Cortical thinning in patients with recent onset post-traumatic stress disorder after a single prolonged trauma exposure

Most of magnetic resonance imaging (MRI) studies about post-traumatic stress disorder (PTSD) focused primarily on measuring of small brain structure volume or regional brain volume changes. There were rare reports investigating cortical thickness alterations in recent onset PTSD. Recent advances in computational analysis made it possible to measure cortical thickness in a fully automatic way, along with voxel-based morphometry (VBM) that enables an exploration of global structural changes throughout the brain by applying statistical parametric mapping (SPM) to high-resolution MRI. In this paper, Laplacian method was utilized to estimate cortical thickness after automatic segmentation of gray matter from MR images under SPM. Then thickness maps were analyzed by SPM8. Comparison between 10 survivors from a mining disaster with recent onset PTSD and 10 survivors without PTSD from the same trauma indicates cortical thinning in the left parietal lobe, right inferior frontal gyrus, and right parahippocampal gyrus. The regional cortical thickness of the right inferior frontal gyrus showed a significant negative correlation with the CAPS score in the patients with PTSD. Our study suggests that shape-related cortical thickness analysis may be more sensitive than volumetric analysis to subtle alteration at early stage of PTSD.     

Reduced Right Frontal Fractional Anisotropy Correlated with Early Elevated Plasma LDL Levels in Obese Young Adults

Objective

To investigate the underlying physiological mechanisms of the structural differences in gray matter (GM) and white matter (WM) associated with obesity in young Chinese adults.

Materials and Methods

A total of 49 right-handed obese or overweight (n = 22, mean age 31.72±8.04 years) and normal weight (n = 27, mean age 29.04±7.32 years) Han Chinese individuals were recruited. All participants underwent voxel-based morphometry analysis of T1-weighted MRI and tract-based spatial statistics analysis of diffusion tensor imaging. Partial correlation analysis was performed between the physiological data obtained and the abnormal structural alterations.

Results

In the OO group, GM atrophy occurred in the left prefrontal cortex, bilateral cingulate gyrus, and the right temporal lobe, while enlargement was observed in the bilateral putamen. WM atrophy was observed predominantly in the regions that regulate food intake, such as the bilateral basal ganglia, the right amygdala, and the left insula. The OO group exhibited lower fractional anisotropy (FA) in bilateral frontal corticospinal tracts and the right brainstem. Significant negative correlations were observed between FA values of those three clusters and BMI, and waist circumference, while the volume of bilateral putamen positively correlated with both BMI and waist circumference. High plasma LDL levels were correlated with low FA values in the right frontal corticospinal tract. Interestingly, the negative correlation was limited to male participants.

Conclusions

Obesity-related alterations of GM and WM volumes were observed predominantly in food reward circuit, which may motivate abnormal dietary intake. Further, early elevated plasma LDL might contribute to low right frontal FA values of male adults, which requires further demonstration by larger-scale and longitudinal studies.     

Identify Changes of Brain Regional Homogeneity in Bipolar Disorder and Unipolar Depression Using Resting-State fMRI

Background

To identify changes in brain activation patterns in bipolar disorder (BD) and unipolar depression (UD) patients.

Methodology/Principal Findings

Resting-state fMRI scans of 16 healthy controls, 17 BD and 16 UD patients were obtained. T-test of normalized regional homogeneity (ReHo) was performed in a voxel-by-voxel manner. A combined threshold of á = 0.05, minimum cluster volume of V = 10503 mm³ (389 voxels) were used to determine ReHo differences between groups. In UD group, fMRI revealed ReHo increases in the left middle occipital lobe, right inferior parietal lobule, right precuneus and left convolution; and ReHo decreases in the left parahippocampalgyrus, right precentralgyrus, left postcentralgyrus, left precentralgyrus and left cingulated. In BD group, ReHo increases in the right insular cortex, left middle frontal gyrus, left precuneus, left occipital lobe, left parietal, left superior frontal gyrus and left thalamus; and ReHo decreases in the right anterior lobe of cerebellum, pons, right precentralgyrus, left postcentralgyrus, left inferior frontal gyrus, and right cingulate. There were some overlaps in ReHo profiles between UD and BD groups, but a marked difference was seen in the thalamus of BD.

Conclusions/Significance

The resting-state fMRI and ReHo mapping are a promising tool to assist the detection of functional deficits and distinguish clinical and pathophysiological signs of BD and UD.     

Childhood Maltreatment Is Associated with Larger Left Thalamic Gray Matter Volume in Adolescents with Generalized Anxiety Disorder

Background

Generalized anxiety disorder (GAD) is a common anxiety disorder that usually begins in adolescence. Childhood maltreatment is highly prevalent and increases the possibility for developing a variety of mental disorders including anxiety disorders. An earlier age at onset of GAD is significantly related to maltreatment in childhood. Exploring the underpinnings of the relationship between childhood maltreatment and adolescent onset GAD would be helpful in identifying the potential risk markers of this condition.

Methods

Twenty-six adolescents with GAD and 25 healthy controls participated in this study. A childhood trauma questionnaire (CTQ) was introduced to assess childhood maltreatment. All subjects underwent high-resolution structural magnetic resonance scans. Voxel-based morphometry (VBM) was used to investigate gray matter alterations.

Results

Significantly larger gray matter volumes of the right putamen were observed in GAD patients compared to healthy controls. In addition, a significant diagnosis-by-maltreatment interaction effect for the left thalamic gray matter volume was revealed, as shown by larger volumes of the left thalamic gray matter in GAD patients with childhood maltreatment compared with GAD patients without childhood maltreatment as well as with healthy controls with/without childhood maltreatment. A significant positive association between childhood maltreatment and left thalamic gray matter volume was only seen in GAD patients.

Conclusions

These findings revealed an increased volume in the subcortical regions in adolescent GAD, and the alterations in the left thalamus might be involved in the association between childhood maltreatment and the occurrence of GAD.     

Decrease in temporal gyrus gray matter volume in first-episode, early onset schizophrenia: an MRI study

Background

Loss of gray matter has been previously found in early-onset schizophrenic patients. However, there are no consistent findings between studies due to different methods used to measure grey matter volume/density and influences of confounding factors.

Methods

The volume of gray matter (GM) was measured in 29 first episode early-onset schizophrenia (EOS) and 34 well-matched healthy controls by using voxel-based morphometry (VBM). Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS). The correlations between the GM volume and PANSS scores, age of psychosis onset, duration of psychosis, and chlorpromazine (CPZ) equivalent value were investigated.

Results

Relative to healthy subjects, the patients with first episode EOS showed significantly lower GM volume in the left middle and superior temporal gyrus. The loss of GM volume negatively correlated with PANSS-positive symptoms (p = 0.002), but not with PANSS-negative symptoms, PANSS-general psychopathology, and PANSS-total score. No significant correlation was found between GM volume and age of psychosis onset, duration of psychosis, and CPZ equivalent value.

Conclusion

Patients with first episode EOS have evidence of reduced GM in the left middle and superior temporal gyrus. Structural abnormalities in the left middle and superior temporal gyrus may contribute to the pathophysiology of schizophrenia.     

Early PTSD Symptom Trajectories: Persistence,Recovery, and Response to Treatment: Results from the Jerusalem Trauma Outreach and Prevention Study (J-TOPS)

Context

Uncovering heterogeneities in the progression of early PTSD symptoms can improve our understanding of the disorder''s pathogenesis and prophylaxis.

Objectives

To describe discrete symptom trajectories and examine their relevance for preventive interventions.

Design

Latent Growth Mixture Modeling (LGMM) of data from a randomized controlled study of early treatment. LGMM identifies latent longitudinal trajectories by exploring discrete mixture distributions underlying observable data.

Setting

Hadassah Hospital unselectively receives trauma survivors from Jerusalem and vicinity.

Participants

Adult survivors of potentially traumatic events consecutively admitted to the hospital''s emergency department (ED) were assessed ten days and one-, five-, nine- and fifteen months after ED admission. Participants with data at ten days and at least two additional assessments (n = 957) were included; 125 received cognitive behavioral therapy (CBT) between one and nine months.

Approach

We used LGMM to identify latent parameters of symptom progression and tested the effect of CBT on these parameters. CBT consisted of 12 weekly sessions of either cognitive therapy (n = 41) or prolonged exposure (PE, n = 49), starting 29.8±5.7 days after ED admission, or delayed PE (n = 35) starting at 151.8±42.4 days. CBT effectively reduced PTSD symptoms in the entire sample.

Main Outcome Measure

Latent trajectories of PTSD symptoms; effects of CBT on these trajectories.

Results

Three trajectories were identified: Rapid Remitting (rapid decrease in symptoms from 1- to 5-months; 56% of the sample), Slow Remitting (progressive decrease in symptoms over 15 months; 27%) and Non-Remitting (persistently elevated symptoms; 17%). CBT accelerated the recovery of the Slow Remitting class but did not affect the other classes.

Conclusions

The early course of PTSD symptoms is characterized by distinct and diverging response patterns that are centrally relevant to understanding the disorder and preventing its occurrence. Studies of the pathogenesis of PTSD may benefit from using clustered symptom trajectories as their dependent variables.     

Reduced Cingulate Gyrus Volume Associated with Enhanced Cortisol Awakening Response in Young Healthy Adults Reporting Childhood Trauma

Background

Preclinical studies have demonstrated the relationship between stress-induced increased cortisol levels and atrophy of specific brain regions, however, this association has been less revealed in clinical samples. The aim of the present study was to investigate the changes and associations of the hypothalamic-pituitary-adrenal (HPA) axis activity and gray matter volumes in young healthy adults with self-reported childhood trauma exposures.

Methods

Twenty four healthy adults with childhood trauma and 24 age- and gender-matched individuals without childhood trauma were recruited. Each participant collected salivary samples in the morning at four time points: immediately upon awakening, 30, 45, and 60 min after awakening for the assessment of cortisol awakening response (CAR). The 3D T1-weighted magnetic resonance imaging data were obtained on a Philips 3.0 Tesla scanner. Voxel-based morphometry analyses were conducted to compare the gray matter volume between two groups. Correlations of gray matter volume changes with severity of childhood trauma and CAR data were further analyzed.

Results

Adults with self-reported childhood trauma showed an enhanced CAR and decreased gray matter volume in the right middle cingulate gyrus. Moreover, a significant association was observed between salivary cortisol secretions after awaking and the right middle cingulate gyrus volume reduction in subjects with childhood trauma.

Conclusions

The present research outcomes suggest that childhood trauma is associated with hyperactivity of the HPA axis and decreased gray matter volume in the right middle cingulate gyrus, which may represent the vulnerability for developing psychosis after childhood trauma experiences. In addition, this study demonstrates that gray matter loss in the cingulate gyrus is related to increased cortisol levels.     

Dorsal Visual Pathway Changes in Patients with Comitant Extropia

Background

Strabismus is a disorder in which the eyes are misaligned. Persistent strabismus can lead to stereopsis impairment. The effect of strabismus on human brain is not unclear. The present study is to investigate whether the brain white structures of comitant exotropia patients are impaired using combined T1-weighted imaging and diffusion tensor imaging (DTI).

Principal Findings

Thirteen patients with comitant strabismus and twelve controls underwent magnetic resonance imaging (MRI) with acquisition of T1-weighted and diffusion tensor images. T1-weighted images were used to analyze the change in volume of white matter using optimized voxel-based morphology (VBM) and diffusion tensor images were used to detect the change in white matter fibers using voxel-based analysis of DTI in comitant extropia patients. VBM analysis showed that in adult strabismus, white matter volumes were smaller in the right middle occipital gyrus, right occipital lobe/cuneus, right supramarginal gyrus, right cingulate gyrus, right frontal lobe/sub-gyral, right inferior temporal gyrus, left parahippocampa gyrus, left cingulate gyrus, left occipital lobe/cuneus, left middle frontal gyrus, left inferior parietal lobule, and left postcentral gyrus, while no brain region with greater white matter volume was found. Voxel-based analysis of DTI showed lower fractional anisotropy (FA) values in the right middle occipital gyrus and right supramarginal gyrus in strabismus patients, while brain region with increased FA value was found in the right inferior frontal gyrus.

Conclusion

By combining VBM and voxel-based analysis of DTI results, the study suggests that the dorsal visual pathway was abnormal or impaired in patients with comitant exotropia.     

Microstructure abnormalities in adolescents with internet addiction disorder

Background

Recent studies suggest that internet addiction disorder (IAD) is associated with structural abnormalities in brain gray matter. However, few studies have investigated the effects of internet addiction on the microstructural integrity of major neuronal fiber pathways, and almost no studies have assessed the microstructural changes with the duration of internet addiction.

Methodology/Principal Findings

We investigated the morphology of the brain in adolescents with IAD (N = 18) using an optimized voxel-based morphometry (VBM) technique, and studied the white matter fractional anisotropy (FA) changes using the diffusion tensor imaging (DTI) method, linking these brain structural measures to the duration of IAD. We provided evidences demonstrating the multiple structural changes of the brain in IAD subjects. VBM results indicated the decreased gray matter volume in the bilateral dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the orbitofrontal cortex (OFC), the cerebellum and the left rostral ACC (rACC). DTI analysis revealed the enhanced FA value of the left posterior limb of the internal capsule (PLIC) and reduced FA value in the white matter within the right parahippocampal gyrus (PHG). Gray matter volumes of the DLPFC, rACC, SMA, and white matter FA changes of the PLIC were significantly correlated with the duration of internet addiction in the adolescents with IAD.

Conclusions

Our results suggested that long-term internet addiction would result in brain structural alterations, which probably contributed to chronic dysfunction in subjects with IAD. The current study may shed further light on the potential brain effects of IAD.     

Early-Stage Psychotherapy Produces Elevated Frontal White Matter Integrity in Adult Major Depressive Disorder

Background

Psychotherapy has demonstrated comparable efficacy to antidepressant medication in the treatment of major depressive disorder. Metabolic alterations in the MDD state and in response to treatment have been detected by functional imaging methods, but the underlying white matter microstructural changes remain unknown. The goal of this study is to apply diffusion tensor imaging techniques to investigate psychotherapy-specific responses in the white matter.

Methods

Twenty-one of forty-five outpatients diagnosed with major depression underwent diffusion tensor imaging before and after a four-week course of guided imagery psychotherapy. We compared fractional anisotropy in depressed patients (n = 21) with healthy controls (n = 22), and before-after treatment, using whole brain voxel-wise analysis.

Results

Post-treatment, depressed subjects showed a significant reduction in the 17-item Hamilton Depression Rating Scale. As compared to healthy controls, depressed subjects demonstrated significantly increased fractional anisotropy in the right thalamus. Psychopathological changes did not recover post-treatment, but a novel region of increased fractional anisotropy was discovered in the frontal lobe.

Conclusions

At an early stage of psychotherapy, higher fractional anisotropy was detected in the frontal emotional regulation-associated region. This finding reveals that psychotherapy may induce white matter changes in the frontal lobe. This remodeling of frontal connections within mood regulation networks positively contributes to the “top-down” mechanism of psychotherapy.     

Gray Matter Abnormalities in Schizophrenia Patients with Tardive Dyskinesia: A Magnetic Resonance Imaging Voxel-Based Morphometry Study

Objective

The pathophysiological mechanism of TD remains unknown. All previous studies, using the region-of-interest method, focused on basal ganglion areas, were with inconsistent results. This whole-brain voxel-based morphometry (VBM) study investigate the grey matter abnormality of TD and its correlates with clinical ratings.

Method

High resolution T1-weighted brain volumetric MRI from 25 schizophrenia patients with TD (TD group), 25 age-, gender-, and handedness-matched schizophrenia patients without TD (non-TD group), and 25 matched healthy subjects (NC group) were analyzed using a VBM approach. Clinical ratings included the Positive and Negative Symptom Scale (PANSS), Abnormal Involuntary Movement Scale (AIMS), and the Simpson-Angus Scale (SAS).

Results

The TD group had significantly smaller total gray matter volumes than the NC group (p = 0.05). Compared to the non-TD group, the TD group had significantly higher PANSS negative (p<0.001), SAS (p<0.001), and AIMS (p<0.001) scores; and smaller bilateral inferior frontal gyrus, which correlated negatively with the PANSS negative scores (r = −0.366, p<0.05); and smaller right superior frontal gyrus, which correlated negatively with AIMS scores (r = −0.399, p<0.001), and PANSS general score (r = −0.338, p<0.05).

Limitations

The cross-section design can’t separate the gray matter change to TD from the context of the illness of schizophrenia, although TD with more severe clinical psychopathology could be a phenotype.

Conclusions

The schizophrenia patients with TD had significantly reduced gray matter, mostly at the bilateral inferior frontal gyrus and the right superior frontal gyrus, which correlated with severity of clinical symptoms and involuntary movement, respectively.     

Regional Brain Structural Abnormality in Meal-Related Functional Dyspepsia Patients: A Voxel-Based Morphometry Study

Background and Aims

Brain dysfunction in functional dyspepsia (FD) has been identified by multiple neuroimaging studies. This study aims to investigate the regional gray matter density (GMD) changes in meal-related FD patients and their correlations with clinical variables, and to explore the possible influence of the emotional state on FD patients’s brain structures.

Methods

Fifty meal-related FD patients and forty healthy subjects (HS) were included and underwent a structural magnetic resonance imaging scan. Voxel-based morphometry analysis was employed to identify the cerebral structure alterations in meal-related FD patients. Regional GMD changes'' correlations with the symptoms and their durations, respectively, have been analyzed.

Results

Compared to the HS, the meal-related FD patients showed a decreased GMD in the bilateral precentral gyrus, medial prefrontal cortex (MPFC), anterior cingulate cortex (ACC) and midcingulate cortex (MCC), left orbitofrontal cortex (OFC) and right insula (p<0.05, FWE Corrected, Cluster size>50). After controlling for anxiety and depression, the meal-related FD patients showed a decreased GMD in the bilateral middle frontal gyrus, left MCC, right precentral gyrus and insula (p<0.05, FWE Corrected, Cluster size>50). Before controlling psychological factors, the GMD decreases in the ACC were negatively associated with the symptom scores of the Nepean Dyspepsia Index (NDI) (r = −0.354, p = 0.048, Bonferroni correction) and the duration of FD (r = −0.398, p = 0.02, Bonferroni correction) respectively.

Conclusions

The regional GMD of meal-related FD patients, especially in the regions of the homeostatic afferent processing network significantly differed from that of the HS, and the psychological factors might be one of the essential factors significantly affecting the regional brain structure of meal-related FD patients.     

Convergent evidence from multimodal imaging reveals amygdala abnormalities in schizophrenic patients and their first-degree relatives

Background

Shared neuropathological features between schizophrenic patients and their first-degree relatives have potential as indicators of genetic vulnerability to schizophrenia. We sought to explore genetic influences on brain morphology and function in schizophrenic patients and their relatives.

Methods

Using a multimodal imaging strategy, we studied 33 schizophrenic patients, 55 of their unaffected parents, 30 healthy controls for patients, and 29 healthy controls for parents with voxel-based morphometry of structural MRI scans and functional connectivity analysis of resting-state functional MRI data.

Results

Schizophrenic patients showed widespread gray matter reductions in the bilateral frontal cortices, bilateral insulae, bilateral occipital cortices, left amygdala and right thalamus, whereas their parents showed more localized reductions in the left amygdala, left thalamus and right orbitofrontal cortex. Patients and their parents shared gray matter loss in the left amygdala. Further investigation of the resting-state functional connectivity of the amygdala in the patients showed abnormal functional connectivity with the bilateral orbitofrontal cortices, bilateral precunei, bilateral dorsolateral frontal cortices and right insula. Their parents showed slightly less, but similar changes in the pattern in the amygdala connectivity. Co-occurrences of abnormal connectivity of the left amygdala with the left orbitofrontal cortex, right dorsolateral frontal cortex and right precuneus were observed in schizophrenic patients and their parents.

Conclusions

Our findings suggest a potential genetic influence on structural and functional abnormalities of the amygdala in schizophrenia. Such information could help future efforts to identify the endophenotypes that characterize the complex disorder of schizophrenia.     

Changes in White Matter Integrity before Conversion from Mild Cognitive Impairment to Alzheimer’s Disease

Background

Mild cognitive impairment (MCI) may represent an early stage of dementia conferring a particularly high annual risk of 15–20% of conversion to Alzheimer’s disease (AD). Recent findings suggest that not only gray matter (GM) loss but also a decline in white matter (WM) integrity may be associated with imminent conversion from MCI to AD.

Objective

In this study we used Voxel-based morphometry (VBM) to examine if gray matter loss and/or an increase of the apparent diffusion coefficient (ADC) reflecting mean diffusivity (MD) are an early marker of conversion from MCI to AD in a high risk population.

Method

Retrospective neuropsychological and clinical data were collected for fifty-five subjects (MCI converters n = 13, MCI non-converters n = 14, healthy controls n = 28) at baseline and one follow-up visit. All participants underwent diffusion weighted imaging (DWI) and T1-weighted structural magnetic resonance imaging scans at baseline to analyse changes in GM density and WM integrity using VBM.

Results

At baseline MCI converters showed impaired performance in verbal memory and naming compared to MCI non-converters. Further, MCI converters showed decreased WM integrity in the frontal, parietal, occipital, as well as the temporal lobe prior to conversion to AD. Multiple regression analysis showed a positive correlation of gray matter atrophy with specific neuropsychological test results.

Conclusion

Our results suggest that additionally to morphological changes of GM a reduced integrity of WM indicates an imminent progression from MCI stage to AD. Therefore, we suggest that DWI is useful in the early diagnosis of AD.     

Duration of Untreated Psychosis Is Associated with Temporal and Occipitotemporal Gray Matter Volume Decrease in Treatment Na?ve Schizophrenia

Background

Long duration of untreated psychosis (DUP) is associated with poor treatment outcome. Whether or not DUP is related to brain gray matter volume abnormalities in antipsychotic medication treatment naïve schizophrenia remains unclear at this time.

Methods

Patients with treatment-naïve schizophrenia and healthy controls went through brain scan using high resolution Magnetic Resonance Imaging. DUP was evaluated using the Nottingham Onset Schedule (NOS), and dichotomized as short DUP (≤ 26 weeks) or long DUP (>26 weeks). Voxel-based methods were used for volumetric measure in the brain.

Results

Fifty-seven patients (27 short DUP and 30 long DUP) and 30 healthy controls were included in the analysis. There were significant gray matter volumetric differences among the 3 groups in bilateral parahippocampus gyri, right superior temporal gyrus, left fusiform gyrus, left middle temporal gyrus, and right superior frontal gyrus (p''s<0.01). Compared with healthy controls, the long DUP group had significantly smaller volume in all these regions (p''s <0.05). Compared with the short-DUP group, the long-DUP group had significantly smaller volume in right superior temporal gyrus, left fusiform gyrus, and left middle temporal gyrus (p''s<0.01).

Conclusion

Our findings suggest that DUP is associated with temporal and occipitotemporal gray matter volume decrease in treatment naïve schizophrenia. The brain structural changes in untreated psychosis might contribute to poor treatment response and long-term prognosis in this patient population.     

A Systematic Review of PTSD Prevalence and Trajectories in DSM-5 Defined Trauma Exposed Populations: Intentional and Non-Intentional Traumatic Events

Objective

We conducted a systematic review of the literature to explore the longitudinal course of PTSD in DSM-5-defined trauma exposed populations to identify the course of illness and recovery for individuals and populations experiencing PTSD.

Methods

We reviewed the published literature from January 1, 1998 to December 31, 2010 for longitudinal studies of directly exposed trauma populations in order to: (1) review rates of PTSD in the first year after a traumatic event; (2) examine potential types of proposed DSM-5 direct trauma exposure (intentional and non-intentional); and (3) identify the clinical course of PTSD (early onset, later onset, chronicity, remission, and resilience). Of the 2537 identified articles, 58 articles representing 35 unique subject populations met the proposed DSM-5 criteria for experiencing a traumatic event, and assessed PTSD at two or more time points within 12 months of the traumatic event.

Results

The mean prevalence of PTSD across all studies decreases from 28.8% (range  = 3.1–87.5%) at 1 month to 17.0% (range  = 0.6–43.8%) at 12 months. However, when traumatic events are classified into intentional and non-intentional, the median prevalences trend down for the non-intentional trauma exposed populations, while the median prevalences in the intentional trauma category steadily increase from 11.8% to 23.3%. Across five studies with sufficient data, 37.1% of those exposed to intentional trauma develop PTSD. Among those with PTSD, about one third (34.8%) remit after 3 months. Nearly 40% of those with PTSD (39.1%) have a chronic course, and only a very small fraction (3.5%) of new PTSD cases appears after three months.

Conclusions

Understanding the trajectories of PTSD over time, and how it may vary by type of traumatic event (intentional vs. non-intentional) will assist public health planning and treatment.     

Global and Regional Associations of Smaller Cerebral Gray and White Matter Volumes with Gait in Older People

Background

Gait impairments increase with advancing age and can lead to falls and loss of independence. Brain atrophy also occurs in older age and may contribute to gait decline. We aimed to investigate global and regional relationships of cerebral gray and white matter volumes with gait speed, and its determinants step length and cadence, in older people.

Methods

In a population-based study, participants aged >60 years without Parkinson''s disease or brain infarcts underwent magnetic resonance imaging and gait measurements using a computerized walkway. Linear regression was used to study associations of total gray and white matter volumes with gait, adjusting for each other, age, sex, height and white matter hyperintensity volume. Other covariates considered in analyses included weight and vascular disease history. Voxel-based morphometry was used to study regional relationships of gray and white matter with gait.

Results

There were 305 participants, mean age 71.4 (6.9) years, 54% male, mean gait speed 1.16 (0.22) m/s. Smaller total gray matter volume was independently associated with poorer gait speed (p = 0.001) and step length (p<0.001), but not cadence. Smaller volumes of cortical and subcortical gray matter in bilateral regions important for motor control, vision, perception and memory were independently associated with slower gait speed and shorter steps. No global or regional associations were observed between white matter volume and gait independent of gray matter volume, white matter hyperintensity volume and other covariates.

Conclusion

Smaller gray matter volume in bilaterally distributed brain networks serving motor control was associated with slower gait speed and step length, but not cadence.     

Alterations in Low-Level Perceptual Networks Related to Clinical Severity in PTSD after an Earthquake: A Resting-State fMRI Study

Background

Several task-based functional MRI (fMRI) studies have highlighted abnormal activation in specific regions involving the low-level perceptual (auditory, visual, and somato-motor) network in posttraumatic stress disorder (PTSD) patients. However, little is known about whether the functional connectivity of the low-level perceptual and higher-order cognitive (attention, central-execution, and default-mode) networks change in medication-naïve PTSD patients during the resting state.

Methods

We investigated the resting state networks (RSNs) using independent component analysis (ICA) in 18 chronic Wenchuan earthquake-related PTSD patients versus 20 healthy survivors (HSs).

Results

Compared to the HSs, PTSD patients displayed both increased and decreased functional connectivity within the salience network (SN), central executive network (CEN), default mode network (DMN), somato-motor network (SMN), auditory network (AN), and visual network (VN). Furthermore, strengthened connectivity involving the inferior temporal gyrus (ITG) and supplementary motor area (SMA) was negatively correlated with clinical severity in PTSD patients.

Limitations

Given the absence of a healthy control group that never experienced the earthquake, our results cannot be used to compare alterations between the PTSD patients, physically healthy trauma survivors, and healthy controls. In addition, the breathing and heart rates were not monitored in our small sample size of subjects. In future studies, specific task paradigms should be used to reveal perceptual impairments.

Conclusions

These findings suggest that PTSD patients have widespread deficits in both the low-level perceptual and higher-order cognitive networks. Decreased connectivity within the low-level perceptual networks was related to clinical symptoms, which may be associated with traumatic reminders causing attentional bias to negative emotion in response to threatening stimuli and resulting in emotional dysregulation.     

Impact of the genome wide supported NRGN gene on anterior cingulate morphology in schizophrenia

Background

The rs12807809 single-nucleotide polymorphism in NRGN is a genetic risk variant with genome-wide significance for schizophrenia. The frequency of the T allele of rs12807809 is higher in individuals with schizophrenia than in those without the disorder. Reduced immunoreactivity of NRGN, which is expressed exclusively in the brain, has been observed in Brodmann areas (BA) 9 and 32 of the prefrontal cortex in postmortem brains from patients with schizophrenia compared with those in controls.

Methods

Genotype effects of rs12807809 were investigated on gray matter (GM) and white matter (WM) volumes using magnetic resonance imaging (MRI) with a voxel-based morphometry (VBM) technique in a sample of 99 Japanese patients with schizophrenia and 263 healthy controls.

Results

Although significant genotype-diagnosis interaction either on GM or WM volume was not observed, there was a trend of genotype-diagnosis interaction on GM volume in the left anterior cingulate cortex (ACC). Thus, the effects of NRGN genotype on GM volume of patients with schizophrenia and healthy controls were separately investigated. In patients with schizophrenia, carriers of the risk T allele had a smaller GM volume in the left ACC (BA32) than did carriers of the non-risk C allele. Significant genotype effect on other regions of the GM or WM was not observed for either the patients or controls.

Conclusions

Our findings suggest that the genome-wide associated genetic risk variant in the NRGN gene may be related to a small GM volume in the ACC in the left hemisphere in patients with schizophrenia.     

Structural and Functional Brain Alterations in End Stage Renal Disease Patients on Routine Hemodialysis: A Voxel-Based Morphometry and Resting State Functional Connectivity Study

Background and Purpose

Cognitive impairment is a well-described phenomenon in end-stage renal disease (ESRD) patients. However, its pathogenesis remains poorly understood. The primary focus of this study was to examine structural and functional brain deficits in ESRD patients.

Materials and Methods

Thirty ESRD patients on hemodialysis (without clinical neurological disease) and 30 age- and gender-matched control individuals (without renal or neurological problems) were recruited in a prospective, single-center study. High-resolution structural magnetic resonance imaging (MRI) and resting state functional MRI were performed on both groups to detect the subtle cerebral deficits in ESRD patients. Voxel-based morphometry was used to characterize gray matter deficits in ESRD patients. The impact of abnormal morphometry on the cerebral functional integrity was investigated by evaluating the alterations in resting state functional connectivity when brain regions with gray matter volume reduction were used as seed areas.

Results

A significant decrease in gray matter volume was observed in ESRD patients in the bilateral medial orbito-prefrontal cortices, bilateral dorsal lateral prefrontal cortices, and the left middle temporal cortex. When brain regions with gray matter volume reduction were used as seed areas, the integration was found to be significantly decreased in ESRD patients in the fronto-cerebellum circuits and within prefrontal circuits. In addition, significantly enhanced functional connectivity was found between the prefrontal cortex and the left temporal cortex and within the prefrontal circuits.

Conclusions

Our study revealed that both the structural and functional cerebral cortices were impaired in ESRD patients on routine hemodialysis.