Measuring Brain Activity of School Age Children

Study Overview
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Brief Summary
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This observational study will investigate whether differences in birth events and oxygen levels during the newborn period affects the brain activity of children during the middle childhood years.

Detailed Description
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The investigators will conduct an observational study comparing two groups of children to determine whether differences in birth events and oxygen levels during the newborn period lead to structural and functional impairment within the brain's dopaminergic pathways and the cortical regions innervated by those pathways. The dopaminergic system is involved in modulating motor control and cognitive function. Using magnetic resonance diffusion tensor imaging, structural integrity of dopaminergic circuits will be quantified and compared in post-hypoxic former preterm children versus healthy control children born at term closely matched by age/sex/race. Functional activity during executive function tasks will be quantified and compared in post-hypoxic former preterm children versus healthy control children born at term using functional magnetic resonance imaging-blood oxygen level dependent (fMRI-BOLD). Assessment of motor function (grooved pegboard task) will also be performed.

Official Title
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Structure & Function of Dopaminergic Brain Networks Following Postnatally-Occurring Hypoxic Insults

Conditions
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Perinatal Hypoxia, Dopamine, Neurobehavioral Manifestations

Intervention / Treatment
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* Other: Magnetic Resonance Imaging
* Other: Cognitive Performance Testing


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Study Group Children: Birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA) with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11) For Healthy Control Children: Birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children. Born in years 2005-2009 (age range will be 8-15 years during the funding period) Ability of the child to provide assent, with the parent/legal guardian able to provide written informed consent for study procedures. Sensory and motor capability to complete study tasks (i.e. Grooved Pegboard test). Mental Development index must be > 80 at 2-year-old follow-up for preterm cohort. Exclusion Criteria: Past history of concussion requiring medical treatment to avoid confounding of MRI data Current diagnosis of autism. Child who suffers from claustrophobia (per parent report). Unable to participate in neuroimaging due to claustrophobia, or medical contraindication to MRI including any implanted medical device, dental braces, surgical clips for aneurysms in the head, heart valve prostheses, electrodes or other metallic objects, pregnancy. Healthy control children who were treated in the Neonatal ICU in the newborn period for breathing difficulties. Healthy control children who were hospitalized for breathing problems in the first 3 months of infancy.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 15 Years

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 |
| --- | --- |
| Post-hypoxic former preterm<br>Born in the years 2005-2009 with birth gestational age between 23-28 weeks and birth weight appropriate for gestational age (AGA). Part of a research cohort with available oxygen saturation level data recorded continuously from the first day of life to 8 weeks postnatal age (n=11).Children will undergo Magnetic Resonance Imaging and Cognitive Performance Testing. | Other: Magnetic Resonance Imaging<br>* MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel.<br>* Other names: fMRI-BOLD;Other: Cognitive Performance Testing<br>* For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.<br>* Other names: Grooved pegboard task;|
| Healthy term-born children<br>Born in the years 2005-2009 with birth gestational age ≥ 38 weeks gestation and birth weight appropriate for term gestation (n=10) matched by age/sex/race to participating cohort children with no history of respiratory difficulty suggesting hypoxic exposure. Children will undergo Magnetic Resonance Imaging and Cognitive Performance Testing. | Other: Magnetic Resonance Imaging<br>* MRI uses a strong magnetic field and radio waves to create detailed images of the brain while the person's head is positioned inside a round tunnel.<br>* Other names: fMRI-BOLD;Other: Cognitive Performance Testing<br>* For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.<br>* Other names: Grooved pegboard task;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Structural Integrity of Dopaminergic Circuits | Assessment of dopaminergic circuits originating in the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Includes right and left nucleus accumbens, right and left mamillary body, right and left hippocampus. Measured using Magnetic Resonance T1-weighted magnetization prepared rapid gradient echo (MPRAGE) scans with three-dimensional volumetrics analysis | 30 minutes | 
| Functional Activity During Executive Function Tasks | Subjects in each group were evaluated for changes in functional connectivity between the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA), as evaluated by functional magnetic resonance imaging blood oxygen level dependent (fMRI-BOLD), using whole brain analysis. The measurement is increase/decrease of MRI signal intensity in a given region, thresholded at p <0.05, summarized into a value representing 'size of region of increase' or 'size of region of decrease' after subjects' scans were combined/mapped onto a standard MNI brain. Only clusters of over 50 voxels were included, and the size of the region is reported in voxel size. The averaged brains for prematurely born fMRI was subtracted from the full term treatment for each group, and then these averaged differences were subtracted from each other. While other areas of the brain met threshold criteria in the analysis, only brain regions innervated by primary or collateral dopaminergic pathways are reported. | 30 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Performance-Fine Motor Function | Measured using the grooved pegboard task (number of seconds required to place 25 pegs using the dominant hand) | 20 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxia, Brain, Neural networks, Magnetic Resonance Imaging