Growth in early infancy drives optimal brain functional connectivity which predicts cognitive flexibility in later childhood

Abstract

Functional brain network organization, measured by functional connectivity (FC), reflects key neurodevelopmental processes for healthy development. Early exposure to adversity, e.g. undernutrition, affects neurodevelopment, observable via disrupted FC, and leads to poorer outcomes from preschool age onward. We assessed longitudinally the impact of early growth trajectories on developmental FC in a rural Gambian population from age 5 to 24 months. To investigate how these early trajectories relate to later childhood outcomes, we assessed cognitive flexibility at 3-5 years. We observed that early physical growth before the fifth month of life drove optimal developmental trajectories of FC that in turn predicted cognitive flexibility at pre-school age. In contrast to previously studied developmental populations, this Gambian sample exhibited long-range interhemispheric FC that decreased with age. Our results highlight the measurable effects that poor growth in early infancy has on brain development and the subsequent impact on pre-school age cognitive development, underscoring the need for early life interventions throughout global settings of adversity.

Figure 1.. Experimental design.

(A) Measures taken in the BRIGHT project used in this work. The measuring tape represents anthropometric measures, the brain represents fNIRS FC and the test represents the cognitive flexibility assessment. (B) Schematic representation of the spatial layout of the fNIRS array. Sources are marked with red stars, detectors are marked with blue circles, channels are marked with grey lines and numbered with black circles. The channels/optodes used as a reference for the tragus are highlighted in green. (C) Participants undergoing fNIRS testing at different ages. Image reproduced with permission from (95).

Figure 2.. Linear mixed models results showing FC that displayed a statistically significant change with age.

(A) Significant results of the linear mixed model, blue indicates connections that decreased with age, red indicates connections that increase with age. (B) Mean and standard error of the mean (SE) of the functional connections that changed with age. Error bars are 1 SE. (C) Violin plot showing the mean ± standard deviation (SD) (red circles and lines) and the individual variability (coloured dots) of the FC that showed a change with time.

Figure 3.. Associations between FC, early growth and later cognitive flexibility.

(A) Significant positive associations are in green, significant negative associations are in orange, and non-significant associations are in blue. * indicates regressions that survived FDR correction for multiple comparisons. (B) Schematic representations of the early FC connections shown to predict cognitive flexibility in preschoolers. Significant positive associations are in green, significant negative associations are in orange.