Imaging Cerebral Energy Metabolism in Healthy Infants.

Broadband near-infrared spectroscopy (bNIRS) has the potential to provide non-invasive measures of cerebral haemodynamic changes alongside changes in cellular oxygen utilisation through the measurement of mitochondrial enzyme cytochrome-c-oxidase (oxCCO). It therefore provides the opportunity to explore brain function and specialisation, which remains largely unexplored in infancy. We used bNIRS to measure changes in haemodynamics and changes in oxCCO in 4-to-7-month-old infants over the occipital and right temporal and parietal cortices in response to social and non-social visual and auditory stimuli. Changes in concentration of oxygenated-haemoglobin (Δ[HbO2]), deoxygenated haemoglobin (Δ[HHb]) and change in the oxidation state of oxCCO (Δ[oxCCO]) were calculated using changes in attenuation of light at 120 wavelengths between 780 and900 nm, using the UCLn algorithm. For 4 infants, the attenuation changes in a subset of wavelengths were used to perform image reconstruction, in an age-matched infant model, for channels over the right parietal and temporal cortices, using a multispectral approach which allows direct reconstruction of concentration change data. The volumetric reconstructed images were mapped onto the cortical surface to visualise the reconstructed changes in concentration of HbO2 and HHb and changes in metabolism for both social and non-social stimuli. Spatially localised activation was observed for Δ[oxCCO] and Δ[HbO2] over the temporo-parietal region, in response to the social stimulus. This study provides the first reconstructed images of changes in metabolism in healthy, awake infants.

Hand or spoon? Exploring the neural basis of affective touch in 5-month-old infants.

In adults, affective touch leads to widespread activation of cortical areas including posterior Superior Temporal Sulcus (pSTS) and Inferior Frontal Gyrus (IFG). Using functional Near Infrared Spectroscopy (fNIRS), we asked whether similar areas are activated in 5-month-old infants, by comparing affective to non-affective touch. We contrasted a human touch stroke to strokes performed with a cold metallic spoon. The hypothesis that adult-like activation of cortical areas would be seen only in response to the human touch stroke was not confirmed. Similar patterns of activation were seen in both conditions. We conclude that either the posterior STS and IFG have not yet developed selective responses to affective touch, or that additional social cues are needed to be able to identify this type of touch.

Changes in Cytochrome-C-Oxidase Account for Changes in Attenuation of Near-Infrared Light in the Healthy Infant Brain.

A novel multi-wavelength broadband near infrared spectroscopy (NIRS) system has been employed to simultaneously measure haemodynamic changes alongside changes in cellular oxygen utilization by measurement of oxidation state of mitochondrial enzyme cytochrome-c-oxidase (oxCCO). The aim of this study was to investigate the role of oxCCO in neural responses to functional activation in infants. Studies were performed using a NIRS broadband system in 33 typically developing infants aged between 4 and 6 months. Responses were recorded over the right temporal lobe while infants were presented with engaging videos containing social and non-social content. Changes in the concentration of oxyhaemoglobin (Δ[HbO2]), deoxyhaemoglobin (Δ[HHb]) and Δ[oxCCO] were calculated using changes in attenuation of light at 120 wavelengths between 780 and 900 nm using the UCLn algorithm. The algorithm was also used to fit (a) HbO2 and HHb spectra (2 component fit) and (b) HbO2, HHb and oxCCO (3 component fit) to the change in attenuation occurring within an experimental block in different participants. Residuals resulting from these two fits were compared with oxidized-minus reduced CCO spectrum, calculated using the CCO specific extinction coefficient. A significant increase in oxCCO was found in response to the social stimuli (maximum increase 0.238 ± 0.13 µM). Residuals analysis showed that the best fits were achieved when oxCCO was included as a tissue chromophore. These results are the first reported significant change in oxCCO to stimulus-evoked activation in infants and may reveal vital information about oxygen metabolism during functional activation in the developing human brain.

Cortical responses before 6 months of life associate with later autism.

Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

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 1000days (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.

Using fNIRS to Study Working Memory of Infants in Rural Africa.

A pilot study was conducted to assess the feasibility of using fNIRS as an alternative to behavioral assessments of cognitive development with infants in rural Africa. We report preliminary results of a study looking at working memory in 12-16-month-olds and discuss the benefits and shortcomings for the potential future use of fNIRS to investigate the effects of nutritional insults and interventions in global health studies.

Neural Mechanisms of Body Awareness in Infants.

The ability to differentiate one's body from others is a fundamental aspect of social perception and has been shown to involve the integration of sense modalities attributable to the self. Though behavioral studies in infancy have investigated infants' discrimination of body-related multisensory stimuli, whether they attribute this information as belonging to the self is still unknown. In human adults, neuroimaging studies have demonstrated the recruitment of a specific set of brain regions in response to body-related multisensory integration. To test whether the infant brain integrates this information similarly to adults, in a first functional near-infrared spectroscopy study we investigated the role of visual-proprioceptive feedback when temporal cues are manipulated by showing 5-month-old infants an online video of their own face while the infant was performing movements. To explore the role of body-related contingency further, in a second study we investigated whether cortical activation in response to self-initiated movements and external tactile stimulation was similar to that found in the first study. Our results indicate that infants' specialized cortical activation in response to body-related contingencies is similar to brain activation seen in response to body awareness in adults.

Optical imaging of brain activation in Gambian infants.

We used optical topography (OT) to investigate cognitive function in infants in rural Gambia. Images of changes in oxyhaemoglobin and deoxyhaemoglobin concentrations were reconstructed using a multispectral algorithm which uses the finite element method (FEM) to model the propagation of light through scattering tissue using the diffusion equation. High quality OT data enabled us to reconstruct images with robust representation of haemodynamic changes. OT is a feasible neuroimage technology for this resource-poor setting.

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.

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.

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.