Publications by authors named "Zhengge Wang"

29 Publications

  • Page 1 of 1

Causal structural covariance network revealing atrophy progression in Alzheimer's disease continuum.

Hum Brain Mapp 2021 May 12. Epub 2021 May 12.

Department of Radiology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

The structural covariance network (SCN) has provided a perspective on the large-scale brain organization impairment in the Alzheimer's Disease (AD) continuum. However, the successive structural impairment across brain regions, which may underlie the disrupted SCN in the AD continuum, is not well understood. In the current study, we enrolled 446 subjects with AD, mild cognitive impairment (MCI) or normal aging (NA) from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The SCN as well as a casual SCN (CaSCN) based on Granger causality analysis were applied to the T1-weighted structural magnetic resonance images of the subjects. Compared with that of the NAs, the SCN was disrupted in the MCI and AD subjects, with the hippocampus and left middle temporal lobe being the most impaired nodes, which is in line with previous studies. In contrast, according to the 194 subjects with records on CSF amyloid and Tau, the CaSCN revealed that during AD progression, the CaSCN was enhanced. Specifically, the hippocampus, thalamus, and precuneus/posterior cingulate cortex (PCC) were identified as the core regions in which atrophy originated and could predict atrophy in other brain regions. Taken together, these findings provide a comprehensive view of brain atrophy in the AD continuum and the relationships among the brain atrophy in different regions, which may provide novel insight into the progression of AD.
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http://dx.doi.org/10.1002/hbm.25531DOI Listing
May 2021

Atrophy in the Left Amygdala Predicted Drug Responses in Idiopathic Generalized Epilepsy Patients With Tonic-Clonic Seizures.

Front Neurosci 2021 31;15:640016. Epub 2021 Mar 31.

Department of Radiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.

We aimed to determine the alterations in the subcortical structures of patients with idiopathic generalized epilepsy with tonic-clonic seizures (IGE-GTCS) MRI volumetry and vertex-based shape analysis and to evaluate the relationships between MRI measures and drug responses. In a follow-up sample of 48 patients with IGE-GTCS and 48 matched normal controls (NCs), high-resolution 3D TWI was performed at baseline. After 1 year of follow-up, 31 patients were classified as seizure free (SF) and 17 as drug resistant (DR). The volumes of subcortical structures were extracted, and vertex-based shape analysis was performed using FSL-Integrated Registration and Segmentation Toolbox (FSL-FIRST). Comparisons among groups were calculated adjusting for covariates [age, sex, and intracranial volume (ICV)]. Analysis of the relationships among imaging biomarkers along with frequency and duration was assessed using partial correlations. The differential imaging indicators were used as features in a linear support vector machine (LSVM). The DR group displayed significant regional atrophy in the volume of the left amygdala compared with NCs ( = 0.004, false discovery rate corrected) and SF patients ( = 0.029, uncorrected). Meanwhile, vertex-based shape analysis showed focal inward deformation in the basolateral subregion of the left amygdala in DR compared with the results for SF and NC ( < 0.05, FWE corrected). There were significant correlations between the volume changes and seizure frequency ( = -0.324, = 0.030) and between shape ( = -0.438, = 0.003) changes and seizure frequency. Moreover, the volume of the left thalamus in the DR group was significantly correlated with seizure frequency ( = -0.689, = 0.006). The SVM results revealed areas under the receiver operating characteristic curve of 0.82, 0.68, and 0.88 for the classification between SF and DR, between SF and NC, and between DR and NC, respectively. This study indicates the presence of focal atrophy in the basolateral region of the left amygdala in patients with IGE drug resistance; this finding may help predict drug responses and suggests a potential therapeutic target.
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http://dx.doi.org/10.3389/fnins.2021.640016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8044327PMC
March 2021

Functional connectome contractions in temporal lobe epilepsy: Microstructural underpinnings and predictors of surgical outcome.

Epilepsia 2020 06 26;61(6):1221-1233. Epub 2020 May 26.

Multimodal Imaging and Connectome Analysis Laboratory, McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Montreal, Quebec, Canada.

Objective: Temporal lobe epilepsy (TLE) is the most common drug-resistant epilepsy in adults. Although it is commonly related to hippocampal pathology, increasing evidence suggests structural changes beyond the mesiotemporal lobe. Functional anomalies and their link to underlying structural alterations, however, remain incompletely understood.

Methods: We studied 30 drug-resistant TLE patients and 57 healthy controls using multimodal magnetic resonance imaging (MRI) analyses. All patients had histologically verified hippocampal sclerosis and underwent postoperative imaging to outline the extent of their surgical resection. Our analysis leveraged a novel resting-state functional MRI framework that parameterizes functional connectivity distance, consolidating topological and physical properties of macroscale brain networks. Functional findings were integrated with morphological and microstructural metrics, and utility for surgical outcome prediction was assessed using machine learning techniques.

Results: Compared to controls, TLE patients showed connectivity distance reductions in temporoinsular and prefrontal networks, indicating topological segregation of functional networks. Testing for morphological and microstructural associations, we observed that functional connectivity contractions occurred independently from TLE-related cortical atrophy but were mediated by microstructural changes in the underlying white matter. Following our imaging study, all patients underwent an anterior temporal lobectomy as a treatment of their seizures, and postsurgical seizure outcome was determined at a follow-up at least 1 year after surgery. Using a regularized supervised machine learning paradigm with fivefold cross-validation, we demonstrated that patient-specific functional anomalies predicted postsurgical seizure outcome with 76 ± 4% accuracy, outperforming classifiers operating on clinical and structural imaging features.

Significance: Our findings suggest connectivity distance contractions as a macroscale substrate of TLE. Functional topological isolation may represent a microstructurally mediated network mechanism that tilts the balance toward epileptogenesis in affected networks and that may assist in patient-specific surgical prognostication.
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http://dx.doi.org/10.1111/epi.16540DOI Listing
June 2020

Clinical characteristics of patients with anti-EJ antisynthetase syndrome associated interstitial lung disease and literature review.

Respir Med 2020 Apr - May;165:105920. Epub 2020 Mar 3.

Department of Respiratory and Critical Care Medicine, Drum Tower Clinical Medical College of Nanjing Medical University, The Affiliated Drum Tower Hospital of Nanjing University Medical School, 321 Zhongshan Road, 210008, Nanjing, China. Electronic address:

Aim: Interstitial lung disease (ILD) is an extra-muscular manifestation of antisynthetase syndrome (ASS). The aim of this study is to analyze the clinical characteristics of anti-EJ associated ILD in a large cohort of patients.

Methods: Retrospective cohort study of patients with anti-EJ associated ILD. All available data of clinical and laboratory characteristics, pulmonary function tests, laboratory parameters, high resolution computed tomography (HRCT) and treatment were collected and analyzed from medical records.

Results: We identified 51 subjects. Average age at diagnosis was 55.6 years. Thirty-two of 51 patients were female. Concurrent autoantibodies against Ro52 were seen in 92.2% patients studied. HRCT patterns were mainly non-specific interstitial pneumonia (NSIP). The predominant myositis subset was amyopathic dermatomyositis (ADM) (41.2%) followed by dermatomyositis and polymyositis. Thirty-four patients improved on corticosteroids alone or in combination with immunosuppressive drugs as treatment and ten patients were stabilized. However, eleven patients (21.6%) initially improved during 12.0 ± 4.4 months, then progressively recurred despite steroid treatment (mean prednisone dose 11.6 ± 3.5 mg). The recurrence group included a significantly higher proportion of patients with NSIP pattern (p < 0.05). In the literature review the most common manifestations of anti-EJ ASS were ILD (89.3%) and myositis (58.9%).

Conclusion: ILD are common features of the anti-EJ ASS. Patients with anti-EJ ILD often had an onset of ILD with lower lung-predominant opacities and NSIP. Although the disease responded well to the initial combination therapy of corticosteroid and immunosuppressant, recurrence was frequent. NSIP pattern was significantly more frequent in the recurrence group.
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http://dx.doi.org/10.1016/j.rmed.2020.105920DOI Listing
January 2021

Interaction of COMT and KIBRA modulates the association between hippocampal structure and episodic memory performance in healthy young adults.

Behav Brain Res 2020 04 10;384:112550. Epub 2020 Feb 10.

Department of Radiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, 210008, China; Department of Radiology, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China; Institute for Brain Sciences, Nanjing University, Nanjing, 210008, China. Electronic address:

Genetic variations of COMT and KIBRA, which were reported to be expressed in the hippocampus, have been linked to memory function. However, their interaction on the hippocampal structure remains unknown. This study aimed to explore the interaction effects of COMT rs4680 and KIBRA rs17070145 on the hippocampal subfield volumes and test their associations with hippocampus-memory relationship in 187 healthy young adults. Two-way analysis of covariance was applied to the alterations in hippocampal subfield volumes among COMT and KIBRA genotypes. Significant interaction effects of these two genes were found in the right CA1 and CA3 subfields. Among KIBRA C-allele carriers, COMT Val/Val homozygotes showed greater volume in these regions than COMT Met-allele carriers. Furthermore, the slope of the correlation between right CA1 volume and immediate recall on the California Verbal Learning Test-II (CVLT-II) (F = 4.36, p = 0.041) as well as CVLT-II delayed recall (F = 6.44, p = 0.014) were significantly different between COMT Val/Val homozygotes and Met-allele carriers, which were positive or tend to be positive in COMT Val/Val group (CVLT immediate recall, r = 0.319, p = 0.040; CVLT delayed recall, r = 0.304, p = 0.051), but absent in COMT Met-allele carriers (CVLT immediate recall, r = -0.263, p = 0.205; CVLT delayed recall, r = -0.351, p = 0.086). These findings may provide a novel insight into the genetic effects upon the hippocampal structure and suggest that the conjoint effects of COMT and KIBRA played a modulatory role in the hippocampus-episodic memory correlation.
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http://dx.doi.org/10.1016/j.bbr.2020.112550DOI Listing
April 2020

Community-informed connectomics of the thalamocortical system in generalized epilepsy.

Neurology 2019 09 12;93(11):e1112-e1122. Epub 2019 Aug 12.

From the Departments of Radiology (Z.W., B.Z., B.Z.) and Neurology (Z.W., Y.X.), Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, China; Multimodal Imaging and Connectome Analysis Laboratory (Z.W., S.L., R.V.d.W., S.-J.H., B.C.B.) and Neuroimaging of Epilepsy Laboratory (S.-J.H., N.B., A.B.), McConnell Brain Imaging Centre, Montreal Neurological Institute and Hospital, McGill University, Quebec, Canada; and Department of Medical Imaging (Q.X., Z.Z.), Jinling Hospital, Nanjing University School of Medicine, China.

Objective: To study the intrinsic organization of the thalamocortical circuitry in patients with generalized epilepsy with tonic-clonic seizures (GTCS) via resting-state fMRI (rs-fMRI) connectome analysis and to evaluate its relation to drug response.

Methods: In a prospectively followed-up sample of 41 patients and 27 healthy controls, we obtained rs-fMRI and structural MRI. After 1 year of follow-up, 27 patients were classified as seizure-free and 14 as drug-resistant. We examined connectivity within and between resting-state communities in cortical and thalamic subregions. In addition to comparing patients to controls, we examined associations with seizure control. We assessed reproducibility in an independent cohort of 21 patients.

Results: Compared to controls, patients showed a more constrained network embedding of the thalamus, while frontocentral neocortical regions expressed increased functional diversity. Findings remained significant after regressing out thalamic volume and cortical thickness, suggesting independence from structural alterations. We observed more marked network imbalances in drug-resistant compared to seizure-free patients. Findings were similar in the reproducibility dataset.

Conclusions: Our findings suggest a pathoconnectomic mechanism of generalized epilepsy centered on diverging changes in cortical and thalamic connectivity. More restricted thalamic connectivity could reflect the tendency to engage in recursive thalamocortical loops, which may contribute to hyperexcitability. Conversely, increased connectional diversity of frontocentral networks may relay abnormal activity to an extended bilateral territory. Network imbalances were observed shortly after diagnosis and related to future drug response, suggesting clinical utility.
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http://dx.doi.org/10.1212/WNL.0000000000008096DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6746209PMC
September 2019

Impaired hippocampal functional connectivity in patients with drug resistant, generalized tonic-clonic seizures.

Neuroreport 2019 07;30(10):700-706

Neurology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, China.

The aim of this study was to better understand the imaging features of drug-resistant epilepsy (DRE), especially in idiopathic generalized tonic-clonic seizure (GTCS), as well as to discover the associated mechanisms and functional connectivity (FC). A total of 31 idiopathic generalized epilepsy-GTCS patients and 17 healthy controls were enrolled. For each patient, resting-state functional MRI was performed. After a 12-month follow-up observation, patients were further divided into either drug-resistant (DR) or drug-sensitive (DS) groups. Compared to the DS group, DR patients had previously received more types of antiepileptic drugs and had taken more types of failed antiepileptic drugs. There were distinct FC changes toward the left thalamus, left putamen, left precuneus, and right precentral gyrus in the left hippocampus between DR and DS patients. FCs in the DR group largely decreased or remained unchanged, while DS patients exhibited compensatory enhancement. Disease duration was negatively correlated with FC between the left hippocampus and the left thalamus-putamen in patients with DRE. Further, DRE patients had an extremely high area under the curve (0.978) and a cut-off FC between the left hippocampus and thalamus-putamen of 0.282. Together, hippocampal FCs in patients with DR GTCS were impaired and time-dependently correlated with disease duration. Hippocampal FCs in DS patients showed overall compensatory enhancement, which could be used as a sensitive and specific marker to identify and predict DR GTCS.
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http://dx.doi.org/10.1097/WNR.0000000000001262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6571184PMC
July 2019

Functional Connectome before and following Temporal Lobectomy in Mesial Temporal Lobe Epilepsy.

Sci Rep 2016 Mar 22;6:23153. Epub 2016 Mar 22.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.

As mesial temporal lobe epilepsy (mTLE) has been recognized as a network disorder, a longitudinal connectome investigation may shed new light on the understanding of the underlying pathophysiology related to distinct surgical outcomes. Resting-state functional MRI data was acquired from mTLE patients before (n = 37) and after (n = 24) anterior temporal lobectomy. According to surgical outcome, patients were classified as seizure-free (SF, n = 14) or non-seizure-free (NSF, n = 10). First, we found higher network resilience to targeted attack on topologically central nodes in the SF group compared to the NSF group, preoperatively. Next, a two-way mixed analysis of variance with between-subject factor 'outcome' (SF vs. NSF) and within-subject factor 'treatment' (pre-operation vs. post-operation) revealed divergent dynamic reorganization in nodal topological characteristics between groups, in the temporoparietal junction and its connection with the ventral prefrontal cortex. We also correlated the network damage score (caused by surgical resection) with postsurgical brain function, and found that the damage score negatively correlated with postoperative global and local parallel information processing. Taken together, dynamic connectomic architecture provides vital information for selecting surgical candidates and for understanding brain recovery mechanisms following epilepsy surgery.
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http://dx.doi.org/10.1038/srep23153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4802388PMC
March 2016

Connectome Reorganization Associated With Surgical Outcome in Temporal Lobe Epilepsy.

Medicine (Baltimore) 2015 Oct;94(40):e1737

From the Laboratory of Cognitive Neuropsychology, Department of Medical Psychology, Anhui Medical University, Hefei (G-JJ); Center for Cognition and Brain Disorders and the Affiliated Hospital, Hangzhou Normal University (G-JJ, JW, WL); Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments, Hangzhou (G-JJ, JW, WL); Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine (ZZ, QX, WW, GL); Department of Medical Imaging, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School (ZW); Department of Neurology, Jinling Hospital (FY); Department of Neurosurgery, Jinling Hospital, Nanjing University School of Medicine, Nanjing (KS); Department of Radiology, Taishan Medical University, Tai'an (QJ); and Key Laboratory for Neuroinformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, China (WL).

To identify the distinct pattern of anatomical network reorganization in surgically refractory mesial temporal lobe epilepsy (MTLE) patients using a longitudinal design. We collected longitudinal diffusion-weighted images of 19 MTLE patients before and after anterior temporal lobectomy. Patients were classified as seizure-free (SF) or nonseizure-free (NSF) at least 1 year after surgery. We constructed whole-brain anatomical networks derived from white matter tractography and evaluated network connectivity measures by graph theoretical analysis. The reorganization trajectories of network measures in SF and NSF patients were investigated by two-way mixed analysis of variance, with factors "group" (SF vs NSF) and "treatment" (presurgery vs postsurgery). Widespread brain structures showed opposite reorganization trajectories in FS and NSF groups (interaction effect). Most of them showed group difference before surgery and then converge after surgery, suggesting that surgery remodeled these structures into a similar status. Conversly, contralateral amygdala-planum-temporale and thalamic-parietal tracts showed higher connectivity strength in NSF than in SF patients after surgery, indicating maladaptive neuroplastic responses to surgery in NSF patients. Our findings suggest that surgical outcomes are associated not only with the preoperative pattern of anatomical connectivity, but also with connectome reconfiguration following surgery. The reorganization of contralateral temporal lobe and corticothalamic tracts may be particularly important for seizure control in MTLE.
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http://dx.doi.org/10.1097/MD.0000000000001737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616737PMC
October 2015

Frequency-Specific Alterations of Local Synchronization in Idiopathic Generalized Epilepsy.

Medicine (Baltimore) 2015 Aug;94(32):e1374

From the Center for Cognition and Brain Disorders and the Affiliated Hospital (JW, G-JJ, Y-FZ, WL), Hangzhou Normal University; Zhejiang Key Laboratory for Research in Assessment of Cognitive Impairments (JW, G-JJ, Y-FZ, WL), Hangzhou; Department of Medical Imaging (ZZ, QX, YH, WL, GL), Jinling Hospital, Nanjing University School of Medicine; Department of Medical Imaging (ZW), Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing; Department of Radiology (QJ), Taishan Medical University, Tai'an; and Department of Neurology (FY), Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Recurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a "conscious perception network," which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency-specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands.
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http://dx.doi.org/10.1097/MD.0000000000001374DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616718PMC
August 2015

Pathological uncoupling between amplitude and connectivity of brain fluctuations in epilepsy.

Hum Brain Mapp 2015 Jul 16;36(7):2756-66. Epub 2015 Apr 16.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Amplitude and functional connectivity are two fundamental parameters for describing the spontaneous brain fluctuations. These two parameters present close coupling in physiological state, and present different alteration patterns in epilepsy revealed by functional MRI (fMRI). We hypothesized that the alteration of coupling between these two imaging parameters may be underpinned by specific pathological factors of epilepsy, and can be employed to improve the capability for epileptic focus detection. Forty-seven patients (26 left- and 21 right-sided) with mesial temporal lobe epilepsy (mTLE) and 32 healthy controls underwent resting-state fMRI scans. All patients were detected to have interictal epileptic discharges on simultaneous electroencephalograph (EEG) recordings. Amplitude-connectivity coupling was calculated by correlating amplitude and functional connectivity density of low-frequency brain fluctuations. We observed reduced amplitude-connectivity coupling associated with epileptic discharges in the mesial temporal regions in both groups of patients, and increased coupling associated with epilepsy durations in the posterior regions of the default-mode network in the right-sided patients. Moreover, we proposed a new index of amplitude subtracting connectivity, which elevated imaging contrast for differentiating the patients from the controls. The findings indicated that epileptic discharges and chronic damaging effect of epilepsy might both contribute to alterations of amplitude-connectivity coupling in different pivotal regions in mTLE. Investigation on imaging coupling provides synergistic approach for describing brain functional changing features in epilepsy.
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http://dx.doi.org/10.1002/hbm.22805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6869589PMC
July 2015

Brain iron redistribution in mesial temporal lobe epilepsy: a susceptibility-weighted magnetic resonance imaging study.

BMC Neurosci 2014 Nov 21;15:117. Epub 2014 Nov 21.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, 305# Eastern Zhongshan Rd, Nanjing, 210002, China.

Background: The roles of iron in epilepsy and its pathophysiological significance are poorly understood, especially whether iron levels are abnormal in subcortcal structures. This study aims to demonstrate whole-brain iron alterations and its clinical relevancies in mesial temporal lobe epilepsy (mTLE) in vivo, using susceptibility-weighted magnetic resonance imaging (SWI).

Methods: We studied 62 patients with mTLE and 62 healthy controls. Brain iron concentration was quantified using SWI phase values. Voxel-wise analysis was carried out to compare iron levels between mTLE and controls, and to assess the relationship between altered iron concentration and clinical parameters in mTLE.

Results: Patients with mTLE showed decreases of iron levels in the subcortical structures such as substantia nigra, red nucleus, and basal ganglia. Conversely, iron levels were decreased in the cortex. Subcortical iron levels were negatively correlated to those in the cortex. Moreover, cortical and basal ganglia iron levels were related to clinical variables including epilepsy duration, age at seizures onset, and histories of precipitating factors.

Conclusions: Our SWI findings suggest a redistribution of iron between subcortical and cortical structures in mTLE. The degree of redistribution is affected by both progression of epilepsy and precipitating factors. Investigation on brain iron redistribution offers new insights into the pathogenesis of mTLE, and may be a potential biomarker for monitoring the clinical progression of epilepsy.
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http://dx.doi.org/10.1186/s12868-014-0117-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243317PMC
November 2014

Frequency-dependent amplitude alterations of resting-state spontaneous fluctuations in idiopathic generalized epilepsy.

Epilepsy Res 2014 Jul 26;108(5):853-60. Epub 2014 Mar 26.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China; Jinling Hospital-Fudan University Computational Translational Medicine Center, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China.

Purpose: Amplitude of low-frequency fluctuation (ALFF) of blood-oxygenation level-dependent (BOLD) has proven a promising way to detect disease-related local brain activity. However, routine approach employs an arbitrary frequency band of 0.01-0.08 Hz, which lacks frequency specificity and blinds to the information contained in other frequency bands. This study investigated the amplitude of fluctuations in full BOLD frequency bands, and addressed how amplitudes of fluctuations change in each specific frequency range in idiopathic generalized epilepsy (IGE).

Methods: Thirty-four IGE patients with generalized tonic-clonic seizure and the same number of age- and sex-matched healthy controls were included. Functional MRI data were acquired using a 2s repetition time. Routine amplitude of low-frequency fluctuation analysis was first performed. The regions showing group difference were set as Region-of-interest for analysis of amplitudes of full-frequency. The amplitudes of BOLD fluctuations were consecutively performed at each frequency bin of 0.002 Hz, and specific frequency amplitude analyses were performed in five different frequency ranges (0-0.01 Hz, 0.01-0.027 Hz, 0.027-0.073 Hz, 0.073-0.198 Hz, and 0.198-0.25 Hz).

Key Findings: The thalamus and prefrontal cortex showed significant group differences in routine amplitude analysis. For amplitude of full-frequency analysis, a reverse pattern was found in the dynamic changes between the thalamus and prefrontal cortex in IGE. Moreover, the prefrontal cortex showed amplitude difference in the 0.01-0.027 Hz band, while the thalamus showed amplitude difference in the 0.027-0.073 Hz band. Both these two regions showed amplitude differences in 0.198-0.25 Hz band.

Significance: We demonstrated the characteristic alterations of amplitude of BOLD fluctuations in IGE in frequency domain. The amplitude analysis of full frequency may potentially help to select specific frequency range for detecting epilepsy-related brain activity, and provide insights into the pathophysiological mechanism of IGE.
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http://dx.doi.org/10.1016/j.eplepsyres.2014.03.003DOI Listing
July 2014

Epileptic discharges specifically affect intrinsic connectivity networks during absence seizures.

J Neurol Sci 2014 Jan 24;336(1-2):138-45. Epub 2013 Oct 24.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China. Electronic address:

Intrinsic connectivity network (ICN) technique provides a feasible way for evaluating cognitive impairments in epilepsy. This EEG-fMRI study aims to comprehensively assess the alterations of ICNs affected by generalized spike-and-wave discharge (GSWD) during absence seizure (AS). Twelve fMRI sessions with GSWD, and individually paired non-GSWD sessions were acquired from 16 patients with AS. Ten ICNs corresponding to seizure origination and cognitive processes were extracted using independent component analysis. Intra- and inter-network connectivity alterations of the ICNs were observed through comparisons between GSWD and non-GSWD sessions. Sequential correlation analysis between GSWD and the ICN time courses addressed the immediate effects of GSWD on ICNs during AS. GSWD-related increase of intra-network connectivity was found only in the thalamus, and extensive decreases were found in the ICNs corresponding to higher-order cognitive processes including the default-mode network, dorsal attention network, central executive network and salience network. The perceptive networks and motor network were less affected by GSWD. Sequential correlation analysis further demonstrated different responses of the ICNs to GSWD. In addition to GSWD-related functional excitation in the thalamus and functional suspension in the default-mode network, this study revealed extensive inhibitions in the other ICNs corresponding to higher-order cognitive processes, and spared perceptive and motor processes in AS. GSWD elevated synchronization of brain network activity and sequentially affected the ICNs.
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http://dx.doi.org/10.1016/j.jns.2013.10.024DOI Listing
January 2014

Impaired self-referential processing in mesial temporal lobe epilepsy: a functional MRI study.

Neurosci Lett 2013 Oct 30;555:187-92. Epub 2013 Sep 30.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China; Department of Medical Imaging, Jiangsu Province Traditional Chinese Medicine Hospital, Nanjing 210029, China; Institute of Mental Health Research, University of Ottawa, 1145 Carling Avenue, Ottawa, ON K1Z 7K4, Canada.

Mesial temporal lobe epilepsy (mTLE) presents typical symptoms of cognitive impairments and mental disorders, which is presumed to be related to impairment of self-referential processing. This study aims to investigate the alterations of self-reference in mTLE using functional magnetic resonance imaging (fMRI). Fifty patients with unilateral mTLE (26 left- and 24 right-sided mTLE) were recruited in the present study. Traditional task paradigm of internally-cued condition vs. externally-cued condition was employed to induce self-referential activation. FMRI activation in each group of patients was compared with that of 30 healthy controls. Moreover, fMRI responses in the dorsal mesial prefrontal cortex were specifically addressed by correlating with behavioral data of reaction times and clinical data of epilepsy duration, respectively. Compared with the healthy controls, both two groups of patients showed decreased behavioral performance (reaction times) and decreased fMRI activation of self-reference in the anterior and posterior cortical midline structures. Moreover, fMRI activation was found to be negatively correlated with behavioral performance and epilepsy duration. The present findings implicate functional impairment of self-reference caused by epilepsy in mTLE. This study provided imaging evidence for functional impairments of self-referential processing and brain default-mode function in mTLE.
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http://dx.doi.org/10.1016/j.neulet.2013.09.054DOI Listing
October 2013

Dynamical intrinsic functional architecture of the brain during absence seizures.

Brain Struct Funct 2014 Nov 4;219(6):2001-15. Epub 2013 Aug 4.

Center for Cognition and Brain Disorders and the Affiliated Hospital, Hangzhou Normal University, Hangzhou, 310015, China,

Epilepsy is characterized by recurrent and temporary brain dysfunction due to discharges of interconnected groups of neurons. The brain of epilepsy patients has a dynamic bifurcation that switches between epileptic and normal states. The dysfunctional state involves large-scale brain networks. It is very important to understand the network mechanisms of seizure initiation, maintenance, and termination in epilepsy. Absence epilepsy provides a unique model for neuroimaging investigation on dynamic evolutions of brain networks over seizure repertoire. By using a dynamic functional connectivity and graph theoretical analyses to study absence seizures (AS), we aimed to obtain transition of network properties that account for seizure onset and offset. We measured resting-state functional magnetic resonance imaging and simultaneous electroencephalography (EEG) from children with AS. We used simultaneous EEG to define the preictal, ictal and postictal intervals of seizures. We measured dynamic connectivity maps of the thalamus network and the default mode network (DMN), as well as functional connectome topologies, during the three different seizure intervals. The analysis of dynamic changes of anti-correlation between the thalamus and the DMN is consistent with an inhibitory effect of seizures on the default mode of brain function, which gradually fades out after seizure onset. Also, we observed complex transitions of functional network topology, implicating adaptive reconfiguration of functional brain networks. In conclusion, our work revealed novel insights into modifications in large-scale functional connectome during AS, which may contribute to a better understanding the network mechanisms of state bifurcations in epileptogenesis.
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http://dx.doi.org/10.1007/s00429-013-0619-2DOI Listing
November 2014

Bronchial varices in congenital unilateral pulmonary vein atresia.

Am J Respir Crit Care Med 2013 Jun;187(11):1267-8

Department of Respiratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.

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http://dx.doi.org/10.1164/rccm.201211-1974IMDOI Listing
June 2013

Relationship between large-scale functional and structural covariance networks in idiopathic generalized epilepsy.

Brain Connect 2013 ;3(3):240-54

Center for Cognition and Brain Disorders and the Affiliated Hospital, Hangzhou Normal University, Hangzhou, China.

The human brain can be modeled as a network, whose structure can be revealed by either anatomical or functional connectivity analyses. Little is known, so far, about the topological features of the large-scale interregional functional covariance network (FCN) in the brain. Further, the relationship between the FCN and the structural covariance network (SCN) has not been characterized yet, in the intact as well as in the diseased brain. Here, we studied 59 patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures and 59 healthy controls. We estimated the FCN and the SCN by measuring amplitude of low-frequency fluctuations (ALFF) and gray matter volume (GMV), respectively, and then we conducted graph theoretical analyses. Our ALFF-based FCN and GMV-based results revealed that the normal human brain is characterized by specific topological properties such as small worldness and highly-connected hub regions. The patients had an altered overall topology compared to the controls, suggesting that epilepsy is primarily a disorder of the cerebral network organization. Further, the patients had altered nodal characteristics in the subcortical and medial temporal regions and default-mode regions, for both the FCN and SCN. Importantly, the correspondence between the FCN and SCN was significantly larger in patients than in the controls. These results support the hypothesis that the SCN reflects shared long-term trophic mechanisms within functionally synchronous systems. They can also provide crucial information for understanding the interactions between the whole-brain network organization and pathology in generalized tonic-clonic seizures.
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http://dx.doi.org/10.1089/brain.2012.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3685391PMC
October 2013

Impairments of thalamic nuclei in idiopathic generalized epilepsy revealed by a study combining morphological and functional connectivity MRI.

PLoS One 2012 11;7(7):e39701. Epub 2012 Jul 11.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.

Objective: Neuroimaging evidence suggested that the thalamic nuclei may play different roles in the progress of idiopathic generalized epilepsy (IGE). This study aimed to demonstrate the alterations in morphometry and functional connectivity in the thalamic nuclei in IGE.

Methods: Fifty-two patients with IGE characterized by generalized tonic-clonic seizures and 67 healthy controls were involved in the study. The three-dimensional high-resolution T1-weighted MRI data were acquired for voxel-based morphometry (VBM) analysis, and resting-state blood-oxygenation level functional MRI data were acquired for functional connectivity analysis. The thalamic nuclei of bilateral medial dorsal nucleus (MDN) and pulvinar, as detected with decreased gray matter volumes in patients with IGE through VBM analysis, were selected as seed regions for functional connectivity analysis.

Results: Different alteration patterns were found in functional connectivity of the thalamic nuclei with decreased gray matter volumes in IGE. Seeding at the MDN, decreased connectivity in the bilateral orbital frontal cortex, caudate nucleus, putamen and amygdala were found in the patients (P<0.05 with correction). However, seeding at the pulvinar, no significant alteration of functional connectivity was found in the patients (P<0.05 with correction).

Conclusions: Some specific impairment of thalamic nuclei in IGE was identified using morphological and functional connectivity MRI approaches. These findings may strongly support the different involvement of the thalamocortical networks in IGE.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039701PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394762PMC
March 2013

Pattern classification of large-scale functional brain networks: identification of informative neuroimaging markers for epilepsy.

PLoS One 2012 17;7(5):e36733. Epub 2012 May 17.

Centre for Computational Systems Biology, Fudan University, Shanghai, People's Republic of China.

The accurate prediction of general neuropsychiatric disorders, on an individual basis, using resting-state functional magnetic resonance imaging (fMRI) is a challenging task of great clinical significance. Despite the progress to chart the differences between the healthy controls and patients at the group level, the pattern classification of functional brain networks across individuals is still less developed. In this paper we identify two novel neuroimaging measures that prove to be strongly predictive neuroimaging markers in pattern classification between healthy controls and general epileptic patients. These measures characterize two important aspects of the functional brain network in a quantitative manner: (i) coordinated operation among spatially distributed brain regions, and (ii) the asymmetry of bilaterally homologous brain regions, in terms of their global patterns of functional connectivity. This second measure offers a unique understanding of brain asymmetry at the network level, and, to the best of our knowledge, has not been previously used in pattern classification of functional brain networks. Using modern pattern-recognition approaches like sparse regression and support vector machine, we have achieved a cross-validated classification accuracy of 83.9% (specificity: 82.5%; sensitivity: 85%) across individuals from a large dataset consisting of 180 healthy controls and epileptic patients. We identified significantly changed functional pathways and subnetworks in epileptic patients that underlie the pathophysiological mechanism of the impaired cognitive functions. Specifically, we find that the asymmetry of brain operation for epileptic patients is markedly enhanced in temporal lobe and limbic system, in comparison with healthy individuals. The present study indicates that with specifically designed informative neuroimaging markers, resting-state fMRI can serve as a most promising tool for clinical diagnosis, and also shed light onto the physiology behind complex neuropsychiatric disorders. The systematic approaches we present here are expected to have wider applications in general neuropsychiatric disorders.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0036733PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3355144PMC
September 2012

Resting-state brain organization revealed by functional covariance networks.

PLoS One 2011 13;6(12):e28817. Epub 2011 Dec 13.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, Jiangsu Province, China.

Background: Brain network studies using techniques of intrinsic connectivity network based on fMRI time series (TS-ICN) and structural covariance network (SCN) have mapped out functional and structural organization of human brain at respective time scales. However, there lacks a meso-time-scale network to bridge the ICN and SCN and get insights of brain functional organization.

Methodology And Principal Findings: We proposed a functional covariance network (FCN) method by measuring the covariance of amplitude of low-frequency fluctuations (ALFF) in BOLD signals across subjects, and compared the patterns of ALFF-FCNs with the TS-ICNs and SCNs by mapping the brain networks of default network, task-positive network and sensory networks. We demonstrated large overlap among FCNs, ICNs and SCNs and modular nature in FCNs and ICNs by using conjunctional analysis. Most interestingly, FCN analysis showed a network dichotomy consisting of anti-correlated high-level cognitive system and low-level perceptive system, which is a novel finding different from the ICN dichotomy consisting of the default-mode network and the task-positive network.

Conclusion: The current study proposed an ALFF-FCN approach to measure the interregional correlation of brain activity responding to short periods of state, and revealed novel organization patterns of resting-state brain activity from an intermediate time scale.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0028817PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3236756PMC
April 2012

Altered functional-structural coupling of large-scale brain networks in idiopathic generalized epilepsy.

Brain 2011 Oct;134(Pt 10):2912-28

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, PR China.

The human brain is a large-scale integrated network in the functional and structural domain. Graph theoretical analysis provides a novel framework for analysing such complex networks. While previous neuroimaging studies have uncovered abnormalities in several specific brain networks in patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures, little is known about changes in whole-brain functional and structural connectivity networks. Regarding functional and structural connectivity, networks are intimately related and share common small-world topological features. We predict that patients with idiopathic generalized epilepsy would exhibit a decoupling between functional and structural networks. In this study, 26 patients with idiopathic generalized epilepsy characterized by tonic-clonic seizures and 26 age- and sex-matched healthy controls were recruited. Resting-state functional magnetic resonance imaging signal correlations and diffusion tensor image tractography were used to generate functional and structural connectivity networks. Graph theoretical analysis revealed that the patients lost optimal topological organization in both functional and structural connectivity networks. Moreover, the patients showed significant increases in nodal topological characteristics in several cortical and subcortical regions, including mesial frontal cortex, putamen, thalamus and amygdala relative to controls, supporting the hypothesis that regions playing important roles in the pathogenesis of epilepsy may display abnormal hub properties in network analysis. Relative to controls, patients showed further decreases in nodal topological characteristics in areas of the default mode network, such as the posterior cingulate gyrus and inferior temporal gyrus. Most importantly, the degree of coupling between functional and structural connectivity networks was decreased, and exhibited a negative correlation with epilepsy duration in patients. Our findings suggest that the decoupling of functional and structural connectivity may reflect the progress of long-term impairment in idiopathic generalized epilepsy, and may be used as a potential biomarker to detect subtle brain abnormalities in epilepsy. Overall, our results demonstrate for the first time that idiopathic generalized epilepsy is reflected in a disrupted topological organization in large-scale brain functional and structural networks, thus providing valuable information for better understanding the pathophysiological mechanisms of generalized tonic-clonic seizures.
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http://dx.doi.org/10.1093/brain/awr223DOI Listing
October 2011

Increased activity imbalance in fronto-subcortical circuits in adolescents with major depression.

PLoS One 2011 16;6(9):e25159. Epub 2011 Sep 16.

Department of Medical Imaging, Nanjing Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Background: A functional discrepancy exists in adolescents between frontal and subcortical regions due to differential regional maturational trajectories. It remains unknown how this functional discrepancy alters and whether the influence from the subcortical to the frontal system plays a primacy role in medication naïve adolescent with major depressive disorder (MDD).

Methodology/principal Findings: Eighteen MDD and 18 healthy adolescents were enrolled. Depression and anxiety severity was assessed by the Short Mood and Feeling Questionnaire (SMFQ) and Screen for Child Anxiety Related Emotional Disorders (SCARED) respectively. The functional discrepancy was measured by the amplitude of low-frequency fluctuations (ALFF) of resting-state functional MRI signal. Correlation analysis was carried out between ALFF values and SMFQ and SCARED scores. Resting brain activity levels measured by ALFF was higher in the frontal cortex than that in the subcortical system involving mainly (para) limbic-striatal regions in both HC and MDD adolescents. The difference of ALFF values between frontal and subcortical systems was increased in MDD adolescents as compared with the controls.

Conclusions/significance: The present study identified an increased imbalance of resting-state brain activity between the frontal cognitive control system and the (para) limbic-striatal emotional processing system in MDD adolescents. The findings may provide insights into the neural correlates of adolescent MDD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025159PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175001PMC
February 2012

Gray-matter volume reduction in the thalamus and frontal lobe in epileptic patients with generalized tonic-clonic seizures.

J Neuroradiol 2011 Dec 26;38(5):298-303. Epub 2011 Feb 26.

Department of Medical Imaging, Nanjing Jinling Hospital, Nanjing University School of Medicine, 305# Eastern Zhongshan Rd, Nanjing 210002, China.

Background And Purpose: Generalized tonic-clonic seizures (GTCS) comprise a common subsyndrome of idiopathic generalized epilepsy (IGE). Previous studies found that patients with GTCS had structural abnormalities in a few specific brain regions. However, the underlying clinical cause leading to these abnormalities remains unclear. The present study aimed to explore the relationship between changes in gray-matter (GM) volume and duration of epilepsy, based on GM volume differences observed between GTCS patients and healthy controls.

Patients And Methods: Voxel-based morphometry (VBM) analysis with DARTEL (diffeomorphic anatomical registration through exponential Lie algebra) was used to investigate GM volume differences in 31 GTCS patients compared with 37 age- and gender-matched healthy controls. Voxel-based correlation analysis was used to explore the relationship between GM volume and duration of epilepsy in GTCS patients.

Results: Compared with healthy controls, GTCS patients showed significant decreases in GM volume in the bilateral thalami, frontal lobe, insula and cerebellum. In addition, GM volume in the bilateral thalami and left medial frontal gyrus had a negative correlation with duration of epilepsy.

Conclusion: GM volume changes in the thalamus and frontal lobe were associated with progressive epileptic seizures. The results indicate the presence of an abnormal thalamocortical network, which may reflect an underlying pathophysiological mechanism of GTCS.
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http://dx.doi.org/10.1016/j.neurad.2010.12.007DOI Listing
December 2011

Altered resting state networks in epileptic patients with generalized tonic-clonic seizures.

Brain Res 2011 Feb 16;1374:134-41. Epub 2010 Dec 16.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, #305 Eastern Zhongshan Rd., Nanjing 210002, PR China.

Recent functional magnetic resonance imaging (fMRI) studies have demonstrated that the resting state networks (RSNs) are impaired in various neuropsychiatric disorders. However, little is known about the changes in the functional architecture of the RSNs in idiopathic generalized epilepsy patients with generalized tonic-clonic seizures (GTCS). Resting state fMRI data were acquired from 16 GTCS patients and 16 healthy subjects. The data were acquired during interictal without combined EEG confirmation. Functional connectivity among the RSNs was examined using individual-based independent component analysis. Six RSNs were identified in both the GTCS and control groups. Compared with the healthy subjects, decreased functional connectivity in the self-referential, somatosensory, visual, and auditory networks, and both the decreased and increased functional connectivities in the classic default-mode and dorsal attention networks were found in the GTCS patients. Furthermore, the present study revealed a negative correlation between the seizure duration and functional connectivity changes in the medial prefrontal cortex in the GTCS patients. These results indicate that there are impairments in the RSNs and possible reorganization of the default-mode network and dorsal attention network in patients with GTCS. Our findings may also suggest that the medial prefrontal cortex and its associated network play a role in the development of GTCS.
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http://dx.doi.org/10.1016/j.brainres.2010.12.034DOI Listing
February 2011

Granger causal influence predicts BOLD activity levels in the default mode network.

Hum Brain Mapp 2011 Jan;32(1):154-61

Department of Medical Imaging, Nanjing Jinling Hospital, Medical School of Nanjing University, Nanjing, China.

Although the brain areas in the default-mode network (DMN) act in a coordinated way during rest, the activity levels in the individual areas of the DMN are highly heterogeneous. The relation between the activity levels and the pattern of causal interaction among the DMN areas remains unknown. In the present fMRI study, seven nodes of the DMN were identified and their activity levels were rank-ordered based on a power spectral analysis of the resting blood oxygenation level-dependent (BOLD) signals. Furthermore, the direction of information flow among these DMN nodes was determined using Granger causality analysis and graph-theoretic methods. We found that the activity levels in these seven DMN nodes had a highly consistent hierarchical distribution, with the highest activity level in the posterior cingulate/precuneus cortices, followed by ventral medial prefrontal cortex and dorsal medial prefrontal cortex, and with the lowest level in the left inferior temporal gyrus. Importantly, a significant correlation was found between the activity levels and the In-Out degrees of information flow across the DMN nodes, suggesting that Granger causal influences can be used to predict BOLD activity levels. These findings shed light on the dynamical organization of cortical neuronal networks and may provide the basis for characterizing network disruption by brain disorders.
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http://dx.doi.org/10.1002/hbm.21065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870036PMC
January 2011

Small-world directed networks in the human brain: multivariate Granger causality analysis of resting-state fMRI.

Neuroimage 2011 Feb 10;54(4):2683-94. Epub 2010 Nov 10.

Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, PR China.

Small-world organization is known to be a robust and consistent network architecture, and is a hallmark of the structurally and functionally connected human brain. However, it remains unknown if the same organization is present in directed influence brain networks whose connectivity is inferred by the transfer of information from one node to another. Here, we aimed to reveal the network architecture of the directed influence brain network using multivariate Granger causality analysis and graph theory on resting-state fMRI recordings. We found that some regions acted as pivotal hubs, either being influenced by or influencing other regions, and thus could be considered as information convergence regions. In addition, we observed that an exponentially truncated power law fits the topological distribution for the degree of total incoming and outgoing connectivity. Furthermore, we also found that this directed network has a modular structure. More importantly, according to our data, we suggest that the human brain directed influence network could have a prominent small-world topological property.
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http://dx.doi.org/10.1016/j.neuroimage.2010.11.007DOI Listing
February 2011

Default mode network abnormalities in mesial temporal lobe epilepsy: a study combining fMRI and DTI.

Hum Brain Mapp 2011 Jun 9;32(6):883-95. Epub 2010 Jun 9.

Key Laboratory for NeuroInformation of Ministry of Education, School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu, People's Republic of China.

Studies of in mesial temporal lobe epilepsy (mTLE) patients with hippocampal sclerosis (HS) have reported reductions in both functional and structural connectivity between hippocampal structures and adjacent brain regions. However, little is known about the connectivity among the default mode network (DMN) in mTLE. Here, we hypothesized that both functional and structural connectivity within the DMN were disturbed in mTLE. To test this hypothesis, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) were applied to examine the DMN connectivity of 20 mTLE patients, and 20 gender- and age-matched healthy controls. Combining these two techniques, we explored the changes in functional (temporal correlation coefficient derived from fMRI) and structural (path length and connection density derived from DTI tractography) connectivity of the DMN. Compared to the controls, we found that both functional and structural connectivity were significantly decreased between the posterior cingulate cortex (PCC)/precuneus (PCUN) and bilateral mesial temporal lobes (mTLs) in patients. No significant between-group difference was found between the PCC/PCUN and medial prefrontal cortex (mPFC). In addition, functional connectivity was found to be correlated with structural connectivity in two pairwise regions, namely between the PCC/PCUN and bilateral mTLs, respectively. Our results suggest that the decreased functional connectivity within the DMN in mTLE may be a consequence of the decreased connection density underpinning the degeneration of structural connectivity.
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http://dx.doi.org/10.1002/hbm.21076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6870458PMC
June 2011

Altered spontaneous neuronal activity of the default-mode network in mesial temporal lobe epilepsy.

Brain Res 2010 Apr 2;1323:152-60. Epub 2010 Feb 2.

Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing 210002, China.

Increasing evidence from behavioral and neuroimaging studies suggests that mesial temporal lobe epilepsy (mTLE) is possibly associated with the default-mode brain function. However, the alteration of coherent neural activities in such a default-mode network (DMN) in mTLE has yet to be investigated. The present study analyzed the resting-state functional MRI data from two groups of mTLE patients with left and right hippocampal sclerosis using independent component analysis. In comparison with healthy controls, decreased functional connectivity in the dorsal mesial prefrontal cortex, mesial temporal lobe and inferior temporal cortex was observed in these two patient groups. Moreover, the right but not left mTLE patients showed bilaterally decreased functional connectivity in the mesial temporal lobe and increased functional connectivity in the posterior cingulate cortex. The decreased functional connectivity of the mesial temporal lobe was related to the epilepsy duration, suggesting that the posterior cingulate cortex may play a compensatory role for the altered DMN in the right mTLE. These findings indicate that the DMN is widely affected even if a single network node is impaired. An extensive regional overlap between the DMN and the previously described epileptic network suggests that the widespread functional impairments in mTLE may attribute to an aberrant DMN. The distinct patterns of the DMN between the left and right mTLE support a view that there are different pathological mechanisms underlying these two types of epilepsies.
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http://dx.doi.org/10.1016/j.brainres.2010.01.042DOI Listing
April 2010