4. Using Infant fMRI to Study the Developing Social Brain in the First Year of Life

COEX 

Over 100 million children worldwide show social deficits in the first year of life that develop into mental health or neurodevelopmental disorders between ages 2 to 8 years. In addition, over 250 million children worldwide live with at least one risk factor (e.g., neglect, domestic violence, parental psychiatric disorder) known to undermine social development. The fundamental architecture of the social brain is developed in infancy, and early deficits in social development are difficult to compensate for later in life. However, current techniques limit our ability to assess early differences and deficits in the infant’s social brain. This has limited our fundamental knowledge of the developing social brain in human infants and has delayed the development of new diagnostics and therapeutics targeting these crucial earliest years. The goal of the present study was to demonstrate the feasibility of using a novel fMRI paradigm to measure infants’ developing social responsiveness to the first social partner—the mother—at 6 months of age.

Our novel fMRI paradigm uses an established MRI protocol to scan infants during natural sleep and relies on the infant’s fully developed auditory responsiveness which is present by 6 months and well preserved under sleep. Twenty-four (15 males) typically developing 6-month-old (± 1 month) infants underwent scanning during natural sleep, listening to maternal voice, unfamiliar female voice, and speech-shaped noise (15-sec-long blocks; 7.5-sec inter-block intervals). We measured maternal cue responsiveness, defined as the infant’s fMRI response to maternal voice, compared to unfamiliar voice and speech-shaped noise. Unfamiliar voices were identified to be distinct from maternal voice on 512 features extracted by the Pyannote machine learning model. Speech-shaped noise consisted of white noise that was edited to match maternal voice on frequency and loudness. FMRI data processing was carried out using FEAT (FMRI Expert Analysis Tool) version 6.00, part of FSL. A total of 54 runs from 18 infants (11 males) passed quality assurance, showing distinct auditory activation and no excessive movement, and were included in the analysis. Voxel-wise whole-brain analyses examined the infant’s fMRI response to: (a) human (maternal and unfamiliar) voice compared to speech-shaped noise (Human Voice > Noise contrast), and (b) maternal voice compared to unfamiliar voice (Maternal > Unfamiliar Voice contrast), adjusting for infant sex, infant age (in weeks), and maternal age. Z-statistic images were thresholded using clusters determined by Z > 3.1 and a corrected cluster threshold of p = .05. Exploratory correlational analysis examined Pearson’s r between the infant’s fMRI responses to Maternal > Unfamiliar Voice contrast and concurrently administered behavioral measures of maternal anxiety (State-Trait Anxiety Inventory), maternal stress (Perceived Stress Scale), maternal depression (Edinburgh Postnatal Depression Scale), and infant negative affectivity (Infant Behavior Questionnaire-Revised, Very Short Form).

Compared to speech-shaped noise, human voice elicited increased activations in multiple cortical regions (all corrected p < .05) of the infant’s social brain, including the superior temporal gyrus (Z = 12.75), anterior cingulate gyrus (Z = 3.20), and temporoparietal junction (Z = 8.17). Compared to unfamiliar voice, maternal voice elicited increased activations in all aforementioned cortical regions, and additionally in key dopamine- and oxytocin-rich subcortical regions (all corrected p < .05), including the striatum (Z = 4.40), amygdala (Z = 3.79), and ventral diencephalon (encompassing the hypothalamus, ventral tegmental area/substantia nigra; Z = 3.58). Compared to maternal voice, unfamiliar voice did not elicit any additional activations in the infant’s brain. Exploratory correlational analyses suggested that maternal anxiety, stress, depression, and infant negative affectivity were negatively correlated with the infant’s preferential brain responses to maternal voice in several important social brain regions, including the striatum, amygdala, ventral diencephalon, and anterior cingulate gyrus (ps < .05).

Six-month-old infants show preferential brain responses to human voice (compared to speech-shaped noise) and voice of their first social partner (compared to unfamiliar voice). Our findings provide support for the feasibility of using fMRI to measure the developing brain’s responsiveness to socially salient cues at 6 months of age. Our findings also provide preliminary evidence that the infant’s preferential response to socially salient cues is negatively associated with maternal anxiety, stress, and depression, and infant’s negative affectivity. When extended to at-risk infants, this work has the potential to yield breakthroughs in identifying novel neural markers that can detect early differences and deficits in an infant’s developing social brain.