Addiction history moderates the effect of prefrontal 10-Hz transcranial alternating current stimulation on habitual action selection

Individuals with substance use disorders (SUDs) transition more quickly from goal-directed to habitual action-selection, but the neural mechanisms underlying this phenomenon remain unclear. Data from animal models suggest that drugs of abuse can modify the neurocircuits that regulate action-selection, enhancing circuits that drive inflexible, habit-based stimulusresponse (S-R) action-selection and weakening circuits that drive flexible, goal-directed actions. Here, we tested the effect of bilateral 10-Hz transcranial alternating current stimulation (10Hz-tACs) of the dorsolateral prefrontal cortex on actionselection in men and women with a SUD history and an age- and sex-matched control group. We tested the hypothesis that true 10Hz-tACS versus active sham stimulation would reduce perseverative errors after changed response contingencies for well-learned S-R associations, reflecting reduced habit-based action-selection, specifically in the SUD group. We found that 10 Hz-tACS increased perseverative errors in the control group, but in the SUD group, 10 Hz-tACS effects on perseverative errors depended on substance abuse duration: a longer addiction history was associated with a greater reduction of perseverative errors. These results suggest that 10Hz-tACs altered circuit level dynamics regulating behavioral flexibility, and provide a foundation for future studies to test stimulation site, frequency, and timing specificity. Moreover, these data suggest that chronic substance abuse is associated with altered circuit dynamics that are ameliorated by 10Hz-tACs. Determining the generalizability of these effects and their duration merits investigation as a direction for novel therapeutic interventions. These findings are timely based on growing interest in transcranial stimulation methods for treating SUDs. NEW & NOTEWORTHY Treating the executive dysfunction associated with addiction is hampered by redundancies in pharmacological regulation of different behavioral control circuits. Thus, nonpharmacological interventions hold promise for addiction treatment. Here, we show that, among people with an addiction history, 10-Hz transcranial alternating current stimulation (10Hz-tACS) of the dorsolateral prefrontal cortex can reduce habitual actions. The fact that 10Hz-tACS can regulate behavioral flexibility suggests its possible utility in reducing harmful habitual actions.

Automated summary

This study found that 10Hz-tACs can alter the behavioral selection of individuals with substance use disorders (SUDs), with a longer history of addiction associated with a greater reduction in perseverative errors. The results suggest that 10Hz-tACs may regulate behavioral flexibility, providing a foundation for future research on stimulation specificity.