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Background : Functional specialization is a feature of human brain for understanding the pathophysiology of major depressive disorder (MDD). The degree of human specialization refers to within and cross hemispheric interactions. However, most previous studies only focused on interhemispheric connectivity in MDD, and the results varied across studies. Hence, brain functional connectivity asymmetry in MDD should be further studied. Methods : Resting-state fMRI data of 753 patients with MDD and 451 healthy controls were provided by REST-meta-MDD Project. Twenty-five project contributors preprocessed their data locally with the Data Processing Assistant State fMRI software and shared final indices. The parameter of asymmetry (PAS), a novel voxel-based whole-brain quantitative measure that reflects inter- and intrahemispheric asymmetry, was reported. We also examined the effects of age, sex and clinical variables (including symptom severity, illness duration and three depressive phenotypes). Results : Compared with healthy controls, patients with MDD showed increased PAS scores (decreased hemispheric specialization) in most of the areas of default mode network, control network, attention network and some regions in the cerebellum and visual cortex. Demographic characteristics and clinical variables have significant effects on these abnormalities. Limitations : Although a large sample size could improve statistical power, future independent efforts are needed to confirm our results. Conclusions : Our results highlight the idea that many brain networks contribute to broad clinical pathophysiology of MDD, and indicate that a lateralized, efficient and economical brain information processing system is disrupted in MDD. These findings may help comprehensively clarify the pathophysiology of MDD in a new hemispheric specialization perspective.

Background: Depression has been a common mental health problem during the COVID-19 epidemic. From a network perspective, depression can be conceptualized as the result of mutual interactions among individual symptoms, an approach that may elucidate the structure and mechanisms underlying this disorder. This study aimed to examine the structure of depression among residents in Wuhan, the epicenter of the COVID-19 outbreak in China, in the later stage of the COVID-19 pandemic.Methods: A total of 2,515 participants were recruited from the community via snowball sampling. The Patient Health Questionnaire was used to assess self-reported depressive symptoms with the QuestionnaireStar program. The network structure and relevant centrality indices of depression were examined in this sample.Results: Network analysis revealed Fatigue, Sad mood, Guilt and Motor disturbances as the most central symptoms, while Suicide and Sleep problems had the lowest centrality. No significant differences were found between women and men regarding network structure (maximum difference = 0.11, p = 0.44) and global strength (global strength difference = 0.04; female vs. male: 3.78 vs. 3.83, p = 0.51), a finding that suggests there are no gender differences in the structure or centrality of depressive symptoms.Limitations: Due to the cross-sectional study design, causal relationships between these depressive symptoms or dynamic changes in networks over time could not be established.Conclusions: Fatigue, Sad mood, Guilt, and Motor disturbances should be prioritized as targets in interventions and prevention efforts to reduce depression among residents in Wuhan, in the later stage of the COVID-19 pandemic.

Thousands of resting state functional magnetic resonance imaging (RS-fMRI) articles have been published on brain disorders. For precise localization of abnormal brain activity, a voxel-level comparison is needed. Because of the large number of voxels in the brain, multiple comparison correction (MCC) must be performed to reduce false positive rates, and a smaller P value (usually including either liberal or stringent MCC) is widely recommended. The study suggests that a stringent MCC may reduce the number of false positive results and that the brain regions surviving MCC are true positive results and thus can improve the reproducibility between studies. However, determining the clusters that represent true positives is difficult because ground truths have not been established for many brain disorders that do not present visible structural abnormalities, e.g., Parkinson's disease (PD) and many psychiatric disorders. Meta-analysis provides robust results that can be used to investigate reproducibility across studies. However, most existing neuroimaging meta-analytic articles are based on only a few peak coordinates reported in the original articles, namely coordinate-based meta-analysis (CB-meta). The current REST-meta-PD study included raw RS-fMRI data from 15 cohorts of PD patients and performed a meta-analysis of the amplitude of low frequency fluctuations (ALFF). We used the robustness results of the meta-analysis to test whether liberal or stringent MCC could increase reproducibility and reduce false positive rates.

Volitional eye closure is observed only in conscious and awake humans, and is rare in animals. It is believed that eye closure can focus one's attention inward and facilitate activities such as meditation and mental imagery. Congenital blind individuals are also required to close their eyes for these activities. Resting-state functional magnetic resonance imaging (RS-fMRI) studies have found robust differences between the eyes-closed (EC) and eyes-open (EO) conditions in some brain regions in the sighted. This study analyzed data from 21 congenital blind individuals and 21 sighted controls by using amplitude of low-frequency fluctuation (ALFF) of RS-fMRI. The blind group and the sighted group shared similar pattern of differences between the EC and EO condition: ALFF was higher in the EC condition than the EO condition in the bilateral primary sensorimotor cortex, bilateral supplementary motor area, and inferior occipital cortex, while ALFF was lower in the EC condition than the EO condition in the medial prefrontal cortex, highlighting the “nature” effect on the difference between the EC and EO conditions. The results of other matrices such as fractional ALFF (fALFF) and regional homogeneity (ReHo) showed similar patterns to that of ALFF. Moreover, no significant difference was observed between the EC-EO pattern of the two subgroups of congenital blind (i.e., with and without light perception), suggesting that the EC-EO difference is irrespective of residual light perception which reinforced the “nature” effect. We also found between-group differences, i.e., more probably “nurture effect”, in the posterior insula and fusiform. Our results suggest that the acts of closing and opening the eyes are of importance for the congenital blind, and that these actions and their differences might be inherent in the nature of humans.

Background and Objectives: Asymmetric onset of motor symptoms in PD can affect cognitive function. We examined whether motor-symptom laterality could affect feedback-based associative learning and explored its underlying neural mechanism by functional magnetic resonance imaging in PD patients. Methods: We recruited 63 early-stage medication-naive PD patients (29 left-onset medication-naive patients, 34 right-onset medication-naive patients) and 38 matched normal controls. Subjects completed an acquired equivalence task (including acquisition, retention, and generalization) and resting-state functional magnetic resonance imaging scans. Learning accuracy and response time in each phase of the task were recorded for behavioral measures. Regional homogeneity was used to analyze resting-state functional magnetic resonance imaging data, with regional homogeneity lateralization to evaluate hemispheric functional asymmetry in the striatum. Results: Left-onset patients made significantly more errors in acquisition (feedback-based associative learning) than right-onset patients and normal controls, whereas right-onset patients performed as well as normal controls. There was no significant difference among these three groups in the accuracy of either retention or generalization phase. The three groups did not show significant differences in response time. In the left-onset group, there was an inverse relationship between acquisition errors and regional homogeneity in the right dorsal rostral putamen. There were no significant regional homogeneity changes in either the left or the right dorsal rostral putamen in right-onset patients when compared to controls. Conclusions: Motor-symptom laterality could affect feedback-based associative learning in PD, with left-onset medication-naive patients being selectively impaired. Dysfunction in the right dorsal rostral putamen may underlie the observed deficit in associative learning in patients with left-sided onset.© 2016 International Parkinson and Movement Disorder Society

Cognitive-coping therapy (CCT), integrating cognitive theory with stress-coping theory, is an efficacious therapy for obsessive-compulsive disorder (OCD). However, the potential brain mediation for the effectiveness remains unclear. We sought to investigate differences of resting-state brain function between OCD and healthy controls and if such differences would be changed by a four-week CCT.Thirty-one OCD patients were recruited and randomized into CCT (n=15) and pharmacotherapy plus CCT (pCCT, n=16) groups, together with 25 age-, gender- and education-matched healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was scored to evaluate the severity in symptoms. Resting-state functional magnetic resonance imaging was scanned pre- and post-treatment.For patients, Y-BOCS scores were reduced during four-week treatment for CCT and pCCT (P0.001), but no group difference was observed. No differences in amplitude of low-frequency fluctuation (ALFF) values were found between CCT and pCCT either pre- or post-treatment. Compared to controls, ALFF in OCD patients was higher in the left hippocampus, parahippocampus, and temporal lobes, but lower in the right orbitofrontal cortex, rectus, bilateral calcarine, cuneus, lingual, occipital, left parietal, postcentral, precentral, and parietal (corrected P0.05). The ALFF in those regions was not significantly correlated to the severity of OCD symptoms. After a 4-week treatment, the ALFF differences between OCD patients and controls disappeared.The pharmacotherapy group was not included since OCD patients generally do not respond to pharmacotherapy in four weeks.Our data indicated that resting-state brain function was different between OCD and controls; such differences disappeared after OCD symptoms were relieved.

Many studies have shown abnormal functional connectivity in children with attention deficit hyperactivity disorder (ADHD) by using resting-state functional magnetic resonance imaging (rs-fMRI). However, few studies illustrated that to what extent these findings were consistent across different datasets. The present study aimed to assess the consistency of abnormal functional connectivity in children with ADHD across the four datasets from a public-assess rs-fMRI ADHD cohort, namely, ADHD-200. We employed the identical analysis process of previous studies and examined a few factors, including connectivity with the seed regions of the bilateral dorsal anterior cingulate cortex, bilateral inferior frontal gyrus, and bilateral middle frontal gyrus; connectivity between default mode network and executive control network; stringent and lenient statistical thresholds; and the ADHD subtypes. Our results revealed a high inconsistency of abnormal seed-based connectivity in children with ADHD across all datasets, even across three datasets from the same research site. This inconsistency could also be observed with a lenient statistical threshold. Besides, each dataset did not show abnormal connectivity between default mode network and executive control network for ADHD, albeit this abnormal connectivity between networks was intensively reported in previous studies. Importantly, the ADHD combined subtype showed greater consistency than did the inattention subtype. These findings provided methodological insights into the studies on spontaneous brain activity of ADHD, and the ADHD subtypes deserve more attention in future studies.

Objective: This study evaluated the functional networks of amygdala subregions (basolateral [BLA], centromedial [CMA], and superficial amygdala [SFA]) in ADHD and their association with emotional lability (EL) symptoms. Method: Resting-state functional connectivity (RSFC) of amygdala subregions and their correlations with EL scores were evaluated in 35 drug-naïve boys with ADHD and 30 age-matched healthy controls (HC). Results: Compared with HC, altered RSFC were detected differently for each amygdala subregion in ADHD: altered RSFC of BLA with the thalamus and vermis; aberrant RSFC of CMA with the superior temporal gyrus/pole and insula, precuneus and cerebellum; reduced RSFC of SFA with dorsal frontoparietal cortices. Within ADHD, higher EL scores were associated with reduced negative RSFC of SFA with the dorsolateral prefrontal cortex and inferior parietal lobe. Conclusion: Diffuse alterations of amygdala subregion-based networks are associated with ADHD, and the weaker SFA–frontoparietal networks might be involved in the hypothesized top–down effortful regulation of emotion.

Background: Major Depressive Disorder (MDD) is common and disabling, but its neural pathophysiology remains unclear. Functional brain network studies in MDD have largely had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. Methods: The 25 research groups in China composing the REST-meta-MDD Project contributed R-fMRI data of 1,300 patients with MDD and 1,128 normal controls (NCs). The data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to show increased FC in MDD. Outcomes: We found decreased instead of increased DMN FC in MDD compared to NCs. We found FC reduction only in recurrent MDD, not in first-episode drug-naive MDD. Decreased DMN FC was associated with medication usage but not with MDD duration or severity. Exploratory analyses also revealed alterations of local intrinsic activity in MDD. Interpretation: We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates treatment response. All the R-fMRI indices have been made publicly available via the R-fMRI Maps Project. The REST-meta-MDD model can be generalized to longitudinal MDD studies and to other psychiatric disorders. Funding Statement: This work was supported by the National Key R&D Program of China (2017YFC1309902), the National Natural Science Foundation of China (81671774, 81630031 and 81371488), the Hundred Talents Program of the Chinese Academy of Sciences, Beijing Municipal Science & Technology Commission (Z161100000216152 and Z171100000117016), Department of Science and Technology, Zhejiang Province (2015C03037). Declaration of Interests: All the authors declare no competing financial interests. Ethics Approval Statement: All contributed data were from studies approved by local Institutional Review Boards. Data submitted to the consortium were fully deidentified and anonymized.

Highlights • Gray matter density asymmetry in the dACC is region-specific in children. • Superior dACC has greater connectivity with right control/left default network. • Inferior dACC has greater connectivity with right visual and default network. • Boys are more lateralized in ipsilateral connectivity with visual cortex than girls. • Boys and girls differ in age-related laterality changes of dACC connectivity., We aimed to elucidate the dACC laterality in typically developing children and their sex/age-related differences with a sample of 84 right-handed children (6–16 years, 42 boys). We first replicated the previous finding observed in adults that gray matter density asymmetry in the dACC was region-specific: leftward (left > right) in its superior part, rightward (left

This work examines the effect of midazolam‐induced light sedation on intrinsic functional connectivity of human brain, using a randomized, double‐blind, placebo‐controlled, cross‐over, within‐subject design. Fourteen healthy young subjects were enrolled and midazolam (0.03 mg/kg of the participant's body mass, to a maximum of 2.5 mg) or saline were administrated with an interval of one week. Resting‐state fMRI was conducted before and after administration for each subject. We focus on two types of networks: sensory related lower‐level functional networks and higher‐order functions related ones. Independent component analysis (ICA) was used to identify these resting‐state functional networks. We hypothesize that the sensory (visual, auditory, and sensorimotor) related networks will be intact under midazolam‐induced light sedation while the higher‐order (default mode, executive control, salience networks, etc.) networks will be functionally disconnected. It was found that the functional integrity of the lower‐level networks was maintained, while that of the higher‐level networks was significantly disrupted by light sedation. The within‐network connectivity of the two types of networks was differently affected in terms of direction and extent. These findings provide direct evidence that higher‐order cognitive functions including memory, attention, executive function, and language were impaired prior to lower‐level sensory responses during sedation. Our result also lends support to the information integration model of consciousness. Hum Brain Mapp 36:4247–4261, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Benign epilepsy with centrotemporal spikes (BECTS) is often associated with neural circuit dysfunction, particularly during the transient active state characterized by interictal epileptiform discharges (IEDs). Little is known, however, about the functional neural circuit abnormalities in BECTS without IEDs, or if such abnormalities could be used to differentiate BECTS patients without IEDs from healthy controls (HCs) for early diagnosis. To this end, we conducted resting-state functional magnetic resonance imaging (RS-fMRI) and simultaneous Electroencephalogram (EEG) in children with BECTS (n = 43) and age-matched HC (n = 28). The simultaneous EEG recordings distinguished BECTS with IEDs (n = 20) from without IEDs (n = 23). Intrinsic brain activity was measured in all three groups using the amplitude of low frequency fluctuation at rest. Compared to HC, BECTS patients with IEDs exhibited an intrinsic activity abnormality in the thalamus, suggesting that thalamic dysfunction could contribute to IED emergence while patients without IEDs exhibited intrinsic activity abnormalities in middle frontal gyrus and superior parietal gyrus. Using multivariate pattern classification analysis, we were able to differentiate BECTS without IEDs from HCs with 88.23% accuracy. BECTS without epileptic transients can be distinguished from HC and BECTS with IEDs by unique regional abnormalities in resting brain activity. Both transient abnormalities as reflected by IEDs and chronic abnormalities as reflected by RS-fMRI may contribute to BECTS development and expression. Intrinsic brain activity and multivariate pattern classification techniques are promising tools to diagnose and differentiate BECTS syndromes. Hum Brain Mapp 36:3878-3889, 2015. © 2015 Wiley Periodicals, Inc.

Many papers have shown results from the multi-site dataset of resting-state fMRI (rs-fMRI) in attention deficit hyperactivity disorder (ADHD), a data-sharing project named ADHD-200. However, few studies have illustrated that to what extent the pooled findings were consistent across cohorts. The present study analyzed three voxel-wise whole-brain metrics, i.e., amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) based on the pooled dataset as well as individual cohort of ADHD-200. In addition to the conventional frequency band of 0.01–0.08 Hz, sub-frequency bands of 0–0.01, 0.01–0.027, 0.027–0.073, 0.073–0.198, and 0.198–0.25 Hz, were assessed. While the pooled dataset showed abnormal activity in some brain regions, e.g., the bilateral sensorimotor cortices, bilateral cerebellum, and the bilateral lingual gyrus, these results were highly inconsistent across cohorts, even across the three cohorts from the same research center. The standardized effect size was rather small. These findings suggested a high heterogeneity of spontaneous brain activity in ADHD. Future studies based on multi-site large-sample dataset should be performed on pooled data and single cohort data, respectively and the effect size must be shown.

Physical exercise can improve physical and mental health. A number of imaging studies have examined the role of neuroplasticity in improving cognition with physical exercise; however, such neuroplasticity changes are not consistent across the reports partly due to small sample sizes in some studies. We thought to explore the concept that identifying consistent findings across multi-modality imaging measures would provide relatively reliable results. We designed a 6-week quasi-experiment with Wii-fitness exercise program in 24 healthy adults older than 60, and then examined the changes on neuroimaging measures including brain volume, the amplitude of low-frequency oscillation function (ALFF), regional homogeneity (ReHo), seed-based functional connectivity (FC), and the global efficiency of nodal connectivity during resting state. We focused on whether there were common regions showing changes after exercise across these measures and which measure was closely correlated with cognitive improvement. After the six-week exercise program, participants demonstrated a significant improvement in memory and executive function on neuropsychological tests, and in memory recall on an emotional memory task. The common brain regions that showed significant changes across different measures were the right striatum and the posterior cingulate (PCC). After exercise, the PCC showed decreased ReHo and increased volume, and the striatum did not show volume loss as the control group did and increased its FC with the cingulate, temporal, parietal, and occipital regions. Moreover, the connectivity change between the striatum and the thalamus was correlated with the improvement of executive function. This result implicates the striatum and the PCC associated network in physical exercise. Our work highlights the effectiveness of multi-modality neuroimaging measures in investigating neuroplasticity.

Objective:Few studies have investigated verbal working memory-related functional connectivity patterns in participants with attention-deficit/hyperactivity disorder (ADHD). Thus, we aimed to compare working memory-related functional connectivity patterns in healthy children and those with ADHD, and study effects of methylphenidate (MPH).Method:Twenty-two boys with ADHD were scanned twice, under either MPH (single dose, 10 mg) or placebo, in a randomised, cross-over, counterbalanced placebo-controlled design. Thirty healthy boys were scanned once. We used fMRI during a numerical n-back task to examine functional connectivity patterns in case-control and MPH-placebo comparisons, using independent component analysis.Results:There was no significant difference in behavioural performance between children with ADHD, treated with MPH or placebo, and healthy controls. Compared with controls, participants with ADHD under placebo showed increased functional connectivity within fronto-parietal and auditory networks, and decreased functional connectivity within the executive control network. MPH normalized the altered functional connectivity pattern and significantly enhanced functional connectivity within the executive control network, though in non-overlapping areas.Conclusion:Our study contributes to the identification of the neural substrates of working memory. Single dose of MPH normalized the altered brain functional connectivity network, but had no enhancing effect on (non-impaired) behavioural performance.

Objective Increased levels of reaction time variability (RTV) are characteristics of sustained attention deficits. The clinical significance of RTV has been widely recognized. However, the reliability of RTV measurements has not been widely studied. The present study aimed to assess the test-retest reliability of RTV conventional measurements, e.g., the standard deviation (SD), the coefficient of variation (CV), and a new measurement called the amplitude of low frequency fluctuation (ALFF) of RT. In addition, we aimed to assess differences and similarities of these measurements between different tasks. Method Thirty-seven healthy college students participated in 2 tasks, i.e., an Eriksen flanker task (EFT) and a simple reaction task (SRT), twice over a mean interval of 56 days. Conventional measurements of RTV including RT-SD and RT-CV were assessed first. Then the RT time series were converted into frequency domains, and RT-ALFF was further calculated for the whole frequency band (0.0023–0.167 Hz) and for a few sub-frequency bands including Slow-6 (

Opening and closing the eyes are fundamental behaviors for directing attention to the external versus internal world. However, it remains unclear whether the states of eyes-open (EO) relative to eyes-closed (EC) are associated with different topological organizations of functional neural networks for exteroceptive and interoceptive processing (processing the external world and internal state, respectively). Here, we used resting-state functional magnetic resonance imaging and neural network analysis to investigate the topological properties of functional networks of the human brain when the eyes were open versus closed. The brain networks exhibited higher cliquishness and local efficiency, but lower global efficiency during the EO state compared to the EC state. These properties suggest an increase in specialized information processing along with a decrease in integrated information processing in EO (vs. EC). More importantly, the "exteroceptive" network, including the attentional system (e.g., superior parietal gyrus and inferior parietal lobule), ocular motor system (e.g., precentral gyrus and superior frontal gyrus), and arousal system (e.g., insula and thalamus), showed higher regional nodal properties (nodal degree, efficiency and betweenness centrality) in EO relative to EC. In contrast, the "interoceptive" network, composed of visual system (e.g., lingual gyrus, fusiform gyrus and cuneus), auditory system (e.g., Heschl's gyurs), somatosensory system (e.g., postcentral gyrus), and part of the default mode network (e.g., angular gyrus and anterior cingulate gyrus), showed significantly higher regional properties in EC vs. EO. In addition, the connections across sensory modalities were altered by volitional eye opening. The synchronicity between the visual system and the motor, somatosensory and auditory systems, characteristic of EC, was attenuated in EO. Further, the connections between the visual system and the attention, arousal and subcortical systems were increased in EO. These results may indicate that EO leads to a suppression of sensory modalities (other than visual) to allocate resources to exteroceptive processing. Our findings suggest that the topological organization of human brain networks dynamically switches corresponding to the information processing modes as we open or close our eyes. (C) 2014 Published by Elsevier Inc.

Resting-state functional MRI (R-fMRI) has emerged as a promising neuroimaging technique used to identify global hubs of the human brain functional connectome. However, most R-fMRI studies on functional hubs mainly utilize traditional R-fMRI data with relatively low sampling rates (e.g., repetition time [TR]=2 s). R-fMRI data scanned with higher sampling rates are important for the characterization of reliable functional connectomes because they can provide temporally complementary information about functional integration among brain regions and simultaneously reduce the effects of high frequency physiological noise. Here, we employed a publicly available multiband R-fMRI dataset with a sub-second sampling rate (TR=645 ms) to identify global hubs in the human voxel-wise functional networks, and further examined their test-retest (TRT) reliability over scanning time. We showed that the functional hubs of human brain networks were mainly located at the default-mode regions (e.g., medial prefrontal and parietal cortex as well as the lateral parietal and temporal cortex) and the sensorimotor and visual cortex. These hub regions were highly anatomically distance-dependent, where short-range and long-range hubs were primarily located at the primary cortex and the multimodal association cortex, respectively. We found that most functional hubs exhibited fair to good TRT reliability using intraclass correlation coefficients. Interestingly, our analysis suggested that a 6-minute scan duration was able to reliably detect these functional hubs. Further comparison analysis revealed that these results were approximately consistent with those obtained using traditional R-fMRI scans of the same subjects with TR=2500 ms, but several regions (e.g., lateral frontal cortex, paracentral lobule and anterior temporal lobe) exhibited different TRT reliability. Finally, we showed that several regions (including the medial/lateral prefrontal cortex and lateral temporal cortex) were identified as brain hubs in a high frequency band (0.2-0.3 Hz), which is beyond the frequency scope of traditional R-fMRI scans. Our results demonstrated the validity of multiband R-fMRI data to reliably detect functional hubs in the voxel-wise whole-brain networks, which motivated the acquisition of high temporal resolution R-fMRI data for the studies of human brain functional connectomes in healthy and diseased conditions.

As researchers increase their efforts to characterize variations in the functional connectome across studies and individuals, concerns about the many sources of nuisance variation present and their impact on resting state fMRI (R-fMRI) measures continue to grow. Although substantial within-site variation can exist efforts to aggregate data across multiple sites such as the 1000 Functional Connectomes Project (FCP) and International Neuroimaging Data-sharing Initiative (INDI) datasets amplify these concerns. The present work draws upon standardization approaches commonly used in the microarray gene expression literature, and to a lesser extent recent imaging studies, and compares them with respect to their impact on relationships between common R-fMRI measures and nuisance variables (e.g., imaging site, motion), as well as phenotypic variables of interest (age, sex). Standardization approaches differed with regard to whether they were applied post-hoc vs. during pre-processing, and at the individual vs. group level; additionally they varied in whether they addressed additive effects vs. additive + multiplicative effects, and were parametric vs. non-parametric. While all standardization approaches were effective at reducing undesirable relationships with nuisance variables, post-hoc approaches were generally more effective than global signal regression (GSR). Across approaches, correction for additive effects (global mean) appeared to be more important than for multiplicative effects (global SD) for all R-fMRI measures, with the exception of amplitude of low frequency fluctuations (ALFF). Group-level post-hoc standardizations for mean-centering and variance-standardization were found to be advantageous in their ability to avoid the introduction of artifactual relationships with standardization parameters; though results between individual and group-level post-hoc approaches were highly similar overall. While post-hoc standardization procedures drastically increased test-retest (TRT) reliability for ALFF, modest reductions were observed for other measures after post-hoc standardizations a phenomena likely attributable to the separation of voxel-wise from global differences among subjects (global mean and SD demonstrated moderate TRT reliability for these measures). Finally, the present work calls into question previous observations of increased anatomical specificity for GSR over mean centering, and draws attention to the near equivalence of global and gray matter signal regression. (C) 2013 Elsevier Inc. All rights reserved.

Regional homogeneity (ReHo) and the amplitude of low-frequency fluctuation (ALFF) are two approaches to depicting different regional characteristics of resting-state functional magnetic resonance imaging (RS-fMRI) data. Whether they can complementarily reveal brain regional functional abnormalities in attention-deficit/hyperactivity disorder (ADHD) remains unknown. In this study, we applied ReHo and ALFF to 23 medication-naïve boys diagnosed with ADHD and 25 age-matched healthy male controls using whole-brain voxel-wise analysis. Correlation analyses were conducted in the ADHD group to investigate the relationship between the regional spontaneous brain activity measured by the two approaches and the clinical symptoms of ADHD. We found that the ReHo method showed widely-distributed differences between the two groups in the fronto-cingulo-occipito-cerebellar circuitry, while the ALFF method showed a difference only in the right occipital area. When a larger smoothing kernel and a more lenient threshold were used for ALFF, more overlapped regions were found between ALFF and ReHo, and ALFF even found some new regions with group differences. The ADHD symptom scores were correlated with the ReHo values in the right cerebellum, dorsal anterior cingulate cortex and left lingual gyrus in the ADHD group, while no correlation was detected between ALFF and ADHD symptoms. In conclusion, ReHo may be more sensitive to regional abnormalities, at least in boys with ADHD, than ALFF. And ALFF may be complementary to ReHo in measuring local spontaneous activity. Combination of the two may yield a more comprehensive pathophy-siological framework for ADHD.

Attention-deficit/hyperactivity disorder (ADHD), which is characterized by core symptoms of inattention and hyperactivity/impulsivity, is one of the most common neurodevelopmental disorders of childhood. Neuroimaging studies have suggested that these behavioral disturbances are associated with abnormal functional connectivity among brain regions. However, the alterations in the structural connections that underlie these behavioral and functional deficits remain poorly understood. Here, we used diffusion magnetic resonance imaging and probabilistic tractography method to examine whole-brain white matter (WM) structural connectivity in 30 drug-naive boys with ADHD and 30 healthy controls. The WM networks of the human brain were constructed by estimating inter-regional connectivity probability. The topological properties of the resultant networks (e.g., small-world and network efficiency) were then analyzed using graph theoretical approaches. Nonparametric permutation tests were applied for between-group comparisons of these graphic metrics. We found that both the ADHD and control groups showed an efficient small-world organization in the whole-brain WM networks, suggesting a balance between structurally segregated and integrated connectivity patterns. However, relative to controls, patients with ADHD exhibited decreased global efficiency and increased shortest path length, with the most pronounced efficiency decreases in the left parietal, frontal, and occipital cortices. Intriguingly, the ADHD group showed decreased structural connectivity in the prefrontal-dominant circuitry and increased connectivity in the orbitofrontal-striatal circuitry, and these changes significantly correlated with the inattention and hyperactivity/impulsivity symptoms, respectively. The present study shows disrupted topological organization of large-scale WM networks in ADHD, extending our understanding of how structural disruptions of neuronal circuits underlie behavioral disturbances in patients with ADHD.

The pathophysiological changes before the presentation of clinical symptoms in parkinsonism are unclear. In this study, we investigated neural network modulations in persons in the preclinical stage of familial parkinsonism, and how the network interactions change at the clinical stage.We performed functional MRI in a family with SCA2 mutation, including 9 asymptomatic carriers and 10 mutation carriers with parkinsonian symptoms. Functional connectivity from the posterior putamen bilaterally and rostral supplementary motor area was used to explore network interactions in the subjects.Both the asymptomatic carriers and patients had decreased connectivity within the basal ganglia-thalamus-cortical motor loop compared to controls. The asymptomatic carriers showed extensively increased connectivity compared to controls, including the cortico-cortical motor, cortico-cerebellar, cortico-brainstem, and part of the basal ganglia-thalamus-cortical motor circuits. In contrast, the connectivity of most of these networks was decreased in the patients. These abnormalities were relatively normalized after levodopa administration.In the preclinical stage of SCA2 parkinsonism, the connectivity of a part of the basal ganglia motor loop is weakened as a consequence of dopaminergic deficits; meanwhile, the connectivity of other large-scale brain networks is strengthened presumably to compensate for the dysfunction of the basal ganglia to maintain brain function in the early stage of dopaminergic deficits. The simultaneous effects of progressive disruption of basal ganglia motor circuits and failure of compensatory mechanisms as dopaminergic dysfunction progresses may contribute to the onset of clinical symptoms.

Methylphenidate (MPH) is one of the most commonly used stimulants for the treatment of attention deficit hyperactivity disorder (ADHD). Although several studies have evaluated the effects of MPH on human brain activation during specific cognitive tasks using functional magnetic resonance imaging (fMRI), few studies have focused on spontaneous brain activity. In the current study, we investigated the effect of MPH on the intra-regional synchronization of spontaneous brain activity during the resting state in 18 normal adult males. A handedness questionnaire and the Wechsler Adult Intelligence Scale were applied before medication, and a resting-state fMRI scan was obtained 1 h after medication (20 mg MPH or placebo, order counterbalanced between participants). We demonstrated that: (1) there were no significant differences in the performance of behavioral tasks between the MPH and placebo groups; (2) the left middle and superior temporal gyri had stronger MPHrelated regional homogeneity (ReHo); and (3) the left lingual gyrus had weaker MPH-related ReHo. Our findings showed that the ReHo in some brain areas changes with MPH compared to placebo in normal adults, even though there are no behavioral differences. This method can be applied to patients with mental illness who may be treated with MPH, and be used to compare the difference between patients taking MPH and normal participants, to help reveal the mechanism of how MPH works.

Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with ‘pure’ TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients’ bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and limbic networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, medial temporal lobe, and brain stem). Transcranial magnetic stimulation sites defined by previous studies (“hand knob” area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS.

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.

The changes of spontaneous activity from before and after a memory or learning task had been considered to be related to off-line memory consolidation process in human brain by using resting-state functional connectivity (RSFC) MRI (fMRI). However, RSFC reflects temporal synchronization of timecourses of spatially distinct brain regions and therefore could not determine which specific brain region is involved in the memory consolidation process. Here we used regional homogeneity (ReHo), a method for measuring local synchronization, to link the local spontaneous activity change to off-line episodic memory consolidation. We hypothesized that the spontaneous activity change would be different between people with better memory performance and those with worse performance in memory-related regions. All participants completed two resting-state sessions, that is, before (REST-1) and after (REST-2) an episodic memory encoding task (picture indoor or outdoor judgment). Then, based on the d' of a later surprise memory retrieval test, a high-performance group and a low-performance group, each consisting of 16 participants, were chosen from whole 58 participants. We defined a ReHo ratio, that is, ReHo of REST-2 divided by ReHo of REST-1, as a change induced by memory consolidation. The high-performance group showed a significant higher ReHo ratio than low-performance group in medial temporal lobe (MTL) including parahippocampal and anterior temporal regions. The current results provide neuroimaging evidence supporting that the MTL is involved in off-line memory consolidation of episodic memory. Moreover, this study may provide a paradigm for understanding of episodic memory deficit in Alzheimer's disease.

The dorsal anterior cingulate cortex (dACC) has been consistently implicated in cognitive control processes. Many studies have found higher fractional anisotropy (FA) in the left anterior cingulum bundle (aCB) than in the right. However, the asymmetry of gray matter density (GMD) is not clear. Using multiple modalities of MRI, we investigated both FA and GMD in the dACC in two independent groups of healthy participants (50 per group, 18–24 years old, half males and half females). Consistent with previous findings, the mean FA of the left aCB was significantly higher than that of the right. Males showed higher FA in the bilateral aCB than females. Voxel-based analysis of GMD in the dACC presented a region-specific significant asymmetry: right > left in the lower part (around callosal sulcus) but left > right in the upper part (around cingulate sulcus). No significant sex effect was found for GMD in the dACC. All these results were almost the same across the two independent groups. The complex pattern of asymmetry in GMD may imply highly differentiated functions of the dACC. Future fine-scale structural and diffusion MRI studies and a battery of cognitive behavioral measurements are needed to fully elucidate the asymmetry of the dACC.

At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting-state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA-dual regression), and amplitude of low-frequency fluctuations (ALFF) were measured in 45 antidepressant-free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age-, gender- and ethnicity-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter-RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD.

Functional organization of the brain can be fundamentally altered by auditory deprivation. Previous studies found that the superior temporal cortex in deaf people is reorganized to process non-auditory stimuli, as revealed by the extrinsic task-induced brain activities. However, it is unknown how the intrinsic activities of this region are impacted by deafness. This study explored this issue using resting-state functional magnetic resonance imaging. We examined 60 congenitally deaf (CD) individuals, 39 acquired deaf (AD) individuals, and 38 hearing controls (HC), and focused on the effect of deafness on the intra- and inter-regional synchronization of different parts of superior temporal sulcus (STS). We found that intra-regional synchronization or regional homogeneity (ReHo) of the middle STS (mSTS) was decreased in AD compared with HC or CD, while the CD had preserved ReHo in mSTS. Greater connectivity was observed between mSTS and posterior STS in CD and HC than in AD, while both CD and AD had weaker connectivity of mSTS with the anterior STS (aSTS) compared with HC. Moreover, the connectivity of mSTS–aSTS in CD and AD was associated with their language skills. These findings confirmed our hypothesis that the intrinsic function of different parts of STS is distinctly impacted by deafness.

Although resting-state brain activity has been demonstrated to correspond with task-evoked brain activation, the relationship between intrinsic and evoked brain activity has not been fully characterized. For example, it is unclear whether intrinsic activity can also predict task-evoked deactivation and whether the rest-task relationship is dependent on task load. In this study, we addressed these issues on 40 healthy control subjects using resting-state and task-driven [N-back working memory (WM) task] functional magnetic resonance imaging data collected in the same session. Using amplitude of low-frequency fluctuation (ALFF) as an index of intrinsic resting-state activity, we found that ALFF in the middle frontal gyrus and inferior/superior parietal lobules was positively correlated with WM task-evoked activation, while ALFF in the medial prefrontal cortex, posterior cingulate cortex, superior frontal gyrus, superior temporal gyrus, and fusiform gyrus was negatively correlated with WM task-evoked deactivation. Further, the relationship between the intrinsic resting-state activity and task-evoked activation in lateral/superior frontal gyri, inferior/superior parietal lobules, superior temporal gyrus, and midline regions was stronger at higher WM task loads. In addition, both resting-state activity and the task-evoked activation in the superior parietal lobule/precuneus were significantly correlated with the WM task behavioral performance, explaining similar portions of intersubject performance variance. Together, these findings suggest that intrinsic resting-state activity facilitates or is permissive of specific brain circuit engagement to perform a cognitive task, and that resting activity can predict subsequent task-evoked brain responses and behavioral performance. Hum Brain Mapp 34:3204-3215, 2013. (c) 2012 Wiley Periodicals, Inc.

It has been suggested that resting-state functional magnetic resonance imaging (RS-fMRI) is a promising tool to study the relation between spontaneous brain activity and behavioral performance. However, little is known about whether the local synchronization of spontaneous brain activity could predict response inhibition. In the current study, we used regional homogeneity (ReHo) to measure the local synchronization of RS-fMRI signals, and then investigated the relationship between ReHo and individual differences in response inhibition, as evaluated by the stop signal reaction time (SSRT) in a Stop signal task. The results showed that ReHo of RS-fMRI signals could successfully predict SSRT. Specifically, positive ReHo-SSRT correlations were observed in the bilateral inferior frontal cortex (IFC) and three critical components of the default mode network (DMN), and negative ReHo-SSRT correlations were observed in the rolandic area/posterior insula and the bilateral middle occipital cortex. The present results indicate the possible influence of the IFC and rolandic area/posterior insula on the efficiency of response inhibition, and demonstrate the importance of the DMN for the efficiency of cognitive task performance.

A previous study indicated that adults with attention deficit hyperactivity disorder (ADHD) had a decreased anti-correlation between the dorsal anterior cingulate cortex (dACC) and the default mode network (DMN). In this study, we investigated whether children with ADHD also show a decreased anti-correlation between the dACC and the DMN. We also explored the developmental characteristics of the resting-state functional connectivity (RSFC) of the dACC with the DMN in children with ADHD. Resting-state functional magnetic resonance imaging scans were obtained from a 3T scanner in 19 drug-naïve boys with ADHD and 23 controls. Compared with normal controls, the dACC in boys with ADHD showed a significantly decreased negative RSFC with the DMN, including the dorsomedial prefrontal cortex and the posterior cingulate cortex. The RSFC strength between the dACC and the posterior cingulate cortex showed a significantly negative correlation with age in normal controls, but not in boys with ADHD. This decreased anti-correlation may suggest an abnormal balance or interaction between attentional and intrinsic thoughts. Our age-related analysis suggested an abnormal development pattern of the dACC-DMN interaction in ADHD.

Conceptual processing is a crucial brain function for humans. Past research using neuropsychological and task-based functional brain-imaging paradigms indicates that widely distributed brain regions are related to conceptual processing. Here, we explore the potential contribution of intrinsic or spontaneous brain activity to conceptual processing by examining whether resting-state functional magnetic resonance imaging (rs-fMRI) signals can account for individual differences in the conceptual processing efficiencies of healthy individuals. We acquired rs-fMRI and behavioral data on object conceptual processing tasks. We found that the regional amplitude of spontaneous low-frequency fluctuations in the blood oxygen level-dependent signal in the left (posterior) middle temporal gyrus (LMTG) was highly correlated with participants' semantic processing efficiency. Furthermore, the strength of the functional connectivity between the LMTG and a series of brain regions—the left inferior frontal gyrus, bilateral anterior temporal lobe, bilateral medial temporal lobe, posterior cingulate gyrus, and ventromedial and dorsomedial prefrontal cortices—also significantly predicted conceptual behavior. The regional amplitude of low-frequency fluctuations and functionally relevant connectivity strengths of LMTG together accounted for 74% of individual variance in object conceptual performance. This semantic network, with the LMTG as its core component, largely overlaps with the regions reported in previous conceptual/semantic task-based fMRI studies. We conclude that the intrinsic or spontaneous activity of the human brain reflects the processing efficiency of the semantic system.

Typical histopathological findings of multiple system atrophy (MSA) have been observed in motor related cortices, in addition to the common areas of the striatum, substantia nigra, olivopontocerebellar pathways, the intermediolateral cell columns of the spinal cord, and the cerebellum. The purpose of this study is to test the hypothesis that functional impairment associated with the histopathological findings exists in the motor cortex of MSA patients using resting-state fMRI. Twenty clinically probable MSA patients (9 with MSA-P and 11 with MSA-C subtype) and 11 healthy controls (HCs) were studied. The regional homogeneity (ReHo) approach was used to analyze low frequency spontaneous fluctuation of blood oxygen level dependent signal. Compared with the HCs, the MSA patients showed significantly decreased ReHo in the left primary sensorimotor cortex, posterior cingulate cortex, left lateral prefrontal cortex (PFC) and right inferior parietal lobule (IPL), together with increased ReHo in the right primary sensorimotor cortex, bilateral premotor cortices, bilateral supplementary motor areas, medial PFC and left IPL. The results support the hypothesis that motor cortex areas can be functionally involved and likely play a role in motor circuit dysfunction in MSA patients.

Recent findings on intracortical EEG measurements show that the synchrony of localized neuronal networks is altered in epileptogenesis, leading to generalized seizure activity via connector hubs in the neuronal networks. Regional homogeneity (ReHo) analysis of blood oxygen level-dependent (BOLD) signals has demonstrated localized signal synchrony and disease-related alterations in a number of instances. We wanted to find out whether the ReHo of resting-state activity can be used to detect regional signal synchrony alterations in children with non-lesional temporal lobe epilepsy (TLE). Twenty-one TLE patients were compared with age and gender-matched healthy controls. Significantly increased ReHo was discovered in the posterior cingulate gyrus and the right medial temporal lobe of the patients, and they also had significantly decreased ReHo in the cerebellum compared with the healthy controls. However, the alterations in ReHo differed between the patients with normal and abnormal interictal EEGs, the latter showing significantly increased ReHo in the right fusiform gyrus and significantly decreased ReHo in the right medial frontal gyrus relative to the controls, while those with normal EEGs had significantly increased ReHo in the right inferior temporal gyrus and the left posterior cingulate gyrus. We conclude that altered BOLD signal synchrony can be detected in the cerebral and cerebellar cortices of children with TLE even in the absence of interictal EEG abnormalities.

The brain's energy economy excessively favors intrinsic, spontaneous neural activity over extrinsic, evoked activity, presumably to maintain its internal organization. Emerging hypotheses capable of explaining such an investment posit that the brain's intrinsic functional architecture encodes a blueprint for its repertoire of responses to the external world. Yet, there is little evidence directly linking intrinsic and extrinsic activity in the brain. Here we relate differences among individuals in the magnitude of task-evoked activity during performance of an Eriksen flanker task, to spontaneous oscillatory phenomena observed during rest. Specifically, we focused on the amplitude of low-frequency oscillations (LFO, 0.01-0.1 Hz) present in the BOLD signal. LFO amplitude measures obtained during rest successfully predicted the magnitude of task-evoked activity in a variety of regions that were all activated during performance of the flanker task. In these regions, higher LFO amplitude at rest predicted higher task-evoked activity. LFO amplitude measures obtained during rest were also found to have robust predictive value for behavior. In midline cingulate regions, LFO amplitudes predicted not only the speed and consistency of performance but also the magnitude of the behavioral congruency effect embedded in the flanker task. These results support the emerging hypothesis that the brain's repertoire of responses to the external world are represented and updated in the brain's intrinsic functional architecture.

Background: Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disorder that is characterized by recurrent intrusive thoughts, ideas or images and repetitive ritualistic behaviours. Although focal structural and functional abnormalities in specific brain regions have been widely studied in populations with OCD, changes in the functional relations among them remain poorly understood. This study examined OCD-related alterations in functional connectivity patterns in the brain's top-down control network. Methods: We applied resting-state functional magnetic resonance imaging to investigate the correlation patterns of intrinsic or spontaneous blood oxygen level-dependent signal fluctuations in 18 patients with OCD and 16 healthy controls. The brain control networks were first constructed by thresholding temporal correlation matrices of 39 brain regions associated with top-down control and then analyzed using graph theory-based approaches. Results: Compared with healthy controls, the patients with OCD showed decreased functional connectivity in the posterior temporal regions and increased connectivity in various control regions such as the cingulate, precuneus, thalamus and cerebellum. Furthermore, the brain's control networks in the healthy controls showed small-world architecture (high clustering coefficients and short path lengths), suggesting an optimal balance between modularized and distributed information processing. In contrast, the patients with OCD showed significantly higher local clustering, implying abnormal functional organization in the control network. Further analysis revealed that the changes in network properties occurred in regions of increased functional connectivity strength in patients with OCD. Limitations: The patient group in the present study was heterogeneous in terms of symptom clusters, and most of the patients with OCD were medicated. Conclusion: Our preliminary results suggest that the organizational patterns of intrinsic brain activity in the control networks are altered in patients with OCD and thus provide empirical evidence for aberrant functional connectivity in the large-scale brain systems in people with this disorder.

Functional homotopy, the high degree of synchrony in spontaneous activity between geometrically corresponding interhemispheric (i.e., homotopic) regions, is a fundamental characteristic of the intrinsic functional architecture of the brain. However, despite its prominence, the lifespan development of the homotopic resting-state functional connectivity (RSFC) of the human brain is rarely directly examined in functional magnetic resonance imaging studies. Here, we systematically investigated age-related changes in homotopic RSFC in 214 healthy individuals ranging in age from 7 to 85 years. We observed marked age-related changes in homotopic RSFC with regionally specific developmental trajectories of varying levels of complexity. Sensorimotor regions tended to show increasing homotopic RSFC, whereas higher-order processing regions showed decreasing connectivity (i.e., increasing segregation) with age. More complex maturational curves were also detected, with regions such as the insula and lingual gyrus exhibiting quadratic trajectories and the superior frontal gyrus and putamen exhibiting cubic trajectories. Sex-related differences in the developmental trajectory of functional homotopy were detected within dorsolateral prefrontal cortex (Brodmann areas 9 and 46) and amygdala. Evidence of robust developmental effects in homotopic RSFC across the lifespan should serve to motivate studies of the physiological mechanisms underlying functional homotopy in neurodegenerative and psychiatric disorders.

The anatomical connectivity of the human cerebral cortex resembles a ‘‘small-world’’ architecture, which is characterized by the coexistence of structurally segregated and integrative connectivity patterns. However, organizational differences in networks among individuals remain largely unknown. Here, we utilize diffusion tensor imaging tractography and graph-theoretical approaches to investigate the effects of sex and brain size on the topological organization of human cortical anatomical network. Weighted cortical networks were constructed from 72 young healthy participants by measuring anatomical connection densities between 78 cortical regions. As expected, all participants showed a small-world topology (high local clustering and short paths between nodes), which suggests a highly efficient topological organization. Furthermore, we found that females had greater local efficiencies than males. Moreover, smaller brains showed higher local efficiency in females but not in males, suggesting an interaction between sex and brain size. Specifically, we show that several brain regions (e.g., the precuneus, precentral gyrus, and lingual gyrus) had significant associations between nodal centrality and sex or brain size. Our findings suggest that anatomical network organization in the human brain is associated with sex and brain size and provide insights into the understanding of the structural substrates that underlie individual differences in behavior and cognition.

Measures assessing resting-state brain activity with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) can reveal cognitive disorders at an early stage. Analysis of regional homogeneity (ReHo) measures the local synchronization of spontaneous fMRI signals and has been successfully utilized in detecting alterations in subjects with attention-deficit hyperactivity disorder (ADHD), depression, schizophrenia, Parkinson's disease and Alzheimer's dementia. Resting-state brain activity was investigated in 28 adolescents with autism spectrum disorders (ASD) and 27 typically developing controls being imaged with BOLD fMRI and analyzed with the ReHo method. The hypothesis was that ReHo of resting-state brain activity would be different between ASD subjects and controls in brain areas previously shown to display functional alterations in stimulus or task based fMRI studies. Compared with the controls, the subjects with ASD had significantly decreased ReHo in right superior temporal sulcus region, right inferior and middle frontal gyri, bilateral cerebellar crus I, right insula and right postcentral gyrus. Significantly increased ReHo was discovered in right thalamus, left inferior frontal and anterior subcallosal gyrus and bilateral cerebellar lobule VIII. We conclude that subjects with ASD have right dominant ReHo alterations of resting-state brain activity, i.e., areas known to exhibit abnormal stimulus or task related functionality. Our results demonstrate that there is potential in utilizing the ReHo method in fMRI analyses of ASD.

The corpus callosum (CC) is one of focused target areas which may play an important role in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Conventional structural magnetic resonance imaging (MRI) studies have revealed the macrostructural abnormalities of CC and its subdivisions in ADHD compared with controls. However, no study has examined the macrostructural and microstructural characteristics of the CC in the same ADHD group. In this study, MRI morphometric and diffusion tensor imaging (DTI) techniques were combined to explore the area and measure fractional anisotropy (FA) abnormality of CC and its seven subdivisions in children with ADHD. Twenty-eight boys with ADHD (13.3 ± 1.5 years) and 27 age- and gender- matched controls (13.2 ± 0.9 years) were included. We co-registered individual structural MRI and DTI images manually and subdivided the midsagittal CC into seven subdivisions. The area and FA of the CC and its subdivisions were then compared between the patients and the matched controls. Results showed that ADHD had decreased area of entire CC, anterior middle-body, and isthmus. Meanwhile, reduced FA value of the isthmus was found in the ADHD group compared with the controls. Our study indicated that not only macrostructural abnormalities but also microstructural alterations in CC, especially in isthmus occurred in ADHD. The abnormality of the isthmus, the subdivision that contains the fibers connecting posterior regions of brain, may play an important role in the pathophysiology of ADHD and may be implicated in the disorders of attention.

Structural and functional alterations of the putamen have been reported in patients with attention deficit hyperactivity disorder (ADHD), but the functional relationships between this area and other brain regions are seldom explored. In the present study, seed-based correlation analyses were performed in the resting-state functional magnetic resonance imaging (fMRI) data to examine the differences in functional connectivity of the putamen between medication-naïve children with ADHD and normal children. Positive functional connectivity with the putamen-ROIs was seen in bilateral sensorimotor area, prefrontal cortex, insula, superior temporal gyrus and subcortical regions and negative functional connectivity was located in bilateral parietal and occipital cortex as well as clusters in the frontal, middle temporal cortex and cerebellum. Group comparison showed that decreases in functional connectivity with the putamen-ROIs were observed in ADHD relative to the controls, except for the right globus pallidus/thalamus, which showed increased positive connectivity with left putamen-ROI. For children with ADHD, areas exhibiting decreased positive functional connectivity with left putamen-ROI were seen in right frontal and limbic regions, and regions showing decreased negative connectivity with the putamen-ROIs were observed in areas belonging to the default mode network (for left putamen-ROI, including right cerebellum and right temporal lobe; for right putamen-ROI, including left cerebellum and right precuneus). The above results suggest that abnormal functional relationships between the putamen and the cortical-striatal-thalamic circuits as well as the default mode network may underlie the pathological basis of ADHD.

Recent studies have demonstrated small‐world properties in both functional and structural brain networks that are constructed based on different parcellation approaches. However, one fundamental but vital issue of the impact of different brain parcellation schemes on the network topological architecture remains unclear. Here, we used resting‐state functional MRI (fMRI) to investigate the influences of different brain parcellation atlases on the topological organization of brain functional networks. Whole‐brain fMRI data were divided into ninety and seventy regions of interest according to two predefined anatomical atlases, respectively. Brain functional networks were constructed by thresholding the correlation matrices among the parcellated regions and further analyzed using graph theoretical approaches. Both atlas‐based brain functional networks were found to show robust small‐world properties and truncated power‐law connectivity degree distributions, which are consistent with previous brain functional and structural networks studies. However, more importantly, we found that there were significant differences in multiple topological parameters (e.g., small‐worldness and degree distribution) between the two groups of brain functional networks derived from the two atlases. This study provides quantitative evidence on how the topological organization of brain networks is affected by the different parcellation strategies applied. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

Resting state brain activity in Parkinson's disease (PD) can give clues to the pathophysiology of the disorder, and might be helpful in diagnosis, but it has never been explored using functional MRI (fMRI). In the current study, we used a regional homogeneity (ReHo) method to investigate PD‐related modulations of neural activity in the resting state. FMRIs were acquired in 22 patients with PD at both before and after levodopa administration, as well as in 22 age‐ and sex‐matched normal controls. In the PD group compared with the healthy controls, we found ReHo decreased in extensive brain regions, including the putamen, thalamus, and supplementary motor area; and increased in some other areas, including the cerebellum, primary sensorimotor cortex, and premotor area. The ReHo off medication was negatively correlated with the Unified Parkinson's Disease Rating Scale (UPDRS) in the putamen and some other regions, and was positively correlated with the UPDRS in the cerebellum. Administration of levodopa relatively normalized ReHo. Our findings demonstrate that neural activity in the resting state is changed in patients with PD. This change is secondary to dopamine deficiency, and related to the severity of the disease. The different neuronal activity at the baseline state should be considered in explaining fMRI findings obtained during tasks. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.

Most of the resting-state functional magnetic resonance imaging (fMRI) studies demonstrated the correlations between spatially distinct brain areas from the perspective of functional connectivity or functional integration. The functional connectivity approaches do not directly provide information of the amplitude of brain activity of each brain region within a network. Alternatively, an index named amplitude of low-frequency fluctuation (ALFF) of the resting-state fMRI signal has been suggested to reflect the intensity of regional spontaneous brain activity. However, it has been indicated that the ALFF is also sensitive to the physiological noise. The current study proposed a fractional ALFF (fALFF) approach, i.e., the ratio of power spectrum of low-frequency (0.01-0.08 Hz) to that of the entire frequency range and this approach was tested in two groups of resting-state fMRI data. The results showed that the brain areas within the default mode network including posterior cingulate cortex, precuneus, medial prefrontal cortex and bilateral inferior parietal lobule had significantly higher fALFF than the other brain areas. This pattern was consistent with previous neuroimaging results. The non-specific signal components in the cistern areas in resting-state fMRI were significantly suppressed, indicating that the fALFF approach improved the sensitivity and specificity in detecting spontaneous brain activities. Its mechanism and sensitivity to abnormal brain activity should be evaluated in the future studies. (C) 2008 Elsevier B.V. All rights reserved.

Recently, human brain activity during a resting-state has attracted increasing attention. Several studies have found that there are two networks: the default mode network and its anti-correlation network. Some studies have subsequently showed that the functions of brain areas within the default mode network are crucial in human mental activity. To further discern the brain default mode network as well as its anti-correlation network during resting-state, we used three methods to analyze resting-state functional magnetic resonance imaging (fMRI) data; regional homogeneity analysis, linear correlation and independent component analysis, on four groups of dataset. Our results showed the existence of these two networks prominently and consistently during a resting- and conscious-state across the three methods. This consistency was exhibited in four independent groups of normal adults. Moreover, the current results provided evidences that the brain areas within the two anti-correlated networks are highly integrated at both the intra- and inter-regional level.