br Discussion As numerous previous
Discussion As numerous previous studies (Fransson et al., 2007; Gao et al., 2009b; Smyser et al., 2010; Fransson et al., 2011; Gao et al., 2011; Smyser et al., 2011; Alcauter et al., 2013; Gao et al., 2013; Alcauter et al., 2014; Gao et al., 2014a; Gao et al., 2014b; Gao et al., 2014) have delineated the synchronization process of different functional networks during infancy based on correlation measures of BOLD signals, one of the fundamental properties of BOLD signal, its frequency distribution, has been largely ignored. However, BOLD frequency has been consistently linked to both normal (Sambataro et al., 2010; Balsters et al., 2013; Palacios et al., 2013) and abnormal cognitive functioning (Zang et al., 2007; Hoptman et al., 2010; Liang et al., 2014; Yu et al., 2014) thus investigations into the frequency property of BOLD signals during infancy are highly deserved. Such an endeavor would likely provide us new insights beyond temporal synchronization of different functional networks and further the exploration of the niclosamide basis for the emergence of different cognitive functions during this critical period of brain development. In this study, by systematically analyzing the PSD of the whole brain as well as nine specialized functional networks, our results revealed a clear rightward shift of the peak-frequency of spontaneous BOLD signal during the first year of life, resulting in an adult-like frequency profile. Moreover, the spectral power of the peak-frequency showed positive correlations with cognitive scores in 1-year-olds, stressing the relevance of such frequencies for cognitive development. To our knowledge, this is the first study directly delineating the early development of the frequency properties of the spontaneous BOLD signals and their cognitive correlations during infancy. The possible neurophysiological underpinnings and developmental implications are discussed below. The rightward shift of the peak-frequency and the increased spectral power in the frequencies higher than 0.1Hz evidence a general increase in the frequency of spontaneous BOLD fluctuations during the first year of life. This increment in frequency likely results from more efficient signal transmission, which is in line with the observed fast myelination (Flechsig, 1901), dendritic elaboration (Petanjek et al., 2008; Freeman, 2010), synaptogenesis (Rakic et al., 1986; Huttenlocher and Dabholkar, 1997; Elston et al., 2009), and astrocyte proliferation (Bandeira et al., 2009; Ge et al., 2012), which all show their most significant development during the first year after birth. These structural events likely collectively promote faster neuronal signaling and/or neurovascular coupling, thus enhancing the frequency of the observed BOLD signal. Such an increase in frequency is also consistent with the observed significant increase in glucose metabolism during the first year (Chugani et al., 1987). The non-linear developmental trend of the frequency property of the spontaneous BOLD signal is in line with numerous previous studies showing the most dramatic development in different functional networks (Gao et al., 2013; Alcauter et al., 2014; Gao et al., 2014a; Gao et al., 2014) and in system efficiency properties (Gao et al., 2011) during the first year. The peak-frequency reported in adults is between 0.015 and 0.02Hz (Biswal et al., 1995; He et al., 2014) while the peak-frequency is 0.0278Hz for 1- and 2-year-olds, suggesting a possible overshooting of peak-frequency during infancy. Early overshooting and subsequent refinement may represent a universal phenomenon for different developmental events (Tau and Peterson, 2010). The frequency overshooting observed in this study may be underpinned by the initial overproduction of the neurophysiological facilitators of signal-transmission and neurovascular coupling such as synaptogenesis, axons, and astrocytes (Rakic et al., 1986; Chugani et al., 1987; Elston et al., 2009; Petanjek et al., 2011). In contrast, the subsequent pruning of different elements during later development (Rakic et al., 1986; Huttenlocher and Dabholkar, 1997; Elston et al., 2009; Tau and Peterson, 2010; Petanjek et al., 2011) may contribute to the gradual decrement of peak-frequency to its observed adult level. Consistently, Allen et al. (2011) observed a decreasing trend of the low-frequency power from 12 years of age to adulthood. Collectively, findings in this study support that an adult-like frequency profile of spontaneous BOLD fluctuations is established by 1 year of age but with a potential overshooting in the peak-frequency.