Accelerated HF-rTMS protocol has a rate-dependent effect on dACC activation in alcohol-dependent patients: an open-label feasibility study

Background: The application of accelerated high-frequency (HF) repetitive transcranial magnetic stimulation (rTMS) could be a potential treatment option for alcohol-dependent patients and may result in a faster clinical response. In this open-label HF-rTMS feasibility study, we wanted to replicate previous findings of baseline brain activation as a predictor of relapse, and to evaluate how this intervention influences the relapse neurocircuit of "treatment-seeking" alcohol-dependent patients, by means of functional magnetic resonance imaging (fMRI) cue-exposure paradigms. Because relapsing patients have a diminished resilience of the emotion regulation/cognitive control system, before HF-rTMS treatment, we expected lower neuronal activation of especially the ventromedial prefrontal cortex and anterior cingulate cortex (ACC) during the presentation of alcohol-related cues in these patients. The relapse neurocircuit should be modified after accelerated HF-rTMS treatment, only in those patients who did not relapse. Methods: After being administered a single sham-controlled HF-rTMS session (20 Hz to 110% motor threshold), 19 alcohol-dependent patients received an accelerated HF-rTMS protocol, consisting of 14 right dorsolateral prefrontal cortical sessions spread over 3 days. Before and after stimulation, during fMRI patients were confronted with a block and an event-related alcoholic cue-exposure paradigm. Relapse was defined as the consumption of any amount of alcohol within 4 weeks after the stimulation. A region of interest analysis was performed to evaluate how HF-rTMS exerts its effect. Results: After 4 weeks, 13 of 19 patients had already consumed alcohol. When abstainers were compared to patients who had relapsed, we found higher dorsal ACC (dACC) activation at baseline, but only during the blocked cue-exposure paradigm. The effects of HF-rTMS on dACC blood oxygen level-dependent response were negatively correlated with the baseline dACC activation. Due to susceptibility artifacts located at the ventral cortical aspects in 6 of our participants, reliable data were only obtained for the ACC. Conclusions: Our data indicate that higher baseline dACC activation may serve as a protective mechanism regarding relapse. For the first time, it is demonstrated that accelerated HF-rTMS treatment influences dACC activation in a rate-dependent manner: the lower the baseline dACC activation, the more dACC activity was increased after HF-rTMS treatment