Measuring Brain Activity of School Age Children

Neurobehavioral Manifestations Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03407729
• Other study ID #: 12266077
• Secondary ID: 05-17-23
• Status: Completed
• Start date: June 8, 2018
• Est. completion date: February 17, 2020

Study information

• Verified date: October 2022
• Source: Case Western Reserve University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: February 17, 2020
• Est. primary completion date: February 17, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 15 Years

Eligibility

Inclusion Criteria:

1. 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)

2. 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.

3. Born in years 2005-2009 (age range will be 8-15 years during the funding period)

4. Ability of the child to provide assent, with the parent/legal guardian able to provide written informed consent for study procedures.

5. 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:

1. Past history of concussion requiring medical treatment to avoid confounding of MRI data

2. Current diagnosis of autism.

3. Child who suffers from claustrophobia (per parent report).

4. 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.

5. Healthy control children who were treated in the Neonatal ICU in the newborn period for breathing difficulties.

6. Healthy control children who were hospitalized for breathing problems in the first 3 months of infancy.

Related Conditions & MeSH terms

• Dopamine
• Hypoxia
• Neurobehavioral Manifestations
• Perinatal Hypoxia

Intervention

Other:
• Magnetic Resonance Imaging
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.
• Cognitive Performance Testing
For the Grooved Pegboard task: After the MRI scan, children will be timed as they place pegs into holes with randomly positioned slots.

Locations

Country	Name	City	State
United States	Case Western Reserve University	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Case Western Reserve University

Country where clinical trial is conducted

United States, 

References & Publications (20)

Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007 Jul;4(3):316-29. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Galán 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. Epub 2005 Apr 19. — View Citation

Gonçalves 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. Epub 2005 Nov 14. — View Citation

Hüppi 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. — View Citation

Inder TE, Volpe JJ. Mechanisms of perinatal brain injury. Semin Neonatol. 2000 Feb;5(1):3-16. Review. — View Citation

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. — View Citation

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. Review. — View Citation

Langer N, von Bastian CC, Wirz H, Oberauer K, Jäncke 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. — View Citation

Nyakas C, Buwalda B, Luiten PG. Hypoxia and brain development. Prog Neurobiol. 1996 May;49(1):1-51. Review. — View Citation

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. — View Citation

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. — View Citation

Poets CF, Samuels MP, Southall DP. Epidemiology and pathophysiology of apnoea of prematurity. Biol Neonate. 1994;65(3-4):211-9. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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