Functional activation in diverse regions of the developing brain of human infants
Introduction
It was believed that environmental perception is achieved via a hierarchical process in which the type of processing becomes more specialized when inputs pass through the sensory cortex to the association cortex and subsequently, to the prefrontal cortex. Such neural mechanisms have been extensively studied in visual perception (Desimone et al., 1984, Desimone et al., 1985, Tanaka, 1993, Ungerleider and Mishkin, 1982, Van Essen and Maunsell, 1983, Zeki, 1983a, Zeki, 1983b). Neuroimaging studies in human adults have exemplified retinotopic organization of the early visual region (Sereno et al., 1995, Tootell et al., 1998), functional specialization for processing of different visual features such as color, motion, and shape in the region surrounding the early visual region (McKeefry and Zeki, 1997, Tootell et al., 1995), and representation of objects in the higher sensory and association region (Grill-Spector et al., 1998, Kanwisher et al., 1996, Malach et al., 1995). Behavioral studies in human infants have shown that 3- and 4-month-old infants have sophisticated perceptual abilities (Atkinson, 2000, Bremner, 1994 for review). However, very limited information is available as to where and how such functional organization of the cerebral cortex emerges in the course of early development.
A clue to understanding the functional development of the cortex is to scrutinize its structural development (Rakic, 1995 as a review). Studies of the developing brain regarding myelination (Flechsig, 1920, Yakovlev and Lecours, 1967), synaptogenesis (Huttenlocher and Dabholkar, 1997, Huttenlocher and de Courten, 1987), and metabolic activity (Chiron et al., 1992, Chugani and Phelps, 1986, Chugani et al., 1987) tend to support a hierarchical view of cortical development in which maturation of the various cortical areas follows a certain chronological order. The earliest regions to mature are the primary sensory regions whereas protracted development occurs within association regions, and the prefrontal regions are the last to reach adult stages of development (Guillery, 2005 as a review). However, some studies with primates and humans challenge this sequential maturation in cortical ontogeny, exemplifying the production, peak in density, and elimination of synapses that occur concurrently in various cortical regions (Bourgeois and Rakic, 1993, Bourgeois et al., 1994, Rakic et al., 1986). In this way, although the time course and nature of structural and physiological changes during development have been described, very little is known about the functional aspects of development in the diverse cortical regions.
The present study is aimed at an understanding of the functional organization of the developing brain of young infants. A near-infrared spectroscopy (NIRS) is a neuroimaging tool used to assess the activation of selected locations of the cortex on the basis of measuring local cerebral blood oxygenation; changes in concentrations of oxygenated hemoglobin (oxy-Hb) and deoxygenated hemoglobin (deoxy-Hb) (Jöbsis, 1977). Typically, the increase in oxy-Hb and the decrease in deoxy-Hb have been assumed to reflect cortical activation (Obrig and Villringer, 2003, Villringer and Chance, 1997). Since the NIRS is a safe method and can be performed under fewer body constraints, this technique has been used to assess cortical activation in infants (Meek et al., 1998, Peña et al., 2003, Taga et al., 2003). In particular, some studies have used NIRS to demonstrate event-related hemodynamic changes in the early visual region of infants aged less than 4 months, while viewing visual stimuli (Csibra et al., 2004, Meek et al., 1998, Taga et al., 2003). Furthermore, dissociated hemodynamic responses to visual and audio-visual stimuli were reported in the early visual and auditory regions of infants aged 6–9 months (Bortfeld et al., 2007). However, it is not well understood whether or not the association and prefrontal regions show functional activations differentiated from those of the early sensory regions in early infancy. Thus, multichannel NIRS was used to detect spatiotemporal hemodynamic responses in relation to the functional activation of the cortex, including the sensory, association, and prefrontal regions, in 3-month-old infants when they viewed video images on the display (Fig. 1A).
We prepared a video image of colorful moving mobiles, which has also been used in a behavioral study with infants (Watanabe and Taga, 2006). The mobiles comprised some colored objects that moved irregularly with sounds of ringing bells. Since there is evidence that infants aged 3 and 4 months process various features and extract objects per se from the complex visual scene (Bertenthal et al., 1987, Braddick et al., 1983, Braddick et al., 1986, Bushnell and Roder, 1985, Fox and McDaniels, 1982, Ghim, 1990, Hayne et al., 1987, Johnson and Johnson, 2000, Kellman and Spelke, 1983, Otsuka et al., 2004, Taga et al., 2002; see also Atkinson, 2000 for a review), we anticipated that functional activations are observed not only in the early visual region but also in the higher visual region, the association regions of the occipitotemporal cortex and the prefrontal region when infants looked at the mobile objects. In another stimulus condition, to distinguish between functional activation of the early visual regions and that of other regions, we replaced the visual image of mobile objects with black-and-white checkerboard pattern reversals, which has been routinely used to identify activation of the early visual regions in adults (Fox et al., 1987, Kraft et al., 2005, Sereno et al., 1995, Tootell et al., 1998). The sounds of ringing bells in the video image of mobile objects were also presented in video images of checkerboard pattern reversals as we expected that the temporal auditory region might produce equivalent activations in response to sounds under both the visual conditions. To examine the functional activation in diverse regions of the infant cortex, we observed hemodynamic responses over the occipital and prefrontal cortices in Experiment 1 and those over the occipital and temporal cortices in Experiment 2.
Section snippets
Participants
Thirty-five full-term healthy infants participated in Experiment 1 (16 girls and 19 boys, mean age 110.8 days, age range 93–125 days). We studied 52 additional infants but excluded them from the sample due to the following reasons: refusal of probe placement during the preparation of the measurement (n = 5), head movements that produced large motion artifacts in the signals (n = 34), crying or fussiness during the measurement (n = 6), drowsiness during the measurement (n = 5), or failure to obtain
Experiment 1
To quantify event-related hemodynamic responses to the moving mobile and the checkerboard pattern reversals, we investigated the signal change patterns at 48 measurement channels covered over the occipital and prefrontal cortices under each stimulus condition (Fig. 2A). Figs. 2B and C present the time courses of oxy-Hb and deoxy-Hb signals averaged over all 35 infants for each stimulus condition, respectively. The obtained data indicates that most of the channels demonstrated an event-related
Postnatal development of functionally diverse cortical regions
The present study revealed that 3-month-old infants generated differentiated activations across the diverse regions of the cortex when they viewed video images of the mobile objects and checkerboard pattern reversals, as shown in Fig. 8.
The first crucial point in our study with 3-month-old infants was the dissociated functional activation observed between the early visual region and the higher sensory and association region; the equivalent activation in the early visual region regardless of the
Acknowledgments
The authors thank Kayo Asakawa for her assistance with data acquisition, and Takashi Ishizuka for developing the probes for NIRS used for measurement in the infants. We also thank the parents and infants who participated in this study.
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2016, Progress in Brain ResearchCitation Excerpt :Other groups using NIRS have reported fully inverted responses with increases in HbR and decreases in HbO and HbT in response to visual stimulation (Kusaka et al., 2004) suggesting a blood volume decrease in response to stimulation (Fig. 1C). Some groups using both NIRS and fMRI have identified adult-like responses to visual stimulation in early postnatal populations (Anderson et al., 2001; Arichi et al., 2010, 2012; Born et al., 1998, 2000; Hoshi and Tamura, 1993; Karen et al., 2008; Liao et al., 2010; Taga et al., 2003; Watanabe et al., 2008). Notably, however, groups examining these responses via NIRS who reported increases in HbO accompanied by decreases in HbR noted significantly more variability in their HbR responses than HbO responses—and that these responses were occasionally increases (Hoshi et al., 2000; Liao et al., 2010; Taga et al., 2003).