Yuanchao Zhang

Abnormal Cortical Networks in Mild Cognitive Impairment and Alzheimer's Disease

Recently, many researchers have used graph theory to study the aberrant brain structures in Alzheimers disease (AD) and have made great progress. However, the characteristics of the cortical network in Mild Cognitive Impairment (MCI) are still largely unexplored. In this study, the gray matter volumes obtained from magnetic resonance imaging (MRI) for all brain regions except the cerebellum were parcellated into 90 areas using the automated anatomical labeling (AAL) template to construct cortical networks for 98 normal controls (NCs), 113 MCIs and 91 ADs. The measurements of the network properties were calculated for each of the three groups respectively. We found that all three cortical networks exhibited small-world properties and those strong interhemispheric correlations existed between bilaterally homologous regions. Among the three cortical networks, we found the greatest clustering coefficient and the longest absolute path length in AD, which might indicate that the organization of the cortical network was the least optimal in AD. The small-world measures of the MCI network exhibited intermediate values. This finding is logical given that MCI is considered to be the transitional stage between normal aging and AD. Out of all the between-group differences in the clustering coefficient and absolute path length, only the differences between the AD and normal control groups were statistically significant. Compared with the normal controls, the MCI and AD groups retained their hub regions in the frontal lobe but showed a loss of hub regions in the temporal lobe. In addition, altered interregional correlations were detected in the parahippocampus gyrus, medial temporal lobe, cingulum, fusiform, medial frontal lobe, and orbital frontal gyrus in groups with MCI and AD. Similar to previous studies of functional connectivity, we also revealed increased interregional correlations within the local brain lobes and disrupted long distance interregional correlations in groups with MCI and AD.

Abnormal topological organization of structural brain networks in schizophrenia

Schizophrenia is a debilitating mental disorder characterized by disturbances of thought and emotion as well as neurocognitive deficits. It is hypothesized that the core symptoms of schizophrenia arise from the inability to integrate neural processes segregated across distributed brain regions. Graph theory allows us to verify this hypothesis at large-scale structural network level. In this study, a sample of 101 schizophrenic patients and 101 healthy controls was included. We sought to investigate the abnormality of network topological organization in patients with schizophrenia by using the cortical thickness measurement from magnetic resonance imaging. Brain networks were constructed by thresholding cortical thickness correlation matrices of 78 regions and analyzed using graph theoretical approaches. Compared to healthy controls, patients showed increased characteristic path length and clustering coefficient in the structural cortical networks. Moreover, schizophrenia patients were associated with reduced nodal centrality in several regions of the default network and increased nodal centrality mainly in primary cortex and paralimbic cortex regions. These findings suggest that the structural networks of schizophrenic patients have a less optimal topological organization, resulting in reduced capacity to integrate information across brain regions.

Tractography-based parcellation of the human left inferior parietal lobule.

The inferior parietal lobule (IPL) is a functionally and anatomically heterogeneous region. Much of the information about the anatomical connectivity and parcellation of this region was obtained from histological studies on non-human primates. However, whether these findings from non-human primates can be applied to the human inferior parietal lobule, especially the left inferior parietal lobule, which shows evidence of considerable evolution from primates to humans, remains unclear. In this study, diffusion MRI was employed to investigate the anatomical connectivities of the human left inferior parietal lobule. Using a new algorithm, spectral clustering with edge-weighted centroidal voronoi tessellations, to search for regional variations in the probabilistic connectivity profiles of all left inferior parietal lobule voxels with all the rest of the brain identified six subregions with distinctive connectivity properties in the left inferior parietal lobule. Consistent with cytoarchitectonic findings, four subregions were found in the left supramarginal gyrus and two subregions in the left angular gyrus. The specific connectivity patterns of each subregion of the left inferior parietal lobule were supported by both the anatomical and functional connectivity properties for each subregion, as calculated by a meta-analysis-based target method and by voxel-based whole brain anatomical and functional connectivity analyses. The proposed parcellation scheme for the human left inferior parietal lobule and the maximum probability map for each subregion may facilitate more detailed future studies of this brain area.

Connectivity-Based Parcellation of the Human Posteromedial Cortex

Regional structural and functional variations in the posteromedial cortex (PMC) have been found in both animals and humans, strongly suggesting the presence of subdivisions. However, there is no consensus on how to subdivide the human PMC. Here, we investigated the anatomical parcellation scheme and the connectivity pattern of each subdivision of the human PMC using diffusion tensor imaging data from 2 independent groups of volunteers. The parcellation analyses of the 2 datasets consistently demonstrated that the human PMC can be parcellated into 5 subregions. The dorsal portion of the PMC was subdivided into anterior, central, and posterior subregions, which participate in sensorimotor, associative, and visual functions. The ventral PMC contained a transitional region in the dorsal portion and a ventral subregion that is the core of the default mode network. The parcellation results for the human PMC and its anatomical connectivity patterns were further supported by evidence from the macaque PMC. Furthermore, functional connectivity analysis revealed that each subregion exhibited a specific pattern similar to that of its anatomical connectivity. The proposed parcellation scheme may facilitate the study of the human PMC at a subtler level and improve our understanding of its functions.

Decreased gyrification in major depressive disorder

Structural and functional abnormalities have been extensively reported in major depressive disorder, but possible changes in cortical folding have not yet been explored in this disorder. This study investigated this issue in major depressive disorder using the local gyrification index. High-resolution magnetic resonance imaging was performed in 18 patients with first-episode major depressive disorder and 18 age-matched and sex-matched healthy individuals. The local gyrification index was applied to detect brain areas with abnormal cortical folding in major depressive disorder. Compared with healthy participants, patients with major depressive disorder showed significantly decreased local gyrification index in the bilateral mid-posterior cingulate, insula, and orbital frontal cortices, the left anterior cingulate cortex, and the right temporal operculum.

Cortical Gyrification Reductions and Subcortical Atrophy in Parkinson's Disease

Parkinsons disease (PD) is a neurodegenerative disorder characterized by both motor and non‐motor symptoms. Previous morphometric studies of PD were mainly conducted by measuring gray matter volume and cortical thickness, and little attention has been paid to the morphology of the cortical surface.

Dosage Effects of BDNF Val66Met Polymorphism on Cortical Surface Area and Functional Connectivity

The single nucleotide polymorphism (SNP) that leads to a valine-to-methionine substitution at codon 66 (Val66Met) in BDNF is correlated with differences in cognitive and memory functions, as well as with several neurological and psychiatric disorders. MRI studies have already shown that this genetic variant contributes to changes in cortical thickness and volume, but whether the Val66Met polymorphism affects the cortical surface area of healthy subjects remains unclear. Here, we used multimodal MRI to study whether this polymorphism would affect the cortical morphology and resting-state functional connectivity of a large sample of healthy Han Chinese human subjects. An SNP-wise general linear model analysis revealed a “dosage effect” of the Met allele, specifically a stepwise increase in cortical surface area of the right anterior insular cortex with increasing numbers of the Met allele. Moreover, we found enhanced functional connectivity between the anterior insular and the dorsolateral prefrontal cortices that was linked with the dosage of the Met allele. In conclusion, these data demonstrated a “dosage effect” of BDNF Val66Met on normal cortical structure and function, suggesting a new path for exploring the mechanisms underlying the effects of genotype on cognition.

Regional atrophy of the basal ganglia and thalamus in idiopathic generalized epilepsy

To determine the regional changes in the shapes of subcortical structures in idiopathic generalized epilepsy using a vertex‐based analysis method. Earlier studies found that gray matter volume in the frontal, parietal, and temporal lobes is significantly altered in idiopathic generalized epilepsy (IGE). Research has indicated that a relationship exists between the brains subcortical structures and epilepsy. However, little is known about possible changes in the subcortical structures in IGE.

Functional organization of the fusiform gyrus revealed with connectivity profiles.

Within the object recognition‐related ventral visual stream, the human fusiform gyrus (FG), which topographically connects the striate cortex to the inferior temporal lobe, plays a pivotal role in high‐level visual/cognitive functions. However, though there are many previous investigations of distinct functional modules within the FG, the functional organization of the whole FG in its full functional heterogeneity has not yet been established. In the current study, a replicable functional organization of the FG based on distinct anatomical connectivity patterns was identified. The FG was parcellated into medial (FGm), lateral (FGl), and anterior (FGa) regions using diffusion tensor imaging. We validated the reasonability of such an organizational scheme from the perspective of resting‐state whole brain functional connectivity patterns and the involvement of functional subnetworks. We found corroborating support for these three distinct modules, and suggest that the FGm serves as a transition region that combines multiple stimuli, the FGl is responsible for categorical recognition, and the FGa is involved in semantic understanding. These findings support two organizational functional transitions of the ventral temporal gyrus, a posterior/anterior direction of visual/semantic processing, and a media/lateral direction of high‐level visual processing. Our results may facilitate a more detailed study of the human FG in the future. Hum Brain Mapp 37:3003–3016, 2016.

Abnormal functional connectivity density in Parkinson's disease.

The pathology of Parkinsons disease (PD) is not confined to the nigrostriatal pathway, but also involves widespread cerebral cortical areas. Using seed-based resting state functional connectivity, many previous studies have demonstrated that PD patients have abnormal functional integration. However, this technique strongly relies on a priori selection of the seed regions and may miss important unpredictable findings. Using an ultrafast voxel-wise functional connectivity density approach, this study performed a whole brain functional connectivity analysis to investigate the abnormal resting-state functional activities in PD patients. Compared with healthy controls, PD patients exhibited decreased short-range functional connectivity densities in regions that were mainly located in the ventral visual pathway and decreased long-range functional connectivity densities in the right middle and superior frontal gyrus, which have been speculated to be associated with visual hallucinations and cognitive dysfunction, respectively. PD patients also exhibited increased short- and long-range functional connectivity densities in the bilateral precuneus and posterior cingulate cortex, which may represent a compensatory process for maintaining normal brain function. The observed functional connectivity density alterations might be related to the disturbed structural connectivity of PD patients, leading to abnormal functional integration. Our results suggest that functional connectivity density mapping may provide a useful means to assess PD-related neurodegeneration and to study the pathophysiology of PD.