Huiguang He

Glutamatergic and Resting-State Functional Connectivity Correlates of Severity in Major Depression – The Role of Pregenual Anterior Cingulate Cortex and Anterior Insula

Glutamatergic mechanisms and resting-state functional connectivity alterations have been recently described as factors contributing to major depressive disorder (MDD). Furthermore, the pregenual anterior cingulate cortex (pgACC) seems to play an important role for major depressive symptoms such as anhedonia and impaired emotion processing. We investigated 22 MDD patients and 22 healthy subjects using a combined magnetic resonance spectroscopy (MRS) and resting-state functional magnetic resonance imaging (fMRI) approach. Severity of depression was rated using the 21-item Hamilton depression scale (HAMD) and patients were divided into severely and mildly depressed subgroups according to HAMD scores. Because of their hypothesized role in depression we investigated the functional connectivity between pgACC and left anterior insular cortex (AI). The sum of Glutamate and Glutamine (Glx) in the pgACC, but not in left AI, predicted the resting-state functional connectivity between the two regions exclusively in depressed patients. Furthermore, functional connectivity between these regions was significantly altered in the subgroup of severely depressed patients (HAMD > 15) compared to healthy subjects and mildly depressed patients. Similarly the Glx ratios, relative to Creatine, in the pgACC were lowest in severely depressed patients. These findings support the involvement of glutamatergic mechanisms in severe MDD which are related to the functional connectivity between pgACC and AI and depression severity.

Classification of ADHD children through multimodal magnetic resonance imaging

Attention deficit/hyperactivity disorder (ADHD) is one of the most common diseases in school-age children. To date, the diagnosis of ADHD is mainly subjective and studies of objective diagnostic method are of great importance. Although many efforts have been made recently to investigate the use of structural and functional brain images for the diagnosis purpose, few of them are related to ADHD. In this paper, we introduce an automatic classification framework based on brain imaging features of ADHD patients and present in detail the feature extraction, feature selection, and classifier training methods. The effects of using different features are compared against each other. In addition, we integrate multimodal image features using multi-kernel learning (MKL). The performance of our framework has been validated in the ADHD-200 Global Competition, which is a world-wide classification contest on the ADHD-200 datasets. In this competition, our classification framework using features of resting-state functional connectivity (FC) was ranked the 6th out of 21 participants under the competition scoring policy and performed the best in terms of sensitivity and J-statistic.

Gender consistency and difference in healthy adults revealed by cortical thickness

Many previous studies have shown that there exists the gender effect on the structural and functional organization in the human brain. Although the reported functional differences are generally consistent, the structural differences are controversial among the various studies. In this study, we particularly focused on the gender-related effect in the gray matter (GM). We performed a structural magnetic resonance imaging (MRI) study in 184 healthy adults (90 males and 94 females) with ages ranging from 18 to 70 years. Cortical thickness was measured using an automated surface-based method. Based on this surface morphological feature of GM, we first compared their regional differences between males and females. We then constructed the morphometry-based anatomical networks derived from cortical thickness measurement, while the anatomical connection between two cortical areas depended upon the statistical dependence of their cortical thickness across subjects. Subsequently, we applied graph theoretical approaches to investigate the properties of the resultant anatomical networks. The results showed that the significant gender-related differences of cortical thickness appeared extensively in the frontal, parietal and occipital lobes. And there were also some between-group differences in the interregional correlation. Additional graph theoretical analysis on the morphological networks revealed both networks exhibited the small-world efficiency and their patterns of topological vulnerability had no statistical differences. The findings on the large sample may provide the evidences to study the gender consistency and difference in the human brain structures.

Regional Specificity of Sex Effects on Subcortical Volumes Across the Lifespan in Healthy Aging

When conceptualizing age‐specific onsets and sex‐specific characteristics of neuropsychiatric diseases in a neurobiological context, it may be crucially important to consider differential trajectories of aging. Here, we investigated effects of age, sex, and their interactions on absolute and relative volumes of subcortical structures with known involvement in psychiatric disorders, including the basal ganglia, thalamus, hippocampus, and amygdala. Structural MRI data of 76 healthy subjects (38 males, 19–70 years) from the ICBM database were analyzed. Age‐related absolute atrophy was generally found in the basal ganglia and thalamus, while in the hippocampus decline was only observed in males, and was generally absent in the amygdala. Disproportionate degeneration in the basal ganglia and thalamus, exceeding cortical decline was specific for females. When allowing higher‐order models, a quadratic model could better describe the negative relation of absolute volume and age in the basal ganglia in males, and generally in the hippocampus and amygdala. We could show that negative age‐relations are highly specific for certain subcortical structures in either gender. Importantly these findings also emphasize the significant impact of analytical strategies when deciding for correction of subcortical volumes to the whole‐brain decline. Specifically, in the basal ganglia disproportionate shrinkage in females was suggested by the relative analysis while absolute volume analysis rather stressed an accelerating decline in older males. Given strong involvement of the basal ganglia in both cognitive aging and emotional regulation, our findings may be crucial for studies investigating the onset and prevalence of dementia and depressive symptoms in male and female aging. Hum Brain Mapp 35:238–247, 2014.

Altered White Matter Integrity in Adolescents with Prelingual Deafness: A High-Resolution Tract-Based Spatial Statistics Imaging Study

BACKGROUND AND PURPOSE: Prelingual deafness is a hearing loss that occurs before language is acquired and may result in brain structural alterations. We studied microstructural WM alterations in prelingually deaf adolescents by using DTI. We hypothesized that any morphologic alterations are mainly located in the auditory association areas. Furthermore, considering that the developing brain is both more vulnerable to deprivation and more plastic than the adult brain, we speculated that the affected areas should be larger than those previously reported in adult deafness. MATERIALS AND METHODS: Diffusion tensor images were obtained from 16 prelingually deaf adolescents (age range, 10–18 years) and 16 healthy control adolescents matched for age and sex. Both groups were compared in fractional anisotropy and radial diffusivity by tract-based spatial statistics. In addition, we examined the correlation between the structural data (FA, RD) differences and the duration of sign language use and hearing aid experience. RESULTS: Prelingually deaf adolescents had significantly lower FA and increased RD in the bilateral superior temporal gyri, Heschl gyrus, planum polare, and the splenium of the corpus callosum. Only RD values in the right superior temporal gyrus correlated significantly and negatively (r = −0.518; P = .040) with duration of sign language use. These alterations were larger than those previously reported in adult deafness. CONCLUSIONS: As expected, we found severe morphologic changes of decreased FA and increased RD in multiple auditory association areas and in the corpus callosum. These changes are signs of development impairments in prelingually deaf adolescents, possibly reflecting axonal loss or lack of myelination.

Structural Abnormalities in Early Tourette Syndrome Children: A Combined Voxel-Based Morphometry and Tract-Based Spatial Statistics Study

Tourette Syndrome (TS) is characterized with chronic motor and vocal tics beginning in childhood. Abnormality of both gray (GM) and white matter (WM) has been observed in cortico-striato-thalamo-cortical circuits and sensory-motor cortex of adult TS patient. It is not clear if these morphological changes are also present in TS children and if there are any microstructural changes of WM. To understand the developmental cause of such changes, we investigated volumetric changes of GM and WM using VBM and microstructural changes of WM using DTI, and correlated these changes with tic severity and duration. T1 images and Diffusion Tensor Images (DTI) from 21 TS children were compared with 20 age and gender matched health control children using a 1.5T Philips scanner. All of the 21 TS children met the DSM-IV-TR criteria. T1 images were analyzed using DARTEL-VBM in conjunction with statistical parametric mapping (SPM). Diffusion tensor imaging (DTI) analysis was performed using Tract-Based Spatial Statistics (TBSS). Brain volume changes were found in left superior temporal gyrus, left and right paracentral gyrus, right precuneous cortex, right pre- and post- central gyrus, left temporal occipital fusiform cortex, right frontal pole, and left lingual gyrus. Significant axial diffusivity (AD) and mean diffusivity (MD) increases were found in anterior thalamic radiation, right cingulum bundle projecting to the cingulate gurus and forceps minor. Decreases in white matter volume (WMV) in the right frontal pole were inversely related with tic severity (YGTSS), and increases in AD and MD were positively correlated with tic severity and duration, respectively. These changes in TS children can be interpreted as signs of neural plasticity in response to the experiential demand. Our findings may suggest that the morphological and microstructural measurements from structural MRI and DTI can potentially be used as a biomarker of the pathophysiologic pattern of early TS children.

Cortical thickness analysis and optimized voxel-based morphometry in children and adolescents with prelingually profound sensorineural hearing loss

Crossmodal neuroplastic changes following auditory deprivation in individuals with profound sensorineural hearing loss (SNHL) have been well documented in previous literature. However, previous studies have shown very little evidence of structural brain changes in individuals with prelingually profound SNHL and no studies have reported significant differences of gray matter (GM) in deaf subjects. Therefore, it is essential to employ a more specific and sensitive technique to detect subtle structural brain differences in deaf individuals. The objective of our study was to investigate neuroanatomical differences in children and adolescents with profound SNHL by cortical thickness analysis and optimized voxel-based morphometry (VBM). T1-weighted volumetric images of 16 children and adolescents with prelingually profound SNHL and 16 hearing controls were analyzed. The ANCOVA analysis revealed a statistically significant decreased average cortical thickness of the whole brain. As to vertex-based analysis, cortical thickness of the deaf subjects showed significant thinning in the left precentral gyrus, right postcentral gyrus, the left superior occipital gyrus and the left fusiform gyrus compared with the hearing subjects. VBM revealed statistically significant focal reduction of white matter (WM) volume in the left middle frontal gyrus and the right inferior occipital gyrus in deaf subjects without statistically significant differences in GM volume between the two groups. These findings demonstrated that structural changes happened not only in the WM but also in the GM of the subjects with prelingually profound SNHL, which have never been reported before in any previous literature. Our results also implicated the potential neuroplastic changes associated with crossmodal reorganization in the brain after auditory deprivation in the early deafness.

Preliminary system characterization of flat-panel-detector-based cone-beam CT for breast imaging

Conventional film-screen mammography is the most effective tool for the early detection of breast cancer currently available. However, conventional mammography has relatively low sensitivity to detect small breast cancers (under several millimeters) owing to an overlap in the appearances of benign and malignant lesions, and surrounding structure. The limitations accompanying conventional mammography is to be addressed by incorporating a cone beam CT imaging technique with a recently developed flat panel detector. Computer simulation and preliminary studies have been performed to prove the feasibility of developing a flat panel detector-based cone beam CT breast imaging (FPD-CBCTBI) technique. A preliminary system characterization study of flat panel detector-based cone beam CT for breast imaging was performed to confirm the findings in the computer simulation and previous phantom studies using the current prototype cone beam CT scanner. The results indicate that the CBCTBI technique effectively removes structure overlap and significantly improves the detectability of small breast tumors. More importantly, the results also demonstrate CBCTBI offers good image quality with the radiation dose level less than or equal to that of conventional mammography. The results from this study suggest that FPD-CBCTBI is a potentially powerful breast-imaging tool.

Structural and functional deficits in human amblyopia

Many neuroimaging tools have been used to assess the site of the cortical deficits in human amblyopia. In this paper, we aimed at detecting the structural and functional deficits in humans with amblyopia, with the aid of anatomic magnetic resonance imaging (aMRI) and functional MRI (fMRI). We designed the visual stimulus to investigate the functional deficits, and delineated the V1/V2 areas by retinotopic mapping. Then we performed the brain parcellation to calculate the volume of the subcortical structure on each individual, and reconstructed the cortical surfaces to measure the cortical thickness. At last, the statistical comparison was carried out to find the structural abnormities and their relationship to the functional deficits. Compared with the normal controls, it is found that the hemisphere difference existed on the unilateral amblyopia subjects, and the functional deficit might come along with the changes in the cortical volume, especially in the occipital lobe. The examined results may provide insight to the study of the neural substrates of amblyopia.

Dissociation of glutamate and cortical thickness is restricted to regions subserving trait but not state markers in major depressive disorder

BACKGROUND The anterior cingulate cortex (ACC) plays an important role in the neuropathology of major depressive disorder (MDD). So far, the effect of local cortical alteration on metabolites in multiple subdivisions of ACC has not been studied. We aimed to investigate structural and biochemical changes and their relationship in the pregenual ACC (pgACC), dorsal ACC (dACC) in MDD. METHODS We obtained magnetic resonance spectroscopy (MRS) in two investigated regions for 24 depressed patients and matched controls. In each region, cortical thickness (CTh) was calculated within a template mask based on its MRS voxel. We investigated neurotransmitter concentrations of Glx, N-acetyl aspartate (NAA), and myo-inositol (m-Ins) in two investigated regions, as well as their relationships with CTh in depressed individuals and healthy controls. RESULTS Patients showed significantly lower cortical thickness in dACC compared to controls. Glx in dACC significantly correlated with CTh in healthy controls but not MDD patients, while NAA and CTh in dACC significantly correlated in both groups. A marginal decrease of Glx in pgACC was found in the subgroup of more severely depressive patients, compared to the mildly depressed patients. LIMITATIONS Modest sample size and lack of episodes of depression may limit the generalizability of our findings. CONCLUSION Our results indicate an abolished CTh-MRS relation in dACC-associated with structural decline-but not in pgACC, where acute MRS alterations prevailed. Our study provides the first evidence of a neurochemical basis explaining some of the inter-individual variability in CTh in MDD.