Alcohol attention bias modulates neural engagement during moral processing.

The neurobiology of typical moral cognition involves the interaction of frontal, limbic, and temporoparietal networks. There is still much to be understood mechanistically about how moral processing is disrupted; such understanding is key to combating antisociality. Neuroscientific models suggest a key role for attention mechanisms in atypical moral processing. We hypothesized that attention-bias toward alcohol cues in alcohol use disorder (AUD) leads to a failure to properly engage with morally relevant stimuli, reducing moral processing. We recruited patients with AUD (n = 30) and controls (n = 30). During functional magnetic resonance imaging, participants viewed pairs of images consisting of a moral or neutral cue and an alcohol or neutral distractor. When viewing moral cues paired with alcohol distractors, individuals with AUD had lower medial prefrontal cortex engagement; this pattern was also seen for left amygdala in younger iAUDs. Across groups, individuals had less engagement of middle/superior temporal gyri. These findings provide initial support for AUD-related attention bias interference in sociomoral processing. If supported in future longitudinal and causal study designs, this finding carries potential societal and clinical benefits by suggesting a novel, leverageable mechanism and in providing a cognitive explanation that may help combat persistent stigma.

Selecting an optimal real-time fMRI neurofeedback method for alcohol craving control training.

Real-time fMRI neurofeedback (rt-fMRI-NF) is a technique in which information about an individual's neural state is given back to them, typically to enable and reinforce neuromodulation. Its clinical potential has been demonstrated in several applications, but lack of evidence on optimal parameters limits clinical utility of the technique. This study aimed to identify optimal parameters for rt-fMRI-NF-aided craving regulation training in alcohol use disorder (AUD). Adults with AUD (n = 30) participated in a single-session study of four runs of rt-fMRI-NF where they downregulated "craving-related" brain activity. They received one of three types of neurofeedback: multi-region of interest (ROI), support vector machine with continuous feedback (cSVM), and support vector machine with intermittent feedback (iSVM). Performance was assessed on the success rate, change in neural downregulation, and change in self-reported craving for alcohol. Participants had more successful trials in run 4 versus 1, as well as improved downregulation of the insula, anterior cingulate, and dorsolateral prefrontal cortex (dlPFC). Greater downregulation of the latter two regions predicted greater reduction in craving. iSVM performed significantly worse than the other two methods. Downregulation of the striatum and dlPFC, enabled by ROI but not cSVM neurofeedback, was correlated with a greater reduction in craving. rt-fMRI-NF training for downregulation of alcohol craving in individuals with AUD shows potential for clinical use, though this pilot study should be followed with a larger randomized-control trial before clinical meaningfulness can be established. Preliminary results suggest an advantage of multi-ROI over SVM and intermittent feedback approaches.

A Guide to Literature Informed Decisions in the Design of Real Time fMRI Neurofeedback Studies: A Systematic Review.

Background: Although biofeedback using electrophysiology has been explored extensively, the approach of using neurofeedback corresponding to hemodynamic response is a relatively young field. Real time functional magnetic resonance imaging-based neurofeedback (rt-fMRI-NF) uses sensory feedback to operantly reinforce patterns of neural response. It can be used, for example, to alter visual perception, increase brain connectivity, and reduce depression symptoms. Within recent years, interest in rt-fMRI-NF in both research and clinical contexts has expanded considerably. As such, building a consensus regarding best practices is of great value. Objective: This systematic review is designed to describe and evaluate the variations in methodology used in previous rt-fMRI-NF studies to provide recommendations for rt-fMRI-NF study designs that are mostly likely to elicit reproducible and consistent effects of neurofeedback. Methods: We conducted a database search for fMRI neurofeedback papers published prior to September 26th, 2019. Of 558 studies identified, 146 met criteria for inclusion. The following information was collected from each study: sample size and type, task used, neurofeedback calculation, regulation procedure, feedback, whether feedback was explicitly related to changing brain activity, feedback timing, control group for active neurofeedback, how many runs and sessions of neurofeedback, if a follow-up was conducted, and the results of neurofeedback training. Results: rt-fMRI-NF is typically upregulation practice based on hemodynamic response from a specific region of the brain presented using a continually updating thermometer display. Most rt-fMRI-NF studies are conducted in healthy samples and half evaluate its effect on immediate changes in behavior or affect. The most popular control group method is to provide sham signal from another region; however, many studies do not compare use a comparison group. Conclusions: We make several suggestions for designs of future rt-fMRI-NF studies. Researchers should use feedback calculation methods that consider neural response across regions (i.e., SVM or connectivity), which should be conveyed as intermittent, auditory feedback. Participants should be given explicit instructions and should be assessed on individual differences. Future rt-fMRI-NF studies should use clinical samples; effectiveness of rt-fMRI-NF should be evaluated on clinical/behavioral outcomes at follow-up time points in comparison to both a sham and no feedback control group.

Addiction neurocircuitry and negative affect: A role for neuroticism in understanding amygdala connectivity and alcohol use disorder.

The purpose of this study was to investigate the effect neuroticism has on the relationship between alcohol use severity and amygdala connectivity. Previous studies have indicated that amygdala connectivity and negative affect play a role in the cycle of addiction, and that neuroticism, which shares similar qualities with negative affect, is also related to amygdala connectivity, but the role neuroticism plays in mediating the relationship between AUD and amygdala connectivity has not been examined. To complete this study, 158 participants (58 female) enrolled in studies through NIAAA (National Institutes of Alcohol Abuse and Alcoholism) underwent resting state functional MRI (rs-fMRI) scans. The Alcohol Use Disorders Identification Test (AUDIT) was used to quantify alcohol use severity and the Revised NEO Personality Assessment (NEO PI-R) was used to quantify levels of neuroticism. A whole brain analysis was conducted to investigate the relationship of rs-fMRI amygdala connectivity with AUDIT and NEO neuroticism scores. A latent variable model (LVM) was used to measure the mediation effect of neuroticism on alcohol use severity and rs-fMRI amygdala connectivity. The whole brain analysis showed a positive relationship between right amygdala-right temporal fusiform gyrus connectivity and AUDIT scores and a negative relationship between left amygdala-left temporal parietal junction (TPJ) connectivity and NEO neuroticism scores. The indirect effect of neuroticism was significant for the LVMs of left amygdala connectivity with the nucleus accumbens (NAcc), posterior insula, and dorsal anterior cingulate cortex (dACC). These results suggest that personality plays an important role in the cycle of addiction.

Resting state connectivity best predicts alcohol use severity in moderate to heavy alcohol users.

BACKGROUND: In the United States, 13% of adults are estimated to have alcohol use disorder (AUD). Most studies examining the neurobiology of AUD treat individuals with this disorder as a homogeneous group; however, the theories of the neurocircuitry of AUD call for a quantitative and dimensional approach. Previous imaging studies find differences in brain structure, function, and resting-state connectivity in AUD, but few use a multimodal approach to understand the association between severity of alcohol use and the brain differences. METHODS: Adults (ages 22-60) with problem drinking patterns (n = 59) completed a behavioral and neuroimaging protocol at the National Institutes of Health. Alcohol severity was quantified with the Alcohol Use Disorders Identification Test (AUDIT). In a 3 T MRI scanner, participants underwent a structural MRI as well as resting-state, monetary incentive delay, and face matching fMRI scans. Machine learning was applied and trained using the neural data from MRI scanning. The model was tested for generalizability in a validation sample (n = 24). RESULTS: The resting state-connectivity features model best predicted AUD severity in the naïve sample, compared to task fMRI, structural MRI, combined MRI features, or demographic features. Network connectivity features between salience network, default mode network, executive control network, and sensory networks explained 33% of the variance associated with AUDIT in this model. CONCLUSIONS: These findings indicate that the neural effects of AUD vary according to severity. Our results emphasize the utility of resting state fMRI as a neuroimaging biomarker for quantitative clinical evaluation of AUD.