Research report Combined analysis of DTI and fMRI data reveals a joint maturation of white and grey matter in a fronto-parietal network Pernille J. Olesen a, * , Zoltan Nagy a,b , Helena Westerberg a , Torkel Klingberg a a Department of Neuropediatrics, Q2:07, Astrid Lindgren’s Children’s Hospital, Karolinska Institute, S-17176 Stockholm, Sweden b Department of Neonatology, Karolinska Institute, Stockholm, Sweden Accepted 8 September 2003 Abstract The aim of this study was to explore whether there are networks of regions where maturation of white matter and changes in brain activity show similar developmental trends during childhood. In a previous study, we showed that during childhood, grey matter activity increases in frontal and parietal regions. We hypothesized that this would be mediated by maturation of white matter. Twenty-three healthy children aged 8 – 18 years were investigated. Brain activity was measured using the blood oxygen level-dependent (BOLD) contrast with functional magnetic resonance imaging (fMRI) during performance of a working memory (WM) task. White matter microstructure was investigated using diffusion tensor imaging (DTI). Based on the DTI data, we calculated fractional anisotropy (FA), an indicator of myelination and axon thickness. Prior to scanning, WM score was evaluated. WM score correlated independently with FA values and BOLD response in several regions. FA values and BOLD response were extracted for each subject from the peak voxels of these regions. The FA values were used as covariates in an additional BOLD analysis to find brain regions where FA values and BOLD response correlated. Conversely, the BOLD response values were used as covariates in an additional FA analysis. In several cortical and sub-cortical regions, there were positive correlations between maturation of white matter and increased brain activity. Specifically, and consistent with our hypothesis, we found that FA values in fronto-parietal white matter correlated with BOLD response in closely located grey matter in the superior frontal sulcus and inferior parietal lobe, areas that could form a functional network underlying working memory function. D 2003 Elsevier B.V. All rights reserved. Theme: Neural basis of behaviour Topic: Executive function: working memory Keywords: Working memory; Human development; Frontal lobe; Parietal lobe; Myelination; Diffusion tensor imaging; Functional magnetic resonance imaging 1. Introduction Working memory (WM) capacity is the amount of information one can keep in mind for a short period of time [6] and develops throughout childhood and adolescence [16,19]. Development of visuo-spatial WM is associated with increased blood oxygen level-dependent (BOLD) ac- tivity in frontal and parietal cortices [31]. Brain activity measured during a spatial WM task show a similar distri- bution in children and adults [41,52]. The structural changes during development of WM involves maturation of white matter in the prefrontal lobe [30,40], which is one of the last brain regions to mature [18,25,48]. Additional developmen- tal effects on brain structure, in regions important for WM, include synapse production and elimination. This occurs later in the frontal lobes than in other cortical regions [25], and reaches adult levels in mid-adolescence [24,25]. Late synapse formation can be influenced by environmental factors and occurs in relation to learning and memory [28,59], while early synapse formation seems to be mainly intrinsically regulated [8]. The prolonged development of white matter and gradual alteration in synaptic number appear to coincide with the development of cognitive capacities. Data from diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) have been combined in a few previous studies [55–57]. These studies show that 0926-6410/$ - see front matter D 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.cogbrainres.2003.09.003 * Corresponding author. Tel.: +46-8-5177-7348; fax: +46-8-5177- 7349. E-mail address: pernille.olesen@kbh.ki.se (P.J. Olesen). www.elsevier.com/locate/cogbrainres Cognitive Brain Research 18 (2003) 48 – 57