Regional Haemodynamic and Metabolic Coupling in Infants.

Metabolic pathways underlying brain function remain largely unexplored during neurodevelopment, predominantly due to the lack of feasible techniques for use with awake infants. Broadband near-infrared spectroscopy (bNIRS) provides the opportunity to explore the relationship between cerebral energy metabolism and blood oxygenation/haemodynamics through the measurement of changes in the oxidation state of mitochondrial respiratory chain enzyme cytochrome-c-oxidase (ΔoxCCO) alongside haemodynamic changes. We used a bNIRS system to measure ΔoxCCO and haemodynamics during functional activation in a group of 42 typically developing infants aged between 4 and 7 months. bNIRS measurements were made over the right hemisphere over temporal, parietal and central cortical regions, in response to social and non-social visual and auditory stimuli. Both ΔoxCCO and Δ[HbO2] displayed larger activation for the social condition in comparison to the non-social condition. Integration of haemodynamic and metabolic signals revealed networks of stimulus-selective cortical regions that were not apparent from analysis of the individual bNIRS signals. These results provide the first spatially resolved measures of cerebral metabolic activity alongside haemodynamics during functional activation in infants. Measuring synchronised changes in metabolism and haemodynamics have the potential for uncovering the development of cortical specialisation in early infancy.

Non-invasive measurement of a metabolic marker of infant brain function.

While near-infrared spectroscopy (NIRS) haemodynamic measures have proven to be vastly useful in investigating human brain development, the haemodynamic response function (HRF) in infants is not yet fully understood. NIRS measurements of the oxidation state of mitochondrial enzyme cytochrome-c-oxidase (oxCCO) have the potential to yield key information about cellular oxygen utilisation and therefore energy metabolism. We used a broadband NIRS system to measure changes in oxCCO, in addition to haemodynamic changes, during functional activation in a group of 33 typically developing infants aged between 4 and 6 months. The responses were recorded over the right temporal lobe while the infants were presented with engaging videos containing social content. A significant increase in oxCCO was found in response to the social stimuli, with maximum increase of 0.238 ± 0.13 µM. These results are the first reported significant change in oxCCO in response to stimulus-evoked activation in human infants and open new vistas for investigating human infant brain function and its energy metabolism.

Mitochondrial Dysfunction in Autism Spectrum Disorders.

Autism spectrum disorders (ASD) are classified as neurodevelopmental disorders characterised by diminished social communication and interaction. Recently, evidence has accrued that a significant proportion of individuals with autism have concomitant diseases such as mitochondrial disease and abnormalities of energy generation. This has therefore led to the hypothesis that autism may be linked to mitochondrial dysfunction. We review such studies reporting decreased activity of mitochondrial electron transport chain (ETC) complexes and reduced gene expression of mitochondrial genes, in particular genes of respiratory chain complexes, in individuals with autism. Overall, the findings support the hypothesis that there is an association of ASD with impaired mitochondrial function; however, many of the studies have small sample sizes and there is variability in the techniques utilised. There is therefore a vital need to utilise novel imaging techniques, such as near-infrared spectroscopy, that will allow non-invasive measurement of metabolic markers for neuronal activity such as cytochrome c oxidase, in order to better establish the link between autism and mitochondrial dysfunction.