Yong HE

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Abstract: The thalamus and visual cortex are two key components associated with the alpha power of electroencephalography. However, their functional relationship remains to be elucidated. Here, we employ resting-state functional MRI to investigate the temporal correlations of spontaneous fluctuations between the thalamus [the whole thalamus and its three largest nuclei (bilateral mediodorsal, ventrolateral and pulvinar nuclei)] and visual cortex under both eyes open and eyes closed conditions. The whole thalamus show negative correlations with the visual cortex and positive correlations with its contralateral counterpart in eyes closed condition, but which are significantly decreased in eyes open condition, consistent with previous findings of electroencephalography desynchronization during eyes open resting state. Furthermore, we find that bilateral thalamic mediodorsal nuclei and bilateral ventrolateral nuclei have remarkably similar connectivity maps, and resemble to those of the whole thalamus, suggesting their crucial contributions to the thalamus-visual correlations. The bilateral pulvinar nuclei are found to show distinct functional connectivity patterns, compatible with previous findings of the asymmetry of anatomical and functional organization in the nuclei. Our data provides evidence for the associations of intrinsic spontaneous neuronal activity between the thalamus and visual cortex under different resting conditions, which might have implications on the understanding of the generation and modulation of the alpha rhythm. Hum Brain Mapp 2009. (c) 2009 Wiley-Liss, Inc.

Abstract: The current study combined structural magnetic resonance imaging (sMRI) and diffusion tensor MRI (DT-MRI) to investigate both gray matter density (GMD) and white matter integrity (WMI) in 18 pianists and 21 age-matched non-musicians. The pianists began their piano training at a mean age of 12. Voxel-based morphometry of the sMRI data showed that the pianists had higher GMD in the left primary sensorimotor cortex and right cerebellum. Voxel-based analysis of the DT-MRI data showed that pianists had higher fractional anisotropy (FA) (indicating higher WMI) in the right posterior limb of the internal capsule. The sMRI and DT-MRI results indicate that both the GMD and WMI of pianists may exhibit movement-related increases during adolescence or even early adulthood compared with non-musicians.

Abstract: Recent studies have demonstrated small-world properties in both functional and structural brain networks that are constructed based on different parcellation approaches. However, one fundamental but vital issue of the impact of different brain parcellation schemes on the network topological architecture remains unclear. Here, we used resting-state functional MRI (fMRI) to investigate the influences of different brain parcellation atlases on the topological organization of brain functional networks. Whole-brain fMRI data were divided into ninety and seventy regions of interest according to two predefined anatomical atlases, respectively. Brain functional networks were constructed by thresholding the correlation matrices among the parcellated regions and further analyzed using graph theoretical approaches. Both atlas-based brain functional networks were found to show robust small-world properties and truncated power-law connectivity degree distributions, which are consistent with previous brain functional and structural networks studies. However, more importantly, we found that there were significant differences in multiple topological parameters (e.g., small-worldness and degree distribution) between the two groups of brain functional networks derived from the two atlases. This study provides quantitative evidence on how the topological organization of brain networks is affected by the different parcellation strategies applied. Hum Brain Mapp 2008. (c) 2008 Wiley-Liss, Inc.

Abstract: The characterization of the topological architecture of complex networks underlying the structural and functional organization of the brain is a basic challenge in neuroscience. However, direct evidence for anatomical connectivity networks in the human brain remains scarce. Here, we utilized diffusion tensor imaging deterministic tractography to construct a macroscale anatomical network capturing the underlying common connectivity pattern of human cerebral cortex in a large sample of subjects (80 young adults) and further quantitatively analyzed its topological properties with graph theoretical approaches. The cerebral cortex was divided into 78 cortical regions, each representing a network node, and 2 cortical regions were considered connected if the probability of fiber connections exceeded a statistical criterion. The topological parameters of the established cortical network (binarized) resemble that of a "small-world" architecture characterized by an exponentially truncated power-law distribution. These characteristics imply high resilience to localized damage. Furthermore, this cortical network was characterized by major hub regions in association cortices that were connected by bridge connections following long-range white matter pathways. Our results are compatible with previous structural and functional brain networks studies and provide insight into the organizational principles of human brain anatomical networks that underlie functional states.

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Abstract: In this study, we investigated the changes in topological architectures of brain functional networks in attention-deficit/hyperactivity disorder (ADHD). Functional magnetic resonance images (fMRI) were obtained from 19 children with ADHD and 20 healthy controls during resting state. Brain functional networks were constructed by thresholding the correlation matrix between 90 cortical and subcortical regions and further analyzed by applying graph theoretical approaches. Experimental results showed that, although brain networks of both groups exhibited economical small-world topology, altered functional networks were demonstrated in the brain of ADHD when compared with the normal controls. In particular, increased local efficiencies combined with a decreasing tendency in global efficiencies found in ADHD suggested a disorder-related shift of the topology toward regular networks. Additionally, significant alterations in nodal efficiency were also found in ADHD, involving prefrontal, temporal, and occipital cortex regions, which were compatible with previous ADHD studies. The present study provided the first evidence for brain dysfunction in ADHD from the viewpoint of global organization of brain functional networks by using resting-state fMRI.

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Abstract: Resting-state functional MRI (fMRI) could be an advantageous choice for clinical applications by virtue of its clinical convenience and non-invasiveness. Without explicit stimulus, resting-state brain activity patterns cannot be obtained using any model-driven method. In this study, we advanced a measure named resting-state activity index (RSAI) to evaluate the resting-state brain activities. Using RSAI, we first investigated the resting-state brain activity patterns in normal adolescents to test the validity of this RSAI measure. Then we compared the resting-state brain activity patterns of Attention deficit hyperactivity disorder (ADHD) patients to those of their matched controls. According to the resultant brain activity patterns, we suggest that RSAI could be an applicable measure to evaluate resting-state brain activities. As compared to the controls, the ADHD patients exhibited more significant resting-state activities in basic sensory and sensory-related cortices. This finding was in accordance with ADHD symptoms of inattention.

Abstract: In this study, a resting-state fMRI based classifier, for the first time, was proposed and applied to discriminate children with attention-deficit/hyperactivity disorder (ADHD) from normal controls. On the basis of regional homogeneity (ReHo), a mapping of brain function at resting state, PCA-based Fisher discriminative analysis (PC-FDA) was trained to build a linear classifier. Permutation test was then conducted to identify the brain areas with the most significant contribution to the final discrimination. Experimental results showed a correct classification rate of 85% using a leave-one-out cross-validation. Moreover, some highly discriminative brain regions, like the prefrontal cortex and anterior cingulate cortex, well confirmed the previous findings on ADHD. Interestingly, some important but less reported regions such as the thalamus were also identified. We conclude that the classifier, using resting-state brain function as classification feature, has potential ability to improve current diagnosis and treatment evaluation of ADHD.

Abstract: We investigated the effect of transient dopamine depletion on functional connectivity during performance of the Wisconsin Card Sorting Task. Functional magnetic resonance imaging data were analyzed as a psychophysiological interaction, a statistical method used to identify functional connectivity during experimental manipulations. Nineteen healthy subjects were scanned, double blind, on 2 separate days: once after drinking an amino acid mixture deficient in the dopamine precursors tyrosine and phenylalanine, and once after drinking a nutritionally balanced mixture. In the balanced drink session, statistically significant connectivity between the frontal lobes and striatum was observed during set shifting, and the greater the prefrontostriatal connectivity, the faster the response time after a shift. Neither of these associations were observed after dopamine depletion. Moreover, dopamine depletion also reduced the degree of deactivation in areas normally suppressed during attention-demanding tasks, including the medial prefrontal cortex, posterior cingulate cortex, and hippocampus. Together, these results suggest that functional connectivity between the frontal lobes and basal ganglia during set shifting contributes to more efficient performance and that dopamine modulates this corticostriatal connectivity.

Abstract: Modularity, presumably shaped by evolutionary constraints, underlies the functionality of most complex networks ranged from social to biological networks. However, it remains largely unknown in human cortical networks. In a previous study, we demonstrated a network of correlations of cortical thickness among specific cortical areas and speculated that these correlations reflected an underlying structural connectivity among those brain regions. Here, we further investigated the intrinsic modular architecture of the human brain network derived from cortical thickness measurement. Modules were defined as groups of cortical regions that are connected morphologically to achieve the maximum network modularity. We show that the human cortical network is organized into 6 topological modules that closely overlap known functional domains such as auditory/language, strategic/executive, sensorimotor, visual, and mnemonic processing. The identified structure-based modular architecture may provide new insights into the functionality of cortical regions and connections between structural brain modules. This study provides the first report of modular architecture of the structural network in the human brain using cortical thickness measurements.

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Abstract: The human brain has been described as a large, sparse, complex network characterized by efficient small-world properties, which assure that the brain generates and integrates information with high efficiency. Many previous neuroimaging studies have provided consistent evidence of 'dysfunctional connectivity' among the brain regions in schizophrenia; however, little is known about whether or not this dysfunctional connectivity causes disruption of the topological properties of brain functional networks. To this end, we investigated the topological properties of human brain functional networks derived from resting-state functional magnetic resonance imaging (fMRI). Data was obtained from 31 schizophrenia patients and 31 healthy subjects; then functional connectivity between 90 cortical and sub-cortical regions was estimated by partial correlation analysis and thresholded to construct a set of undirected graphs. Our findings demonstrated that the brain functional networks had efficient small-world properties in the healthy subjects; whereas these properties were disrupted in the patients with schizophrenia. Brain functional networks have efficient small-world properties which support efficient parallel information transfer at a relatively low cost. More importantly, in patients with schizophrenia the small-world topological properties are significantly altered in many brain regions in the prefrontal, parietal and temporal lobes. These findings are consistent with a hypothesis of dysfunctional integration of the brain in this illness. Specifically, we found that these altered topological measurements correlate with illness duration in schizophrenia. Detection and estimation of these alterations could prove helpful for understanding the pathophysiological mechanism as well as for evaluation of the severity of schizophrenia.

Abstract: Resting-state functional magnetic resonance imaging (fMRI), a promising technique for measuring brain activities during rest, has attracted much attention in the past few years. In this paper, we review recent progress on the study of Alzheimer's disease (AD) based on resting-state fMRI. First, we briefly introduce some AD-related studies from other groups. Then we describe our AD-related work in detail from three aspects: (1) alterations in regional homogeneity (ReHo) of the fMRI signal in the resting state, (2) altered patterns of functional connectivity from regions of interest and whole brain analyses, and (3) discriminative analyses based on classification features from resting-state fMRI data for differentiating AD patients from healthy elders. Finally, we summarize the main results and some prospects for future work.

Abstract: Resting-state functional MRI and structural MRI were used to study correlations of spontaneous activity and gray matter density between the left and right primary sensorimotor areas in pianists and nonmusicians. Functional MRI analysis showed significant correlation of spontaneous activity between the left and right primary sensorimotor area in both groups; however, there was no between-group difference. Structural MRI analysis showed significant correlation in gray matter density between the left and right sensorimotor areas in nonmusicians (r=0.65, P=0.001), but not in pianists (r=0.07, P=0.78), with a significant between-group difference (P=0.035). The lack of correlation of gray matter density between the left and right sensorimotor areas might be the basis of bimanual coordination of the pianists.

Abstract: Recent research on Alzheimer's disease (AD) has shown that cognitive and memory decline in this disease is accompanied by disrupted changes in the coordination of large-scale brain functional networks. However, alterations in coordinated patterns of structural brain networks in AD are still poorly understood. Here, we used cortical thickness measurement from magnetic resonance imaging to investigate large-scale structural brain networks in 92 AD patients and 97 normal controls. Brain networks were constructed by thresholding cortical thickness correlation matrices of 54 regions and analyzed using graph theoretical approaches. Compared with controls, AD patients showed decreased cortical thickness intercorrelations between the bilateral parietal regions and increased intercorrelations in several selective regions involving the lateral temporal and parietal cortex as well as the cingulate and medial frontal cortex regions. Specially, AD patients showed abnormal small-world architecture in the structural cortical networks (increased clustering and shortest paths linking individual regions), implying a less optimal topological organization in AD. Moreover, AD patients were associated with reduced nodal centrality predominantly in the temporal and parietal heteromodal association cortex regions and increased nodal centrality in the occipital cortex regions. Finally, the brain networks of AD were about equally as robust to random failures as those of controls, but more vulnerable against targeted attacks, presumably because of the effects of pathological topological organization. Our findings suggest that the coordinated patterns of cortical morphology are widely altered in AD patients, thus providing structural evidence for disrupted integrity in large-scale brain networks that underlie cognition. This work has implications for our understanding of how functional deficits in patients are associated with their underlying structural (morphological) basis.

Abstract: 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.

Abstract: An important issue in neuroscience is the characterization for the underlying architectures of complex brain networks. However, little is known about the network of anatomical connections in the human brain. Here, we investigated large-scale anatomical connection patterns of the human cerebral cortex using cortical thickness measurements from magnetic resonance images. Two areas were considered anatomically connected if they showed statistically significant correlations in cortical thickness and we constructed the network of such connections using 124 brains from the International Consortium for Brain Mapping database. Significant short- and long-range connections were found in both intra- and interhemispheric regions, many of which were consistent with known neuroanatomical pathways measured by human diffusion imaging. More importantly, we showed that the human brain anatomical network had robust small-world properties with cohesive neighborhoods and short mean distances between regions that were insensitive to the selection of correlation thresholds. Additionally, we also found that this network and the probability of finding a connection between 2 regions for a given anatomical distance had both exponentially truncated power-law distributions. Our results demonstrated the basic organizational principles for the anatomical network in the human brain compatible with previous functional networks studies, which provides important implications of how functional brain states originate from their structural underpinnings. To our knowledge, this study provides the first report of small-world properties and degree distribution of anatomical networks in the human brain using cortical thickness measurements.

Abstract: Compared with positive correlations, negative correlations of blood oxygen level-dependent (BOLD) signals (NCOBSs) have been much less studied. In most related studies, the NCOBSs have been accepted as stable without further consideration. To investigate the stabilities of NCOBSs associated with the auditory, motor, and visual cortices, we evaluated the negative correlation maps of each brain region under different "task-backgrounds" within the same subject-group, as well as within different subject-groups during a conscious resting state. These "task-backgrounds" refer to tasks not expected to activate the specific ROI under consideration and are in some sense analogous to "resting states." We found that the negative correlation maps of the motor and visual cortices were quite variable between either different task-backgrounds or different subject-groups, whereas those of the auditory cortex exhibited some similarities. These results indicate that the NCOBSs associated with the motor and visual cortices were unstable both under task-backgrounds and during the conscious resting state. The auditory cortex tended to have stable NCOBSs during these "resting states" (but scanner noise could make the auditory cortex "less resting"). This study highlights the importance of paying attention to the influence of the stabilities of NCOBSs in related studies and establishes the need for further studies on NCOBSs.

Abstract: In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, left sensorimotor cortex, and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.

Abstract: 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.

Abstract: Dorsal anterior cingulate cortex (dACC) has been found to function abnormally in attention deficit hyperactivity disorder (ADHD) patients in several former functional MRI (fMRI) studies. Resting-state low-frequency fluctuations (LFFs) of blood oxygen level-dependent (BOLD) fMRI signals have been proved to be quite informative. This study used resting-state LFFs to investigate the resting-state functional connectivity pattern differences of dACC in adolescents with and without ADHD. As compared to the controls, the ADHD patients exhibited more significant resting-state functional connectivities with the dACC in bilateral dACC, bilateral thalamus, bilateral cerebellum, bilateral insula and bilateral brainstem (pons). No brain region in the controls was found to exhibit more significant resting-state functional connectivity with the dACC. We suggest these abnormally more significant functional connectivities in the ADHD patients may indicate the abnormality of autonomic control functions in them.

Abstract: Functional neuroimaging studies of handedness have traditionally focused on exploring regionally activated discrepancies, yet little is known regarding the effect of handedness on functional connections of brain regions. Here, we reported the relationship between cerebellar functional connectivity patterns and handedness by low-frequency blood oxygenation level-dependent fluctuations. Compared with the right-handers, the left-handers show higher cerebellar-prefrontal, cerebellar-parietal, and cerebellar-temporal functional connectivity, and lower cerebellar-limbic connectivity. Previous non-human primate studies have shown that these regions with known contributions to higher cognitive functions have afferent or efferent connections with the cerebellum. Our findings suggest that these observed low-frequency fluctuation correlations may reflect actually anatomic connections between the cerebellum and cerebral cortex, and the cerebellar involvement in higher function may be associated with handedness.

Abstract: In order to explore the microstructure of bilateral cingulum bundles associated with side and handedness, fractional anisotropy was extracted from diffusion tensor imaging. Distinguished from the conventional region of interest-based method, a fiber-based analysis method called scale-invariant parameterization method was employed to ascertain the anisotropy along the cingulum bundle in 31 normal right-handers and 14 normal left-handers. The statistical results showed a remarkable left-greater-than-right asymmetry pattern of anisotropy in most segments of cingulum bundles except the most posterior segment, for both right-handers and left-handers. Interestingly, higher anisotropy of the right-hander than the left-hander was found in the bilateral cingulum bundles. No significant handedness-by-side interaction was obtained in the present study, however.

Abstract: 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.

Abstract: Quite a few studies in functional magnetic resonance imaging (fMRI) have tested that, even in a resting state, motor cortices constitute a network. It has never been investigated how the network modulates from the resting state to the motor task state. In this report, by a newly developed approach taking into account n-to-1 connectivity using 1-to-1 connectivity measures instead of conventional pairwise connectivity, we show the existence of a large organized functional connectivity network related to motor function in the resting brain with fMRI. More importantly, we found that such a network can be modulated from a conscious resting state to planning, initiation, coordination, guidance, and termination of voluntary movement state, exhibited by significant changes of functional connectivity of some brain regions in different brain activity. Moreover, a quantitative description of such a functional modulation has also been presented.