von Rhein, M. | bioRxiv Science

bioRxiv2024

Altered connectome topology in newborns at risk for cognitive developmental delay: a cross-etiologic study

The human brain connectome is characterized by the duality of highly modular structure and efficient integration, supporting information processing. Newborns with congenital heart disease (CHD), prematurity, or spina bifida aperta (SBA) constitute a population at risk for altered brain development and developmental delay (DD). We hypothesize that, independent of etiology, alterations of connectomic organization reflect neural circuitry impairments in cognitive DD. Our study aim is to address this knowledge gap by using a multi-etiologic neonatal dataset to reveal potential commonalities and distinctions in the structural brain connectome and their associations with DD. We used diffusion tensor imaging (DTI) of 187 newborns (42 controls, 51 with CHD, 51 with prematurity, and 43 with SBA). Structural weighted connectomes were constructed using constrained spherical deconvolution based probabilistic tractography and the Edinburgh Neonatal Atlas. Assessment of brain network topology encompassed the analysis of global graph features, network-based statistics, and low-dimensional representation of global and local graph features. The Cognitive Composite Score of the Bayley Scales of Infant and Toddler Development 3rd edition was used as outcome measure at corrected 2 years for the preterm born individuals and SBA patients, and at 1 year for the healthy controls and CHD. We revealed differences in the connectomic structure of newborns across the four groups after visualizing the connectomes in a two-dimensional space defined by network integration and segregation. Further, ANCOVA analyses revealed differences in global efficiency (p < 0.0001), modularity (p < 0.0001), mean rich club coefficient (p = 0.017) and small-worldness (p = 0.016) between groups after adjustment for postmenstrual age at scan and gestational age at birth. Moreover, small-worldness was significantly associated with poorer cognitive outcome, specifically in the CHD cohort (r = -0.41, p = 0.005). Our cross-etiologic study identified divergent structural brain connectome profiles linked to deviations from optimal network integration and segregation in newborns at risk for DD. Small-worldness emerges as a key feature, associating with early cognitive outcomes, especially within the CHD cohort, emphasizing small-worldness crucial role in shaping neurodevelopmental trajectories. Neonatal connectomic alterations associated with DD may serve as a marker identifying newborns at-risk for DD and provide early therapeutic interventions.

neuroscience↗

bioRxiv2018

Left planum temporale growth predicts language development in newborns with congenital heart disease

Congenital heart diseases (CHD) are the most common congenital anomalies, accounting for a third of all congenital anomaly cases. While surgical correction dramatically improved survival rates, the lag behind normal neurodevelopment appears to persist. Deficits of higher cognitive functions are particularly common, including developmental delay in communication and oral-motor apraxia. It remains unclear whether the varying degree of cognitive developmental delay is reflected in variability in brain growth patterns. To answer this question, we aimed to investigate whether the rate of regional brain growth is correlated with later life neurodevelopment. 44 newborns were included in our study, out of whom 33 were diagnosed with dextro-transposition of the great arteries (d-TGA) and 11 with other forms of severe CHD. During the first month of life, neonates underwent corrective or palliative cardiovascular bypass surgery, pre- and postoperative cerebral MRI were performed 18.7 {+/-} 7.03 days apart. MRI was performed in natural sleep on a 3.0T scanner using an 8-channel head coil, fast spin-echo T2-weighted anatomical sequences were acquired in three planes. Based on the principles of deformation based morphometry, we calculated brain growth rate maps that reflected the rate of non-linear deformation that occurs between pre- and post-operative brain images. An explorative, whole-brain, threshold-free cluster enhancement analysis revealed strong correlation between the growth rate of the left planum temporale and the posterior operculum of the left frontal lobe and language score at 12 months of age, corrected for demographic variables (p=0.018, t=5.656). No significant correlation was found between brain growth rates and motor or cognitive scores. Post hoc analysis showed that the length of hospitalization interacts with this correlation with longer hospitalization stay results in faster enlargement of the internal cerebro-spinal fluid spaces. Our study provides evidence to the early importance of left-dominant perisylvian regions in language development even before the direct postnatatal exposure to native language. In CHD patients, the perioperative period results in a critical variability of brain growth rate in this region, which is a reliable neural correlate of language development at one year of age.

neuroscience↗