Abnormal brain activation during working memory in children with prenatal exposure to drugs of abuse: The effects of methamphetamine, alcohol, and polydrug exposure

Department of Neurology, David Geffen School of Medicine at UCLA, University of California, Los Angeles, CA 90095-7332, USA.
NeuroImage (Impact Factor: 6.36). 10/2010; 54(4):3067-75. DOI: 10.1016/j.neuroimage.2010.10.072
Source: PubMed

ABSTRACT Structural and metabolic abnormalities in fronto-striatal structures have been reported in children with prenatal methamphetamine (MA) exposure. The current study was designed to quantify functional alterations to the fronto-striatal circuit in children with prenatal MA exposure using functional magnetic resonance imaging (fMRI). Because many women who use MA during pregnancy also use alcohol, a known teratogen, we examined 50 children (age range 7-15), 19 with prenatal MA exposure, 15 of whom had concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but no MA exposure (ALC group), and 18 unexposed controls (CON group). We hypothesized that MA exposed children would demonstrate abnormal brain activation during a visuospatial working memory (WM) "N-Back" task. As predicted, the MAA group showed less activation than the CON group in many brain areas, including the striatum and frontal lobe in the left hemisphere. The ALC group showed less activation than the MAA group in several regions, including the right striatum. We found an inverse correlation between performance and activity in the striatum in both the CON and MAA groups. However, this relationship was significant in the caudate of the CON group but not the MAA group, and in the putamen of the MAA group but not the CON group. These findings suggest that structural damage in the fronto-striatal circuit after prenatal MA exposure leads to decreased recruitment of this circuit during a WM challenge, and raise the possibility that a rewiring of cortico-striatal networks may occur in children with prenatal MA exposure.

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Available from: Lorna C Quandt, Jul 15, 2014
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    • "This effect was not observed in the alcohol-exposed group, suggesting that children with PME may have more severe cognitive outcomes than those exposed to alcohol alone. Given the prevalence of concomitant alcohol exposure in PME research, as indicated by the several of the studies reviewed here (Lu et al. 2009; Roussotte et al. 2011), such findings warrant further replication. "
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    ABSTRACT: Prenatal methamphetamine exposure (PME) is a significant problem in several parts of the world and poses important health risks for the developing fetus. Research on the short- and long-term outcomes of PME is scarce, however. Here, we summarize present knowledge on the cognitive and behavioral outcomes of PME, based on a review of the neuroimaging, neuropsychology, and neuroscience literature published in the past 15 years. Several studies have reported that the behavioral and cognitive sequelae of PME include broad deficits in the domains of attention, memory, and visual-motor integration. Knowledge regarding brain-behavior relationships is poor, however, in large part because imaging studies are rare. Hence, the effects of PME on developing neurocircuitry and brain architecture remain speculative, and are largely deductive. Some studies have implicated the dopamine-rich fronto-striatal pathways; however, cognitive deficits (e.g., impaired visual-motor integration) that should be associated with damage to those pathways are not manifested consistently across studies. We conclude by discussing challenges endemic to research on prenatal drug exposure, and argue that they may account for some of the inconsistencies in the extant research on PME. Studies confirming predicted brain-behavior relationships in PME, and exploring possible mechanisms underlying those relationships, are needed if neuroscience is to address the urgency of this growing public health problem.
    Metabolic Brain Disease 12/2013; 29(2). DOI:10.1007/s11011-013-9470-7 · 2.64 Impact Factor
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    • "Those clinical FASD face/brain studies that have been reported have shown facial anomalies to be significantly associated with smaller frontal, ventral diencephalon, and several subcortical brain structures (Astley et al. 2009; Roussotte et al. 2011). These findings are consistent with animal studies showing concurrent insult to the upper midface, eyes, and brain following alcohol exposure at discrete early stages of prenatal development (Sulik 2005; Parnell et al. 2009; Godin, Dehart, et al. 2010; Godin, O'Leary-Moore, et al. 2010; Roussotte et al. 2011). Furthermore, evidence from functional neuroimaging and lesion studies suggest that the right inferior frontal gyrus is heavily involved in cognitive control processes related to response inhibition and stimulus-driven attention (Aron et al. 2003, 2004, 2007; Westlye et al. 2011), which have been found impaired in FASD subjects (Fryer et al. 2007; Chlodo et al. 2010; Burden et al. 2011). "
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    ABSTRACT: Accumulating evidence from structural brain imaging studies on individuals with fetal alcohol spectrum disorder (FASD) has supported links between prenatal alcohol exposure and brain morphological deficits. Although global and regional volumetric reductions appear relatively robust, the effects of alcohol exposure on cortical thickness and relationships with facial dysmorphology are not yet known. The structural magnetic resonance imaging data from 69 children and adolescents with FASD and 58 nonexposed controls collected from 3 sites were examined using FreeSurfer to detect cortical thickness changes across the entire brain in FASD and their associations with facial dysmorphology. Controlling for brain size, subjects with FASD showed significantly thicker cortices than controls in several frontal, temporal, and parietal regions. Analyses conducted within site further revealed prominent group differences in left inferior frontal cortex within all 3 sites. In addition, increased inferior frontal thickness was significantly correlated with reduced palpebral fissure length. Consistent with previous reports, findings of this study are supportive of regional increases in cortical thickness serving as a biomarker for disrupted brain development in FASD. Furthermore, the significant associations between thickness and dysmorphic measures suggest that the severity of brain anomalies may be reflected by that of the face.
    Cerebral Cortex 07/2011; 22(5):1170-9. DOI:10.1093/cercor/bhr193 · 8.67 Impact Factor
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    ABSTRACT: Methamphetamine/polysubstance abuse in women of childbearing age is a major concern because of the potential long-term detrimental effects on the brain function of the fetus following in utero exposure. A battery of established tests, including the Wechsler Abbreviated Scale of Intelligence, Conners' Continuous Performance Test II, Behavioral Rating Inventory of Executive Function, the CMS Family Pictures and Dot Location tests, the Spatial Span test from the WISC-IV-Integrated, and a recently developed spatial learning and memory measure (Memory Island), was used to assess the effects of prenatal drug exposure on neurobehavioral performance. Participants were 7 to 9 year old children from similar socioeconomic backgrounds who either had (N=31) or had not (N=35) been exposed to methamphetamine/polysubstance during pregnancy. Compared to unexposed children, exposed children showed pronounced elevations (i.e. more problems) in parental ratings of executive function, including behavioral regulation and metacognition. Exposed children also exhibited subtle reductions in spatial performance in the Memory Island test. In contrast, IQ, Spatial Span, Family Pictures, Dot Location, and vigilance performance were unaffected by prenatal drug exposure history. Thus, children of women who reported using methamphetamine and other recreational drugs during pregnancy showed a selective profile of abnormalities in parentally rated executive function.
    Pharmacology Biochemistry and Behavior 02/2011; 98(3):432-9. DOI:10.1016/j.pbb.2011.02.013 · 2.78 Impact Factor
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