Working memory training and brain structure and function in extremely preterm or extremely low birth weight children

Abstract

This study in children born extremely preterm (EP; <28 weeks' gestational age) or extremely low birth weight (ELBW; <1,000 g) investigated whether adaptive working memory training using Cogmed® is associated with structural and/or functional brain changes compared with a placebo program. Ninety-one EP/ELBW children were recruited at a mean (standard deviation) age of 7.8 (0.4) years. Children were randomly allocated to Cogmed or placebo (45-min sessions, 5 days a week over 5-7 weeks). A subset had usable magnetic resonance imaging (MRI) data pretraining and 2 weeks posttraining (structural, n = 48; diffusion, n = 43; task-based functional, n = 18). Statistical analyses examined whether cortical morphometry, white matter microstructure and blood oxygenation level-dependent (BOLD) signal during an n-back working memory task changed from pretraining to posttraining in the Cogmed and placebo groups separately. Interaction analyses between time point and group were then performed. There was a significant increase in neurite density in several white matter regions from pretraining to posttraining in both the Cogmed and placebo groups. BOLD signal in the posterior cingulate and precuneus cortices during the n-back task increased from pretraining to posttraining in the Cogmed but not placebo group. Evidence for group-by-time interactions for the MRI measures was weak, suggesting that brain changes generally did not differ between Cogmed and placebo groups. Overall, while some structural and functional MRI changes between the pretraining and posttraining period in EP/ELBW children were observed, there was little evidence of training-induced neuroplasticity, with changes generally identified in both groups. Trial registration Australian New Zealand Clinical Trials Registry, anzctr.org.au; ACTRN12612000124831.

Keywords: Cogmed; diffusion imaging; functional imaging; magnetic resonance imaging; microstructure; preterm birth.

Figure 1

Participant flow chart. This figure shows the number of children who were enrolled into the trial and randomised to either Cogmed or placebo, and of those, the number who had usable scans at both pretraining and posttraining time points and were thus included in the current analysis. MRI, magnetic resonance imaging; TBSS, tract‐based spatial statistics

Figure 2

FreeSurfer results. (a) The cluster of vertices in the left lateral occipital cortex in which thickness decreased significantly (p < .05, multiple comparison corrected) between pretraining and posttraining in the placebo group, shown in blue. (b) The cluster of vertices that had a significant group‐by‐time interaction for cortical thickness, shown in red. For each cluster, the number of vertices it occupies and its size in mm², are shown. The percentage refers to the cluster's size relative to the total cortical surface area (65,416.6 mm²)

Figure 3

Tract‐based spatial statistics results. Regions where neurite density based on Neurite Orientation Dispersion and Density Imaging (NODDI) and the Spherical Mean Technique (SMT) increased significantly from pretraining to posttraining in the Cogmed and placebo groups. The number of voxels that increased significantly over time and their percentage of the mean fractional anisotropy (FA) skeleton (total 68,099 voxels) are also shown. All results are presented at p < .05, family‐wise error rate (FWE)‐corrected. p values are overlaid on the study specific template (mean FA image). TFCE, threshold‐free cluster enhancement

Figure 4

Task‐based functional MRI results. The regions where the blood oxygenation level‐dependent (BOLD) signal increase during completion of the n‐back task (one‐back condition vs. zero‐back condition) increased significantly from pretraining to posttraining in the Cogmed group. The number of significant voxels is shown. Results are presented at Z‐score >2.3 and p < .05, family wise error rate corrected. The coordinates beneath the images are MNI coordinates