A First-ever Research Collaboration to Characterize MRI Measured Neural Flexibility Development in Chinese Toddlers

Study Overview
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Brief Summary
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The overall objective is to characterize the developmental characteristics of MRI measured neural flexibility, as an index of cognitive flexibility, in Chinese toddlers (32 to 42 months old).

Detailed Description
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The primary objective of this clinical study is to characterize in Chinese toddlers ages 32 - 42 months old the developmental characteristics of MRI measured neural flexibility, as an index of cognitive flexibility, and to assess a range of executive functions (inhibit, shift, emotional control, working memory, plan/organize) using the Global Executive Composite summary score obtained from the BRIEF-P standardized rating scale.

Official Title
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A First-ever Research Collaboration to Characterize MRI Measured Neural Flexibility Development in Chinese Toddlers

Conditions
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Growth & Development, Brain

Intervention / Treatment
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* Radiation: MRI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent has been obtained from the parent/legally acceptable representative. Full-term birth (more than 37 weeks and >2.5kg) Children aged between 32 to 34 mo or 2.8 to 2.10 years at enrollment Neurotypical development as assessed by interview No major risk factors for learning, neurologic, or psychiatric disorder as assessed by interview [defined as a diagnosed learning neurologic or psychiatric disorder in a first degree relative (e.g. parents, siblings)]. Dietary requirement detailed below: S-26 GOLD or ULTIMA GUM--fed group: I. Daily consumption of S-26 GOLD or ULTIMA GUM for the last 60 days (2 months) II. Desire of the parent to continue feeding GUM during the course of the study Cow's milk-fed group: I. Daily consumption of cow's milk or for the last 60 days (2 months) II. Desire of the parent to continue feeding cow's milk during the course of the study Exclusion Criteria: Delayed birth ( > 41 weeks gestation) as reported in medical record Birth Weight < 2500 g or small for gestational age (birth weight below the 10th percentile) or large for gestational age (birth weight above the 90th percentile) as reported in medical record History of neurological (e.g., head injury, epilepsy), psychiatric or developmental disorder in the toddler as assessed by interview History of diagnosed neurological (e.g., head injury, epilepsy), psychiatric or developmental disorder in parents or siblings, as assessed by interview In utero exposure to alcohol abuse or illicit substances as defined as diagnosis of current substance use disorder in the biological mother and guidelines set by the American College of Obstetricians and Gynecologists and the Royal College of Physicians Multiple birth as reported in medical record Complicated pregnancy (e.g., preeclampsia, gestational diabetes) as assessed by medical interview/ medical record Abnormal screening laboratory values and studies considered to be clinically significant in the opinion of the Investigator (e.g., metabolic disease screening, neonatal bilirubin)

Ages Eligible for Study
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Minimum Age: 32 Months
Maximum Age: 34 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| S-26 GOLD/ULTIMA GUM-fed group:<br>Parent(s) to continue feeding their child S-26 GOLD or ULTIMA GUM during the course of the study. We will collect information from parents on the S-26 GOLD/ ULTIMA GUM for a maximum of 2 months prior to the study start and during the course of the study. | Radiation: MRI<br>* MRI is a safe, non-invasive, cutting edge imaging technology widely used to study the human brain both internationally (NIH connectome project) and in China (China Brain Project). The Baby Connectome Project (BCP) led by NIH scientists has begun data collection on the structural and functional brain development among American infants (Howell, Styner et al. 2019).<br>|
| Cow's milk-fed group:<br>Parent(s) to continue feeding their child cow's milk during the course of the study. We will collect information from parents on the cow's milk consumed for a maximum of 2 months prior to the study start and during the course of the study. | Radiation: MRI<br>* MRI is a safe, non-invasive, cutting edge imaging technology widely used to study the human brain both internationally (NIH connectome project) and in China (China Brain Project). The Baby Connectome Project (BCP) led by NIH scientists has begun data collection on the structural and functional brain development among American infants (Howell, Styner et al. 2019).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neural flexibility | Neural flexibility is a quantitative measure of the frequency at which brain regions change their allegiance from one functional module to another during a given time period. It will be measured by MRI at the brain regions implicated to be associated with cognitive flexibility (including anterior cingulate cortex, dorsolateral prefrontal cortex, ventrolateral prefrontal cortex, anterior insula, interior frontal junction, superior parietal lobule, precuneus, intraparietal sulcus, frontal eye fields, and temporoparietal junction) | at baseline and 8 months after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain structure (brain regions volume) | Brain structure (brain regions volume) measured using MRI, including the hippocampal and frontal lobe volume (in cubic millimeter) | at baseline and 8 months after baseline | 
| Brain structure (cortical surface area) | Brain structure (cortical surface area) measured using MRI | at baseline and 8 months after baseline | 
| Brain structure (cortical thickness) | Brain structure (cortical thickness) measured using MRI | at baseline and 8 months after baseline | 
| Brain structure (myelination) | Brain structure (myelination) measured using MRI | at baseline and 8 months after baseline | 
| Brain function (network topologies) | Brain functional network topologies of the nine commonly assessed brain functional networks, including the primary visual, secondary visual, visual association, motosensory, default mode, frontoparietal, medial frontal, subcortical and cerebellum networks using MRI | at baseline and 8 months after baseline | 
| Brain function (connection strengths) | Brain functional connection strengths of the nine commonly assessed brain functional networks, including the primary visual, secondary visual, visual association, motosensory, default mode, frontoparietal, medial frontal, subcortical and cerebellum networks using MRI | at baseline and 8 months after baseline | 
| Children development | Using the Griffiths Mental Development Scales for China (GDS-C). Gross and fine motor, personal-social-emotional, language and communication and learning development will be assessed | at baseline and 8 months after baseline | 
| Children attention | Using an established eye tracking protocol in Chinese pediatric population (using the Tobii TX300 eye tracker) | at baseline and 8 months after baseline | 
| Children behavior (for infants) | Using the Infant Behavior Questionnaire (IBQ) for age 3-12 months | at baseline and 8 months after baseline | 
| Children behavior (for toddlers) | Using the Early Childhood Behavioral Questionnaire (ECBQ) for age 13 - 36 months | at baseline and 8 months after baseline | 
| Sleep quality | Sleep quality, duration and efficiency (total sleep time / duration of sleep episode *100) computed using the Brief Infant Sleep Questionnaire (BISQ). In addition, an actigraphy in combination with a sleep diary will be used during home period and their relationship will indicate the sleep quality | at baseline and 8 months after baseline | 
| Fecal microbiota composition | Measured via the shotgun metagenomics sequencing for species composition and functional pathways through stool samples collected | at baseline and 8 months after baseline | 
| Breast milk composition | Breast milk composition (lipids, carbohydrates, proteins, minerals and vitamins) will be measured by the MIRIS analyzer through breast milk samples collected (only for breast-fed subjects) | at baseline and 8 months after baseline | 
| Feeding practice | Using validated Child Feeding Practice Questionnaire. In addition, to complete the feeding and adverse events calendar monthly during home period | at baseline and 8 months after baseline | 
| Home environment | Using Home Environment questionnaire to collect information on household: siblings, and whether parents receive help on feeding the child. | at baseline and 8 months after baseline | 
| Cognitive flexibility | Using the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) and the Dimensional Change Card Sort (DCCS) task | at 36 months of age |