Hemodynamic responses to visual stimulation in occipital and frontal cortex of newborn infants: a near-infrared optical topography study
Introduction
A fundamental issue in the human brain development is how structurally and functionally specialized regions of the cerebral cortex arise. Brain imaging studies using fMRI have revealed that the localized area of the occipital cortex in young infants responds to visual stimulation [1], [2], [3], [4], [5], [6], [7], [8]. As the subjects had to remain completely immobile throughout the experiment to ensure the acquisition of motion-free images, they were studied asleep, either spontaneously or after sedation. These studies have shown interesting observation: BOLD signal decreases during visual stimulation, while an identical stimulation in adults causes a BOLD signal increase. Yamada et al. [5], [6] reported a rapid age-dependent reverse in BOLD signal; infants older than 8 weeks showed a stimulus-induced signal decrease, whereas infants younger than 7 weeks showed a signal increase. They argued that the signal decrease may be dominated by a greater proportional increase in oxygen consumption relative to regional cerebral blood flow (rCBF) increase during visual stimulation and that this increase may be related to rapid synapse formation and accompanying increase metabolism. Born et al. [3] addressed the issue whether this negative response pattern is of developmental origin particular to a given age or to a general effect of sleep or sedation. They used fMRI and positron emission tomography (PET) to study the brain activation pattern during visual stimulation in spontaneously sleeping adults and found a negative BOLD response and a decrease in rCBF [4]. While a negative BOLD signal change in sleeping infants has been confirmed by several studies, it remains unclear why newborns show a positive BOLD signal.
Study of brain imaging in young infants has been limited, since fMRI and PET can not been approved for use with infants in nonclinical settings. In contrast, near-infrared spectroscopy (NIRS) has permitted noninvasive and safe measurement of cerebral blood oxygenation changes: oxyhemoglobin and deoxyhemoglobin changes in relation to brain activation [9], [10], [11], [12], [13]. Meek et al. [9] examined awake infants aged 3 days to 14 weeks and showed that an increase in both oxyhemoglobin and deoxyhemoglobin concentrations in response to a visual stimulus of checkerboard pattern reversal was observed in the occipital cortex and not in a frontparietal region. Hoshi et al. used three-channel NIRS for measuring the oxygenation of the occipital cortex in newborns during photic stimulation. An increase in oxyhemoglobin concentration was consistently observed, while changes in deoxyhemoglobin concentration differed in each subject [10]. Studies on hemodynamic responses to auditory stimulation in newborns consistently observed an increase in oxyhemoglobin at a frontal region [11] and at the bilateral temporal cortex [12]. NIRS has been applied to awake and behaving infants aged 5–12 months to reveal that the emergence of object permanence was related to an increase in oxyhemoglobin in the frontal cortex [13]. Taken together, NIRS studies on young infants have consistently shown oxyhemoglobin increases in activated areas of the cortex.
Recent advances in the multichannel NIRS technique, near-infrared optical topography (OT), have provided functional brain imaging with improved spatial resolution and higher temporal resolution in adults [14], [15]. OT has been also used to study spontaneous changes in oxygenation of the occipital cortex of sleeping infants [16]. OT has great advantages in brain imaging of young infants not only for safety and portability but also for sensitivity to detect dynamic changes in cerebral oxygenation in relation to the focal brain activation.
In the present study, we addressed two important issues on the newborns' brain development. First, we examined whether the brain of newborns exhibited event-related hemodynamic responses to a brief visual stimulation. Second, we asked whether the cortical development of primary sensory area preceded the development of association area that mediates higher functions in adults. We measured hemodynamic changes of the occipital and frontal cortex in response to brief visual stimulation by means of the near infrared OT.
Section snippets
Subjects and methods
We studied 25 neonates (male 8 subjects and female 17 subjects) born at 36–41 weeks. These experiments were approved by the ethics committee of Tokyo Women's Medical University. Informed consent was obtained from the parents of infants prior to the initiation of experiments.
We used a near infrared OT instrument (Hitachi Medical) [14], [15]. In brief, this instrument generated two wavelengths NIR (780 and 830 nm) and measured time courses of the levels of oxyhemoglobin and deoxyhemoglobin
Results
We obtained data from 16 infants. Nine infants were tested, but not included in the sample, because we could not obtain data including at least seven epochs due to their head movements during measurement. The time series were analyzed with the ANOVA method described above on a channel-by-channel basis and the analyzed data are summarized in Table 1. When the entire infants were evaluated, the visual stimulation produced significant changes in [oxy-Hb] in 11 out of 16 infants. These infants can
Discussion
Our study demonstrated that a localized area of the occipital cortex of newborn infants responded to brief visual stimulation and produced event-related changes in cerebral blood oxygenation, which was robustly detected as a focal increase in [oxy-Hb]. Since previous studies used block designs with long periods of stimulation and rest [9], [10], this is the first report on the event-related hemodynamics in newborns. Interestingly, the pattern of hemodynamic response is qualitatively similar to
Acknowledgments
We thank T. Hasegawa for assistance of the experiment.
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