Top-down modulation in the infant brain: Learning-induced expectations rapidly affect the sensory cortex at 6 months

Recent theoretical work emphasizes the role of expectation in neural processing, shifting the focus from feed-forward cortical hierarchies to models that include extensive feedback (e.g., predictive coding). Empirical support for expectation-related feedback is compelling but restricted to adult humans and nonhuman animals. Given the considerable differences in neural organization, connectivity, and efficiency between infant and adult brains, it is a crucial yet open question whether expectation-related feedback is an inherent property of the cortex (i.e., operational early in development) or whether expectation-related feedback develops with extensive experience and neural maturation. To determine whether infants’ expectations about future sensory input modulate their sensory cortices without the confounds of stimulus novelty or repetition suppression, we used a cross-modal (audiovisual) omission paradigm and used functional near-infrared spectroscopy (fNIRS) to record hemodynamic responses in the infant cortex. We show that the occipital cortex of 6-month-old infants exhibits the signature of expectation-based feedback. Crucially, we found that this region does not respond to auditory stimuli if they are not predictive of a visual event. Overall, these findings suggest that the young infant’s brain is already capable of some rudimentary form of expectation-based feedback.Over the past two decades, theoretical focus has shifted from predominantly feed-forward hierarchies of cortical function, where sensory cortex propagates information to higher level analyzers on the way to decision and motor control areas, to models in which feedback connections to lower-level cortical regions allow extensive top-down functional modulation based on expectation (1). An influential model for incorporating feedback is predictive coding, which compares expectations or predictions to input at each level of the processing hierarchy (2–4). There is extensive and compelling evidence for expectation-based modulation even at the earliest levels of sensory processing in both humans (5–7) and nonhuman animals (8). Because complex, naturalistic sensory input is characterized by temporal, spatial, and contextual regularities, the ability to modulate early sensory function as a result of expectations is believed to support adaptive perceptual abilities (4).Empirical evidence for expectation-based feedback, however, is restricted to adult humans and nonhuman animals. With their extensive experience, adults already have developed sophisticated internal models of the environment and have a highly interconnected brain and efficient neural processing. Comparatively, human infants are born with a demonstratively immature behavioral repertoire, have underdeveloped sensorimotor and cognitive capacities, and lack sophisticated internal models of the environment. These internal models undergo substantial postnatal development even in the early sensory cortex. For example, spontaneous activity of primary visual cortex (V1) in ferrets converges with evoked visual responses to naturalistic stimuli across development but does not converge with evoked responses to nonnaturalistic stimuli (9). Thus, statistics in sensory input progressively create an adaptive, internal model of the environment that is evident in V1, and, therefore, the neonate brain does not have access to sophisticated expectations about sensory input. Moreover, converging evidence from both anatomical (10) and functional connectivity analyses (11) has demonstrated that human infants have a much less interconnected brain and instead have a predominance of local connections and a slow development of long-range interactions (12). Finally, human infants exhibit characteristically slower neural processing even for basic sensory stimuli (13).Given the considerable differences between infant and adult brains, it is unclear whether the infant brain is capable of the sophisticated expectation-based modulation of sensory cortices that has been observed in adult brains. Relatedly, the developmental process by which feedback comes to modulate neural function based on changing expectations is entirely unknown. One possibility is that infants do not exhibit expectation-based feedback, but rely on a predominantly feed-forward architecture. In this case, a feed-forward neural architecture would be a developmental precursor to the feedback mechanisms that would emerge after extensive postnatal experience and would be consistent with the immaturity of infant cognition and sensorimotor control. Another possibility is that the fundamental architecture that allows expectation-based feedback is present in early infancy and provides a scaffold for the development of efficient internal models of the environment. Here, we ask whether expectation-based feedback is evident in the infant brain: specifically, in the sensory cortex.Despite extensive behavioral evidence that infants can form expectations in many perceptual and cognitive domains (14, 15) and are able to quickly and robustly respond to new information in their environment (e.g., statistical learning abilities) (16, 17), it remains unclear how their expectations about future sensory input are instantiated neurally. The infant event-related potentials (ERPs) literature provides a glimpse but falls short of clarifying the underlying neural mechanism. The traditional oddball design, which presents a frequent stimulus and an infrequent stimulus (e.g., 80% and 20% respectively), reveals a robust novelty response in several waveform components (delayed version of the P300 and the mismatch negativity) (18–20). However, the ERP is exquisitely sensitive to the properties of the stimuli, and so the enhanced response to the infrequent stimulus could be a prediction error, a nonspecific surprise effect, or a recovery to the greater repetition of the frequent stimulus (i.e., rebound from repetition suppression) (21). Using similar designs with similar interpretative limitations, recent work with functional near-infrared spectroscopy (fNIRS) (an optical imaging method for noninvasively recording functional changes in the hemodynamics of the infant cortex while the infant is awake and behaving) (22, 23) has revealed increased neural responses to the presentation of novel acoustic stimuli (24) and evidence of stimulus anticipation (25).A more interpretively transparent design for assessing whether expectations can modulate responses in sensory cortex is the stimulus-omission paradigm. Here, two or more stimuli are presented in a predictable temporal order, and one of the expected stimuli is occasionally and unexpectedly omitted. Because there is no sensory input during stimulus omission, the response cannot be due to recovery from repetition suppression, and, if the effect is localized (i.e., does not occur in all cortical regions), it cannot be due to nonspecific surprise. This stimulus-omission paradigm has been used with mice to record from V1 with multielectrode arrays (8), with human adults to record from auditory and frontal areas with magnetoencephalography (MEG) (7), from V1 using fMRI (26), and with presurgical epilepsy patients to record from temporal-parietal areas with cortical electrodes (27). A particularly impressive variation is the ability of a recently learned cross-modal association (e.g., audiovisual stimuli) to generate responses to the unexpected omission of one of the previously paired stimuli, as recently demonstrated in human adults (5, 28).We used the cross-modal stimulus omission paradigm to determine whether a recently learned audiovisual association drives occipital cortex responses during an unexpected visual omission in young human infants. We presented 36 6-month-old infants (Materials and Methods) with novel sounds and visual stimuli such that a sound predicted the presentation of a visual stimulus. Infants can rapidly learn arbitrary audiovisual associations even from a young age (29, 30). Therefore, after a brief period of familiarization (less than 2 min, 18 audiovisual or A+V+ events), infants were presented with trials where the predictive auditory stimulus was presented and the visual stimulus was unexpectedly withheld (see Fig. 1 and Materials and Methods). These unexpected visual omission trials violate sensory expectations but do not present any sensory input. Therefore, any occipital cortex responses to unexpected visual omissions were evidence of a neural response generated as a result of a violation of sensory expectation and not a result of lower-level neural adaptation effects, such as repetition suppression or generalized novelty responses.Open in a separate windowFig. 1.Schematic of the two trial types: A+V+ (audiovisual trials) and A+V− (visual omission trials). After a period of familiarization to only A+V+ trials, infants saw visual stimuli accompanying auditory stimuli 80% of the time. Thus, infants expected to see the visual stimulus after each auditory stimulus.