Background Adolescents with a family history of alcoholism (FHP) are at risk for developing an alcohol use disorder (AUD), and some studies indicate that FHP individuals show deficits in executive functioning. The ability to make adaptive decisions is one aspect of successful executive functioning that is often measured during risk-taking tasks; however, this behavior has not been examined in FHP youth. Since impaired decision-making could predispose FHP youth to make poor choices related to alcohol use, the current study examined the neural substrates of risk-taking in FHP adolescents and their family history negative (FHN) peers. Methods Thirty-one (18 FHP, 13 FHN) youth between 13-15 years old were included in this study. All youth had used little to no alcohol prior to study involvement. Functional magnetic resonance imaging was used to examine the neural substrates of risk-taking during the Wheel of Fortune (WOF) decision-making task (Ernst et al., 2004) in FHP and FHN youth. Results FHP youth did not differ from FHN youth in risk-taking behavior, but showed less brain response during risky decision-making in right dorsolateral prefrontal cortex and right cerebellar regions compared to FHN peers. Conclusions Despite no behavioral differences on the WOF decision-making task, FHP youth exhibited atypical neural response during risk-taking compared to FHN peers. Atypical brain activity, in regions implicated in executive functioning could lead to reduced cognitive control, which may result in risky choices regarding alcohol use. This could help explain the higher rates of AUDs seen in FHP adolescents. Further examination of risky behavior and associated brain response over the course of adolescence is necessary to characterize the vulnerabilities of FHP youth in the absence of alcohol abuse.

Introduction: Adolescence and young adulthood are periods of continued biological and psychosocial maturation. Thus, there may be deleterious effects of consuming large quantities of alcohol on neural development and associated cognition during this time. The purpose of this mini review is to highlight neuroimaging research that has specifically examined the effects of binge and heavy drinking on adolescent and young adult brain structure and function.Methods: We review cross-sectional and longitudinal studies of young binge and heavy drinkers that have examined brain structure (e.g., gray and white matter volume, cortical thickness, white matter microstructure) and investigated brain response using functional magnetic resonance imaging (fMRI).Results: Binge and heavy-drinking adolescents and young adults have systematically thinner and lower volume in prefrontal cortex and cerebellar regions, and attenuated white matter development. They also show elevated brain activity in fronto-parietal regions during working memory, verbal learning, and inhibitory control tasks. In response to alcohol cues, relative to controls or light-drinking individuals, binge and heavy drinkers show increased neural response mainly in mesocorticolimbic regions, including the striatum, anterior cingulate cortex (ACC), hippocampus, and amygdala. Mixed findings are present in risky decision-making tasks, which could be due to large variation in task design and analysis.Conclusions: These findings suggest altered neural structure and activity in binge and heavy-drinking youth may be related to the neurotoxic effects of consuming alcohol in large quantities during a highly plastic neurodevelopmental period, which could result in neural reorganization, and increased risk for developing an alcohol use disorder (AUD).

Background Individuals with a family history of alcoholism are at much greater risk for developing an alcohol use disorder (AUD) than youth or adults without such history. A large body of research suggests that there are premorbid differences in brain structure and function in family history positive (FHP) individuals relative to their family history negative (FHN) peers. Methods This review summarizes the existing literature on neurobiological phenotypes present in FHP youth and adults by describing findings across neurophysiological and neuroimaging studies. Results Neuroimaging studies have shown FHP individuals differ from their FHN peers in amygdalar, hippocampal, basal ganglia, and cerebellar volume. Both increased and decreased white matter integrity has been reported in FHP individuals compared with FHN controls. Functional magnetic resonance imaging studies have found altered inhibitory control and working memory-related brain response in FHP youth and adults, suggesting neural markers of executive functioning may be related to increased vulnerability for developing AUDs in this population. Additionally, brain activity differences in regions involved in bottom-up reward and emotional processing, such as the nucleus accumbens and amygdala, have been shown in FHP individuals relative to their FHN peers. Conclusions It is critical to understand premorbid neural characteristics that could be associated with cognitive, reward-related, or emotional risk factors that increase risk for AUDs in FHP individuals. This information may lead to the development of neurobiologically informed prevention and intervention studies focused on reducing the incidence of AUDs in high-risk youth and adults.

During adolescence, considerable social and biological changes occur that interact with functional brain maturation, some of which are sex-specific. The amygdala is one brain area that has displayed sexual dimorphism, specifically in socio-affective (superficial amygdala [SFA]), stress (centromedial amygdala [CMA]), and learning and memory (basolateral amygdala [BLA]) processing. The amygdala has also been implicated in mood and anxiety disorders which also display sex-specific features, most prominently observed during adolescence. Using functional magnetic resonance imaging (fMRI), the present study examined the interaction of age and sex on resting state functional connectivity (RSFC) of amygdala sub-regions, BLA and SFA, in a sample of healthy adolescents between the ages 10-16 years (n=122, 71 boys). Whole-brain, voxel-wise partial correlation analyses were conducted to determine RSFC of bilateral BLA and SFA seed regions, created using the Eickhoff-Zilles maximum probability maps based on cytoarchitectonic mapping and FMRIB's Integrated Registration and Segmentation Tool (FIRST). Monte Carlo simulation was implemented to correct for multiple comparisons (threshold of 53 contiguous voxels with a z-value ≥ 2.25). Results indicated that with increasing age, there was a corresponding decrease in RSFC between both amygdala sub-regions and parieto-occipital cortices, with a concurrent increase in RSFC with medial prefrontal cortex (mPFC). Specifically, boys and girls demonstrated increased coupling of mPFC and left and right SFA with age, respectively; however, neither sex showed increased connectivity between mPFC and BLA, which could indicate relative immaturity of fronto-limbic networks that is similar across sex. A dissociation in connectivity between BLA- and SFA- parieto-occipital RSFC emerged, in which girls had weaker negative RSFC between SFA and parieto-occipital regions and boys had weaker negative RSFC of BLA and parieto-occipital regions with increased age, both standing in contrast to adult patterns of amygdala sub-regional RSFC. The present findings suggest relative immaturity of amygdala sub-regional RSFC with parieto-occipital cortices during adolescence, with unique patterns in both sexes that may support memory and socio-affective processing in boys and girls, respectively. Understanding the underlying normative functional architecture of brain networks associated with the amygdala during adolescence may better inform future research of the neural features associated with increased risk for internalizing psychopathology.

Adolescents with a family history of alcoholism (FHP) are at heightened risk for developing alcohol use disorders (AUDs). The nucleus accumbens (NAcc), a key brain region for reward processing, is implicated in the development of AUDs. Thus, functional connectivity of the NAcc may be an important marker of risk in FHP youth. Resting state functional magnetic resonance imaging (rs-fcMRI) was used to examine the intrinsic connectivity of the NAcc in 47 FHP and 50 family history negative (FHN) youth, ages 10–16 years old. FHP and FHN adolescents showed significant group differences in resting state synchrony between the left NAcc and bilateral inferior frontal gyri and the left postcentral gyrus (PG). Additionally, FHP youth differed from FHN youth in right NAcc functional connectivity with the left orbitofrontal cortex (OFC), left superior temporal gyrus, right cerebellum, left PG, and right occipital cortex. These results indicate that FHP youth have less segregation between the NAcc and executive functioning brain regions, and less integration with reward-related brain areas, such as the OFC. The findings of the current study highlight that premorbid atypical connectivity of appetitive systems, in the absence of heavy alcohol use, may be a risk marker in FHP adolescents.

Previous research has shown that personality characteristics, such as sensation seeking (SS), are strong predictors of risk-taking behavior during adolescence. However, the relationship between levels of SS and brain response has not been studied during this time period. Given the prevalence of risky behavior during adolescence, it is important to understand neurobiological differences in reward sensitivity between youth with high and low SS personalities. To this end, we used functional magnetic resonance imaging (fMRI) to examine differences in brain activity in an adolescent sample that included 27 high (HSS) and 27 low sensation seekers (LSS), defined by the Impulsive Sensation Seeking scale of the Zuckerman-Kuhlman Personality Questionnaire (Zuckerman et al., 1993). In the scanner, participants played a modified Wheel of Fortune decision-making task (Cservenka and Nagel, 2012) that resulted in trials with monetary Wins or No Wins. We compared age- and sex-matched adolescent HSS and LSS (mean age = 13.94 ± 1.05) on brain activity by contrasting Win versus No Win trials. Our findings indicate that HSS show greater bilateral insular and prefrontal cortex (PFC) brain response on Win vs. No Win compared to LSS. Analysis of simple effects showed that while LSS showed comparable brain activity in these areas during Wins and No Wins, HSS showed significant differences in brain response to winning (activation) versus not winning (deactivation), with between-group comparison suggesting significant differences in brain response, largely to reward absence. Group differences in insular activation between reward receipt and absence may suggest weak autonomic arousal to negative outcomes in HSS compared with LSS. Additionally, since the PFC is important for goal-directed behavior and attention, the current results may reflect that HSS allocate fewer attentional resources to negative outcomes than LSS. This insensitivity to reward absence in HSS may lead to a greater likelihood of maladaptive choices when negative consequences are not considered, and may be an early neural marker of decreased loss sensitivity that has been seen in addiction. This neurobiological information may ultimately be helpful in establishing prevention strategies aimed at reducing youth risk-taking and suggests value in further examination of neural associations with personality characteristics during adolescence.

Adolescence is a period of vulnerability for developing substance use disorder. Recent neuropsychological and neuroimaging studies have elucidated underlying neural vulnerabilities that contribute to initiation of substance use during adolescence. Findings suggest poorer performance on tasks of inhibition and working memory, smaller brain volumes in reward and cognitive control regions, less brain activation during executive functioning tasks, and heightened reward responsivity are predictive of youth initiating substance use during adolescence. In youth who are family history positive (FHP) for substance use disorder, poorer executive functioning, smaller volume of limbic brain regions (e.g., amygdala), sex-specific patterns of hippocampal volume, and a positive association between nucleus accumbens volume and family history density have been reported. Further, reduced white matter integrity, altered brain response during inhibitory control, including both greater and less frontal lobe response, blunted emotional processing, and weaker neural connectivity have also been found in FHP youth. Thus, there is significant overlap among the neural precursors shown to be predictive of alcohol and substance use initiation during adolescence and those that distinguish FHP from youth without a family history of substance use disorder, suggesting common targets for prevention and intervention. Understanding these predictive factors helps identify at-risk youth for prevention efforts, as well as create interventions targeting cognitive weaknesses or brain regions involved in substance use initiation.

Background Even in the absence of heavy alcohol use, youth with familial alcoholism (family history positive [FHP]) exhibit atypical brain functioning and behavior. Although emotional and cognitive systems are affected in alcohol use disorders (AUDs), little attention has focused on whether brain and behavior phenotypes related to the interplay between affective and executive functioning may be a premorbid risk factor for the development of AUDs in FHP youth. Methods Twenty-four FHP and 22 family history negative (FHN) 12- to 16-year-old adolescents completed study procedures. After exclusion of participants with clinically significant depressive symptoms and those who did not meet performance criteria during an Emotional Go-NoGo task, 19 FHP and 17 FHN youth were included in functional magnetic resonance imaging (fMRI) analyses. Resting state functional connectivity MRI, using amygdalar seed regions, was analyzed in 16 FHP and 18 FHN youth, after exclusion of participants with excessive head movement. Results fMRI showed that brain activity in FHP youth, compared with FHN peers, was reduced during emotional processing in the superior temporal cortex, as well as during cognitive control within emotional contexts in frontal and striatal regions. Group differences in resting state amygdalar connectivity were seen bilaterally between FHP and FHN youth. In FHP youth, reduced resting state synchrony between the left amygdala and left superior frontal gyrus was related to poorer response inhibition, as measured during the fMRI task. Conclusions To our knowledge, this is the first study to examine emotion–cognition interactions and resting state functional connectivity in FHP youth. Findings from this research provide insight into neural and behavioral phenotypes associated with emotional processing in familial alcoholism, which may relate to increased risk of developing AUDs.