Supplementary Material
Experimental Design and Procedure
Participants filled out a series of questionnaires probing the level of response to alcohol
(Schuckit et al. 1997), quantity and frequency of alcohol use (adapted from Cahalan et al. 1969;
Mills et al. 1983), severity of their alcoholism-related symptoms (Short Michigan Alcoholism
Screening Test, SMAST, Selzer 1971), and handedness (Oldfield 1971). A battery of
questionnaires was used in order to obtain a comprehensive dispositional profile for each subject,
particularly with respect to disinhibitory, novelty seeking, and socialization traits. The battery
contained the following questionnaires: Childhood Hyperactivity Questionnaire (Tarter et al.
1977); Eysenck Personality Questionnaire (EPQ, Eysenck and Eysenck 1975); Eysenck
Impulsiveness and Venturesomeness Scale (Eysenck and Eysenck 1978); Socialization Scale of
the California Psychological Inventory (Gough 1994); and Zuckerman Sensation Seeking Scale
(Zuckerman 1971).
Eye Movement Data - Acquisition and Analysis
Eye movements were monitored and recorded with an infrared pupil/corneal reflection
tracker system RK-826PCI (ISCAN, Inc., Woburn, MA) specifically designed for use in the MRI
environment. It was comprised of an eye-image sensor (camera) mounted at the rear of the
magnet bore, an infrared fiber optic eye illuminator, and an infrared mirror fitted onto the head
coil. The infrared beam was invisible and did not affect participants' experience during scanning.
The level of infrared illumination was carefully tested and was found to be safely in compliance
with OSHA's standards. Acquisition parameters were calibrated by instructing participants to
look at fixation dots in the corners and the center of the screen and to make step-wise saccades to
seven points on the horizontal axis spaced apart in 50 increments. Eye movements were tracked
at 120 Hz during the functional scans and were analyzed off-line with a semi-automatic
MATLAB program (Mathworks, Natick MA) that recorded vector directions and saccadic
response latencies from target onset. Fig. S1 shows a sample tracing of the PS and AS trials.
Trials with latencies <130 ms were discarded from the analysis as they likely reflected
anticipatory saccades (Fischer et al. 1997; Lee et al. 2011; Manoach et al. 2007). Performance
accuracy and saccadic reaction time (SRT) were analyzed for all responses, but only correct
trials were included in the overall BOLD signal analysis. Erroneous responses were mostly selfcorrected, but when a saccade was performed in a wrong direction with no evidence of selfcorrection, they were classified as "uncorrected". The performance measures were analyzed with
a mixed model ANOVA with gender as a between-group factor, and beverage (alcohol, placebo)
and trial type (AS, PS) as within-subject factors (Woodward et al. 1990) (Fig 2).
Structural Imaging Data
Two high-resolution 3D MPRAGE (magnetization-prepared rapid gradient echo) T1weighted sequences were obtained for each subject with the following parameters: TR = 2.53
sec, TE = 3.25 msec, flip angle = 70, FOV = 256, 128 sagittal slices, 1.33 mm thickness, in-plane
resolution 1 x 1 mm.
Blood Flow Quantification - Arterial Spin Labeling (ASL.
In an attempt to mitigate possible vasoactive effects of alcohol on the BOLD signal,
resting perfusion ASL scans were obtained in each session and the regional perfusion values
were used as covariates. Detailed description of the methods and results of the ASL analysis
have been reported separately (Rickenbacher et al. 2011) and only a brief outline is included
here. Resting state perfusion was quantified with pulsed ASL (Kim 1995), combining a single
subraction-second version (QUIPSS-II) with the flow-sensitive alternating inversion recovery,
slice- and nonslice-selective hyperbolic secant inversion pulse labeling scheme (Wong et al.
1998). Twenty-four slices with 5 mm thickness and 3.1 x 3.1 mm in-plane resolution were
acquired in the AC-PC axial-oblique orientation (van der Kouwe et al. 2005) aligned with the
functional BOLD slices. The ASL data were analyzed with the FreeSurfer analysis package
(surfer.nmr.mgh.harvard.edu) (Dale et al. 1999; Fischl et al. 1999). Complete sets of resting ASL
and task-related BOLD scans across both beverage conditions were available for 18 participants.
In an effort to partial out potential vascular influences, regional perfusion measures were used as
covariates in the BOLD analysis of beverage effects. Since the ACC was the only area showing a
significant effect of beverage on the BOLD signal (Table 1), the ASL perfusion values were
entered into the analysis of covariance for the ACC ROI.
Results
Post-experimental questionnaire
When asked to rate whether the beverage contained "definitely no alcohol" (1) or
"definitely alcohol" (5), the participants correctly estimated the beverage content (4.7 ± 0.5 for
alcohol and 1.7 ± 0.8 for placebo). These ratings indicate that participants were able to easily
discriminate between the two beverage conditions. Evidence from studies using balanced
placebo design in which the factors of beverage and "expectancy" are fully crossed clearly shows
that brain activity is influenced only by the pharmacological effects of alcohol and not by
expectancy (Marinkovic et al. 2000; Marinkovic et al. 2001; 2004). However, it is likely that in
real life situations especially in those involving social settings, the effects of alcohol are a
combination of these two influences. Being intoxicated did not make subjects feel more
nauseous. They reported feeling slightly, but significantly more dizzy (F1,20 = 11.6, p < 0.01),
means: 1.7 ± 0.8 under alcohol and 1.1 ± 0.3 under placebo.
Figure Captions:
Fig S1. A sample tracing of the eye movements on four consecutive trials recorded at 120 Hz
with the infrared pupil/corneal reflection tracker system RK-826PCI (ISCAN, Inc.). Saccadic
reaction times and accuracy were analyzed for all responses with respect to the triggers sent out
concurrently with each stimulus presentation
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