Alcohol dependent patients who underwent cue-exposure extinction training had larger decreases in neural alcohol cue-reactivity in mesocorticolimbic reward circuitry than patients who had standard clinic treatment. Cognitive bias modification training, which similarly trains individuals to reduce attentional bias towards alcohol cues, resulted indecreased neural alcohol cue-reactivity in the amygdala and reduced medial prefrontal cortex activation when approaching alcohol cues . These studies suggest that fMRI tasks may be sensitive to treatment response. Further, neurobiological circuits identified using fMRI can be used to predict treatment and drinking outcomes, providing unique information beyond that of self-report and behavior. Individuals with alcohol use disorder who return to use demonstrate increased activation in the mPFC to alcohol cues compared to individuals with AUD who remain abstinent . Moreover, the degree that the mPFC was activated was associated with the amount of subsequent alcohol intake, but not alcohol craving . Activation in the dorsolateral PFC to alcohol visual cues has been associated with higher percent heavy drinking days in treatment-seeking alcohol dependent individuals . Increased activation in the mPFC, orbitofrontal cortex, and caudate in response to alcohol cues has also been associated with the escalation of drinking in young adults . Mixed findings have been reported for the direction of the association between cue-induced striatal activation and return to use. Increases and decreases in ventral and dorsal striatal activation to alcohol cues have been associated with subsequent return to use. Utilizing a different paradigm, Seo and colleagues found that increased mPFC, ventral striatal,industrial drying racks and precuneus activation to individually tailored neutral imagery scripts predicted subsequent return to use in treatment-seeking individuals with AUD . Interestingly, brain activity during individually tailored alcohol and stress imagery scripts was not associated with return to use .
While initial evidence indicates that psychological interventions are effective at reducing mesocorticolimbic response to alcohol-associated cues, few studies have prospectively evaluated if psychosocial interventions attenuate neural cue-reactivity that in turn reduces drinking in the same population. Furthermore, no previous studies have used neural reactivity to alcohol cues to understand the mechanisms of brief interventions. Therefore, this study aimed to examine the effect of a brief intervention on drinking outcomes, neural alcohol cue-reactivity, and the ability of neural alcohol cue-reactivity to predict drinking outcomes. Specifically, this study investigated: 1) if the brief intervention would reduce percent heavy drinking days or drinks per week in non-treatment seeking heavy drinkers in the month following the intervention and 2) if the brief intervention would attenuate neural alcohol cue-reactivity. In the first case, we predicted significant effects on drinking based on the existing clinical literature and, in the second case, we predicted decrements in alcohol’s motivational salience based on the feedback about the participant’s drinking levels relative to clinical recommendations and their personal negative consequences of drinking. The effects of neural cue reactivity on subsequent drinking outcomes were tested in order to elucidate patterns of neural cue-reactivity that predict drinking behavior prospectively. Participants were recruited between November 2015 and February 2017 from the greater Los Angeles metropolitan area. Study advertisements described a research study investigating the effects of a brief health education session on beliefs about the risks and benefits of alcohol use. Inclusion criteria were as follows: engaged in regular heavy drinking, as indicated by consuming 5 or more drinks per occasion for men or 4 or more drinks per occasion for women at least 4 times in the month prior to enrollment ; a score of ≥8 on the Alcohol Use Disorder Identification Test .
Exclusion criteria included under the age of 21; currently receiving treatment for alcohol problems, history of treatment in the 30 days before enrollment, or currently seeking treatment; a positive urine toxicology screen for any drug other than cannabis; a lifetime history of schizophrenia, bipolar disorder, or other psychotic disorder; serious alcohol withdrawal symptoms as indicated by a score of ≥10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised ; history of epilepsy, seizures, or severe head trauma; non-removable ferromagnetic objects in body; claustrophobia; and pregnancy. Initial assessment of the eligibility criteria was conducted through a telephone interview. Upon arrival, participants read and signed an informed consent form. Participants then completed a series of individual differences measures and interviews, including a demographics questionnaire and the Timeline Follow-back to assess for quantity and frequency of drinking over the past 30 days. All participants were required to test negative on a urine drug test . A total of 120 participants were screened in the laboratory, 38 did not meet inclusion criteria and 12 decided not to participate in the trial, leaving 60 participants who enrolled and were randomized. Of the 60 individuals randomized, 46 completed the entire study. See Figure 1 for a CONSORT Diagram for this trial. The study was a randomized controlled trial. Participants were assessed at baseline for study eligibility and eligible participants returned for the randomization visit up to two weeks later. During their second visit, participants completed assessments, and then were were randomly assigned to receive a 1-session brief intervention or to an attention-matched control condition. Immediately after the conclusion of the session participants completed a functional magnetic resonance imaging scan to assess brain activity during exposure to alcohol cues and completed additional assessments. Participants were followed up 4 weeks later to assess alcohol use since the intervention through the 30-day Timeline Follow back interview. Participants who completed all study measures were compensated $160. The brief intervention consisted of a 30–45 minute individual face-to-face session based on the principles of motivational interviewing .
The intervention adhered to the FRAMES model which includes personalized feedback , emphasizing personal responsibility , providing brief advice , offering a menu of change options, conveying empathy , and encouraging self-efficacy . In accordance with MI principles the intervention was non-confrontational and emphasized participants’ autonomy. The content of the intervention mirrored brief interventions to reduce alcohol use that have been studied with non-treatment seeking heavy drinkers. The intervention included the following specific components: 1) giving normative feedback about frequency of drinking and of heavy drinking; 2) Alcohol Use Disorders Identification Test score and associated risk level ; 3) potential health risks associated with alcohol use; 4) placing the responsibility for change on the individual; 5) discussing the reasons for drinking and downsides of drinking; and 6) setting a goal and change plan if the participant was receptive . The aim of the intervention was to help participants understand their level of risk and to help them initiate changes in their alcohol use. Sessions were delivered by master’s-level therapists who received training in MI techniques, including the use of open-ended questions, reflective listening, summarizing, and eliciting change talk,commercial greenhouse benches and in the content of the intervention. All sessions were audiotaped and rated by author MPK for fidelity and for quality of MI interventions using the Global Rating of Motivational Interviewing Therapists . On the 7-point scale, session scores ranged from 5.87 to 6.93 with an average rating of 6.61 ± 0.23, which indicates that the MI techniques used in the intervention were delivered with good quality. Supervision and feedback were provided to therapists by author MPK following each intervention session. The treatment manual is available from the last author upon request. Participants randomized to the attention-matched control condition viewed a 30-minute video about astronomy. In the control condition there was no mention of alcohol or drug use beyond completion of research assessments. Both the intervention and attention-matched control sessions took place within the UCLA Center for Cognitive Neuroscience in separate rooms from the neuroimaging suite. The following individual questionnaires and interviews were administered during the study: the 30-day timeline follow-back was administered in interview format to capture daily alcohol and marijuana use over the 30 days prior to the visit by trained research assistants ; the self-report alcohol use disorders identification test was administered in order to assess for drinking severity ; the Penn Alcohol Craving Scale to measure alcohol craving over the past week . Participants also completed the Fagerstrom Test for Nicotine Dependence .
Lastly, participants completed a demographics questionnaire reporting, among other variables, age, sex, and level of education. The Alcohol Cues Task involves the delivery of oral alcohol or control tastes to elicit physiological reward responses and subjective urges to drink . During the task, each trial began with the presentation of a visual cue such that the words Alcohol Taste or Control Taste were visually presented to participants. This was followed by a fixation cross , delivery of the taste , and a fixation cross . Alcohol and water tastes were delivered through Teflon tubing using a computer controlled delivery system as described by Filbey and colleagues . Participants were instructed to press a button on a response box placed in their right hand upon swallowing. Alcohol tastes consisted of participants’ preferred alcoholic beverage . Beer could not be administered due to incompatibility of the alcohol administration device with carbonated liquids. The presentation of visual stimuli and response collection were programmed using MATLAB and the Psychtoolbox on an Apple MacBook running Mac OSX , and visual stimuli were presented using MRI compatible goggles . The Alcohol Cues Task was administered over the course of two runs with 50 trials/run. For the analysis of the cues task, all first-level analyses of imaging data were conducted within the context of the general linear model , modeling the combination of the cue and taste delivery periods convolved with a double-gamma hemodynamic response function , and accounting for temporal shifts in the HRF by including the temporal derivative. Alcohol and water taste cues were modeled as separate event types. The onset of each event was set at the cue period with a duration of 11 seconds. Six motion regressors representing translational and rotational head movement were also entered as regressors of no interest. Data for each subject were registered to the MBW, followed by the MPRAGE using affine linear transformations, and then normalized to the Montreal Neurologic Institute template. Registration was further refined using FSL’s nonlinear registration tool . The Alcohol Taste > Water Taste contrast was specified in the first level models. Higher level analyses combined these contrast images within subjects and between subjects . Age, sex, cigarette smoking status, and positive urine THC were included as covariates. Additional analyses evaluated if neural response to alcohol taste cues was predictive of drinking outcomes. Two models were run, evaluating percent heavy drinking days and the average number of drinks per week in the 4 weeks following the intervention or matched-control. Both models controlled for age, sex, cigarette smoking status, positive urine THC, and baseline percent heavy drinking days or average drinks per week depending on the drinking outcome model. Z-statistic images were thresholded with cluster-based corrections for multiple comparisons based on the theory of Gaussian Random Fields with a cluster-forming threshold of Z > 2.3 and a corrected cluster-probability threshold of p < 0.05 . This study examined the effect of a brief intervention on drinking outcomes, neural alcohol cue-reactivity, and the ability of neural alcohol cue-reactivity to predict drinking outcomes. Results did not find an effect of the brief intervention on alcohol use in this sample, and the intervention was not associated with differential neural alcohol cue reactivity. Exploratory secondary analyses revealed inverse relationships between differential neural activity in the precuneus and medial frontal gyrus in relation to alcohol-related outcomes, but these relationships were across conditions. The lack of main effect of intervention on either drinking outcomes or on neural alcohol cue reactivity is contrary to the study hypothesis whereby individuals assigned to the brief intervention condition were expected to show greater reductions in alcohol use compared to a no-intervention control condition . In the present study, reductions in alcohol use were observed for both conditions and it appears that simply participating in an alcohol research study at an academic medical center prompted notable behavioral changes. Reductions in drinking following study participation may be attributable to assessment reactivity, in which participants curb drinking after completing alcohol-related assessments and interviews . This phenomenon has been well-documented across several assessment modalities , including the AUDIT and TLFB interviews, which were used in the present study. In addition, recent studies have highlighted the fact that single session interventions, while efficacious in relatively large RCTS, have modest effect sizes .