The main finding of this study was that an acute moderate dose of alcohol resulted in attenuation of bilateral insula activation during the Hariri Emotion Face Assessment Task, in contrast to placebo activation patterns. The effect of alcohol on BOLD response to emotional face processing was specific to the insula; response differences were not observed in the amygdala, as had been hypothesized, nor in any other brain region, a finding that differs from previous research (Gilman et al., 2008
). Although the amygdala has repeatedly been implicated in processing emotional or affective information (Pessoa et al., 2010
), previous studies suggest that acute alcohol may not exert its strongest effects directly on the amygdala during emotion processing (Gilman et al., 2008
). Further, the insular functioning effect was equivalent across emotion types (fearful, angry and happy faces). As no differences in task accuracy or response latency were observed, the blunted insular response may suggest reduced interoceptive awareness during emotional processing when under the influence of a moderate dose of alcohol.
Increased insula activation relates to various trait measures of affective distress such as anxiety (
,Simmons et al., 2006
; Stein et al
., 2007), harm avoidance (Paulus et al., 2003
) and intolerance of uncertainty (Simmons et al., 2008
). In addition, several studies have shown that the anticipation of aversive events involves the insular cortex. For example, brain areas activated by anticipation of aversive pictures include dorsal amygdala, anterior insula, dorsal anterior cingulate cortex, right dorsolateral prefrontal cortex and right posterior orbitofrontal cortex (Simmons et al., 2004
; Nitschke et al., 2006
). This network of activation in relation to the anticipation of aversive stimuli extends to other modalities such as monetary losses (Samanez-Larkin et al., 2008
), conditioned stimulus predicting an aversive stimulus (Marschner et al., 2008
) and the expectation of pain (Ploghaus et al., 1999
). Moreover, insula activation is an important processing area for the affective elements of an individual's pain experience in subjects with depression (Giesecke et al., 2005
; Strigo et al., 2008
). Some have argued that the insula and anterior cingulate are relatively more sensitive to the expectation of unpleasant stimuli relative to expecting pleasant or neutral stimuli (Herwig et al., 2007
). Finally, uncertainty or ambiguity is an important aspect of anticipatory processing. Thus, it is not surprising that the degree to which an individual is sensitive to uncertainty correlates positively with activation in bilateral insula during affective ambiguity (Simmons et al., 2008
Unpredictable stimulus presentations have been linked to brain activity in the anterior insula (Carlsson et al., 2006
). The insula is also involved in modulating autonomic arousal (Critchley et al., 2004
) and connecting visceral changes to facial emotion processing (Critchley et al., 2004
). Taken together, these data suggest that the insula plays an important role in processing the anticipation and subjective experience of aversive stimuli across a number of different modalities. Furthermore, insular functioning appears to be related to alcohol and drug-induced craving and relapse (Tapert et al., 2004
; Naqvi et al., 2007
). Our finding of alcohol-attenuated neural response to all facial emotions in the insula may relate to reduced anticipatory processing of potentially aversive events or of events that are judged to be potentially aversive following moderate alcohol consumption. However, alcohol has been associated with better discrimination of positive stimuli (happy faces), and this may be due to suppression of these interoceptive systems allowing positive stimuli to be more readily processed via disinhibition (Steele and Southwick 1985
; Kano et al., 2003
). This is the first study to our knowledge that examined the neural mechanisms of positive or happy affective processing following a moderate dose of alcohol; therefore future studies are needed to replicate these results. In the current pilot study, the acute effect of alcohol on the insula may be related to its anxiolytic and pro-social effects (Gilman et al., 2008
). However, future study will need to examine this relationship more directly.
The present study is limited by a small sample size, the restriction to Caucasian race, the modest age range and the relatively intelligent participants selected from a college population. Additional caveats include the reliance on estimation of blood alcohol concentration during the scan session by controlling the time after drinking when the task was administered instead of exact BrAC, the relatively narrow focus of the fMRI regressions evaluated, the absence of a direct placebo manipulation check and the lack of data on cerebral perfusion, which could potentially account for alcohol condition findings. Future studies should address these limitations, as well as attempt to address within subject longitudinal data including blood alcohol concentration to understand the interaction of time by alcohol.
In summary, this preliminary study suggests that reduced insula activation may be one source of decreased interoceptive awareness that is often described during moderate intoxication. Future studies may determine if the degree of interoceptive attenuation relates to the risk for an alcohol use disorder. Knowledge of the effects of alcohol on affective information processing may provide new clues as to why alcohol is used and misused, and may help clarify the positively and negatively reinforcing mechanisms of alcohol.