Increased Inhibition of the Amygdala by the mPFC may Reflect a Resilience Factor in Post-traumatic Stress Disorder: A Resting-State fMRI Granger Causality Analysis

Purpose: To determine whether effective connectivity of the amygdala is altered in traumatized subjects with and without post-traumatic stress disorder (PTSD).Materials and Methods: Resting-state functional MRI data were obtained for 27 patients with typhoon-related PTSD, 33 trauma-exposed controls (TEC), and 30 healthy controls (HC). Effective connectivity of the bilateral amygdala was examined with Granger causality analysis and then compared between groups by conducting an analysis of variance.Results: Compared to the HC group, both the PTSD group and the TEC group showed increased effective connectivity from the amygdala to the medial prefrontal cortex (mPFC). The TEC group showed increased effective connectivity from the mPFC to the amygdala relative to the HC group. Compared to the TEC group, the PTSD group showed increased effective connectivity from the amygdala to the supplementary motor area (SMA), whereas decreased effective connectivity was detected from the SMA to the amygdala. Both the PTSD group and the TEC group showed decreased effective connectivity from the superior temporal gyrus (STG) to the amygdala relative to the HC group. Compared to the HC group, the TEC group showed increased effective connectivity from the amygdala to the dorsolateral prefrontal cortex (dlPFC), while both the PTSD group and the TEC group showed decreased effective connectivity from the dlPFC to the amygdala. The PTSD group showed decreased effective connectivity from the precuneus to the amygdala relative to both control groups, but increased effective connectivity from the amygdala to the precuneus relative to the HC group.Conclusion: Trauma leads to an increased down-top excitation from the amygdala to the mPFC and less regulation of the amygdala by the dlPFC. The results suggest that increased inhibition of the amygdala by the mPFC may reflect a resilience factor, and altered amygdala-SMA and amygdala-STG effective connectivity may reflect compensatory mechanisms of brain function. These data raise the possibility that insufficient inhibition of the amygdala by the mPFC might lead to PTSD in those who have been exposed to traumatic incidents, and may inform future therapeutic interventions

Gender differences of brain glucose metabolic networks revealed by FDG-PET: evidence from a large cohort of 400 young adults.

BACKGROUND: Gender differences of the human brain are an important issue in neuroscience research. In recent years, an increasing amount of evidence has been gathered from noninvasive neuroimaging studies supporting a sexual dimorphism of the human brain. However, there is a lack of imaging studies on gender differences of brain metabolic networks based on a large population sample. MATERIALS AND METHODS: FDG PET data of 400 right-handed, healthy subjects, including 200 females (age: 25:45 years, mean age ± SD: 40.9 ± 3.9 years) and 200 age-matched males were obtained and analyzed in the present study. We first investigated the regional differences of brain glucose metabolism between genders using a voxel-based two-sample t-test analysis. Subsequently, we investigated the gender differences of the metabolic networks. Sixteen metabolic covariance networks using seed-based correlation were analyzed. Seven regions showing significant regional metabolic differences between genders, and nine regions conventionally used in the resting-state network studies were selected as regions-of-interest. Permutation tests were used for comparing within- and between-network connectivity between genders. RESULTS: Compared with the males, females showed higher metabolism in the posterior part and lower metabolism in the anterior part of the brain. Moreover, there were widely distributed patterns of the metabolic networks in the human brain. In addition, significant gender differences within and between brain glucose metabolic networks were revealed in the present study. CONCLUSION: This study provides solid data that reveal gender differences in regional brain glucose metabolism and brain glucose metabolic networks. These observations might contribute to the better understanding of the gender differences in human brain functions, and suggest that gender should be included as a covariate when designing experiments and explaining results of brain glucose metabolic networks in the control and experimental individuals or patients

The effect of hepatic encephalopathy, hepatic failure, and portosystemic shunt on brain volume of cirrhotic patients: a voxel-based morphometry study.

PURPOSE: To evaluate the effect of hepatic encephalopathy (HE), hepatic failure, and portosystemic shunt (PS) on the brain volume alteration in cirrhotic patients with MRI voxel-based morphometry (VBM). METHODS: Sixty cirrhotic patients (overt HE [OHE], n = 11; minimal HE [MHE], n = 19; non HE [nHE], n = 30) including 12 with pre- and post-transjugular intrahepatic portosystemic shunt (TIPS) scanning and 40 healthy controls were recruited. Neuropsychological and laboratory tests were performed in all patients. VBM was analyzed with ANOVA test among 4 groups, and t-tests for patients with different hepatic function, PS scores, and TIPS. Multiple linear regression was performed to investigate the effect of venous blood ammonia levels, Child-Pugh scores, and PS on the brain volumes in all patients. RESULTS: Cirrhotic patients exhibited decreased volume in many areas of gray matter (GM), increased volume in thalamus, and increased whiter matter (WM) volume, with the extent of affected brain volume greater in HE patients than nHE patients. Hepatic failure also resulted in decreased GM volume. Patients with high PS scores and TIPS displayed decreased GM and increased WM volume in some regions. Post-TIPS patients displayed increased GM volume in the thalamus. Multiple covariate regression results suggested that Child-Pugh score was a major factor to affect GM volume, while PS mainly affected WM volume. CONCLUSION: Brain structure abnormalities appeared bilaterally symmetrical in cirrhotic patients, and the impairment was more extensive in HE patients than those without HE. Increased thalamus volume was not associated with HE progression. Hepatic failure and PS altered cirrhotic patients' brain structure

Disturbed Interhemispheric Functional Connectivity Rather than Structural Connectivity in Irritable Bowel Syndrome

Neuroimaging studies have demonstrated that irritable bowel syndrome (IBS)—a relapsing functional bowel disorder—presents with disrupted brain connections. However, little is known about the alterations of interhemispheric functional connectivity and underlying structural connectivity in IBS. This study combined resting-state functional magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) to investigate changes in interhemispheric coordination in IBS patients. Resting-state functional and structural magnetic resonance images were acquired from 65 IBS patients and 67 healthy controls (matched for age, sex and educational level). Interhemispheric voxel-mirrored homotopic connectivity (VMHC) was calculated and compared between groups. Homotopic regions showing abnormal VMHC in patients were targeted as regions of interest for analysis of DTI tractography. The fractional anisotropy, fiber number, and fiber length were compared between groups. Statistical analysis was also performed by including anxiety and depression as covariates to evaluate their effect. A Pearson correlation analysis between abnormal interhemispheric connectivity and clinical indices of IBS patients was performed. Compared to healthy controls, IBS patients had higher interhemispheric functional connectivity between bilateral thalami, cuneus, posterior cingulate cortices, lingual gyri and inferior occipital/cerebellum lobes, as well as lower interhemispheric functional connectivity between bilateral ventral anterior cingulate cortices (vACC) and inferior parietal lobules (IPL). The inclusion of anxiety and depression as covariates abolished VMHC difference in vACC. Microstructural features of white matter tracts connecting functionally abnormal regions did not reveal any differences between the groups. VMHC values in vACC negatively correlated with the quality of life scores of patients. In conclusion, this study provides preliminary evidence of the disrupted functional coordination rather than anatomic coordination between interhemispheric regions within the cortex-thalamus circuit in IBS patients, which could partly account for the enhanced visceral information processing and impaired endogenous pain or emotion inhibition associated with IBS