Cortical Processing of Multimodal Sensory Learning in Human Neonates

Abstract

Following birth, infants must immediately process and rapidly adapt to the array of unknown sensory experiences associated with their new ex-utero environment. However, although it is known that unimodal stimuli induce activity in the corresponding primary sensory cortices of the newborn brain, it is unclear how multimodal stimuli are processed and integrated across modalities. The latter is essential for learning and understanding environmental contingencies through encoding relationships between sensory experiences; and ultimately likely subserves development of life-long skills such as speech and language. Here, for the first time, we map the intracerebral processing which underlies auditory-sensorimotor classical conditioning in a group of 13 neonates (median gestational age at birth: 38 weeks + 4 days, range: 32 weeks + 2 days to 41 weeks + 6 days; median postmenstrual age at scan: 40 weeks + 5 days, range: 38 weeks + 3 days to 42 weeks + 1 days) with blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (MRI) and magnetic resonance (MR) compatible robotics. We demonstrate that classical conditioning can induce crossmodal changes within putative unimodal sensory cortex even in the absence of its archetypal substrate. Our results also suggest that multimodal learning is associated with network wide activity within the conditioned neural system. These findings suggest that in early life, external multimodal sensory stimulation and integration shapes activity in the developing cortex and may influence its associated functional network architecture.

Keywords: brain plasticity; classical conditioning; functional MRI; multisensory integration; neonate.

Figure 1

Schematic of the associative learning paradigm. Yellow areas depict the occurrence of the sound (6 s, CS), blue the occurrence of the passive movement (US), and highlighted in green a CR trial in which the sound was played alone. Blocks of paired sound and passive movement (starting with 500 ms lag and coterminating) are repeated a variable number of times (4–6) following two trials: one coupled and one sound alone (CR). The paradigm comprised 11 CR trials lasting 22 minutes in total.

Figure 2

FMRI group results of baseline (left) and learning (right) sequences. Significant clusters of functional response are projected onto the surface of an age specific 3D brain template; infant group maps are shown on the top row (n = 11 baseline sound, n = 13 baseline movement and learning) and adult group maps (n = 10 baselines and learning) are shown on the bottom row. Group maps of the baseline functional response to passive hand/fingers movement are shown in blue with localization to the contralateral SM1 for infants and also in the ipsilateral S1 and SMA for adults. Group maps of the baseline functional response to sound are shown in red, with localization to the left auditory cortex for both infants and adults. In red–yellow are shown the group maps during the learning condition (coupled sound and movement), which cover the areas activated during the baseline as well as additional activation in the midline SMA. The CR to the sound alone condition is shown in green, showing additional activity in the contralateral SM1 for infants and S1 for adults.

Figure 3

Measure of BOLD percentage signal change in SM1 calculated within a mask (blue) derived from the response to the passive movement baseline response. The absolute value of the percent signal change was calculated for the sound and movement prelearning (Base, n = 11, n = 13), and learning blocks (Learn, n = 13) and sound alone (CR, n = 13). On the top box-plot, infants’ data show a significant difference of response between the sound prelearning and both prelearning hand movement and sound alone during learning. On the bottom box-plot, adult data show a significant difference between the amplitude of BOLD responses within the SM1 mask in the baseline sound and prelearning hand movement (blue, Friedman test applied to all conditions), and baseline sound to both learning conditions (paired stimuli and CR) (red, Wilcoxon signed rank test).

Figure 4

Measure of BOLD percentage signal in SM1 calculated within a mask (blue) derived from the area of response to the passive movement baseline response. Absolute value of percent signal change was calculated for the sound response in the learning group n (n = 13) and control group (n = 4).