Computational protocol: Long-term impacts of prenatal synthetic glucocorticoids exposure on functional brain correlates of cognitive monitoring in adolescence

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Protocol publication

[…] We re-recruited participants from a previous child developmental sample,. All participants were term-born (>37 weeks of gestation) and were between 14 to 18 years of age (mean = 16) at the time of our data collection. The original sample was recruited in cooperation with the Dresden Neustadt Hospital and the Department of Gynecology and Obstetrics at the unversity hospital (Universitätsklinikum Carl Gustav Carus) in Dresden. Only mothers of healthy term-born infants without receiving pediatric intensive care were contacted. Main exclusion criteria were gestational diabetes, placental insufficiency and regular alcohol, nicotine or drug consumption during pregnancy. The original sample included a comparison group, the PP/sGC group with children born to mothers who underwent pregnancy complications and received sGC treatment, and a third group of children whose mothers although underwent problematic pregnancy but did not receive the sGC treatment. The number of children in the third group was much less than the other two groups, we thus could not re-recruit sufficient number of participants from this subgroup 8 years after the initial study for further control analyses in the current study (other procedural details and criteria for recruiting the original sample can be found in the prior studies,). For the current study, 34,57% of participants in the PP/sGC group and 28,23% of the comparison group of the original sample could be re-recruited. Ethic approval in accordance with the Helsinki declaration for this study was granted by the TU Dresden ethic committee (EK235062014). Informed consents from both custodians of the teenagers were obtained. All aspects of the experiment were performed in accordance with relevant guidelines and regulations. The final sample consisted of 52 teenagers (see Table  for details of sample characteristics). Mothers of adolescents in the PP/sGC group (n = 28) were hospitalized (on average during the 30th week of gestation) due to pregnancy complications associated with risks of preterm delivery (e.g., premature labor pain, vaginal bleeding, cervical insufficiency) and were treated with the standard sGCs therapy. The treatment included one single course of either 2 doses of 12 mg betamethasone given intramuscularly, 24 hours apart or dexamethasone administered as four doses of 6 mg given intramuscularly, 12 hours apart. The comparison group (n = 24) comprised teenagers of mothers without any pregnancy complications, nor were they hospitalized or given the sGC therapy. To assure that our sample size has sufficient power to detect the group and group × condition interaction effects, we conducted power calculations using G*Power (Version 3.1.9.2) based on effect sizes estimated from the prior developmental study, which showed medium effect sizes for the effects of prenatal sGC exposure on stress reactivity and the associated sex interaction. The a-priori power analyses using medium effect size f = 32 (partial η2 = 0.09) indicated that our sample size (n = 52) yields sufficient power in the range of 0.8 for detecting between-group effects and desirable power in the range >0.95 for detecting group × experimental condition effects. [...] EEG data was re-referenced offline to an averaged-mastoid reference using the Brain Vision Analyzer. Further preprocessing of the EEG data was done using the open-source EEGLAB toolbox and Fieldtrip toolbox for MATLAB. Data was down sampled to 256 Hz and segmented into epochs of 1500 ms before and 2500 ms after each stimulus. Epochs with severe muscular artifacts were rejected manually first. Independent Component Analysis (ICA) was further applied to the data to detect and remove components of ocular and muscular artifacts. The artifact free data was then bandpass-filtered in the range of 0.5 to 25 Hz and epoched according to the time window of interest from 100 ms before and 1000 ms after Go and prime-based NoGo stimuli, applying a baseline correction 100 ms prior to stimulus onset. We focused on prime-based NoGo pairs only, as they elicited greater response conflict. For further ERP and source localization analyses only epochs with correct responses were considered. [...] To localize neuronal generators of the NoGo-N2 component and test for group effects at the cortical source level, source reconstruction was performed using the sLORETA algorithm integrated in the Brainstorm toolbox (http://neuroimage.usc.edu/brainstorm).The current source density was estimated from 60 EEG signal channels in a realistic head model by using the ICBM152 template in Brainstorm. The four different compartments of the head model (scalp, outer and inner skull, cortex) were extracted using the Boundary Element Method (BEM) that is also implemented in OpenMEEG. A Brainstorm provided default brain surface of 15002 nodes was used for computing the aforementioned compartments. sLORETA computes the current source density distribution for every cortical dipole, resulting in a transition kernel from our 60 averaged scalp EEG signals to 15002 cortical signals. Cortical surface signals within the N2 time window (250 to 280 ms) were averaged and their absolute values were projected to the standard volumetric space in Brainstorm with a spatial resolution of 3 × 3 × 3 mm. The resulted volumetric signals were then imported to SPM8 (http://www.fil.ion.ucl.ac.uk/spm/) for statistical analysis. A full factorial ANOVA was conducted to compare the main effects of Condition (Go vs. NoGo), Group (PP/sGC vs. comparison group) and their interactions with respect to the volumetric activations. For correlational analyses, individual maximum activations of significant clusters were extracted and averaged. […]

Pipeline specifications

Software tools G*Power, EEGLAB, FieldTrip, Brainstorm, OpenMEEG, SPM
Applications Miscellaneous, Clinical electrophysiology
Chemicals Hydrocortisone