Brain functional near infrared spectroscopy in human infants : cerebral cortical haemodynamics coupled to neuronal activation in response to sensory stimulation

Sammanfattning: The assessment of cortical activation in the neonatal brain is crucial in the study of brain development, as it provides precious information for how the newborn infant processes external or internal stimuli. Thus far functional studies of neonates aimed to assess cortical responses to certain external stimuli are very few, due to the lack of suitable techniques to monitor brain activity of the newborn. Near Infrared Spectroscopy (NIRS) has been found to be suitable for functional studies of the infant brain. By this method haemodynamic changes coupled to cortical activity can be monitored. The overall aim of the research is to assess how the brain is processing sensory stimuli (pleasant and unpleasant) in infants using a non-invasive technique such as NIRS. Studies of smell perception (studies 1 & 2) Olfaction was mainly used as the paradigm in these studies. Smelling is essential for neonatal behavioural adaptation in many mammals, including humans. Methods Study 1 Twenty-three healthy, full-term newborn infants were included in the study at a postnatal age between 6 hours and 192 hours. As odorant sources we used (i) the own mother's colostrum; (ii) vanilla essence; (iii) distilled water as a negative control. The i NIRS optodes were placed over left orbito-frontal gyrus of the frontal lobe. Study 2 Twenty preterm newborn infants in stable condition at testing were studied. As odorant sources a disinfectant solution containing benzalconio chlorate (0.25%), ethylic alcohol (66.29%), excipients such as lemon oil, acetone, iso-propilic alcohol, camphor and a detergent containing dipropylene glycol methyl ether, water and mineral essences were used. The NIRS optodes were placed bilaterally over left orbitofrontal gyrus of the frontal lobe. Main findings and conclusion Study 1 The main finding of this study was that the NIRS technique can be used in the neonatal period to record activity in the orbito-frontal cortex - as mirrored by changes in blood circulation during exposure to biologically meaningful as well as artificial odors, colostrum and vanilla, respectively. The magnitude of the response in the illuminated region during colostrum exposure was inversely related to postnatal age. Study 2 This study demonstrated that the odors of solutions commonly used in NICUs might elicit a decrease in blood oxygenation in an area likely to include the orbito-frontal olfactory area. These haemodynamic changes are likely to be the result of a dynamic, physiological regulation of regional CBF based upon the olfactory- and trigeminus-related areas of the brain. Study of pain perception (study 3) Supraspinal pain processing of pain in neonates and preemies is still poorly understood. Methods Forty preterm neonates at 28-36 weeks of gestation and mean postnatal age of 30.7 h were studied following standardized tactile (skin disinfection) and painful (venipuncture) stimuli. Changes in regional cerebral haemodynamics were monitored by near infrared spectroscopy (NIRS) over both somatosensory cortices in 29 newborns, and over the contralateral somatosensory and occipital areas in 11 newborns. Main findings and conclusion Painful and tactile stimuli elicit specific haemodynamic responses in the somatosensory cortex, implying conscious sensory perception in preterm neonates. Somatosensory cortical activation occurs bilaterally following unilateral stimulation and these changes are more pronounced in male neonates and preterm neonates at lower gestational ages. Study of auditory perception (study 4) The aim of the study was to assess differences in activation pattern in response to auditory stimuli before and after the induction of anaesthesia with sevoflurane. Methods The 'Water music", by Handel, was presented to 7 infants aged between 18 and 22 months. NIRS was recorded in different conditions: baseline with no music when the child was asleep, during the music with the child sleeping before anaesthesia, and during the music when the child was in deep anaesthesia. Main Endings and conclusion We observed pronounced bilateral [HbO2] increase during sleeping, similar to that previously reported in waken subjects and suggesting that the infant perceives the auditory stimulus and likely processes it. When the infant is anaesthetised and many neuronal circuits are not functioning, the auditory stimulus can still be perceived as suggested by the increase of Hb02 in one hemisphere, but processing might be altered. Overall conclusion These studies and other studies that have been carried out in parallel by other groups demonstrate that NIRS is a suitable technique to assess cortical activation in response to varying forms of sensory stimulation in human infants. The technique is likely to play an important role in providing new insights into the ontogeny of cortical function, as well as possibly providing a sensitive means for the early detection of perinatal cortical impairment.