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

Abstract

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.

Keywords: alcohol use disorder; craving; fMRI; methods; neurofeedback; neuromodulation.

Figure 1.

Diagram of neurofeedback tasks paradigms. A) Diagram of multi ROI and continuous SVM neurofeedback tasks. 16 total trials each consisting of stimulus presentation with continuous feedback presented for 17 seconds followed by summary feedback presented for 5 seconds. Top- Example of successful trial. Bottom- Example of unsuccessful trial. B) Diagram of intermittent SVM neurofeedback task. 18 total trials each consisting of stimulus presentation for 12 seconds followed by summary and interim feedback for 5 seconds. C) Diagram of pre-neurofeedback functional localizer and baseline cue reactivity blocks. For the functional localizer, used for SVM neurofeedback, participants saw 5 of each non-craving and craving block (5 seconds per image, 4 images per block), interleaved. A 6 second “Rest” screen was displayed between blocks. Order and images were randomized across blocks. For the baseline cue-reactivity (all neurofeedback types), one non-craving block and one craving block were shown prior to the neurofeedback trials.

Figure 2.

Plots of behavioral measures over time. Error bars correspond to standard error. Bars represent mean. A) Plots of the rate of successful trials by run, where Success Rate is percent of neurofeedback trials where participant lowered their brain activity below the goal line. B) Plots of craving ratings on the ACQ self-report measure (where 0 is the lowest and 5 is the highest) prior to neurofeedback training and after neurofeedback training. Top (A&B): overall, collapsed across neurofeedback types. Bottom (A&B): broken down by neurofeedback type. Abbreviations: NF- neurofeedback; iSVM- intermittent support vector machine neurofeedback; cSVM- continuous support vector machine neurofeedback; ROI- multi region of interest continuous neurofeedback. Significance levels as follow: ^t p < 0.10; *p < 0.05; ** p < 0.01.

Figure 3.

Plots of brain activity during “Control” downregulation neurofeedback trials by run. Error bars correspond to standard error. Betas from each region of interest are plotted separately. Bars represent mean brain activity. A) Overall brain activity per run, collapsed across neurofeedback types. B) Brain activity broken down by neurofeedback type. For each group, a linear fitted line is also plotted to summarize the change in activity within neurofeedback type. Abbreviations: NF- neurofeedback; iSVM- intermittent support vector machine neurofeedback; cSVM- continuous support vector machine neurofeedback; ROI- multi region of interest continuous neurofeedback.

Figure 4.

Plots of the association between change in craving and change in brain activity during “Control” downregulation neurofeedback trials. X-axis “Change in Betas” represents the Run 1 level of brain activity during “Control” trials minus the Run 4 level of brain activity during “Control” trials. Y-axis “Change in Craving” represents the Post-scan ACQ measure of craving minus the Pre-scan ACQ measure of craving. These subtractions were chosen for the plots such that they would correspond to the intuitive interpretation (i.e., that lowering activity more during regulation corresponded to more reduction in craving); thus, a negatively sloping line on these plots corresponds to the positive correlations (i.e., that more downregulation corresponded to more reduction in craving) reported in the manuscript and in the Tables (and vice versa). Dots represent individual data points; lines are fitted linear best fit lines. Results from each region of interest are plotted separately. A) Overall association between change in brain activity and change in craving, collapsed across neurofeedback types. B) Overall association between change in brain activity and change in craving, broken down by neurofeedback type. Abbreviations: NF- neurofeedback; iSVM- intermittent support vector machine neurofeedback; cSVM- continuous support vector machine neurofeedback; ROI- multi region of interest continuous neurofeedback.