Anna Blasi

Illuminating the developing brain: The past, present and future of functional near infrared spectroscopy

A decade has passed since near infrared spectroscopy (NIRS) was first applied to functional brain imaging in infants. As part of the team that published the first functional near infrared spectroscopy (fNIRS) infant study in 1998, we have continued to develop and refine both the technology and methods associated with these measurements. The increasing international interest that this technology is generating among neurodevelopmental researchers and the recent technical developments in biomedical optics have prompted us to compile this review of the challenges that have been overcome in this field, and the practicalities of performing fNIRS in infants. We highlight the increasingly diverse and ambitious studies that have been undertaken and review the technological and methodological advances that have been made in the study design, optical probe development, and interpretation and analyses of the haemodynamic response. A strong emphasis is placed on the potential of the technology and future prospects of fNIRS in the field of developmental neuroscience.

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.

Social Perception in Infancy: A Near Infrared Spectroscopy Study

The capacity to engage and communicate in a social world is one of the defining characteristics of the human species. While the network of regions that compose the social brain have been the subject of extensive research in adults, there are limited techniques available for monitoring young infants. This study used near infrared spectroscopy to investigate functional activation in the social brain network of 36 five-month-old infants. We measured the hemodynamic responses to visually presented stimuli in the temporal lobes. A significant increase in oxyhemoglobin was localized to 2 posterior temporal sites bilaterally, indicating that these areas are involved in the social brain network in young infants.

Reduced neural sensitivity to social stimuli in infants at risk for autism

In the hope of discovering early markers of autism, attention has recently turned to the study of infants at risk owing to being the younger siblings of children with autism. Because the condition is highly heritable, later-born siblings of diagnosed children are at substantially higher risk for developing autism or the broader autism phenotype than the general population. Currently, there are no strong predictors of autism in early infancy and diagnosis is not reliable until around 3 years of age. Because indicators of brain functioning may be sensitive predictors, and atypical social interactions are characteristic of the syndrome, we examined whether temporal lobe specialization for processing visual and auditory social stimuli during infancy differs in infants at risk. In a functional near-infrared spectroscopy study, infants aged 4–6 months at risk for autism showed less selective neural responses to social stimuli (auditory and visual) than low-risk controls. These group differences could not be attributed to overall levels of attention, developmental stage or chronological age. Our results provide the first demonstration of specific differences in localizable brain function within the first 6 months of life in a group of infants at risk for autism. Further, these differences closely resemble known patterns of neural atypicality in children and adults with autism. Future work will determine whether these differences in infant neural responses to social stimuli predict either later autism or the broader autism phenotype frequently seen in unaffected family members.

Selective cortical mapping of biological motion processing in young infants

How specialized is the infant brain for perceiving the facial and manual movements displayed by others? Although there is evidence for a network of regions that process biological motion in adults—including individuated responses to the perception of differing facial and manual movements—how this cortical specialization develops remains unknown. We used functional near-infrared spectroscopy [Lloyd-Fox, S., Blasi, A., & Elwell, C. Illuminating the developing brain: The past, present and future of functional near-infrared spectroscopy. Neuroscience and Biobehavioral Reviews, 34, 269–284, 2010] to investigate the ability of 5-month-old infants to process differing biological movements. Infants watched videos of adult actors moving their hands, their mouth, or their eyes, all in contrast to nonbiological mechanical movements, while hemodynamic responses were recorded over the their frontal and temporal cortices. We observed different regions of the frontal and temporal cortex that responded to these biological movements and different patterns of cortical activation according to the type of movement watched. From an early age, our brains selectively respond to biologically relevant movements, and further, selective patterns of regional specification to different cues occur within what may correspond to a developing “social brain” network. These findings illuminate hitherto undocumented maps of selective cortical activation to biological motion processing in the early postnatal development of the human brain.

Investigation of depth dependent changes in cerebral haemodynamics during face perception in infants

Near-infrared spectroscopy has been used to record oxygenation changes in the visual cortex of 4 month old infants. Our in-house topography system, with 30 channels and 3 different source-detector separations, recorded changes in the concentration of oxy-, deoxy- and total haemoglobin (HbO2, HHb and HbT) in response to visual stimuli (face, scrambled visual noise and cartoons as rest). The aim of this work was to demonstrate the capability of the system to spatially localize functional activation and study the possibility of depth discrimination in the haemodynamic response. The group data show both face stimulation and visual noise stimulation induced significant increases in HbO2 from rest, but the increase in HbO2 with face stimulation was not significantly different from that seen with visual noise stimulation. The face stimuli induced increases in HbO2 were spread across a greater area across all depths than visual noise induced changes. In results from a single subject there was a significant increase of HbO2 in the inferior area of the visual cortex in response to both types of stimuli, and a larger number of channels (source-detector pairs) showed HbO2 increase to face stimuli, especially at the greatest depth. Activation maps were obtained using 3D reconstruction methods on multi source-detector separation optical topography data.

Coregistering functional near-infrared spectroscopy with underlying cortical areas in infants

Abstract. Functional near-infrared spectroscopy (fNIRS) is becoming a popular tool in developmental neuroscience for mapping functional localized brain responses. However, as it cannot provide information about underlying anatomy, researchers have begun to conduct spatial registration of fNIRS channels to cortical anatomy in adults. The current work investigated this issue with infants by coregistering fNIRS and magnetic resonance imaging (MRI) data from 55 individuals. Our findings suggest that fNIRS channels can be reliably registered with regions in the frontal and temporal cortex of infants from 4 to 7 months of age. Although some macro-anatomical regions are difficult to consistently define, others are more stable and fNIRS channels on an age-appropriate MRI template are often consistent with individual infant MRIs. We have generated a standardized scalp surface map of fNIRS channel locators to reliably locate cortical regions for fNIRS developmental researchers. This new map can be used to identify the inferior frontal gyrus, superior temporal sulcus (STS) region [which includes the superior and middle temporal gyri (MTG) nearest to the STS], and MTG and temporal-parietal regions in 4- to 7-month-old infants. Future work will model data for the whole head, taking into account the properties of light transport in tissue, and expanding to different ages across development.

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.

A Nonlinear Model of Cardiac Autonomic Control in Obstructive Sleep Apnea Syndrome

Using the Volterra–Wiener approach, we employed a minimal model to quantitatively characterize the linear and nonlinear effects of respiration (RCC) and arterial blood pressure (ABR) on heart rate variability (HRV) in normal controls and subjects with moderate-to-severe obstructive sleep apnea syndrome (OSAS). Respiration, R–R interval (RRI), blood pressure (BP) and other polysomnographic variables were recorded in eight normal controls and nine OSAS subjects in wakefulness, Stage 2 and rapid eye-movement sleep. To increase respiratory and cardiovascular variability, a preprogrammed ventilator delivered randomly timed inspiratory pressures that were superimposed on a baseline continuous positive airway pressure. Except for lower resting RRI in OSAS subjects, summary statistical measures of RRI and BP and their variabilities were similar in controls and OSAS. In contrast, RCC and ABR gains were significantly lower in OSAS. Nonlinear ABR gain and the interaction between respiration and blood pressure in modulating RRI were substantially reduced in OSAS. ABR gain increased during sleep in controls but remained unchanged in OSAS. These findings suggest that normotensive OSAS subjects have impaired daytime parasympathetic and sympathetic function. Nonlinear minimal modeling of HRV provides a useful, insightful, and comprehensive approach for the detection and assessment of abnormal autonomic function in OSAS.

Cortical specialisation to social stimuli from the first days to the second year of life: a rural Gambian cohort

Brain and nervous system development in human infants during the first 1000 days (conception to two years of age) is critical, and compromised development during this time (such as from under nutrition or poverty) can have life-long effects on physical growth and cognitive function. Cortical mapping of cognitive function during infancy is poorly understood in resource-poor settings due to the lack of transportable and low-cost neuroimaging methods. Having established a signature cortical response to social versus non-social visual and auditory stimuli in infants from 4 to 6 months of age in the UK, here we apply this functional Near Infrared Spectroscopy (fNIRS) paradigm to investigate social responses in infants from the first postnatal days to the second year of life in two contrasting environments: rural Gambian and urban UK. Results reveal robust, localized, socially selective brain responses from 9 to 24 months of life to both the visual and auditory stimuli. In contrast at 0–2 months of age infants exhibit non-social auditory selectivity, an effect that persists until 4–8 months when we observe a transition to greater social stimulus selectivity. These findings reveal a robust developmental curve of cortical specialisation over the first two years of life.