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Tianzi Jiang

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IJCAI Conference 2024 Conference Paper

ATTA: Adaptive Test-Time Adaptation for Multi-Modal Sleep Stage Classification

  • Ziyu Jia
  • Xihao Yang
  • Chenyang Zhou
  • Haoyang Deng
  • Tianzi Jiang

Sleep stage classification is crucial for sleep quality assessment and disease diagnosis. Although some recent studies have made great strides in sleep stage classification performance, direct application to multi-modal sleep data with cross-domain distributional variations still poses challenges: 1) How to retain the sleep knowledge acquired by the model from the source domain during cross-domain adaptation to avoid catastrophic forgetting. 2) How to evaluate the contribution of different modalities in identifying specific sleep stages to serve test-time adaptation (TTA). 3) How to dynamically adapt the sleep model to different distribution shift in data domains of different subjects. To address these challenges, we propose an Adaptive Test-Time Adaptation (ATTA) method, a multi-modal test-time adaptation method for sleep stage classification. Specifically, the intra-modal retained-adaptive module is proposed for adapting to the target domain data while retaining the sleep knowledge acquired from the source domain to avoid catastrophic forgetting. The inter-modal contribution assessment module is designed to adaptively assess the contribution of each modality to the identification of specific sleep stages. Furthermore, the adaptive learning rate strategy utilizes a memory bank to record data from different subjects during testing, and based on this, it measures the differences between the target subject and those in the memory bank. According to the difference, the model adapts to the subject samples with different learning rates. We conduct experiments on mutual migration on two sleep datasets, SleepEDF and SHHS. The results show that our ATTA method outperforms state-of-the-art baselines in sleep stage classification.

IJCAI Conference 2024 Conference Paper

Multi-level Disentangling Network for Cross-Subject Emotion Recognition Based on Multimodal Physiological Signals

  • Ziyu Jia
  • Fengming Zhao
  • Yuzhe Guo
  • Hairong Chen
  • Tianzi Jiang

Emotion recognition based on multimodal physiological signals is attracting more and more attention. However, how to deal with the consistency and heterogeneity of multimodal physiological signals, as well as individual differences across subjects, pose two significant challenges. In this paper, we propose a Multi-level Disentangling Network named MDNet for cross-subject emotion recognition based on multimodal physiological signals. Specifically, MDNet consists of a modality-level disentangling module and a subject-level disentangling module. The modality-level disentangling module projects multimodal physiological signals into modality-invariant subspace and modality-specific subspace, capturing modality-invariant features and modality-specific features. The subject-level disentangling module separates subject-shared features and subject-private features among different subjects from multimodal data, which facilitates cross-subject emotion recognition. Experiments on two multimodal emotion datasets demonstrate that MDNet outperforms other state-of-the-art baselines.

YNIMG Journal 2024 Journal Article

Neuro-immune communication at the core of craving-associated brain structural network reconfiguration in methamphetamine users

  • Yanyao Du
  • Jiaqi Zhang
  • Dan Cao
  • Wenhan Yang
  • Jin Li
  • Deying Li
  • Ming Song
  • Zhengyi Yang

Methamphetamine (MA) use disorder is a chronic neurotoxic brain disease characterized by a high risk of relapse driven by intense cravings. However, the neurobiological signatures of cravings remain unclear, limiting the effectiveness of various treatment methods. Diffusion MRI (dMRI) scans from 62 MA users and 57 healthy controls (HC) were used in this study. The MA users were longitudinally followed up during their period of long-term abstinence (duration of long-term abstinence: 347. 52±99. 25 days). We systematically quantified the control ability of each brain region for craving-associated state transitions using network control theory from a causal perspective. Craving-associated structural alterations (CSA) were investigated through multivariate group comparisons and biological relevance analysis. The neural mechanisms underlying CSA were elucidated using transcriptomic and neurochemical analyses. We observed that long-term abstinence-induced structural alterations significantly influenced the state transition energy involved in the cognitive control response to external information, which correlated with changes in craving scores (r ∼ 0. 35, P <0. 01). Our causal network analysis further supported the crucial role of the prefrontal cortex (PFC) in craving mechanisms. Notably, while the PFC is central to the craving, the CSAs were distributed widely across multiple brain regions (PFDR <0. 05), with strong alterations in somatomotor regions (PFDR <0. 05) and moderate alterations in high-level association networks (PFDR <0. 05). Additionally, transcriptomic, chemical compounds, cell-type analyses, and molecular imaging collectively highlight the influence of neuro-immune communication on human craving modulation. Our results offer an integrative, multi-scale perspective on unraveling the neural underpinnings of craving and suggest that neuro-immune signaling may be a promising target for future human addiction therapeutics.

JBHI Journal 2023 Journal Article

MLDA: Multi-Loss Domain Adaptor for Cross-Session and Cross-Emotion EEG-Based Individual Identification

  • Yifan Miao
  • Wanqing Jiang
  • Nuo Su
  • Jun Shan
  • Tianzi Jiang
  • Nianming Zuo

Traditional individual identification methods, such as face and fingerprint recognition, carry the risk of personal information leakage. The uniqueness and privacy of electroencephalograms (EEG) and the popularization of EEG acquisition devices have intensified research on EEG-based individual identification in recent years. However, most existing work uses EEG signals from a single session or emotion, ignoring large differences between domains. As EEG signals do not satisfy the traditional deep learning assumption that training and test sets are independently and identically distributed, it is difficult for trained models to maintain good classification performance for new sessions or new emotions. In this article, an individual identification method, called Multi-Loss Domain Adaptor (MLDA), is proposed to deal with the differences between marginal and conditional distributions elicited by different domains. The proposed method consists of four parts: a) Feature extractor, which uses deep neural networks to extract deep features from EEG data; b) Label predictor, which uses full-layer networks to predict subject labels; c) Marginal distribution adaptation, which uses maximum mean discrepancy (MMD) to reduce marginal distribution differences; d) Associative domain adaptation, which adapts to conditional distribution differences. Using the MLDA method, the cross-session and cross-emotion EEG-based individual identification problem is addressed by reducing the influence of time and emotion. Experimental results confirmed that the method outperforms other state-of-the-art approaches.

YNIMG Journal 2022 Journal Article

The human mediodorsal thalamus: Organization, connectivity, and function

  • Kaixin Li
  • Lingzhong Fan
  • Yue Cui
  • Xuehu Wei
  • Yini He
  • Jiyue Yang
  • Yuheng Lu
  • Wen Li

The human mediodorsal thalamic nucleus (MD) is crucial for higher cognitive functions, while the fine anatomical organization of the MD and the function of each subregion remain elusive. In this study, using high-resolution data provided by the Human Connectome Project, an anatomical connectivity-based method was adopted to unveil the topographic organization of the MD. Four fine-grained subregions were identified in each hemisphere, including the medial (MDm), central (MDc), dorsal (MDd), and lateral (MDl), which recapitulated previous cytoarchitectonic boundaries from histological studies. The subsequent connectivity analysis of the subregions also demonstrated distinct anatomical and functional connectivity patterns, especially with the prefrontal cortex. To further evaluate the function of MD subregions, partial least squares analysis was performed to examine the relationship between different prefrontal-subregion connectivity and behavioral measures in 1012 subjects. The results showed subregion-specific involvement in a range of cognitive functions. Specifically, the MDm predominantly subserved emotional-cognition domains, while the MDl was involved in multiple cognitive functions especially cognitive flexibility and inhibition. The MDc and MDd were correlated with fluid intelligence, processing speed, and emotional cognition. In conclusion, our work provides new insights into the anatomical and functional organization of the MD and highlights the various roles of the prefrontal-thalamic circuitry in human cognition.

YNIMG Journal 2021 Journal Article

Imaging evolution of the primate brain: the next frontier?

  • Patrick Friedrich
  • Stephanie J. Forkel
  • Céline Amiez
  • Joshua H. Balsters
  • Olivier Coulon
  • Lingzhong Fan
  • Alexandros Goulas
  • Fadila Hadj-Bouziane

Evolution, as we currently understand it, strikes a delicate balance between animals' ancestral history and adaptations to their current niche. Similarities between species are generally considered inherited from a common ancestor whereas observed differences are considered as more recent evolution. Hence comparing species can provide insights into the evolutionary history. Comparative neuroimaging has recently emerged as a novel subdiscipline, which uses magnetic resonance imaging (MRI) to identify similarities and differences in brain structure and function across species. Whereas invasive histological and molecular techniques are superior in spatial resolution, they are laborious, post-mortem, and oftentimes limited to specific species. Neuroimaging, by comparison, has the advantages of being applicable across species and allows for fast, whole-brain, repeatable, and multi-modal measurements of the structure and function in living brains and post-mortem tissue. In this review, we summarise the current state of the art in comparative anatomy and function of the brain and gather together the main scientific questions to be explored in the future of the fascinating new field of brain evolution derived from comparative neuroimaging.

YNICL Journal 2021 Journal Article

Multisite schizophrenia classification by integrating structural magnetic resonance imaging data with polygenic risk score

  • Ke Hu
  • Meng Wang
  • Yong Liu
  • Hao Yan
  • Ming Song
  • Jun Chen
  • Yunchun Chen
  • Huaning Wang

Previous brain structural magnetic resonance imaging studies reported that patients with schizophrenia have brain structural abnormalities, which have been used to discriminate schizophrenia patients from normal controls. However, most existing studies identified schizophrenia patients at a single site, and the genetic features closely associated with highly heritable schizophrenia were not considered. In this study, we performed standardized feature extraction on brain structural magnetic resonance images and on genetic data to separate schizophrenia patients from normal controls. A total of 1010 participants, 508 schizophrenia patients and 502 normal controls, were recruited from 8 independent sites across China. Classification experiments were carried out using different machine learning methods and input features. We tested a support vector machine, logistic regression, and an ensemble learning strategy using 3 feature sets of interest: (1) imaging features: gray matter volume, (2) genetic features: polygenic risk scores, and (3) a fusion of imaging features and genetic features. The performance was assessed by leave-one-site-out cross-validation. Finally, some important brain and genetic features were identified. We found that the models with both imaging and genetic features as input performed better than models with either alone. The average accuracy of the classification models with the best performance in the cross-validation was 71.6%. The genetic feature that measured the cumulative risk of the genetic variants most associated with schizophrenia contributed the most to the classification. Our work took the first step toward considering both structural brain alterations and genome-wide genetic factors in a large-scale multisite schizophrenia classification. Our findings may provide insight into the underlying pathophysiology and risk mechanisms of schizophrenia.

YNIMG Journal 2020 Journal Article

Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

  • Joanes Grandjean
  • Carola Canella
  • Cynthia Anckaerts
  • Gülebru Ayrancı
  • Salma Bougacha
  • Thomas Bienert
  • David Buehlmann
  • Ludovico Coletta

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories worldwide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a mouse default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. RSN spatial specificity was enhanced in datasets acquired at higher field strength, with cryoprobes, in ventilated animals, and under medetomidine-isoflurane combination sedation. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

YNIMG Journal 2019 Journal Article

Corresponding anatomical and coactivation architecture of the human precuneus showing similar connectivity patterns with macaques

  • Jiaojian Wang
  • Benjamin Becker
  • Lijie Wang
  • Hai Li
  • Xudong Zhao
  • Tianzi Jiang

The precuneus (PCun) is one of the most expanded areas of the association cortex and plays an important role in integrating information from different modalities. However, whether the functional architecture of PCun is shared by humans and macaques is an open question. We used both anatomical connectivity and task-dependent coactivation patterns to parcellate the human PCun and consistently identified three subregions in the human PCun using two independent datasets. Two subregions were located in the dorsal PCun and one subregion was located in the ventral PCun. This parcellation scheme for the PCun was supported by identifying the subregion-specific networks and by functional characterization. Then, the absolute and relative gray matter volume of precuneus in human and macaque was calculated and significantly smaller absolute and relative gray matter volume in macaque was identified. Next, three macaque PCun subregions were defined based on our tractographic atlas. Finally, the whole brain anatomical connectivity patterns and connectivity fingerprints with 17 predefined homologous target brain areas were mapped for each PCun subregion and revealed that the PCun shares similar anatomical connectivity patterns in humans and macaques. The similar anatomical connectivity patterns of PCun were validated by an independent in-house dataset. Our findings demonstrated that anatomical connectivity patterns can reflect the functional architecture of the PCun in humans and that the functional architecture of the PCun is similar in humans and macaques.

YNIMG Journal 2018 Journal Article

Connectome-based individualized prediction of temperament trait scores

  • Rongtao Jiang
  • Vince D. Calhoun
  • Nianming Zuo
  • Dongdong Lin
  • Jin Li
  • Lingzhong Fan
  • Shile Qi
  • Hailun Sun

Temperament consists of multi-dimensional traits that affect various domains of human life. Evidence has shown functional connectome-based predictive models are powerful predictors of cognitive abilities. Putatively, individuals' innate temperament traits may be predictable by unique patterns of brain functional connectivity (FC) as well. However, quantitative prediction for multiple temperament traits at the individual level has not yet been studied. Therefore, we were motivated to realize the individualized prediction of four temperament traits (novelty seeking [NS], harm avoidance [HA], reward dependence [RD] and persistence [PS]) using whole-brain FC. Specifically, a multivariate prediction framework integrating feature selection and sparse regression was applied to resting-state fMRI data from 360 college students, resulting in 4 connectome-based predictive models that enabled prediction of temperament scores for unseen subjects in cross-validation. More importantly, predictive models for HA and NS could be successfully generalized to two relevant personality traits for unseen individuals, i. e. , neuroticism and extraversion, in an independent dataset. In four temperament trait predictions, brain connectivities that show top contributing power commonly concentrated on the hippocampus, prefrontal cortex, basal ganglia, amygdala, and cingulate gyrus. Finally, across independent datasets and multiple traits, we show person's temperament traits can be reliably predicted using functional connectivity strength within frontal-subcortical circuits, indicating that human social and behavioral performance can be characterized by specific brain connectivity profile.

YNICL Journal 2018 Journal Article

Influence of inter-stimulus interval of spinal cord stimulation in patients with disorders of consciousness: A preliminary functional near-infrared spectroscopy study

  • Yujin Zhang
  • Yi Yang
  • Juanning Si
  • Xiaoyu Xia
  • Jianghong He
  • Tianzi Jiang

Spinal cord stimulation (SCS) is a promising treatment for disorders of consciousness (DOC), but the underlying mechanism and most effective procedures remain uncertain. To optimize the protocol, previous studies evaluated the frequency-specific effects of SCS on neurophysiological activities. However, whether and how the inter-stimulus interval (ISI) parameter affects the SCS neuromodulation in DOC remains unknown. We enrolled nine DOC patients who had implanted SCS devices and conducted three different durations of ISIs. Using functional near-infrared spectroscopy (fNIRS), we monitored the blood volume fluctuations in the prefrontal and occipital cortices during the SCS. The results showed that short stimuli (30 s) induced significant cerebral blood volume changes, especially in the prefrontal cortex, an important area in the consciousness system. By comparing the mean value of the responses from the first and the last block in each session, a shorter ISI was found to improve the blood volume in the prefrontal cortex. This phenomenon was more significant for the subgroup of patients with a favorable prognosis. These preliminary results imply that the ISI may be an important factor for SCS. The research paradigm proposed here also provides insights for further quantitative evaluations of the therapeutic effects of neuromodulation.

YNICL Journal 2018 Journal Article

Subdivisions of the posteromedial cortex in disorders of consciousness

  • Yue Cui
  • Ming Song
  • Darren M. Lipnicki
  • Yi Yang
  • Chuyang Ye
  • Lingzhong Fan
  • Jing Sui
  • Tianzi Jiang

Evidence suggests that disruptions of the posteromedial cortex (PMC) and posteromedial corticothalamic connectivity contribute to disorders of consciousness (DOCs). While most previous studies treated the PMC as a whole, this structure is functionally heterogeneous. The present study investigated whether particular subdivisions of the PMC are specifically associated with DOCs. Participants were DOC patients, 21 vegetative state/unresponsive wakefulness syndrome (VS/UWS), 12 minimally conscious state (MCS), and 29 healthy controls. Individual PMC and thalamus were divided into distinct subdivisions by their fiber tractograpy to each other and default mode regions, and white matter integrity and brain activity between/within subdivisions were assessed. The thalamus was represented mainly in the dorsal and posterior portions of the PMC, and the white matter tracts connecting these subdivisions to the thalamus had less integrity in VS/UWS patients than in MCS patients and healthy controls. In addition, these tracts had less integrity in DOC patients who did not recover after 12 months than in patients who did. The structural substrates were validated by resting state fMRI finding impaired functional activity within these PMC subdivisions. This study is the first to show that tracts from dorsal and posterior subdivisions of the PMC to the thalamus contribute to DOCs.

YNIMG Journal 2018 Journal Article

The heterogeneity of the left dorsal premotor cortex evidenced by multimodal connectivity-based parcellation and functional characterization

  • Sarah Genon
  • Andrew Reid
  • Hai Li
  • Lingzhong Fan
  • Veronika I. Müller
  • Edna C. Cieslik
  • Felix Hoffstaedter
  • Robert Langner

Despite the common conception of the dorsal premotor cortex (PMd) as a single brain region, its diverse connectivity profiles and behavioral heterogeneity argue for a differentiated organization of the PMd. A previous study revealed that the right PMd is characterized by a rostro-caudal and a ventro-dorsal distinction dividing it into five subregions: rostral, central, caudal, ventral and dorsal. The present study assessed whether a similar organization is present in the left hemisphere, by capitalizing on a multimodal data-driven approach combining connectivity-based parcellation (CBP) based on meta-analytic modeling, resting-state functional connectivity, and probabilistic diffusion tractography. The resulting PMd modules were then characterized based on multimodal functional connectivity and a quantitative analysis of associated behavioral functions. Analyzing the clusters consistent across all modalities revealed an organization of the left PMd that mirrored its right counterpart to a large degree. Again, caudal, central and rostral modules reflected a cognitive-motor gradient and a premotor eye-field was found in the ventral part of the left PMd. In addition, a distinct module linked to abstract cognitive functions was observed in the rostro-ventral left PMd across all CBP modalities, implying greater differentiation of higher cognitive functions for the left than the right PMd.

YNIMG Journal 2017 Journal Article

Altered regional connectivity reflecting effects of different anaesthesia protocols in the mouse brain

  • Tong Wu
  • Joanes Grandjean
  • Simone C. Bosshard
  • Markus Rudin
  • David Reutens
  • Tianzi Jiang

Studies in mice using resting-state functional magnetic resonance imaging (rs-fMRI) have provided opportunities to investigate the effects of pharmacological manipulations on brain function and map the phenotypes of mouse models of human brain disorders. Mouse rs-fMRI is typically performed under anaesthesia, which induces both regional suppression of brain activity and disruption of large-scale neural networks. Previous comparative studies using rodents investigating various drug effects on long-distance functional connectivity (FC) have reported agent-specific FC patterns, however, effects of regional suppression are sparsely explored. Here we examined changes in regional connectivity under six different anaesthesia conditions using mouse rs-fMRI with the goal of refining the framework of understanding the brain activation under anaesthesia at a local level. Regional homogeneity (ReHo) was used to map local synchronization in the brain, followed by analysis of several brain areas based on ReHo maps. The results revealed high local coherence in most brain areas. The primary somatosensory cortex and caudate-putamen showed agent-specific properties. Lower local coherence in the cingulate cortex was observed under medetomidine, particularly when compared to the combination of medetomidine and isoflurane. The thalamus was associated with retained local coherence across anaesthetic levels and multiple nuclei. These results show that anaesthesia induced by the investigated anaesthetics through different molecular targets promote agent-specific regional connectivity. In addition, ReHo is a data-driven method with minimum user interaction, easy to use and fast to compute. Given that examination of the brain at a local level is widely applied in human rs-fMRI studies, our results show its sensitivity to extract information on varied neuronal activity under six different regimens relevant to mouse functional imaging. These results, therefore, will inform future rs-fMRI studies on mice and the type of anaesthetic agent used, and will help to bridge observations between this burgeoning research field and ongoing human research across analytical scales.

YNIMG Journal 2017 Journal Article

Cross-cultural consistency and diversity in intrinsic functional organization of Broca's Region

  • Yu Zhang
  • Lingzhong Fan
  • Svenja Caspers
  • Stefan Heim
  • Ming Song
  • Cirong Liu
  • Yin Mo
  • Simon B. Eickhoff

As a core language area, Broca's region was consistently activated in a variety of language studies even across different language systems. Moreover, a high degree of structural and functional heterogeneity in Broca's region has been reported in many studies. This raised the issue of how the intrinsic organization of Broca's region effects by different language experiences in light of its subdivisions. To address this question, we used multi-center resting-state fMRI data to explore the cross-cultural consistency and diversity of Broca's region in terms of its subdivisions, connectivity patterns and modularity organization in Chinese and German speakers. A consistent topological organization of the 13 subdivisions within the extended Broca's region was revealed on the basis of a new in-vivo parcellation map, which corresponded well to the previously reported receptorarchitectonic map. Based on this parcellation map, consistent functional connectivity patterns and modularity organization of these subdivisions were found. Some cultural difference in the functional connectivity patterns was also found, for instance stronger connectivity in Chinese subjects between area 6v2 and the motor hand area, as well as higher correlations between area 45p and middle frontal gyrus. Our study suggests that a generally invariant organization of Broca's region, together with certain regulations of different language experiences on functional connectivity, might exists to support language processing in human brain.

YNICL Journal 2017 Journal Article

Polygenic risk for five psychiatric disorders and cross-disorder and disorder-specific neural connectivity in two independent populations

  • Tianqi Wang
  • Xiaolong Zhang
  • Ang Li
  • Meifang Zhu
  • Shu Liu
  • Wen Qin
  • Jin Li
  • Chunshui Yu

Major psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), autism (AUT), bipolar disorder (BD), major depressive disorder (MDD), and schizophrenia (SZ), are highly heritable and polygenic. Evidence suggests that these five disorders have both shared and distinct genetic risks and neural connectivity abnormalities. To measure aggregate genetic risks, the polygenic risk score (PGRS) was computed. Two independent general populations (N = 360 and N = 323) were separately examined to investigate whether the cross-disorder PGRS and PGRS for a specific disorder were associated with individual variability in functional connectivity. Consistent altered functional connectivity was found with the bilateral insula: for the left supplementary motor area and the left superior temporal gyrus with the cross-disorder PGRS, for the left insula and right middle and superior temporal lobe associated with the PGRS for autism, for the bilateral midbrain, posterior cingulate, cuneus, and precuneus associated with the PGRS for BD, and for the left angular gyrus and the left dorsolateral prefrontal cortex associated with the PGRS for schizophrenia. No significant functional connectivity was found associated with the PGRS for ADHD and MDD. Our findings indicated that genetic effects on the cross-disorder and disorder-specific neural connectivity of common genetic risk loci are detectable in the general population. Our findings also indicated that polygenic risk contributes to the main neurobiological phenotypes of psychiatric disorders and that identifying cross-disorder and specific functional connectivity related to polygenic risks may elucidate the neural pathways for these disorders.

YNIMG Journal 2017 Journal Article

Predicting individualized clinical measures by a generalized prediction framework and multimodal fusion of MRI data

  • Xing Meng
  • Rongtao Jiang
  • Dongdong Lin
  • Juan Bustillo
  • Thomas Jones
  • Jiayu Chen
  • Qingbao Yu
  • Yuhui Du

Neuroimaging techniques have greatly enhanced the understanding of neurodiversity (human brain variation across individuals) in both health and disease. The ultimate goal of using brain imaging biomarkers is to perform individualized predictions. Here we proposed a generalized framework that can predict explicit values of the targeted measures by taking advantage of joint information from multiple modalities. This framework also enables whole brain voxel-wise searching by combining multivariate techniques such as ReliefF, clustering, correlation-based feature selection and multiple regression models, which is more flexible and can achieve better prediction performance than alternative atlas-based methods. For 50 healthy controls and 47 schizophrenia patients, three kinds of features derived from resting-state fMRI (fALFF), sMRI (gray matter) and DTI (fractional anisotropy) were extracted and fed into a regression model, achieving high prediction for both cognitive scores (MCCB composite r =0. 7033, MCCB social cognition r =0. 7084) and symptomatic scores (positive and negative syndrome scale [PANSS] positive r =0. 7785, PANSS negative r =0. 7804). Moreover, the brain areas likely responsible for cognitive deficits of schizophrenia, including middle temporal gyrus, dorsolateral prefrontal cortex, striatum, cuneus and cerebellum, were located with different weights, as well as regions predicting PANSS symptoms, including thalamus, striatum and inferior parietal lobule, pinpointing the potential neuromarkers. Finally, compared to a single modality, multimodal combination achieves higher prediction accuracy and enables individualized prediction on multiple clinical measures. There is more work to be done, but the current results highlight the potential utility of multimodal brain imaging biomarkers to eventually inform clinical decision-making.

YNIMG Journal 2016 Journal Article

Altered structural connectome in adolescent socially isolated mice

  • Cirong Liu
  • Yonghui Li
  • Timothy J. Edwards
  • Nyoman D. Kurniawan
  • Linda J. Richards
  • Tianzi Jiang

Social experience is essential for adolescent development and plasticity of social animals. Deprivation of the experience by social isolation impairs white matter microstructures in the prefrontal cortex. However, the effect of social isolation may involve highly distributed brain networks, and therefore cannot be fully explained by a change of a single region. Here, we compared the connectomes of adolescent socially-isolated mice and normal-housed controls via diffusion magnetic resonance imaging. The isolated mice displayed an abnormal connectome, characterized by an increase in degree and reductions in measures such as modularity, small-worldness, and betweenness. The increase in degree was most evident in the dorsolateral orbitofrontal cortex, entorhinal cortex, and perirhinal cortex. In a connection-wise comparison, we revealed that most of the abnormal edges were inter-modular and inter-hemispheric connections of the dorsolateral orbitofrontal cortex. Further tractography-based analyses and histological examinations revealed microstructural changes in the forceps minor and lateral-cortical tracts that were associated with the dorsolateral orbitofrontal cortex. These changes of connectomes were correlated with fear memory deficits and hyper-locomotion activities induced by social isolation. Considering the key role of the orbitofrontal cortex in social behaviors, adolescent social isolation may primarily disrupt the orbitofrontal cortex and its neural pathways thereby contributing to an abnormal structural connectome.

YNIMG Journal 2016 Journal Article

Identifying functional subdivisions in the human brain using meta-analytic activation modeling-based parcellation

  • Yong Yang
  • Lingzhong Fan
  • Congying Chu
  • Junjie Zhuo
  • Jiaojian Wang
  • Peter T. Fox
  • Simon B. Eickhoff
  • Tianzi Jiang

Parcellation of the human brain into fine-grained units by grouping voxels into distinct clusters has been an effective approach for delineating specific brain regions and their subregions. Published neuroimaging studies employing coordinate-based meta-analyses have shown that the activation foci and their corresponding behavioral categories may contain useful information about the anatomical–functional organization of brain regions. Inspired by these developments, we proposed a new parcellation scheme called meta-analytic activation modeling-based parcellation (MAMP) that uses meta-analytically obtained information. The raw meta data, including the experiments and the reported activation coordinates related to a brain region of interest, were acquired from the Brainmap database. Using this data, we first obtained the “modeled activation” pattern by modeling the voxel-wise activation probability given spatial uncertainty for each experiment that featured at least one focus within the region of interest. Then, we processed these “modeled activation” patterns across the experiments with a K-means clustering algorithm to group the voxels into different subregions. In order to verify the reliability of the method, we employed our method to parcellate the amygdala and the left Brodmann area 44 (BA44). The parcellation results were quite consistent with previous cytoarchitectonic and in vivo neuroimaging findings. Therefore, the MAMP proposed in the current study could be a useful complement to other methods for uncovering the functional organization of the human brain.

YNIMG Journal 2015 Journal Article

Co-activation Probability Estimation (CoPE): An approach for modeling functional co-activation architecture based on neuroimaging coordinates

  • Congying Chu
  • Lingzhong Fan
  • Claudia R. Eickhoff
  • Yong Liu
  • Yong Yang
  • Simon B. Eickhoff
  • Tianzi Jiang

Recent progress in functional neuroimaging has prompted studies of brain activation during various cognitive tasks. Coordinate-based meta-analysis has been utilized to discover the brain regions that are consistently activated across experiments. However, within-experiment co-activation relationships, which can reflect the underlying functional relationships between different brain regions, have not been widely studied. In particular, voxel-wise co-activation, which may be able to provide a detailed configuration of the co-activation network, still needs to be modeled. To estimate the voxel-wise co-activation pattern and deduce the co-activation network, a Co-activation Probability Estimation (CoPE) method was proposed to model within-experiment activations for the purpose of defining the co-activations. A permutation test was adopted as a significance test. Moreover, the co-activations were automatically separated into local and long-range ones, based on distance. The two types of co-activations describe distinct features: the first reflects convergent activations; the second represents co-activations between different brain regions. The validation of CoPE was based on five simulation tests and one real dataset derived from studies of working memory. Both the simulated and the real data demonstrated that CoPE was not only able to find local convergence but also significant long-range co-activation. In particular, CoPE was able to identify a ‘core’ co-activation network in the working memory dataset. As a data-driven method, the CoPE method can be used to mine underlying co-activation relationships across experiments in future studies.

YNIMG Journal 2015 Journal Article

The cortical surface area of the insula mediates the effect of DBH rs7040170 on novelty seeking

  • Jin Li
  • Yue Cui
  • Karen Wu
  • Bing Liu
  • Yun Zhang
  • Chao Wang
  • Tianzi Jiang

Novelty seeking (NS) is a personality trait important for adaptive functioning, but an excessive level of NS has been linked to psychiatric disorders such as ADHD and substance abuse. Previous research has investigated separately the neural and genetic bases of the NS trait, but results were mixed and neural and genetic bases have yet to be examined within the same study. In this study, we examined the interrelationships among the dopamine beta-hydroxylase (DBH) gene, brain structure, and the NS trait in 359 healthy Han Chinese subjects. We focused on the DBH gene because it encodes a key enzyme for dopamine metabolism, NS is believed to be related to the dopaminergic system and has been reported associated with DBH variation. Results showed a significant positive association between the cortical surface area of the left insula and NS score. Furthermore, the DBH genetic polymorphism at the SNP rs7040170 was strongly associated with both the surface area of the left insula and NS score, with G carriers having a larger left insula surface area and a higher NS score than AA homozygotes. Subsequent path analysis suggested that the insula partially mediated the association between the DBH gene and the NS trait. Our data provided the first evidence for the involvement of the insula in the dopamine–NS relationship. Future studies of molecular mechanisms underlying the NS personality trait and related psychiatric disorders should consider the mediation effect of the neural structure.

YNIMG Journal 2014 Journal Article

Non-Negative Spherical Deconvolution (NNSD) for estimation of fiber Orientation Distribution Function in single-/multi-shell diffusion MRI

  • Jian Cheng
  • Rachid Deriche
  • Tianzi Jiang
  • Dinggang Shen
  • Pew-Thian Yap

Spherical Deconvolution (SD) is commonly used for estimating fiber Orientation Distribution Functions (fODFs) from diffusion-weighted signals. Existing SD methods can be classified into two categories: 1) Continuous Representation based SD (CR-SD), where typically Spherical Harmonic (SH) representation is used for convenient analytical solutions, and 2) Discrete Representation based SD (DR-SD), where the signal profile is represented by a discrete set of basis functions uniformly oriented on the unit sphere. A feasible fODF should be non-negative and should integrate to unity throughout the unit sphere S 2. However, to our knowledge, most existing SH-based SD methods enforce non-negativity only on discretized points and not the whole continuum of S 2. Maximum Entropy SD (MESD) and Cartesian Tensor Fiber Orientation Distributions (CT-FOD) are the only SD methods that ensure non-negativity throughout the unit sphere. They are however computational intensive and are susceptible to errors caused by numerical spherical integration. Existing SD methods are also known to overestimate the number of fiber directions, especially in regions with low anisotropy. DR-SD introduces additional error in peak detection owing to the angular discretization of the unit sphere. This paper proposes a SD framework, called Non-Negative SD (NNSD), to overcome all the limitations above. NNSD is significantly less susceptible to the false-positive peaks, uses SH representation for efficient analytical spherical deconvolution, and allows accurate peak detection throughout the whole unit sphere. We further show that NNSD and most existing SD methods can be extended to work on multi-shell data by introducing a three-dimensional fiber response function. We evaluated NNSD in comparison with Constrained SD (CSD), a quadratic programming variant of CSD, MESD, and an L1-norm regularized non-negative least-squares DR-SD. Experiments on synthetic and real single-/multi-shell data indicate that NNSD improves estimation performance in terms of mean difference of angles, peak detection consistency, and anisotropy contrast between isotropic and anisotropic regions.

YNIMG Journal 2013 Journal Article

Brainnetome: A new -ome to understand the brain and its disorders

  • Tianzi Jiang

The human brain can be studied as a hierarchy of complex networks on different temporal and spatial scales. On each scale, from gene, protein, synapse, neuron and microcircuit, to area, pathway and the whole brain, many advances have been made with the development of related techniques. Brain network studies on different temporal and spatial scales are booming. However, such studies have focused on single levels, and can only reflect limited aspects of how the brain is formed and how it works. Therefore, it is increasingly urgent to integrate a variety of techniques, methods and models, and to merge fragmented findings into a uniform research framework or platform. To this end, we have proposed the concept of the brainnetome and several related programs/projects have been launched in China. In this paper, we offer a brief review on the methodologies of the brainnetome, which include techniques on different scales, the brainnetome atlas, and methods of brain network analysis. We then take Alzheimer's disease and schizophrenia as examples to show how the brainnetome can be studied in neurological and psychiatric disorders. We also review the studies of how risk genes for brain diseases affect the brain networks. Finally, we summarize the challenges for the brainnetome, and what actions and measures have been taken to address these challenges in China. It is envisioned that the brainnetome will open new avenues and some long-standing issues may be solved by combining the brainnetome with other “omes”.

YNIMG Journal 2013 Journal Article

Groupwise spatial normalization of fMRI data based on multi-range functional connectivity patterns

  • Di Jiang
  • Yuhui Du
  • Hewei Cheng
  • Tianzi Jiang
  • Yong Fan

Spatial alignment of functional magnetic resonance images (fMRI) of different subjects is a necessary precursor to improve functional consistency across subjects for group analysis in fMRI studies. Traditional structural MRI (sMRI) based registration methods cannot achieve accurate inter-subject functional consistency in that functional units are not necessarily located relative to anatomical structures consistently due to functional variability across subjects. Although spatial smoothing commonly used in fMRI data preprocessing can reduce the inter-subject functional variability, it may blur the functional signals and thus lose the fine-grained information. To overcome the limitations of exiting techniques, in this paper, we propose a novel method for spatial normalization of fMRI data by matching their multi-range functional connectivity patterns progressively. In particular, the image registration of different subjects is achieved by maximizing inter-subject similarity of their functional images' local functional connectivity patterns that characterize functional connectivity information for each voxel of the images to its spatial neighbors. The neighborhood size for computing the local functional connectivity patterns is gradually increased with the progression of image registration to capture the functional connectivity information in larger ranges. We also adopt the congealing groupwise image registration strategy to simultaneously warp a group of subjects to an unbiased template. Experimental comparisons between the proposed method and other fMRI image registration methods have demonstrated that the proposed method could achieve superior registration performance for resting state fMRI data. Experiment results based on real resting-state fMRI data have further demonstrated that the proposed fMRI registration method can achieve a statistically significant improvement in functional consistency across subjects.

YNIMG Journal 2013 Journal Article

KIBRA gene variants are associated with synchronization within the default-mode and executive control networks

  • Dawei Wang
  • Bing Liu
  • Wen Qin
  • Junping Wang
  • Yunting Zhang
  • Tianzi Jiang
  • Chunshui Yu

Genetic variation at the KIBRA rs17070145 polymorphism has been linked to episodic memory, executive function, and Alzheimer's disease (AD), which are related to the structural and functional integrity of the default-mode network (DMN) and executive control network (ECN). We hypothesize that the KIBRA polymorphism could modulate the structure and function of the DMN and ECN in healthy young subjects, which might underlie the association between this gene and cognitive function. To test our hypothesis, we analyzed the resting-state synchronization in the DMN and ECN in 288 young, healthy Chinese Han subjects. We found that carriers of the KIBRA C-allele demonstrated an increased synchronization in the posterior cingulate cortex (PCC) and medial prefrontal cortex (MPFC) of the DMN and in the right anterior insula, bilateral caudate nuclei, and bilateral dorsal anterior cingulate cortices (dACC) of the ECN compared to individuals with a TT genotype. Moreover, KIBRA C-allele carriers also showed a smaller gray matter volume (GMV) in the MPFC and bilateral dACCs than TT individuals. In contrast, there were no significant genotype differences in the synchronization of either the visual network or the sensorimotor network. These findings suggest that the polymorphism in the KIBRA gene affects GMV and the function of the DMN and ECN. This increased synchronization is likely a reflection of compensation for the regional gray matter deficits in these networks in young healthy subjects. The association between KIBRA polymorphisms and the DMN and ECN should be further explored in a healthy older population and in patients with AD.

YNIMG Journal 2013 Journal Article

Subregions of the human superior frontal gyrus and their connections

  • Wei Li
  • Wen Qin
  • Huaigui Liu
  • Lingzhong Fan
  • Jiaojian Wang
  • Tianzi Jiang
  • Chunshui Yu

The superior frontal gyrus (SFG) is located at the superior part of the prefrontal cortex and is involved in a variety of functions, suggesting the existence of functional subregions. However, parcellation schemes of the human SFG and the connection patterns of each subregion remain unclear. We firstly parcellated the human SFG into the anteromedial (SFGam), dorsolateral (SFGdl), and posterior (SFGp) subregions based on diffusion tensor tractography. The SFGam was anatomically connected with the anterior and mid-cingulate cortices, which are critical nodes of the cognitive control network and the default mode network (DMN). The SFGdl was connected with the middle and inferior frontal gyri, which are involved in the cognitive execution network. The SFGp was connected with the precentral gyrus, caudate, thalamus, and frontal operculum, which are nodes of the motor control network. Resting-state functional connectivity analysis further revealed that the SFGam was mainly correlated with the cognitive control network and the DMN; the SFGdl was correlated with the cognitive execution network and the DMN; and the SFGp was correlated with the sensorimotor-related brain regions. The SFGam and SFGdl were further parcellated into three and two subclusters that are well corresponding to Brodmann areas. These findings suggest that the human SFG consists of multiple dissociable subregions that have distinct connection patterns and that these subregions are involved in different functional networks and serve different functions. These results may improve our understanding on the functional complexity of the SFG and provide us an approach to investigate the SFG at the subregional level.

YNIMG Journal 2013 Journal Article

Variant in OXTR gene and functional connectivity of the hypothalamus in normal subjects

  • Junping Wang
  • Wen Qin
  • Bing Liu
  • Dawei Wang
  • Yunting Zhang
  • Tianzi Jiang
  • Chunshui Yu

The oxytocin receptor gene (OXTR) rs53576A has been associated with autism spectrum disorders (ASDs). A smaller hypothalamic volume has been reported in healthy male A-allele carriers than in male GG homozygotes and in patients with ASDs than in healthy controls. These findings prompt the hypothesis that male AA homozygotes may have weaker hypothalamic functional connectivity when compared to male G-allele carriers. We calculated local functional connectivity density (FCD) using a voxel-wise data-driven approach based on resting-state functional MRI data in 270 young healthy subjects. Both the main effect of genotype and the gender-by-genotype interaction were considered. Of the whole brain, only the local FCD of the hypothalamus exhibited the main effect of genotype. Post-hoc testing revealed significantly lower local FCD in male AA homozygotes compared to male G-allele carriers although there was only a trend of significance in the gender-by-genotype interaction. We further analyzed the resting-state functional connectivity (rsFC) of the hypothalamic region that demonstrating significant genotype differences in local FCD. We found a significant gender-by-genotype interaction in rsFC between the hypothalamic region and the left dorsolateral prefrontal cortex, but no significant main effect of genotype was found. Post-hoc testing revealed that this rsFC was significantly weaker in male AA homozygotes compared to male G-allele carriers. Our findings identify gender-dependent mechanisms of OXTR rs53576 gene variation impacting the functional connectivity of the hypothalamus in healthy individuals and suggest that these mechanisms are important for understanding ASDs.

YNIMG Journal 2012 Journal Article

Altered spontaneous activity in Alzheimer's disease and mild cognitive impairment revealed by Regional Homogeneity

  • Zengqiang Zhang
  • Yong Liu
  • Tianzi Jiang
  • Bo Zhou
  • Ningyu An
  • Haitao Dai
  • Pan Wang
  • Yixuan Niu

Alzheimer's disease (AD), the most prevalent cause of dementia in the elderly, is characterized by progressive cognitive and intellectual deficits. Most patients with mild cognitive impairment (MCI) are thought to be in a very early stage of AD. Resting-state functional magnetic resonance imaging reflects spontaneous brain activities and/or the endogenous/background neurophysiological process of the human brain. Regional Homogeneity (ReHo) can provide a fast method for mapping regional activity across the whole brain. Little has been previously published about where or how spontaneous activity differs between MCI and AD, although many previous fMRI studies have shown that the activity pattern is altered in MCI/AD. In the present study, we first used the ReHo method to explore differences in regional spontaneous activities throughout the whole brain between normal controls (NC) and people with MCI and with AD. A one-way ANOVA was performed to determine the regions in which the ReHo differs between the three groups, and then a post hoc analysis was performed to evaluate differences in the pattern among the three groups. Finally a correlation analysis was done between the ReHo index of these regions and clinical variables in order to evaluate the relationship between ReHo and cognitive measures in the AD and MCI groups. An exploratory classification analysis also demonstrated that ReHo measures were able to correctly separate subjects in 71. 4% of the cases. Altered brain spontaneous activations were found in the medial prefrontal cortex, the bilateral posterior cingulate gyrus/precuneus and the left inferior parietal lobule (IPL) in both MCI and AD. In MCI, the ReHo index in the left IPL was higher than that of the NC, which could indicate the presence of a compensatory mechanism in MCI. More obviously, the correlation analysis indicated that the lower the memory and other cognitive abilities, the lower the ReHo in patients with MCI and AD. Combining our findings with the results in earlier studies, we propose that the spontaneous activity pattern in the resting state could potentially be used as a clinical marker for MCI/AD.

YNIMG Journal 2012 Journal Article

Anatomical insights into disrupted small-world networks in schizophrenia

  • Qifeng Wang
  • Tung-Ping Su
  • Yuan Zhou
  • Kun-Hsien Chou
  • I-Yun Chen
  • Tianzi Jiang
  • Ching-Po Lin

Schizophrenia is characterized by lowered efficiency in distributed information processing, as indicated by research that identified a disrupted small-world functional network. However, whether the dysconnection manifested by the disrupted small-world functional network is reflected in underlying anatomical disruption in schizophrenia remains unresolved. This study examined the topological properties of human brain anatomical networks derived from diffusion tensor imaging in patients with schizophrenia and in healthy controls. We constructed the weighted brain anatomical network for each of 79 schizophrenia patients and for 96 age and gender matched healthy subjects using diffusion tensor tractography and calculated the topological properties of the networks using a graph theoretical method. The topological properties of the patients' anatomical networks were altered, in that global efficiency decreased but local efficiency remained unchanged. The deleterious effects of schizophrenia on network performance appear to be localized as reduced regional efficiency in hubs such as the frontal associative cortices, the paralimbic/limbic regions and a subcortical structure (the left putamen). Additionally, scores on the Positive and Negative Symptom Scale correlated negatively with efficient network properties in schizophrenia. These findings suggest that complex brain network analysis may potentially be used to detect an imaging biomarker for schizophrenia.

YNIMG Journal 2012 Journal Article

Resting-state functional connectivity of the vermal and hemispheric subregions of the cerebellum with both the cerebral cortical networks and subcortical structures

  • Li Sang
  • Wen Qin
  • Yong Liu
  • Wei Han
  • Yunting Zhang
  • Tianzi Jiang
  • Chunshui Yu

The human cerebellum is a heterogeneous structure, and the pattern of resting-state functional connectivity (rsFC) of each subregion has not yet been fully characterized. We aimed to systematically investigate rsFC pattern of each cerebellar subregion in 228 healthy young adults. Voxel-based analysis revealed that several subregions showed similar rsFC patterns, reflecting functional integration; however, different subregions displayed distinct rsFC patterns, representing functional segregation. The same vermal and hemispheric subregions showed either different patterns or different strengths of rsFCs with the cerebrum, and different subregions of lobules VII and VIII displayed different rsFC patterns. Region of interest (ROI)-based analyses also confirmed these findings. Specifically, strong rsFCs were found: between lobules I–VI and vermal VIIb–IX and the visual network; between hemispheric VI, VIIb, VIIIa and the auditory network; between lobules I–VI, VIII and the sensorimotor network; between lobule IX, vermal VIIIb and the default-mode network; between lobule Crus I, hemispheric Crus II and the fronto-parietal network; between hemispheric VIIb, VIII and the task-positive network; between hemispheric VI, VIIb, VIII and the salience network; between most cerebellar subregions and the thalamus; between lobules V, VIIb and the midbrain red nucleus; between hemispheric Crus I, Crus II, vermal VIIIb, IX and the caudate nucleus; between lobules V, VI, VIIb, VIIIa and the pallidum and putamen; and between lobules I–V, hemispheric VIII, IX and the hippocampus and amygdala. These results confirm the existence of both functional integration and segregation among cerebellar subregions and largely improve our understanding of the functional organization of the human cerebellum.

YNIMG Journal 2012 Journal Article

Tractography‐based parcellation of the human left inferior parietal lobule

  • Jiaojian Wang
  • Lingzhong Fan
  • Yu Zhang
  • Yong Liu
  • Di Jiang
  • Yuanchao Zhang
  • Chunshui Yu
  • Tianzi Jiang

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.

YNIMG Journal 2011 Journal Article

Discriminant analysis of functional connectivity patterns on Grassmann manifold

  • Yong Fan
  • Yong Liu
  • Hong Wu
  • Yihui Hao
  • Haihong Liu
  • Zhening Liu
  • Tianzi Jiang

The functional brain networks, extracted from fMRI images using independent component analysis, have been demonstrated informative for distinguishing brain states of cognitive function and brain disorders. Rather than analyzing each network encoded by a spatial independent component separately, we propose a novel algorithm for discriminant analysis of functional brain networks jointly at an individual level. The functional brain networks of each individual are used as bases for a linear subspace, referred to as a functional connectivity pattern, which facilitates a comprehensive characterization of fMRI data. The functional connectivity patterns of different individuals are analyzed on the Grassmann manifold by adopting a principal angle based Riemannian distance. In conjunction with a support vector machine classifier, a forward component selection technique is proposed to select independent components for constructing the most discriminative functional connectivity pattern. The discriminant analysis method has been applied to an fMRI based schizophrenia study with 31 schizophrenia patients and 31 healthy individuals. The experimental results demonstrate that the proposed method not only achieves a promising classification performance for distinguishing schizophrenia patients from healthy controls, but also identifies discriminative functional brain networks that are informative for schizophrenia diagnosis.

YNIMG Journal 2011 Journal Article

Functional segregation of the human cingulate cortex is confirmed by functional connectivity based neuroanatomical parcellation

  • Chunshui Yu
  • Yuan Zhou
  • Yong Liu
  • Tianzi Jiang
  • Haiwei Dong
  • Yunting Zhang
  • Martin Walter

The four-region model with 7 specified subregions represents a theoretical construct of functionally segregated divisions of the cingulate cortex based on integrated neurobiological assessments. Under this framework, we aimed to investigate the functional specialization of the human cingulate cortex by analyzing the resting-state functional connectivity (FC) of each subregion from a network perspective. In 20 healthy subjects we systematically investigated the FC patterns of the bilateral subgenual (sACC) and pregenual (pACC) anterior cingulate cortices, anterior (aMCC) and posterior (pMCC) midcingulate cortices, dorsal (dPCC) and ventral (vPCC) posterior cingulate cortices and retrosplenial cortices (RSC). We found that each cingulate subregion was specifically integrated in the predescribed functional networks and showed anti-correlated resting-state fluctuations. The sACC and pACC were involved in an affective network and anti-correlated with the sensorimotor and cognitive networks, while the pACC also correlated with the default-mode network and anti-correlated with the visual network. In the midcingulate cortex, however, the aMCC was correlated with the cognitive and sensorimotor networks and anti-correlated with the visual, affective and default-mode networks, whereas the pMCC only correlated with the sensorimotor network and anti-correlated with the cognitive and visual networks. The dPCC and vPCC involved in the default-mode network and anti-correlated with the sensorimotor, cognitive and visual networks, in contrast, the RSC was mainly correlated with the PCC and thalamus. Based on a strong hypothesis driven approach of anatomical partitions of the cingulate cortex, we could confirm their segregation in terms of functional neuroanatomy, as suggested earlier by task studies or exploratory multi-seed investigations.

YNIMG Journal 2010 Journal Article

Haplotypes of catechol-O-methyltransferase modulate intelligence-related brain white matter integrity

  • Bing Liu
  • Jun Li
  • Chunshui Yu
  • Yonghui Li
  • Yong Liu
  • Ming Song
  • Ming Fan
  • Kuncheng Li

Twin studies have indicated a common genetic origin for intelligence and for variations in brain morphology. Our previous diffusion tensor imaging studies found an association between intelligence and white matter integrity of specific brain regions or tracts. However, specific genetic determinants of the white matter integrity of these brain regions and tracts are still unclear. In this study, we assess whether and how catechol-O-methyltransferase (COMT) gene polymorphisms affect brain white matter integrity. We genotyped twelve single nucleotide polymorphisms (SNPs) within the COMT gene and performed haplotype analyses on data from 79 healthy subjects. Our subjects had the same three major COMT haplotypes (termed the HPS, APS and LPS haplotypes) as previous studies have reported as regulating significantly different levels of enzymatic activity and dopamine. We used the mean fractional anisotropy (FA) values from four regions and five tracts of interest to assess the effect of COMT polymorphisms, including the well-studied val158met SNP and the three main haplotypes that we had identified, on intelligence-related white matter integrity. We identified an association between the mean FA values of two regions in the bilateral prefrontal lobes and the COMT haplotypes, rather than between them and val158met. The haplotype-FA value associations modulated nonlinearly and fit an inverted U-model. Our findings suggest that COMT haplotypes can nonlinearly modulate the intelligence-related white matter integrity of the prefrontal lobes by more significantly influencing prefrontal dopamine variations than does val158met.

YNIMG Journal 2008 Journal Article

Brain spontaneous functional connectivity and intelligence

  • Ming Song
  • Yuan Zhou
  • Jun Li
  • Yong Liu
  • Lixia Tian
  • Chunshui Yu
  • Tianzi Jiang

Many functional imaging studies have been performed to explore the neural basis of intelligence by detecting brain activity changes induced by intelligence-related tasks, such as reasoning or working memory. However, little is known about whether the spontaneous brain activity at rest is relevant to the differences in intelligence. Here, 59 healthy adult subjects (Wechsler Adult Intelligence Scale score, 90–138) were studied with resting state fMRI. We took the bilateral dorsolateral prefrontal cortices (DLPFC) as the seed regions and investigated the correlations across subjects between individual intelligence scores and the strength of the functional connectivity (FC) between the seed regions and other brain regions. We found that the brain regions in which the strength of the FC significantly correlated with intelligence scores were distributed in the frontal, parietal, occipital and limbic lobes. Stepwise linear regression analysis also revealed that the FCs within the frontal lobe and between the frontal and posterior brain regions were both important predictive factors for the differences in intelligence. These findings support a network view of intelligence, as suggested in previous studies. More importantly, our findings suggest that brain activity may be relevant to the differences in intelligence even in the resting state and in the absence of an explicit cognitive demand. This could provide a new perspective for understanding the neural basis of intelligence.

YNIMG Journal 2008 Journal Article

White matter tract integrity and intelligence in patients with mental retardation and healthy adults

  • Chunshui Yu
  • Jun Li
  • Yong Liu
  • Wen Qin
  • Yonghui Li
  • Ni Shu
  • Tianzi Jiang
  • Kuncheng Li

It is well known that brain structures correlate with intelligence but the association between the integrity of brain white matter tracts and intelligence in patients with mental retardation (MR) and healthy adults remains unknown. The aims of this study are to investigate whether the integrity of corpus callosum (CC), cingulum, uncinate fasciculus (UF), optic radiation (OR) and corticospinal tract (CST) are damaged in patients with MR, and to determine the correlations between the integrity of these tracts and full scale intelligence quotient (FSIQ) in both patients and controls. Fifteen MR patients and 79 healthy controls underwent intelligence tests and diffusion tensor imaging examinations. According to the FSIQ, all healthy controls were divided into general intelligence (GI: FSIQ<120; n=42) and high intelligence (HI: FSIQ≥120; n=37) groups. Intelligence was assessed by Chinese Revised Wechsler Adult Intelligence Scale, and white matter tract integrity was assessed by fractional anisotropy (FA). MR patients showed significantly lower FA than healthy controls in the CC, UF, OR and CST. However, GI subjects only demonstrated lower FA than HI subjects in the right UF. Partial correlation analysis controlling for age and sex showed that FSIQ scores were significantly correlated with the FA of the bilateral UF, genu and truncus of CC, bilateral OR and left CST. While FSIQ scores were only significantly correlated with the FA of the right UF when further controlling for group. This study indicate that MR patients show extensive damage in the integrity of the brain white matter tracts, and the right UF is an important neural basis of human intelligence.

YNIMG Journal 2007 Journal Article

Plasticity of the corticospinal tract in early blindness revealed by quantitative analysis of fractional anisotropy based on diffusion tensor tractography

  • Chunshui Yu
  • Ni Shu
  • Jun Li
  • Wen Qin
  • Tianzi Jiang
  • Kuncheng Li

Early visual deprivation may induce plastic changes, not only in the visual system, but also in the remaining sensory systems, secondary to altered experience in these spared modalities. Most of previous studies were focused on the plasticity of cortical areas of sensory modalities, but little attention was paid to the plasticity of motor system and white matter fiber tracts. Our purpose is to investigate the plasticity of the corticospinal tract (CST) in early blindness by tract-based quantitative analysis of fractional anisotropy (FA). Diffusion tensor imaging was performed in 17 early blind and 17 gender- and age-matched sighted subjects. The entire CST of each subject was reconstructed and the average FA of the tract was analyzed. To validate the results derived from the entire CST, we further analyzed a segment of the CST between the lowest slice of the cerebral peduncle and the uppermost slice of the lateral ventricle, in which the fibers are coherently arranged and the anatomical correspondence of the CST across subjects is established. On comparison with matched sighted participants, the average FA of the CST was significantly increased in the early blind men, but not in the early blind women. In conclusion, the plasticity of the CST is present in the early blind men, which might be related to the changes of motor experience during critical developmental period of the CST. This study also supports the perspective that experience-dependent plasticity occurs not only in the cortical areas but also in the white matter fiber tracts.

YNIMG Journal 2007 Journal Article

Regional coherence changes in the early stages of Alzheimer’s disease: A combined structural and resting-state functional MRI study

  • Yong He
  • Liang Wang
  • Yufeng Zang
  • Lixia Tian
  • Xinqing Zhang
  • Kuncheng Li
  • Tianzi Jiang

Recent functional imaging studies have indicated that the pathophysiology of Alzheimer’s disease (AD) can be associated with the changes in spontaneous low-frequency (<0. 08 Hz) blood oxygenation level-dependent fluctuations (LFBF) measured during a resting state. The purpose of this study was to examine regional LFBF coherence patterns in early AD and the impact of regional brain atrophy on the functional results. Both structural MRI and resting-state functional MRI scans were collected from 14 AD subjects and 14 age-matched normal controls. We found significant regional coherence decreases in the posterior cingulate cortex/precuneus (PCC/PCu) in the AD patients when compared with the normal controls. Moreover, the decrease in the PCC/PCu coherence was correlated with the disease progression measured by the Mini-Mental State Exam scores. The changes in LFBF in the PCC/PCu may be related to the resting hypometabolism in this region commonly detected in previous positron emission tomography studies of early AD. When the regional PCC/PCu atrophy was controlled, these results still remained significant but with a decrease in the statistical power, suggesting that the LFBF results are at least partly explained by the regional atrophy. In addition, we also found increased LFBF coherence in the bilateral cuneus, right lingual gyrus and left fusiform gyrus in the AD patients. These regions are consistent with previous findings of AD-related increased activation during cognitive tasks explained in terms of a compensatory-recruitment hypothesis. Finally, our study indicated that regional brain atrophy could be an important consideration in functional imaging studies of neurodegenerative diseases.

YNIMG Journal 2007 Journal Article

The relationship within and between the extrinsic and intrinsic systems indicated by resting state correlational patterns of sensory cortices

  • Lixia Tian
  • Tianzi Jiang
  • Yong Liu
  • Chunshui Yu
  • Kun Wang
  • Yuan Zhou
  • Ming Song
  • Kuncheng Li

Much Research has been done on extrinsic and intrinsic systems, which consist of brain regions associated with the processing of externally and internally oriented stimuli, respectively. However, understanding of the underlying relationships within and between these two systems is relatively limited. To improve our understanding of these underlying relationships, we investigated the positive and negative correlations of three regions of interest (ROIs) located in the auditory, visual and somatosensory systems by using resting state functional MRI (fMRI) with a large sample size. We found that all three sensory systems exhibited significant negative correlation with the intrinsic system. In contrast, positive correlations between these sensory cortices and brain regions outside their respective system were limited. The present study extended former findings by indicating that multiple subsystems rather than a single subsystem of the extrinsic system are inherently negatively correlated with the intrinsic system. We suggest that these negative correlations between the extrinsic and intrinsic systems may explain the phenomenon that externally and internally oriented processes can always disturb or even interrupt each other.

YNIMG Journal 2006 Journal Article

Changes in hippocampal connectivity in the early stages of Alzheimer's disease: Evidence from resting state fMRI

  • Liang Wang
  • Yufeng Zang
  • Yong He
  • Meng Liang
  • Xinqing Zhang
  • Lixia Tian
  • Tao Wu
  • Tianzi Jiang

A selective distribution of Alzheimer's disease (AD) pathological lesions in specific cortical layers isolates the hippocampus from the rest of the brain. However, functional connectivity between the hippocampus and other brain regions remains unclear in AD. Here, we employ a resting state functional MRI (fMRI) to examine changes in hippocampal connectivity comparing 13 patients with mild AD versus 13 healthy age-matched controls. Hippocampal connectivity was investigated by examination of the correlation between low frequency fMRI signal fluctuations in the hippocampus and those in all other brain regions. We found that functional connectivity between the right hippocampus and a set of regions was disrupted in AD; these regions are: medial prefrontal cortex (MPFC), ventral anterior cingulate cortex (vACC), right inferotemporal cortex, right cuneus extending into precuneus, left cuneus, right superior and middle temporal gyrus and posterior cingulate cortex (PCC). We also found increased functional connectivity between the left hippocampus and the right lateral prefrontal cortex in AD. In addition, rightward asymmetry of hippocampal connectivity observed in elderly controls was diminished in AD patients. The disrupted hippocampal connectivity to the MPFC, vACC and PCC provides further support for decreased activity in “default mode network” previously shown in AD. The decreased connectivity between the hippocampus and the visual cortices might indicate reduced integrity of hippocampus-related cortical networks in AD. Moreover, these findings suggest that resting-state fMRI might be an appropriate approach for studying pathophysiological changes in early AD.

YNIMG Journal 2006 Journal Article

Discriminative analysis of relapsing neuromyelitis optica and relapsing–remitting multiple sclerosis based on two-dimensional histogram from diffusion tensor imaging

  • Fuchun Lin
  • Chunshui Yu
  • Tianzi Jiang
  • Kuncheng Li
  • Chaozhe Zhu
  • Wanlin Zhu
  • Wen Qin
  • Yunyun Duan

It is difficult to completely differentiate patients with relapsing neuromyelitis optica (RNMO) from relapsing–remitting multiple sclerosis (RRMS) for their similarities in clinical manifestation. In this study, we proposed a novel approach, using two-dimensional histogram of apparent diffusion coefficient (ADC) and fractional anisotropy (FA) of the brain derived from diffusion tensor imaging (DTI) as classification feature, to discriminate patients with RNMO from RRMS. In this approach, two-dimensional principal component analysis (2D-PCA) was used to extract feature and reduce dimensionality of matrix-formed data efficiently. Then linear discriminant analysis (LDA) was performed on these extracted features to find the best projection direction to separate patients with RNMO from RRMS. Finally, a minimum distance classifier was generated on the basis of projection scores. The correct recognition rate of our method reached 85. 7%, validated by the leave-one-out method. This result was much higher than that using feature of ADC or FA separately (59. 5% for ADC, 76. 2% for FA). In conclusion, the proposed method on the basis of combined features is more effective for classification than those merely using the features separately, and it may be helpful in differentiating RNMO from RRMS patients.

YNIMG Journal 2006 Journal Article

Quantitative analysis along the pyramidal tract by length-normalized parameterization based on diffusion tensor tractography: Application to patients with relapsing neuromyelitis optica

  • Fuchun Lin
  • Chunshui Yu
  • Tianzi Jiang
  • Kuncheng Li
  • Xiaobo Li
  • Wen Qin
  • Hong Sun
  • Piu Chan

In this study, we introduced a length-normalized parameterization method to establish anatomical correspondence of white matter fiber tracts across subjects and applied this method to investigate the presence of abnormal diffusion along the pyramidal tract (PYT) of relapsing neuromyelitis optica (RNMO) patients without visible brain lesions. In this approach, the part of the PYT between the lowest slice of the cerebral peduncle and the uppermost slice of the lateral ventricle was reconstructed to establish the anatomical correspondence across subjects using diffusion tensor tractography. Then it was parameterized by normalizing its length and dividing equally the normalized length into a certain number of segments, so that the comparability of each segment across subjects along the PYT was established. Tract-specific diffusion indices, including directionally averaged diffusivity (D av), fractional anisotropy (FA), primary diffusivity (λ 1) and transverse diffusivity (λ 23), were obtained from each segment. Thus, the distribution maps of these indices along the PYT were obtained. The distribution maps of D av, FA, and λ 23 of RNMO patients were significantly different from those of healthy controls, especially in the lower part of the PYT. The differences may be caused by secondary degeneration to lesions in the spinal cord. In conclusion, a length-normalized parameterization method is proposed to establish anatomical correspondence for the PYT. Compared with existed methods, a major merit of our method is to provide comparability across subjects along the PYT on the basis of diffusion tensor tractography and to make it possible for the quantitative analysis along the fiber tract. This method can also be used to quantitatively analyze other white matter fiber tracts between two definite anatomic landmarks in many neurological or psychiatric diseases.

YNIMG Journal 2004 Journal Article

Regional homogeneity approach to fMRI data analysis

  • Yufeng Zang
  • Tianzi Jiang
  • Yingli Lu
  • Yong He
  • Lixia Tian

Kendall's coefficient concordance (KCC) can measure the similarity of a number of time series. It has been used for purifying a given cluster in functional MRI (fMRI). In the present study, a new method was developed based on the regional homogeneity (ReHo), in which KCC was used to measure the similarity of the time series of a given voxel to those of its nearest neighbors in a voxel-wise way. Six healthy subjects performed left and right finger movement tasks in event-related design; five of them were additionally scanned in a rest condition. KCC was compared among the three conditions (left finger movement, right finger movement, and the rest). Results show that bilateral primary motor cortex (M1) had higher KCC in either left or right finger movement condition than in rest condition. Contrary to prediction and to activation pattern, KCC of ipsilateral M1 is significantly higher than contralateral M1 in unilateral finger movement conditions. These results support the previous electrophysiologic findings of increasing ipsilateral M1 excitation during unilateral movement. ReHo can consider as a complementary method to model-driven method, and it could help reveal the complexity of the human brain function. More work is needed to understand the neural mechanism underlying ReHo.

YNIMG Journal 2003 Journal Article

Multicontext fuzzy clustering for separation of brain tissues in magnetic resonance images

  • Chaozhe Zhu
  • Tianzi Jiang

A local image model is proposed to eliminate the adverse impact of both artificial and inherent intensity inhomogeneities in magnetic resonance imaging on intensity-based image segmentation methods. The estimation and correction procedures for intensity inhomogeneities are no longer indispensable because the highly convoluted spatial distribution of different tissues in the brain is taken into consideration. On the basis of the local image model, multicontext fuzzy clustering (MCFC) is proposed for classifying 2D and 3D MR data into tissues of white matter, gray matter, and cerebral spinal fluid automatically. In MCFC, multiple clustering contexts are generated for each pixel, and fuzzy clustering is independently performed in each context to calculate the degree of membership of a pixel to each tissue class. To maintain the statistical reliability and spatial continuity of membership distributions, a fusion strategy is adopted to integrate the clustering outcomes from different contexts. The fusion result is taken as the final membership value of the pixel. Experimental results on both real MR images and simulated volumetric MR data show that MCFC outperforms the classic fuzzy c-means (FCM) as well as other segmentation methods that deal with intensity inhomogeneities.

YNIMG Journal 2003 Journal Article

Region growing method for the analysis of functional MRI data

  • Yingli Lu
  • Tianzi Jiang
  • Yufeng Zang

Existing analytical techniques for functional magnetic resonance imaging (fMRI) data always need some specific assumptions on the time series. In this article, we present a new approach for fMRI activation detection, which can be implemented without any assumptions on the time series. Our method is based on a region growing method, which is very popular for image segmentation. A comparison of performance on fMRI activation detection is made between the proposed method and the deconvolution method and the fuzzy clustering method with receiver operating characteristic (ROC) methodology. In addition, we examine the effectiveness and usefulness of our method on real experimental data. Experimental results show that our method outperforms over the deconvolution method and the fuzzy clustering method on a number of aspects. These results suggest that our region growing method can serve as a reliable analysis of fMRI data.

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