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Brain Maturation

Objectives

We focus on brain and behavioral development during childhood and adolescence, and on the impact of genetic, biological, and environmental factors. We use multimodal MRI techniques as well as cognitive and clinical assessments to assess brain and behavioral developmental trajectories in health and disease. In our studies, we investigate how measures, such as brain structure volumes, cortical thickness and area, white matter fiber bundles characteristics, and brain activation at rest or during the performance of specific psychological tasks, are related to and modulated by clinical, behavioral, hormonal and genetic variables. We closely collaborate with the Developmental Psychiatry group on different project.

Research projects

HUBU (“Hjernens Udvikling hos Børn og Unge“: Brain maturation in children and adolescents)

This project aims to define the degree of variability in the maturational trajectories of different brain circuits among healthy children, and to link these to developing cognitive, emotional and neuroendocrine functions. Moreover, we examine the impact of environmental factors, e.g. alcohol use, physical activity and stress, as well as intrinsic factors, e.g. genetic polymorphisms and hormones, on such development. The work addresses critical questions regarding the factors that place young people at risk for developing emotional problems and substance abuse, as well as related questions regarding the consequences of early stress and exposure to alcohol and drugs on continuing biological development of the brain.

 

brain maturation

 

HUBU is an ongoing longitudinal project, which started in Spring 2007, and included 95 typically-developing children aged 7-13 years at baseline. The first 10 assessments were conducted with 6-month intervals, the 11th assessment one year later (2013), and the 12th assessment three years later (2016). The 13th assessment (no MRI) was conducted in 2019. At each assessment, participants underwent approximately one hour MRI, and two hours of clinical and behavioral assessments, including computerized cognitive and emotional tasks, questionnaires, e.g. personality traits, stressful life events, physical activity, and saliva samples. Moreover, in parallel to the first five assessments the Danish School of Education and the National Center for Reading tested children's math and reading skills at their schools. Presently, we are analyzing the wealth of longitudinal data and finalizing papers.

Since January 2017, the HUBU project has been part of the Horizon 2020 project Lifebrain (see below).

The Glucocorticoid Project

The project examines potential long-term effects of glucocorticoid treatment for non-cerebral diseases in early life on brain structure and function in children and adolescents aged 7-14 years. To examine the long-term effects of glucocorticoids, two clinical groups diagnosed with rheumatic or nephritic disorder were enrolled in the study alongside a control group matched on sex and age. The two clinical groups have been treated with high doses of exogenous glucocorticoid in (pre)school years. All participants underwent structural MRI and DWI, and clinical and neuropsychological assessments. Furthermore, two fMRI paradigms designed to engage brain regions enriched with glucocorticoid receptors were implemented. Salivary cortisol and alpha-amylase samples were collected during scanning and on two separate normal weekdays. The project started in Summer 2010, and the data acquisition was completed May 2012. The project resulted in two PhD theses and several journal papers. Currently, the study’s outcomes are being finalized.

Lifebrain; Healthy minds from 0-100 years: Optimising the use of European brain imaging cohorts:

Lifebrain is a European consortium coordinated by the University of Oslo, consisting of 14 partners (https://www.drcmr.dk/lifebrain). Lifebrain started in 2017 and aims (i) to establish a solid foundation of knowledge for understanding how brain, cognitive and mental health can be optimized through the lifespan and (ii) to identify determinants of brain, cognitive and mental health at different stages of life by creating a large database of detailed information about brain imaging relating to cognitive function, mental health, and genetics. Life brain incorporates more than 5000 individual participants and exceeds 27.000 examinations in total.

 

Dissertations

  • PhD thesis: 4 finalized, 1 ongoing
  • MSc Thesis: 6 finalized, 1 ongoing
  • Research year projects: 3 finalized
  • BSc Thesis: 2 finalized

Funding

FSS (Frie Forskningsråd | Sundhed og Sygdom)
The Lundbeck Foundation
Hvidovre Hospital's Research Foundation
Faculty of Health Sciences (SUND), University of Copenhagen
Institute of Psychology, University of Copenhagen
Savværksejer Jeppe Juhl og Hustru Evita Juhls mindelegat

 

Selected Publications

Marybel Robledo Gonzalez , William F.C. Baaré, Donald J. Hagler Jr., Sarah Archibald, Martin Vestergaard, Kathrine Skak Madsen. Brain structure associations with phonemic and semantic fluency in typically-developing children. Developmental Cognitive Neuroscience. 2021. https://doi.org/10.1016/j.dcn.2021.100982

Vestergaard M, Baaré WFC, Holm SK, Madsen CG, Paulson OB, Born AP, Uldall P, Siebner HR, Madsen KS (2021) Glucocorticoid treatment for non-cerebral diseases in children and adolescents is associated with differences in uncinate fasciculus microstructure. Pediatric Research. https://www.nature.com/articles/s41390-021-01394-w

Madsen KS, Johansen LB, Thompson WK, Siebner HR, Jernigan TL, Baaré WFC (2020). Maturational trajectories of white matter microstructure underlying the right presupplementary motor area reflect individual improvements in motor response cancellation in children and adolescents. Neuroimage, doi: 10.1016/j.neuroimage.2020.117105

Holm, S. K., Madsen, K. S., Vestergaard, M., Born, A. P., Paulson, O. B., Siebner, H. R., Uldall, P. & Baaré, W. F. C. (2019) Previous glucocorticoid treatment in childhood and adolescence is associated with long-term differences in subcortical grey matter volume and microstructure. NeuroImage. Clinical. 23, p. 1-11, 101825.

Madsen KS, Jernigan TL, Vestergaard M, Mortensen EL, Baare WFC. (2018). Neuroticism is linked to microstructural left-right asymmetry of fronto-limbic fibre tracts in adolescents with opposite effects in boys and girls. Neuropsychologia. 114, 1-10. 

Holm SK, Madsen KS, Vestergaard M, Paulson OB, Uldall P, Siebner HR, Born AP, Baare WFC. (2018). Total brain, cortical, and white matter volumes in children previously treated with glucocorticoids. Pediatr Res. 83(4), 804-812.

Vestergaard M, Holm SK, Uldall P, Siebner HR, Paulson OB, Baaré WFC, Madsen KS. Glucocorticoid treatment earlier in childhood and adolescence show dose-response associations with diurnal cortisol levels. Developmental Psychobiology, 2017, 59(8): 1010-1020.

Angstman S, Madsen KS, Skimminge A, Jernigan TL, Baaré WF, Siebner HR. Microstructural asymmetry of the corticospinal tracts predict right-left differences incircle drawing skill in right-handed adolescents. Brain Structure and Function, 2016, Brain Struct Funct. 2016 Dec;221(9):4475-4489.

Holm SK, Vestergaard M, Madsen KS, Baaré WF, Hammer TB, Born AP, Siebner HR, Paulson OB, Uldall PV. Children and adolescents previously treated with glucocorticoids display lower verbal intellectual abilities. Acta Paediatrica, 2015, 104(8): 784-91.

Aarnink SH, Vos SB, Leemans A, Jernigan TL, Madsen KS, Baaré WFC. Automated Longitudinal Intra-Subject Analysis (ALISA) for diffusion MRI tractography. Neuroimage, 2014, 86:404-416.

Klarborg B; Madsen KS; Vestergaard M; Skimminge A; Jernigan TL; Baaré WFC. Sustained attention is associated with right superior longitudinal fasciculus and superior parietal white matter microstructure in children. Human Brain Mapping, 2013, 34(12): 3216-32.

Madsen KS, Jernigan TL, Iversen P, Frokjaer VG, Mortensen EL, Knudsen GM, Baare WF. (2012). Cortisol awakening response and negative emotionality linked to asymmetry in major limbic fibre bundle architecture. Psychiatry Res. 201(1), 63-72.

Madsen KS, Jernigan TL, Iversen P, Frokjaer VG, Knudsen GM, Siebner HR, Baare WF. (2012). Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry. Neuroimage. 63(1), 95-103.

Madsen KS; Baaré WF; Skimminge A; Vestergaard M; Siebner HR; Jernigan TL. Brain microstructural correlates of visuospatial choice reaction time in children. Neuroimage, 2011, 58(4): 1090-1100.

Jernigan TL; Baare WF; Stiles J; Madsen KS. Postnatal brain development: Structural imaging of dynamic neurodevelopmental processes. Progress in Brain Research 2011, 189: 77-92.

Vestergaard M; Madsen KS; Baare WF; Skimminge A; Ejersbo LR; Ramsoy TZ; Gerlach C; Akeson P; Paulson OB; Jernigan TL. White matter microstructure in superior longitudinal fasciculus associated with spatial working memory performance in children. Journal of Cognitive Neuroscience, 2011, 23(9): 2135-2146.

Madsen KS; Baare WF; Vestergaard M; Skimminge A; Ejersbo LR; Ramsoy TZ; Gerlach C; Akeson P; Paulson OB; Jernigan TL. Response inhibition is associated with white matter microstructure in children. Neuropsychologia, 2010, 48(4): 854-862.

Group Members

Kathrine Skak Madsen

Group Leader

William Frans Christiaan Baaré

Line Korsgaard Johnsen

Kevin Pedersen

Show all group members (8)

External Collaborators

Prof. Wesley Thompson

Population Neuroscience and Genetics Center
Laurate Institute for Brain Research, US


Prof. Rogier Kievit

Lifespan Cognitive Dynamics lab 
Donders Institute for Brain, Cognition and Behavior, The Netherlands


Dr. Delia Fuhrman

Development & Environment Research Group
King’s College, London, UK


Prof. Terry Jernigan

Center for Human Development
University of California, San Diego, US


Dr. Marybel Gonzales

Department of Psychiatry
University of California, San Diego, US


Profs. Kristine Walhovd, Anders Fjell and Øystein Sørensen

Center for Lifespan Changes in Brain and Cognition
University of Oslo, Norway


Prof. Sven Kreiborg

Craniofacial Unit, Department of Clinical Genetics
Copenhagen University Hospital - Rigshospitalet, Denmark


Assoc. Prof. Melanie Ganz

Department of Computer Science
University of Copenhagen, Denmark