AP1903 cost The present study is the first to

The present study is the first to investigate whether increased cerebral blood flow (CBF) in the hippocampus is associated with aerobic fitness during childhood. This hypothesis cannot be directly tested with traditional BOLD techniques, given that BOLD can change depending on a number of factors related to local metabolism and neural function, including blood volume, perfusion, blood velocity, and cerebral metabolic rate of oxygen (Hoge et al., 1999). Hence, here we use arterial spin labeling (ASL) perfusion MRI to provide a quantitative measure of blood flow and a more direct link to local neuronal activity (Alsop and Detre, 1996). Specifically, an ASL signal arises from the delivery of magnetically tagged arterial water into an imaging slice of interest, where the blood water exchanges in the tissue. The output measure of CBF, or the blood supply to a AP1903 cost area in a given time (mL/100g/min), is known to provide information regarding how the brain meets and regulates its metabolic demands via the delivery of metabolites, oxygen and nutrients to activated neurons (Hales et al., 2014; Sokoloff et al., 1977) (see ASL Scan Acquisition section in the Method for more information about ASL). We specifically focused on CBF in the hippocampus, in view of converging evidence that demonstrates positive physical activity-related brain changes in the hippocampus in rodents and humans across the lifespan (Bugg and Head, 2011; Burdette et al., 2010; Chaddock et al., 2010a; Erickson et al., 2009, 2011; Honea et al., 2009; Pereira et al., 2007; van Praag et al., 1999b). For example, voluntary wheel running in rodents has been found to enhance learning and memory (van Praag et al., 2005) as well as induce angiogenesis and increased vascular density (Black et al., 1990; Clark et al., 2009; Kleim et al., 2002; Rhyu et al., 2010), and the growth of new neurons in the hippocampus (van Praag et al., 1999a). In humans, physical activity and aerobic fitness are associated with a greater number of small-caliber vessels (Bullitt et al., 2009), increased cerebral blood volume in the hippocampus in middle-aged adults (Pereira et al., 2007; age 21–45) and increased hippocampal blood flow in older adults (Burdette et al., 2010). Cognitively, increased hippocampal CBF has been linked to higher task performance on a spatial memory task in middle-aged and older adults (Heo et al., 2010; Pereira et al., 2007). It is possible that these findings extend to children, such that aerobic fitness relates to greater perfusion in the hippocampus, which may suggest improved microcirculation, cerebral vasculature, and function. We hypothesized that aerobic fitness in 7- to 9-year-old preadolescent children would be associated with increased resting CBF in the hippocampus. We explored anterior and posterior subsections of the hippocampus to examine whether aerobic fitness had selective effects on hippocampal blood flow, and to investigate distinct contributions of different anatomical regions within the hippocampus given that functional distinctions have been described along the anterior/posterior axis of the hippocampus (i.e., spatial versus relational processing) (Giovanello et al., 2009; Sperling et al., 2003). To provide additional specificity to a fitness-CBF relationship, we also measured CBF in the brainstem as a control region. Like the hippocampus, the brainstem is a subcortical structure in the midbrain included in our ASL slice acquisition, yet this region has not been found to relate to aerobic fitness. Thus, we did not predict an association between aerobic fitness and brainstem CBF. Given these hypotheses, the present study will provide insight into a potential cerebrovascular mechanism by which aerobic fitness enhances brain health in children.
Method
Results Younger age was associated with greater CBF in the hippocampus (r=−0.393; p=0.01) and brainstem (r=−0.289; p=0.013), and aerobic fitness was associated with sex such that females had lower fitness scores than males (r=0.311, p=0.007). Thus, we included age and sex as covariates in the regression model. Despite no significant correlations between hippocampal CBF and hippocampal volume (r=0.004, p>0.05), or brainstem CBF and brainstem volume (r=−0.015, p>0.05), we also included volume as a covariate to confirm that blood flow effects were independent of the size of the brain region.