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Influence of Alcohol on Cognitive Functioning and Neural Functional Connectivity in Adolescents
Get PDFRationale: Neurodevelopment may be shaped by environmental factors such as alcohol intake. More than 20% of U.S. high school students began drinking before age 14. Adults who initiated drinking before age 14 are four times more likely to develop psychosocial and psychiatric difficulties than those who began drinking after turning 20. Little is known, however, about how the age of alcohol use onset influences brain development.Design: This study prospectively examined the effects of alcohol use onset age on neurocognitive functioning in healthy adolescent drinkers. Youth underwent a neuropsychological battery and neuroimaging session at baseline (M = 13.6 years-old, SD = 0.8), before substance use initiation, and at follow-up (M = 20.2 years-old, SD = 1.5), to evaluate changes in frontoparietal context-dependent functional connectivity (cdFC) during a visual working memory task, and neuropsychological performance. Hierarchical linear regressions examined if earlier ages of onset for first and regular alcohol use adversely influenced neurocognition and functional connectivity, above and beyond baseline neurocognition, substance use severity, and familial and social environment factors.Results: As hypothesized, an earlier age of first drinking onset predicted poorer performances in psychomotor speed and visual attention (ps<.05; N = 215) and an earlier age of weekly drinking onset predicted poorer performances in cognitive inhibition and working memory, controlling for baseline neuropsychological performance, drinking duration, and past-year marijuana use (ps<.05; N = 127). Age of first and regular drinking onset did not significantly predict follow-up frontoparietal cdFC. Exploratory whole brain analyses suggested that, as hypothesized, earlier ages of regular drinking onset were associated with higher cdFC between subcortical and fronto-temporal areas, and linked to poorer neuropsychological performance. Conclusion: This was the first study to assess the association between age of onset on neurocognition and cdFC in adolescents. Initiation of any or weekly alcohol use at younger ages are risk factors for poorer neuropsychological functioning and subcortical-cortical hyper-connectivity. This may have important implications for public policies related to the legal drinking age and prevention programming, as this study suggests that early onset of drinking increases risk alcohol-related neurocognitive vulnerabilities. Further studies are needed to replicate these preliminary findings
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The Structure and Function of Interoceptive Brain Regions in Adolescent Substance Users
Get PDFBackground: Interoception refers to the central nervous system processes through which individuals become aware of their visceral feelings and internal body state. The interoceptive brain network, comprised of the insula, striatum, cingulate, and prefrontal cortex serves a homeostatic purpose, integrating internal and external signals with cognition, affect, and motivation to guide the regulation of body physiology. Substance use disorder (SUD) may be a manifestation of chronic, maladaptive attempts to regulate homeostasis via alcohol and other drug use. Yet little is known about how dysregulated interoception develops and whether interoceptive alteration precedes or is a consequence of heavy substance use. This project begins to address these questions with a series of three neuroimaging studies examining the functional and structural neural underpinnings of interoception in adolescent substance users. Methods: Adolescents ages 15-17 who met diagnostic criteria for SUD (SUD+ group), adolescents who had experimented with substances but did not meet criteria for SUD (EXP group), and non-using control adolescents (CON group) completed a clinical interview, questionnaires, structural neuroimaging, and two functional magnetic resonance imaging (fMRI) paradigms designed to induce pleasant and aversive interoceptive sensations. In the pleasant paradigm, adolescents experienced a soft brush stroke to the skin (17 SUD+, 19 EXP, 19 CON); during the aversive paradigm, adolescents were subjected to an inspiratory breathing load (17 SUD+, 15 EXP, 19 CON). fMRI analyses examined group differences in blood oxygen level dependent (BOLD) signal change with linear mixed effects models. Gray matter volume, cortical surface area, and cortical thickness of key interoceptive regions were estimated using T1-weighted structural data (24 SUD+, 28 EXP, 23 CON) and group differences were examined via ANOVA. Regression analyses were used to probe the relationship of substance use, clinical symptoms, and subject characteristics to neural structure and function of the insular cortex. Results: Group differences were observed in BOLD response contrast within the interoceptive network (ps<.05), despite comparable task performance, similar levels of body awareness, and similar ratings of the pleasant and aversive sensations. During pleasant stimulation, SUD+ and EXP showed less BOLD response in posterior insula (PIC), anterior cingulate (ACC), and numerous frontal cortical regions compared to CON. SUD+ also demonstrated heightened BOLD response in the lentiform nucleus and had the greatest activation change from anticipation to stimulation in the dorsal anterior insula (AIC). During aversive stimulation, both SUD+ and EXP had exaggerated activation patterns in the dorsal AIC, but only the SUD+ group showed a significantly elevated response relative to CON in the PIC. By contrast, the rostral AIC was sensitive to anticipating the aversive stimulus in the CON group but deactivated during this condition in the SUD+ group. In the frontal cortex, SUD+ had elevated activation to the aversive stimulus in the left ACC, yet blunted reactivity in the left middle frontal gyrus and right rostral ACC. Across all subjects, higher levels of sensation seeking were associated with decreased insula activation during aversive loaded breathing (p=.01) Groups did not differ on any brain volumetric, surface area, or cortical thickness variable examined (ps>.05) Conclusions: Findings indicate that adolescent substance use history is associated with aberrant brain response patterns of interoceptive processing in the absence of group differences in subjective interoceptive awareness or gray matter morphology. The nature of this functional dysregulation depends on the valence of the physiological experience. That aberrant activation patterns were seen in youth with SUD, but also in adolescents with sub-clinical substance exposure advances the theory that differences in the perception and processing of visceral sensations may be, at least in part an early predisposing factor for substance misuse, rather than a consequence of addiction or long-term substance exposure. By further elucidating a novel mechanism that may contribute to addiction risk, this study may aid in the development of innovative interventions to improve visceral processing
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A Prospective Investigation of Youth Alcohol Experimentation and Reward Responsivity
Get PDFGreater risk-taking behaviors, such as alcohol experimentation, are associated with different patterns of brain functioning in regions implicated in reward (nucleus accumbens, NA) and cognitive control (inferior frontal gyrus, IFG). These neural features have been observed in youth with greater risk-taking tendencies prior to substance use initiation, suggesting NA-IFG disruption may serve as an early marker for subsequent substance use disorders. Prospective studies are needed to determine if NA-IFG disruption predicts future substance use in school-age children, including those with minimal use of alcohol (e.g., sipping). The present large-sample prospective study sought to: (1) examine alcohol sipping at ages 9-10 as a potential behavioral indicator of concurrent underlying altered neural responsivity to reward, and (2) determine if alcohol sipping and NA-IFG activation at ages 9-10 predicts increased alcohol use at ages 10-11. This project used data from the baseline (Time 1) and two-year follow-up (Time 2) assessments of the Adolescent Brain Cognitive Development (ABCD) Study (Release 3.0). Support Vector Machine (SVM) learning determined if: (1) NA-IFG neural activity could correctly identify youth who reported alcohol sipping at Time 1 (n = 7409), and (2) NA-IFG and alcohol sipping frequency at Time 1 could correctly identify youth who reported drinking alcohol at Time 2 (n = 4000). The context in which youth first tried sips of alcohol was also characterized (e.g., with or without parental permission, as part of a religious experience).
Approximately 24% of the sample reported having tried sips of alcohol by ages 9-10, with 76% reporting doing so outside of the context of a religious ceremony. The first SVM model classified youth according to alcohol sipping status at Time 1 with an accuracy of .35 (sensitivity = .24, specificity = .80). The second SVM model classified youth according to alcohol drinking status at Time 2 with an accuracy of .76 (sensitivity = .21, specificity = .91). Linear regression demonstrated that frequency of alcohol sipping at Time 1 predicted frequency of alcohol use at Time 2 (p < .001, adjusted R2 =.08). Activity in the three subsections of the IFG at Time 1 predicted activity in those same regions at Time 2 (all ps < .02). All other relationships were not significant.
Early sips of alcohol, across environmental contexts, appear to predict frequency of alcohol use in early adolescence. Findings do not provide strong evidence for minimal early alcohol use (i.e., sipping) as a behavioral marker of underlying alterations in NA-IFG neural responsivity to reward. Improving our understanding of the neural and behavioral factors that indicate a greater propensity for future substance use is crucial for identifying at-risk youth and potential targets for preventative efforts
White matter integrity and executive dysfunction in children with heavy prenatal alcohol exposure : a diffusion tensor imaging study
No full textIncludes bibliographical references (p. 42-54).Fetal alcohol spectrum disorder (FASD) affects 2-5% of the population and is associated with cognitive deficits in overall intellectual functioning and on indices of learning, memory, and attention. Individuals with prenatal alcohol exposure may demonstrate behavioral problems including hyperactivity and impulsivity and show neural abnormalities including reductions in overall and regional brain volumes, reduced white matter density, and increased gray matter density. White matter abnormalities throughout the brain have been recognized in children with prenatal exposure to alcohol. These structural abnormalities have been hypothesized to underlie many of the cognitive and behavioral deficits observed in this population. The purpose of the current study was to use diffusion tensor imaging (DTI) to examine white matter integrity in children with and without prenatal alcohol exposure. Participants included 47 children between the ages 10-16 years: children with heavy prenatal exposure to alcohol (AE = 25) and non-exposed children (CON = 22). Consistent with previous studies, prenatal alcohol exposure was associated with low fractional anisotropy (FA), high mean diffusivity (MD), and high radial diffusivity (RD), compared to non-exposed controls, in clusters in the frontal and parietal lobes, as well as the brainstem, fornix, external capsule, and cerebellum. More surprisingly, prenatal alcohol exposure was associated with clusters of high FA and low MD/RD in white matter tracts in all four lobes of the brain. To better understand these novel results, correlations between measures of white matter integrity and behavioral performance on measures of executive functioning (EF) using the Delis-Kaplan Executive Function System (D-KEFS) were assessed. In clusters in the frontal and parietal lobe, decreased FA and increased MD/RD in the AE group were associated with impaired performance on several EF measures. Within areas where the AE group showed more homogenous white matter than controls, clusters in the temporal and occipital indicated that high FA and/or low MD/RD in the AE group were negatively associated with verbal and non-verbal fluency, while clusters showing reduced MD/RD (but not high FA) in the AE group in frontal-striatal tracts were positively associated with EF performance across several domains. These results suggest that white matter abnormalities in individuals with prenatal alcohol exposure may be more complex than initially believed, and are characterized by areas of both increased and decreased anisotropy relative to unaffected controls. Consistent with previous reports, we identified several clusters in which the AE group showed less homogenous white matter that were associated with impaired neuropsychological performance. However, this study also found that the AE group demonstrated higher FA and lower MD/RD than the CON group in clusters throughout the brain. This novel finding may be explained by either decreased neural branching (associated with impaired executive functioning) or compensatory mechanisms for other damaged structures (associated with improved cognition) differentially throughout the brain in individuals with prenatal alcohol exposure
An fMRI study of spatial working memory in children with prenatal alcohol exposure : contribution of familial history of alcohol use disorders
No full textIncludes bibliographical references (p. 38-48)The adverse effects of prenatal alcohol exposure have been documented for nearly four decades. Fetal Alcohol Syndrome (FAS) is defined by facial dysmorphology, growth deficits, and central nervous system abnormalities. A larger range of effects, including neurocognitive and behavioral dysfunction in the absence of these criteria is reflected in the non-diagnostic term Fetal Alcohol Spectrum Disorders (FASD). Understanding the neural basis of these effects is essential for treatment and intervention development. Neuroimaging studies report structural and functional abnormalities in FASD, but interpretations are complicated by comorbid disorders and genetic influences. One influence, also linked to neurocognitive deficits and functional abnormalities, is a family history of alcoholism. Because individuals with FASD may have an underlying familial history of alcoholism, it is difficult to determine the extent to which deficits are unique to prenatal alcohol exposure. The current study used functional magnetic resonance imaging to examine BOLD response (p[less than].01, clusters [greater than or equal to]864 ??l) during a task assessing memory for spatial locations relative to a vigilance condition assessing attention. Three comparisons were made: (1) children with histories of heavy prenatal alcohol exposure (ALC) vs. typically developing controls (CON); (2) ALC vs. those with no prenatal alcohol exposure, but a confirmed positive family history of alcoholism (FHP); and (3) FHP vs. CON. Fifty-four, age-matched children (18 FASD, 18 FHP, 17 CON), were selected from two ongoing neuroimaging studies examining spatial working memory (SWM). Analyses were performed using Analysis of Functional NeuroImages and SPSS. The ALC group had lower IQ, was less accurate, and showed slower response during vigilance relative to both other groups, which did not differ from each other. It was hypothesized that the ALC group would show greater BOLD response in frontal brain regions during SWM demands relative to FHP and CON youth, who would not differ from each other. In support of this hypothesis, relative to both the CON and FHP groups, the ALC group showed increased BOLD response in the left middle and superior frontal gyri during the spatial working memory condition relative to the vigilance condition (SWM contrast). Additionally, the ALC group showed unique increases in BOLD response to the SWM contrast in the left lingual gyrus and the right middle frontal gyrus in comparison to CON, and the left cuneus and precuneus in comparison to FHP. Contrary to the hypothesis, relative to CON, both ALC and FHP showed greater activation to the SWM contrast than CON in the lentiform nucleus and insular region. The FHP group showed further differences from CON in the thalamus. These results confirm previous studies suggesting SWM deficits in FASD. In addition, differences between the ALC group and the CON and FHP groups suggest the left middle and superior frontal region may be especially affected in children with FASD. Conversely, differences from the CON group in the lentiform nucleus and insular region for both the ALC and FHP groups may indicate this region is associated with family history of alcoholism rather than specifically associated with prenatal alcohol exposure
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
An fMRI study of behavioral response inhibition in adolescents with and without histories of heavy prenatal alcohol exposure
No full textIncludes bibliographical references (pages 41-54).The consequences of heavy prenatal alcohol exposure occur on a continuum, affecting cognitive, behavioral, and physical outcomes. Fetal alcohol syndrome (FAS) is the most severe consequence of prenatal exposure to alcohol and is diagnosed in the presence of craniofacial anomalies, growth deficiency, and central nervous system dysfunction. However, the majority of alcohol-exposed children do not meet diagnostic criteria for FAS; fetal alcohol spectrum disorders (FASD) encompass individuals affected by alcohol, including those with and without FAS. Among the cognitive deficits following prenatal alcohol exposure is perseveration, suggesting underlying response inhibition (RI) impairment. RI deficits are also supported by deficits in behavior, including high rates of disruptive disorders, including attention-deficit/hyperactivity disorder (ADHD) and conduct disorder, in addition to anatomical and functional brain abnormalities. Anatomically, research suggests that RI is associated with the middle and inferior frontal and subcortical regions. Prenatal alcohol exposure results in disproportionately reduced volumes in cortical and subcortical regions, including the prefrontal cortex and basal ganglia. Functional abnormalities are also reported in middle frontal gyrus and striatum following prenatal alcohol exposure. Although previous functional magnetic resonance imaging (fMRI) and electrophysiological studies have indicated aberrant brain functioning during a well-known response inhibition task, the go/no-go, recent studies suggest this task may measure action selection rather than RI. Thus, a more in depth investigation of neural functioning during RI is necessary to understand brain functioning and RI following prenatal alcohol exposure. The stop-signal task (SST) is hypothesized to provide a more accurate assessment of RI. The current study examined RI using the SST in alcohol-exposed and control adolescents. We hypothesized that the alcohol-exposed group would exhibit greater BOLD activation in prefrontal and subcortical areas during RI compared to controls. Subjects were two groups (ages 13-16y) of adolescents with histories of heavy prenatal alcohol exposure (AE, n=20) and unexposed controls (CON, n=20) who underwent fMRI while performing the SST. Task performance was measured using percent correct inhibits during easy, medium, and hard inhibit trials. Group differences on BOLD response were examined on 5 conditions: Allstop (all stop trials vs. Nostop trials), Easy, Medium, Hard, and Hard minus Easy. Groups were similar on demographic and behavioral outcomes, except FSIQ (AE<CON). During the Allstop condition, the AE group demonstrated greater BOLD activation in sensorimotor areas, striatum, and temporal regions relative to controls. As task difficulty increased, the AE group demonstrated greater activation compared to controls in frontal and subcortical regions, insula, sensory-motor area, and cingulate. On the Hard minus Easy condition, the AE group showed greater BOLD response relative to controls in right middle and superior frontal gyrus and the cingulate. Results were unchanged after demographic, medication, and FAS diagnosis were statistically controlled. Consistent with previous studies and our hypotheses, alcohol-exposed children demonstrated greater activation than controls in regions associated with RI, despite similar task performance and utilized greater neural resources in inhibition-related regions as task difficulty increased. These results may suggest that prenatal alcohol exposure leads to immature cognitive processing and motor-coordination and frontal-striatal inefficiency during executive control
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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