The Neurocognitive Bases of Trust in Intellectual Disability

Official title

The Neurocognitive Bases of Trust in Intellectual Disability: Affective Evaluation, Trait Attribution, and Epistemic Vigilance

Overview

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people with Fragile X syndrome, who are often characterized by a completely opposite social behaviour profile, with a withdrawn attitude and significant social anxiety.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

• Other Confidence 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.
• Other clinical 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.
• Other Cognitive 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.
• Other Executive function assessment
  Executive function assessment including Laby 5-12 test, day/night Test, Questionnaire BRIEF-2, will be performed at visit V1.
• Other Sociability 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.
• Other Brain MRI (structural and functional)
  Optional brain MRI acquisition (structural and functional) will be performed at ancillary visit

Primary outcome measures

• Error rate (percentage) for each of the four paradigms. [Time frame: Day 1]
• Response time (millisecond) for two of the four paradigms. [Time frame: Day 1]
• Analysis of visual strategies for eye-tracking experiments. [Time frame: Day 1]

Secondary outcome measures (12)

• Presence of epilepsy (Yes/No) [Time frame: Day 1]
• Developmental trajectory [Time frame: Day 1]
• Mental age, in years, [4-12 years] assessed with the Raven's Progressive Matrices test [Time frame: Day 1]
• Presence of an associated autism spectrum disorder (Yes/No) [Time frame: Day 1]
• Existence of cardiac malformation (Yes/No). [Time frame: Day 1]
• 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) [Time frame: Day 1]
• 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. [Time frame: Day 1]
• Receptive and expressive lexical age [2-19] (in years) with PPVT5 and EVT3 tests respectively [Time frame: Day 1]
• Z scores [-5; +5] for the General Error Index, the Delay Aversion Index, and the Inhibition Index with Laby 5-12 test. [Time frame: Day 1]
• Score [0 -16] for the control condition and for the test condition with the Day/night test. [Time frame: Day 1]
• T-scores [0 -100] for the overall executive score with the BRIEF-2 questionnaire [Time frame: Day 1]
• Total T scores [30 - 90] with SRS-2 scale [Time frame: Day 1]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Observational model

Other

Study locations

France · 1 center

• Reference Center of Rare Disease with Intellectual Disability in Lyon, Woman Mother and Ch — Bron

Identifiers

NCT: NCT07434037 · 69HCL19_0237 · 2025-A02283-46

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗