title: Functional co-activation within the prefrontal cortex supports the maintenance of behavioural performance in fear-relevant situations before an iTBS modulated virtual reality challenge in participants with spider phobia.
abstract: A number of studies/meta-analyses reported moderate antidepressant effects of activating repetitive transcranial magnetic stimulation (rTMS) over the prefrontal cortex (PFC). Regarding the treatment of anxiety, study outcomes are inconsistent, probably because of the heterogenity of anxiety disorders/study designs. To specifically evaluate the impact of rTMS on emotion regulation in fear-relevant situations we applied a sham-controlled activating protocol (intermittent Theta Burst Stimulation/iTBS) over the left PFC (F3) succeeded by a virtual reality (VR) challenge in n=41 participants with spider phobia and n=42 controls. Prior to/after iTBS and following VR prefrontal activation was assessed by functional near-infrared spectroscopy during an emotional Stroop paradigm. Performance (reaction times/error rates) was evaluated. Stimuli were rated regarding valence/arousal at both measurements. We found diminished activation in the left inferior frontal gyrus (IFG) of participants with spider phobia compared to controls, particularly elicited by emotionally-irrelevant words. Simultaneously, a functional connectivity analysis showed increased co-activation between the left IFG and the contra-lateral hemisphere. Behavioural performance was unimpaired. After iTBS/VR no significant differences in cortical activation between the phobic and control group remained. However, verum-iTBS did not cause an additional augmentation. We interpreted our results in terms of a prefrontal network which gets activated by emotionally-relevant stimuli and supports the maintenance of adequate behavioural reactions. The missing add-on effects of iTBS might be due to a ceiling effect of VR, thereby supporting its potential during exposure therapy. Concurrently, it implies that the efficient application of iTBS in the context of emotion regulation still needs to be studied further.
authors.affiliation: Department of Psychiatry and Psychotherapy, Calwerstr. 14, University of Tuebingen, 72076 Tuebingen, Germany, Germany. Electronic address: saskia.deppermann@med.uni-tuebingen.de.
authors.forename: S
authors.initials: S
authors.lastname: Deppermann
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, Albert-Schweitzer-Campus 1, Gebaeude A9, University of Muenster, Muenster, Germany, Germany. Electronic address: swantje.notzon@gmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Notzon
authors.affiliation: Department of Psychiatry and Psychotherapy, Calwerstr. 14, University of Tuebingen, 72076 Tuebingen, Germany, Germany. Electronic address: Agnes.Kroczek@med.uni-tuebingen.de.
authors.forename: A
authors.initials: A
authors.lastname: Kroczek
authors.affiliation: Department of Psychiatry and Psychotherapy, Calwerstr. 14, University of Tuebingen, 72076 Tuebingen, Germany, Germany. Electronic address: David.Rosenbaum@med.uni-tuebingen.de.
authors.forename: D
authors.initials: D
authors.lastname: Rosenbaum
authors.affiliation: Department of Psychiatry and Psychotherapy, Calwerstr. 14, University of Tuebingen, 72076 Tuebingen, Germany, Germany. Electronic address: Florian.Haeussinger@med.uni-tuebingen.de.
authors.forename: F B
authors.initials: FB
authors.lastname: Haeussinger
authors.affiliation: Department of Psychology (Clinical Psychology) and Psychotherapy, Universitaetsstr. 31, University of Regensburg, 93053 Regensburg, Germany, Germany. Electronic address: Julia.Diemer@psychologie.uni-regensburg.de.
authors.forename: J
authors.initials: J
authors.lastname: Diemer
authors.affiliation: Department of Psychiatry, University of Wuerzburg, Germany, Germany. Electronic address: Domschke_K@ukw.de.
authors.forename: K
authors.initials: K
authors.lastname: Domschke
authors.affiliation: Department of Psychiatry and Psychotherapy, Calwerstr. 14, University of Tuebingen, 72076 Tuebingen, Germany, Germany. Electronic address: Andreas.Fallgatter@med.uni-tuebingen.de.
authors.forename: A J
authors.initials: AJ
authors.lastname: Fallgatter
authors.affiliation: Department of Psychiatry and Psychotherapy, Calwerstr. 14, University of Tuebingen, 72076 Tuebingen, Germany, Germany. Electronic address: Ann-Christine.Ehlis@med.uni-tuebingen.de.
authors.forename: A-C
authors.initials: AC
authors.lastname: Ehlis
authors.affiliation: Mood and Anxiety Disorders Research Unit, Department of Psychiatry and Psychotherapy, Albert-Schweitzer-Campus 1, Gebaeude A9, University of Muenster, Muenster, Germany, Germany. Electronic address: Peter.Zwanzger@kbo.de.
authors.forename: P
authors.initials: P
authors.lastname: Zwanzger
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D001931:Brain Mapping; D004569:Electroencephalography; D005239:Fear / Q000523:psychology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D008297:Male; D010698:Phobic Disorders / Q000000981:diagnostic imaging / Q000628:therapy*; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000502:physiology*; D011930:Reaction Time; D016037:Single-Blind Method; D019265:Spectroscopy, Near-Infrared; D013112:Spiders; D050781:Transcranial Magnetic Stimulation / Q000379:methods*; D063367:Virtual Reality Exposure Therapy / Q000379:methods*; D055815:Young Adult
keywords: Emotion regulation; Functional connectivity; Functional near-infrared spectroscopy; Intermittent theta burst stimulation; Spider phobia; Virtual reality