A Magnetic Resonance Imaging Study On The Resting-state Regional Brain Function And Functional Connectivity In Posttraumatic Stress Disorder Patients

Objective:Little is known about how brain systems may be altered in posttraumatic stress disorder (PTSD) compared with traumatized individuals not diagnosed with the disorder. The present study investigated the intrinsic brain functional activities using functional magnetic resonance imaging (fMRI) under resting state and identified neurobiological mechanisms of the disorder and targets for intervention.Methods:On May12th,2008, an8.0-magnitude earthquake hit Sichuan Province of China, exerting wide and tremendous range of traumatic experience and mental influence on survivors. All subjects for the current study were drawn from a large-scale PTSD survey in those post-earthquake survivors. In brief, investigation was carried out in two most devastated regions8months after the earthquake. A total of3100survivors in Hanwang town were interviewed and screened with the PTSD checklist (PCL). Survivors scoring≥35points were given the Clinician-Administered PTSD Scale (CAPS) and the Structured Clinical Interview for DSM-Ⅳ Axis Ⅰ Disorders (SCID-Ⅰ) by psychiatrists to confirm the PTSD diagnosis. A total of1100survivors in Beichuan county were interviewed and screened with the PCL. Survivors scoring≥45points were given the CAPS and SCID-Ⅰ to confirm the PTSD diagnosis. From these pools of PTSD subjects identified with the above procedure,415with PTSD diagnosis were further selected as eligible for the current functional MRI study. In addition,109non-PTSD controls with PCL total scores below30points and eligibility for MRI were selected as a comparison group. These subjects were further assessed with the SCID-Ⅰ to exclude any psychiatric co-morbidity. At last,72 medication-naive PTSD subjects and86age-, gender-matched traumatized non-PTSD comparison subjects took part in the subsequent resting state fMRI scans. from9months to15months post-earthquake and their data were processed. We analyzed resting fMRI data using regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) as well as functional connectivity measures. ReHo and ALFF are two measures which quantify the function of the brain locally can be implemented in resting-state fMRI studies. ReHo reflects the synchronization of regional neuronal activities and ALFF measures amplitude of spontaneous activity of each pixel in regional sites under resting condition and characterize regional cerebral function, while functional connectivity explores the correlation of activities in different brain regions or explains the relationship of activities between one and the other brain regions. Using two sample t-test, we analyzed the differences of ReHo, ALFF and functional connectivity between the PTSD and comparison groups during the resting state. Results:(1) PTSD patients presented enhanced regional homogeneity signals in left parietal lobule and right frontal gyrus and reduced ReHo values in right middle temporal gyrus and lingual gyrus relative to traumatized individuals without PTSD (P<0.01, corrected). Significant positive correlations were observed between ReHo values in the left parietal lobule and the right frontal gyrus in the patient group (r=0.356, P=0.008).(2) PTSD patients showed decreased ALFF values in right lingual gyrus, cuneus, middle occipital gyrus, insula, and cerebellum, and increased ALFF values in right medial and middle frontal gyri, relative to traumatized individuals without PTSD (P<0.01, corrected). The ALFF value in the right medial frontal gyrus was positively correlated with severity of the disorder (r=0.335, P=0.014).(3) In the PTSD group, the thalamus-ROIs showed decreased positive functional connectivity to particular brain regions including the right medial frontal gyrus and the left anterior cingulate cortex. Importantly, we further found increased positive functional connectivity of thalamus-ROIs with the bilateral inferior frontal and left middle frontal gyrus, as well as left inferior parietal lobule and right precuneus in the PTSD participants when compared with the traumatized controls without PTSD (P<0.05, corrected). The strength of functional connectivity of the left thalamus-ROI to right precuneus showed significant negative correlation with the PTSD symptom severity (r=-0.33, P=0.014).Conclusion:Our findings showed that abnormality of intrinsic brain activity exists under resting conditions in recent-onset PTSD exposed to a major earthquake.(1) Altered regional function found predominantly in right-hemisphere, including frontal lobe, temporal lobe, parietal lobe, visual association cortex, insula and cerebellum areas are likely to contribute to the neural mechanisms underlying traumatic memory and symptoms in PTSD.(2) Abnormal resting state functional connections linking the thalamus to cortical regions (involving frontal and parietal) may be involved in the underlying pathology to contribute to the altered memory and symptoms such as hyperarousal in PTSD and potential compensatory mechanism.