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    • The present study has several notable strengths

    2018-11-03

    The present study has several notable strengths, including focus on a young age range during which a known developmental transition occurs in memory ability (i.e., 4–6 years). To achieve this, we related resting-state functional connectivity measures to performance on an episodic memory task outside the scanner. This approach allowed for the examination of relations between hippocampal function and behavior in young children. In addition, great attention was paid to quality control in terms of acquiring data with very minimal artifact from both age groups. This was also coupled with adhering to current recommendations for analysis, including those designed to address the influence of motion (e.g., scrubbing, Power et al., 2012), 24 motion parameters (Friston et al., 1996) and multiple nuisance regressors (components from CSF and WM masks) to account for physiological noise (see Behzadi et al., 2007). Our analyses revealed there were no significant differences in motion between age groups and that motion was not correlated with either performance on the memory task nor age. Therefore, observed effects are likely not due to these nuisance variables. Despite these strengths, there are also some limitations that should be noted. First, the present analyses only included a subset of children tested. Thus, results are conservative and can only be generalized to children similar to our sample who are able to undergo and complete fMRI testing. Second, given the sample size and distribution of gender within the age groups, differences between genders could not be addressed. This is an important direction for future research as previous research suggests a gender effect on hippocampal volume in children and adolescents (e.g., Gogtay et al., 2006). Third, although use of rs-fcMRI allowed for the examination of hippocampal function in young children, these findings would be strengthened if they sodium butyrate were replicated using a traditional task-based fMRI paradigm in conjunction with resting-state analyses. Finally, longitudinal studies would be necessary to confirm that these differential relations between episodic memory performance and hippocampal connectivity between 4 and 6 years of age represent a developmental shift. Although challenging, efforts to collect task-based and longitudinal fMRI data from children as young as 4 years of age are underway in our lab. This study is the first, to our knowledge, to address relations between functional development of the hippocampus and episodic memory during early childhood. Taken together, the present findings are consistent with an interactive specialization framework, which proposes that brain development is not a unidirectional maturational process, but rather results from complex and dynamic interactions between brain regions (Johnson, 2001). Specifically, our results suggest that during early childhood the hippocampus becomes progressively (1) integrated with cortical regions that are part of the hippocampal memory network in adults and (2) segregated from regions unrelated to memory in adults, both of which result in age-related improvements in episodic memory ability. This pattern has also been observed in empirical studies examining anatomical connections between MTL and ITG early in life in macaques that then disappear by adulthood, which suggests that “extra” connections may be useful early in life but not later (e.g., Webster et al., 1991). This pattern is also supported by findings from other rs-fcMRI studies in developmental samples (see Uddin et al., 2010 for review). These results provide (1) initial insight into neuroanatomical correlates of developmental change in behavior during a relatively unexplored, yet critical, age window, (2) possible mechanisms underlying variability in episodic memory ability during early childhood, and (3) typical development of the structural and functional architecture of the brain network supporting memory. Data that speak to these issues are important as they not only increase our understanding of the development of brain networks supporting behavior, but also have strong relevance to public health as they can potentially be used to develop interventions targeting memory early in life when impact may be largest (Nelson, 2000; Ramey and Ramey, 1998). Finally, results from the present investigation fill a significant gap in the literature between what is known regarding memory processes early vs later in life, which is essential for a complete understanding of memory ability to be achieved.