Resting-state fMRI in sleeping infants more closely resembles adult sleep than adult wakefulness

Abstract

Resting state functional magnetic resonance imaging (rs-fMRI) in infants enables important studies of functional brain organization early in human development. However, rs-fMRI in infants has universally been obtained during sleep to reduce participant motion artifact, raising the question of whether differences in functional organization between awake adults and sleeping infants that are commonly attributed to development may instead derive, at least in part, from sleep. This question is especially important as rs-fMRI differences in adult wake vs. sleep are well documented. To investigate this question, we compared functional connectivity and BOLD signal propagation patterns in 6, 12, and 24 month old sleeping infants with patterns in adult wakefulness and non-REM sleep. We find that important functional connectivity features seen during infant sleep closely resemble those seen during adult sleep, including reduced default mode network functional connectivity. However, we also find differences between infant and adult sleep, especially in thalamic BOLD signal propagation patterns. These findings highlight the importance of considering sleep state when drawing developmental inferences in infant rs-fMRI.

Fig 1. Zero-lag functional connectivity (covariance) matrices, sorted into cortical networks.

(A) Functional connectivity in adults, in wake (N0) and in non-REM sleep (N1-N3). (B) Functional connectivity in 6, 12 and 24 month old children. (C) Functional connectivity (FC) similarity between each childhood matrix and adult wake/sleep stages (N0-N3). Similarity is computed by taking the correlation over all unique (matrix upper triangle) pairs of covariance values over the entire brain. At all ages, infant functional connectivity is more correlated with adult sleep (N1-N3) than adult wake (N0); * = p < 0.01 from permutation resampling on adult N0 vs. N1-N3 matrices with Bonferroni correction for multiple comparisons. Early childhood functional connectivity is most correlated with adult N3 sleep functional connectivity at all ages, although the difference between N2 and N3 sleep is not statistically significant.

Fig 2. Principal component structure of adult N3 (slow wave) sleep best matches early childhood data.

(A) First 3 principal components (PCs) in adult N0 (wake), adult N3 (slow wave sleep), and 24 month olds, ordered by variance explained. The topographies of the first 3 PCs in N0 (wake) adults reflect the default mode network (DMN), visual network (VIS), and somatomotor network (SMN), respectively. In contrast, it is visually evident that the component order in adult N3 (slow wave sleep) and 24 months old is visual network, somatosensory network, and default mode network, respectively. (B) Quantitative analysis of spatial correlations between the first 3 PCs in adult N3 vs. the first three components in adult N0 (labeled DMN, VIS, and SMN) demonstrates that the first adult N3 component most closely matches the N0 visual topography, the second adult N3 component most closely matches the N0 somatomotor topography, and the third adult N3 component most closely matches the N0 default mode network topography. (C) Quantitative analysis of spatial correlations between the first 3 PCs in data collected at 24, 12, and 6 months of age vs. adult N0 shows the same pattern of component re-ordering as in the adult N3 vs. adult N0 comparison.

Fig 3. Propagation analysis of the resting-state fMRI BOLD signal in adult sleep and early childhood.

Columns show temporal lag projection maps in adult wake/sleep stages as well as in children aged 6–24 months. Blue colors indicate regions where spontaneous BOLD signal activity tends to be early with respect to the rest of the brain; red colors indicate regions which tend to be late with respect to the rest of the brain. Pink circles contrast visual earliness in adult N3 sleep and infants against adult N0 wake.

Fig 4. Propagation patterns in early childhood vs. adult wake/sleep.

(A) Temporal lag projection maps at all ages (6–24 months) most closely match adult N3 sleep; * = p < 0.01 from permutation resampling on adult N0 vs. N3 lag projections with Bonferroni correction for multiple comparisons. (B) Despite the overall spatial correlation between early childhood lag projections and adult N3 sleep lag projections, there are critical differences in the thalamus (highlighted in pink circles). Thalamus is generally late with respect to the rest of the brain in adult N3 sleep. In contrast, in 6 month olds, the thalamus is early with respect to the rest of the brain, more akin to adult N0 wake. Note that this earliness fades with aging (e.g., the thalamus becomes less blue), indicating a possible development toward adult-like sleep features.

Fig 5. Thalamic lag structure in early childhood vs. adult wake/sleep.

(A) Whole thalamus seed-region. (B) Thalamus-seeded lag maps in adult wake (N0) and slow wave sleep (N3). As previously published, cortex is generally late (red) with respect to thalamus during wake, but generally early (blue) with respect to thalamus during N3 sleep. (C) Thalamus-seeded lag maps in early childhood. The 6-month old lag map shows most of cortex is late with respect to thalamus, akin to adult wake. In contrast, the 24-month old lag map shows most of cortex is early with respect to thalamus, akin to adult N3 sleep. (D) Thalamic lag map in sleeping 6-month olds is significantly more correlated with adult wake than adult sleep, whereas the opposite is true for sleeping 24-month olds; * = p < 0.01 from permutation resampling on adult N0 vs. N3 lag projections with Bonferroni correction for multiple comparisons. No statistically significant difference was found at 24-months.