Cited by 120Posttraumatic Stress Disorder ResearchPsychoanalysis and Psychopathology ResearchPsychotherapy Techniques and Applications

Selective Effects of Psychotherapy on Frontopolar Cortical Function in PTSD

Open access
Fonzo, Gregory A., Goodkind, Madeleine S., Oathes, Desmond J., Zaiko, Yevgeniya V., Harvey, Meredith, Peng, Kathy K., Weiss, M. Elizabeth, Thompson, Allison L. +12 more·2017·American Journal of Psychiatry

Abstract

OBJECTIVE: Exposure therapy is an effective treatment for posttraumatic stress disorder (PTSD), but a comprehensive, emotion-focused perspective on how psychotherapy affects brain function is lacking. The authors assessed changes in brain function after prolonged exposure therapy across three emotional reactivity and regulation paradigms. METHOD: Individuals with PTSD underwent functional MRI (fMRI) at rest and while completing three tasks assessing emotional reactivity and regulation. Individuals were then randomly assigned to immediate prolonged exposure treatment (N=36) or a waiting list condition (N=30) and underwent a second scan approximately 4 weeks after the last treatment session or a comparable waiting period, respectively. RESULTS: Treatment-specific changes were observed only during cognitive reappraisal of negative images. Psychotherapy increased lateral frontopolar cortex activity and connectivity with the ventromedial prefrontal cortex/ventral striatum. Greater increases in frontopolar activation were associated with improvement in hyperarousal symptoms and psychological well-being. The frontopolar cortex also displayed a greater variety of temporal resting-state signal pattern changes after treatment. Concurrent transcranial magnetic stimulation and fMRI in healthy participants demonstrated that the lateral frontopolar cortex exerts downstream influence on the ventromedial prefrontal cortex/ventral striatum. CONCLUSIONS: Changes in frontopolar function during deliberate regulation of negative affect is one key mechanism of adaptive psychotherapeutic change in PTSD. Given that frontopolar connectivity with ventromedial regions during emotion regulation is enhanced by psychotherapy and that the frontopolar cortex exerts downstream influence on ventromedial regions in healthy individuals, these findings inform a novel conceptualization of how psychotherapy works, and they identify a promising target for stimulation-based therapeutics.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1176/appi.ajp.2017.16091073

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Frontopolar connectivity with ventromedial regions during emotion regulation is a possible key mechanism of psychotherapeutic improvement in PTSD.

    “Given these findings, the authors argue that frontopolar connectivity with ventromedial regions during emotion regulation is a possible key mechanism of psychotherapeutic improvement in PTSD.”
  • Further analysis of the Fonzo et al. study suggested that psychotherapy increased lateral frontopolar cortex activity and connectivity with the vmPFC.

    “Further analysis of this study suggested that psychotherapy increased lateral frontopolar cortex activity and connectivity with the vmPFC [168].”
  • Greater increases in frontopolar activation were associated with improvements in hyperarousal symptoms and psychological well-being.

    “Additionally, greater increases in frontopolar activation were associated with improvements in hyperarousal symptoms and psychological well-being.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 34

  1. [2]Schnurr PP Lunney CA Bovin MJ Marx BP Posttraumatic stress disorder and quality of life: extension of findings to veterans of the wars in Iraq and Afghanistan Clin Psychol Rev 2009 29 727 735 19744758
  2. [4]Foa EB Gillihan SJ Bryant RA Challenges and Successes in Dissemination of Evidence-Based Treatments for Posttraumatic Stress: Lessons Learned From Prolonged Exposure Therapy for PTSD Psychological science in the public interest: a journal of the American Psychological Society 2013 14 65 111 25722657 PMC4338436
  3. [5]Foa EB Hembree EA Rothbaum BO Prolonged Exposure Therapy for PTSD Oxford Oxford University Press 2007
  4. [6]Foa EB Kozak MJ Emotional processing of fear: exposure to corrective information Psychol Bull 1986 99 20 35 2871574
  5. [7]Bohning DE Shastri A McGavin L McConnell KA Nahas Z Lorberbaum JP Roberts DR George MS Motor cortex brain activity induced by 1-Hz transcranial magnetic stimulation is similar in location and level to that for volitional movement Investigative radiology 2000 35 676 683 11110304
  6. [8]Levin P Lazrove S van der Kolk B What psychological testing and neuroimaging tell us about the treatment of Posttraumatic Stress Disorder by Eye Movement Desensitization and Reprocessing J Anxiety Disord 1999 13 159 172 10225506
  7. [9]Lansing K Amen DG Hanks C Rudy L High-resolution brain SPECT imaging and eye movement desensitization and reprocessing in police officers with PTSD The Journal of neuropsychiatry and clinical neurosciences 2005 17 526 532 16387993
  8. [10]Peres JF Newberg AB Mercante JP Simao M Albuquerque VE Peres MJ Nasello AG Cerebral blood flow changes during retrieval of traumatic memories before and after psychotherapy: a SPECT study Psychological medicine 2007 37 1481 1491 17288648
  9. [13]Rabe S Zoellner T Beauducel A Maercker A Karl A Changes in brain electrical activity after cognitive behavioral therapy for posttraumatic stress disorder in patients injured in motor vehicle accidents Psychosom Med 2008 70 13 19 17991819
  10. [14]Thomaes K Dorrepaal E Draijer N de Ruiter MB Elzinga BM van Balkom AJ Smit JH Veltman DJ Treatment effects on insular and anterior cingulate cortex activation during classic and emotional Stroop interference in child abuse-related complex post-traumatic stress disorder Psychological medicine 2012 42 2337 2349 22436595
  11. [15]Felmingham K Kemp A Williams L Das P Hughes G Peduto A Bryant R Changes in anterior cingulate and amygdala after cognitive behavior therapy of posttraumatic stress disorder Psychol Sci 2007 18 127 129 17425531
  12. [16]Peres JF Foerster B Santana LG Fereira MD Nasello AG Savoia M Moreira-Almeida A Lederman H Police officers under attack: resilience implications of an fMRI study Journal of psychiatric research 2011 45 727 734 21159352
  13. [17]Roy MJ Francis J Friedlander J Banks-Williams L Lande RG Taylor P Blair J McLellan J Law W Tarpley V Patt I Yu H Mallinger A Difede J Rizzo A Rothbaum B Improvement in cerebral function with treatment of posttraumatic stress disorder Ann N Y Acad Sci 2010 1208 142 149 20955336
  14. [19]Etkin A Klemenhagen KC Dudman JT Rogan MT Hen R Kandel ER Hirsch J Individual differences in trait anxiety predict the response of the basolateral amygdala to unconsciously processed fearful faces Neuron 2004 44 1043 1055 15603746
  15. [20]Etkin A Schatzberg AF Common abnormalities and disorder-specific compensation during implicit regulation of emotional processing in generalized anxiety and major depressive disorders Am J Psychiatry 2011 168 968 978 21632648
  16. [21]Minkel JD McNealy K Gianaros PJ Drabant EM Gross JJ Manuck SB Hariri AR Sleep quality and neural circuit function supporting emotion regulation Biology of mood & anxiety disorders 2012 2 22 23216889 PMC3542038
  17. [22]Chen AC Oathes DJ Chang C Bradley T Zhou ZW Williams LM Glover GH Deisseroth K Etkin A Causal interactions between fronto-parietal central executive and default-mode networks in humans Proc Natl Acad Sci U S A 2013 110 19944 19949 24248372 PMC3856839
  18. [23]Shannon CE A mathematical theory of communication The Bell System Technical Journal 1948 27 379 423
  19. [24]Wang Z Li Y Childress AR Detre JA Brain entropy mapping using fMRI PloS one 2014 9 e89948 24657999 PMC3962327
  20. [25]Shuiabi E Thomson V Bhuiyan N Entropy as a measure of operational flexibility European Journal of Operational Research 2005 165 696 707
  21. [28]Daw ND O’Doherty JP Dayan P Seymour B Dolan RJ Cortical substrates for exploratory decisions in humans Nature 2006 441 876 879 16778890 PMC2635947
  22. [29]Burgess PW Dumontheil I Gilbert SJ The gateway hypothesis of rostral prefrontal cortex (area 10) function Trends Cogn Sci 2007 11 290 298 17548231
  23. [30]Turner MS Simons JS Gilbert SJ Frith CD Burgess PW Distinct roles for lateral and medial rostral prefrontal cortex in source monitoring of perceived and imagined events Neuropsychologia 2008 46 1442 1453 18294660 PMC2697314
  24. [31]Ramnani N Owen AM Anterior prefrontal cortex: insights into function from anatomy and neuroimaging Nat Rev Neurosci 2004 5 184 194 14976518
  25. [32]Milad MR Rosenbaum BL Simon NM Neuroscience of fear extinction: implications for assessment and treatment of fear-based and anxiety related disorders Behav Res Ther 2014 62 17 23 25204715
  26. [34]Fonzo GA Goodkind MS Oathes DJ Zaiko YV Harvey M Peng KK Weiss ME Thompson AL Zack SE Lindley SE Arnow BA Jo B Gross JJ Rothbaum BO Etkin A Brain activation during emotional reactivity and regulation predicts psychotherapy outcome in posttraumatic stress disorder Am J Psychiatry Under review PMC5711543 28715908
  27. [39]Patel R Spreng RN Shin LM Girard TA Neurocircuitry models of posttraumatic stress disorder and beyond: a meta-analysis of functional neuroimaging studies Neurosci Biobehav Rev 2012 36 2130 2142 22766141
  28. [40]Critchley HD Nagai Y Gray MA Mathias CJ Dissecting axes of autonomic control in humans: Insights from neuroimaging Autonomic neuroscience: basic & clinical 2011 161 34 42 20926356
  29. [42]Burgess PW Gilbert SJ Dumontheil I Function and localization within rostral prefrontal cortex (area 10) Philosophical transactions of the Royal Society of London Series B, Biological sciences 2007 362 887 899 17403644 PMC2430004
  30. [43]Kilts CD Kelsey JE Knight B Ely TD Bowman FD Gross RE Selvig A Gordon A Newport DJ Nemeroff CB The neural correlates of social anxiety disorder and response to pharmacotherapy Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 2006 31 2243 2253 16525417
  31. [44]Klumpp H Fitzgerald DA Phan KL Neural predictors and mechanisms of cognitive behavioral therapy on threat processing in social anxiety disorder Prog Neuropsychopharmacol Biol Psychiatry 2013 45 83 91 23665375 PMC3951971
  32. [45]Nahas Z Anderson BS Borckardt J Arana AB George MS Reeves ST Takacs I Bilateral epidural prefrontal cortical stimulation for treatment-resistant depression Biol Psychiatry 2010 67 101 109 19819427 PMC2863140
  33. [46]Yamanishi T Nakaaki S Omori IM Hashimoto N Shinagawa Y Hongo J Horikoshi M Tohyama J Akechi T Soma T Iidaka T Furukawa TA Changes after behavior therapy among responsive and nonresponsive patients with obsessive-compulsive disorder Psychiatry research 2009 172 242 250 19346109
  34. [47]Nagai Y Critchley HD Featherstone E Trimble MR Dolan RJ Activity in ventromedial prefrontal cortex covaries with sympathetic skin conductance level: a physiological account of a “default mode” of brain function Neuroimage 2004 22 243 251 15110014

Cited by

Sorted by citations

Authors
Fonzo, G. A., Goodkind, M. S., Oathes, D. J., Zaiko, Y. V., Harvey, M., Peng, K. K., Weiss, M. E., Thompson, A. L., Zack, S. E., Mills-Finnerty, C. E., Rosenberg, B. M., Edelstein, R., Wright, R. N., Kole, C. A., Lindley, S. E., Arnow, B. A., Jo, B., Gross, J. J., Rothbaum, B. O., & Etkin, A.
Affiliations
  • Stanford Medicine (US)
  • From the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; the Stanford Neurosciences Institute, Stanford University, Stanford; the Veterans Affairs Palo Alto Healthcare System and the Sierra Pacific Mental Illness, Research, Education, and Clinical Center (MIRECC), Palo Alto, Calif.; the New Mexico Veterans Affairs Healthcare System, Albuquerque; the Center for Neuromodulation in Depression and Stress, Department of Psychiatry, University of...
Venue
American Journal of Psychiatry
Published
2017-12
Volume
174
Issue
12
Pages
1175-1184
ISSN
  • 0002-953X (ISSN-L)
  • 1535-7228
OpenAlex
W2739099034
Cited by
120
References
14
Citations by year
2026: 6 · 2025: 15 · 2024: 13 · 2023: 12 · 2022: 10 · 2021: 9 · 2020: 27 · 2019: 9 · 2018: 14 · 2017: 5
FWCI
18.66
Type
journal article
Language
en
Open access
Locations
  • American Journal of Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R01MH103324, R01MH094757, R01MH091860, T32MH019938)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Social Sciences › Psychology › Clinical Psychology › Psychoanalysis and Psychopathology Research
  • Social Sciences › Psychology › Clinical Psychology › Psychotherapy Techniques and Applications
Keywords
post-traumatic stress disorder, prolonged exposure therapy, frontopolar cortex, emotion regulation, cognitive reappraisal, ventromedial prefrontal cortex, ventral striatum, hyperarousal, resting-state brain activity, transcranial magnetic stimulation
MeSH terms
Adolescent, Adult, Corpus Striatum, Emotions, Female, Frontal Lobe, Humans, Implosive Therapy, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Stress Disorders, Post-Traumatic, Treatment Outcome, Prefrontal Cortex, Transcranial Magnetic Stimulation, Young Adult, Functional Neuroimaging

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review