State Key Laboratory of Cognitive Neuroscience and Learning

Diffusion magnetic resonance imaging (dMRI) is widely used in both scientific research and clinical practice in in-vivo studies of the human brain. While a number of post-processing packages have been developed, fully automated processing of dMRI datasets remains challenging. Here, we developed a MATLAB toolbox named "Pipeline for Analyzing braiN Diffusion imAges" (PANDA) for fully automated processing of brain diffusion images. The processing modules of a few established packages, including FMRIB Software Library (FSL), Pipeline System for Octave and Matlab (PSOM), Diffusion Toolkit and MRIcron, were employed in PANDA. Using any number of raw dMRI datasets from different subjects, in either DICOM or NIfTI format, PANDA can automatically perform a series of steps to process DICOM/NIfTI to diffusion metrics [e.g., fractional anisotropy (FA) and mean diffusivity (MD)] that are ready for statistical analysis at the voxel-level, the atlas-level and the Tract-Based Spatial Statistics (TBSS)-level and can finish the construction of anatomical brain networks for all subjects. In particular, PANDA can process different subjects in parallel, using multiple cores either in a single computer or in a distributed computing environment, thus greatly reducing the time cost when dealing with a large number of datasets. In addition, PANDA has a friendly graphical user interface (GUI), allowing the user to be interactive and to adjust the input/output settings, as well as the processing parameters. As an open-source package, PANDA is freely available at http://www.nitrc.org/projects/panda/. This novel toolbox is expected to substantially simplify the image processing of dMRI datasets and facilitate human structural connectome studies.

BACKGROUND: Patients with Parkinson's disease (PD) have great difficulty in performing two tasks simultaneously, but the neural contribution to this problem has not been identified. In the current study, we investigated the pathophysiology of dual task performance in PD. METHODS: We studied 15 patients with PD and 14 healthy controls. Functional MRIs were obtained before and after practicing dual tasks with different complexities. RESULTS: After practice, 12 normal subjects performed all dual tasks correctly. Twelve patients performed the simpler dual tasks correctly. However, only 3 patients could perform the more complex dual task correctly. Dual tasks activated similar brain regions in both groups. The bilateral precuneus was additionally activated during performance of dual tasks compared with the component tasks in both groups. Patients had greater activity in the cerebellum, premotor area, parietal cortex, precuneus and prefrontal cortex compared with normal subjects. CONCLUSIONS: Difficulty in performing two tasks simultaneously in patients with PD is probably due to limited attentional resources, defective central executive function and less automaticity in performing the tasks. Practice can diminish dual task interference and improve performance in patients with PD.

Although there has been extensive research on children's moral knowledge about lying and truth-telling and their actual lie- or truth-telling behaviors, research to examine the relation between these two is extremely rare. This study examined one hundred and twenty 7-, 9-, and 11-year-olds' moral understanding of lies and their actual lying behaviors in a politeness situation. Results revealed that as age increased, children increasingly evaluated others' lying in politeness situations less negatively and were more inclined to tell lies in such situations themselves. Contrary to previous findings, children's sociomoral knowledge about lying was significantly related to their actual behaviors, particularly when children's rationales underlying their moral judgments were consistent with their motives for actual lie- or truth-telling in the politeness situation.

Hierarchy is a major organizational principle of the cortex and underscores modern computational theories of cortical function. The local microcircuit amplifies long-distance inter-areal input, which show distance-dependent changes in their laminar profiles. Statistical modeling of these changes in laminar profiles demonstrates that inputs from multiple hierarchical levels to their target areas show remarkable consistency, allowing the construction of a cortical hierarchy based on a principle of hierarchical distance. The statistical modeling that is applied to structure can also be applied to laminar differences in the oscillatory coherence between areas thereby determining a functional hierarchy of the cortex. Close examination of the anatomy of inter-areal connectivity reveals a dual counterstream architecture with well-defined distance-dependent feedback and feedforward pathways in both the supra- and infragranular layers, suggesting a multiplicity of feedback pathways with well-defined functional properties. These findings are consistent with feedback connections providing a generative network involved in a wide range of cognitive functions. A dynamical model constrained by connectivity data sheds insight into the experimentally observed signatures of frequency-dependent Granger causality for feedforward versus feedback signaling. Concerted experiments capitalizing on recent technical advances and combining tract-tracing, high-resolution fMRI, optogenetics and mathematical modeling hold the promise of a much improved understanding of lamina-constrained mechanisms of neural computation and cognition. However, because inter-areal interactions involve cortical layers that have been the target of important evolutionary changes in the primate lineage, these investigations will need to include human and non-human primate comparisons.

Alzheimer's disease (AD) is the most common form of dementia. As an incurable, progressive, and neurodegenerative disease, it causes cognitive and memory deficits. However, the biological mechanisms underlying the disease are not thoroughly understood. In recent years, non-invasive neuroimaging and neurophysiological techniques [e.g., structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, and EEG/MEG] and graph theory based network analysis have provided a new perspective on structural and functional connectivity patterns of the human brain (i.e., the human connectome) in health and disease. Using these powerful approaches, several recent studies of patients with AD exhibited abnormal topological organization in both global and regional properties of neuronal networks, indicating that AD not only affects specific brain regions, but also alters the structural and functional associations between distinct brain regions. Specifically, disruptive organization in the whole-brain networks in AD is involved in the loss of small-world characters and the re-organization of hub distributions. These aberrant neuronal connectivity patterns were associated with cognitive deficits in patients with AD, even with genetic factors in healthy aging. These studies provide empirical evidence to support the existence of an aberrant connectome of AD. In this review we will summarize recent advances discovered in large-scale brain network studies of AD, mainly focusing on graph theoretical analysis of brain connectivity abnormalities. These studies provide novel insights into the pathophysiological mechanisms of AD and could be helpful in developing imaging biomarkers for disease diagnosis and monitoring.

This study aimed to investigate the impact of perceived social support on the depression of postpartum women, and mainly focuses on confirming the mediator role of self-efficacy. A total of 427 new mothers from two general hospitals in Beijing accomplished the Multidimensional Scale of Perceived Social Support, General Self-efficacy Scale, and Edinburgh Postnatal Depression Scale. The results revealed that both social support and self-efficacy significantly correlate with postpartum depression. Structural equation modeling indicated that self-efficacy partially mediates the relationship between social support and postpartum depression.

This 2-year longitudinal study examined both concurrent and longitudinal relations of a variety of reading-related cognitive tasks and Chinese word reading and word dictation among 187 Hong Kong Chinese kindergarteners aged 4-6. Homophone awareness, visual skills and syllable awareness were all uniquely associated with Chinese word reading across time, with age, vocabulary knowledge and nonverbal IQ statistically controlled. Only visual skill and syllable deletion uniquely explained early Chinese word dictation, however. Results extend previous research on cognitive correlates of Chinese literacy and highlight the small but unique contribution of homophone awareness for early reading acquisition in Chinese. © 2011 UKLA.

Abstract Introduction Evidence for the efficacy of cognitive training in patients with subcortical vascular cognitive impairment no dementia is still lacking. Methods A randomized, active controlled design using multidomain, adaptive, computerized cognitive training for 30 minutes, 5 days/week for 7 weeks. Assessments included global cognitive function and executive function (primary outcomes) and brain functional connectivity and structural changes (secondary outcomes). Results Sixty patients were randomized across three medical centers in Beijing. At the end of the intervention, the cognitive training group showed significant improvement in Montreal Cognitive Assessment relative to the active control group ( P = .013) and significantly increased functional connectivity between the left dorsolateral prefrontal cortex and medial prefrontal cortex, which was significantly correlated with Montreal Cognitive Assessment change ( P = .017). Discussion Computerized cognitive training significantly improved global cognitive function, which was supported by the improved brain plasticity. Incorporation of biomarkers should be implemented in cognitive training trials.

Functional connectivity has become one of the important approaches to understanding the functional organization of the human brain. Recently, functional near-infrared spectroscopy (fNIRS) was demonstrated as a feasible method to study resting-state functional connectivity (RSFC) in the sensory and motor systems. However, whether such fNIRS-based RSFC can be revealed in high-level and complex functional systems remains unknown. In the present study, the feasibility of such an approach is tested on the language system, of which the neural substrates have been well documented in the literature. After determination of a seed channel by a language localizer task, the correlation strength between the low frequency fluctuations of the fNIRS signal at the seed channel and those at all other channels is used to evaluate the language system RSFC. Our results show a significant RSFC between the left inferior frontal cortex and superior temporal cortex, components both associated with dominant language regions. Moreover, the RSFC map demonstrates left lateralization of the language system. In conclusion, the present study successfully utilized fNIRS-based RSFC to study a complex and high-level neural system, and provides further evidence for the validity of the fNIRS-based RSFC approach.

Significance: Attention-deficit/hyperactivity disorder (ADHD) is the most common psychological disease in childhood. Currently, widely used neuroimaging techniques require complete body confinement and motionlessness and thus are extremely hard for brain scanning of ADHD children.

BRUCE/Apollon is a membrane-associated inhibitor of apoptosis protein that is essential for viability and has ubiquitin-conjugating activity. On initiation of apoptosis, the ubiquitin ligase Nrdp1/RNF41 promotes proteasomal degradation of BRUCE. Here we demonstrate that BRUCE together with the proteasome activator PA28γ causes proteasomal degradation of LC3-I and thus inhibits autophagy. LC3-I on the phagophore membrane is conjugated to phosphatidylethanolamine to form LC3-II, which is required for the formation of autophagosomes and selective recruitment of substrates. SIP/CacyBP is a ubiquitination-related protein that is highly expressed in neurons and various tumors. Under normal conditions, SIP inhibits the ubiquitination and degradation of BRUCE, probably by blocking the binding of Nrdp1 to BRUCE. On DNA damage by topoisomerase inhibitors, Nrdp1 causes monoubiquitination of SIP and thus promotes apoptosis. However, on starvation, SIP together with Rab8 enhances the translocation of BRUCE into the recycling endosome, formation of autophagosomes, and degradation of BRUCE by optineurin-mediated autophagy. Accordingly, deletion of SIP in cultured cells reduces the autophagic degradation of damaged mitochondria and cytosolic protein aggregates. Thus, by stimulating proteasomal degradation of LC3-I, BRUCE also inhibits autophagy. Conversely, SIP promotes autophagy by blocking BRUCE-dependent degradation of LC3-I and by enhancing autophagosome formation and autophagic destruction of BRUCE. These actions of BRUCE and SIP represent mechanisms that link the regulation of autophagy and apoptosis under different conditions.

Functional near-infrared spectroscopy (fNIRS) is recently utilized as a new approach to assess resting-state functional connectivity (RSFC) in the human brain. For any new technique or new methodology, it is necessary to be able to replicate similar experiments using different instruments in order to establish its liability and reproducibility. We apply two different diffuse optical tomographic (DOT) systems (i.e., DYNOT and CW5), with various probe arrangements to evaluate RSFC in the sensorimotor cortex by utilizing a previously published experimental protocol and seed-based correlation analysis. Our results exhibit similar spatial patterns and strengths in RSFC between the bilateral motor cortexes. The consistent observations are obtained from both DYNOT and CW5 systems, and are also in good agreement with the previous fNIRS study. Overall, we demonstrate that the fNIRS-based RSFC is reproducible by various DOT imaging systems among different research groups, enhancing the confidence of neuroscience researchers and clinicians to utilize fNIRS for future applications.

Flattening the fundamental frequency (F0) contours of Mandarin Chinese sentences reduces their intelligibility in noise but not in quiet. It is unclear, however, how the absence of primary acoustic cue for lexical tones might be compensated with the top-down information of sentence context. In this study, speech intelligibility was evaluated when participants listened to sentences and word lists with or without F0 variations in quiet and noise. The results showed that sentence context partially explained the unchanged intelligibility of monotonous Chinese sentences in quiet and further indicate that F0 variations and sentence context act in concert during speech comprehension.

BACKGROUND AND PURPOSE: AD has been documented as a kind of disconnection syndrome by functional neuroimaging studies. The primary focus of this study was to examine, with the use of resting-state fMRI, whether AD would impact connectivity among RSNs. MATERIALS AND METHODS: Fourteen patients with AD and 16 NC were recruited and scanned by using resting-state fMRI. Group independent-component analysis and the BN learning approach were used, respectively, to separate the RSNs and construct the network-to-network connectivity patterns for each group. The convergence index for the special network DMN was measured. RESULTS: Three of the 4 connections were significantly lower in AD compared with NC. Although numerically the AD group had more connections, none was statistically different from that in the NC group except for 1 increased connection from the DMN to the DAN. The convergence index for the DMN node was lower in AD than in NC. CONCLUSIONS: Connections among cognitive networks in AD were more vulnerable to impairment than sensory networks. The DMN decreased its integration function for other RSNs but may also play a role in compensating for the disrupted connections in AD.

Sleep loss can alter extrinsic, task-related functional MRI signals involved in attention, memory, and executive function. However, the effects of sleep loss on brain structure have not been well characterized. Recent studies with patients with sleep disorders and animal models have demonstrated reduction of regional brain structure in the hippocampus and thalamus. In this study, using T1-weighted MRI, we examined the change of regional gray matter volume in healthy adults after long-term total sleep deprivation (∼72 h). Regional volume changes were explored using voxel-based morphometry with a paired two-sample t-test. The results revealed significant loss of gray matter volume in the thalamus but not in the hippocampus. No overall decrease in whole brain gray matter volume was noted after sleep deprivation. As expected, sleep deprivation significantly reduced visual vigilance as assessed by the continuous performance test, and this decrease was correlated significantly with reduced regional gray matter volume in thalamic regions. This study provides the first evidence for sleep loss-related changes in gray matter in the healthy adult brain.

Proteasomes are responsible for the turnover of most cellular proteins, and thus are critical to almost all cellular activities. A substrate entering the proteasome must first bind to a substrate receptor. Substrate receptors can be classified as ubiquitin receptors and non-ubiquitin receptors. The intrinsic ubiquitin receptors, including proteasome regulatory particle base subunits 1, 10 and 13 (Rpn1, Rpn10, and Rpn13), determine the capability of the proteasome to recognize a ubiquitin chain, and thus provide selectivity for the 26S proteasome. However, the non-ubiquitin receptors, including proteasome activator 200 (PA200) and PA28γ, have received great attention due to their remarkable compensatory roles relative to canonical ubiquitin-mediated proteasomal degradation. Herein we review recent advances in understanding the contributions of these substrate receptors to proteasomal degradation, and introduce their substrates and interacting factors. We also provide insights into their biological functions related to spermatogenesis, immune responses, cellular homeostasis, and tumour development. Finally, we summarize advances in developing small-molecule inhibitors of these substrate receptors and discuss their potential as drug targets.

SignificanceDecline in cognitive ability is a significant issue associated with healthy aging. Transcranial photobiomodulation (tPBM) is an emerging non-invasive neuromodulation technique and has shown promise to overcome this challenge.AimThis study aimed to investigate the effects of seven-day repeated tPBM, compared to those of single tPBM and baseline, on improving N-back working memory in healthy older adults and to evaluate the persistent efficacy of repeated tPBM.ApproachIn a sham-controlled and within-subject design, 61 healthy older adults were recruited to participate in a longitudinal study involving an experimental baseline, seven days of tPBM treatment (12 min daily, 1064-nm laser, 250 mW / cm2) in the left dorsolateral prefrontal cortex and three weeks of follow-ups. Behavioral performance in the N-back (N = 1,2 , 3) was recorded poststimulation during the baseline, the first and seventh days of the tPBM session, and the three weekly follow-ups. A control group with 25 participants was included in this study to rule out the practice and placebo effects. The accuracy rate and response time were used in the statistical analysis.ResultsRepeated and single tPBM significantly improved accuracy rate in 1- and 3-back tasks and decreased response time in 3-back compared to the baseline. Moreover, the repeated tPBM resulted in a significantly higher improvement in accuracy rate than the single tPBM. These improvements in accuracy rate and response time lasted at least three weeks following repeated tPBM. In contrast, the control group showed no significant improvement in behavioral performance.ConclusionsThis study demonstrated that seven-day repeated tPBM improved the working memory of healthy older adults more efficiently, with the beneficial effect lasting at least three weeks. These findings provide fundamental evidence that repeated tPBM may be a potential intervention for older individuals with memory decline.

This study investigated effects of cross-language similarity on within- and between-language Stroop interference and facilitation in three groups of trilinguals. Trilinguals were either proficient in three languages that use the same-script (alphabetic in German-English-Dutch trilinguals), two similar scripts and one different script (Chinese and alphabetic scripts in Chinese-English-Malay trilinguals), or three completely different scripts (Arabic, Chinese, and alphabetic in Uyghur-Chinese-English trilinguals). The results revealed a similar magnitude of within-language Stroop interference for the three groups, whereas between-language interference was modulated by cross-language similarity. For the same-script trilinguals, the within- and between-language interference was similar, whereas the between-language Stroop interference was reduced for trilinguals with languages written in different scripts. The magnitude of within-language Stroop facilitation was similar across the three groups of trilinguals, but smaller than within-language Stroop interference. Between-language Stroop facilitation was also modulated by cross-language similarity such that these effects became negative for trilinguals with languages written in different scripts. The overall pattern of Stroop interference and facilitation effects can be explained in terms of diverging and converging color and word information across languages.

BACKGROUND: The neurophysiologic mechanisms of propofol-induced loss of consciousness have been studied in detail at the macro (scalp electroencephalogram) and micro (spiking or local field potential) scales. However, the changes in information integration and cortical connectivity during propofol anesthesia at the mesoscopic level (the cortical scale) are less clear. METHODS: The authors analyzed electrocorticogram data recorded from surgical patients during propofol-induced unconsciousness (n = 9). A new information measure, genuine permutation cross mutual information, was used to analyze how electrocorticogram cross-electrode coupling changed with electrode-distances in different brain areas (within the frontal, parietal, and temporal regions, as well as between the temporal and parietal regions). The changes in cortical networks during anesthesia-at nodal and global levels-were investigated using clustering coefficient, path length, and nodal efficiency measures. RESULTS: In all cortical regions, and in both wakeful and unconscious states (early and late), the genuine permutation cross mutual information and the percentage of genuine connections decreased with increasing distance, especially up to about 3 cm. The nodal cortical network metrics (the nodal clustering coefficients and nodal efficiency) decreased from wakefulness to unconscious state in the cortical regions we analyzed. In contrast, the global cortical network metrics slightly increased in the early unconscious state (the time span from loss of consciousness to 200 s after loss of consciousness), as compared with wakefulness (normalized average clustering coefficient: 1.05 ± 0.01 vs. 1.06 ± 0.03, P = 0.037; normalized average path length: 1.02 ± 0.01 vs. 1.04 ± 0.01, P = 0.021). CONCLUSIONS: The genuine permutation cross mutual information reflected propofol-induced coupling changes measured at a cortical scale. Loss of consciousness was associated with a redistribution of the pattern of information integration; losing efficient global information transmission capacity but increasing local functional segregation in the cortical network.

Recently, resting-state functional near-infrared spectroscopy (rs-fNIRS) research has experienced tremendous progress. Resting-state functional connectivity (RSFC) has been adopted as a pivotal biomarker in rs-fNIRS studies. However, it is yet to be clear if the RSFC derived from rs-fNIRS is reliable. This concern impedes extensive utilization of rs-fNIRS. We systematically address the issue of reliability. Sixteen subjects participate in two rs-fNIRS sessions held one week apart. RSFC in sensorimotor system is calculated using the seed-correlation approach. Then, test-retest reliability is evaluated at three different scales (map-, cluster-, and channelwise) for individual- and group-level RSFC derived from different types of fNIRS signals [oxygenated (HbO), deoxygenated (HbR), and total hemoglobin (HbT)]. The results show that, for HbO signals, individual-level RSFC generally has good-to-excellent map-/clusterwise reliability, while group-level RSFC has excellent reliability. For HbT signals, the results are similar. For HbR signals, the clusterwise reliability is comparable to that for HbO while the mapwise reliability is slightly lower (fair to good). Focusing on RSFC at a single channel, we report poor channelwise reliability for all three types of signals. We hereby propose that fNIRS-derived RSFC is a reliable biomarker if interpreted in map- and clusterwise manners. However, channelwise interpretation of individual RSFC should proceed with caution.