Self-reported alcohol affects
All participants tolerated the infusion without complications. The average BrAC reached during the familiarization session was 0.070 mg% (SD = 0.008). All participants reported both stimulation and sedation effects on the BAES during this session. We saw the expected subjective effects of alcohol on the DEQ, with significant increases in high, intoxication, “feeling effects,” “liking” the drug, and “wanting more” of the drug, compared to baseline. Participants reported peak ratings of intoxication and feeling high at 25 min after the start of the infusion.
During the scanning sessions, the average blood alcohol concentration was 0.0 g% on the placebo day, and 0.072 g% (SD = 0.009) at the end of the infusion on the alcohol day. Participants were asked to report subjective feelings of intoxication and high using the DEQ every 10 min during the scans. None of the participants reported feeling any alcohol effects on the placebo day, and during the alcohol day, they reported peak intoxication from 25–45 min after the start of the infusion.
Participants did not differ significantly in self-report of positive or negative affect, measured by the PANAS, between the alcohol and the placebo day either before of after the scan. On the alcohol day, there was no change in negative or positive affect from pre- to post-scan, but on the saline day, participants reported a decrease in positive affect from pre- to post-scan (p = 0.003).
To test for the main effects of the alcohol and the facial emotion type, as well as the interaction between them, we used a GLM where alcohol (alcohol or placebo) and facial emotion (fearful or neutral) were fixed factors, and subject was a random factor. We found a significant main effect of alcohol intoxication on activation of VS across facial emotion types (; ). Activation was also significant in the right parahippocampal gyrus, left precuneus, left anterior cingulate, and left superior temporal gyrus. Conversely, we found a significant main effect of facial emotion irrespective of alcohol administration in the right amygdala, bilateral lingual gyrus, left superior temporal gyrus, right superior temporal gyrus, and right anterior cingulate (). Significant interactions between alcohol and facial emotion were seen in the several regions, including the left insula, right lingual gyrus, left nucleus accumbens, and bilateral middle frontal gyri (). These interactions were characterized in post hoc volume of interest analyses ().
Main effects of alcohol and emotion, and their interaction, on brain response.
Figure 1 Main effect of (A) alcohol, (B) fearful facial emotion, and (C) the interaction between them on regional brain activation. Anatomical maps of t statistics were spatially normalized by warping to Talairach space and combined into a group map. Radiological (more ...)
Figure 3 Percent signal change in volumes of interest in each condition. Values were entered into the GLM to test for main effects of alcohol, emotion, and an interaction. * indicates a significant main effect of alcohol; ** indicates a significant main effect (more ...)
During the placebo infusion, fearful faces (in contrast with neutral faces) activated the amygdala, insula, and parahippocampal gyrus, as well as visual processing areas, with no regions showing greater activations to the neutral compared to fearful faces (; ). In contrast, when participants were intoxicated, the fearful faces did not elicit a larger response than the neutral faces in any region.
Brain activation by linear contrasts between each session and stimulus class.
Figure 2 Linear contrasts between the alcohol and placebo condition under each emotion type (alcohol: fearful > neutral; and placebo: fearful > neutral), as well as linear contrasts between the fearful and neutral conditions separately under the (more ...)
Although we detected a main effect of alcohol intoxication in the striatum, this effect was primarily driven by the participants’ reaction to neutral, but not fearful, stimuli. Neutral faces elicited ventral striatum activation when subjects were intoxicated, but not when they were sober (). Fearful faces elicited increased activation in the left putamen, but in a much smaller and more ventral region than in the neutral face condition.
We characterized BOLD signal changes in volumes of interest (VOIs) that have previously been implicated in either brain reward circuits (e.g. NAcc, putamen and caudate) or emotional-visual circuits (e.g. amygdala, fusiform gyrus, and lingual gyrus). Fearful faces elicited greater activation than neutral faces in the right-lateralized amygdala, fusiform gyrus, and lingual gyrus (). Alcohol main effects were not statistically significant in these regions (see for values). The alcohol × facial emotion interaction effect on amygdalar BOLD signal change reached trend level significance (p = 0.08). Pairwise simple effect t-tests clarified this trend, demonstrating that whereas fearful faces activated amygdala significantly more than did neutral faces (p < .05) during placebo infusion (as seen in both the time-series linear contrast maps, and in the extracted VOI data), while this effect was no longer significant (p > .10) during alcohol intoxication.
ANOVA results of volume-of-interest analyses in striatal and visual-emotional brain regions.
In the striatal VOIs, there were no main effects of emotion, but there were significant main effects of alcohol in the right NAcc, right caudate, right putamen, and left putamen, and significant interactions between alcohol and emotion in the left NAcc and the left caudate (; see for values). In these two regions, post-hoc one-way comparisons indicated significant differences between the alcohol and the placebo condition when participants viewed the neutral faces, but no differences during the fearful face condition ().
Figure 4 (A) Where we observed significant interactions in the GLM (in the left NAcc and left caudate), we performed one-way ANOVAs. In these regions, there was a significant difference between the alcohol and the placebo condition when participants viewed the (more ...)
Association between self-reported intoxication and neural activity
There was a significant positive association between subjective ratings of intoxication and BOLD change scores in the neutral facial expression condition in the left NAcc (r2 = 0.467, p = 0.020) and in the left caudate (r2= 0.354, p = 0.045). This indicates that participants who reported feeling more intoxicated showed a larger BOLD response to alcohol in these regions (). Stepwise multiple regression indicated no effect of actual BAC levels, gender, or pre-scan mood ratings of negative or positive affect on BOLD activation. There was no correlation between subjective intoxication ratings and BAC levels, probably as a result of the minimal inter-subject variability in BAC using our ethanol infusion method. We also did not find the session order to have a significant effect in any of our analyses.