Measuring Brain Activity of School Age Children

NCT03407729 | Completed Results DMC

• 2 other identifiers: 1226607705-17-23
• Study Type: observational
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Perinatal Hypoxia; Dopamine; Neurobehavioral Manifestations

Keywords

Hypoxia, Brain; Neural networks; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (1)

• Cognitive Performance-Fine Motor Function

  20 minutes

Study Arms (2)

Post-hypoxic former preterm

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; Other: Cognitive Performance Testing

Healthy term-born children

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; Other: Cognitive Performance Testing

Interventions

Magnetic Resonance Imaging OTHER

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.

Also known as: T-1 MPRAGE, fMRI-BOLD

Healthy term-born children; Post-hypoxic former preterm

Cognitive Performance Testing OTHER

For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.

Also known as: Grooved pegboard task

Healthy term-born children; Post-hypoxic former preterm

Eligibility Criteria

• Age: 8 Years - 15 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Study Group Children (n=11) will be drawn from a cohort currently maintained by the investigators. Healthy Control Children will be recruited using various strategies: (1) study flyers given to the parents of the prematurely born cohort children to pass along to parents of other children with ages similar to their own child. (2) study flyers posted in the hospital's primary care pediatric clinics asking interested children/families to contact us to learn more about the study; (3) study flyers distributed by professional colleagues/pediatric physicians to potential candidate children/families meeting study inclusion criteria.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Case Western Reserve University: lead

Study Sites (1)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Related Publications (20)

• Poets CF, Samuels MP, Southall DP. Epidemiology and pathophysiology of apnoea of prematurity. Biol Neonate. 1994;65(3-4):211-9. doi: 10.1159/000244055.

  PMID: 8038285 BACKGROUND

• Huppi PS, Murphy B, Maier SE, Zientara GP, Inder TE, Barnes PD, Kikinis R, Jolesz FA, Volpe JJ. Microstructural brain development after perinatal cerebral white matter injury assessed by diffusion tensor magnetic resonance imaging. Pediatrics. 2001 Mar;107(3):455-60. doi: 10.1542/peds.107.3.455.

  PMID: 11230582 BACKGROUND

• Inder TE, Volpe JJ. Mechanisms of perinatal brain injury. Semin Neonatol. 2000 Feb;5(1):3-16. doi: 10.1053/siny.1999.0112.

  PMID: 10802746 BACKGROUND

• Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, Bairam A, Moddemann D, Peliowski A, Rabi Y, Solimano A, Nelson H; Canadian Oxygen Trial Investigators. Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. JAMA. 2015 Aug 11;314(6):595-603. doi: 10.1001/jama.2015.8841.

  PMID: 26262797 BACKGROUND

• Janvier A, Khairy M, Kokkotis A, Cormier C, Messmer D, Barrington KJ. Apnea is associated with neurodevelopmental impairment in very low birth weight infants. J Perinatol. 2004 Dec;24(12):763-8. doi: 10.1038/sj.jp.7211182.

  PMID: 15329741 BACKGROUND

• Perna R, Cooper D. Perinatal cyanosis: long-term cognitive sequelae and behavioral consequences. Appl Neuropsychol Child. 2012;1(1):48-52. doi: 10.1080/09084282.2011.643946.

  PMID: 23428277 BACKGROUND

• Smith TF, Schmidt-Kastner R, McGeary JE, Kaczorowski JA, Knopik VS. Pre- and Perinatal Ischemia-Hypoxia, the Ischemia-Hypoxia Response Pathway, and ADHD Risk. Behav Genet. 2016 May;46(3):467-77. doi: 10.1007/s10519-016-9784-4. Epub 2016 Feb 26.

  PMID: 26920003 BACKGROUND

• Decker MJ, Hue GE, Caudle WM, Miller GW, Keating GL, Rye DB. Episodic neonatal hypoxia evokes executive dysfunction and regionally specific alterations in markers of dopamine signaling. Neuroscience. 2003;117(2):417-25. doi: 10.1016/s0306-4522(02)00805-9.

  PMID: 12614682 BACKGROUND

• Decker MJ, Jones KA, Solomon IG, Keating GL, Rye DB. Reduced extracellular dopamine and increased responsiveness to novelty: neurochemical and behavioral sequelae of intermittent hypoxia. Sleep. 2005 Feb;28(2):169-76. doi: 10.1093/sleep/28.2.169.

  PMID: 16171240 BACKGROUND

• Decker MJ, Jones KA, Keating GL, Rye DB. Postnatal hypoxia evokes persistent changes within the male rat's dopaminergic system. Sleep Breath. 2018 May;22(2):547-554. doi: 10.1007/s11325-017-1558-6. Epub 2017 Aug 22.

  PMID: 28828549 BACKGROUND

• Rocha-Ferreira E, Hristova M. Plasticity in the Neonatal Brain following Hypoxic-Ischaemic Injury. Neural Plast. 2016;2016:4901014. doi: 10.1155/2016/4901014. Epub 2016 Mar 7.

  PMID: 27047695 BACKGROUND

• Nyakas C, Buwalda B, Luiten PG. Hypoxia and brain development. Prog Neurobiol. 1996 May;49(1):1-51. doi: 10.1016/0301-0082(96)00007-x.

  PMID: 8817697 BACKGROUND

• Stollstorff M, Foss-Feig J, Cook EH Jr, Stein MA, Gaillard WD, Vaidya CJ. Neural response to working memory load varies by dopamine transporter genotype in children. Neuroimage. 2010 Nov 15;53(3):970-7. doi: 10.1016/j.neuroimage.2009.12.104. Epub 2010 Jan 4.

  PMID: 20053379 BACKGROUND

• Langer N, von Bastian CC, Wirz H, Oberauer K, Jancke L. The effects of working memory training on functional brain network efficiency. Cortex. 2013 Oct;49(9):2424-38. doi: 10.1016/j.cortex.2013.01.008. Epub 2013 Jan 31.

  PMID: 23489778 BACKGROUND

• Allin MP, Kontis D, Walshe M, Wyatt J, Barker GJ, Kanaan RA, McGuire P, Rifkin L, Murray RM, Nosarti C. White matter and cognition in adults who were born preterm. PLoS One. 2011;6(10):e24525. doi: 10.1371/journal.pone.0024525. Epub 2011 Oct 12.

  PMID: 22022357 BACKGROUND

• Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007 Jul;4(3):316-29. doi: 10.1016/j.nurt.2007.05.011.

  PMID: 17599699 BACKGROUND

• D'Ardenne K, McClure SM, Nystrom LE, Cohen JD. BOLD responses reflecting dopaminergic signals in the human ventral tegmental area. Science. 2008 Feb 29;319(5867):1264-7. doi: 10.1126/science.1150605.

  PMID: 18309087 BACKGROUND

• Kim SG, Ogawa S. Biophysical and physiological origins of blood oxygenation level-dependent fMRI signals. J Cereb Blood Flow Metab. 2012 Jul;32(7):1188-206. doi: 10.1038/jcbfm.2012.23. Epub 2012 Mar 7.

  PMID: 22395207 BACKGROUND

• Goncalves SI, de Munck JC, Pouwels PJ, Schoonhoven R, Kuijer JP, Maurits NM, Hoogduin JM, Van Someren EJ, Heethaar RM, Lopes da Silva FH. Correlating the alpha rhythm to BOLD using simultaneous EEG/fMRI: inter-subject variability. Neuroimage. 2006 Mar;30(1):203-13. doi: 10.1016/j.neuroimage.2005.09.062. Epub 2005 Nov 14.

  PMID: 16290018 BACKGROUND

• Galan RF, Ermentrout GB, Urban NN. Efficient estimation of phase-resetting curves in real neurons and its significance for neural-network modeling. Phys Rev Lett. 2005 Apr 22;94(15):158101. doi: 10.1103/PhysRevLett.94.158101. Epub 2005 Apr 19.

  PMID: 15904191 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

MRI neuroimages

MeSH Terms

Conditions

Neurobehavioral Manifestations; Hypoxia, Brain

Interventions

Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases; Hypoxia; Signs and Symptoms, Respiratory

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques

Limitations and Caveats

Insufficient numbers of children studied due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic research shut-down. When research protocols were permitted to resume, parents were reluctant to bring children for a voluntary research study. Data collection also terminated early for technical reasons; the magnetic resonance imaging (MRI) scanner was replaced during the pandemic shut-down with a different model that did not produce comparable results to the earlier scans.

Results Point of Contact

• Title: Dr. Michael J. Decker
• Organization: Case Western Reserve University

mjd6@case.edu

2163682467

Study Officials

• Michael J Decker, PhD

  Case Western Reserve University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 16, 2018
• First Posted: January 23, 2018
• Study Start: June 8, 2018
• Primary Completion: February 17, 2020
• Study Completion: February 17, 2020
• Last Updated: October 10, 2022
• Results First Posted: October 10, 2022

Record last verified: 2022-10

Locations

US (1)