Prenatal exposure to alcohol can result in neuroanatomical and neurocognitive deficits. High-resolution magnetic resonance imaging, surface-based image analytic methods, and neuropsychological measures were used to characterize the cerebellar vermis and to evaluate potential cognitive correlates of vermal morphology in 21 children and adolescents with prenatal alcohol exposure and 21 normally developing individuals. Alcohol-exposed individuals showed statistically significant reductions in the midline sagittal areas of the anterior vermis and posterior-inferior vermis, and significant displacement of the anterior and posterior-inferior vermal regions. Anterior vermal dysmorphology was negatively correlated with verbal learning and memory performance within the alcohol-exposed group. These observations expand on previous reports of cerebellar abnormalities in prenatal alcohol exposure, in that they localize the specific pattern of cerebellar vermal dysmorphology.

Fluid reasoning is the cornerstone of human cognition, both during development and in adulthood. Despite this, the neural mechanisms underlying the development of fluid reasoning are largely unknown. In this review, we provide an overview of this important cognitive ability, the method of measurement, its changes over the childhood and adolescence of an individual, and its underlying neurobiological underpinnings. We review important findings from psychometric, cognitive, and neuroscientific literatures, and outline important future directions for this interdisciplinary research.

We examined functional MRI activation patterns corresponding to verbal paired associate learning in a group of 11 children with heavy prenatal alcohol exposure compared with 16 typically developing children. Among the typically developing children, prominent activation was observed in the left medial temporal lobe, left dorsal frontal lobe and bilateral posterior temporal cortices during learning and recall. Analyses revealed significantly less activation in left medial and posterior temporal regions and significantly more activation in right dorsal frontal cortex in the alcohol-exposed children relative to controls, even when group differences in memory test performance were statistically controlled. These results may indicate an increased reliance on frontal memory systems in the children with heavy prenatal alcohol exposure, perhaps compensating for dysfunctional medial temporal memory systems. Our findings are consistent with neuropsychological and structural imaging studies, and provide the first evidence for brain activation abnormalities, independent of group performance differences, during verbal learning and recall in children with heavy prenatal alcohol exposure.

Development of working memory (WM) aptitude parallels structural changes in the frontal-parietal association cortices important for performance within this cognitive domain. The cerebellum has been proposed to function in support of the postulated phonological loop component of verbal WM, and along with frontal and parietal cortices, has been shown to exhibit linear WM load-dependent activation in adults. It is not known if these kinds of WM load-dependent relationships exist for cerebro-cerebellar networks in developmental populations, and whether there are age-related changes in the nature of load-dependency between childhood, adolescence, and adulthood. The present study used fMRI and a verbal Sternberg WM task with three load levels to investigate developmental changes in WM load-dependent cerebro-cerebellar activation in a sample of 30 children, adolescents, and young adults between the ages of 7 and 28. The neural substrates of linear load-dependency were found to change with age. Among adolescents and adults, frontal, parietal and cerebellar regions showed linear load-dependency, or increasing activation under conditions of increasing WM load. In contrast, children recruited only left ventral prefrontal cortex in response to increasing WM load. These results demonstrate that, while children, adolescents, and young adults activate similar cerebro-cerebellar verbal working memory networks, the extent to which they rely on parietal and cerebellar regions in response to increasing task difficulty changes significantly between childhood and adolescence.

Relational reasoning, or the ability to identify and consider relationships between multiple mental representations, is a fundamental component of high-level cognition (Robin & Holyoak, 1995). The capacity to reason with relations enables abstract thought, and may be at the core of what makes human cognition unique (Penn et al., 2008). This capacity improves throughout childhood and adolescence (Ferrer et al., 2009). Here, we sought to better understand the neural mechanisms that support its emergence. We have hypothesized previously, based on fMRI research in adults, that 1) inferior parietal lobe (IPL) plays a central role in representing relationships between mental representations (1st-order relations), and 2) rostrolateral prefrontal cortex (RLPFC) integrates inputs from IPL to build 2nd-order relational structures (i.e., relations between relations). In the present study, we examined fMRI and cortical thickness data from 85 children and adolescents (ages 6–18). Participants performed a relational matching task in which they viewed arrays of four visual stimuli, and determined whether two stimuli shared a particular feature (a 1st-order relational judgment), or whether two pairs of stimuli matched according to the same feature (a 2nd-order relational judgment). FMRI results provide evidence for increased functional selectivity across ages 6 to 18 in RLPFC and IPL. Specifically, young children engaged RLPFC and IPL indiscriminately for 1st-order and 2nd-order relational judgments, and activation for 1st-order relations diminished with age while activation for 2nd-order relations stayed elevated. Examination of cortical thickness revealed that increased functional selectivity in RLPFC could be partly accounted for by cortical thinning in IPL.

Dynamic changes in brain structure, activation, and cognitive abilities co-occur during development, but little is known about how changes in brain structure relate to changes in cognitive function or brain activity. By using cortical pattern matching techniques to correlate cortical gray matter thickness and functional brain activity over the entire brain surface in 24 typically developing children, we integrated structural and functional magnetic resonance imaging data with cognitive test scores to identify correlates of mature performance during orthographic processing. Fast-naming individuals activated the right fronto-parietal attention network in response to novel fonts more than slow-naming individuals, and increased activation of this network was correlated with more mature brain morphology in the same fronto-parietal region. These relationships remained even after effects of age or general cognitive ability were statistically controlled. These results localized cortical regions where mature morphology corresponds to mature patterns of activation, and may suggest a role for experience in mediating brain structure-activation relationships.

This study evaluated the neural basis of verbal working memory (WM) function in a group of 20 children and adolescents with fetal alcohol spectrum disorders (FASDs) and 20 typically developing comparison participants using functional magnetic resonance imaging (fMRI). Both groups showed prominent activation in the frontal-parietal-cerebellar network known to be important for verbal WM. Despite equivalent behavioral performance between groups, alcoholexposed individuals showed increased activation relative to typically developing individuals in left dorsal frontal and left inferior parietal cortices, and bilateral posterior temporal regions during verbal WM. These effects remained even when group differences on IQ were statistically controlled. This pattern of increased activation coupled with equivalent behavioral performance between groups suggests that individuals with FASD recruit a more extensive network of brain regions during verbal WM relative to typically developing individuals. These findings may suggest that frontal-parietal processing during verbal WM is less efficient in alcohol-exposed individuals.

Objective-Efforts to understand specific effects of prenatal methamphetamine exposure on cognitive processing are hampered by high rates of concomitant alcohol use during pregnancy. We examined whether neurocognitive systems differed among children with differing prenatal teratogenic exposures when they engaged in a verbal memory task.Patients and Methods-Participants (7-15 years old) engaged in a verbal paired associate learning task while undergoing functional magnetic resonance imaging. The MA group included 14 children with prenatal methamphetamine exposure, 12 of whom had concomitant alcohol exposure. They were compared to 9 children with prenatal alcohol but not methamphetamine exposure (ALC) and 20 unexposed controls (CON). Groups did not differ in age, gender, or socioeconomic status. Participants' IQ and verbal learning performance were measured using standardized instruments.Results-The MA group activated more diffuse brain regions, including bilateral medial temporal structures known to be important for memory, than both the ALC and the CON groups. These group differences remained after IQ was covaried. More activation in medial temporal structures by the MA group compared to the ALC group cannot be explained by performance differences because both groups performed at similar levels on the verbal memory task.Conclusions-More diffuse activation in the MA group during verbal memory may reflect recruitment of compensatory systems to support a weak verbal memory network. Differences in activation patterns between the MA and ALC groups suggest that prenatal MA exposure influences the development of the verbal memory system above and beyond effects of prenatal alcohol exposure. The effects of prenatal exposure to methamphetamine on neurocognitive skills are not well understood. Chang and colleagues documented lower scores on measures of verbal memory, spatial memory, attention, and visual motor integration in methamphetamine-exposed children compared to unexposed participants (1). However, the largest reported sample of prenatal MA exposure reported that 49% of participating methamphetamine users also used alcohol during pregnancy, and only 10% used methamphetamine alone (2). These high rates of co-exposure to alcohol during pregnancy render it difficult to separate effects of methamphetamine exposure from alcohol exposure.Heavy prenatal alcohol exposure is known to detrimentally affect verbal memory (3). Verbal memory encompasses learning and recall of verbal information from long-term storage. Verbal learning is an important cognitive skill because it underlies basic academic skills such as vocabulary acquisition. The verbal nature of classroom instruction implicates that deficits in verbal learning may detrimentally influence achievement in other areas such as math and science. Three independent research groups have shown that children with prenatal exposure to alcohol perform more poorly on both immediate and delayed recall of verbal information compared to unexposed participants (4-6). All thre...