White matter microstructure changes folloWing Working-memory training in survivors of neonatal critical illness : a randomized controlled trial

Objective to test the effect of cogmed Working-memory training (cWmt) on white matter microstructure following neonatal ecmo and/or cdh. Design a nationwide randomized controlled trial assessing white matter microstructure immediately post-cWmt (t1) and its association with neuropsychological outcome immediately and one year (t2) post-cWmt, conducted between october 2014-June 2017. researchers involved in the follow-up assessments were blinded to group allocation. setting erasmus mc-sophia children’s hospital, rotterdam and radboud university medical center, nijmegen, the netherlands. Patients eligible participants were neonatal ecmo and/or cdh survivors (8-12 years) with an iQ ≥ 80 and a z-score ≤ -1.5 on at least one (working)memory test at first assessment. Interventions cWmt, comprising 25 sessions of 45 minutes for five consecutive weeks at home. Measurements and Main results Participants were randomized to cWmt (n = 14) or non-training (n = 20). global fractional anisotropy (fa) increased significantly in the cWmt group compared to the non-training group (estimated coefficient = .007, p = .015). increased fa (estimated coefficient = .009, p = .033) and decreased mean diffusivity (estimated coefficient = -.010, p = .018) were found in the left superior longitudinal fasciculus in the cWmt group compared to the non-training group at t1. children in the cWmt who improved with at least 1 sd on verbal working-memory from t0 to t1 had significantly higher fa in the left slf at t1 (n = 6; fa left slf at t1 = .408±.01) compared to children that did not show this improvement after cWmt (n = 6; fa left slf at t1 = .384±.02), F(1,12) = 6.22, p = .041, hp = .47. no other structure-function relationships were found after cWmt. conclusions White matter microstructure is affected by cWmt in school-age survivors of neonatal ecmo and/or cdh. our findings demonstrate that white matter microstructure and associated cognitive outcomes are malleable in these children. trial registration ntr4571: http://www.trialregister.nl/trialreg/admin/rctview.asp?tc=4571. 2 Erasmus Medical Center Rotterdam