Table 3.
Effect of rTMS on fear extinction in clinical groups.
| References | Study type | N/Groups | Syndrome | Gender, M/F (age, Mean ± SD) | Target area | Coil position | Online/offline stimulation | Pulses per session/duration | Frequency/Intensity/Coil shape | Outcome measures | Outcome direction |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Notzon et al. (2015) | RCT, Single blind, active (control site) and sham controlled | 83/4 | Spider phobia | 1) 4/37 (27.51 ± 9.4) 2) 5/37 (25.43 ± 7.37) 3) 4/36 (25.85 ± 7.65) 4) 5/38 (27.02 ± 9.23) |
Left dlPFC | F3 | Offline, before the VR challenge | iTBS/600/3 min | 15 Hz/80% RMT/figure of 8 | FSQ, SPQ, ASI, psychophysiological measures (HR, HRV, SCR) | iTBS - had no general effect of on anxiety, disgust, HR and SCR. - significantly increased sympathetic activity |
| Herrmann et al. (2017) | RCT, Double blind, sham controlled | 39/2 | Acrophobia | 1) 6/13 (46.6 ± 13.7) 2) 7/13 13/26 (43.2 ± 12.6) |
mPFC | Fpz | Offline, before exposure | rTMS/1560/2 × 20 minutes | 10 Hz/100% RMT/Round | AQ, BAT | - rTMS reduced phobic anxiety immediately after two sessions of VR exposure therapy. - No differences between active and sham rTMS stimulation at follow up. |
| Osuch et al. (2009) | Double-blind, sham controlled | 9/1 | PTSD | 1/8 (41.4 ± 12.3) | Right dlPFC | 5 cm rostral to APB muscle hotspot | Online, during exposure to emotionally provoking memories. | rTMS/1800/30 min per session/20 sessions | 1 Hz/100% RMT/figure of 8 | CAPS, IES, HDRS | - Active rTMS showed a larger improvement of hyperarousal symptoms compared to sham |
| Isserles et al. (2013) | RCT, Double-blind, sham controlled, controlled for traumatic event as well | 26/3 | PTSD | 1) 7/2 (49 ± 12.5) 2) 8/1 (40.4 ± 10.5) 3) 5/3 (40.5 ± 9.8) |
mPFC | H-Coil designed tostimulate the mPFC. | Offline, after exposure to the traumatic event | Deep rTMS/1680/15.5 min per session/12 sessions | 20 Hz/120% RMT/H-coil | CAPS, PSS-SR, HDRS, BDI, psychophysiological data (HR) | -Symptom improvement by dTMS (revealed by changes in CAPS, PSS-SR, HDRS, BDI and HR) |
| Fryml et al. (2019) | RCT, Double blind, sham controlled | 8/2 | PTSD | 1) 2/1 (30 ± 2.6) 2) 5/0 (27 ± 2.1) |
Leftor right dlPFC | 6 cm anterior to the right hand motor thumb area | Online, duringprolonged exposure therapy | rTMS/6000/30 min per session/8 sessions | 10Hz/120% RMT/figure of 8 | CAPS, HRSD | - Change in HRSD showed antidepressant benefit of rTMS. - CAPS scores showed no significant improvement |
| Carmi et al. (2018) | RCT, Double blind, sham controlled | 41/3 | OCD | 1) 9/7 (36 ± 2.1) 2) 4/4 (28 ± 3.1) 3) 7/7 (35 ± 3.5) |
mPFCand ACC | 4 cm anterior to theleg motor spot at midline | Offline, following symptom provocation | Deep rTMS/HF: 2000 LF: 900/25 sessions | HF: 20 Hz, LF: 1 Hz/HF: 100% RMT, LF: 110% RMT/H7 Coil | YBOCS, CGI-I | - Symptoms improved by high frequency deep rTMS (YBOCS, CGI-I) |
| Carmi et al. (2019) | RCT, Double blind, sham controlled | 94/2 | OCD | 1) 20/27; (41.1 ± 11.97) 2) 19/28 (36.5 ± 11.38) |
mPFCand ACC | 4 cm anterior to the foot motor spot | Offline, following symptom provocation | Deep rTMS/2,000/29 sessions | 20 Hz/100% RMT/H7 coil | YBOCS, CGI-I, CGI-S, and Sheehan Disability Scale scores | - Symptom improvement by dTMS (YBOCS, CGI-I, CGI-S) |
| Adams et al. (2014) | Case study, Single blind | 1 | OCD | 1/0 (52 yo) | Pre-supplementary motor area | 50% of the distance between the Fz and FCz | Offline, immediately prior ERP exercises | rTMS/1200/20 min per session/15 sessions | 1 Hz/110% RMT/figure of 8 | YBOCS,PHQ-9,GAD-7, DOCS | - Symptom improvement in YBOCS, DOCS, GAD-7, and PHQ-9 |
| Grassi et al. (2015) | Case study | 1 | OCD | 0/1 (32 yo) | Left dlPFC | N.R. | Offline, immediately prior ERP exercises. | rTMS/1800/N.A./10 sessions | 10 Hz/80% RMT/NR | Y-BOCS, CGI-I, HAM-D, GAF | - Symptom improvement in Y-BOCS, CGI-I, GAF |
ACC, Anterior cingulate cortex; dlPFC, dorsolateral prefrontal cortex; mPFC, medial prefrontal cortex; vmPFC, ventromedial prefrontal cortex; iTBS, intermittent theta burst stimulation; rTMS, repetitive transcranial magnetic stimulation; LF, low frequency; HF, high frequency; MEP, motor evoked potential; RMT, resting motor threshold; PTSD, Posttraumatic stress disorder; OCD, Obsessive-Compulsive disorder; HR, heart rate; HRV, heart rate variability; SCR, Skin conductance response; EEG, electroencephalography; FPS, Fear potentiated startle; fNIRS, Functional near-infrared spectroscopy; CAPS, Clinician Administered PTSD Scale; IES, The Impact of Event Scale; SPQ, Spider Phobia Questionnaire; FSQ, Fear of Spiders Questionnaire; ASI, Anxiety Sensitivity Index; AQ, acrophobia questionnaire; BAT, Behavioral Avoidance Test; BDI, Beck Depression Inventory; HDS, Hamilton Depression scale; HDRS, Hamilton Rating Scale for Depression; PGI-T, Patient Global Impression of Improvement; Y-BOCS, Yale-Brown Obsessive-Compulsive Scale; GAF, Global Assessment of Functioning; GAD-7, General Anxiety Disorder Scale; PHQ-9, Patient Health Questionnaire; DOCS, Dimensional Obsessive-Compulsive Scale; CGI-S, Clinical Global Impression—severity scale; CGI-I, The CGI—improvement scale; ERP, Exposure Response Prevention; N/A, not applicable; N.R., not reported.