies using eye gaze-based assessments have directly examined visual perception and/or language-based concepts like size and colour, while others have explored cognitive aspects such as attention and visual or social preferences (Baptista, Mercadante, Macedo, & Schwartzman, 2006; de Lima Velloso, de Araújo, & Schwartzman, 2009; Djukic, Valicenti McDermott, Mavrommatis, & Martins, 2012; Rose et al., 2013; Rose, Djukic, Jankowski, Feldman, & Rimlerd, 2016; Rose, Wass, Jankowski, Feldman, & Djukic, 2017; Vignoli et al., 2010; von Tetzchner et al., 1996). Two recent studies that have adapted formal or standardised assessments for use with children with RTT are those conducted by Ahonniska-Assa, Polack, and Saraf (2018) and Clarkson, LeBlanc, and DeGregorio (2017).
Opinions about the cognitive and receptive language skills of people with Rett syndrome (RTT) range from severe intellectual impairment to near-normal development. Assessment is challenging because most are non-verbal, with no purposeful hand use. Clarkson et al. (2017) adapted the Mullen Scales of Early Learning for use with eye gaze technology (MSEL-A/ET) for people with RTT.
To investigate and compare the performance of children with RTT on formal and newly-designed informal assessments of language and cognition using eye gaze/tracking technology.
Ten children with RTT aged 4:0–6:8 were assessed on the MSEL-A/ET for Visual Reception (VR) and Receptive Language (RL), and standard MSEL for Expressive Language (EL). Informal assessments of the same skills were embedded in activities such as reading and cake-decorating.
Standard scores on MSEL-A/ET VR and RL subtests ranged from ‘very low’ to ‘above average’. All children scored ‘very low’ on standard EL assessment. Informal assessments added information about EL, with children producing 1–3 word utterances and a range of communicative functions through an eye gaze device.
Combining low-tech augmentative and alternative communication, eye gaze technology, informal activities and formal assessment, yields greater insight into children’s abilities. This is important in informing suitable support and education for the individual.
Longitudinal cognitive rehabilitation applied with eye-tracker for patients with Rett Syndrome
2021, Research in Developmental Disabilities
longitudinal effects of cognitive rehabilitation in Rett Syndrome (RTT) have been poorly investigated and the mechanisms do not appear to have been described in detail.
the aim of this study was to examine the effects of cognitive rehabilitation with eye-tracker technology on attention, choice behaviours and language over a 2-year period in patients with RTT.
28 participants with RTT, ranging from age 4–22 years old (M = 13.85 years, SD = 5.89), received 30 min of cognitive rehabilitation with eye-tracker for 3 days a week over a 1-month for 2 years. They then underwent cognitive assessment to evaluate attention, choice, language and global functioning in four specific times: before cognitive rehabilitation (T1), after six months of cognitive rehabilitation (T2), six months after the second cognitive rehabilitation phase (T3) and at the end of the third cognitive rehabilitation phase (T4).
patients with RTT show long-term improvements in seconds of attention and number of choice behaviours, with barely any improvement in global functioning. No improvement in language was found.
this is the first study aimed at examining longitudinal effects of cognitive rehabilitation in patients with RTT, demonstrating a linear improvement across time in attention and choice.
Challenges in evaluating the oculomotor function in individuals with Rett syndrome using electronystagmography
2019, European Journal of Paediatric Neurology
Citation Excerpt :
From clinical observation, a better response was seen when a new and novel picture was introduced. This accords with the finding reported by Djukic et al., whereby individuals with RTT exhibited a preference for novel stimuli over a stimulus they had previously seen.32 The other major challenge explored in this study was the quality of the signals.
Rett syndrome (RTT) is a neurological disorder characterized by a broad spectrum of symptoms. Communication is a major area of difficulty. Use of eye tracking technology offers a potentially effective method of communication when underpinned by intact oculomotor function. In this study, oculomotor function was assessed using electronystagmography (ENG). However, challenges were encountered when examining individuals with RTT.
To improve oculomotor examination in individuals with RTT by evaluating the challenges encountered during ENG examination.
Oculomotor function was examined in 17 girls and young women with RTT and 16 typically developing (TD) individuals using ENG. Observational analysis of both performance and results indicated that challenges in examination were mainly related to quality of attention and quality of signals. Subsequently these outcome values were explored quantitatively according to percentage looking time for attention and drift for signal quality.
A significantly reduced level of attention and suboptimal electrode signals were evident in the RTT group when compared with the TD group for all tests except torsion swing.
The challenges in testing confirm that regular oculomotor examination should be adjusted to meet the needs of individuals with RTT. It is hypothesized that the RTT group's higher quality of attention on the torsion swing can be explained by the more forceful vestibular rather than visual-ocular stimulus operating in this test. Suggested adaptations include reducing the number of electrodes, changing the picture stimuli and bringing them closer, performing observational assessments rather than ENG, and using virtual reality goggles.
Oculomotor Function in Individuals With Rett Syndrome
2018, Pediatric Neurology
Citation Excerpt :
In recent years, eye tracking technology has been increasingly used by individuals with RTT as a way of accessing communication and developing a means of self-expression. Eye tracking technology has also been used as a medium for assessing the cognitive and receptive language skills of individuals with RTT.47-57 Most common eye tracking systems used for communication depend upon a camera measuring the reflection of near infrared light on the cornea and pupil of each eye to determine where the gaze is directed on screen.58
Individuals with Rett syndrome (RTT) are notoriously reliant on the use of eye gaze as a primary means of communication. Underlying an ability to communicate successfully via eye gaze is a complex matrix of requirements, with an intact oculomotor system being just one element. To date, the underlying neural and motor pathways associated with eye gaze are relatively under-researched in RTT.
This study was undertaken to plug this gap in knowledge and to further the understanding of RTT in one specific area of development and function, namely oculomotor function.
The eye movements of 18 girls and young women with RTT were assessed by electronystagmography (ENG). This tested their horizontal saccadic and smooth pursuit eye movements as well as optokinetic nystagmus and vestibulo-ocular reflex. Their results were compared with normative data collected from 16 typically developing children and teenagers.
Overall, the individuals with RTT demonstrated a range of eye movements on a par with their typically developing peers. However, there were a number of difficulties in executing the ENG testing with the RTT cohort which made quantitative analysis tricky, such as reduced motivation and attention to test materials and low-quality electrode signals.
This study suggests that individuals with RTT have an intact oculomotor system. However, modifications should be made to the ENG assessment procedure to combat problems in testing and add strength to the results. Further investigation into these testing difficulties is warranted in order to inform such modifications.
Distinguishing response to names in Rett and MECP2 Duplication syndrome: An ERP study of auditory social information processing
2017, Brain Research
Citation Excerpt :
Cognitive neuroscience methods utilizing event-related-potentials (ERP), a portion of EEG time-locked to a stimulus event, have been successfully used in infants and individuals with no speech to document cognitive and language functioning (Mills et al., 2004; Yoder et al., 2006), predict developmental outcomes (Kuhl et al., 2013; Molfese, 2000), and provide evidence of treatment effects without relying on overt behaviors by the participant (Yoder et al., 2013). In RTT, neuroscience investigations thus far have focused primarily on visual processing and the use of eye gaze while participants attend to stimuli on a screen (Djukic et al., 2012). There is some evidence of alterations in cortical/sensory processing in basic models of RTT (Goffin et al., 2014).
Despite significant advances at the level of basic research, the characterization of higher-level processes in Rett and MECP2 Duplication syndrome remains understudied. In this pilot study, we assessed social-emotional information processing by testing whether children (ages 4–12 years) with Rett (n = 9) and MECP2 Duplication syndrome (n = 7) distinguished their own spoken name from other names. We hypothesized that own and familiar names would elicit more positive parietal P300 responses than unknown names, and that the groups would have different neural responses to these stimuli. The MECP2 Duplication group partially mirrored the parietal responses to own name observed in typically developing participants, and better name discrimination correlated with more adaptive behaviors. Conversely, participants with RTT did not resemble the typical group, and showed greater responses to close other names at frontal/central regions. These results may reflect the different consequences of too much (MECP2 Duplication) vs. too little (RTT) MeCP2 protein.

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Pediatric Neurology

Abstract

Introduction

Section snippets

Study Design and Methods

Results

Discussion

References (21)

Communication assessment for individuals with Rett syndrome: A systematic review

Res Autism Spectrum Disord

Social preferences in Rett syndrome

Pediatr Neurol

Response to novelty: Continuity versus discontinuity in the developmental course of intelligence

Adv Child Dev Behav

Oxytocin increases gaze to the eye region of human faces

Biol Psychiatry

Parsing heterogeneity in autism spectrum disorders: Visual scanning of dynamic social scenes in school-aged children

J Am Acad Child Adolesc Psychiatry

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2

Nat Genet

On an unusual brain atrophy syndrome in hyperammonemia in childhood

Wien Med Wochenschr

Assessment of potential communicative acts in three individuals with Rett syndrome

J Dev Phys Disabil

Vision, cognition and developmental characteristics of girls and women with Rett syndrome

Dev Med Child Neurol

Cognitive profile of Rett syndrome

J Child Neurol

Cited by (42)

Sleep and the Social Profiles of Individuals With Rett Syndrome

A comparison of formal and informal methods for assessing language and cognition in children with Rett syndrome

Longitudinal cognitive rehabilitation applied with eye-tracker for patients with Rett Syndrome

Challenges in evaluating the oculomotor function in individuals with Rett syndrome using electronystagmography

Oculomotor Function in Individuals With Rett Syndrome

Distinguishing response to names in Rett and MECP2 Duplication syndrome: An ERP study of auditory social information processing

Original ArticleRett Syndrome: Basic Features of Visual Processing—A Pilot Study of Eye-Tracking

Abstract

Introduction

Section snippets

Study Design and Methods

Results

Discussion

Res Autism Spectrum Disord

Pediatr Neurol

Adv Child Dev Behav

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2

Nat Genet

On an unusual brain atrophy syndrome in hyperammonemia in childhood

Wien Med Wochenschr

Assessment of potential communicative acts in three individuals with Rett syndrome

J Dev Phys Disabil

Vision, cognition and developmental characteristics of girls and women with Rett syndrome

Dev Med Child Neurol

Cognitive profile of Rett syndrome

J Child Neurol

Original Article
Rett Syndrome: Basic Features of Visual Processing—A Pilot Study of Eye-Tracking