Prenatal Exposure to Maternal Mood Entropy Is Associated With a Weakened and Inflexible Salience Network in Adolescence

Abstract

Background: Fetal exposure to maternal mood dysregulation influences child cognitive and emotional development, which may have long-lasting implications for mental health. However, the neurobiological alterations associated with this dimension of adversity have yet to be explored. Here, we tested the hypothesis that fetal exposure to entropy, a novel index of dysregulated maternal mood, would predict the integrity of the salience network, which is involved in emotional processing.

Methods: A sample of 138 child-mother pairs (70 females) participated in this prospective longitudinal study. Maternal negative mood level and entropy (an index of variable and unpredictable mood) were assessed 5 times during pregnancy. Adolescents engaged in a functional magnetic resonance imaging task that was acquired between 2 resting-state scans. Changes in network integrity were analyzed using mixed-effect and latent growth curve models. The amplitude of low frequency fluctuations was analyzed to corroborate findings.

Results: Prenatal maternal mood entropy, but not mood level, was associated with salience network integrity. Both prenatal negative mood level and entropy were associated with the amplitude of low frequency fluctuations of the salience network. Latent class analysis yielded 2 profiles based on changes in network integrity across all functional magnetic resonance imaging sequences. The profile that exhibited little variation in network connectivity (i.e., inflexibility) consisted of adolescents who were exposed to higher negative maternal mood levels and more entropy.

Conclusions: These findings suggest that fetal exposure to maternal mood dysregulation is associated with a weakened and inflexible salience network. More broadly, they identify maternal mood entropy as a novel marker of early adversity that exhibits long-lasting associations with offspring brain development.

Keywords: Dysregulation; Emotional processing; Maternal mood entropy; Neurodevelopment; Salience network; fMRI.

Figure 1.

Fearful faces elicited greater activation in salience processing regions. Group-level analyses of task-evoked activation yielded 6 clusters that were significantly more active for fearful faces than neutral ones. The following is a list of each cluster ordered from biggest to smallest, with parentheses to denote its corresponding number of voxels and z score, respectively: 1) lingual gyrus and occipital pole (n = 9427, z = 8.29); 2) cingulate gyrus (n = 637, z = 5.65); 3) left (L) inferior frontal gyrus (n = 465, z = 5.34); 4) right (R) middle frontal gyrus (n = 250, z = 4.65); 5) left amygdala (n = 215, z = 5.84); 6) left inferior frontal gyrus (n = 164, z = 4.68).

Figure 2.

Prenatal maternal mood entropy was negatively associated with integrity of the salience network across functional magnetic resonance imaging (fMRI) sequences. Integrity was derived from person-specific spatial maps for each intrinsic connectivity network. Brainwide analyses suggested that significant relationships were only detected with integrity of the salience network; relationships with all other intrinsic connectivity networks were nonsignificant.

Figure 3.

Data-driven clustering of network integrity derived 2 latent profiles that were differentiated by their degree of change between functional magnetic resonance imaging (fMRI) sequences. Participants engaged in a task-based scan that was acquired in between 2 resting-state scans. This experimental design enabled us to cluster participants based on changes in brain connectivity across the entire fMRI scanning session. A 2-class solution fit the data best, yielding 2 clusters that were best distinguished by the degree of fluctuations in brain integrity. Specifically, the histograms demonstrate that the integrity of the salience network differed significantly with these 2 clusters because the cluster displayed in black exhibited relatively few changes to the MRI task conditions. Adolescents in the inflexible cluster were exposed to significantly higher negative maternal mood level and more mood entropy during gestation.

Figure 4.

Amplitudes of low-frequency fluctuations (ALFFs) mapped onto patterns of change that were derived from fluctuations in network integrity. Each line in the scatterplot above represents the fully processed blood oxygen level–dependent (BOLD) signal for a given participant, which is concatenated and color coded by the order in which functional magnetic resonance imaging (fMRI) sequences were collected. The scatterplot illustrates converging evidence that the BOLD fluctuations of the salience network were smaller for the inflexible latent profile. The histograms also highlight the fact that such differences between latent profiles were apparent within each sequence and across the entire fMRI scanning session.