We examined the ability of alcohol-related, drug-related and emotionally valenced picture cues to induce brain response in college students at increased risk for hazardous alcohol use. The resemblance of the present participants’ brain response to that of individuals with alcohol use disorders suggests that some indicants of neural reactivity to alcohol and drug cues may exist prior to, or very early in the course of, problem use. Left prefrontal, anterior cingulate and right insula activation in response to substance-related cues suggests neural processing of cues in a healthy, but high-risk, college group that parallels neural ‘craving’ responses previously found in persons with substance use disorders, compared with controls without substance use disorders (Paulus et al., 2005
; Tapert et al., 2004
). These preliminary results tentatively suggest that neural responses may be early markers of progression to drug abuse, or perhaps represent neural signatures of risk. This interpretation of the present findings is tentative, given that the present at-risk college students’ brain response was not compared with a control group that comprised alcohol naïve or low-quantity–frequency drinkers. Nevertheless, the present results suggest that larger, comparative studies may be useful for identifying neural reactivity patterns that signal risk in young binge drinkers.
In particular, the higher brain activation found in right insula, left anterior cingulate, left caudate and left prefrontal regions in response to alcohol-related stimuli relative to neutral stimuli is consistent with the findings of significantly higher amplitude in event-related potentials to alcohol-related words in alcohol-dependent patients compared with controls (Herrmann et al., 2000
), and in heavy social drinkers when compared with light drinkers (Herrmann et al., 2001
). The present findings extend the results of George et al. (2001)
, Myrick et al. (2004)
and Tapert et al. (2004)
in adolescents and adults with alcohol use disorders, to college students who are at high risk for alcohol abuse (Barnett and Read, 2005
). At-risk college students’ brain response resembled those with alcohol use disorders who, after a sip of alcohol, showed an enhanced activation in anterior cingulate, right insula and the left prefrontal cortex in response to alcohol beverage pictures compared with neutral pictures (George et al., 2001
; Myrick et al., 2004
; Tapert et al., 2004
). Tapert et al. (2004)
and Myrick et al. (2004)
found an enhanced activation in bilateral insula regions, whereas in the present study activation was localized only in the right insula region. Two studies found that social drinkers showed no activation difference between alcohol beverage pictures and neutral pictures in anterior cingulate and the left prefrontal brain areas (George et al., 2001
; Myrick et al., 2004
). The previous cocaine cue reactivity literature showed that chronic users of cocaine exhibited activation in right insula while viewing a cocaine film, but not during viewing of a neutral film, whereas the no cocaine history group did not show any activation in this area during presentation of either cocaine or neutral film (Garavan et al., 2000
). Taken together, the present and these previous results suggest that the current ADAPS-referred college students may have displayed an at-risk neural response to alcohol-related stimuli, consistent with their risky alcohol use behavior (e.g. binge drinking, and scores on standardized alcohol problem assessments) and their higher cardiovascular response to alcohol cues compared with neutral cues.
Club drug- and cocaine-related picture cues also produced an increased BOLD signal in the right insula and left prefrontal regions and, in the parent study, participants also showed heightened cardiovascular reactivity to these cue types. Marijuana-related picture cues produced an increased BOLD signal in the left anterior cingulate and left prefrontal regions. These results generally parallel the findings of Brody et al. (2002)
and Naqvi et al. (2007)
in nicotine-dependent individuals, Garavan et al. (2000)
, Childress et al. (1999)
, Grant et al. (1996)
, Maas et al. (1998)
and Wexler et al. (2001)
in cocaine-dependent individuals, and Paulus et al. (2005)
in methamphetamine dependent individuals. In some cases, these studies found the same laterality patterns as did the present study, while in others bilateral activation was found in dependent persons.
Our finding of enhanced right anterior insula activation for alcohol- and polydrug-related stimuli and enhanced cardiovascular reactivity to these cue types is consistent with literature linking anterior insula to limbic, olfactory, gustatory and visceral-autonomic function (Naidicha et al., 2004
). Naqvi et al. (2007)
previously found that cigarette smokers who suffer damage to the insular region no longer exhibit addiction to nicotine. Naqvi's findings suggest a significant role for the insular cortex in both addiction and the maintenance of addiction. The present results suggest that insula activation to alcohol and drug cues may begin to appear early in the course of at-risk substance use.
In the present study, only negatively valenced picture cues activated amygdala. In addition to right amygdala activation, negatively valenced picture cues compared with neutral picture cues produced an enhanced activation in left parahippocampal gyrus, and right insula, whereas both negatively and positively valenced picture cues activated right prefrontal, right middle temporal and right superior temporal and right middle occipital regions. Thus, our results suggest that the prefrontal cortex is sensitive to arousal, that is, to cues eliciting positive and negative emotions. Consistent with our hypothesis, prefrontal (right) activation was observed for positive emotional picture cues as well as for alcohol- and polydrug-related picture cues. The present findings are consistent with theories that highlight the importance of circuitry-linking subcortical and cortical structures in the processing of emotion laden information (Lee et al., 2004
). Thus, the present results support the utility of IAPS pictures in studying neurophysiological correlates of emotionally valenced stimuli as these cues elicited brain response in the aversive systems such as in the prefrontal, amygdala and occipito-temporal regions, and also in the appetitive system such as in the prefrontal cortex, consistent with other works (Meseguer et al., 2007
). Participants showed significantly higher cardiovascular reactivity to negative, but not positive, cue types compared with neutral. We previously found increased levels of the 0.1 Hz index in response to both types of emotional picture cues (Vaschillo et al., 2008
). In the present study, it is likely that the small sample size compromised power to detect a statistically significant difference between positive and neutral cue reactivities.
Overall, this at-risk college sample appeared to demonstrate neural activity related to cue reactivity in response to alcohol-related cues in four brain areas (insula, anterior cingulate, caudate and prefrontal), whereas cue reactivity responses for marijuana and polydrug cues were observed in two brain areas (anterior cingulate and prefrontal for marijuana; insula and prefrontal for polydrug). This pattern appears to be consistent with participants’ greater use of alcohol than other drugs. Four of the 10 participants had a positive family history of alcohol use disorder. Owing to power limitations, we were not able to examine the role of family history in cue reactivity and brain response. However, given that individuals with a positive family history of alcohol or drug use disorders are at a greater risk of developing a substance use disorder in their lifetime (Eng et al., 2005
), the influence of family history on cue reactivity merits further study to determine the role of family history in mediating brain response and cue reactivity to alcohol- and drug-related cues.
Although the present findings regarding neural signatures of risk are provocative, several methodological limitations need to be considered. First, a low-risk control group was not included, so it was not possible to directly compare at-risk and low-risk participants’ BOLD responses to the cues used in this study. Nonetheless, our single group design is consistent with past addiction neuroimaging studies that used a single group (Janse Van et al., 2009
; Li et al., 2000
; McClernon et al., 2005
) and a number of participants ranging between 7 and 13. Second, no subjective report of craving was obtained from the participants. An important goal for future research is to compare self-reported arousal, valence/liking and craving to brain activation patterns. Similarly, simultaneous assessment of cardiovascular and neural response to emotional and appetitive cues would be more informative about the integrated operation of neurophysiological system responsivity. Finally, we verified zero blood alcohol concentration prior to the scanning session; however, a urine drug screen was not employed. Although participants self-reported no recent drug use, we cannot unequivocally rule out the contribution of acute drug effects. The likelihood of acute drug effects in this study was not high, given the present sample characteristics, although this may be an important concern in heavier drug use and clinical populations.