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Cited by 352Posttraumatic Stress Disorder ResearchFunctional Brain Connectivity StudiesTraumatic Brain Injury Research

Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder

Open access
Sripada, Rebecca K., King, Anthony P., Garfinkel, Sarah N., Wang, Xin, Sripada, Chandra S., Welsh, Robert C., Liberzon, Israel·2012·Journal of Psychiatry and Neuroscience
DOI 10.1503/jpn.110069PMC PMC3380095
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Abstract

Background: Converging neuroimaging research suggests altered emotion neurocircuitry in individuals with posttraumatic stress disorder (PTSD). Emotion activation studies in these individuals have shown hyperactivation in emotion-related regions, including the amygdala and insula, and hypoactivation in emotion-regulation regions, including the medial prefrontal cortex (mPFC) and anterior cingulate cortex (ACC). However, few studies have examined patterns of connectivity at rest in individuals with PTSD, a potentially powerful method for illuminating brain network structure. Methods: Using the amygdala as a seed region, we measured resting-state brain connectivity using 3 T functional magnetic resonance imaging in returning male veterans with PTSD and combat controls without PTSD. Results: Fifteen veterans with PTSD and 14 combat controls enrolled in our study. Compared with controls, veterans with PTSD showed greater positive connectivity between the amygdala and insula, reduced positive connectivity between the amygdala and hippocampus, and reduced anticorrelation between the amygdala and dorsal ACC and rostral ACC. Limitations: Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD. Conclusion: These results demonstrate that studies of functional connectivity during resting state can discern aberrant patterns of coupling within emotion circuits and suggest a possible brain basis for emotion-processing and emotion-regulation deficits in individuals with PTSD.

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Written from the paper’s full text.

TL;DR

Resting-state fMRI in male combat veterans found that PTSD was associated with altered amygdala connectivity: greater amygdala–insula coupling and weaker amygdala–hippocampus and amygdala–ACC coupling. These patterns suggest disrupted emotion-generation and emotion-regulation circuit coupling in PTSD.

Key findings

  • Compared with 14 combat controls, 15 veterans with PTSD showed greater positive connectivity between the right amygdala and right insula/superior temporal gyrus (MNI 48, −39, 21; k = 26; z = 3.38; p < 0.005) and reduced anticorrelation between the right amygdala and dorsal ACC (MNI −12, 24, 30; k = 24; z = 3.32; p < 0.005).
  • Combat controls showed greater positive connectivity than PTSD patients between the right amygdala and left hippocampus (MNI −30, −21, −9; k = 20; z = 3.48; p < 0.005) and left inferior orbital frontal gyrus (MNI −30, 36, −9; k = 22; z = 3.45; p < 0.005).
  • For the left amygdala seed, PTSD patients showed greater positive connectivity with the right insula (MNI 54, 0, −3; k = 28; Z = 3.56; p < 0.005) and reduced anticorrelation with the rostral ACC (MNI 6, 36, 12; k = 20; Z = 3.64; p < 0.005).
  • Within the PTSD group, CAPS symptom severity was not significantly associated with amygdala connectivity to the a priori ROIs.

Methods

  • Resting-state functional connectivity study using 3 T fMRI in returning male veterans from Operation Enduring Freedom/Operation Iraqi Freedom with current PTSD (n = 15) versus combat controls without PTSD (n = 14); 30 were scanned and 1 control’s imaging data were lost.
  • PTSD diagnosis was assessed with the Clinician Administered PTSD Scale (CAPS); PTSD group CAPS mean 75.9 (SD 17.2) versus control mean 10.9 (SD 7.7), t26 = 12.9, p < 0.001.
  • Seed-based analysis used right and left amygdala ROIs, band-pass filtering at 0.01–0.10 Hz, Fisher r-to-z transformation, and second-level random-effects tests; whole-brain maps were thresholded at p < 0.005, uncorrected, extent k = 20, with ROI small-volume correction for hippocampus, ACC, and insula.

Limitations

  • Stated: only male veterans with combat exposure were tested, so findings cannot be generalized to women or to individuals with non–combat-related PTSD.
  • Stated: the PTSD sample included 7 participants with comorbid major depression; results were not affected by removing participants with current comorbid depression, so they were retained. Other stated limitations include possible differential anxiety during scanning, correlational methods that cannot infer causality, and controversy about whether global-signal regression introduces artifactual anticorrelation.
  • Evident from the text: the final sample was small (15 PTSD, 14 controls), and the design was cross-sectional, which limits statistical power and causal interpretation.

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Registry

Crossref · 10.1503/jpn.110069

Cites

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Claims the paper makes

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  • Findingown data
    § Results

    Compared with patients with PTSD, combat controls showed greater positive connectivity between the right amygdala seed and the left inferior orbital frontal gyrus (MNI coordinates x, y, z = −30, 36, −9; k = 22; z score = 3.45; p < 0.005).

    “and left inferior orbital frontal gyrus (MNI coordinates x, y, z = −30, 36, −9; k = 22; z score = 3.45; p < 0.005; Table 2 and Fig. 1)”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    Compared with combat controls, patients with PTSD showed reduced anticorrelation between the right amygdala seed and the rostral ACC (MNI coordinates x, y, z = 6, 36, 12; k = 20; Z = 3.64, p < 0.005).

    “and reduced anticorrelation between the right amygdala seed and the rostral ACC (MNI coordinates x, y, z = 6, 36, 12; k = 20; Z = 3.64, p < 0.005; Table 2 and Fig. 1)”
    Quote in the paperSubstantial claim
  • Findingown data
    § Results

    There were no other current Axis I or Axis II disorders in the PTSD group.

    “There were no other current Axis I or Axis II disorders in the PTSD group.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Results

    Within the PTSD group, symptom severity, as measured by the CAPS, was not significantly associated with connectivity between the amygdala and ROIs.

    “Within the PTSD group, symptom severity, as measured by the CAPS, was not significantly associated with connectivity between the amygdala and ROIs.”
    Quote in the paperNot a substantial claim
  • Findingown data
    § Results

    Compared with combat controls, patients with PTSD showed greater positive connectivity between the right amygdala seed and the right insula/superior temporal gyrus (MNI coordinates x, y, z = 48, −39, 21; k = 26; z score = 3.38; p < 0.005).

    “Compared with combat controls, patients with PTSD showed greater positive connectivity between the right amygdala seed and the right insula/superior temporal gyrus (MNI coordinates x, y, z = 48, −39, 21; k = 26; z score = 3.38; p < 0.005)”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. 57
  • May combine two claims. 38

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data
    § Results

    The mean age of the participants was 27.3 (SD 4.5) years in the PTSD group and 26.6 (SD 3.3) years in the control group (t26 = 0.477, p = 0.64).

    “The mean age of the participants was 27.3 (SD 4.5) years in the PTSD group and 26.6 (SD 3.3) years in the control group (t26 = 0.477, p = 0.64).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data
    § Results

    Seven patients in the PTSD group met diagnostic criteria for depression and 1 had comorbid panic disorder, assessed by the MINI.

    “Seven patients in the PTSD group met diagnostic criteria for depression and 1 had comorbid panic disorder, assessed by the MINI.46”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [46] Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(Suppl 20):22–33. quiz 4–57. [PubMed] [Google Scholar]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Findingown data
    § Results

    We scanned 30 veterans from OEF and OIF with (n = 15) or without (n = 15) a current PTSD diagnosis.

    “We scanned 30 veterans from OEF and OIF with (n = 15) or without (n = 15) a current PTSD diagnosis.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    All CAPS scores in the PTSD group were greater than or equal to 50 (mean 75.9, SD 17.2), and CAPS scores in the control group (mean 10.9, SD 7.7) were significantly lower than in the PTSD group (t26 = 12.9, p < 0.001).

    “All CAPS scores in the PTSD group were greater than or equal to 50 (mean 75.9, SD 17.2), and CAPS scores in the control group (mean 10.9, SD 7.7) were significantly lower than in the PTSD group (t26 = 12.9, p < 0.001).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data
    § Results

    All participants were right-handed men between 21 and 37 years old.

    “All participants were right-handed men between 21 and 37 years old.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Results

    In combat controls, the left amygdala seed showed positive connectivity with the right amygdala, periamygdala, bilateral hippocampus and middle temporal gyrus, and anticorrelation with the dorsal ACC, rostral ACC, lateral PFC, inferior parietal cortex and precuneus.

    “The left amygdala seed showed positive connectivity with the right amygdala, periamygdala, bilateral hippocampus and middle temporal gyrus, and anticorrelation with the dorsal ACC, rostral ACC, lateral PFC, inferior parietal cortex and precuneus (Table 1 and Fig. 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    In patients with PTSD, the right amygdala seed showed positive connectivity with the left amygdala, periamygdala, bilateral hippocampus and bilateral insula, and anticorrelation with the dorsal mPFC, rostral ACC and inferior parietal cortex.

    “The right amygdala seed showed positive connectivity with a number of regions, including the left amygdala, periamygdala, bilateral hippocampus and bilateral insula, and anticorrelation with the dorsal mPFC, rostral ACC and inferior parietal cortex (Table 1 and Fig. 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    In patients with PTSD, the left amygdala seed showed positive connectivity with the right amygdala, periamygdala, bilateral hippocampus and bilateral insula, and anticorrelation with the dorsal ACC, lateral PFC, inferior parietal cortex and precuneus.

    “The left amygdala seed showed positive connectivity with the right amygdala, periamygdala, bilateral hippocampus and bilateral insula, and anticorrelation with the dorsal ACC, lateral PFC, inferior parietal cortex and precuneus (Table 1 and Fig. 1).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Methods

    Using the thresholds and cluster sizes defined above, the corrected voxel-wise probabilities are: hippocampus, p < 0.00097; ACC, p < 0.0003; and insular cortex, p < 0.00045.

    “Using the thresholds and cluster sizes defined above, the corrected voxel-wise probabilities are as follows: hippocampus, p < 0.00097; ACC, p < 0.0003; and insular cortex, p < 0.00045.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data
    § Results

    In combat controls, the right amygdala seed showed positive connectivity with the left amygdala, bilateral periamygdala and bilateral hippocampus, and anticorrelation with the dorsal mPFC, dorsal ACC, precuneus, lateral PFC and inferior parietal cortex.

    “The right amygdala seed showed positive connectivity with a number of regions, including the left amygdala, bilateral periamygdala and bilateral hippocampus, and anticorrelation with the dorsal mPFC, dorsal ACC, precuneus, lateral PFC and inferior parietal cortex (Table 1 and Fig. 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data
    § Discussion

    In patients with PTSD, the amygdala was less anti-correlated with the PCC/precuneus than in controls, though the extent was small (less than 10 voxels).

    “In our study, the amygdala was less anti-correlated with the PCC/precuneus in patients with PTSD than controls, though the extent of this activation was small (less than 10 voxels).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Introduction

    Relatively few studies have examined patterns of connectivity in the brains of patients with PTSD at rest.

    “relatively few have examined patterns of connectivity in the brains of patients with PTSD at rest”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35:169–91. doi: 10.1038/npp.2009.83. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Amygdala hyperactivity tends to coincide with mPFC hypoactivity in healthy individuals.

    “As amygdala hyperactivity tends to coincide with mPFC hypoactivity in healthy individuals,9,14”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [9] Phan KL, Wager T, Taylor SF, et al. Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage. 2002;16:331–48. doi: 10.1006/nimg.2002.1087. [DOI] [PubMed] [Google Scholar] source

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    • cites [14] Kim MJ, Gee DG, Loucks RA, et al. Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest. Cereb Cortex. 2011;21:1667–73. doi: 10.1093/cercor/bhq237. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    The amygdala has tight structural connections and reciprocal feedback loops with the mPFC and orbitofrontal cortex as well as with the dorsolateral PFC and ACC.

    “The amygdala has tight structural connections and reciprocal feedback loops with the mPFC and orbitofrontal cortex11 as well as with the dorsolateral PFC12 and ACC.13”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [11] Ghashghaei HT, Hilgetag CC, Barbas H. Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala. Neuroimage. 2007;34:905–23. doi: 10.1016/j.neuroimage.2006.09.046. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    The mPFC is a modulatory region interconnected with limbic structures and involved in emotion regulation.

    “of the mPFC as a modulatory region interconnected with limbic structures8 and involved in emotion regulation.9”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [8] Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology. 2010;35:192–216. doi: 10.1038/npp.2009.104. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    • cites [9] Phan KL, Wager T, Taylor SF, et al. Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage. 2002;16:331–48. doi: 10.1006/nimg.2002.1087. [DOI] [PubMed] [Google Scholar] source

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    Interpretationcitation
    § Introduction

    The pattern of amygdala hyperactivity and mPFC hypoactivity is generally understood to reflect a lack of regulatory control over emotion in individuals with PTSD.

    “and is generally understood to reflect a lack of regulatory control over emotion in individuals with PTSD.”
    Quote in the paperNot a substantial claim

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    Premisecitation
    § Introduction

    Most PTSD neuroimaging studies to date have described abnormalities in emotion-generation regions, such as the amygdala or insula, and emotion-regulation regions, including the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC).

    “Most PTSD neuroimaging studies to date have described abnormalities in emotion-generation regions, such as the amygdala or insula, and emotion-regulation regions, including the anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35:169–91. doi: 10.1038/npp.2009.83. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    A [15O]-H2O PET study of recently traumatized individuals found positive functional connectivity between the amygdala and ACC in response to trauma scripts.

    “a [15O]-H2O positron emission tomography (PET) study of recently traumatized individuals found positive functional connectivity between the amygdala and ACC in response to trauma scripts.16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Osuch EA, Willis MW, Bluhm R, et al. Neurophysiological responses to traumatic reminders in the acute aftermath of serious motor vehicle collisions using [15O]-H2O positron emission tomography. Biol Psychiatry. 2008;64:327–35. doi: 10.1016/j.biopsych.2008.03.010. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Roy and colleagues reported functional connectivity of the amygdala with ventral medial prefrontal regions, insula, thalamus and striatum at rest and anticorrelations with the dorsal ACC, superior frontal gyrus, bilateral middle frontal gyrus and posterior cingulate cortex.

    “Roy and colleagues15 reported functional connectivity of the amygdala with ventral medial prefrontal regions (including the medial frontal gyrus and rostral ACC), insula, thalamus and striatum at rest and anticorrelations with the dorsal ACC, superior frontal gyrus, bilateral middle frontal gyrus and posterior cingulate cortex (PCC)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation
    § Introduction

    In individuals with PTSD, amygdala connectivity during task-based studies has yielded inconsistent findings.

    “In individuals with PTSD, amygdala connectivity during task-based studies has yielded inconsistent findings.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [16] Osuch EA, Willis MW, Bluhm R, et al. Neurophysiological responses to traumatic reminders in the acute aftermath of serious motor vehicle collisions using [15O]-H2O positron emission tomography. Biol Psychiatry. 2008;64:327–35. doi: 10.1016/j.biopsych.2008.03.010. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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      Not checked in the free run.

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    Premisecitation
    § Introduction

    The amygdala is a key region in threat detection, fear conditioning and emotional salience.

    “the known role of the amygdala as a key region in threat detection,5 fear conditioning6 and emotional salience,7”
    Quote in the paperSubstantial claim0 of 3 sources checked
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    Interpretationreasoning
    § Introduction

    Connectivity analyses at rest might potentially be better assessed without the confounds of tasks that may be biased to elicit amygdala activity or provoke PTSD symptoms.

    “These relationships might potentially be better assessed, however, through connectivity analyses at rest, without the confounds of tasks that may be biased to elicit amygdala activity or provoke PTSD symptoms.”
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    Premisecitation
    § Introduction

    Etkin and Wager's meta-analysis suggests coactivation of the right amygdala and insula across studies.

    “Etkin and Wager’s meta-analysis10 also suggests coactivation of the right amygdala and insula across studies”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry. 2007;164:1476–88. doi: 10.1176/appi.ajp.2007.07030504. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    The hippocampus is a medial temporal lobe region adjacent to the amygdala that is implicated in declarative memory, contextual memory and fear conditioning.

    “the hippocampus, a medial temporal lobe region adjacent to the amygdala that is implicated in declarative memory,27 contextual memory28 and fear conditioning,29”
    Quote in the paperNot a substantial claim0 of 3 sources checked
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    Premisecitation
    § Introduction

    The amygdala and insula are structurally interconnected.

    “The amygdala and insula are structurally interconnected,23”
    Quote in the paperNot a substantial claim0 of 1 sources checked
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    Premisecitation
    § Introduction

    Early PET studies reported increased insula activity in response to trauma script-driven imagery in individuals with PTSD, though in some studies no more than in combat-exposed controls.

    “early PET studies reported increased insula activity in response to trauma script–driven imagery in individuals with PTSD,24 though in some studies no more than in combat-exposed controls.25”
    Quote in the paperNot a substantial claim0 of 2 sources checked
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    Premisecitation
    § Introduction

    The insula is responsible for interoception, disgust, emotion processing, emotion recall and anticipation of aversive stimuli.

    “an area responsible for interoception,20 disgust,21 emotion processing,22 emotion recall9 and anticipation of aversive stimuli.19”
    Quote in the paperSubstantial claim0 of 5 sources checked
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      Not checked in the free run.

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    Premisecitation
    § Introduction

    Recent fMRI studies have reported greater insula activation in anticipation of negative images and negative emotional faces in individuals with PTSD as well as enhanced coupling between the insula and amygdala during negative emotion induction in healthy volunteers and during symptom provocation in recently traumatized individuals.

    “Recent fMRI studies have reported greater insula activation in anticipation of negative images19 and negative emotional faces18 in individuals with PTSD as well as enhanced coupling between the insula and amygdala during negative emotion induction in healthy volunteers26 and during symptom provocation in recently traumatized individuals.16”
    Quote in the paperSubstantial claim0 of 4 sources checked
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    • cites [18] Fonzo GA, Simmons AN, Thorp SR, et al. Exaggerated and disconnected insular-amygdalar blood oxygenation level-dependent response to threat-related emotional faces in women with intimate-partner violence posttraumatic stress disorder. Biol Psychiatry. 2010;68:433–41. doi: 10.1016/j.biopsych.2010.04.028. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    • cites [26] van Marle HJ, Hermans EJ, Qin S, et al. Enhanced resting-state connectivity of amygdala in the immediate aftermath of acute psychological stress. Neuroimage. 2010;53:348–54. doi: 10.1016/j.neuroimage.2010.05.070. [DOI] [PubMed] [Google Scholar] source

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    • cites [16] Osuch EA, Willis MW, Bluhm R, et al. Neurophysiological responses to traumatic reminders in the acute aftermath of serious motor vehicle collisions using [15O]-H2O positron emission tomography. Biol Psychiatry. 2008;64:327–35. doi: 10.1016/j.biopsych.2008.03.010. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Functional MRI studies of individuals with PTSD have demonstrated aberrant activity in the insula.

    “Functional MRI studies of individuals with PTSD have also demonstrated aberrant activity in the insula”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Simmons AN, Paulus MP, Thorp SR, et al. Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violence. Biol Psychiatry. 2008;64:681–90. doi: 10.1016/j.biopsych.2008.05.027. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [18] Fonzo GA, Simmons AN, Thorp SR, et al. Exaggerated and disconnected insular-amygdalar blood oxygenation level-dependent response to threat-related emotional faces in women with intimate-partner violence posttraumatic stress disorder. Biol Psychiatry. 2010;68:433–41. doi: 10.1016/j.biopsych.2010.04.028. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    A quantitative meta-analysis suggested overall reduced hippocampal activity in individuals with PTSD.

    “A quantitative meta-analysis, however, suggested overall reduced hippocampal activity in individuals with PTSD.10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry. 2007;164:1476–88. doi: 10.1176/appi.ajp.2007.07030504. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Intrinsic connections between brain networks have been linked to important functions such as processing speed and cognitive flexibility in health and in disease.

    “which in turn have been linked to important functions such as processing speed37 and cognitive flexibility38 in health and in disease.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [37] Kelly AM, Uddin LQ, Biswal BB, et al. Competition between functional brain networks mediates behavioral variability. Neuroimage. 2008;39:527–37. doi: 10.1016/j.neuroimage.2007.08.008. [DOI] [PubMed] [Google Scholar] source

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    • cites [38] Wig GS, Buckner RL, Schacter DL. Repetition priming influences distinct brain systems: evidence from task-evoked data and resting-state correlations. J Neurophysiol. 2009;101:2632–48. doi: 10.1152/jn.91213.2008. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Recent studies have reported alterations in subcortical and default network connectivity in individuals with PTSD.

    “Recent studies have begun to investigate resting-state connectivity in individuals with PTSD and have reported alterations in subcortical31 and default network connectivity.32–35”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [31] Yin Y, Jin C, Hu X, et al. Altered resting-state functional connectivity of thalamus in earthquake-induced posttraumatic stress disorder: a functional magnetic resonance imaging study. Brain Res. 2011;1411:98–107. doi: 10.1016/j.brainres.2011.07.016. [DOI] [PubMed] [Google Scholar] source

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    • cites [32] Bluhm RL, Williamson PC, Osuch EA, et al. Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma. J Psychiatry Neurosci. 2009;34:187–94. [PMC free article] [PubMed] [Google Scholar]

      Not checked in the free run.

    • cites [33] Lanius RA, Bluhm RL, Coupland NJ, et al. Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects. Acta Psychiatr Scand. 2010;121:33–40. doi: 10.1111/j.1600-0447.2009.01391.x. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [34] Daniels JK, Frewen P, McKinnon MC, et al. Default mode alterations in posttraumatic stress disorder related to early-life trauma: a developmental perspective. J Psychiatry Neurosci. 2011;36:56–9. doi: 10.1503/jpn.100050. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    • cites [35] Wu RZ, Zhang JR, Qiu CJ, et al. [Study on resting-state default mode network in patients with posttraumatic stress disorder after the earthquake] [Article in Chinese] Sichuan Da Xue Xue Bao Yi Xue Ban. 2011;42:397–400. [PubMed] [Google Scholar]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted). May combine two claims.

    Premisecitation
    § Introduction

    The hippocampus integrates context into emotional memories and modulates amygdala activity according to context.

    “it has been hypothesized that the hippocampus integrates context into emotional memories and modulates amygdala activity according to context,30”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [30] Liberzon I, Sripada CS. The functional neuroanatomy of PTSD: a critical review. Prog Brain Res. 2008;167:151–69. doi: 10.1016/S0079-6123(07)67011-3. [DOI] [PubMed] [Google Scholar] source

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  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Introduction

    Resting-state amygdala connectivity has been reported to be altered in individuals with generalized anxiety disorder, social phobia, major depressive disorder and bipolar disorder.

    “it has been reported to be altered in individuals with generalized anxiety disorder (GAD),39 social phobia,40 major depressive disorder (MDD)41,42 and bipolar disorder;43”
    Quote in the paperSubstantial claim0 of 5 sources checked
    • cites [39] Etkin A, Prater KE, Schatzberg AF, et al. Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Arch Gen Psychiatry. 2009;66:1361–72. doi: 10.1001/archgenpsychiatry.2009.104. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    • cites [40] Hahn A, Stein P, Windischberger C, et al. Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. Neuroimage. 2011;56:881–9. doi: 10.1016/j.neuroimage.2011.02.064. [DOI] [PubMed] [Google Scholar] source

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    • cites [41] Anand A, Li Y, Wang Y, et al. Activity and connectivity of brain mood regulating circuit in depression: a functional magnetic resonance study. Biol Psychiatry. 2005;57:1079–88. doi: 10.1016/j.biopsych.2005.02.021. [DOI] [PubMed] [Google Scholar] source

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    • cites [42] Veer IM, Beckmann CF, van Tol MJ, et al. Whole brain resting-state analysis reveals decreased functional connectivity in major depression. Front Syst Neurosci. 2010;4:41. doi: 10.3389/fnsys.2010.00041. [DOI] [PMC free article] [PubMed] [Google Scholar]

      Not checked in the free run.

    • cites [43] Chepenik LG, Raffo M, Hampson M, et al. Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder. Psychiatry Res. 2010;182:207–10. doi: 10.1016/j.pscychresns.2010.04.002. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation
    § Introduction

    Resting-state connectivity offers a powerful way to assess intrinsic connections between brain networks.

    “Resting-state connectivity offers a powerful way to assess intrinsic connections between brain networks,3,4,36”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [3] Raichle ME, MacLeod AM, Snyder AZ, et al. A default mode of brain function. Proc Natl Acad Sci U S A. 2001;98:676–82. doi: 10.1073/pnas.98.2.676. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [4] Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci. 2007;8:700–11. doi: 10.1038/nrn2201. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [36] Fox MD, Snyder AZ, Vincent JL, et al. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005;102:9673–8. doi: 10.1073/pnas.0504136102. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Introduction

    Functional neuroimaging studies of the hippocampus in individuals with PTSD have yielded conflicting findings, with some showing hyperactivity and some showing hypoactivity.

    “Functional neuroimaging studies of the hippocampus in individuals with PTSD have yielded conflicting findings, with some showing hyperactivity and some showing hypoactivity.2”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Shin LM, Liberzon I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology. 2010;35:169–91. doi: 10.1038/npp.2009.83. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning
    § Introduction

    This hippocampal function might be disrupted in individuals with PTSD.

    “a function that might be disrupted in individuals with PTSD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Results

    Groups did not differ by race (n = 28, χ25 = 4.18, p = 0.52), marital status (n = 28, χ23 = 6.27, p = 0.099) or level of education (n = 26, χ23 = 5.39, p = 0.15).

    “Groups did not differ by race (n = 28, χ25 = 4.18, p = 0.52), marital status (n = 28, χ23 = 6.27, p = 0.099) or level of education (n = 26, χ23 = 5.39, p = 0.15).”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductcitation
    § Methods

    These combinations of activation threshold and cluster size were determined using AlphaSim to correspond to a false-positive rate of p < 0.05, corrected for multiple comparisons within ROIs.

    “These combinations of activation threshold and cluster size were determined using AlphaSim52 to correspond to a false-positive rate of p < 0.05, corrected for multiple comparisons within ROIs.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [52] Ward B. Simultaneous inference for fMRI data. Milwaukee (WI): Bio-physics Research Institute, Medical College of Wisconsin; 2000. [accessed 2011 Dec. 6]. Available from: http://afni.nimh.nih.gov/pub/dist/doc/manual/AlphaSim.pdf. [Google Scholar]

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  • Classified as probably not a substantial claim.

    Study design and conductcitation
    § Methods

    Participants were screened for comorbid disorders using the Mini-International Neuropsychiatric Interview (MINI).

    “Participants were screened for comorbid disorders using the Mini-International Neuropsychiatric Interview (MINI).46”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Sheehan DV, Lecrubier Y, Sheehan KH, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry. 1998;59(Suppl 20):22–33. quiz 4–57. [PubMed] [Google Scholar]

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    Study design and conductcitation
    § Methods

    The variance owing to physiologic responses (i.e., cardiac and respiratory sources) was removed using regression.

    “The variance owing to physiologic responses (i.e., cardiac and respiratory sources) was removed using regression.47”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Glover GH, Li TQ, Ress D. Image-based method for retrospective correction of physiological motion effects in fMRI: RETROICOR. Magn Reson Med. 2000;44:162–7. doi: 10.1002/1522-2594(200007)44:1<162::aid-mrm23>3.0.co;2-e. [DOI] [PubMed] [Google Scholar] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given
    § Results

    Two patients with PTSD were using trazodone as a sleep aid; no other psychiatric medications were permitted.

    “Two patients with PTSD were using trazodone as a sleep aid; no other psychiatric medications were permitted.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data
    § Results

    Imaging data from 1 control participant was lost owing to scanner malfunction, leaving a final sample of 15 patients with PTSD and 14 combat controls.

    “Imaging data from 1 control participant was lost owing to scanner malfunction, leaving a final sample of 15 patients with PTSD and 14 combat controls.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation
    § Discussion

    Training patients with PTSD in emotion-regulation strategies has been shown to reduce negative emotional responses and normalize PFC responses to aversive stimuli.

    “Moreover, training patients with PTSD in emotion-regulation strategies has been shown to reduce negative emotional responses and normalize PFC responses to aversive stimuli.58”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [58] New AS, Fan J, Murrough JW, et al. A functional magnetic resonance imaging study of deliberate emotion regulation in resilience and posttraumatic stress disorder. Biol Psychiatry. 2009;66:656–64. doi: 10.1016/j.biopsych.2009.05.020. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    If the ACC and mPFC play an important inhibitory role in modulating amygdala signal, the weaker anti-correlation between the amygdala and ACC in PTSD might reflect diminished capacity of medial prefrontal regions to suppress amygdala activity.

    “If the ACC and mPFC play an important inhibitory role in modulating amygdala signal, our findings of a weaker anti-correlation between the amygdala and ACC might reflect diminished capacity of the medial prefrontal regions in individuals with PTSD to suppress amygdala activity.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Both groups responded similarly to the scanning environment.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Discussion

    Gilboa and colleagues reported that during neutral emotion conditions, the ACC exerts an inhibitory influence on the amygdala, and this relation is diminished in individuals with PTSD.

    “Gilboa and colleagues17 reported that during neutral emotion conditions, the ACC exerts an inhibitory influence on the amygdala, and this relation is diminished in individuals with PTSD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Gilboa A, Shalev AY, Laor L, et al. Functional connectivity of the prefrontal cortex and the amygdala in posttraumatic stress disorder. Biol Psychiatry. 2004;55:263–72. doi: 10.1016/j.biopsych.2003.08.004. [DOI] [PubMed] [Google Scholar] source

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  • May combine two claims.

    Interpretationcitation
    § Discussion

    A lack of inhibition from dorsal medial regions to the amygdala can be interpreted as a deficit in automatic emotion regulation or a lack of cognitive control over emotion.

    “Such a lack of inhibition from dorsal medial regions to the amygdala can be interpreted as a deficit in automatic emotion regulation10 or a lack of cognitive control over emotion.54”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Etkin A, Wager TD. Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. Am J Psychiatry. 2007;164:1476–88. doi: 10.1176/appi.ajp.2007.07030504. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [54] Phan KL, Britton JC, Taylor SF, et al. Corticolimbic blood flow during nontraumatic emotional processing in posttraumatic stress disorder. Arch Gen Psychiatry. 2006;63:184–92. doi: 10.1001/archpsyc.63.2.184. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • The authors state this as an assumption: Both groups responded similarly to the scanning environment.

  • May combine two claims.

    Interpretationreasoning
    § Results

    Only male veterans with combat exposure were tested, thus the findings cannot be generalized to women or to individuals with non-combat related PTSD.

    “Only male veterans with combat exposure were tested, thus our findings cannot be generalized to women or to individuals with non–combat related PTSD.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation
    § Discussion

    Individuals with PTSD demonstrate both automatic emotion regulation deficits and lack of cognitive control over emotion in clinical settings.

    “It is noteworthy that individuals with PTSD demonstrate both of these deficits in clinical settings.57”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [57] Ehring T, Quack D. Emotion regulation difficulties in trauma survivors: the role of trauma type and PTSD symptom severity. Behav Ther. 2010;41:587–98. doi: 10.1016/j.beth.2010.04.004. [DOI] [PubMed] [Google Scholar] source

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    Premisecitation
    § Discussion

    Animal studies of fear conditioning establish mPFC involvement in the extinction of conditioned fear.

    “Animal studies of fear conditioning establish mPFC involvement in the extinction of conditioned fear,55”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [55] Milad MR, Quirk GJ. Neurons in medial prefrontal cortex signal memory for fear extinction. Nature. 2002;420:70–4. doi: 10.1038/nature01138. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    Resting-state amygdala connectivity studies reveal anticorrelations between the dorsal mPFC and amygdala in low-anxious individuals and a lack of coupling in high-anxious individuals.

    “Resting-state amygdala connectivity studies also reveal anticorrelations between the dorsal mPFC and amygdala in low-anxious individuals and, interestingly, a lack of coupling in high-anxious individuals.14”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [14] Kim MJ, Gee DG, Loucks RA, et al. Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest. Cereb Cortex. 2011;21:1667–73. doi: 10.1093/cercor/bhq237. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    The amygdala and insula have strong structural connections and exhibit high functional connectivity at rest.

    “The amygdala and insula have strong structural connections61 and exhibit high functional connectivity at rest.62”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [61] Reynolds SM, Zahm DS. Specificity in the projections of prefrontal and insular cortex to ventral striatopallidum and the extended amygdala. J Neurosci. 2005;25:11757–67. doi: 10.1523/JNEUROSCI.3432-05.2005. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    • cites [62] Salvador R, Martinez A, Pomarol-Clotet E, et al. A simple view of the brain through a frequency-specific functional connectivity measure. Neuroimage. 2008;39:279–89. doi: 10.1016/j.neuroimage.2007.08.018. [DOI] [PubMed] [Google Scholar] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    In individuals with PTSD, insula activation has been associated with trauma recall and viewing fearful faces.

    “In individuals with PTSD, insula activation has been associated with trauma recall21 and viewing fearful faces,18”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [21] Britton JC, Phan KL, Taylor SF, et al. Neural correlates of social and nonsocial emotions: an fMRI study. Neuroimage. 2006;31:397–409. doi: 10.1016/j.neuroimage.2005.11.027. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [18] Fonzo GA, Simmons AN, Thorp SR, et al. Exaggerated and disconnected insular-amygdalar blood oxygenation level-dependent response to threat-related emotional faces in women with intimate-partner violence posttraumatic stress disorder. Biol Psychiatry. 2010;68:433–41. doi: 10.1016/j.biopsych.2010.04.028. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Discussion

    In a more recent study with acutely traumatized individuals, PCC/precuneus-to-amygdala connectivity was found to be positively correlated with PTSD symptoms.

    “however, in a more recent study with acutely traumatized individuals, they found PCC/precuneus-to-amygdala connectivity to be positively correlated with PTSD symptoms.33”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [33] Lanius RA, Bluhm RL, Coupland NJ, et al. Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects. Acta Psychiatr Scand. 2010;121:33–40. doi: 10.1111/j.1600-0447.2009.01391.x. [DOI] [PubMed] [Google Scholar] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion

    Insula responsivity to negative images in individuals with PTSD has been shown to be positively correlated with hyperarousal symptoms, re-experiencing symptoms and flashback intensity.

    “Indeed, insula responsivity to negative images in individuals with PTSD has previously been shown to be positively correlated with hyperarousal symptoms,19 re-experiencing symptoms63 and flashback intensity.64”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [19] Simmons AN, Paulus MP, Thorp SR, et al. Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violence. Biol Psychiatry. 2008;64:681–90. doi: 10.1016/j.biopsych.2008.05.027. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [63] Hopper JW, Frewen PA, van der Kolk BA, et al. Neural correlates of reexperiencing, avoidance, and dissociation in PTSD: symptom dimensions and emotion dysregulation in responses to script-driven trauma imagery. J Trauma Stress. 2007;20:713–25. doi: 10.1002/jts.20284. [DOI] [PubMed] [Google Scholar] source

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    • cites [64] Osuch EA, Benson B, Geraci M, et al. Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder. Biol Psychiatry. 2001;50:246–53. doi: 10.1016/s0006-3223(01)01107-6. [DOI] [PubMed] [Google Scholar] source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation
    § Discussion

    Patients with PTSD show exaggerated activity in both the amygdala and hippocampus while recollecting negative autobiographical memories and while viewing negative pictures, and the degree of this hyperactivity correlated with symptom severity.

    “For example, patients with PTSD show exaggerated activity in both the amygdala and hippocampus while recollecting negative autobiographical memories65 and while viewing negative pictures,66 and the degree of this hyperactivity correlated with symptom severity.66”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [65] St Jacques PL, Botzung A, Miles A, et al. Functional neuroimaging of emotionally intense autobiographical memories in post-traumatic stress disorder. J Psychiatr Res. 2011;45:630–7. doi: 10.1016/j.jpsychires.2010.10.011. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [66] Brohawn KH, Offringa R, Pfaff DL, et al. The neural correlates of emotional memory in posttraumatic stress disorder. Biol Psychiatry. 2010;68:1023–30. doi: 10.1016/j.biopsych.2010.07.018. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

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    Premisecitation
    § Discussion

    Enhanced connectivity between the insula and amygdala was previously reported in studies of recently traumatized individuals during symptom provocation.

    “Similar findings of enhanced connectivity between the insula and amygdala were previously reported in studies of recently traumatized individuals during symptom provocation.16”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Osuch EA, Willis MW, Bluhm R, et al. Neurophysiological responses to traumatic reminders in the acute aftermath of serious motor vehicle collisions using [15O]-H2O positron emission tomography. Biol Psychiatry. 2008;64:327–35. doi: 10.1016/j.biopsych.2008.03.010. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based). May combine two claims.

    Premisenone given
    § Discussion

    To our knowledge, there have been 4 previous studies of resting-state connectivity in individuals with PTSD, all using a thalamus or PCC/precuneus seed for connectivity analysis.

    “To our knowledge, there have been 4 previous studies of resting-state connectivity in individuals with PTSD, all using a thalamus or PCC/precuneus seed for connectivity analysis.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion

    Co-occurring increases in insula and amygdala activity were greater in individuals with PTSD than combat-exposed or non-combat exposed controls during trauma reminders and fear acquisition.

    “co-occurring increases in insula and amygdala activity were found to be greater in individuals with PTSD than combat-exposed or non–combat exposed controls during trauma reminders59 and fear acquisition.60”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [59] Vermetten E, Schmahl C, Southwick SM, et al. Positron tomographic emission study of olfactory induced emotional recall in veterans with and without combat-related posttraumatic stress disorder. Psychopharmacol Bull. 2007;40:8–30. [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [60] Bremner JD, Vermetten E, Schmahl C, et al. Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder. Psychol Med. 2005;35:791–806. doi: 10.1017/s0033291704003290. [DOI] [PMC free article] [PubMed] [Google Scholar] source

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    Premisecitation
    § Discussion

    Bluhm and colleagues reported reduced functional connectivity between the PCC/precuneus and amygdala in individuals with PTSD.

    “Bluhm and colleagues32 reported reduced functional connectivity between the PCC/precuneus and amygdala in individuals with PTSD;”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Bluhm RL, Williamson PC, Osuch EA, et al. Alterations in default network connectivity in posttraumatic stress disorder related to early-life trauma. J Psychiatry Neurosci. 2009;34:187–94. [PMC free article] [PubMed] [Google Scholar]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion

    One study found that amygdala hyperactivity during fear extinction and hippocampal hypoactivity during extinction recall was associated with a behavioural deficit in extinction recall in individuals with PTSD.

    “One study found that amygdala hyperactivity during fear extinction and hippocampal hypoactivity during extinction recall was associated with a behavioural deficit in extinction recall in individuals with PTSD.68”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [68] Milad MR, Pitman RK, Ellis CB, et al. Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder. Biol Psychiatry. 2009;66:1075–82. doi: 10.1016/j.biopsych.2009.06.026. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning
    § Discussion

    A failure to properly contextualize threat and safety signals, or integrate corrective information into fear schemas, may be relevant to the development of PTSD symptomatology.

    “A failure to properly contextualize threat and safety signals, or integrate corrective information into fear schemas, may be relevant to the development of PTSD symptomatology.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning
    § Discussion

    Inclusion of depressed participants may render some effects attributable to the presence of depression independently or in interaction with PTSD.

    “our inclusion of depressed participants may render some of our effects attributable to the presence of depression independently or in interaction with PTSD.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation
    § Discussion

    It has been convincingly argued that global regression does not introduce large-scale artifacts, and globally regressed connectivity maps more accurately depict known anticorrelations between functional networks in the brain.

    “Recently, however, it had been convincingly argued that global regression does not introduce large-scale artifacts, and globally regressed connectivity maps more accurately depict the known anticorrelations between functional networks in the brain.72,73”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [72] Fox MD, Zhang D, Snyder AZ, et al. The global signal and observed anticorrelated resting state brain networks. J Neurophysiol. 2009;101:3270–83. doi: 10.1152/jn.90777.2008. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

    • cites [73] Weissenbacher A, Kasess C, Gerstl F, et al. Correlations and anti-correlations in resting-state functional connectivity MRI: a quantitative comparison of preprocessing strategies. Neuroimage. 2009;47:1408–16. doi: 10.1016/j.neuroimage.2009.05.005. [DOI] [PubMed] [Google Scholar]

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion

    Recent resting-state functional connectivity studies of the amygdala have used global regression and identified networks proposed to be anticorrelated with the amygdala.

    “In sum, recent resting-state functional connectivity studies of the amygdala have used global regression and identified networks proposed to be anticorrelated with the amygdala (for example, see Roy and colleagues15)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Roy AK, Shehzad Z, Margulies DS, et al. Functional connectivity of the human amygdala using resting state fMRI. Neuroimage. 2009;45:614–26. doi: 10.1016/j.neuroimage.2008.11.030. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given
    § Discussion

    The methods are essentially correlational and thus do not allow for inferences about causal relationships.

    “Fourth, our methods are essentially correlational and thus do not allow for inferences about causal relationships.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation
    § Discussion

    Depression commonly co-occurs with PTSD in veteran populations, with estimates up to 80%.

    “Though depression commonly co-occurs with PTSD in veteran populations (up to 80% by some estimations70)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] Hankin CS, Spiro A, III, Miller DR, et al. Mental disorders and mental health treatment among U.S. Department of Veterans Affairs outpatients: the Veterans Health Study. Am J Psychiatry. 1999;156:1924–30. doi: 10.1176/ajp.156.12.1924. [DOI] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation
    § Discussion

    A recent connectivity modelling analysis found a strong functional link between the PCC and the amygdala in healthy individuals.

    “A recent connectivity modelling analysis found a strong functional link between the PCC and the amygdala in healthy individuals.15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] Roy AK, Shehzad Z, Margulies DS, et al. Functional connectivity of the human amygdala using resting state fMRI. Neuroimage. 2009;45:614–26. doi: 10.1016/j.neuroimage.2008.11.030. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationown data
    § Discussion

    Disruptions in the PCC-amygdala connection may point to default network disturbances in individuals with PTSD.

    “Disruptions in this connection may point to default network disturbances in individuals with PTSD, a hypothesis that merits further research.”
    Quote in the paperNot a substantial claim
    • The authors state this as an assumption: Both groups responded similarly to the scanning environment.

  • May combine two claims.

    Interpretationown data
    § Discussion

    The findings of enhanced connectivity in emotion-experience regions and reduced connectivity between these regions and emotion-regulation regions suggest plausible mechanisms involved in exaggerated emotional responses and apparent regulation dysfunction seen in patients with PTSD.

    “Our findings of enhanced connectivity in emotion-experience regions (amygdala and insula) and reduced connectivity between these regions and emotion-regulation regions suggest plausible mechanisms involved in exaggerated emotional responses and apparent regulation dysfunction seen in patients with PTSD.”
    Quote in the paperSubstantial claim
    • The authors state this as an assumption: Both groups responded similarly to the scanning environment.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation
    § Discussion

    Use of global regression is a limitation because there is continued controversy about whether global regression introduces artifactual anticorrelation.

    “However, our use of global regression is a limitation in that there is continued controversy about whether global regression introduces artifactual anticorrelation.71”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Murphy K, Birn RM, Handwerker DA, et al. The impact of global signal regression on resting state correlations: Are anti-correlated networks introduced? Neuroimage. 2009;44:893–905. doi: 10.1016/j.neuroimage.2008.09.036. [DOI] [PMC free article] [PubMed] [Google Scholar] source

      Not checked in the free run.

71 of 71

  • The paper relies on this without support.

    Amygdala connectivity at rest in individuals with PTSD has not been studied.

    “however, amygdala connectivity at rest in individuals with PTSD has not been studied.”

  • The authors state this as an assumption.

    Both groups responded similarly to the scanning environment.

    “we have interpreted our findings under the assumption that both groups responded similarly to the scanning environment.”
2 of 2

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?

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • Consistentz = 3.64reported p < .005 · recomputed p < .001

    “Z = 3.64, p < .005”

1 of 1

Self-check

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

Each contradiction between two passages listed here was confirmed by an independent check.

  • Rostral ACC result attributed to different amygdala seeds

    Minor

    The results text attributes the reduced anticorrelation with the rostral ACC to the right amygdala seed, but Table 2 lists the same coordinates and statistics under the left amygdala seed.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 6

  1. Bluhm RL, 2009, J Psychiatry Neurosci, 34, 187
  2. Wu RZ, 2011, Sichuan Da Xue Xue Bao Yi Xue Ban, 42, 397
  3. Veer IM, 2010, Front Syst Neurosci, 4, 41
  4. Blake DD, 1995, J Trauma Stress, 8, 75
  5. Sheehan DV, 1998, J Clin Psychiatry, 59, 22
  6. Vermetten E, 2007, Psychopharmacol Bull, 40, 8

Cited by

Sorted by citations

Related

Authors
Sripada, R. K., King, A. P., Garfinkel, S. N., Wang, X., Sripada, C. S., Welsh, R. C., & Liberzon, I.
Affiliations
Brighton and Sussex Medical School (GB)
ORCID
Venue
Journal of Psychiatry and Neuroscience
Publisher
Canadian Science Publishing
Published
2012-07
Volume
37
Issue
4
Pages
241-249
ISSN
  • 1180-4882 (ISSN-L)
  • 1488-2434
DOI
10.1503/jpn.110069
PMC
PMC3380095
OpenAlex
W2117925162
Semantic Scholar
34cd382a6541d0ca6fb28f6209d84d6fd7957ec8
Cited by
352
References
74
Citations by year
2026: 12 · 2025: 15 · 2024: 16 · 2023: 23 · 2022: 21 · 2021: 29 · 2020: 26 · 2019: 25 · 2018: 30 · 2017: 35 · 2016: 31 · 2015: 32 · 2014: 29 · 2013: 19 · 2012: 8
FWCI
31.91
Type
journal article
Language
en
Open access
Licence
www.nrcresearchpress.com/page/about/CorporateTextAndDataMining (tdm)
Locations
  • Journal of Psychiatry and Neuroscience (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Sussex Research Online (University of Sussex) (submittedVersion)
  • Figshare (submittedVersion, cc-by)
Funders
National Institute of Mental Health (R24MH075999)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
Keywords
post-traumatic stress disorder, resting-state functional connectivity, amygdala, combat veterans, insula, hippocampus, anterior cingulate cortex, emotion regulation, emotional processing, brain networks, male veterans
MeSH terms
Adult, Amygdala, Brain, Brain Mapping, Combat Disorders, Emotions, Humans, Magnetic Resonance Imaging, Male, Stress Disorders, Post-Traumatic, Veterans, 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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

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