Working memory processing deficit associated with a nonlinear response pattern of the anterior cingulate cortex in first-episode and drug-naïve schizophrenia.

Impaired working memory (WM) is a core neuropsychological dysfunction of schizophrenia, however complex interactions among the information storage, information processing and attentional aspects of WM tasks make it difficult to uncover the psychophysiological mechanisms of this deficit. Thirty-six first-episode and drug-naïve schizophrenia and 29 healthy controls (HCs) were enrolled in this study. Here, we modified a WM task to isolate components of WM storage and WM processing, while also varying the difficulty level (load) of the task to study regional differences in load-specific activation using mixed effects models, and its relationship to distributed gene expression. Comparing patients with HCs, we found both attentional deficits and WM deficits, with WM processing being more impaired than WM storage in patients. In patients, but not controls, a linear modulation of brain activation was observed mainly in the frontoparietal and dorsal attention networks. In controls, an inverted U-shaped response pattern was identified in the left anterior cingulate cortex. The vertex of this inverted U-shape was lower in patients than controls, and a left-shifting axis of symmetry was associated with better WM performance in patients. Both the above linear and U-shaped modulation effects were associated with the expressions of the genes enriched in the dopamine neurotransmitter system across all cortical brain regions. These findings indicate that a WM processing deficit is evident in schizophrenia from an early stage before antipsychotic treatment, and associated with a dopamine pathway related aberration in nonlinear response pattern at the cingulate cortex when processing WM load.

Research on Pathogenic Hippocampal Voxel Detection in Alzheimer's Disease Using Clustering Genetic Random Forest.

Alzheimer's disease (AD) is an age-related neurological disease, which is closely associated with hippocampus, and subdividing the hippocampus into voxels can capture subtle signals that are easily missed by region of interest (ROI) methods. Therefore, studying interpretable associations between voxels can better understand the effect of voxel set on the hippocampus and AD. In this study, by analyzing the hippocampal voxel data, we propose a novel method based on clustering genetic random forest to identify the important voxels. Specifically, we divide the left and right hippocampus into voxels to constitute the initial feature set. Moreover, the random forest is constructed using the randomly selected samples and features. The genetic evolution is used to amplify the difference in decision trees and the clustering evolution is applied to generate offspring in genetic evolution. The important voxels are the features that reach the peak classification. The results demonstrate that our method has good classification and stability. Particularly, through biological analysis of the obtained voxel set, we find that they play an important role in AD by affecting the function of the hippocampus. These discoveries demonstrate the contribution of the voxel set to AD.

Research on Frequent Itemset Mining of Imaging Genetics GWAS in Alzheimer's Disease.

As an efficient method, genome-wide association study (GWAS) is used to identify the association between genetic variation and pathological phenotypes, and many significant genetic variations founded by GWAS are closely associated with human diseases. However, it is not enough to mine only a single marker effect variation on complex biological phenotypes. Mining highly correlated single nucleotide polymorphisms (SNP) is more meaningful for the study of Alzheimer's disease (AD). In this paper, we used two frequent pattern mining (FPM) framework, the FP-Growth and Eclat algorithms, to analyze the GWAS results of functional magnetic resonance imaging (fMRI) phenotypes. Moreover, we applied the definition of confidence to FP-Growth and Eclat to enhance the FPM framework. By calculating the conditional probability of identified SNPs, we obtained the corresponding association rules to provide support confidence between these important SNPs. The resulting SNPs showed close correlation with hippocampus, memory, and AD. The experimental results also demonstrate that our framework is effective in identifying SNPs and provide candidate SNPs for further research.

Hippocampal Subregion and Gene Detection in Alzheimer's Disease Based on Genetic Clustering Random Forest.

The distinguishable subregions that compose the hippocampus are differently involved in functions associated with Alzheimer's disease (AD). Thus, the identification of hippocampal subregions and genes that classify AD and healthy control (HC) groups with high accuracy is meaningful. In this study, by jointly analyzing the multimodal data, we propose a novel method to construct fusion features and a classification method based on the random forest for identifying the important features. Specifically, we construct the fusion features using the gene sequence and subregions correlation to reduce the diversity in same group. Moreover, samples and features are selected randomly to construct a random forest, and genetic algorithm and clustering evolutionary are used to amplify the difference in initial decision trees and evolve the trees. The features in resulting decision trees that reach the peak classification are the important "subregion gene pairs". The findings verify that our method outperforms well in classification performance and generalization. Particularly, we identified some significant subregions and genes, such as hippocampus amygdala transition area (HATA), fimbria, parasubiculum and genes included RYR3 and PRKCE. These discoveries provide some new candidate genes for AD and demonstrate the contribution of hippocampal subregions and genes to AD.

Multi-dimensional persistent feature analysis identifies connectivity patterns of resting-state brain networks in Alzheimer's disease.

Objective.The characterization of functional brain network is crucial to understanding the neural mechanisms associated with Alzheimer's disease (AD) and mild cognitive impairment (MCI). Some studies have shown that graph theoretical analysis could reveal changes of the disease-related brain networks by thresholding edge weights. But the choice of threshold depends on ambiguous cognitive conditions, which leads to the lack of interpretability. Recently, persistent homology (PH) was proposed to record the persistence of topological features of networks across every possible thresholds, reporting a higher sensitivity than graph theoretical features in detecting network-level biomarkers of AD. However, most research on PH focused on zero-dimensional features (persistence of connected components) reflecting the intrinsic topology of the brain network, rather than one-dimensional features (persistence of cycles) with an interesting neurobiological communication pattern. Our aim is to explore the multi-dimensional persistent features of brain networks in the AD and MCI patients, and further to capture valuable brain connectivity patterns.Approach.We characterized the change rate of the connected component numbers across graph filtration using the functional derivative curves, and examined the persistence landscapes that vectorize the persistence of cycle structures. After that, the multi-dimensional persistent features were validated in disease identification using a K-nearest neighbor algorithm. Furthermore, a connectivity pattern mining framework was designed to capture the disease-specific brain structures.Main results.We found that the multi-dimensional persistent features can identify statistical group differences, quantify subject-level distances, and yield disease-specific connectivity patterns. Relatively high classification accuracies were received when compared with graph theoretical features.Significance.This work represents a conceptual bridge linking complex brain network analysis and computational topology. Our results can be beneficial for providing a complementary objective opinion to the clinical diagnosis of neurodegenerative diseases.