The goal of the current study was to investigate reward-based decision making and associated brain activity in adolescents at risk for alcoholism, to better understand vulnerabilities that may lead to the development of an AUD. Contrary to our hypothesis, FHP youth did not differ from FHN youth in risk-taking behavior; however, despite comparable task performance, there were significant between-group differences in risk-related PFC and cerebellar brain response.
To our knowledge, no studies have previously examined risk-taking behavior in FHP youth, an adolescent group with an even greater propensity toward alcohol use (Dawson et al., 1992
). Since some studies indicate that FHP youth show deficits in executive functioning (Harden and Pihl, 1995
), we hypothesized that such individuals would exhibit greater risk-taking, secondary to reduced cognitive control, even in the absence of alcohol abuse. Unexpectedly, we found a trend for FHP youth to make fewer risky choices on the WOF task than FHN youth. While family history of alcoholism is a robust risk factor for developing an AUD (Dawson et al., 1992
), certainly not all FHP individuals go on to develop alcoholism. This may be due to environmental protective factors, such as positive family functioning (Hill et al., 1992
) that could reduce risk-taking propensity in some FHP youth. Additionally, some studies suggest that anxiety during decision-making may promote risk avoidance (Maner et al., 2007
), and neuroticism may lead to avoidance of anxiety associated with bad outcomes (i.e. not winning money), with this latter personality factor shown to mediate the relationship between family history of alcoholism and alcohol abuse (Loukas et al., 2000
). Although our groups did not differ on the personality trait of neuroticism, we did not assess anxiety associated with making decisions during the WOF, and this may be another possibility for the lower risky choices observed in FHP youth. Furthermore, since risky behaviors, such as alcohol use, are positively associated with peer drinking (Curran et al., 1997
), examining risky decision-making in social situations may produce different findings. Thus, future fMRI studies should devise tasks to examine social influence on risk-taking in FHP youth and controls, since adolescents are particularly susceptible to risky decisions in the presence of peers (Chein et al., 2011
; Gardner and Steinberg, 2005
Notably, both groups of adolescents in this study showed comparable brain response to a previous study that examined whole-brain activity in this task during risky decision-making in adults (Ernst et al., 2004
). As hypothesized, FHP youth displayed reduced risk-related activation in the right DLPFC compared to FHN peers. The DLPFC develops substantially during adolescence (Gogtay et al., 2004
), is believed to subserve many aspects of executive functioning (Tamm et al., 2002
; Thomas et al., 1999
), and has been implicated for its role in decision-making (Van Leijenhorst et al., 2010
). While we also hypothesized that less neural response to risky decision-making would be observed in the vmPFC in FHP youth, our data did not support this result. It is possible that the lack of group differences seen in this region may indicate that atypical vmPFC activity during risk-taking, as seen in alcoholics (Bechara et al., 2001
), is a result of alcohol abuse itself, and may not be aberrant in high-risk FHP youth. Thus, our findings indicate that weaker risk-related brain response in the DLPFC may contribute to poorer cognitive control, which could render FHP adolescents vulnerable to poor behavioral regulation, resulting in the decision to use alcohol.
To better understand the nature of risk-related brain activity in FHP youth, BOLD response during each decision type was compared to baseline brain activity. Interestingly, this analysis showed that FHP youth did not differ in DLPFC brain response during either type of decision, while FHN youth showed significantly greater DLPFC activity during overall risky vs. safe choices. This may indicate that FHN youth are evaluating these decisions differently, while FHP youth do not differentiate between the two choices, as observed in the similar patterns of brain activity seen regardless of the decision they made. Thus, the current findings support recent literature suggesting atypical brain activity (Heitzeg et al., 2010
; Silveri et al., 2011
) during tasks of executive functioning in FHP youth compared to their peers in brain regions important for cognitive control.
In addition to differences in DLPFC activity, FHP youth showed less risk-related BOLD response in the cerebellum. Although the function of the cerebellum in motor control has long been established (McLeod and Van der Meulen, 1968
), recent studies have implicated the cerebellum in executive functioning (Lie et al., 2006
). Specifically, cerebellar tonsil involvement has been shown during tasks of working memory (Desmond et al., 1997
) and attention (Allen et al., 1997
). This role of the cerebellar tonsil in executive functioning is not surprising given the reciprocal anatomical projections between the cerebellum and the PFC (Brodal, 1978
). Interestingly, previous studies have found morphometric cerebellar abnormalities (Chanraud et al., 2007
) and disrupted fronto-cerebellar systems (Sullivan et al., 2003
) in alcoholics, while FHP youth also show structural abnormalities in the cerebellum (Hill et al., 2007
), as well as atypical fronto-cerebellar circuitry (Herting et al., 2011
). In the current study, hypoactivity of the DLPFC and cerebellum during decision-making in largely alcohol-naïve FHP youth lends further support to the hypothesis that fronto-cerebellar systems may be disrupted in individuals at high risk for alcoholism, even prior to the onset of alcohol abuse.
To further clarify the nature of our group differences in brain response during decision-making, we also analyzed brain activity during chance decisions, and found no group differences. This indicates that differences in brain response between FHP and FHN youth are not present when making decisions that do not involve risk, and suggests that FHP youth have weaker neural response specifically related to risky decision-making, which may render them at greatest risk for poor choices regarding alcohol use. Also, in order to understand whether FHP and FHN youth engage computational neurocircuitry differently during decision making, we analyzed brain activity during risky and safe decisions vs. chance selections. FHP youth engaged parietal areas, important for computational calculations (Dehaene et al., 2003
), to a greater extent than FHN youth, suggesting that aberrant brain response in fronto-parietal areas is another feature of family history risk for AUD. Given that differences in brain activity in the risky and safe decisions vs. chance selection contrast were not seen in the same regions as those present during risky vs. safe decision-making, these findings may suggest atypical brain response that is independent of differences seen during risk taking-related brain activity.
While this study is the first to investigate risk-taking behavior and associated neural activity in FHP and FHN youth, limitations and future directions should be discussed. First, since the current findings indicate atypical frontal and cerebellar risk-related brain activity in FHP adolescents, which might help to explain the greater alcohol-associated risk-taking later seen in FHP young adults (LaBrie et al., 2009
), prospective longitudinal study designs are crucial for determining these cause and effect relationships. Second, the current study did not find any relationship between FHD and decision-making related behavior or brain response. This may be due to a narrow range and overall low mean of FHD scores in this sample, which may have precluded detection of these relationships. Additionally, the influence of both genetic and environmental factors on brain and behavior phenotypes related to a family history of alcoholism may differ by participant, increasing the difficulty of FHD to provide a clear linear relationship to brain and behavioral measures. While we assessed family history of alcoholism by interviewing both parent and youth, multiple adult informants could provide more precise information. Third, due to a small sample size, we were unable to analyze sex differences associated with family history status risk, an important future direction, particularly given previous work indicating sex differences in FHP youth (Silveri et al., 2008
). Finally, since there are limitations in interpreting the relationship of risk-taking during a monetary decision-making task to risky behaviors surrounding alcohol use, developing non-monetary tasks to assess risky decision-making during adolescence will also be important.
In conclusion, the current study found weaker risk-related brain activity during decision-making in prefrontal and cerebellar regions in FHP youth compared to FHN peers. Importantly, despite the lack of differences in risk-taking behavior, these findings emphasize that atypical neural activity exists during decision-making, in the absence of alcohol abuse, in youth with a familial history of alcoholism. This could render FHP youth vulnerable to poor decision-making, such as the initiation of heavy alcohol use. Previous studies showing atypical brain response in FHP youth during tasks of executive functioning (Schweinsburg et al., 2004
; Spadoni et al., 2008
), along with current findings of aberrant brain activity in regions implicated in cognitive control, indicate that future work is necessary to understand how these deficits contribute to the higher rates of AUDs seen in FHP adolescents.