Hippocampal subfield volumes are nonspecifically reduced in premature‐born adults

Abstract

Reduced global hippocampus volumes have been demonstrated in premature-born individuals, from newborns to adults; however, it is unknown whether hippocampus subfield (HCSF) volumes are differentially affected by premature birth and how relevant they are for cognitive performance. To address these questions, we investigated magnetic resonance imaging (MRI)-derived HCSF volumes in very premature-born adults, and related them with general cognitive performance in adulthood. We assessed 103 very premature-born (gestational age [GA] <32 weeks and/or birth weight <1,500 g) and 109 term-born individuals with cognitive testing and structural MRI at 26 years of age. HCSFs were automatically segmented based on threedimensional T1-and T2-weighted sequences and studied both individually and grouped into three functional units, namely hippocampus proper (HP), subicular complex (SC), and dentate gyrus (DG). Cognitive performance was measured using the Wechsler-Adult-Intelligence-Scale (full-scale intelligence quotient [FS-IQ]) at 26 years. We observed bilateral volume reductions for almost all HCSF volumes in premature-born adults and associations with GA and neonatal treatment intensity

Decreased amygdala volume in adults after premature birth

“…Our study sample was previously described in 12 , 73 – 75 : All subjects were part of the Bavarian Longitudinal Study (BLS), a geographically defined, whole-population sample of neonatal at-risk children and healthy FT controls who were followed from birth, between January 1985 and March 1986, into adulthood 73 – 75 . 682 infants were born VP (< 32 weeks of gestation) and/or with very low birth weight (VLBW, birth weight < 1500 g).…”

“…Previous analyses of this dataset using structural MRI include investigations of cortical architecture 7 , 8 , 12 , white matter 15 , 27 , 28 , subcortical structures 9 , 10 , and incidental findings on routine brain MRI 76 .…”

“…MRI data acquisition was previously described in 9,12 : At both sites, Bonn and Munich, MRI data acquisition was performed on Philips Achieva 3T TX systems or Philips Ingenia 3T system using an 8-channel SENSE head coil. Subject distribution among scanners: Bonn Achieva 3T: 5 VP/VLBW, 12 FT, Bonn Ingenia 3T: 33 VP/VLBW, 17 FT, Munich Achieva 3T: 60 VP/VLBW, 65 FT, Munich Ingenia 3T: 3 VP/VLBW, 17 FT. To account for possible confounds by scanner differences, data analyses included scanner dummy-variables www.nature.com/scientificreports/ as covariates of no interest.…”

“…For example, very premature-born adults, i.e. born very preterm (VP) before 32 weeks of GA and/or with very low birth weight (VLBW) below 1500 g, have on average more than 10 points lower full-scale IQ scores compared to full-term (FT) controls, which is mediated by aberrant development of distinct brain structures or processes such as cortical folding, white matter integrity and subcortical grey matter volume [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] . Causes of aberrant brain development are inflammatory, hypoxic-ischemic and/or stress-related events, which not only affect vulnerable developmental processes, for example pre-oligodendrocyte or subplate neuron (SPN) development at microscopic level [24][25][26] , but also lead to altered macroscopic brain development such as cortical gyri development or white matter integrity 7,8,10,12,15,18,27,28 .…”

Within amygdala: Basolateral parts are selectively impaired in premature-born adults

“…cortico-thalamic structural connectivity, and subcortical grey matter structures, e.g. multi-nuclei structures such as thalamus and neuromodulatory nuclei such as basal cholinergic forebrain, with most of these structural changes being linked with adverse neurodevelopmental outcomes ( Ball et al, 2013 , Berndt et al, 2019 , Eikenes et al, 2011 , Grothe et al, 2017 , Hedderich et al, 2019 , Hedderich et al, 2020a , Hedderich et al, 2020b , Menegaux et al, 2020 , Menegaux et al, 2021 , Meng et al, 2016 , Northam et al, 2011 , Nosarti et al, 2002 , Nosarti et al, 2008 , Pascoe et al, 2019 , Rimol et al, 2019 , Schmitz‐Koep et al, 2020 , Skranes et al, 2007 , Skranes et al, 2013 ). One subcortical grey matter structure of particular interest is the amygdala, which is thought to mediate the brain’s stress response to environmental stressors in the context of premature birth ( Chau et al, 2019 , Scheinost et al, 2016 , Schmitz-Koep et al, 2021 ).…”