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Resilience, the ability for a system to maintain its basic functionality when suffering from lesions, is a critical property for human brain, especially in the brain aging process. This study adopted a novel metric of network resilience, the Resilience Index (RI), to assess human brain resilience with three different lifespan datasets. Based on the structural brain networks constructed from diffusion tensor imaging (DTI), we observed an inverted-U relationship between RI and age, that is, RI increased during development and early adulthood, reached a peak at about 35 years old, and then decreased during aging, which suggested that brain resilience could be quantified by RI. Furthermore, we studied brain network vulnerability by the decreases in RI when virtual lesions occurred to nodes (i.e., brain regions) or edges (i.e., structural brain connectivity). We found that the strong edges were markedly vulnerable, and the homotopic edges were the most prominent representatives of vulnerable edges. In other words, an arbitrary attack on homotopic edges would have a high probability to degrade brain network resilience. These findings suggest the change of human brain resilience across the lifespan and provide a new perspective for exploring human brain vulnerability.

Background Intracellular acidosis in the ischemic penumbra can contribute to further cell death, effectively enlarging the infarct core. Restoring the acid-base balance may enhance tissue survivability after cerebral ischemia. Objective This study investigated whether translocating protons out of penumbral neurons could mitigate tissue acidification and induce neuroprotection in a rodent model of acute cerebral ischemia. Methods We modulated the penumbral neurons via a light-driven pump to translocate protons out (i.e., archaerhodopsin/ArchT group) or into (i.e., channelrhodopsin-2/ChR2 group) neurons after focal cerebral ischemia in rats. Intracellular pH values were imaged via neutral red (NR) fluorescence and cerebral blood flow (CBF) was monitored through laser speckle contrast imaging (LSCI). Global CBF responses to electrical stimulation of the hindlimbs were obtained 24 h and 48 h after ischemia to assess neurological function. Behavioral and histological outcomes were evaluated 48 h after ischemia. A control group without gene modification was included. Results The reduction of relative pH (RpH), the amplitude of negative peak of hypoemic response (RNP) and the hemispheric lateralization index (LI) in ArchT group were significantly less than those of the ChR2 or control group. Moreover, RpH was strongly correlated with RNP (r = 0.60) and LI (r24h = 0.80, r48h = 0.59). In addition, behavioral and histological results supported a neuroprotective effect of countering neuronal acidosis in penumbra through optogenetic stimulation. Conclusion(s) These results indicate that countering intracellular acidosis by optogenetically translocating protons out of penumbral neurons during the acute ischemic stage could induce protection after ischemic brain injury.

Laser speckle contrast imaging (LSCI) is a full-field, high spatiotemporal resolution and low-cost optical technique for measuring blood flow, which has been successfully used for neurovascular imaging. However, due to the low signal–noise ratio and the relatively small sizes, segmenting the cerebral vessels in LSCI has always been a technical challenge. Recently, deep learning has shown its advantages in vascular segmentation. Nonetheless, ground truth by manual labeling is usually required for training the network, which makes it difficult to implement in practice. In this manuscript, we proposed a deep learning-based method for real-time cerebral vessel segmentation of LSCI without ground truth labels, which could be further integrated into intraoperative blood vessel imaging system. Synthetic LSCI images were obtained with a synthesis network from LSCI images and public labeled dataset of Digital Retinal Images for Vessel Extraction, which were then used to train the segmentation network. Using matching strategies to reduce the size discrepancy between retinal images and laser speckle contrast images, we could further significantly improve image synthesis and segmentation performance. In the testing LSCI images of rodent cerebral vessels, the proposed method resulted in a dice similarity coefficient of over 75%.

Control of attention is thought to be specifically impaired in schizophrenia due to abnormal function in the prefrontal cortex (PFC). The PFC plays a critical role in the identification of relevant stimuli and the development of appropriate biases for the identified signals, including selection of an appropriate attentional ‘zoom’. We examined how demands associated with changes in attentional requirements in a Sustained Attention Task (SAT) may contribute to differences in functional involvement of the PFC and relation to clinical status. A group of 24 individuals with schizophrenia and 16 healthy controls (N = 40) performed the SAT and a visuospatial condition (vSAT) while activity in the bilateral anterior PFC was monitored using functional Near Infrared Spectroscopy (fNIRS). The results confirm that the right frontopolar region plays a role in control of attention for both patients and healthy controls. However, patients with schizophrenia exhibited a general attentional deficit and inefficient right-medial PFC activation. Additionally, we observed a strong regional association between left Middle Frontal Gyrus (MFG) activity during the vSAT task and the PANSS score driven by the negative symptom subscale. The presence of aberrant activation differences within the left-MFG region may describe a dysregulation of attentional networks linked to the clinical expression of negative and general symptoms.

Objective: Directly modulating targeted cortical function, brain stimulation provides promising techniques for stroke intervention. However, the cellular level mechanisms underlying preserved neurovascular function remains unclear. Optogenetics provides a cell-specific approach to modulate the neuronal activity. This study aims to investigate whether the exclusive excitation of sensorimotor neurons using optogenetics in an acute stroke can protect neurovascular function and reduce infarct size. Methods: Sensorimotor neurons were transfected with channelrhodopsin-2 and excited by a 473-nm laser. The photothrombotic stroke was induced in the ipsilateral parietal cortex and the targeted area for modulation remained intact. Optogenetic stimulation was carried out within 2 h after stroke in the modulation group. Using a laser speckle contrast imaging technique, we measured the cerebral blood flow at baseline, 0, 2, and 24 h after stroke, and analyzed the hemodynamic changes in both modulation ( n = 12) and control ( n = 9) groups. Also, the neurovascular response was measured 24 h after stroke. Results: We found that neuronal-specific excitation of an ipsilesional sensorimotor cortex at an acute stage could reduce the expansion of an ischemic area and promote the neurovascular response at 24 h after stroke. The histological and behavioral results consolidate the protective effects of optogenetic-guided neuronal modulation in acute stroke. Conclusion: Excitatory stimulation of ipsilesional sensorimotor neurons in an acute stroke could protect neurovascular function and reduces the expansion of ischemic area. Significance: For the first time, this work demonstrates that specific neuronal modulation in the acute stroke is neuroprotective and reduces the infarct size.

Multisensory stimulation plays an important role in the recovery of ischemic stroke. However, little is known about the interactions between neuronal activities with multi-afferent stimulations and their effects on hemodynamic responses. Optogenetics has been a useful tool in neuroscience research to unravel the mechanisms of neurovascular coupling at cell-specific level. In this study, we applied laser speckle contrast imaging (LSCI) to map the cortical hemodynamic response with high spatiotemporal resolution. The results showed that optogenetic inhibition of pyramidal neurons in sensorimotor cortex induced both local and distant increases of cerebral blood flow (CBF) with dual peaks, and the full width at half maximum (FWHM) was significantly larger than that of the CBF response to optogenetic excitation. Furthermore, optogenetic excitation of pyramidal neurons could significantly increase the local CBF response to sensory stimulation, whereas optogenetic inhibition of pyramidal neurons decreased the local CBF response at the early stage after sensory stimulation and increased the distant CBF response during the recovery period. Our work provided useful insights into the mechanisms of brain stimulation, which might help in clinical neurological applications.

Healthy aging is associated with structural and functional changes in sensorimotor systems, leading to a deterioration in motor function. However, most of the previous studies focused on the descriptive measures of alteration, little is known about how structural network facilitate functional dynamics during aging. Based on the structural brain network constructed by diffusion-weighted imaging, we employed recent network control theory to evaluate the control energy necessary to drive the state transition from baseline condition with default mode network (DMN) activation to motor network activation in a large cohort (n = 625; 18–88 years). We found at the whole, the control energy required to activate the motor network declined with aging, in which the motor network contributed most of the control energy. The control energy of nodes within motor network showed both positive and negative age effects, reflecting an aberrant functional integration associated with aging. Interestingly, the control energy of subcortical network most significantly increased with aging, suggesting an altered motor-subcortical circuit, thus requiring more energy for the optimal control. Moreover, the control energy of bilateral putamen showed the largest positive age effect, and this pattern was also supported by the energetic impact of nodes, implying a key role for motor modulation associated with aging. Taken together, our results offer insights of control energy cost necessary for the age-dependent decline in motor task, and provide new clues for brain optimal control of neuromodulation in older adults.

Supplemental material, supplemental_material_clean for Motor Imagery Training After Stroke Increases Slow-5 Oscillations and Functional Connectivity in the Ipsilesional Inferior Parietal Lobule by Xu Wang, Hewei Wang, Xin Xiong, Changhui Sun, Bing Zhu, Yiming Xu, Mingxia Fan, Shanbao Tong, Limin Sun and Xiaoli Guo in Neurorehabilitation and Neural Repair

Recently frontal midline theta (FMθ, 4–8 Hz) oscillations have been consistently reported and proposed as the potential neural mechanism for response inhibition, a core component of human executive functions. However, it remains unclear to what extent the increase of FMθ power during response inhibition tasks is influenced by other non-inhibitory cognitive processes that are usually required for the tasks. In this study, we examined attention-related effects on FMθ during response inhibition by revisiting the EEG data from healthy young adults (N = 30) while performing a spatial cueing Go/NoGo task (Hong et al., 2017). Such an experimental design enabled us to manipulate selective attention that was voluntarily deployed to the stimuli triggering response inhibition. Although commission error rates were low for the NoGo trials, response preparation and prepotent motor activities were qualified by observing significant contingent negative variation (CNV) and lateralized readiness potential (LRP) in both the Go and the NoGo trials. We observed an increase of FMθ power in both attended and ignored conditions of the NoGo trials compared with the Go trials, while FMθ power was significantly smaller in the ignored condition than in the attended condition. Furthermore, source localization analysis suggested cingulate cortex as the main origin for FMθ in the NoGo trials, and FMθ power differences between the attended and ignored conditions were localized in cingulate gyrus. We further provided evidence for attention-dependent FMθ generation by correlating theta source density with ERP signatures of attention (N1), response preparation (CNV), and motor activity (LRP). Overall, our findings suggest that during the Go/NoGo task, the increase of FMθ power was not purely driven by response inhibition, and part of FMθ generators in cingulate gyrus was significantly modulated by attention-related processing (possibly conflict monitoring).

Voluntarily shifting attention to a location of the visual field improves the perception of stimulus at the attended location and suppresses information processing at unattended locations, something referred to as visual spatial attention. Previous studies have shown that alpha band phase synchronization between frontal and posterior regions was modulated by visual spatial attention. However, the causality of such long-range connectivity is still unknown, which makes it difficult to assess its relation to the underlying neural mechanisms of visual spatial attention. In this study, 64-channel scalp electroencephalography (EEG) was collected from 26 healthy adults when performing a visual spatial-cueing attention task, and a recently proposed algorithm, phase transfer entropy (PTE), was used to study the directed alpha phase interactions between frontal and posterior regions during attention orienting. We found that: (i) The PTE from frontal regions to posterior regions significantly increased after cue onset; (ii) The PTE from frontal regions (especially the right hemisphere) to posterior regions showed significant lateralization during late cue-target interval, with the greater PTE of contralateral frontal-to-posterior pair than that of ipsilateral pair relative to cue direction. These results suggest that alpha phase interactions might reveal top-down control signals from frontal to posterior regions during visual spatial attention, and support the right frontal regions as the causal role in top-down attentional control.

Background: The capacity for TMS to elicit neural activity and manipulate cortical excitability has created significant expectation regarding its use in both cognitive and clinical neuroscience. However, the absence of an ability to quantify stimulation effects, particularly outside of the motor cortex, has led clinicians and researchers to pair noninvasive brain stimulation with noninvasive neuroimaging techniques. fNIRS, as an optical and wearable neuroimaging technique, is an ideal candidate for integrated use with TMS. Together, TMS+fNIRS may offer a hybrid alternative to “blind” stimulation to assess NIBS in therapy and research. Objective: In this systematic review, the current body of research into the transient and prolonged effects of TMS on fNIRS-based cortical hemodynamic measures while at rest and during tasks are discussed. Additionally, studies investigating the relation of fNIRS to measures of cortical excitability as produced by TMS-evoked Motor-Evoked-Potential (MEP) are evaluated. The aim of this review is to outline the integrated use of TMS+fNIRS and consolidate findings related to use of fNIRS to monitor changes attributed to TMS and the relationship of fNIRS to cortical excitability itself. Methods: Key terms were searched in PubMed and Web-of-Science to identify studies investigating the use of both fNIRS and TMS. Works from Google-Scholar and referenced works in identified papers were also assessed for relevance. All published experimental studies using both fNIRS and TMS techniques in the study methodology were included. Results: A combined literature search of neuroimaging and neurostimulation studies identified 53 papers detailing the joint use of fNIRS and TMS. 22/53 investigated the immediate effects of TMS at rest in the DLPFC and M1 as measured by fNIRS. 21/22 studies reported a significant effect in [HbO] for 40/54 stimulation conditions with 14 resulting an increase and 26 in a decrease. While 15/22 studies also reported [HbR], only 5/37 conditions were significant. Task effects of fNIRS+TMS were detailed in 16 studies, including 10 with clinical populations. Most studies only reported significant changes in [HbO] related measures. Studies comparing fNIRS to changes in MEP-measured cortical excitability suggest that fNIRS measures may be spatially more diffuse but share similar traits. Conclusion: This review summarizes the progress in the development of this emerging hybrid neuroimaging & neurostimulation methodology and its applications. Despite encouraging progress and novel applications, a lack of replicated works, along with highly disparate methodological approaches, highlight the need for further controlled studies. Interpretation of current research directions, technical challenges of TMS+fNIRS, and recommendations regarding future works are discussed.

Parkinson's disease (PD) is a neurodegenerative disease characterized by dysfunction in distributed functional brain networks. Previous studies have reported abnormal changes in static functional connectivity using resting-state functional magnetic resonance imaging (fMRI). However, the dynamic characteristics of brain networks in PD is still poorly understood. This study aimed to quantify the characteristics of dynamic functional connectivity in PD patients at nodal, intra- and inter-subnetwork levels. Resting-state fMRI data of a total of 42 PD patients and 40 normal controls (NCs) were investigated from the perspective of the temporal variability on the connectivity profiles across sliding windows. The results revealed that PD patients had greater nodal variability in precentral and postcentral area (in sensorimotor network, SMN), middle occipital gyrus (in visual network), putamen (in subcortical network) and cerebellum, compared with NCs. Furthermore, at the subnetwork level, PD patients had greater intra-network variability for the subcortical network, salience network and visual network, and distributed changes of inter-network variability across several subnetwork pairs. Specifically, the temporal variability within and between subcortical network and other cortical subnetworks involving SMN, visual, ventral and dorsal attention networks as well as cerebellum was positively associated with the severity of clinical symptoms in PD patients. Additionally, the increased inter-network variability of cerebellum-auditory pair was also correlated with clinical severity of symptoms in PD patients. These observations indicate that temporal variability can detect the distributed abnormalities of dynamic functional network of PD patients at nodal, intra- and inter-subnetwork scales, and may provide new insights into understanding PD.

Speed of Processing (SoP) represents a fundamental limiting step in cognitive performance which may underlie General Intelligence. The measure of SoP is particularly sensitive to aging, neurological or cognitive diseases, and has become a benchmark for diagnosis, cognitive remediation, and enhancement. Neural efficiency of the Dorsolateral Prefrontal Cortex (DLPFC) is proposed to account for individual differences in SoP. However, the mechanisms by which DLPFC efficiency is shaped by training and whether it can be enhanced remain elusive. To address this, we monitored the brain activity of sixteen healthy participants using functional Near Infrared Spectroscopy (fNIRS) while practicing a common SoP task (Symbol Digit Substitution Task) across 4 sessions. Furthermore, in each session, participants received counterbalanced excitatory repetitive transcranial magnetic stimulation (rTMS) during mid-session breaks. Results indicate a significant involvement of the left-DLPFC in SoP, whose neural efficiency is consistently increased through task practice. Active neurostimulation, but not Sham, significantly enhanced the neural efficiency. These findings suggest a common mechanism by which neurostimulation may aid to accelerate learning.

Supplemental material, Revised_Supplementary for Camera-Based Mirror Visual Input for Priming Promotes Motor Recovery, Daily Function, and Brain Network Segregation in Subacute Stroke Patients by Li Ding, Xu Wang, Shugeng Chen, Hewei Wang, Jing Tian, Jifeng Rong, Peng Shao, Shanbao Tong, Xiaoli Guo and Jie Jia in Neurorehabilitation and Neural Repair

Cerebrovascular dysfunction characterized by the neurovascular unit (NVU) impairment contributes to the pathogenesis of Alzheimer's disease (AD). In this study, a cerebrovascular‐targeting multifunctional lipoprotein‐biomimetic nanostructure (RAP‐RL) constituted with an antagonist peptide (RAP) of receptor for advanced glycation end‐products (RAGE), monosialotetrahexosyl ganglioside, and apolipoprotein E3 is developed to recover the functional NVU and normalize the cerebral vasculature. RAP‐RL accumulates along the cerebral microvasculature through the specific binding of RAP to RAGE, which is overexpressed on cerebral endothelial cells in AD. It effectively accelerates the clearance of perivascular Aβ, normalizes the morphology and functions of cerebrovasculature, and restores the structural integrity and functions of NVU. RAP‐RL markedly rescues the spatial learning and memory in APP/PS1 mice. Collectively, this study demonstrates the potential of the multifunctional nanostructure RAP‐RL as a disease‐modifying modality for AD treatment and provides the proof of concept that remodeling the functional NVU may represent a promising therapeutic approach toward effective intervention of AD., RAP‐RL, a multifunctional lipoprotein‐like nanostructure, which contains RAGE antagonist peptide (RAP), GM1 and ApoE3, is designed to rescue AD cognitive deficits through remodeling the neurovascular unit. RAP‐RL accumulates along the cerebral microvasculature through the specific binding of RAP to RAGE. It decreases neuroinflammation, accelerates the perivascular Aβ clearance, restores the structure and function of the cerebrovasculature system, and efficiently alleviates spatial learning and memory in AD model mice.

OCCUPATIONAL APPLICATIONS Our results illustrate the enhanced functional connectivity between motor-related brain regions and high-level cognitive brain regions during the transition period between rest and hand movements. These results suggest that the sensorimotor network is interacting with prefrontal areas during the transition period to maintain the preparation state. Both actual movement and the transition period without actual movement modulate brain activities. Capturing the detailed relationship of movement intention could be utilized to improve precision and latency of anticipation-based brain–computer interfaces. Furthermore, consistent with the neuroergonomic approach, this study demonstrates that functional near-infrared spectroscopy is a suitable tool for region-specific, task-related, and resting-state functional connectivity analysis. Our findings could enhance the development of more intuitive and natural interfaces between human and machine systems in diverse areas. The approach presente...

Subjects may voluntarily implement an internal or external strategy during mental rotation (MR) task. However, few studies have reported the spatiotemporal differences of brain activation between the two MR strategies. This study aims to compare the two strategies from the perspective of behavioral performance and spatiotemporal brain activations in each cognitive sub-stage using EEG measurements. Both the internal (IN) and external (EX) groups showed a significant 'angle effect' on reaction time (RT) and accuracy (ACC). However, a smaller increase of RT with rotation angle was observed in the EX group. Event-related (de)synchronization in the beta band revealed similar temporal patterns of brain activation in the two groups, but with a stronger activation in the MR sub-stage in the EX group. We speculate that MR of 3D abstract objects is easier when an external strategy is used, and would be promoted by an additional visual-spatial process involving the parietal-occipital areas. Our results suggested that the differences between the two strategies were mainly induced by main MR rather than other cognitive processes.

The basal ganglia (BG) is involved in higher order motor control such as movement planning and execution of complex motor synergies. Neuroimaging study on stroke patients specifically with BG lesions would help to clarify the consequence of BG damage on motor control. In this paper, we performed a longitudinal study in the stroke patients with lesions in BG regions across three motor recovery stages, i.e., less than 2week (Session 1), 1-3m (Session 2) and more than 3m (Session 3). The patients showed an activation shift from bilateral hemispheres during early sessions (3m) to the ipsilesional cortex in late session (3m), suggesting a compensation effect from the contralesional hemisphere during motor recovery. We found that the lateralization of cerebellum(CB) for affected hand task correlated with patients' concurrent Fugl-Meyer index (FMI) in Session 2. Moreover, the cingulate cortex lateralization index in Session 2 was shown to significantly correlate with subsequent FMI change between Session 3 and Session 2, which serves as a prognostic marker for motor recovery. Our findings consolidated the close interactions between BG and CB during the motor recovery after stroke. The dominance of activation in contralateral cingulate cortex was associated with a better motor recovery, suggesting the important role of ipsilesional attention modulation in the early stage after BG stroke.

Despite accumulating evidence suggesting improvement in one's well-being as a result of meditation, little is known about if or how the brain and the periphery interact to produce these behavioral and mental changes. We hypothesize that meditation reflects changes in the neural representations of visceral activity, such as cardiac behavior, and investigated the integration of neural and visceral systems and the spontaneous whole brain spatiotemporal dynamics underlying traditional Tibetan Buddhist meditation. In a large cohort of long-term Tibetan Buddhist monk meditation practitioners, we found distinct transient modulations of the neural response to heartbeats in the default mode network (DMN), along with large-scale network reconfigurations in the gamma and theta bands of electroencephalography (EEG) activity induced by meditation. Additionally, temporal-frontal network connectivity in the EEG theta band was negatively correlated with the duration of meditation experience, and gamma oscillations were uniquely, directionally coupled to theta oscillations during meditation. Overall, these data suggest that the neural representation of cardiac activity in the DMN and large-scale spatiotemporal network integrations underlie the fundamental neural mechanism of meditation and further imply that meditation may utilize cortical plasticity, inducing both immediate and long-lasting changes in the intrinsic organization and activity of brain networks.

Brain plasticity after amputation is related to the short-term unmasking of latent synapses as well as the long-term reorganization due to the sprouting new synaptic connections. The cortical functional reorganization has been reported along the intact somatosensory pathway after unilateral deafferentation. Cerebral blood flow (CBF) change serves as an important biomarker of the functional reorganization of brain. Using laser speckle contrast imaging (LSCI) technology, we performed a longitudinal study to unveil the cortical functional reorganization after forelimb amputation in rodent model, particularly along the intact somatosensory pathway. Our results showed that the CBF response to electrical stimulation of the intact forepaw increased significantly at 9 hours after amputation in acute stage. While in chronic stage (>14 days), the CBF response showed a pattern similar to the control group. The results showed the dynamic brain functional response along the intact somatosensory pathway at different stages after amputation and indicated that cortical functional reorganization occurred within the acute stage. Our work provided additional insights in understanding the inter-hemispheric functional changes from acute to chronic stages of amputation.

Task-related reorganization of functional connectivity (FC) has been widely investigated. Under classic static FC analysis, brain networks under task and rest have been demonstrated a general similarity. However, brain activity and cognitive process are believed to be dynamic and adaptive. Since static FC inherently ignores the distinct temporal patterns between rest and task, dynamic FC may be more a suitable technique to characterize the brain’s dynamic and adaptive activities. In this study, we adopted [Formula: see text]-means clustering to investigate task-related spatiotemporal reorganization of dynamic brain networks and hypothesized that dynamic FC would be able to reveal the link between resting-state and task-state brain organization, including broadly similar spatial patterns but distinct temporal patterns. In order to test this hypothesis, this study examined the dynamic FC in default-mode network (DMN) and motor-related network (MN) using Blood-Oxygenation-Level-Dependent (BOLD)-fMRI data from 26 healthy subjects during rest (REST) and a hand closing-and-opening (HCO) task. Two principal FC states in REST and one principal FC state in HCO were identified. The first principal FC state in REST was found similar to that in HCO, which appeared to represent intrinsic network architecture and validated the broadly similar spatial patterns between REST and HCO. However, the second FC principal state in REST with much shorter “dwell time” implied the transient functional relationship between DMN and MN during REST. In addition, a more frequent shifting between two principal FC states indicated that brain network dynamically maintained a “default mode” in the motor system during REST, whereas the presence of a single principal FC state and reduced FC variability implied a more temporally stable connectivity during HCO, validating the distinct temporal patterns between REST and HCO. Our results further demonstrated that dynamic FC analysis could offer unique insights in understanding how the brain reorganizes itself during rest and task states, and the ways in which the brain adaptively responds to the cognitive requirements of tasks.

In this paper, we review the current state-of-the-art techniques used for understanding the inner workings of the brain at a systems level. The neural activity that governs our everyday lives involves an intricate coordination of many processes that can be attributed to a variety of brain regions. On the surface, many of these functions can appear to be controlled by specific anatomical structures; however, in reality, numerous dynamic networks within the brain contribute to its function through an interconnected web of neuronal and synaptic pathways. The brain, in its healthy or pathological state, can therefore be best understood by taking a systems-level approach. While numerous neuroengineering technologies exist, we focus here on three major thrusts in the field of systems neuroengineering: neuroimaging, neural interfacing, and neuromodulation. Neuroimaging enables us to delineate the structural and functional organization of the brain, which is key in understanding how the neural system functions in both normal and disease states. Based on such knowledge, devices can be used either to communicate with the neural system, as in neural interface systems, or to modulate brain activity, as in neuromodulation systems. The consideration of these three fields is key to the development and application of neuro-devices. Feedback-based neuro-devices require the ability to sense neural activity (via a neuroimaging modality) through a neural interface (invasive or noninvasive) and ultimately to select a set of stimulation parameters in order to alter neural function via a neuromodulation modality. Systems neuroengineering refers to the use of engineering tools and technologies to image, decode, and modulate the brain in order to comprehend its functions and to repair its dysfunction. Interactions between these fields will help to shape the future of systems neuroengineering—to develop neurotechniques for enhancing the understanding of whole-brain function and dysfunction, and the management of neurological and mental disorders.

Dynamic functional connectivity analysis, a rapidly growing method, has been demonstrated to provide new spatiotemporal information about how brain motor network would reorganize from rest to motor tasks. Phase synchronization analysis, which has been widely applied in EEG-based FC analysis, is a promising alternative method in dynamic FC analysis. In this study, fMRI data were recorded from 28 healthy volunteers when they are resting and performing hand closing and opening (HCO) task. Dynamic FC was estimated by phase synchronization analysis. In addition, functional connectivity variability (FCV) was compared between rest and HCO to investigate the modulation induced by motor task on dynamics of motor-related FC and network. Results showed that the FCVs in network-of-interest, including default-mode network and motor network, decreased during HCO comparing with rest. Our results demonstrated that the unconstrained mental activities, which resulted in high FCV during rest, would focus on motor execution during HCO and thus led to decreased FCV during HCO.

Major depressive disorder (MDD) is associated with excessive self-focus and a tendency to engage in self-reflection. Women are more inclined to form negative thoughts when facing problems such as social rejection. The neuroimaging studies addressing MDD females are still rare. The medial prefrontal cortex, a central node of anterior default mode network (DMN), plays an important role in the pathophysiology of MDD. In this study, we explored the inter-regional correlation feature of mPFC with whole brain through functional connectivity (FC) analysis of resting state functional magnetic resonance imaging (rs-fMRI) data. Increased FC with left anterior cingulate cortex (ACC_L) was found in female MDD patients compared with healthy controls. Furthermore, the FC strength of ACC_L was positively correlated with clinical scores, which implied the important role of mPFC-ACC pathway in MDD females. Moreover, decreased FC with right middle temporal gyrus (mTG_R) and left middle temporal gyrus (mTG_L) was found in MDD females, which may result from the low self-evaluation in MDD. This work provides additional insights in understanding the pathophysiological mechanisms of MDD women.

To study the metabolic changes following amputation, we investigated the metabolite concentrations in the secondary somatosensory cortex and thalamus from twenty-three upper limb amputees and sixteen age-matched healthy controls using proton magnetic resonance spectroscopy (MRS). The ratios of major metabolites to the creatine (Cr) peak were quantified to indicate metabolite levels. Compared with the healthy controls, the amputees showed significantly reduced NAA/Cr and Cho/Cr ratios in the secondary somatosensory cortex and thalamus contralateral to the amputation side, indicating neuronal loss and dysfunctions in these brain regions due to the loss of sensory input. Meanwhile, the stump sensation was found to be positively correlated with NAA/Cr ratio and negatively correlated with GSH/Cr ratio in the thalamus. The results suggested that both the thalamus and somatosensory cortex may undergo metabolic changes after amputation.

Plasticity-based spontaneous recovery and rehabilitation intervention of stroke-induced hemianopia have drawn great attention in recent years. However, the underlying neural mechanism remains unknown. This study aims to investigate brain network disruption and reorganization in hemianopia patients due to mild occipital stroke. Resting-state networks were constructed from 12 hemianopia patients with right occipital infarct by partial directed coherence analysis of multi-channel electroencephalograms. Compared with control subjects, the patients presented enhanced connectivity owing to newly formed connections. Compensational connections mostly originated from the peri-infarct area and targeted contralesional frontal, central, and parietal cortices. These new ipsilesional-to-contralesional inter-hemispheric connections coordinately presented significant correlation with the extent of vision loss. The enhancement of connectivity might be the neural substrate for brain plasticity in stroke-induced hemianopia and may shed light on plasticity-based recovery or rehabilitation.

As a key high-level cognitive function in human beings, response inhibition is crucial for adaptive behavior. Previous neuroimaging studies have shown that older individuals exhibit greater neural activation than younger individuals during response inhibition tasks. This finding has been interpreted within a neural compensation framework, in which additional neural resources are recruited in response to age-related cognitive decline. Although this interpretation has received empirical support, the precise event-related temporal course of this age-related compensatory neural response remains unexplored. In the present study, we conducted source analysis on inhibition-related ERP components (i.e., N2 and P3) that were recorded while healthy younger and older adults participated in a visual Go/NoGo task. We found that older adults showed increased source current densities of the N2 and P3 components than younger adults, which support previous hemodynamic findings. Further, such age-related differences in neural activation were successfully separated between the N2 and P3 periods by source localization analysis. Interestingly, the increased activations in older adults were primarily localized to the right precentral and postcentral gyri during the N2 period, which shifted to the right dorsolateral prefrontal cortex and the right inferior frontal gyrus during the P3 period. Taken together, our results clearly illustrate the spatiotemporal dynamics of age-related functional brain reorganization, and further specify the exact temporal course at the millisecond scale by which age-related compensatory neural responses occur during response inhibition.

Functional connectivity (FC), obtained from functional magnetic resonance imaging (fMRI), brings insights into the functional organization of the brain. Recently, rich and complex behaviour of brain has been revealed by the dynamic fluctuation of FC, which had previously been regarded as confounding ‘noise’. While the dynamics of long-distance, inter-regional FC has been extensively studied, the dynamics of local FC within a few millimetres in space remains largely unexplored. In this study, the local FC was depicted by regional homogeneity (ReHo), and the dynamics of local FC was obtained using sliding windows method. We observed a robust positive correlation between ReHo and its temporal variability, which was shown to be an intrinsic feature of the brain rather than a pure stochastic effect. Furthermore, fluctuation of ReHo was associated with global functional organization: (i) brain regions with higher centrality of inter-regional FC tended to possess higher ReHo variability; (ii) coherence of ReHo fluctuation was higher within brain’s functional modules. Finally, we observed alteration of ReHo variability during a motor task compared with resting-state. Our findings associated the temporal fluctuation of ReHo with brain function, opening up the possibility of dynamic local FC study in the future.

Although inter-regional phase synchrony of neural oscillations has been proposed as a plausible mechanism for response control, little is known about the possible effects due to normal aging. We recorded multi-channel electroencephalography (EEG) from healthy younger and older adults in a Go/NoGo task, and examined the aging effects on synchronous brain networks with graph theoretical analysis. We found that in both age groups, brain networks in theta, alpha or beta band for either response execution (Go) or response inhibition (NoGo) condition showed prominent small-world property. Furthermore, small-world property of brain networks showed significant differences between different task conditions. Further analyses of node degree suggested that frontal-central theta band phase synchrony was enhanced during response inhibition, whereas during response execution, increased phase synchrony was observed in beta band over central-parietal regions. More interestingly, these task-related modulations on brain networks were well preserved and even more robust in older adults compared with younger adults. Taken together, our findings not only suggest that response control involves synchronous brain networks in functionally-distinct frequency bands, but also indicate an increase in the recruitment of brain network resources due to normal aging.

Emerging evidence has suggested that the pathophysiology of obsessive compulsive disorder (OCD) might involve widely distributed large-scale brain systems. The dysfunction within salience network, which is comprised of dorsal anterior cingulated cortex (dACC) and bilateral insular areas, has been proposed to contribute to OCD onset. The mechanism underlying salience network abnormality remains unclear and it is worthwhile to investigate its clinical relevance using functional neuroimaging approaches. In this study, we performed the spontaneous brain activity measurement using resting-state functional magnetic resonance imaging (fMRI) on unmedicated OCD patients (n=23). Specifically, the amplitude of low frequency (0.01–0.08 Hz) fluctuations (ALFF) was calculated for regions in salience network. The voxel-based Pearson's correlative analysis was conducted to explore the relationship beween ALFF measures and symptom severity for OCD patients. The results showed that the spontaneous neuronal activity in insula was significantly correlated to OCD clinical symptoms, especially compulsive behaviors. Our findings consolidated that the salience network played an important role in the pathogenesis of OCD and the intensity of intrinsic brain activity in insula provided a predictive biomarker for OCD symptom severity.

The intact crossed pathway via which the contralesional hemisphere responds to the ipsilesional somatosensory input has shown to be affected by unilateral stroke. The aim of this study was to investigate the plasticity of the intact crossed pathway in response to different intensities of stimulation in a rodent photothrombotic stroke model. Using optical intrinsic signal imaging, an overall increase of the contralesional cortical response was observed in the acute phase (≤48 hours) after stroke. In particular, the contralesional hyperactivation is more prominent under weak stimulations, while a strong stimulation would even elicit a depressed response. The results suggest a distinct stimulation-response pattern along the intact crossed pathway after stroke. We speculate that the contralesional hyperactivation under weak stimulations was due to the reorganization for compensatory response to the weak ipsilateral somatosensory input.

Major depressive disorder (MDD) is twice more prevalent in females than in males. Yet, there have only been a few studies on the functional brain activity in female MDD patients and the detailed mechanisms underlying their neurobiology merit further investigations. In the present work, we used combined fMRI-MRS methods to investigate the altered intrinsic neuronal activity and its association with neurotransmitter concentration in female MDD patients.The whole brain amplitude of low frequency fluctuation (ALFF) analysis using resting state functional magnetic resonance imaging (fMRI) was performed to explore the alteration of intrinsic neuronal signals in MDD females (n=11) compared with female healthy controls (n=11). With a specific interest in the medial prefrontal cortex (mPFC) area, we quantified the concentration of amino acid neurotransmitters including GABA ((r-aminobutyric acid)), Glu (Glutamate), and Glx (Glutamate + Glutamine) using (1)H-MRS technology. Moreover, we conducted Pearson correlation analysis between the ALFF value and neurotransmitter concentration to find out the functional-biochemical relation in mPFC area. The relationship between the metabolites concentration and MDD symptomatology was also examined through Spearman correlation analysis.We found that the female MDD patients showed increased neuronal spontaneous activity in left medial prefrontal cortex (mPFC) and left middle frontal cortex, with decreased ALFF level in right putamen and right middle temporal cortex (p0.01, Alphasim corrected). The ALFF in mPFC was shown positively correlated with Glu concentration in female MDD patients (r=0.67, p=0.023). The Glu concentration in mPFC was positively correlated with patients HAMA scores (r=0.641, p=0.033).The relatively small sample size, metabolite information acquired only in mPFC and not all patients were unmedicated are the major limitations of our study.Using combined fMRI-MRS methods, we found increased spontaneous neuronal activity was correlated with Glu concentration in mPFC of female MDD patients. Other regions including left middle frontal gyrus, right putamen and middle temporal gyrus also showed altered spontaneous neuronal activities. The abnormal intrinsic neuronal activities in fronto-cortical regions shed light on the pathogenesis underlying MDD females. The multimodal resting-state neuroimaging technique served as a useful tool for functional-biochemical investigation of MDD pathophysiology.

Cross-modal sensory integration between the auditory and visual systems has long been a topic of interest in cognitive neuroscience, but spatiotemporal cortical interdependence under audiovisual stimulation is still poorly understood. In this letter, parametric spectral analysis, specifically partial directed coherence (PDC), is used to study the cortical connective causal-interdependence network under audiovisual cognitive processes within the time window of the N1 component, i.e., 96-145 ms poststimulus in the event-related potential (ERP). A total of 13 subjects (age: 22.9 plusmn 0.8 years; male/female = 9/4) performed an audiovisual recognition task. Multichannel EEG signals were analyzed using an adaptive multivariate autoregressive model to identify causal influences between different cortical areas. Three different cortical connective networks were detected, and by comparing the cortical PDC network in the early cognitive process of audiovisual (VA) perception with that in unimodal situations (V or A), it was found that the left temporal cortex (TC) might be responsible for audiovisual integration. Such electrophysiological findings were highly consistent with previous functional neuroimaging results. Moreover, the results presented here show the dynamics of lateral causal influences during audiovisual integration.

Traumatic brain injury (TBI) is the leading cause of death and disability among children in the United States. Affected children will often suffer from emotional, cognitive and neurological impairments throughout life. In the controlled cortical impact (CCI) animal model of pediatric TBI (postnatal day 16–17) it was demonstrated that injury results in abnormal neuronal hypoactivity in the non-injured primary somatosensory cortex (S1). It materializes that reshaping the abnormal post-injury neuronal activity may provide a suitable strategy to augment rehabilitation. We tested whether high-frequency, non-invasive transcranial magnetic stimulation (TMS) delivered twice a week over a four-week period can rescue the neuronal activity and improve the long-term functional neurophysiological and behavioral outcome in the pediatric CCI model. The results show that TBI rats subjected to TMS therapy showed significant increases in the evoked-fMRI cortical responses (189%), evoked synaptic activity (46%), evoked neuronal firing (200%) and increases expression of cellular markers of neuroplasticity in the non-injured S1 compared to TBI rats that did not receive therapy. Notably, these rats showed less hyperactivity in behavioral tests. These results implicate TMS as a promising approach for reversing the adverse neuronal mechanisms activated post-TBI. Importantly, this intervention could readily be translated to human studies.

The coupling of cerebral blood flow (CBF) to neuronal activation, referred to as activation flow coupling (AFC), has been a fundamental brain physiology property. The stimulus-evoked CBF response was usually considered as a surrogate marker for neuronal activity in AFC studies. The selection of appropriate stimulation parameters, e.g., current amplitude and pulse width, is of great importance yet the effect of pulse width changes remained contradictory in previous studies. In this work, we use laser speckle contrast imaging (LSCI) to study the spatiotemporal CBF response to hindpaw somatosensory stimulation of different pulse widths (0.3 ms vs 1 ms) and current amplitudes (3 mA vs 6 mA) in a rodent experiment. The results showed that the change of pulse width significantly affected the CBF peak value at a lower current level (p;0.05). In addition, the duration for observing significantly different average CBF response, denoted as td, at various pulse widths, was dependent on stimulus current amplitude. At a lower amplitude (3 mA), td was 6.5 s; While at a higher amplitude (6 mA), td was 2.5 s. It was indicated that the changes of pulse width had longer influence on the average CBF response at a lower current amplitude. Our findings may help to understand and explain the inconsistent AFC with different stimulation parameters in fundamental brain physiology.

Numerous studies focused on brain reorganization after stroke from aspects of task-related brain activity and resting-state brain networks. However, studies focusing on the longitudinal reorganization of task-state brain networks were scarce. In this study, functional magnetic resonance imaging data were collected from twelve stroke patients during blocked finger-tapping task at four post-stroke time points (less than 10 days, around 2 weeks, 1 month and 3 months), respectively. The dynamic changes and prognostic value of the network parameters (i.e., topological parameters, functional connectivity and nodal parameters) in task-state motor execution networks were thoroughly evaluated. We found that the topological configuration (clustering coefficient and characteristic path length) of task-state motor execution networks underwent significant shift during stroke recovery. Especially, we found the topological configuration of task-state motor execution networks at the early recovery stage were capable of predicting the motor function restoration during sub-acute phase. In addition, we found increasing functional connectivity between ipsilesional cerebellum and motor cortices in task-state motor execution networks. In general, this study demonstrated the reorganization and prognostic value of task-state brain network after stroke, which provides new insights into understanding the brain reorganization and rehabilitation after stroke.

Stroke recovery involves a battery of plastic changes in the brain. Blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) provides brain activation information with exquisite spatial resolution as a powerful tool for investigating changes in brain plasticity. In this paper, we performed a longitudinal study examining plasticity of functional activation by BOLD-fMRI following stroke. Data were collected from 11 patients with corticospinal tract (CST) damage at three stages of recovery, i.e., acute stage ( 3mons) post stroke. The evolution of cortical activations for both affected and unaffected hand motion tasks were studied. Quantitative activation measurements including the effective size and sum of t values were calculated and the correlations with patient Fugl-Meyer index were analyzed across all stages. Stroke patients showed a shift from bilateral activation in acute and early stage to the ipsilesional activation in chronic stage when performing a movement task with the affected hand, which suggests a compensation effect from the contralesional hemisphere during the recovery process. The correlation analysis showed a significantly negative correlation with cingulate cortex activity at early stage from both quantitative activation measurements, implying the special role of cingulate cortex in stroke recovery. Further investigations are in need to improve the understanding of brain plasticity in stroke patients.

Stroke could result in both structural and functional impairments. Sensory remapping is believed to play a special role in cortical plasticity, which contributes to the recovery after ischemic stroke. Previous studies using imaging and electrophysiological methods have found that sensory representations after stroke can remap not only to the surrounding areas, but also to remote areas. Based on a rodent photothrombotic stroke model using optical intrinsic signal (OIS) imaging, the present study attempts to investigate the remapping of sensory representation in contralesional cortex to ipsilesional hindlimb stimulation. Quantitative analysis revealed an overall expansion of hindlimb representation in contralesional cortex after stroke. Moreover, results indicated that hindlimb representation became less correlated to different stimulation intensity in contrast to the previous positive correlation before stroke. We speculate that diaschisis in the acute stage of stroke might account for such a change in contralesional sensory representation.

Changes in neuronal activity have been shown to be accompanied by alteration in regional cerebral blood flow . In the present study, laser speckle imaging (LSI) was employed to measure stimulus-evoked neuronal activities in rat barrel cortex. The spatiotemporal characteristics of hemodynamic response to mechanical stimuli from 1 to 3 Hz were examined. Time to peak amplitude reduced from 4.5 to 3.5 s with increasing frequencies. Spatially, the response was confined to a small circular region at the beginning and then spread out asymmetrically to the surrounding regions. The maximal area of activation ranged from 2.2 to 3.5 mm/sup 2/, while the time to reach maximal area occurred between 5.5 and 6 s. Moreover, there was a high correlation between LSI and laser-Doppler flowmetry in terms of peak response magnitude and the time to reach peak. These two values were linearly dependent on stimulus frequency whereas area of activation and time to maximal area appeared to be independent of this parameter. LSI's high sensitivity, low cost of the equipment, and size and complexity make this a suitable technique for fundamental neurophysiological investigations.

In the present study Tsallis and Renyi entropy methods were used to study the electric activity of brain following hypoxic–ischemic (HI) injury. We investigated the performances of these parameterized information measures in describing the electroencephalogram (EEG) signal of controlled experimental animal HI injury. The results show that (a): compared with Shannon and Renyi entropy, the parameterized Tsallis entropy acts like a spatial filter and the information rate can either tune to long range rhythms or to short abrupt changes, such as bursts or spikes during the beginning of recovery, by the entropic index q ; (b): Renyi entropy is a compact and predictive indicator for monitoring the physiological changes during the recovery of brain injury. There is a reduction in the Renyi entropy after brain injury followed by a gradual recovery upon resuscitation.

Transcranial magnetic stimulation (TMS) is a noninvasive method used to excite or inhibit cortical activity for experimental, diagnostic, and therapeutic interventions. However, nonmotor regions of the brain targeted in TMS therapies, such as the dorsolateral prefrontal cortex (DLPFC), offer no extrinsic response to stimulation, resulting in a need for a practical method for the evaluation of treatment. We sought to determine the capability of a continuous-wave light emitting diodes (LED)-based functional near-infrared spectroscopy (fNIRS) system to measure evoked cortical hemoglobin changes in the DLPFC during the simultaneous application of TMS to the left-DLPFC under brief stimulation paradigms used in the clinic. Seventeen healthy participants received short TMS trains at F3 in four different stimulation conditions (single pulse, high frequency, intermittent theta burst, and sham) while adjacent fNIRS measurements were recorded. Ten 2-s trains of each stimulation type were delivered with an intertrial interval of 40 s. Results indicated that high-frequency stimulation produces a larger and more evident response than other measured conditions. These findings show that a continuous-wave LED-based fNIRS system can be used to measure TMS-evoked responses and that future TMS applications can benefit from concurrent assessment of localized cortical activation changes.

Background Previous neuroimaging studies implied that the dysfunction of cortico–striato–thalamo–cortical (CSTC) circuit served as the neural basis for the pathophysiology of obsessive–compulsive disorder (OCD). The imbalances in neuronal metabolite and neurotransmitter within CSTC circuit have been shown as the leading reasons of the OCD onset. The aim of this study is to investigate the metabolic alterations, especially the glutamatergic signal dysfunction within CSTC circuit, and the relationships between neural metabolites and the symptom severity of OCD patients. Methods Single voxel magnetic resonance spectroscopy (MRS) was conducted in medial prefrontal cortex (mPFC) and bilateral thalamus areas for thirteen unmedicated adult OCD patients with age-, gender-, and education-matched healthy controls. Quantification and multivariate analysis were performed to identify vital metabolic biomarkers for patients and healthy controls group differentiation. Moreover, we performed Spearman׳s rank correlation analysis for OCD patients to examine the relationship between the metabolite concentration level and OCD symptomatology. Results Patients with OCD showed significantly decreased glutamate level in mPFC ( p =0.021) and right thalamus ( p =0.039), and significantly increased choline compounds in left thalamus ( p =0.044).The glutamate in right thalamus was shown as the most important metabolite for group separation from multivariate analysis ( Q 2 =0.134) and was significantly correlated with the patients׳ compulsion scores (Spearman r =−0.674, p =0.016). Limitations Limited sample size, the use of creatine and phosphocreatine (Cr) ratios rather than absolute concentrations and unresolved glutamine (Gln) are limitations of the present study. Conclusion Our study results consolidated the hypothesis about glutamatergic signaling dysfunction in OCD. To our knowledge, it is the first finding about a reduced thalamic glutamate level in adult unmedicated OCD patients. The dysregulation of glutamate serves as a potential target for the OCD pharmacotherapy and the detailed mechanisms underlying the glutamate alterations within CSTC circuits merit further investigations.

This study investigated mental rotation for identical stimuli and mirrored stimuli by both behavior response and event-related desynchronization (ERD) of EEG signals. Results showed that subjects had longer response time for mirrored stimuli than identical stimuli. Beta-band desynchronization appeared in whole brain with the parietal-occipital dominance. The ERD in beta band recovered slowly in an angular order after 450-600 ms of stimulus onset except the sharp rebound in the case of identical stimuli with rotation at 0 °. This temporal difference of beta ERD between the identical and the mirrored stimuli at 0° rotation and the ERD topographic difference in left fronto-parietal regions, together with the behavior difference, may imply an extra flip process in mirrored condition.

Neuronal oscillations reflect the activity of neuronal ensembles engaged in integrative cognition, and may serve as a functional measure for the cognitive impairment in schizophrenia. This study aims to reveal the abnormal amplitude dynamics of electroencephalogram (EEG) oscillations in schizophrenia patients on multiple time scales. EEGs were recorded from schizophrenia patients ( $n$ = 19) and healthy controls ( $n$ = 16) while they were at resting state with eyes closed, at resting state with eyes open, and at watching video. Detrended fluctuation analysis and measures of life-time and waiting-time were used to characterize the abnormal dynamics of EEG oscillations on both long (1–20 s) and short (≤1 s) time scales. Abnormal dynamics of EEG oscillations in alpha and beta bands were observed. In particular, compared with healthy controls, schizophrenia patients have smaller DFA exponent (implying weaker long-range temporal correlation) in the left fronto-temporal area and smaller DFA exponent, smaller life-time (indicating shorter oscillation burst), and smaller waiting-time in the occipital area in beta band at resting state with eyes open. In addition, schizophrenia patients have larger DFA exponent, larger life-time, and larger waiting-time at some clustered channels in the temporo-parietal area in alpha band at watching video. The present results provide new insights for cognitive deficits and the underlying neuronal dysfunction in schizophrenia.

Recent studies on Alzheimer's disease (AD) have shown disrupted topological organizations of both functional and anatomical brain networks in AD patients, suggesting that AD might be a disease related to disconnection between brain regions. White matter (WM)-based anatomical network can be weighted by fractal anisotropy (FA), which reflects the integrity of axons and myelin sheaths. Thus, study on the WM-based brain network from the perspectives of topological organization and pair-wise edges might provide information about global organization alteration and WM integrity impairment in AD. In the current work, in addition to the topological characteristics of brain networks, we further investigated the disconnection of edges in anatomical brain networks of AD patients via diffusion tensor tractography. The results showed that both the brain networks of AD patients and normal controls (NCs) exhibited small-world property and such small-world property tended to decline with cognitive impairment. Some network metrics (e.g., clustering coefficient, and characteristic path length and mean FA of all edges) were found to be correlated with the cognitive performance. More importantly, compared to NCs, AD patients had decreased FA weight of edges between certain cortical regions, indicating network disconnection and damage of WM integrity. In summary, our results provided further support for the existence of small-world property in anatomical brain networks of AD patients, and revealed reduced edge weights in AD patients' anatomical brain networks.

Sensory maintenance in top-down selective attention to audiovisual inputs involves distributed cortical activations, while the connectivity between the widespread cortical regions has not been well understood. Graph theory has been demonstrated to be a useful tool in the analysis of brain networks. In this study, we used graph theoretical analysis to investigate the functional brain networks for sensory maintenance in top-down selective attention to audiovisual inputs. Electroencephalograms (EEGs) of 30 channels were recorded from 13 young healthy subjects during a passive view task and a top-down intersensory selective attention task. Phase synchronization indices of EEG signals in pair were computed to construct weighted brain networks. We found small-world properties of the brain networks during both passive view state and top-down selective attentional state in α, β, and γ bands. In addition, the significantly increased clustering coefficient and decreased characteristic path length were observed for brain networks during attentional state compared with passive view state in both β band and γ band. Our results suggest that functional brain networks in higher frequency bands, i.e., β band and γ band, are integrated in different ways during attentional state compared with passive view state.

Visual cortical stroke patients may have hemianopia symptom, which affects a number of visual functions. Most studies on hemianopia stroke have mainly focused on cortical activation during visual stimulation, leaving the pattern of functional connectivity between different brain regions uncovered yet. In the present study, we investigate the resting neural networks of hemianopia stroke patients by graph theoretical analysis of functional brain networks constructed with phase synchronization indexes of multichannel electroencephalography (EEG) signals. Our results showed that although the global network topological metrics, i.e., weighted clustering coefficient and characteristic path length of patients and healthy controls are comparable, the left primary visual cortex of patients tend to be less active than that of age-matched healthy subjects. However, hemianopia patients showed greater activation in the ipsilesional (left) temporopolar and orbit frontal areas and the contralesional (right) associative visual cortex. These results may offer new insight into neural substrates of the hemianopia stroke, and the further study of neural plasticity and brain reorganization after hemianopia.

Auditory attentional effort (AAE) could be tuned to different levels in a top-down manner, while its neural correlates are still poorly understood. In this paper, we investigate the cortical connectivity under different levels of AAE. Multichannel EEG signals were recorded from nine subjects (male/female=6=3) in an auditory discrimination task under low or high AAE. Behavioral results showed that subjects paid more attention under high AAE and detected the probe stimuli better than low AAE. Partial directed coherence (PDC) was used to study the cortical functional connectivity within the first 300 ms post-stimulus period which includes the N100 and P200 components in the event-related potential (ERP). Majority of the cortical connections were strengthened with the increase of AAE. The right hemispheric dominance of connectivity in maintaining auditory attention was found under low AAE, which disappeared when the AAE was increased, indicating that the right hemispheric dominance previously reported might be due to a relatively lower AAE. Besides, most cortical connections under high AAE were found to be from the parietal cortex to the prefrontal cortex, which suggested the initiative role of parietal cortex in maintaining a high AAE.

Studies have demonstrated that reorganization of the cortex after stroke contributed to the recovery of motor function. However, these studies paid much more attention to the reorganization of motor-related brain regions and motor executive network which only contained tens of brain regions, ignoring the change in brain-wide network during the restoration of motor function. Based on this consideration, this paper investigated the functional reorganization of brain-wide network during the recovery after stroke from the perspective of graph theory. At four time points (less than 10 days, around 2 weeks, 1 month and 3 months) after stroke onset, we obtained the functional MRI (fMRI) data of stroke patients when they were doing finger tapping task. Based on the fMRI data, we constructed the brain-wide functional network which consisted of 264 putative functional areas for each subject at each time point. Then the topological parameters (e.g., characteristic path length and cluster coefficient) of these brain networks were examined. Results showed that the brain networks shifted towards a non-optimal topological configuration with low small-worldness during the process of recovery. And this finding may broaden our knowledge about the reorganization of brain function during recovery after stroke.