Pairs Of Brain Regions Research Articles

Prediction of baseline expressive and receptive language function in children with focal epilepsy using diffusion tractography-based deep learning network

PurposeFocal epilepsy is a risk factor for language impairment in children. We investigated whether the current state-of-the-art deep learning network on diffusion tractography connectome can accurately predict expressive and receptive language scores of children with epilepsy. MethodsWe studied 37 children with a diagnosis of drug-resistant focal epilepsy (age: 11.8 ± 3.1 years) using 3 T MRI and diffusion tractography connectome: G = (S, Ω), where S is an adjacency matrix of edges representing the connectivity strength (number of white-matter tract streamlines) between each pair of brain regions, and Ω reflects a set of brain regions. A convolutional neural network (CNN) was trained to learn the nonlinear relationship between ‘S (input)’ and ‘language score (output)’. Repeated hold-out validation was then employed to measure the Pearson correlation and mean absolute error (MAE) between CNN-predicted and actual language scores. ResultsWe found that CNN-predicted and actual scores were significantly correlated (i.e., Pearson’s R/p-value: 0.82/<0.001 and 0.75/<0.001), yielding MAE: 7.77 and 7.40 for expressive and receptive scores, respectively. Specifically, sparse connectivity not only within the left cortico-cortical network but also involving the right subcortical structures was predictive of language impairment of expressive or receptive domain. Subsequent subgroup analyses inferred that the effectiveness of diffusion tractography-based prediction of language outcome was independent of clinical variables. Intrinsic diffusion tractography connectome properties may be useful for predicting the severity of baseline language dysfunction and possibly provide a better understanding of the biological mechanisms of epilepsy-related language impairment in children.

Resting-state functional connectivity predicts recovery from visually induced motion sickness.

Movies depicting certain types of motion often provoke uncomfortable symptoms similar to motion sickness, termed visually induced motion sickness (VIMS). VIMS generally evolves slowly during the viewing of a motion stimulus and, when the stimulus is removed, the recovery proceeds over time. Recent human neuroimaging studies have provided new insights into the neural bases of the evolution of VIMS. In contrast, no study has investigated the neural correlates of the recovery from VIMS. Study of the recovery process is critical for the development of a way to promote recovery and could provide further clues for understanding the mechanisms of VIMS. We thus investigated brain activity during the recovery from VIMS with functional connectivity magnetic resonance imaging. We found enhanced recovery-related functional connectivity patterns involving brain areas such as the insular, cingulate and visual cortical regions, which have been suggested to play important roles in the emergence of VIMS. These regions also constituted large interactive networks. Furthermore, the increase in functional connectivity was correlated with the subjective awareness of recovery for the following five pairs of brain regions: insula-superior temporal gyrus, claustrum-left and right inferior parietal lobules, claustrum-superior temporal gyrus and superior frontal gyrus-lentiform nucleus. Considering the previous findings on the functions of these regions and the present results, it is suggested that the increase in FC may reflect brain processes such as enhanced interoceptive awareness to one's own bodily state, a neuroplastic change in visual-processing circuits and/or the maintenance of visual spatial memory.

Multivariate Analysis of Bivariate Phase-Amplitude Coupling in EEG Data Using Tensor Robust PCA.

Cross-frequency coupling is emerging as a crucial mechanism that coordinates the integration of spectrally and spatially distributed neuronal oscillations. Recently, phase-amplitude coupling, a form of cross-frequency coupling, where the phase of a slow oscillation modulates the amplitude of a fast oscillation, has gained attention. Existing phase-amplitude coupling measures are mostly confined to either coupling within a region or between pairs of brain regions. Given the availability of multi-channel electroencephalography recordings, a multivariate analysis of phase amplitude coupling is needed to accurately quantify the coupling across multiple frequencies and brain regions. In the present work, we propose a tensor based approach, i.e., higher order robust principal component analysis, to identify response-evoked phase-amplitude coupling across multiple frequency bands and brain regions. Our experiments on both simulated and electroencephalography data demonstrate that the proposed multivariate phase-amplitude coupling method can capture the spatial and spectral dynamics of phase-amplitude coupling more accurately compared to existing methods. Accordingly, we posit that the proposed higher order robust principal component analysis based approach filters out the background phase-amplitude coupling activity and predominantly captures the event-related phase-amplitude coupling dynamics to provide insight into the spatially distributed brain networks across different frequency bands.

Detection of functional connectivity in the brain during visuo-guided grip force tracking tasks: A functional near-infrared spectroscopy study.

The functional connectivity (FC) between multiple brain regions during tasks is currently gradually being explored with functional near-infrared spectroscopy (fNIRS). However, the FC present during grip force tracking tasks performed under visual feedback remains unclear. In the present study, we used fNIRS to measure brain activity during resting states and grip force tracking tasks at 25%, 50%, and 75% of maximum voluntary contraction (MVC) in 11 healthy subjects, and the activity was measured from four target brain regions: the left prefrontal cortex (lPFC), right prefrontal cortex (rPFC), left sensorimotor cortex (lSMC), and right sensorimotor cortex (rSMC). We determined the FC between these regions utilizing three different methods: Pearson's correlation method, partial correlation method, and a pairwise maximum entropy model (MEM). The results showed that the FC of lSMC-rSMC and lPFC-rPFC (interhemispheric homologous pairs) were significantly stronger than those of other brain region pairs. Moreover, FC of lPFC-rPFC was strengthened during the 75% MVC task compared to the other task states and the resting states. The FC of lSMC-lPFC and rSMC-rPFC (intrahemispheric region pairs) strengthened with a higher task load. The results provided new insights into the FC between brain regions during visuo-guided grip force tracking tasks.

Recognition of Cognitive Impairment in Adult Moyamoya Disease: A Classifier Based on High-Order Resting-State Functional Connectivity Network.

Objective: Vascular cognitive impairment (VCI) is a common complication in adult patients with moyamoya disease (MMD), and is reversible by surgical revascularization in its early stage of mild VCI. However, accurate diagnosis of mild VCI is difficult based on neuropsychological examination alone. This study proposed a method of dynamic resting-state functional connectivity (FC) network to recognize global cognitive impairment in MMD.Methods: For MMD, 36 patients with VCI and 43 patients with intact cognition (Non-VCI) were included, as well as 26 normal controls (NCs). Using resting-state fMRI, dynamic low-order FC networks were first constructed with multiple brain regions which were generated through a sliding window approach and correlated in temporal dimension. In order to obtain more information of network interactions along the time, high-order FC networks were established by calculating correlations among each pair of brain regions. Afterwards, a sparse representation-based classifier was constructed to recognize MMD (experiment 1) and its cognitive impairment (experiment 2) with features extracted from both low- and high-order FC networks. Finally, the ten-fold cross-validation strategy was proposed to train and validate the performance of the classifier.Results: The three groups did not differ significantly in demographic features (p > 0.05), while the VCI group exhibited the lowest MMSE scores (p = 0.001). The Non-VCI and NCs groups did not differ significantly in MMSE scores (p = 0.054). As for the classification between MMD and NCs, the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity of the classifier reached 90.70, 88.57, 93.67, and 73.08%, respectively. While for the classification between VCI and Non-VCI, the AUC, accuracy, sensitivity, and specificity of the classifier reached 91.02, 84.81, 80.56, and 88.37%, respectively.Conclusion: This study not only develops a promising classifier to recognize VCI in adult MMD in its early stage, but also implies the significance of time-varying properties in dynamic FC networks.

Multiview Feature Learning With Multiatlas-Based Functional Connectivity Networks for MCI Diagnosis.

Functional connectivity (FC) networks built from resting-state functional magnetic resonance imaging (rs-fMRI) has shown promising results for the diagnosis of Alzheimer's disease and its prodromal stage, that is, mild cognitive impairment (MCI). FC is usually estimated as a temporal correlation of regional mean rs-fMRI signals between any pair of brain regions, and these regions are traditionally parcellated with a particular brain atlas. Most existing studies have adopted a predefined brain atlas for all subjects. However, the constructed FC networks inevitably ignore the potentially important subject-specific information, particularly, the subject-specific brain parcellation. Similar to the drawback of the "single view" (versus the "multiview" learning) in medical image-based classification, FC networks constructed based on a single atlas may not be sufficient to reveal the underlying complicated differences between normal controls and disease-affected patients due to the potential bias from that particular atlas. In this study, we propose a multiview feature learning method with multiatlas-based FC networks to improve MCI diagnosis. Specifically, a three-step transformation is implemented to generate multiple individually specified atlases from the standard automated anatomical labeling template, from which a set of atlas exemplars is selected. Multiple FC networks are constructed based on these preselected atlas exemplars, providing multiple views of the FC network-based feature representations for each subject. We then devise a multitask learning algorithm for joint feature selection from the constructed multiple FC networks. The selected features are jointly fed into a support vector machine classifier for multiatlas-based MCI diagnosis. Extensive experimental comparisons are carried out between the proposed method and other competing approaches, including the traditional single-atlas-based method. The results indicate that our method significantly improves the MCI classification, demonstrating its promise in the brain connectome-based individualized diagnosis of brain diseases.

Patterns of cortical interactivity supporting speech production and lexical retrieval: A graph signal processing approach at the individual level

Abstract Although seemingly easy, speech production is a complex action involving several processes and brain regions and is often studied through the use of picture naming paradigms. Several brain regions have been identified as being involved in speech production and lexical retrieval, including several areas of the left lateral, ventral, and medial temporal cortex, and of the left lateral and medial prefrontal cortex (PFC). However, little is known about how these regions interact to allow us to produce and retrieve words so efficiently as we speak. In this study, we used graph signal processing, and in particular graph learning, to analyze intracranial electroencephalography data recorded directly at the cortical surface (i.e., electrocorticography, ECoG) in the blocked cyclic picture naming task (recently reported in Ries et al., 2017). In this task, pictures are named several times in semantically homogeneous (HOM) versus heterogeneous (HET) blocks. Lexical retrieval, and in particular our ability to select words from competing alternatives, is hampered in HOM vs. HET blocks with increasing repetitions of the pictures, an effect referred to as the semantic interference effect. The method we used can infer the connectivity between different brain regions from the recorded ECoG signals through an optimization process that considers the entire connectivity map instead of pair-wise methods such as more commonly used correlation measures. Our results show that distant left frontal and temporal brain regions as well as PFC regions are functionally connected in picture naming, and that connection strength is variable between pairs of brain regions and between participants. Semantic interference on naming latencies was not present in all participants and varied in terms of when naming latencies became slower in HOM versus HET blocks. Connection weights were generally sensitive to semantic context in the participants showing a semantic interference effect on behavior but in highly variable ways across participants and in different region pairs. In sum, our results are consistent with the hypotheses that left frontal and temporal regions are functionally connected during picture naming and that intra-frontal connections seem particularly important in this paradigm manipulating lexical retrieval difficulty. Further research is needed to explore the cortical interactions supporting lexical retrieval.

A meta-analytic approach to mapping co-occurrent grey matter volume increases and decreases in psychiatric disorders

Numerous studies have investigated grey matter (GM) volume changes in diverse patient groups. Reports of disorder-related GM reductions are common in such work, but many studies also report evidence for GM volume increases in patients. It is unclear whether these GM increases and decreases are independent or related in some way. Here, we address this question using a novel meta-analytic network mapping approach. We used a coordinate-based meta-analysis of 64 voxel-based morphometry studies of psychiatric disorders to calculate the probability of finding a GM increase or decrease in one region given an observed change in the opposite direction in another region. Estimating this co-occurrence probability for every pair of brain regions allowed us to build a network of concurrent GM changes of opposing polarity. Our analysis revealed that disorder-related GM increases and decreases are not independent; instead, a GM change in one area is often statistically related to a change of opposite polarity in other areas, highlighting distributed yet coordinated changes in GM volume as a function of brain pathology. Most regions showing GM changes linked to an opposite change in a distal area were located in salience, executive-control and default mode networks, as well as the thalamus and basal ganglia. Moreover, pairs of regions showing coupled changes of opposite polarity were more likely to belong to different canonical networks than to the same one. Our results suggest that regional GM alterations in psychiatric disorders are often accompanied by opposing changes in distal regions that belong to distinct functional networks.

Improved dynamic connection detection power in estimated dynamic functional connectivity considering multivariate dependencies between brain regions.

To estimate dynamic functional connectivity (dFC), the conventional method of sliding window correlation (SWC) suffers from poor performance of dynamic connection detection. This stems from the equal weighting of observations, suboptimal time scale, nonsparse output, and the fact that it is bivariate. To overcome these limitations, we exploited the kernel‐reweighted logistic regression (KELLER) algorithm, a method that is common in genetic studies, to estimate dFC in resting state functional magnetic resonance imaging (rs‐fMRI) data. KELLER can estimate dFC through estimating both spatial and temporal patterns of functional connectivity between brain regions. This paper compares the performance of the proposed KELLER method with current methods (SWC and tapered‐SWC (T‐SWC) with different window lengths) based on both simulated and real rs‐fMRI data. Estimated dFC networks were assessed for detecting dynamically connected brain region pairs with hypothesis testing. Simulation results revealed that KELLER can detect dynamic connections with a statistical power of 87.35% compared with 70.17% and 58.54% associated with T‐SWC (p‐value = .001) and SWC (p‐value <.001), respectively. Results of these different methods applied on real rs‐fMRI data were investigated for two aspects: calculating the similarity between identified mean dynamic pattern and identifying dynamic pattern in default mode network (DMN). In 68% of subjects, the results of T‐SWC with window length of 100 s, among different window lengths, demonstrated the highest similarity to those of KELLER. With regards to DMN, KELLER estimated previously reported dynamic connection pairs between dorsal and ventral DMN while SWC‐based method was unable to detect these dynamic connections.

Lorcaserin Alters Serotonin and Noradrenaline Tissue Content and Their Interaction With Dopamine in the Rat Brain.

Lorcaserin is a preferential serotonin2C receptor (5-HT2CR) agonist effective to treat obesity that has also recently been proposed to treat addiction and epilepsy. Central dopamine (DA) mechanisms are likely involved in the lorcaserin mechanism of action, but other monoamines 5-HT and noradrenaline (NA) contents or their interaction with DA might account for its effects. Here we showed that lorcaserin at 3, but not 0.3 mg/kg enhanced 5-HT content in the insular cortex, the core of the nucleus accumbens, and ventral hypothalamus. Without affecting the metabolite 5-hydroxy indole acetic acid, lorcaserin reduced the indirect index of 5-HT turnover in the hippocampus, substantia nigra, and habenula. Lorcaserin at 3 mg/kg increased NA content in the orbitofrontal cortex, the central amygdala (also at 0.3 mg/kg), the ventral hypothalamus, and the shell of the nucleus accumbens. A correlative analysis of the tissue contents between pairs of brain regions revealed that 0.3 mg/kg lorcaserin enhanced the number of correlations for 5-HT, its metabolism, and NA to a lower extent. The correlation profiles were very different between saline, 0.3 and 3 mg/kg lorcaserin. Lorcaserin enhanced the correlations established between NA or 5-HT at 0.3 and 3 mg/kg and reduced the number of correlations established between the index of the turnover for DA and 5-HT. These results show that lorcaserin modulates the biochemistry of NA and 5-HT systems in a subset of brain regions. Qualitatively, they reveal, oppositely to the DA changes, that lorcaserin at 0.3, but not 3 mg/kg, enhanced the number of correlations of 5-HT content between brain regions.

A Hierarchical Bayesian Mixture Model Approach for Analysis of Resting-State Functional Brain Connectivity: An Alternative to Thresholding.

This article proposes a Bayesian hierarchical mixture model to analyze functional brain connectivity where mixture components represent “positively connected” and “non-connected” brain regions. Such an approach provides a data-informed separation of reliable and spurious connections in contrast to arbitrary thresholding of a connectivity matrix. The hierarchical structure of the model allows simultaneous inferences for the entire population as well as for each individual subject. A new connectivity measure, the posterior probability of a given pair of brain regions of a specific subject to be connected given the observed correlation of regions' activity, can be computed from the model fit. The posterior probability reflects the connectivity of a pair of regions relative to the overall connectivity pattern of an individual, which is overlooked in traditional correlation analyses. This article demonstrates that using the posterior probability might diminish the effect of spurious connections on inferences, which is present when a correlation is used as a connectivity measure. In addition, simulation analyses reveal that the sparsification of the connectivity matrix using the posterior probabilities might outperform the absolute thresholding based on correlations. Therefore, we suggest that posterior probability might be a beneficial measure of connectivity compared with the correlation. The applicability of the introduced method is exemplified by a study of functional resting-state brain connectivity in older adults.

An Electroencephalography Connectomic Profile of Posttraumatic Stress Disorder.

The authors sought to identify brain regions whose frequency-specific, orthogonalized resting-state EEG power envelope connectivity differs between combat veterans with posttraumatic stress disorder (PTSD) and healthy combat-exposed veterans, and to determine the behavioral correlates of connectomic differences. The authors first conducted a connectivity method validation study in healthy control subjects (N=36). They then conducted a two-site case-control study of veterans with and without PTSD who were deployed to Iraq and/or Afghanistan. Healthy individuals (N=95) and those meeting full or subthreshold criteria for PTSD (N=106) underwent 64-channel resting EEG (eyes open and closed), which was then source-localized and orthogonalized to mitigate effects of volume conduction. Correlation coefficients between band-limited source-space power envelopes of different regions of interest were then calculated and corrected for multiple comparisons. Post hoc correlations of connectomic abnormalities with clinical features and performance on cognitive tasks were conducted to investigate the relevance of the dysconnectivity findings. Seventy-four brain region connections were significantly reduced in PTSD (all in the eyes-open condition and predominantly using the theta carrier frequency). Underconnectivity of the orbital and anterior middle frontal gyri were most prominent. Performance differences in the digit span task mapped onto connectivity between 25 of the 74 brain region pairs, including within-network connections in the dorsal attention, frontoparietal control, and ventral attention networks. Robust PTSD-related abnormalities were evident in theta-band source-space orthogonalized power envelope connectivity, which furthermore related to cognitive deficits in these patients. These findings establish a clinically relevant connectomic profile of PTSD using a tool that facilitates the lower-cost clinical translation of network connectivity research.

Functional Brain Network Learning Based on Spatial Similarity for Brain Disorders Identification

Functional brain network (FBN) measures based on functional magnetic resonance imaging (fMRI) data, has become important biomarkers for early diagnosis and prediction of clinical outcomes in neurological diseases, such as Alzheimer’s diseases (AD) and its prodromal state (i.e., Mild cognitive impairment, MCI). In the past decades, researchers have developed numbers of approaches for FBN estimation, including Pearson’s correction (PC), sparse representation (SR), and so on. Despite their popularity and wide applications in current studies, most of the approaches for FBN estimation only consider the dependency between the measured blood oxygen level dependent (BOLD) time series, but ignore the spatial relationships between pairs of brain regions. In practice, the strength of functional connection between brain regions will decrease as their distance increases. Inspired by this, we proposed a new approach for FBN estimation based on the assumption that the closer brain regions tend to share stronger relationships or similarities. To verify the effectiveness of the proposed method, we conduct experiments on a public dataset to identify the patients with MCIs from health controls (HCs) using the estimated FBNs. Experimental results demonstrate that the proposed approach yields statistically significant improvement in seven performance metrics over using the baseline methods.

Impaired cerebral blood flow in type 2 diabetes mellitus – A comparative study with subjective cognitive decline, vascular dementia and Alzheimer’s disease subjects

The link between non-demented type 2 diabetes mellitus (T2DM) and different types of cognitive impairment is controversial. By controlling for co-morbidities such as cerebral macrovascular and microvascular changes, cerebral atrophy, amyloid burden, hypertension or hyperlipidemia, the current study investigated the cerebral blood flow of T2DM individuals as compared to cognitively impaired subjects recruited from a memory clinic.15 healthy control (71.8 ± 6.1 years), 18 T2DM (62.5 ± 3.7 years), as well as 8 Subjective Cognitive Decline (69.5 ± 7.5 years), 12 Vascular Dementia (79.3 ± 4.2 years) and 17 Alzheimer’s Disease (75.1 ± 8.2 years) underwent multi-parametric MRI brain scanning. Subjects with T2DM and from the memory clinic also had 18-F Flutametamol PET-CT scanning to look for any amyloid burden. Pseudocontinuous Arterial Spin Labeling (PCASL), MR Angiography Head, 3D FLAIR and 3D T1-weighted sequences were used to quantify cerebral blood flow, cerebrovascular changes, white matter hyperintensities and brain atrophy respectively. Vascular risk factors were retrieved from the medical records. The 37 subjects from memory clinic were classified into subjective cognitive decline (SCD), vascular dementia (VD) and Alzheimer’s disease (AD) subgroups by a multi-disciplinary panel consisting of a neuroradiologist, and 2 geriatricians.Absolute cortical CBF in our cohort of T2DM, SCD, VD and AD was significantly decreased (p < 0.01) as compared to healthy controls (HC) in both whole brain and eight paired brain regions, after age, normalized grey matter volume and gender adjustment and Bonferroni correction.Subgroup analysis between T2DM, SCD, VD, and AD revealed that CBF of T2DM was not significantly different from AD, VD or SCD. By controlling for co-morbidities, impaired cortical CBF in T2DM was not related to microangiopathy or amyloid deposition, but to the interaction of triple risk factors (such as diabetes mellitus, hypertension, and hyperlipidemia).There was statistically significant negative correlation (p ≤ 0.05) between adjusted CBF and HbA1c in all brain regions of T2DM and HC (with partial correlation ranging from −0.30 to −0.46).Taken together, altered cerebral blood flow in T2DM might be related to disruption of cerebrovascular autoregulation related to vascular risk factors, and such oligemia occurred before clinical manifestation due to altered glycemic control.

Communicability distance reveals hidden patterns of Alzheimer's disease.

The communicability distance between pairs of regions in human brain is used as a quantitative proxy for studying Alzheimer’s disease. Using this distance, we obtain the shortest communicability path lengths between different regions of brain networks from patients with Alzheimer’s disease (AD) and healthy cohorts (HC). We show that the shortest communicability path length is significantly better than the shortest topological path length in distinguishing AD patients from HC. Based on this approach, we identify 399 pairs of brain regions for which there are very significant changes in the shortest communicability path length after AD appears. We find that 42% of these regions interconnect both brain hemispheres, 28% connect regions inside the left hemisphere only, and 20% affect vermis connection with brain hemispheres. These findings clearly agree with the disconnection syndrome hypothesis of AD. Finally, we show that in 76.9% of damaged brain regions the shortest communicability path length drops in AD in relation to HC. This counterintuitive finding indicates that AD transforms the brain network into a more efficient system from the perspective of the transmission of the disease, because it drops the circulability of the disease factor around the brain regions in relation to its transmissibility to other regions.

Predictive Models for Functional MRI Data

In this study, we analyze brain activity data describing functional magnetic resonance imaging (MRI) imaging of 820 subjects with each subject being scanned at 4 different times. This multiple scanning gives us an opportunity to observe the consistency of imaging characteristics within the subjects as compared to the variability across the subjects. The most consistent characteristics are then used for the purpose of predicting subjects’ traits. We concentrate on four predictive methods (Regression, Logistic Regression, Linear Discriminant Analysis and Random Forest) in order to predict subjects’ traits such as gender and age based on the brain activities observed between brain regions. Those predictions are done based on the adjusted communication activity among the brain regions, as assessed from 4 scans of each subject. Due to a large number of such communications among the 116 brain regions, we performed a preliminary selection of the most promising pairs of brain regions. Logistic Regression performed best in classifying the subject gender based on communication activity among the brain regions. The accuracy rate was 85.6 percent for an AIC step-wise selected Logistic Regression model. On the other hand, the Logistic Regression model maintaining the entire set of ranked predictor was capable of getting an 87.7 percent accuracy rate. It is interesting to point out that the model with the AIC selected features was better classifying males, whereas the complete ranked model was better classifying females. The Random Forest technique performed best for prediction of age (grouped within five categories as provided by the original data) with 48.8 percent accuracy rate. Any set of predictors between 200 and 1600 was presenting similar rates of accuracy.

Long-range connections are more severely damaged and relevant for cognition in multiple sclerosis.

An efficient network such as the human brain features a combination of global integration of information, driven by long-range connections, and local processing involving short-range connections. Whether these connections are equally damaged in multiple sclerosis is unknown, as is their relevance for cognitive impairment and brain function. Therefore, we cross-sectionally investigated the association between damage to short- and long-range connections with structural network efficiency, the functional connectome and cognition. From the Amsterdam multiple sclerosis cohort, 133 patients (age = 54.2 ± 9.6) with long-standing multiple sclerosis and 48 healthy controls (age = 50.8 ± 7.0) with neuropsychological testing and MRI were included. Structural connectivity was estimated from diffusion tensor images using probabilistic tractography (MRtrix 3.0) between pairs of brain regions. Structural connections were divided into short- (length < quartile 1) and long-range (length > quartile 3) connections, based on the mean distribution of tract lengths in healthy controls. To determine the severity of damage within these connections, (i) fractional anisotropy as a measure for integrity; (ii) total number of fibres; and (iii) percentage of tract affected by lesions were computed for each connecting tract and averaged for short- and long-range connections separately. To investigate the impact of damage in these connections for structural network efficiency, global efficiency was computed. Additionally, resting-state functional connectivity was computed between each pair of brain regions, after artefact removal with FMRIB's ICA-based X-noiseifier. The functional connectivity similarity index was computed by correlating individual functional connectivity matrices with an average healthy control connectivity matrix. Our results showed that the structural network had a reduced efficiency and integrity in multiple sclerosis relative to healthy controls (both P < 0.05). The long-range connections showed the largest reduction in fractional anisotropy (z = -1.03, P < 0.001) and total number of fibres (z = -0.44, P < 0.01), whereas in the short-range connections only fractional anisotropy was affected (z = -0.34, P = 0.03). Long-range connections also demonstrated a higher percentage of tract affected by lesions than short-range connections, independent of tract length (P < 0.001). Damage to long-range connections was more strongly related to structural network efficiency and cognition (fractional anisotropy: r = 0.329 and r = 0.447. number of fibres r = 0.321 and r = 0.278. and percentage of lesions: r = -0.219; r = -0.426, respectively) than damage to short-range connections. Only damage to long-distance connections correlated with a more abnormal functional network (fractional anisotropy: r = 0.226). Our findings indicate that long-range connections are more severely affected by multiple sclerosis-specific damage than short-range connections. Moreover compared to short-range connections, damage to long-range connections better explains network efficiency and cognition.

Age-associated reorganization of metabolic brain connectivity in Chinese children.

The human brain develops rapidly from infant to adolescent. Establishment of the brain developmental trajectory is important to understand cognition, behavior, and emotions, as well to evaluate the risk of neuropsychiatric disorders. 18F-FDG PET has been widely used to study brain glucose metabolism, but functional brain segregation and integration based on 18F-FDG PET remains largely unknown. Two hundred one Chinese child patients with extracranial malignancy were retrospectively enrolled as surrogates to healthy children. All images were spatially normalized into MNI space using pediatric brain template, and the 18F-FDG uptakes were calculated for 90 regions using AAL atlas. The group-level metabolic brain network was constructed by measuring Pearson correlation coefficients between each pair of brain regions in an inter-subject manner for infant (1 to 4years), childhood (5 to 8years), early adolescent (9 to 12years), and adolescent (13 to 18years) group, respectively. Global efficiency of each group was calculated, and the modular architectures were detected by a greedy algorithm. Both metabolic brain network connectivity and global efficiency increased with aging. Brain network was grouped into 4, 6, 4, and 4 modules from infant to adolescent, respectively. The modular architecture dramatically reorganized from childhood to early adolescent. The hubs spatiotemporally rewired. The ratio of the connector hub to the provincial hub increased from infant to early adolescent, but decreased during the adolescent period. The topological properties and modular reorganization of human brain network dramatically changed with age, especially from childhood to early adolescence. These findings would help understand the Chinese developmental trajectory of human brain functional integration and segregation.

Semiparametric Estimation of Task-Based Dynamic Functional Connectivity on the Population Level.

Dynamic functional connectivity (dFC) estimates time-dependent associations between pairs of brain region time series as typically acquired during functional MRI. dFC changes are most commonly quantified by pairwise correlation coefficients between the time series within a sliding window. Here, we applied a recently developed bootstrap-based technique (Kudela et al., 2017) to robustly estimate subject-level dFC and its confidence intervals in a task-based fMRI study (24 subjects who tasted their most frequently consumed beer and Gatorade as an appetitive control). We then combined information across subjects and scans utilizing semiparametric mixed models to obtain a group-level dFC estimate for each pair of brain regions, flavor, and the difference between flavors. The proposed approach relies on the estimated group-level dFC accounting for complex correlation structures of the fMRI data, multiple repeated observations per subject, experimental design, and subject-specific variability. It also provides condition-specific dFC and confidence intervals for the whole brain at the group level. As a summary dFC metric, we used the proportion of time when the estimated associations were either significantly positive or negative. For both flavors, our fully-data driven approach yielded regional associations that reflected known, biologically meaningful brain organization as shown in prior work, as well as closely resembled resting state networks (RSNs). Specifically, beer flavor-potentiated associations were detected between several reward-related regions, including the right ventral striatum (VST), lateral orbitofrontal cortex, and ventral anterior insular cortex (vAIC). The enhancement of right VST-vAIC association by a taste of beer independently validated the main activation-based finding (Oberlin et al., 2016). Most notably, our novel dFC methodology uncovered numerous associations undetected by the traditional static FC analysis. The data-driven, novel dFC methodology presented here can be used for a wide range of task-based fMRI designs to estimate the dFC at multiple levels—group-, individual-, and task-specific, utilizing a combination of well-established statistical methods.

Abnormal resting-state cerebral-limbic functional connectivity in bipolar depression and unipolar depression

BackgroundDistinctive patterns of functional connectivity (FC) abnormalities in neural circuitry has been reported in patients with bipolar depression (BD) and unipolar depression (UD). However, it is unclear that whether this distinct functional connectivity patterns are diagnosis specific between BD and UD. This study aimed to compare patterns of functional connectivity among BD, UD and healthy controls (HC) and determine the distinct functional connectivity patterns which can differentiate BD from UD.MethodTotally 23 BD, 22 UD, and 24 HC were recruited to undergo resting-state fMRI scanning. FC between each pair of brain regions was calculated and compared among the three groups, the associations of FC with depressive symptom were also analyzed.ResultsBoth patient groups showed significantly decreased cerebral-limbic FC located between the default mode network [posterior cingulated gyrus (PCG) and precuneus] and limbic regions (hippocampus, amygdala and thalamus) than HC. Moreover, the BD group exhibited more decreased FC mainly in the cortical regions (middle temporal gyrus, PCG, medial superior frontal gyrus, inferior occipital gyrus and superior temporal gyrus), but the UD group is more associated with limbic alterations. These decreased FCs were negatively correlated with HAMD scores in both BD and UD patients.ConclusionsBD and UD patients demonstrate different patterns of abnormal cerebral-limbic FC, reflected by decreased FC within cerebral cortex and limbic regions in BD and UD, respectively. The distinct FC abnormal pattern of the cerebral-limbic circuit might be applied as biomarkers to differentiate these two depressive patient groups.