title: Accelerated HF-rTMS Protocol has a Rate-Dependent Effect on dACC Activation in Alcohol-Dependent Patients: An Open-Label Feasibility Study.
abstract: 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.
authors.affiliation: Department of Psychiatry, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Herremans
authors.affiliation: Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.
authors.forename: Rudi
authors.initials: R
authors.lastname: De Raedt
authors.affiliation: Department of Radiology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Van Schuerbeek
authors.affiliation: Department of Data Analysis, Faculty of Psychology and Physiological Sciences, Ghent University, Ghent, Belgium.
authors.forename: Daniele
authors.initials: D
authors.lastname: Marinazzo
authors.affiliation: Department of Psychiatry, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors.forename: Frieda
authors.initials: F
authors.lastname: Matthys
authors.affiliation: Department of Radiology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: De Mey
authors.affiliation: Department of Psychiatry, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel (VUB), Brussels, Belgium.|Department of Psychiatry and Medical Psychology, Ghent University, Ghent, Belgium.
authors.forename: Chris
authors.initials: C
authors.lastname: Baeken
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000503:physiopathology / Q000628:therapy*; D003463:Cues; D005240:Feasibility Studies; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000503:physiopathology*; D006801:Humans; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009714:Nucleus Accumbens / Q000503:physiopathology; D010296:Parietal Lobe / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000503:physiopathology*; D012008:Recurrence; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D016896:Treatment Outcome
keywords: Accelerated HF-rTMS; Alcohol Addiction; Cue Exposure; Rate Dependence; Relapse