Developmental coupling of brain iron and intrinsic activity in infants during the first 150 days.

Brain iron is vital for core neurodevelopmental processes including myelination and neurotransmitter synthesis and, accordingly, iron accumulates in the brain with age. However, little is known about the association between brain iron and neural functioning and how they evolve with age in early infancy. This study investigated brain iron in 48 healthy infants (22 females) aged 64.00 ± 33.28 days by estimating R2 * relaxometry from multi-echo functional MRI (fMRI). Linked independent component analysis was performed to examine the association between iron deposition and spontaneous neural activity, as measured by the amplitude of low frequency fluctuations (ALFF) by interrogating shared component loadings across modalities. Further, findings were validated in an independent dataset (n = 45, 24 females, 77.93 ± 26.18 days). The analysis revealed developmental coupling between the global R2 * and ALFF within the default mode network (DMN). Furthermore, we observed that this coupling effect significantly increased with age (r = 0.78, p = 9.2e-11). Our results highlight the importance of iron-neural coupling during early development and suggest that the neural maturation of the DMN may correspond to growth in distributed brain iron.

Fetal Frontolimbic Connectivity Prospectively Associates With Aggression in Toddlers.

Background: Aggression is a major public health concern that emerges early in development and lacks optimized treatment, highlighting need for improved mechanistic understanding regarding the etiology of aggression. The present study leveraged fetal resting-state functional magnetic resonance imaging to identify candidate neurocircuitry for the onset of aggressive behaviors before symptom emergence. Methods: Pregnant mothers were recruited during the third trimester of pregnancy to complete a fetal resting-state functional magnetic resonance imaging scan. Mothers subsequently completed the Child Behavior Checklist to assess child aggression at 3 years postpartum (n = 79). Independent component analysis was used to define frontal and limbic regions of interest. Results: Child aggression was not related to within-network connectivity of subcortical limbic regions or within-medial prefrontal network connectivity in fetuses. However, weaker functional coupling between the subcortical limbic network and medial prefrontal network in fetuses was prospectively associated with greater maternal-rated child aggression at 3 years of age even after controlling for maternal emotion dysregulation and toddler language ability. We observed similar, but weaker, associations between fetal frontolimbic functional connectivity and toddler internalizing symptoms. Conclusions: Neural correlates of aggressive behavior may be detectable in utero, well before the onset of aggression symptoms. These preliminary results highlight frontolimbic connections as potential candidate neurocircuitry that should be further investigated in relation to the unfolding of child behavior and psychiatric risk.

Fetal behavior during MRI changes with age and relates to network dynamics.

Fetal motor behavior is an important clinical indicator of healthy development. However, our understanding of associations between fetal behavior and fetal brain development is limited. To fill this gap, this study introduced an approach to automatically and objectively classify long durations of fetal movement from a continuous four-dimensional functional magnetic resonance imaging (fMRI) data set, and paired behavior features with brain activity indicated by the fMRI time series. Twelve-minute fMRI scans were conducted in 120 normal fetuses. Postnatal motor function was evaluated at 7 and 36 months age. Fetal motor behavior was quantified by calculating the frame-wise displacement (FD) of fetal brains extracted by a deep-learning model along the whole time series. Analyzing only low motion data, we characterized the recurring coactivation patterns (CAPs) of the supplementary motor area (SMA). Results showed reduced motor activity with advancing gestational age (GA), likely due in part to loss of space (r = -.51, p < .001). Evaluation of individual variation in motor movement revealed a negative association between movement and the occurrence of coactivations within the left parietotemporal network, controlling for age and sex (p = .003). Further, we found that the occurrence of coactivations between the SMA to posterior brain regions, including visual cortex, was prospectively associated with postnatal motor function at 7 months (r = .43, p = .03). This is the first study to pair fetal movement and fMRI, highlighting potential for comparisons of fetal behavior and neural network development to enhance our understanding of fetal brain organization.