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. 2019 Jan-Feb:3:2470547019838971.
doi: 10.1177/2470547019838971. Epub 2019 Apr 15.

Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment

Chadi G Abdallah  1   2 , Christopher L Averill  1   2 , Amy E Ramage  3 , Lynnette A Averill  1   2 , Evelyn Alkin  1   2 , Samaneh Nemati  1   2 , John H Krystal  1   2 , John D Roache  4 , Patricia Resick  5 , Stacey Young-McCaughan  4 , Alan L Peterson  4   6   7 , Peter Fox  4   6   8   9 ; STRONG STAR Consortium
Affiliations

Reduced Salience and Enhanced Central Executive Connectivity Following PTSD Treatment

Chadi G Abdallah et al. Chronic Stress (Thousand Oaks). 2019 Jan-Feb.

Abstract

Background: In soldiers with posttraumatic stress disorder (PTSD), symptom provocation was found to induce increased connectivity within the salience network, as measured by functional magnetic resonance imaging (fMRI) and global brain connectivity with global signal regression (GBCr). However, it is unknown whether these GBCr disturbances would normalize following effective PTSD treatment.

Methods: 69 US Army soldiers with (n = 42) and without PTSD (n = 27) completed fMRI at rest and during symptom provocation using subject-specific script imagery. Then, participants with PTSD received 6 weeks (12 sessions) of group cognitive processing therapy (CPT) or present-centered therapy (PCT). At week 8, all participants repeated the fMRI scans. The primary analysis used a region-of-interest approach to determine the effect of treatment on salience GBCr. A secondary analysis was conducted to explore the pattern of GBCr alterations posttreatment in PTSD participants compared to controls.

Results: Over the treatment period, PCT significantly reduced salience GBCr (p = .02). Compared to controls, salience GBCr was high pretreatment (PCT, p = .01; CPT, p = .03) and normalized post-PCT (p = .53), but not post-CPT (p = .006). Whole-brain secondary analysis found high GBCr within the central executive network in PTSD participants compared to controls. Post hoc exploratory analyses showed significant increases in executive GBCr following CPT treatment (p = .01).

Conclusion: The results support previous models relating CPT to central executive network and enhanced cognitive control while unraveling a previously unknown neurobiological mechanism of PCT treatment, demonstrating treatment-specific reduction in salience connectivity during trauma recollection.

Keywords: PTSD; fMRI; functional connectivity; posttraumatic stress disorder; salience network; symptom provocation.

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Conflict of interest statement

Conflicts of Interest CGA has served as a consultant and/or on advisory boards for FSV7, Genentech and Janssen, and editor of Chronic Stress for Sage Publications, Inc.; he has filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). JHK is a consultant for AbbVie, Inc., Amgen, Astellas Pharma Global Development, Inc., AstraZeneca Pharmaceuticals, Biomedisyn Corporation, Bristol-Myers Squibb, Eli Lilly and Company, Euthymics Bioscience, Inc., Neurovance, Inc., FORUM Pharmaceuticals, Janssen Research & Development, Lundbeck Research USA, Novartis Pharma AG, Otsuka America Pharmaceutical, Inc., Sage Therapeutics, Inc., Sunovion Pharmaceuticals, Inc., and Takeda Industries; is on the Scientific Advisory Board for Lohocla Research Corporation, Mnemosyne Pharmaceuticals, Inc., Naurex, Inc., and Pfizer; is a stockholder in Biohaven Pharmaceuticals; holds stock options in Mnemosyne Pharmaceuticals, Inc.; holds patents for Dopamine and Noradrenergic Reuptake Inhibitors in Treatment of Schizophrenia, US Patent No. 5,447,948 (issued September 5, 1995), and Glutamate Modulating Agents in the Treatment of Mental Disorders, U.S. Patent No. 8,778,979 (issued July 15, 2014); and filed a patent for Intranasal Administration of Ketamine to Treat Depression. U.S. Application No. 14/197,767 (filed on March 5, 2014); US application or Patent Cooperation Treaty international application No. 14/306,382 (filed on June 17, 2014). Filed a patent for using mTOR inhibitors to augment the effects of antidepressants (filed on August 20, 2018). All other co-authors declare no conflict of interest.

Figures

Figure 1.
Figure 1.
The effects of psychotherapy on salience connectivity. (a) The Akiki-Abdallah map of 6 intrinsic connectivity networks: ventral salience (blue), dorsal salience (orange), central executive (yellow), default mode (green), visual (red), and sensorimotor (purple). The black lines mark the salience clusters based on previous cross-sectional findings. (b) There was a significant group by task interaction effects on salience global brain connectivity with GBCr. (c) There was significant increase in GBCr during trauma recollection (i.e., script imagery) compared to during resting state in PTSD patients treated with PCT or CPT, but not in CC. The higher GBCr values in PTSD compared to CC were significant only during trauma recollection, but not a rest. (d) PCT, but not CPT, significantly reduced salience GBCr. *p ≤ .05; **p ≤ .01; ***p ≤ .001. PCT: present-centered therapy; CPT: cognitive processing therapy; CC: combat control.
Figure 2.
Figure 2.
Cortical global connectivity posttreatment. (a and b) The red-yellow clusters mark the vertices with increased global brain connectivity with global signal regression (GBCr) in treated posttraumatic stress disorder (PTSD) compared to controls during symptom provocation. The black lines mark the vertices with p < .005 and corrected α = .05. (c and d) The Akiki-Abdallah map of six intrinsic connectivity networks: ventral salience (blue), dorsal salience (orange), central executive (yellow), default mode (green), visual (red), and sensorimotor (purple). The dark yellow lines mark the salience cluster and the red lines mirror the black lines in (a) and (b), marking the executive cluster.
Figure 3.
Figure 3.
The effects of psychotherapy on executive connectivity. (a) There was a significant group by task interaction effects on executive global brain connectivity with GBCr. (b) There was significant increase in GBCr during trauma recollection (i.e., script imagery) compared to during resting state in PTSD patients treated with PCT or CPT, but not in CC. The higher GBCr values in PTSD compared to CC were significant only during trauma recollection, but not a rest. (c) There was a significant time by task interaction effects on executive GBCr. (d) CPT, but not PCT, significantly increased executive GBCr. n.s.: not significant; *p ≤ .05; **p ≤ .01; ***p ≤ .001. PCT: present-centered therapy; CPT: cognitive processing therapy; CC: combat control.
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