Evelyne Mercure

Mapping Infant Brain Myelination with Magnetic Resonance Imaging

Myelination, the elaboration of myelin surrounding neuronal axons, is essential for normal brain function. The development of the myelin sheath enables rapid synchronized communication across the neural systems responsible for higher order cognitive functioning. Despite this critical role, quantitative visualization of myelination in vivo is not possible with current neuroimaging techniques including diffusion tensor and structural magnetic resonance imaging (MRI). Although these techniques offer insight into structural maturation, they reflect several different facets of development, e.g., changes in axonal size, density, coherence, and membrane structure; lipid, protein, and macromolecule content; and water compartmentalization. Consequently, observed signal changes are ambiguous, hindering meaningful inferences between imaging findings and metrics of learning, behavior or cognition. Here we present the first quantitative study of myelination in healthy human infants, from 3 to 11 months of age. Using a new myelin-specific MRI technique, we report a spatiotemporal pattern beginning in the cerebellum, pons, and internal capsule; proceeding caudocranially from the splenium of the corpus callosum and optic radiations (at 3–4 months); to the occipital and parietal lobes (at 4–6 months); and then to the genu of the corpus callosum and frontal and temporal lobes (at 6–8 months). Our results also offer preliminary evidence of hemispheric myelination rate differences. This work represents a significant step forward in our ability to appreciate the fundamental process of myelination, and provides the first ever in vivo visualization of myelin maturation in healthy human infancy.

Differential lateralization for words and faces: Category or psychophysics?

This set of three experiments assessed the influence of different psychophysical factors on the lateralization of the N170 event-related potential (ERP) component to words and faces. In all experiments, words elicited a left-lateralized N170, whereas faces elicited a right-lateralized or nonlateralized N170 depending on presentation conditions. Experiment 1 showed that lateralization for words (but not for faces) was influenced by spatial frequency. Experiment 2 showed that stimulus presentation time influenced N170 lateralization independently of spatial frequency composition. Finally, Experiment 3 showed that stimulus size and resolution did not influence N170 lateralization, but did influence N170 amplitude, albeit differentially for words and faces. These findings suggest that differential lateralization for words and faces, at least as measured by the N170, is influenced by spatial frequency (words), stimulus presentation time, and category.

Featural and configural face processing differentially modulate ERP components

Since all faces share the same first-order configuration, individual faces are recognized by subtle differences in their individual features and second-order configuration. This study asked two questions about the ERP signatures of featural and configural face processing. First, which ERP components are sensitive to subtle modifications of features and second-order configuration? Secondly, does explicitly instructing participants to attend to either the features or the configuration of face stimuli influence the neural processes elicited by these stimuli? In the first part of this experiment, pairs of faces with differences in their features, in their second-order configuration or no difference were presented, with participants making same/different judgments. In the second part, participants were asked to focus on either the features or configuration in pairs of faces and to judge if there was any difference in that aspect while ignoring other differences. The P1 and N170 ERP components were not influenced by feature or second-order configuration differences in faces, indicating that these components could be more sensitive to manipulations that disrupt the first-order configuration of a face. In contrast, the P2 was larger in amplitude for faces with a configuration modification than for faces with a feature modification or for the original face. One explanation of these results is that processing the configuration of a face elicits more visual cortical feedback than processing the features. Finally, modulation of the P300 confirmed that the tasks presented in Part 2 were successful in varying the attention focus on the features or configuration.

The emergence of cerebral specialization for the human voice over the first months of life

How specialized is the infant brain for processing voice within our environment? Research in adults suggests that portions of the temporal lobe play an important role in differentiating vocalizations from other environmental sounds; however, very little is known about this process in infancy. Recent research in infants has revealed discrepancies in the cortical location of voice-selective activation, as well as the age of onset of this response. The current study used functional near-infrared spectroscopy (fNIRS) to further investigate voice processing in awake 4–7-month-old infants. In listening to voice and non-voice sounds, there was robust and widespread activation in bilateral temporal cortex. Further, voice-selective regions of the bilateral anterior temporal cortex evidenced a steady increase in voice selective activation (voice > non-voice activation) over 4–7 months of age. These findings support a growing body of evidence that the emergence of cerebral specialization for human voice sounds evolves over the first 6 months of age.

Audio-visual speech perception: a developmental ERP investigation

Being able to see a talking face confers a considerable advantage for speech perception in adulthood. However, behavioural data currently suggest that children fail to make full use of these available visual speech cues until age 8 or 9. This is particularly surprising given the potential utility of multiple informational cues during language learning. We therefore explored this at the neural level. The event-related potential (ERP) technique has been used to assess the mechanisms of audio-visual speech perception in adults, with visual cues reliably modulating auditory ERP responses to speech. Previous work has shown congruence-dependent shortening of auditory N1/P2 latency and congruence-independent attenuation of amplitude in the presence of auditory and visual speech signals, compared to auditory alone. The aim of this study was to chart the development of these well-established modulatory effects over mid-to-late childhood. Experiment 1 employed an adult sample to validate a child-friendly stimulus set and paradigm by replicating previously observed effects of N1/P2 amplitude and latency modulation by visual speech cues; it also revealed greater attenuation of component amplitude given incongruent audio-visual stimuli, pointing to a new interpretation of the amplitude modulation effect. Experiment 2 used the same paradigm to map cross-sectional developmental change in these ERP responses between 6 and 11 years of age. The effect of amplitude modulation by visual cues emerged over development, while the effect of latency modulation was stable over the child sample. These data suggest that auditory ERP modulation by visual speech represents separable underlying cognitive processes, some of which show earlier maturation than others over the course of development.

Neurophysiological responses to faces and gaze direction differentiate children with ASD, ADHD and ASD + ADHD

Children with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) demonstrate face processing abnormalities that may underlie social impairment. Despite substantial overlap between ASD and ADHD, ERP markers of face and gaze processing have not been directly compared across pure and comorbid cases. Children with ASD (n=19), ADHD (n=18), comorbid ASD+ADHD (n=29) and typically developing (TD) controls (n=26) were presented with upright/inverted faces with direct/averted gaze, with concurrent recording of the P1 and N170 components. While the N170 was predominant in the right hemisphere in TD and ADHD, children with ASD (ASD/ASD+ADHD) showed a bilateral distribution. In addition, children with ASD demonstrated altered response to gaze direction on P1 latency and no sensitivity to gaze direction on midline-N170 amplitude compared to TD and ADHD. In contrast, children with ADHD (ADHD/ASD+ADHD) exhibited a reduced face inversion effect on P1 latency compared to TD and ASD. These findings suggest children with ASD have specific abnormalities in gaze processing and altered neural specialisation, whereas children with ADHD show abnormalities at early visual attention stages. Children with ASD+ADHD are an additive co-occurrence with deficits of both disorders. Elucidating the neural basis of the overlap between ASD and ADHD is likely to inform aetiological investigation and clinical assessment.

The n170 shows differential repetition effects for faces, objects, and orthographic stimuli.

Previous event-related potentials research has suggested that the N170 component has a larger amplitude to faces and words than to other stimuli, but it remains unclear whether it indexes the same cognitive processes for faces and for words. The present study investigated how category-level repetition effects on the N170 differ across stimulus categories. Faces, cars, words, and non-words were presented in homogeneous (1 category) or mixed blocks (2 intermixed categories). We found a significant repetition effect of N170 amplitude for successively presented faces and cars (in homogeneous blocks), but not for words and unpronounceable consonant strings, suggesting that the N170 indexes different underlying cognitive processes for objects (including faces) and orthographic stimuli. The N170 amplitude was significantly smaller when multiple faces or multiple cars were presented in a row than when these stimuli were preceded by a stimulus of a different category. Moreover, the large N170 repetition effect for faces may be important to consider when comparing the relative N170 amplitude for different stimulus categories. Indeed, a larger N170 deflection for faces than for other stimulus categories was observed only when stimuli were preceded by a stimulus of a different category (in mixed blocks), suggesting that an enhanced N170 to faces may be more reliably observed when faces are presented within the context of some non-face stimuli.

Social and attention factors during infancy and the later emergence of autism characteristics.

Characteristic features of autism include atypical social perception and social-communication skills, and atypical visual attention, alongside rigid and repetitive thinking and behavior. Debate has focused on whether the later emergence of atypical social skills is a consequence of attention problems early in life, or, conversely, whether early social deficits have knock-on consequences for the later development of attention skills. We investigated this question based on evidence from infants at familial risk for a later diagnosis of autism by virtue of being younger siblings of children with a diagnosis. Around 9months, at-risk siblings differed as a group from controls, both in measures of social perception and inhibitory control. We present preliminary data from an ongoing longitudinal research program, suggesting clear associations between some of these infant measures and autism-related characteristics at 3years. We discuss the findings in terms of the emergent nature of autism as a result of complex developmental interactions among brain networks.

Gene Expression to Neurobiology and Behavior

Characteristic features of autism include atypical social perception and social-communication skills, and atypical visual attention, alongside rigid and repetitive thinking and behavior. Debate has focused on whether the later emergence of atypical social skills is a consequence of attention problems early in life, or, conversely, whether early social deficits have knock-on consequences for the later development of attention skills. We investigated this question based on evidence from infants at familial risk for a later diagnosis of autism by virtue of being younger siblings of children with a diagnosis. Around 9months, at-risk siblings differed as a group from controls, both in measures of social perception and inhibitory control. We present preliminary data from an ongoing longitudinal research program, suggesting clear associations between some of these infant measures and autism-related characteristics at 3years. We discuss the findings in terms of the emergent nature of autism as a result of complex developmental interactions among brain networks.

Atypical processing of voice sounds in infants at risk for autism spectrum disorder

Adults diagnosed with autism spectrum disorder (ASD) show a reduced sensitivity (degree of selective response) to social stimuli such as human voices. In order to determine whether this reduced sensitivity is a consequence of years of poor social interaction and communication or is present prior to significant experience, we used functional MRI to examine cortical sensitivity to auditory stimuli in infants at high familial risk for later emerging ASD (HR group, N = 15), and compared this to infants with no family history of ASD (LR group, N = 18). The infants (aged between 4 and 7 months) were presented with voice and environmental sounds while asleep in the scanner and their behaviour was also examined in the context of observed parent–infant interaction. Whereas LR infants showed early specialisation for human voice processing in right temporal and medial frontal regions, the HR infants did not. Similarly, LR infants showed stronger sensitivity than HR infants to sad vocalisations in the right fusiform gyrus and left hippocampus. Also, in the HR group only, there was an association between each infants degree of engagement during social interaction and the degree of voice sensitivity in key cortical regions. These results suggest that at least some infants at high-risk for ASD have atypical neural responses to human voice with and without emotional valence. Further exploration of the relationship between behaviour during social interaction and voice processing may help better understand the mechanisms that lead to different outcomes in at risk populations.