The Brain Mechanism of Social Emotion and Communication in Infants Aged 0 to 6 Years

A Cohort Study on the Brain Mechanism of Social Emotion and Communication in Infants Aged 0 to 6 Years

This study explores the relationship between brain development and infants' social emotion and communication ability, as well as the role of genetic factors and maternal exposure during pregnancy (e.g., environmental exposures and maternal inflammatory states). To provide a theoretical basis for precise intervention of infants' social emotion and communication problems and the overall improvement of brain development.

Study Overview

• Status: Recruiting
• Conditions: Brain Development; Behavior Disorders, Child; Intellectual Developmental Disorders
• Intervention / Treatment: Other: maternal exposure during pregnancy

Detailed Description

This study uses functional magnetic resonance imaging (fMRI) is a ultra-fast imaging technology to reflect the changes in brain function when the brain is stimulated or pathologically affected. There are 4 working imaging techniques for fMRI, including blood-oxygen-level dependent fMRI, perfusion weighted imaging (PWI), perfusion weighted imaging (PWI) and MRI spectroscopy. fMRI combine with cloud computing to analyze brain structure, brain function, brain connection, brain development trajectory, multi-modal brain imaging artificial Intelligent calculation, and draw dynamic connection maps of brain development in children aged 0-6 years. In addition, using the Chinese Urban Children's Emotion and Social Assessment Scale (CITSEA) to evaluate children's social and emotional behavior and Gesell Developmental Scale (GDS) to assess the neurological integrity and functional maturity of children, and explore their relationship with brain imaging. The researchers will collect blood samples from the enrollees for whole exome sequencing as well as exposome testing to look for genes related to brain intellectual development and biomarkers related to brain development and to explore their relationship with brain imaging. In addition, the researchers will collect basic information about the family and the mother's health during pregnancy through baseline questionnaires and clinical history data, which will be used to explore pregnancy risk factors for children's brain development and the role of these factors in brain development and the baby's social-emotional and communication skills.

This study explores the relationship between brain development and infants' social emotion and communication ability, as well as the role of genetic factors and maternal exposure during pregnancy (e.g., environmental exposures and maternal inflammatory states). To provide a theoretical basis for precise intervention of infants' social emotion and communication problems and the overall improvement of brain development.

• Study Type: Observational
• Enrollment (Estimated): 3001

Contacts and Locations

• Study Contact: Name: Wenhao Zhou, Prof; Phone Number: (+86) 021-64931168; Email: zwhchfu@126.com
• Study Contact Backup: Name: Deyi Zhuang, Dean; Phone Number: 15959279526; Email: zhuangdy526@163.com

Study Locations

• China
  • Fujian
    • Xiamen, Fujian, China, 361000
      • Recruiting
      • Xiamen Children's Hospital
      • Contact: Deyi Zhuang, Dean; Phone Number: 15959279526; Email: zhuangdy526@163.com
      • Contact: Xianghui Huang, Director; Phone Number: 13799250830; Email: xmhxh2013@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 6 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Infants aged 0-6 years are mainly recruited from the society and Xiamen Children's Hospital.

Description

Inclusion Criteria:

1. Age 0-6 years
2. Born at 34-42 weeks of gestation
3. Birth weight>1500g
4. Normal brain function assessment
5. Parents can understand and sign informed consent

Exclusion Criteria:

1. The mother had severe complications during pregnancy and delivery
2. History of asphyxiation at birth
3. Have congenital structural malformation
4. Have congenital metabolic disease
5. Have major or genetic diseases that affect growth, development or cognition
6. Have contraindications to MRI scanning

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Infant Cohort; Healthy infants aged from 0-72 months.This is an observational trial so no intervention will be provided, with exception of study assessments, including fMRI.	Other: maternal exposure during pregnancy; maternal exposure during pregnancy (e.g., environmental exposures and maternal inflammatory states)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain structure (cortical thickness) change of subjects	Using T1 weighted and T2 weighted images to measure brain cortical thickness, analyzing the brain structural changes (differences of cortical thickness) over time.	at baseline,and 6 months after baseline.
Brain structural connectivity change of subjects	Using diffusion-weighted images to measure the structural connectivity matrix (based on fiber tracking) of brain, analyzing the brain structural connectivity changes (differences in fibers number) over time.	at baseline,and 6 months after baseline.
Brain functional connectivity change of subjects	Using resting state functional MRI (blood-oxygen-level dependent) to measure the functional connectivity matrix, analyzing the brain functional connectivity (differences in connectivity strength) changes over time.	at baseline,and 6 months after baseline.
Cerebral blood flow change of subjects	Using arterial spin labeling (ASL) to measure relative cerebral blood flow (rCBF) can produce quantitative cerebral perfusion images, analyzing the change (differences in rCBF) of brain perfusion over time.	at baseline,and 6 months after baseline.
Developmental level prediction change of subjects (brain age, CITSEA and GDS score)	Using a connectome-based predictive model (CPM) to predict the developmental levels of subjects. In the modal training procedure, extracted multimodal MRI measures (primary outcomes 1 to 4) are input features, and the age, CITSEA and GDS score are ground truths.	at baseline,and 6 months after baseline.
EEG examination change of subjects	EEG data were collected at each follow-up visit. Electroencephalogram (EEG), especially the event-related potential (ERP) technique, can non-invasively explore the cognitive processes of infant speech recognition, language comprehension, phonological awareness, recognition memory, and facial emotion recognition. The study will collect EEG data from children in resting states, including the power spectral density of different frequency bands (e.g., delta, theta, alpha, beta, gamma), ERP waveform, amplitude, and latency during specific cognitive or sensory tasks, and EEG network connectivity in resting and task states. Through an experimental paradigm designed specifically for different age groups, the influential factors of language and social-emotional development in 0-3 years old infants were explored.	at baseline, and 6 months after baseline.
Social and emotional behavior change of subjects (CITSEA score)	Using Chinese Version of Urban Infant-Toddler Social and Emotional Assessment (CITSEA) to evaluate children's social and emotional behavior, including four broad domains: 1) externalizing problems; 2) internalizing problems; 3) dysregulation problems; 4) competencies. The problem behavior domain T score >63 is assessed as suspicious positive, indicating possible social-emotional behavior problems; the competencies domain T score <37 is assessed as suspicious positive, indicating there may be a delay in the development of social-emotional ability, analyzing the CITSEA score changes over time.	at baseline,and 6 months after baseline.
Brain development change of subjects (GDS score)	Using Gesell Development Scale (GDS) to assess neurological integrity and functional maturity of children, including adaptive behavior, gross motor behavior, fine motor behavior, language behavior and personal social behavior. Mild intellectual disability: 55≤DQ≤75; moderate intellectual disability: 40≤DQ≤54; severe mental disability:25≤DQ≤39; extreme intellectual disability: DQ<25, analyzing the GDS score changes over time.	at baseline,and 6 months after baseline.
Child behavioral development change of subjects	Griffiths Development Scales - Chinese Edition (GDSC) : Griffith scale in Chinese children aged 0 ~ 8 speakers of standardized rating scale, with Chinese standard. The scale is divided into two parts, 0-2 years old and 0-8 years old. The 0-2 years old part is composed of 5 fields: The 0-2 years old part is composed of 5 fields, such as "A action ", "B individual-social ", "C language ", "D hand-eye coordination "and "E performance", and the 0-8 years old part adds "F practical reasoning field "on this basis. When the development quotient DQ<70, development is delayed, and when DQ≥85, development is normal.	at baseline,and 6 months after baseline.
Child mental health change of subjects	Ages and Stages Questionnaires: Social-Emotional, Second Edition (ASQ:SE-2) : This scale is used to assess a child's social-emotional development. In general, a higher score means a child needs more attention or is in a higher risk state for social-emotional development.	at baseline, and 6 months after baseline.
Intelligence quotient change of subjects	Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) : Use the Chinese version (revised by Professor Zhang Houcan) to assess children's intelligence level. Choose 10 core tests and 4 auxiliary tests from WISC-IV. Four scores, namely the Verbal Comprehension index (VCI), Perceptual Reasoning Index (PRI), Working memory Index (WMI), and processing speed Index (PSI), were calculated from the question bank, and the four composite scores were recombined to form the General Ability Index (GAI) and Cognitive Ability Index (CPI). The resulting total Intelligence quotient (FSIQ). A FSIQ score between 85 and 115 is considered normal intelligence; Between 70 and 84 are classified as borderline intelligence; Less than 70 is classified as low intelligence.	at 3 years old, 4 years old, 5 years old, and 6 years old.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker Screening	At enrollment, 0.5 ml of blood was drawn from each parent and child for the exposome. High - throughput sequencing technology will be used to screen for biomarkers associated with brain development.	one time blood draw at baseline.
Relationship Assessment between Biomarkers and Development	The relationship between the identified biomarkers and children's cognitive and emotional development will be assessed. This will provide a database for understanding the relationship between environment and development, and a scientific basis for future intervention strategies.	at baseline.

Collaborators and Investigators

• Sponsor: Children's Hospital of Fudan University
• Collaborators: Health Science Center of Xi'an Jiaotong University; Xiamen Children's Hospital; Shanghai University; ShanghaiTech University
• Investigators: Study Chair: Deyi Zhuang, Dean, Xiamen Children's Hospital

Publications and helpful links

General Publications

• Emerson RW, Adams C, Nishino T, Hazlett HC, Wolff JJ, Zwaigenbaum L, Constantino JN, Shen MD, Swanson MR, Elison JT, Kandala S, Estes AM, Botteron KN, Collins L, Dager SR, Evans AC, Gerig G, Gu H, McKinstry RC, Paterson S, Schultz RT, Styner M; IBIS Network; Schlaggar BL, Pruett JR Jr, Piven J. Functional neuroimaging of high-risk 6-month-old infants predicts a diagnosis of autism at 24 months of age. Sci Transl Med. 2017 Jun 7;9(393):eaag2882. doi: 10.1126/scitranslmed.aag2882.
• Ball G, Pazderova L, Chew A, Tusor N, Merchant N, Arichi T, Allsop JM, Cowan FM, Edwards AD, Counsell SJ. Thalamocortical Connectivity Predicts Cognition in Children Born Preterm. Cereb Cortex. 2015 Nov;25(11):4310-8. doi: 10.1093/cercor/bhu331. Epub 2015 Jan 16.
• Cao M, He Y, Dai Z, Liao X, Jeon T, Ouyang M, Chalak L, Bi Y, Rollins N, Dong Q, Huang H. Early Development of Functional Network Segregation Revealed by Connectomic Analysis of the Preterm Human Brain. Cereb Cortex. 2017 Mar 1;27(3):1949-1963. doi: 10.1093/cercor/bhw038.
• Cao M, Huang H, He Y. Developmental Connectomics from Infancy through Early Childhood. Trends Neurosci. 2017 Aug;40(8):494-506. doi: 10.1016/j.tins.2017.06.003. Epub 2017 Jul 3.
• Emerson RW, Gao W, Lin W. Longitudinal Study of the Emerging Functional Connectivity Asymmetry of Primary Language Regions during Infancy. J Neurosci. 2016 Oct 19;36(42):10883-10892. doi: 10.1523/JNEUROSCI.3980-15.2016.
• Tavor I, Parker Jones O, Mars RB, Smith SM, Behrens TE, Jbabdi S. Task-free MRI predicts individual differences in brain activity during task performance. Science. 2016 Apr 8;352(6282):216-20. doi: 10.1126/science.aad8127. Epub 2016 Apr 7.
• Zhang Y, Shi F, Wu G, Wang L, Yap PT, Shen D. Consistent Spatial-Temporal Longitudinal Atlas Construction for Developing Infant Brains. IEEE Trans Med Imaging. 2016 Dec;35(12):2568-2577. doi: 10.1109/TMI.2016.2587628. Epub 2016 Jul 7.
• Zhang W, Li R, Deng H, Wang L, Lin W, Ji S, Shen D. Deep convolutional neural networks for multi-modality isointense infant brain image segmentation. Neuroimage. 2015 Mar;108:214-24. doi: 10.1016/j.neuroimage.2014.12.061. Epub 2015 Jan 3.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: July 29, 2021
• First Submitted That Met QC Criteria: September 3, 2021
• First Posted (Actual): September 10, 2021

Study Record Updates

• Last Update Posted (Estimated): November 19, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Children; Brain; Newborn; Development; Infants; Neonates; Preterm
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Neurodevelopmental Disorders; Developmental Disabilities; Mental Disorders; Intellectual Disability; Child Behavior Disorders
• Other Study ID Numbers: CCBN_01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No