In the analysis of the structural

In the analysis of the structural MRI data it was found that subjects with higher grey matter volume in the right parietal all trans retinoic acid benefitted more from the WMT than subjects in the same training group with lower grey matter volume (p=0.005), although this association did not survive correction for multiple comparisons. Brain activity in the right parietal region, especially the intraparietal sulcus, has been associated with WM capacity (Todd and Marois, 2004), and abnormal morphology of this area has been associated with dyscalculia (Molko et al., 2003; Cohen Kadosh and Walsh, 2007). Moreover, cortical thickness of the intraparietal sulcus has been associated with WM capacity (Darki and Klingberg, 2015). Structural measures can give more predictive information of development of WM above and beyond the predictions made from psychological measures (Ullman et al., 2014; Darki and Klingberg, 2015). It is therefore reasonable that structural measures of this region could give information about the impact of WMT on mathematical ability. Moreover, the parietal cortex is related to both mathematics and WM, but the exact localization of the two functions in relation to each other is still unclear. If some parts are more related to WM than mathematics, this could explain why the grey matter value interacts with WMT and not NLT. The present study thus shows that imaging at baseline is associated with relative improvement or development, confirming finding from previous study (Hoeft et al., 2011; Dumontheil and Klingberg, 2012; Supekar et al., 2013; Ullman et al., 2014). Furthermore, the present findings make one step further in showing that the combination of imaging and behavior can predict an individual’s response to different types of interventions. One limitation of the present study was the lack of a passive control group. Reading and mathematical abilities are highly correlated in children (Hecht et al., 2001), and it is possible that reading training was beneficial for some subjects (Glenberg et al., 2012). Future studies might include more subjects, more subgroups, long-term follow-up and training on other cognitive abilities that have been associated with mathematical ability, such as reasoning (Primi et al., 2010; Fischer et al., 2011) and spatial abilities (Fischer et al., 2011). A second limitation of the study is the limited number of children in each training group included in the neuroimaging arm. Although overall the neuroimaging analyses included a total of 45 subjects, each of the four groups only included between 10 and 13 subjects. For this reason, the neuroimaging results should be regarded as preliminary, and a replication using a bigger sample is needed.
Competing interest
Acknowledgments We thank R. Cohen Kadosh for useful comments on a previous version of this article. This study was supported by a grant from the Marcus and Amalia Wallenberg Foundation awarded to TK. The training software is non-commercial and available upon request.
Introduction Participation in physical activity and higher levels of aerobic fitness are associated with superior scholastic achievement, cognitive control, and memory in children (Buck et al., 2008; Castelli et al., 2007; Chaddock et al., 2010a,b, 2011; Chomitz et al., 2009; Hillman et al., 2009; Pontifex et al., 2011; Voss et al., 2011). Still, little is known about the neural mechanisms by which aerobic fitness influences the developing brain during childhood. Volumetric and functional magnetic resonance imaging (MRI) techniques provide some clues, such that higher fit children show larger brain volumes in the hippocampus and basal ganglia (Chaddock et al., 2010a,b), as well as differences in blood oxygenation level dependent (BOLD) fMRI brain activation in areas of frontal and parietal cortex (Chaddock et al., 2012; Voss et al., 2011), relative to their lower fit peers. Non-human animal work raises the possibility that, mechanistically, children with higher levels of aerobic fitness may have increased growth and expansion of neural tissue and/or increased vasculature (see Voss et al., 2013 for a review).