Functional connectivity in the first year of life in infants at-risk for autism: a preliminary near-infrared spectroscopy study

Abstract

Background: Autism spectrum disorder (ASD) has been called a "developmental disconnection syndrome," however the majority of the research examining connectivity in ASD has been conducted exclusively with older children and adults. Yet, prior ASD research suggests that perturbations in neurodevelopmental trajectories begin as early as the first year of life. Prospective longitudinal studies of infants at risk for ASD may provide a window into the emergence of these aberrant patterns of connectivity. The current study employed functional connectivity near-infrared spectroscopy (NIRS) in order to examine the development of intra- and inter-hemispheric functional connectivity in high- and low-risk infants across the first year of life.

Methods: NIRS data were collected from 27 infants at high risk for autism (HRA) and 37 low-risk comparison (LRC) infants who contributed a total of 116 data sets at 3-, 6-, 9-, and 12-months. At each time point, HRA and LRC groups were matched on age, sex, head circumference, and Mullen Scales of Early Learning scores. Regions of interest (ROI) were selected from anterior and posterior locations of each hemisphere. The average time course for each ROI was calculated and correlations for each ROI pair were computed. Differences in functional connectivity were examined in a cross-sectional manner.

Results: At 3-months, HRA infants showed increased overall functional connectivity compared to LRC infants. This was the result of increased connectivity for intra- and inter-hemispheric ROI pairs. No significant differences were found between HRA and LRC infants at 6- and 9-months. However, by 12-months, HRA infants showed decreased connectivity relative to LRC infants.

Conclusions: Our preliminary results suggest that atypical functional connectivity may exist within the first year of life in HRA infants, providing support to the growing body of evidence that aberrant patterns of connectivity may be a potential endophenotype for ASD.

Keywords: autism; endophenotype; functional connectivity; infancy; near-infrared spectroscopy.

Figure 1

Coded behavioral data for time spent attending to visual stimuli, feeding, and sleeping for LRC and HRA groups at 3-, 6-, 9-, and 12-months.

Figure 2

Four regions of interest (ROI) selected from anterior and posterior recording sites on each hemisphere. Gray circles represent channels included in anterior ROIs; black circles are channels included in posterior ROIs. Probes not included in ROIs are depicted in white. Smaller red and blue circles represent infrared emitters and detectors, respectively.

Figure 3

Intrinsic (left column) and co-activation (right column) connectivity for HRA and LRC groups at 3-, 6-, 9-, and 12-months for all six ROI pairs. Error bars represent one standard error of the mean. ^*p < 0.1, ^**p < 0.05.

Figure 4

Group differences in mean z'-scores for global connectivity and intra- and inter-hemispheric connectivity measures at 3-, 6-, 9-, and 12-months for task-regressed, intrinsic functional (left column) and co-activation (right column) connectivity pipelines. Positive scores reflect LRC > HRA; negative scores reflect HRA > LRC for connectivity measures. Error bars represent one standard error of the mean. ^*p < 0.1, ^**p < 0.05.