A Functional Magnetic Resonance Imaging Study of Spatial Working Memory in Children with Prenatal Alcohol Exposure: Contribution of Familial History of Alcohol Use Disorders

Abstract

Background Heavy prenatal alcohol exposure leads to widespread cognitive deficits, including problems with spatial working memory (SWM). Neuroimaging studies report structural and functional abnormalities in FASD, but interpretations may be complicated by the co-occurrence of a family history of alcoholism. Since, this history is also linked to cognitive deficits and brain abnormalities, it is difficult to determine the extent to which deficits are unique to prenatal alcohol exposure. Methods Age-matched subjects selected from two neuroimaging studies, underwent functional imaging while engaging in a task assessing memory for spatial locations relative to a vigilance condition assessing attention. Pairwise comparisons were made for the following three groups: children with histories of heavy prenatal alcohol exposure (ALC, n=18); those with no prenatal alcohol exposure, but a confirmed family history of alcoholism (FHP, n=18); and non-exposed, family history negative controls (CON, n=17). Results Relative to CON and FHP, the ALC group showed increased BOLD response in the left middle and superior frontal gyri for the spatial working memory condition relative to the vigilance condition (SWM contrast). Additionally, the ALC group showed unique BOLD response increases in the left lingual gyrus and right middle frontal gyrus relative to CON, and left cuneus and precuneus relative to FHP. Both ALC and FHP showed greater activation compared to CON in the lentiform nucleus and insular region. Conclusions These results confirm previous studies suggesting SWM deficits in FASD. Differences between the ALC group and the CON and FHP groups suggest the left middle and superior frontal region may be specifically affected in alcohol-exposed children. Conversely, differences from the CON group in the lentiform nucleus and insular region for the ALC and FHP groups may indicate this region is associated with family history of alcoholism rather than specifically with prenatal alcohol exposure.

Cerebral Magnetic Resonance Imaging in Children With Prenatal Drug Exposure

“…Less efficient task related networks or compensation for other less active regions have been suggested as an explanation to increased activation in alcohol-exposed children. 175,190 Similar compensatory mechanisms could possibly explain our finding of increased prefrontal activation in the opioid-exposed group. On the other hand, several studies have reported working memory deficits with corresponding lower brain activation including prefrontal areas in groups of children with prenatal exposure to alcohol and methamphetamine.…”

“…145,175,189,190 In these studies varying degrees of behavioral differences between alcohol-exposed children and unexposed controls have been found. Less efficient task related networks or compensation for other less active regions have been suggested as an explanation to increased activation in alcohol-exposed children.…”

Human Imaging Studies of Brain Circuitry Disrupted by Alcoholism

“…In addition to examining differences in task-activated patterns between alcoholics and controls, fMRI paradigms have been useful in detecting group differences related to preexisting conditions in and predisposing genetic factors to alcoholism occurring in alcoholism (e.g., Cardenas et al, 2005;Claus, Ewing, Filbey, Sabbineni, & Hutchison, 2011;Cservenka & Nagel, 2012;Hill, Terwilliger, & McDermott, 2012;Jamadar et al, 2012;Kareken et al, 2010;Norman et al, 2013;Schuckit et al, 2011;Silveri, Rogowska, McCaffrey, & Yurgelun-Todd, 2011;Villafuerte et al, 2012;Weiland et al, 2013;Wetherill et al, 2012). Regarding responsivity to alcohol cues (Schacht, Anton, & Myrick, 2013;Squeglia, Jacobus, & Tapert, 2014), one fMRI study used a passive viewing paradigm of positive, negative, or neutral words to examine high (vulnerable)-and low (resilient)-drinking late adolescents of alcoholic parents (Heitzeg, Nigg, Yau, Zubieta, & Zucker, 2008).…”

Review of Current Neuroimaging Studies of the Effects of Prenatal Drug Exposure: Brain Structure and Function

“…The impact of prenatal alcohol exposure can be dissociated from other potential explanatory variables. When examined in relation to family history of alcohol use disorders, prenatal alcohol exposure independently predicted increased activation in left middle and superior frontal brain regions [137]. In a direct comparison of adolescents with prenatal alcohol exposure or ADHD, behavioral profiles were similar but the two groups showed differences in how cortical brain regions were recruited for spatial working memory [138].…”