Andrea D. Spadoni

Initiating Moderate to Heavy Alcohol Use Predicts Changes in Neuropsychological Functioning for Adolescent Girls and Boys

This study prospectively examines the influence of alcohol on neuropsychological functioning in boys and girls characterized prior to initiating drinking (N = 76, ages 12-14). Adolescents who transitioned into heavy (n = 25; 11 girls, 14 boys) or moderate (n = 11; 2 girls, 9 boys) drinking were compared with matched controls who remained nonusers throughout the approximately 3-year follow-up period (N = 40; 16 girls, 24 boys). For girls, more past year drinking days predicted a greater reduction in visuospatial task performance from baseline to follow-up, above and beyond performance on equivalent measures at baseline (R2Delta = 10%, p < .05), particularly on tests of visuospatial memory (R2Delta = 8%, p < .05). For boys, a tendency was seen for more past year hangover symptoms to predict worsened sustained attention (R2Delta = 7%, p < .05). These preliminary longitudinal findings suggest that initiating moderately heavy alcohol use and incurring hangover during adolescence may adversely influence neurocognitive functioning. Neurocognitive deficits linked to heavy drinking during this critical developmental period may lead to direct and indirect changes in neuromaturational course, with effects that would extend into adulthood.

Neural activation during inhibition predicts initiation of substance use in adolescence.

BACKGROUND Problems inhibiting non-adaptive behaviors have been linked to an increased risk for substance use and other risk taking behaviors in adolescence. This study examines the hypothesis that abnormalities in neural activation during inhibition in early adolescence may predict subsequent substance involvement. METHODS Thirty eight adolescents from local area middle schools, ages 12-14, with very limited histories of substance use, underwent functional magnetic resonance imaging (fMRI) as they performed a go/no-go task of response inhibition and response selection. Adolescents and their parents were then followed annually with interviews covering substance use and other behaviors. Based on follow-up data, youth were classified as transitioning to heavy use of alcohol (TU; n=21), or as healthy controls (CON; n=17). RESULTS At baseline, prior to the onset of use, youth who later transitioned into heavy use of alcohol showed significantly less activation than those who went on to remain non to minimal users throughout adolescence. Activation reductions in TU at baseline were seen on no-go trials in 12 brain regions, including right inferior frontal gyrus, left dorsal and medial frontal areas, bilateral motor cortex, cingulate gyrus, left putamen, bilateral middle temporal gyri, and bilateral inferior parietal lobules (corrected p<.01, each cluster ≥32 contiguous voxels). CONCLUSIONS These results support the hypothesis that less neural activity during response inhibition demands predicts future involvement with problem behaviors such as alcohol and other substance use.

Neuroimaging and fetal alcohol spectrum disorders.

Heavy prenatal alcohol exposure causes permanent structural alterations to the brain and can lead to numerous cognitive and behavioral outcomes. Consistent with many of the neuropsychological and behavioral deficits that have been reported, neuroimaging studies reveal a pattern of structural abnormalities associated with prenatal alcohol exposure. This chapter systematically reviews structural anomalies by brain region, identifying cognitive and behavioral correlates when relevant. The consensus shows that in addition to the overall reduction of brain size, prominent brain shape abnormalities have been observed, with narrowing in the parietal region and reduced brain growth in portions of the frontal lobe. Commensurating with these anomalies, volumetric and tissue density findings cite disproportionate reductions in the parietal lobe, cerebellar vermis, corpus callosum, and the caudate nucleus, suggesting that certain areas of the brain may be especially vulnerable to prenatal alcohol exposure. In sum, neuroimaging techniques have greatly advanced our understanding of brain-behavior relationships in fetal alcohol spectrum disorders (FASD), and hopefully will lead to improved diagnosis and treatment options for those affected by prenatal exposure to alcohol.

Characterization of White Matter Microstructure in Fetal Alcohol Spectrum Disorders

BACKGROUND Exposure to alcohol during gestation is associated with CNS alterations, cognitive deficits, and behavior problems. This study investigated microstructural aspects of putative white matter abnormalities following prenatal alcohol exposure. METHODS Diffusion tensor imaging was used to assess white matter microstructure in 27 youth (age range: 8 to 18 years) with (n = 15) and without (n = 12) histories of heavy prenatal alcohol exposure. Voxelwise analyses, corrected for multiple comparisons, compared fractional anisotropy (FA) and mean diffusivity (MD) between groups, throughout the cerebrum. RESULTS Prenatal alcohol exposure was associated with low FA in multiple cerebral areas, including the body of the corpus callosum and white matter innervating bilateral medial frontal and occipital lobes. Fewer between-group differences in MD were observed. CONCLUSIONS These data provide an account of cerebral white matter microstructural integrity in fetal alcohol spectrum disorders and support extant literature showing that white matter is a target of alcohol teratogenesis. The white matter anomalies characterized in this study may relate to the neurobehavioral sequelae associated with gestational alcohol exposure, especially in areas of executive dysfunction and visual processing deficits.

Microstructural integrity of the corpus callosum linked with neuropsychological performance in adolescents

BACKGROUND Diffusion tensor imaging (DTI) has revealed microstructural aspects of adolescent brain development, the cognitive correlates of which remain relatively uncharacterized. METHODS DTI was used to assess white matter microstructure in 18 typically developing adolescents (ages 16-18). Fractional anisotropy (FA) and mean diffusion (MD) were evaluated within the splenium and body of the corpus callosum in relation to cognitive performance. RESULTS Visuospatial construction abilities were associated with white matter integrity in both the splenium and body of the corpus callosum, while only splenium integrity was associated with language and psychomotor function. CONCLUSION Results suggest that, for typically developing adolescents, white matter coherence positively relates to visuospatial, psychomotor, and language skills. These findings may have implications for the cognitive functioning of clinical populations in which typical white matter development is altered.

BOLD Response During Spatial Working Memory in Youth With Heavy Prenatal Alcohol Exposure

BACKGROUND Prenatal alcohol exposure has been consistently linked to neurocognitive deficits and structural brain abnormalities in affected individuals. Structural brain abnormalities observed in regions supporting spatial working memory (SWM) may contribute to observed deficits in visuospatial functioning in youth with fetal alcohol spectrum disorders (FASDs). METHODS We used functional magnetic resonance imaging (fMRI) to assess the blood oxygen level dependent (BOLD) response in alcohol-exposed individuals during a SWM task. There were 22 young subjects (aged 10-18 years) with documented histories of heavy prenatal alcohol exposure (ALC, n = 10), and age- and sex-matched controls (CON, n = 12). Subjects performed a SWM task during fMRI that alternated between 2-back location matching (SWM) and simple attention (vigilance) conditions. RESULTS Groups did not differ on task accuracy or reaction time to the SWM condition, although CON subjects had faster reaction times during the vigilance condition (617 millisecond vs. 684 millisecond, p = 0.03). Both groups showed similar overall patterns of activation to the SWM condition in expected regions encompassing bilateral dorsolateral prefrontal lobes and parietal areas. However, ALC subjects showed greater BOLD response to the demands of the SWM relative to the vigilance condition in frontal, insular, superior, and middle temporal, occipital, and subcortical regions. CON youth evidenced less increased brain activation to the SWM relative to the vigilance task in these areas (p < 0.05, clusters > 1,664 microl). These differences remained significant after including Full Scale IQ as a covariate. Similar qualitative results were obtained after subjects taking stimulant medication were excluded from the analysis. CONCLUSIONS In the context of equivalent performance to a SWM task, the current results suggest that widespread increases in BOLD response in youth with FASDs could either indicate decreased efficiency of relevant brain networks, or serve as a compensatory mechanism for deficiency at neural and/or cognitive levels. In context of existing fMRI evidence of heightened prefrontal activation in response to verbal working memory and inhibition demands, the present findings may indicate that frontal structures are taxed to a greater degree during cognitive demands in individuals with FASDs.

Effects of family history of alcohol use disorders on spatial working memory BOLD response in adolescents.

BACKGROUND A positive family history (FH) of alcohol use disorders (AUD) has been linked to increased risk for the development of AUD, and neurocognitive factors have been postulated as important underlying mechanisms of familial alcoholism transmission. METHODS We used functional magnetic resonance imaging (fMRI) during a spatial working memory (SWM) and vigilance paradigm to investigate potential neurodevelopmental differences linked to familial density of AUD in 72 adolescents aged 12 to 14 years. RESULTS Youth with denser family histories of AUD showed less activation during a simple vigilance condition relative to SWM in cingulate and medial frontal gyri (beta = 0.28, p = 0.03), and a trend for more relative activity during rest (beta = -0.25, p = 0.07) in this cluster. CONCLUSIONS Youth with greater familial densities of AUD may be less successful at modulating activity of the default network, potentially indicating a greater propensity for task-independent thought or reduced inhibition of task-irrelevant processing. Failure to moderate activation of the default network may have implications for cognitive efficiency and goal directed behavior in youth with dense FH. Further, aberrant activation in cingulate regions may be linked to genetic variation in GABA receptor units, suggesting a useful endophenotype for risk associated with alcohol dependence.

Hippocampal Volumes in Adolescents with and without a Family History of Alcoholism

Background and Objectives: The hippocampus may be vulnerable to the effects of heavy alcohol use during adolescence, which is a time of continued neurodevelopment. However, differences in hippocampal volume may be due to risk factors such as a family history (FH) of alcoholism. We examined hippocampal volumes in youth with and without a FH of alcoholism prior to the initiation of alcohol use. Methods: Participants were demographically matched adolescents (aged 12–14) with positive (n = 15; FHP) and negative (n = 15; FHN) FH of alcoholism. Each group consisted of 10 males and 5 females with minimal previous substance use. Manual hippocampal tracings were completed on high-resolution magnetic resonance images by reliable raters, and intracranial volumes were controlled in analyses. Results: FH groups did not differ on memory or hippocampal volumes, but group x gender interactions (p < .05) indicated that FHP males had larger left hippocampi than FHN males. Females showed greater left versus right hippocampal asymmetry, while males showed larger right versus left asymmetry. For all adolescents, larger right hippocampal volumes predicted poorer delayed visual memory (p < .01). Conclusion and Significance: Alcoholism risk factors, such as family history of alcoholism, may differentially influence adolescent hippocampal development for boys as compared to girls. Results suggest that FH does not account for prior findings of reduced left hippocampal volumes in heavy drinking youth. Findings are preliminary, but suggest that future studies examining the effects of alcohol use on the adolescent brain should consider the influence of FH, especially among boys.

Diffusion tensor imaging evidence of white matter disruption associated with loss versus alteration of consciousness in warfighters exposed to combat in Operations Enduring and Iraqi Freedom

The effects on the human brain of mild traumatic brain injury (mTBI), which is defined as a brief alteration (AOC) or loss of consciousness (LOC), are incompletely understood. Major psychiatric illnesses such as major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) are common after mTBI. Prior research suggests that individuals who develop MDD after blast-related mTBI versus those who do not show significant white matter disruption and higher rates of LOC, suggesting that LOC might be uniquely associated with brain changes that increase the risk of developing mental illness after neurotrauma. Therefore, the objective of this study was to examine the effects of LOC, MDD, and PTSD on white matter integrity in individuals who reported experiencing mTBI during combat in Operations Enduring and Iraqi Freedom. We hypothesized that LOC would be associated with significant disruption of white matter, above and beyond putative effects of MDD and PTSD. To test this hypothesis, 46 individuals who experienced blast-related mTBI underwent a detailed clinical assessment and diffusion tensor imaging. As hypothesized, LOC versus AOC individuals displayed significantly lower fractional anisotropy (FA) in 14 regions, which included the superior longitudinal fasciculus and corpus callosum. No regions of significant FA difference were identified between individuals with and without PTSD, or between individuals with and without MDD. These preliminary results show that LOC is associated with detectable alterations in brain microstructure and may suggest a brain basis for psychiatric symptoms and mental illness after mTBI.

A functional magnetic resonance imaging study of spatial working memory in children with prenatal alcohol exposure: contribution of familial history of alcohol use disorders.

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 fetal alcohol spectrum disorders (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 2 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 3 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 nonexposed, family history negative controls (CON, n = 17). RESULTS Relative to CON and FHP, the ALC group showed increased blood oxygen level dependent (BOLD) response in the left middle and superior frontal gyri for the SWM 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.