Down Syndrome (Trisomy 21), Fragile X Syndrome (FXS)
Conditions
Keywords
Trust, Intellectual disability, Eyetracking analysis, Neuroimaging, Down syndrome, Fragile X syndrome
Brief summary
This project studies the neurocognitive basis of trust adjustment in intellectual disability (ID), a source of significant vulnerability for these patients, focusing on two target populations chosen for their specific social characteristics: people with Down syndrome, who are often described as being hypersocial, and people with Fragile X syndrome, who are often characterized by a completely opposite social behaviour profile, with a withdrawn attitude and significant social anxiety. The three different types of mechanisms that contribute to the adjustment of interpersonal trust: affective evaluation, trait attribution, and epistemic evaluation of informants, will be studied. Affective evaluation processes recruit subcortical structures such as the amygdala and assess potential social threats in the environment. The second mechanism for selecting whom to trust consists of forming a representation of a person's dispositions, such as benevolence and competence (also known as traits), and using it to predict that person's future behaviour. Trait attribution processes recruit a cortico-cerebellar network comprising the mPFC, CRUS I and posterior lobule VI. The third mechanism, called epistemic vigilance, allows to adjust our trust in what others communicate to us. This mechanism involves linking the assessment of the reliability of individuals who communicate (based on their benevolence and competence) with the reliability of the communicated information. Epistemic assessment involves frontal areas and areas associated with the representation of mental states in order to enable the evaluation of the truthfulness of the communicated information. All of these mechanisms become functional very early on, before a child's sixth birthday. There are reasons to expect that several of these central mechanisms supporting selective trust will behave atypically in intellectual disability.
Interventions
OTHERConfidence adjustment assessment
Interpersonal trust assessment including a series of behavioural and eye-tracking studies (Paradigm 1 : Forming impressions using facial cues; Paradigm 2 : Forming impressions using behaviors) and assessment of epistemic trust (Paradigm 3 : assessing informants, Paradigm 4 : vigilance towards deception), will be performed at visit V1.
OTHERclinical assessment
Clinical assessment including Medical history, developmental trajectory, epilepsy history, clinical examination, presence of autism spectrum disorder, presence of cardiopathy, will be performed at visit V1.
OTHERCognitive assessment
Cognitive assessment including Raven Matrix, Wechsler Scale (WISC-V or WAIS IV), Vineland Adaptive Behavior Scale II, PPVT5, EVT3, will be performed at visit V1.
Executive function assessment including Laby 5-12 test, day/night Test, Questionnaire BRIEF-2, will be performed at visit V1.
OTHERSociability assessment
Sociability assessment including Social Responsiveness Scale 2, Revised Preschool Anxiety Scale, two eye-tracking tasks (social scenes and social preference), Perception bias task, Distance adjustment task, Social motivation tasks, Examiner's assistance task, will be performed at visit V1.
Optional brain MRI acquisition (structural and functional) will be performed at ancillary visit
Sponsors
Hospices Civils de Lyon
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
3 Years to 29 Years
Healthy volunteers
Yes
Inclusion criteria
: Group of Down Syndrom patients * Complete chromosomal trisomy of the 21st chromosome confirmed by karyotype analysis * Aged 13 to 29 (chronological age) * French as their native language * Having signed an informed consent form and/or whose legal guardians/patient representatives have signed the informed consent form * Affiliated with the French health insurance system (social security) or whose legal guardians are affiliated with the French health insurance system Group of X-Fragile Syndrome * Complete mutation of the FMR1 gene by molecular analysis (more than 200 CGG triplet repeats) * Aged between 13 and 29 (chronological age) * Native French speakers * Having signed an informed consent form and/or whose legal guardians/patient representatives have signed the informed consent form * Affiliated with the French health insurance system (social security) or whose legal guardians are affiliated with the French health insurance system Group of chronological age-matched control * Aged between 13 and 29 * Native French speakers. * Having signed an informed consent form and/or whose legal guardians/patient representatives have signed the informed consent form * Affiliated with the French health insurance system (social security) or whose legal guardians are affiliated with the French health insurance system Group of mental age-matched control * Aged between 3 and 9 * Native French speakers. * Whose legal guardians/patient representatives have signed the informed consent form * Affiliated with the French health insurance system (social security) or whose legal guardians are affiliated with the French health insurance system
Exclusion criteria
Groups of Down Syndrom and X-Fragiles patients * Inability to understand tasks * Significant brain malformation * Uncontrolled epilepsy * Significant hearing impairment * Uncorrected visual impairment * Refusal of the subject and/or legal guardians/representative of the subject to be informed of any abnormalities detected during the neuropsychological assessment. * Subject participating in another interventional study with an exclusion period still ongoing at the time of pre-inclusion. Regarding the neuroimaging (MRI) study: * Having a contraindication to MRI examination (people using a pacemaker or insulin pump, people with metal prostheses or intracerebral clips, people with metal fragments in their eyes, as well as claustrophobic subjects). A comprehensive list of contraindications is provided in Appendix 5. * Inability to perform the MRI without anaesthesia. * Refusal by the subject and/or those exercising parental authority/the subject's representative to be informed of any abnormalities detected during the MRI. Groups of typical development persons (chronological age-matched and mental age-matched) * Known acquired neurological disorders, including epilepsy. * History of head trauma requiring hospitalisation. * Known psychiatric disorders. * Birth complications requiring admission to a neonatal intensive care unit or prematurity of less than 35 weeks. * Ongoing treatment with drugs affecting the central nervous system. * Significant hearing impairment * Uncorrected visual impairment * Repeating a school year * Learning disorders requiring rehabilitation (speech therapy, psychomotor therapy or orthoptics) for more than one year. * Refusal of the subject and/or legal guardians/representative of the subject to be informed of any abnormalities detected during the neuropsychological assessment. * Subject participating in another interventional study with an exclusion period still ongoing at the time of pre-inclusion. Regarding the neuroimaging (MRI) study (only for chronological age-matched group): * Having a contraindication to MRI examination (people using a pacemaker or insulin pump, people with metal prostheses or intracerebral clips, people with metal fragments in their eyes, as well as claustrophobic subjects). A comprehensive list of contraindications is provided in Appendix 5. * Inability to perform the MRI without anaesthesia. * Refusal by the subject and/or those exercising parental authority/the subject's representative to be informed of any abnormalities detected during the MRI.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Error rate (percentage) for each of the four paradigms. | Day 1 | Paradigm 1 /Facial trait assessment : Error rates for each condition (3 levels of difficulty) and 2 types of questions (traits/behaviours) Paradigm 2 / Behaviour assessment: Error rates for each of the three conditions (traits-to-behaviour, behaviour-to-traits, and behaviour-to-behaviour) Paradigm 3/ Assessing informants : error rates for each type of informant Paradigm 4 / Vigilance towards deception: Error rates concerning the location of the pompom, for each of the four conditions: baseline, benevolence, malicious intent, and explicit falsehood of the character. |
| Response time (millisecond) for two of the four paradigms. | Day 1 | Paradigm 1 / Facial trait assessment: Analysis of response times (in milliseconds) for each condition (3 levels of difficulty (easy/moderate/difficult) and 2 types of questions (traits/behaviours) obtained using Presentation® software. Paradigm 2 / Behaviour assessment: Analysis of response times (in milliseconds) for each of the three conditions (traits-to-behaviour, behaviour-to-traits, and behaviour-to-behaviour) using Presentation software. |
| Analysis of visual strategies for eye-tracking experiments. | Day 1 | Paradigm1 / Facial trait assessment: Observation time on different areas of interest (AOI eyes, AOI nose-mouth) obtained using the eye tracker (Tobii ProLab). Paradigm 2 / Behaviour assessment: measurement of time spent on each region of interest corresponding to the task images (in milliseconds) obtained using the eye tracker (Tobii ProLab) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Total score [0 -140] with the Liebowitz Social Anxiety Scale for Children and Adolescents | Day 1 | Sociability assessment A score above 70 indicates a severe social anxiety. |
| Observation time (in seconds) on social AOIs (Areas of Interest) and non-social AOIs for Social scene task in eye-tracking. | Day 1 | Sociability assessment |
| Proportion of fixation time on the social vs non-social AOI for Social preference task in eye-tracking | Day 1 | Sociability assessment |
| Presence of epilepsy (Yes/No) | Day 1 | Data from clinical examination and medical file |
| Developmental trajectory | Day 1 | * Age at head control acquisition in months, * Age at sitting alone in months, * Age at walking alone in months, * Age at running in months, * Age at climbing stairs alternately in months, * Age at voluntary grasping an object in months, * Age at thumb-index pinch in months, * Age at first words utterance in months, * Age at two words association in months, * Age at first sentences production in months, * Age at first responsive smiles in months, * Age at joint attention acquisition in months, * Age at fear of unfamiliar person in months, * Age at pretend to play in month, * Age at daytime toilet training in months, * Age at night-time toilet training in months, |
| Mental age, in years, [4-12 years] assessed with the Raven's Progressive Matrices test | Day 1 | Cognitive assessment |
| Presence of an associated autism spectrum disorder (Yes/No) | Day 1 | Data from clinical examination and medical file |
| Existence of cardiac malformation (Yes/No). | Day 1 | Data from clinical examination and medical file |
| Total IQ [40-160] from Wechsler scales adapted for age (WISC-V for patients aged above 6 years, and WAIS-IV for patients above 16 years) | Day 1 | Cognitive assessment assessing the intelligence quotient of the participant. Intellectually disabled patients have an IQ below 70. |
| Global score [20 - 160] and standard scores [20 - 160] for the areas of adaptive skills (communication, daily life, socialisation, and motor skills) with the VABS2. | Day 1 | Adaptive assessment based on interview with the parents of the patient. A score below 70 is considered as impaired. |
| Receptive and expressive lexical age [2-19] (in years) with PPVT5 and EVT3 tests respectively | Day 1 | Language assessment. These two tests allow the assessment of receptive and expressive language level (lexical age). |
| Z scores [-5; +5] for the General Error Index, the Delay Aversion Index, and the Inhibition Index with Laby 5-12 test. | Day 1 | Executive function assessment (planification) - The Z-score is used to assess a child's performance in relation to that of a normative group. A Z-score \< -2 means a clinically relevant impairment |
| Score [0 -16] for the control condition and for the test condition with the Day/night test. | Day 1 | Executive function assessment (inhibition) A score ≤ 8 indicates a weak performance and a potential weakness in executive functions |
| T-scores [0 -100] for the overall executive score with the BRIEF-2 questionnaire | Day 1 | Executive function assessment A T-score \> 65 means clinically relevant executive difficulties. |
| Score [1-6] for the Distance adjustment task | Day 1 | Sociability assessment The score is determined according to the distance at which the participant sits compared to the position of the unknown person |
| Social motivation score [1-6] for the social motivation task | Day 1 | Sociability assessment |
| Score [0-12] reflecting the willingness of the participant to help the examiner for the Examiner's assistance task | Day 1 | Sociability assessment The score will reflect if the participant does it spontaneously, or only one suggested, or only once explicitly mentioned or not al all. |
| Presence (Yes/No) of cerebral abnormalities from neuroimaging data. | Day 2 | * Presence of white matter abnormality (Yes/No) * Presence of corpus callosum abnormality (Yes/no) * Presence of cerebral atrophy (Yes/No) |
| Brain volume (mm3) and surfacic analysis (in mm) using Freesurfer software on 3DT1 morphometric data. Freesurfer analysis | Day 2 | Neuroimaging analysis. Brain volume and surfacic analysis will be performed using the Freesurfer software, allowing to compare between the 3 groups of participants (Fragile X, DS and controls). |
| Functional anisotropy (FA), mean diffusivity (MD), axial and radial diffusivity using Track-Based Spatial Statistics (TBSS) software. | Day 2 | Neuroimaging diffusion data analysis. |
| Latency, in milliseconds, of the first fixation on each type of AOI for Social preference task in eye-tracking. | Day 1 | Sociability assessment |
| Brain regions (clusters) activation (BOLD signal) during the assessment of the character's reliability. | Day 2 | Neuroimaging functional MRI analysis. The BOLD signal reflects local and transient variations in the amount of oxygen carried by haemoglobin as a function of neuronal activity in the brain. fMRI data will be analyzed using FSL software. |
| Error rate, in percentage, for the Perception bias task | Day 1 | Sociability assessment |
| Total T scores [30 - 90] with SRS-2 scale | Day 1 | Sociability assessment A T-score \> 76 indicates severe social difficulties. |
Countries
France
Contacts
CONTACTCURIE MD AURORE, MD
Outcome results
None listed