Neonatal Brain Response to Deviant Auditory Stimuli and Relation to Maternal Trait Anxiety

Abstract

Objective: Excessive response to unexpected or "deviant" stimuli during infancy and early childhood represents an early risk marker for anxiety disorders. However, research has yet to delineate the specific brain regions underlying the neonatal response to deviant stimuli near birth and the relation to risk for anxiety disorders. The authors used task-based functional MRI (fMRI) to delineate the neonatal response to deviant stimuli and its relationship to maternal trait anxiety.

Methods: The authors used fMRI to measure brain activity evoked by deviant auditory stimuli in 45 sleeping neonates (mean age, 27.8 days; 60% female; 64% African American). In 41 of the infants, neural response to deviant stimuli was examined in relation to maternal trait anxiety on the State-Trait Anxiety Inventory, a familial risk factor for offspring anxiety.

Results: Neonates manifested a robust and widespread neural response to deviant stimuli that resembles patterns found previously in adults. Higher maternal trait anxiety was related to higher responses within multiple brain regions, including the left and right anterior insula, the ventrolateral prefrontal cortex, and multiple areas within the anterior cingulate cortex. These areas overlap with brain regions previously linked to anxiety disorders and other psychiatric illnesses in adults.

Conclusions: The neural architecture sensitive to deviant stimuli robustly functions in newborns. Excessive responsiveness of some circuitry components at birth may signal risk for anxiety and other psychiatric disorders.

Keywords: Anxiety Disorders; Child/Adolescent Psychiatry; Development; Neuroimaging.

Figure 1.

Brain regions with significant activity modulations in neonates following the onset of deviant sounds. Results are whole-brain multiple comparisons corrected at p<0.01, with each significant cluster comprised of a volume of at least 756mm³ in which each voxel is significant at p<0.001 (45, 46). A full list of regions is provided in Supplemental Table 3.

Figure 2.

Proportion of adult-defined networks with significant activity modulations in neonates following the onset of the deviant sounds. Bar length indicates the percentage of cortical surface area for each network in which z>3.3 (p<0.001), the threshold used for multiple comparisons correction in the whole-brain analyses. MotorMouth: mouth representation within motor network; CingOperc: cingulo-opercular; VentAttn: ventral attention; MedPar: medial parietal; MotorHand: hand representation within motor network; Default: default mode; ParOccip: parietal occipital; FrontoPar: fronto-parietal; DorsalAttn: dorsal attention.

Figure 3.

Brain areas in which neonatal neural activity following the onset of deviant sounds varied depending on maternal trait anxiety. Results are whole-brain multiple comparisons corrected at p<0.01, with each significant cluster comprised of a volume of at least 756mm³ in which each voxel is significant at p<0.001. A complete list of regions is provided in Supplemental Table 4.

Figure 4.

Timecourses for a subset of brain regions in which neonatal neural activity following onset of deviant sounds varied as a function of maternal trait anxiety. Note that the brain regions depicted here are identical to the brain regions in Figure 3, which is a statistical map of the same data. Trait anxiety was treated as a continuous measure in the statistical analyses, and a median split was used to generate the timecourses above solely for display purposes. Areas of cortex in red had higher peak activity in neonates born to mothers with higher trait anxiety, while areas of cortex in white had higher peak activity in neonates born to mothers with lower trait anxiety.