Alterations in White Matter Microstructure as Vulnerability Factors and Acquired Signs of Traffic Accident-Induced PTSD

Sun, Yawen; Wang, Zhen; Ding, Weiping; Wan, Jieqing; Zhuang, Zhiguo; Zhang, Yong; Liu, Yijun; Zhou, Yan; Xu, Jikai

doi:10.1371/journal.pone.0083473

Cited by 33 publications

(32 citation statements)

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“…Laboratory stressors are hampered in their limited generalizability to real world challenges; however the stressor task utilized in this study evokes frustration and cognitive challenge, which are similar to many stressful experiences SZ would experience in everyday life. Overall, our finding of a correlation between reduced FA with prolonged cortisol reactivity is consistent with previous reports that chronic stress is associated with WM lesions (34) and reduced FA (57), and supports the a priori hypothesis that poor resolution of cortisol responses could cumulatively lead to WM alterations.…”

Section: Discussionsupporting

confidence: 92%

Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia

Nugent

Chiappelli

Sampath

et al. 2015

Psychosomatic Medicine

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Objective While acute hypothalamic-pituitary-adrenal axis response to stress is often adaptive, prolonged responses may have detrimental effects. Many components of white matter structures are sensitive to prolonged cortisol exposure. We aimed to identify a behavioral laboratory assay for which cortisol response related to brain pathophysiology in schizophrenia. We hypothesized that an abnormally prolonged cortisol response to stress may be linked to abnormal white matter integrity in patients with schizophrenia. Methods Acute and prolonged salivary cortisol response was measured outside the scanner at pre-test and then at 0, 20, and 40 minutes after a psychological stress task in patients with schizophrenia (n=45) and controls (n=53). Tract-averaged white matter was measured by 64-direction diffusion tensor imaging in a subset of patients (n=30) and controls (n=33). Results Patients who did not tolerate and quit the psychological stress task had greater acute (t=2.52, p=0.016; t=3.51, p=0.001 at zero and 20 minutes) and prolonged (t=3.62, p=0.001 at 40 minutes) cortisol reactivity compared with patients who finished the task. Abnormally prolonged cortisol reactivity in patients was significantly associated with reduced white matter integrity (r=−0.468, p=0.009). Regardless of task completion status, acute cortisol response was not related to the white matter measures in patients or controls. Conclusions This paradigm was successful at identifying a subset of patients whose cortisol response was associated with brain pathophysiology. Abnormal cortisol response may adversely affect white matter integrity, partly explaining this pathology observed in schizophrenia. Prolonged stress responses may be targeted for intervention to test for protective effects against white matter damages.

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Section: Discussionsupporting

confidence: 92%

Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia

Nugent

Chiappelli

Sampath

et al. 2015

Psychosomatic Medicine

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“…63 Also, in a prospective imaging study, lower FA and higher MD of vmPFC white matter (measured within 2 days posttrauma) predicted PTSD development at 1 and 6 months posttrauma. 16 Alternatively, lower uncinate fasciculus tract integrity in patients with…”

Section: Discussionmentioning

confidence: 99%

“…13 Moreover, vmPFC white matter integrity measured within 2 days posttrauma was lower in trauma-exposed individuals in whom PTSD developed compared with those who did not develop PTSD at 1 and 6 months posttrauma. 16 Regarding the cingulum bundle, lower white matter integrity of the cingulum (i.e., connecting the cingulate cortex with the hippocampus and amygdala) 17 has been observed in female patients with PTSD compared with trauma-exposed controls, possibly underlying impaired fear extinction learning. 14 However, according to a recent meta-analysis on 7 whole-brain DTI studies in patients with PTSD, increased FA of the cingulum bundle has also been observed in patients with PTSD.…”

Section: J Psychiatry Neurosci 2017;42(5)mentioning

confidence: 99%

Decreased uncinate fasciculus tract integrity in male

Koch

Zuiden

Nawijn

et al. 2017

JPN

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IntroductionApproximately 10% of trauma-exposed individuals have posttraumatic stress disorder (PTSD), 1 characterized by intrusions and avoidance of reminders of the traumatic event, altered cognitions and mood, and hyperarousal.2 The prevailing neurocircuitry model of PTSD postulates amygdala hyperactivity and ventromedial prefrontal cortex (vmPFC) hypoactivity.3,4 The amygdala plays a pivotal role in fear expression and salience processing, 5 whereas the vmPFC is important in top-down control over the fear response.6 Additionally, decreased resting-state functional connectivity between the amygdala and vmPFC has been observed in male patients with PTSD, possibly underlying diminished top-down prefrontal control over the fear response. White matter fibres, which make up more than 40% of total brain volume, 8 allow effective communication between (cortical and subcortical) brain areas. White matter integrity can be investigated noninvasively with diffusion tensor imaging (DTI), which measures the direction and coherence of water diffusion within myelinated and nonmyelinated tissue. 9 The DTI metrics fractional anisotropy (FA) and mean diffusivity (MD) are predominantly used to quantify white matter integrity: FA reflects the extent to which water diffusion is directionally restricted and represents axonal density and coherence, whereas MD (i.e., magnitude of overall diffusion) is sensitive (but not specific) to membrane integrity. 10,11 In line with the prevailing neurocircuitry model of PTSD, lower white matter integrity of tracts connecting the prefrontal cortex with limbic regions, including the cingulum bundle and uncinate fasciculus, has been associated with PTSD and its development. 12-14 The uncinate fasciculus connects the orbital, medial and lateral prefrontal cortex with rostral temporal areas, including the anterior temporal lobe, parahippocampal Background: Posttraumatic stress disorder (PTSD) is a disabling psychiatric disorder that has been associated with lower white matter integrity of tracts connecting the prefrontal cortex with limbic regions. However, previous diffusion tensor imaging (DTI) findings have been inconsistent, showing high variability in the exact location and direction of effects. Methods: We performed probabilistic tractography of the bilateral uncinate fasciculus, cingulum and superior longitudinal fasciculus (both temporal and parietal projections) in male and female police officers with and without PTSD. Results: We included 38 (21 men) police officers with and 39 (20 men) without PTSD in our analyses. Compared with trauma-exposed controls, patients with PTSD showed significantly higher mean diffusivity of the right uncinate fasciculus, the major white matter tract connecting the amygdala to the prefrontal cortex (p = 0.012). No other significant between-group or group × sex differences were observed. Mean diffusivity of the right uncinate fasciculus was positively associated with anxiety symptoms (r = 0.410, p = 0.013) in patients with PTSD as well as with amygdala activi...

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“…41 Future directions potentially include the use of automated tract identification to evaluate the disease trajectory, 40,42–44 modulate radiation therapy 42 or evaluate the response to therapy in patients with gliomas. 45,46 Finally, the integrity of white matter tracts is increasingly being applied in the clinical neurosciences as a biomarker of injury in a range of diseases from traumatic brain injury 47 to early Alzheimer's disease. 48 The ability to use automated, probabilistic methods, has been shown to be more reliable than manual determinations by individual experts, 49,50 as substantiated by the current report.…”

Section: Discussionmentioning

confidence: 99%

Individualized Map of White Matter Pathways

et al. 2016

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Background Advances in white matter tractography enhance neurosurgical planning and glioma resection, but is limited by biological variables such as edema, mass effect, and tract infiltration, or selection biases related to regions of interest (ROIs) or fractional anisotropy (FA) values. Objective To provide an automated tract identification paradigm that corrects for artifacts created by tumor edema and infiltration, as well as providing a consistent, accurate method of fiber tractography. Methods An automated tract identification paradigm was developed and evaluated for glioma surgery. A fiber bundle atlas was generated from six healthy participants. Fibers of a test set (including three healthy participants and ten patients with brain tumors) were clustered adaptively using this atlas. Reliability of identified tracts in both groups was assessed by comparison with two experts, using Cohen's kappa to quantify concurrence. We evaluated six major fiber bundles: cingulum bundle (CB), fornix (FR), uncinate fasciculus (UF), arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), and inferior longitudinal fasciculus (ILF) – the latter three tracts mediating language function. Results The automated paradigm demonstrated a reliable and practical method to identify white mater tracts, despite mass effect, edema, and tract infiltration. When the tumor demonstrated significant mass effect or shift, the automated approach was useful to provide an initialization to guide the expert with identification of the specific tract of interest. Conclusion We report a reliable paradigm for automated identification of white matter pathways in patients with gliomas. This approach should enhance the neurosurgical objective of maximal safe resections.

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Alterations in White Matter Microstructure as Vulnerability Factors and Acquired Signs of Traffic Accident-Induced PTSD

Cited by 33 publications

References 50 publications

Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia

Cortisol Reactivity to Stress and Its Association With White Matter Integrity in Adults With Schizophrenia

Decreased uncinate fasciculus tract integrity in male

Individualized Map of White Matter Pathways

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