Table 1.
provides information on the reviewed studies with functional paradigms including participant characteristics, type and duration of treatment, employed fMRI paradigm, as well as neuroimaging results with (i) findings of pre-post-treatment differences and group-by-time interaction effects, and (ii) findings of correlation analysis between CAPS score change (indicator of symptom improvement) and neural patterns. Only results and sample of subjects are mentioned who completed treatment and the second fMRI scan. Only significant results (p<0.05) are reported. The individual studies are grouped by the type of paradigm applied (mainly emotional vs. cognitively demanding)
|
Study |
Sample size (n) of (R=remitted) patients, number of male subjects, type of trauma event |
Sample size (n) and type of control subjects |
Pre-CAPS scores Mean (and SD) of total CAPS scores |
Post-CAPS scores Mean (and SD) of total scores |
Psychiatric comorbidities in patient group (in subsample size or in percent) |
Type & duration of treatment |
Type of paradigm within (f)MRI scans |
Neuronal alterations from pre- to post-treatment |
Correlation analysis between symptom improvement (reduction in CAPS scores) & neuronal changes ↑ means pos. correlation ↓ means neg. correlation |
|
(Social) emotional processing fMRI paradigms (mainly not cognitively demanding) | |||||||||
| Van Rooij et al. (2016) | R=21 (all male) war veterans |
H-Res=23 Non-R=22 |
R: 66.3 (12.6) Non-R: 74.4 (13.1) |
R: 24.3 (14.1) Non-R: 66.0 (15.3) |
R (Pre/Post): Mood disorder: 10/1 Anxiety disorder: 3/2 Non-R (Pre/Post): Mood: 14/6 Anxiety: 11/5 |
Trauma-focused CBT and/or EMDR R/Non-R (mean): 10.6/7.30 |
Emotional processing task (viewing & rating neutral, positive, negative, trauma-unrelated emotional pictures, only congruent are analyzed) |
ROI analyses (ROIs: amygdala, dACC, insula, hippocampus, vmPFC): R and H-Res show no change Non-R: ↓ amygdala Whole-brain analyses: not significant |
(↓ amygdala (r=-.34, p=.026), but can be explained by change in Non-R group only) |
| Felmingham et al. (2007) | 8 (3 males) assault or car accident |
No control group | 78.1 (20) | 28.9 (20.3) → All patients at least 30% reduction in total CAPS score |
Mood: 4 | Imaginal exposure & cognitive restructuring 8 once-weekly sessions |
Presentation of fearful & neutral facial expressions | Pre-post-comparison: Contrast fearful & neutral faces: ROI analyses (ROIs: amygdala, ACC): ↑ in bilateral rACC (left: p=.021, k=10, right: p=.036, k=36) Whole-brain analysis: ↓ right postcentral gyrus (k=172) ↓ right middle temporal gyrus (k=29) ↓ left superior temporal gyrus (k=41) ↑ left middle temporal gyrus (k=213) ↑ right inferior frontal gyrus (k=57) ↑ left parietotemporal gyrus (k=47) ↑ right hippocampus (p=.001, k=6) |
↑ right rACC activity (r=.84, p<.01) ↓ bilateral amygdala (r=-.85, p<.01) |
| King et al. (2016b) | 13 (all male) combat veterans |
Control group therapy=8 (PTSD patients, all male, combat veterans, PCGT incl. elements of affective PTSD treatment) |
72.29 (18.32) controls: 74.11 (15.34) |
Decrease of average 16 points (ES: d=0.92) controls: decrease of average 7 points (ES d=0.43) |
Mood: 93% Anxiety: 21% Substance: 21% |
Mindfulness-based exposure therapy (MBET) group therapy 16 weeks |
Emotional faces matching task (angry, fearful, neutral faces; instruction: choose target between two faces) |
Whole-brain & ROI analyses (ROIs: amygdala, mPFC/ACC): Group-by-time-interaction: In MBET patients (not in PCGT): Angry faces: ↑ left amygdala (F=10.65, k=16) right parahippocampus (F=21.43, k=25) ↑ right fusiform/lingual gyrus (F=20.8, k=36) right precuneus (F=18.11, k=202) PCC (F=10.76, k=15) Fearful faces: ↑ left medial frontal gyrus (BA10, F=17.19, k=16) Neutral faces: ↑ bilateral fusiform/lingual gyrus (right: F=20.80, k=71, left: F=11.28, k=30) left lingual gyrus (F=12.27, k=73) left caudate body (F=11.12, k=36) |
ROI analyses: in both treatment groups in response to angry faces: ↑ rACC/mPFC (BA32/BA10, k=42) ↑ left amygdala/peri-amygdala area (k=15) |
| Simmons et al. (2013) | R=9 (all male) combat veterans |
Non-R=15 | R: 86.7 (15.4) Non-R: 91.1 (13.4) |
R: 25.8 (16.5) Non-R: 75.1 (16.2) |
R/Non-R: MDD: 8/8 Anxiety: 9/15 Personality disorder: 1/4 |
PE 8-12 weeks à 90 min. |
Affective anticipation task (combat-related/ negative images vs. noncombat-related/positive images) |
Group-by-time interaction: During negative anticipation (after treatment): R: ↓ left ventral anterior insula During positive anticipation (after treatment): Non-R: ↑ left ventral anterior insula Functional Connectivity analysis (seed: left ventral anterior insula): R: ↑ connectivity with right cingulate/medial frontal gyrus right mid-posterior insula/middle frontal gyrus Non-R: Mild reduction in connectivity Regions differed between the groups: left cerebellum |
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| Aupperle et al. (2013) | 14 n=11 meet full PTSD criteria, n=3 partial PTSD (all female) intimate partner violence |
No control group | 66.07 (16.78) | 16.29 (16.81) In 12 patients: symptom reduction ≥ 50% |
BDI-II mean (pre/post): 20.50/7.07 > sign. decline (t(13)=4.71, p <.001) |
Cognitive trauma therapy for battered women Weekly sessions à 90 min., mean sessions=11.57 (SD=1.60) |
Anticipation task (1) continuous performance task (with cues about stimuli) & (2) interspersed presentation of positive & negative affective images |
From pre-to-post-treatment: Image anticipation phase (negative-positive images): Whole-brain analyses: ↑ left PCC (BA29, cluster size=2176 mm3) ↑ left ACC, medial frontal gyrus (BA9 & 32, 1472 mm3) ↑ right cerebellum (2048 mm3) ↑ left cerebellum (1088 mm3) ↑ right superior/middle temporal gyrus (1664 mm3) ↓ right middle frontal gyrus (BA10, 960 mm3) ↓ right mid Insula (BA13, 832 mm3) ROI analyses (bilateral insula, amygdala, cingulate): No additional findings. Image presentation phase: Whole-brain analyses: ↑ right precuneus, inferior parietal (BA40, 1344 mm3) ↑ left precuneus, PCC (BA31, 896 mm3) ↑ right precuneus (BA31, 896 mm3) ↓ left dlPFC (BA9, 1280 mm3) ROI analyses additionally: ↓ right amygdala (448 mm3) |
Linear mixed effect analyses: Image anticipation phase: ↓ left anterior insula (BA 13, 1216 mm3) ↓ PCC (BA 29, 1472 mm3, ROI: BA 31, 448 mm3) ↓ precuneus (BA 7, 896 mm3) ROI analyses additionally: ↑ right posterior insula (384 mm3) Image presentation phase: ↑ bilateral precuneus (BA 18&19, left: 9344 mm3, right: 1664 mm3) ↑ right PCC (BA 31, 832 mm3) ↑ medial frontal gyrus (BA 6, 1920 mm3) ↑ precentral gyrus (BA 4, 1216 mm3) ↑ lingual gyrus (BA 18, 1216 mm3) ↑ cerebellum (2048 mm3) ↑ inferior temporal gyrus (448 mm3) ↓ right superior/ transverse temporal gyrus (BA: 41, 1344 mm3) ↓ cerebellum (3840 mm3) ↓ caudate body (896 mm3) ROI analyses additionally: ↑ left posterior insula (BA:13, 448 mm3) |
| Peres et al. (2011) | 12 partial PTSD (all male) policemen, gunfire attacks |
Wait list=12 (partial PTSD) H-Res=12 (policemen) |
Patients: 48 (3.62) Wait list: 43 (4.82) |
Patients: 19 (5.03) > at least 37% fewer PTSD symptoms Wait list: 46 (2.70) > no sign. change |
No comorbidities | Exposure and Cognitive Restructuring Therapy | Acoustic-cue paradigm: recall/retrieval cued by pleasant, neutral, & traumatic memories =symptom provocation task |
Pre-post-comparison: ROI analyses (ROIs: OFC, PFC, parietal lobes, ACC, amygdala, insula, thalamus, hippocampus): PTSD group during traumatic memory retrieval: ↓ left amygdala than before treatment (Pcorr<.001, k=92) ↑ mPFC than for wait list after treatment R and H-Res: ↓ left amygdala (Pcorr<.001, k=232) ↑ mPFC (Pcorr<.001, k=1852) Wait list at post scan – like pre-scan: ↑ left amygdala (Pcorr<.001, k=576) ↓ mPFC (Pcorr<.001, k=1623) Whole-brain analysis and other ROIs: no significant differences. |
Only in R: ↑ mPFC (r=.82, p=.02) ↓ left amygdala (r=-0.86, p=.04) |
| Roy et al. (2014) | 10 (mainly male) combat veterans (partly with TBI, from Roy et al. (2010) |
H-Res=18 combat-exposed |
VRET + PE: 84.1 (12.62) VRET: 80.44 (13.31) PE: 72.7 (13.01) |
VRET + PE: 80.67 (14.97) > no sign. change VRET: 64.5 (23.07) > sign. change PE: 75.9 (11.79) > no sign. change |
PE: BDI: 27.2 pre-treatment (from (Roy et al., 2010), n=8) |
VRET (n=4) or PE (n=6) 12-20 sessions à 90 min. |
Affective Stroop task (emotions: negative, positive, neutral) |
Whole-brain analyses: VRET + PE: Treatment group emotion-by-time interaction: Response to negative images: ↓ right amygdala ↑ vmPFC Response to neutral images: ↑ ACC (ROIs: amygdala, hippocampus, ACC (Roy et al., 2010) |
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| Thomaes et al. (2012) | 16 (all female) child abuse-related complex PTSD |
H=22 (all female) and TAU treatment group |
EXP and TAU: 88.5 (13.9) EXP: 92.7 (9.5) TAU: 83.1 (17.5) |
EXP and TAU: 66.2 (22.0) > sign. reduction > no sign. diff. between both treatments EXP: 62.4 (27.4) TAU: 71.0 (12.9) |
Anxiety: 76% Mood: 62% Personality: 75% Dissociative symptoms (DES=22.1) |
2 treatments: EXP = 9 (Psycho-educational & cognitive behavioral stabilizing group therapy added to TAU) TAU = 7 (supportive care/pharmacotherapy) 20 weekly 2 hour session about 6 months |
Classical & affective Stroop task (trauma-relevant, general negative, & neutral words) |
Classical stroop task: Treatment type-by-time interaction: Post-treatment in EXP group (post<pre): ↓ dorsal ACC (right: p(SVC)=.008, left: p(SVC)=.032) ↓ left anterior insula (p(SVC)=.038) (ROI: dorsal ACC, anterior insula, superior frontal cortex) |
Emotional stroop task: Negative/trauma vs. neutral words: Positive correlation between CAPS improvement and ↓ dorsal ACC (p(SVC)<.05) |
| Helpman et al. (2016a) |
16 car accidents, sexual or physical assaults, witnessing serious injuries/ deaths |
H-Res=16 |
PTSD: 78.53 (16.31) |
Sign. reduction in CAPS in PTSD group (mean difference= 49.93, SE=3.49, p = 0.001) |
Exclusion criteria: diagnosis of psychosis, substance/ alcohol dependence within the past six months or abuse within past two months; HAM-D-17 score>24 |
PE 10 weeks |
Fear conditioning and extinction on day 1, extinction recall on day 2 |
Pre-post-comparison during extinction recall: ROI analyses (ROIs: amygdala, hippocampus, insula, subcallosal cortex, mPFC, OFC, ACC, thalamus, vmPFC): PTSD group: ↓ right rACC (t(15)=3.79, k=23, p=.021) H-Res: ↑ left vmPFC (t(15)=3.76, k=61, p=.019) Pre- to post-treatment changes during recall and CAPS changes among PTSD group: ↓ right subgenual ACC (cluster size=84, p=0.017) ↓ left hippocampal (cluster size = 45 p = 0.011) ↓ parahippocampal region > were significantly associated with percent decrease in CAPS score See Supplement for further analyses. |
No sign. correlation between CAPS and rACC change. |
|
Cognitively demanding fMRI tasks (mainly with emotional stimuli) | |||||||||
| Fonzo et al. (2017b) | 25 PTSD patients to treatment (23 female) mainly sexual/ physical assault, injury, combat, natural disaster |
Wait list=26 (PTSD patients) |
66.33 (15.17) Wait list: 71.37 (14.99) |
29.60 (21.26) Wait list: 64.23 (21.77) |
Mood: n=23 (64%) | PE 9-12 sessions à 90 min. |
(1) Emotional reactivity task: identify color of presented tinted fearful/neutral faces (2) Emotional conflict task: fearful & happy faces with (in-)congruent emotion words; identify emotion (3) Gender conflict task (as control task): same facial stimuli as in (2); identify gender (4) Reappraisal task: (a) experience emotional response while viewing negative & positive pictures, (b) try to reduce emotional distress while viewing negative pictures |
Voxel-wise analyses (with post hoc): Time-by-treatment arm effects: Reappraisal task (contrast of reducing emotional response to just looking at negative pictures): Treatment group: ↑ left lateral frontopolar cortex (middle frontal gyrus, BA 10) (No change in wait list group) ↑ left lateral frontopolar context-dependent connectivity (by PPI) with vmPFC (spanning olfactory cortex, ACC, mid-orbital gyrus)/ventral striatum No sign. time-by-treatment arm interaction effects in other regions of whole-brain or ROI analyses (ROIs: bilateral amygdala, anterior insula); no sign. effects in emotional reactivity or conflict task. No additional effects of remission status. |
Generalized linear model: Treatment group: ↑ left lateral frontopolar cortex with improvements in CAPS hyperarousal symptoms (Wald X2=7.71, p=.005) |
| Farrow et al. (2005) | 13 (9 males) assault, traffic, or industrial accident |
No control group | 54 | 20 | No comorbidities | Modified CBT: with a forgiveness component in average 7.3 (± 2.4) sessions |
Empathy judgments & social reasoning (reading & judging scenarios: 1) social reasoning as baseline, 2) empathic judgment, 3) forgivability, 4) intention task) |
Post-minus-pre-treatment: Empathic vs. social reasoning judgments: ↑ left middle temporal gyrus (BA 21, k=24) Forgivability vs. social reasoning judgments: ↑ PCC/precuneus (BA31/7, k=19) ↑ left middle frontal gyrus (BA 8/9, k=14) |
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| Van Rooij et al. (2015a) | R=22 (all male) war veterans |
Non-R=17 H-Res=22 (all male) |
R: 71.7 (15.2) Non-R: 70.3 (11.3) |
R: 28.1 (17.8) Non-R: 66.1 (16.2) |
R (Pre/Post): Mood: 11/3 Anxiety: 4/2 Somatic: 1/0 Non-R (Pre/Post): Mood: 9/2 Anxiety: 8/5 Somatic: 1/1 |
Trauma-focused CBT and/or EMDR R/Non-R (mean): 8.8/9.8 |
Inhibition task stop-signal anticipation task withholding response (inhibition) & cues for anticipation (contextual cue processing) |
All patients vs. H-Res: No group-by-time interactions in whole-brain or ROI analyses (ROIs: amygdala, dACC, insula, hippocampus, vmPFC, left motor cortex, rIFG, right striatum). |
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Abbreviations: ACC=anterior cingulate cortex, BA=Brodmann’s area, CAPS=Clinician-Administered PTSD Scale for DSM-IV, CBT=Cognitive Behavioral Therapy, dACC=dorsal ACC, dlPFC=dorsolateral prefrontal cortex, EMDR=Eye Movement Desensitization and Reprocessing, EXP=experimental treatment, FC=functional connectivity, H=healthy, trauma-unexposed subjects (without traumatic event in the past), H-Res=healthy, resilient controls (healthy, trauma-exposed subjects; no fulfilling of PTSD despite exposure to a traumatic event), k=cluster size, Non-R=non-responder (with persistent PTSD diagnosis after therapy; ‘non-remitted’), MBET=Mindfulness-based exposure therapy, OFC=orbitofrontal cortex, mPFC=medial prefrontal cortex, PCC=posterior cingulate cortex, PCGT=Present-Centered Group Therapy, PE=Prolonged exposure therapy, R=responder, rACC=rostral ACC, ROI=region of interest, SD=standard deviation, TAU=treatment as usual, vmPFC=ventromedial prefrontal cortex, VRET=Virtual reality exposure therapy, ↑=significant increase (of activation) in mentioned region, ↓=decrease in mentioned region.