The role of the primary sensorimotor system in generalized epilepsy: Evidence from the cerebello-cerebral functional integration.

The interaction between cerebellum and cerebrum participates widely in function from motor processing to high-level cognitive and affective processing. Because of the motor symptom, idiopathic generalized epilepsy (IGE) patients with generalized tonic-clonic seizure have been recognized to associate with motor abnormalities, but the functional interaction in the cerebello-cerebral circuit is still poorly understood. Resting-state functional magnetic resonance imaging data were collected for 101 IGE patients and 106 healthy controls. The voxel-based functional connectivity (FC) between cerebral cortex and the cerebellum was contacted. The functional gradient and independent components analysis were applied to evaluate cerebello-cerebral functional integration on the voxel-based FC. Cerebellar motor components were further linked to cerebellar gradient. Results revealed cerebellar motor functional modules were closely related to cerebral motor components. The altered mapping of cerebral motor components to cerebellum was observed in motor module in patients with IGE. In addition, patients also showed compression in cerebello-cerebral functional gradient between motor and cognition modules. Interestingly, the contribution of the motor components to the gradient was unbalanced between bilateral primary sensorimotor components in patients: the increase was observed in cerebellar cognitive module for the dominant hemisphere primary sensorimotor, but the decrease was found in the cerebellar cognitive module for the nondominant hemisphere primary sensorimotor. The present findings suggest that the cerebral primary motor system affects the hierarchical architecture of cerebellum, and substantially contributes to the functional integration evidence to understand the motor functional abnormality in IGE patients.

Spatiotemporal dynamics of functional connectivity and association with molecular architecture in schizophrenia.

Schizophrenia is a self-disorder characterized by disrupted brain dynamics and architectures of multiple molecules. This study aims to explore spatiotemporal dynamics and its association with psychiatric symptoms. Resting-state functional magnetic resonance imaging data were collected from 98 patients with schizophrenia. Brain dynamics included the temporal and spatial variations in functional connectivity density and association with symptom scores were evaluated. Moreover, the spatial association between dynamics and receptors/transporters according to prior molecular imaging in healthy subjects was examined. Patients demonstrated decreased temporal variation and increased spatial variation in perceptual and attentional systems. However, increased temporal variation and decreased spatial variation were revealed in higher order networks and subcortical networks in patients. Specifically, spatial variation in perceptual and attentional systems was associated with symptom severity. Moreover, case-control differences were associated with dopamine, serotonin and mu-opioid receptor densities, serotonin reuptake transporter density, dopamine transporter density, and dopamine synthesis capacity. Therefore, this study implicates the abnormal dynamic interactions between the perceptual system and cortical core networks; in addition, the subcortical regions play a role in the dynamic interaction among the cortical regions in schizophrenia. These convergent findings support the importance of brain dynamics and emphasize the contribution of primary information processing to the pathological mechanism underlying schizophrenia.

Progressive trajectories of schizophrenia across symptoms, genes, and the brain.

BACKGROUND: Schizophrenia is characterized by complex psychiatric symptoms and unclear pathological mechanisms. Most previous studies have focused on the morphological changes that occur over the development of the disease; however, the corresponding functional trajectories remain unclear. In the present study, we aimed to explore the progressive trajectories of patterns of dysfunction after diagnosis. METHODS: Eighty-six patients with schizophrenia and 120 healthy controls were recruited as the discovery dataset. Based on multiple functional indicators of resting-state brain functional magnetic resonance imaging, we conducted a duration-sliding dynamic analysis framework to investigate trajectories in association with disease progression. Neuroimaging findings were associated with clinical symptoms and gene expression data from the Allen Human Brain Atlas database. A replication cohort of patients with schizophrenia from the University of California, Los Angeles, was used as the replication dataset for the validation analysis. RESULTS: Five stage-specific phenotypes were identified. A symptom trajectory was characterized by positive-dominated, negative ascendant, negative-dominated, positive ascendant, and negative surpassed stages. Dysfunctional trajectories from primary and subcortical regions to higher-order cortices were recognized; these are associated with abnormal external sensory gating and a disrupted internal excitation-inhibition equilibrium. From stage 1 to stage 5, the importance of neuroimaging features associated with behaviors gradually shifted from primary to higher-order cortices and subcortical regions. Genetic enrichment analysis identified that neurodevelopmental and neurodegenerative factors may be relevant as schizophrenia progresses and highlighted multiple synaptic systems. CONCLUSIONS: Our convergent results indicate that progressive symptoms and functional neuroimaging phenotypes are associated with genetic factors in schizophrenia. Furthermore, the identification of functional trajectories complements previous findings of structural abnormalities and provides potential targets for drug and non-drug interventions in different stages of schizophrenia.

Trait- and State-Dependent Changes in Cortical-Subcortical Functional Networks Across the Adult Lifespan.

BACKGROUND: How the functional interactions of the basal ganglia/thalamus with the cerebral cortex and the cerebellum change over the adult lifespan in movie-watching and resting-state is less clear. PURPOSE: To investigate the functional changes in the organization of the human cortical-subcortical functional networks over the adult lifespan using movie-watching and resting-state fMRI data. STUDY TYPE: Cohort. SUBJECTS: Healthy 467 adults (cross-sectional individuals aged 18-88 years) from the Cambridge Centre for Ageing and Neuroscience (www.cam-can.com). FIELD STRENGTH/SEQUENCE: fMRI using a gradient-echo echo-planar imaging (EPI) sequence at 3 T. ASSESSMENT: Functional connectivities (FCs) of the subcortical subregions (i.e. the basal ganglia and thalamus) with both the cerebral cortex and cerebellum were examined in fMRI data acquired during resting state and movie-watching. And, fluid intelligence scores were also assessed. STATISTICAL TESTS: Student's t-tests, false discovery rate (FDR) corrected. RESULTS: As age increased, FCs that mainly within the basal ganglia and thalamus, and between the basal ganglia/thalamus and cortical networks (including the dorsal attention, ventral attention, and limbic networks) were both increased/decreased during movie-watching and resting states. However, FCs showed a state-dependent component with advancing age. During the movie-watching state, the FCs between the basal ganglia/thalamus and cerebellum/frontoparietal control networks were mainly increased with age, and the FCs in the somatomotor network were decreased with age. During the resting state, the FCs between the basal ganglia/thalamus and default mode/visual networks were mainly increased with age, and the FCs in the cerebellum were mainly decreased with age. Moreover, inverse relationships between FCs and fluid intelligence were mainly found in these network regions. DATA CONCLUSION: Our study may suggest that changes in cortical-subcortical functional networks across the adult lifespan were both state-dependent and stable traits, and that aging fMRI studies should consider the effects of both physiological characteristics and individual situations. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Vascular feature as a modulator of the aging brain.

The cerebral functional reorganization and declined cognitive function of aging might associate with altered vascular features. Here, we explored the altered cerebral hierarchical functional network of 2 conditions (task-free and naturalistic stimuli) in older adults and its relationship with vascular features (systemic microvascular and perfusion features, measured by magnetic resonance imaging) and behavior. Using cerebral gradient analysis, we found that compressive gradient of resting-state mainly located on the primary sensory-motor system and transmodal regions in aging, and further compress in these regions under the continuous naturalistic stimuli. Combining cerebral functional gradient, vascular features, and cognitive performance, the more compressive gradient in the resting-state, the worse vascular state, the lower cognitive function in older adults. Further modulation analysis demonstrated that both vascular features can regulate the relationship between gradient scores in the insula and behavior. Interestingly, systemic microvascular oxygenation also can modulate the relationship between cerebral gradient and cerebral perfusion. Furthermore, the less alteration of the compressive gradient with naturalistic stimuli came with lower cognitive function. Our findings demonstrated that the altered cerebral hierarchical functional structure in aging was linked with changed vascular features and behavior, offering a new framework for studying the physiological mechanism of functional connectivity in aging.

Comprehensive risk assessments and anesthetic management for children with osteogenesis imperfecta: A retrospective review of 252 orthopedic procedures over 5 years.

BACKGROUND: Major anesthetic risks arise in orthopedic surgeries for children with osteogenesis imperfecta, a rare genetically inherited condition presenting diverse skeletal issues. AIM: We aimed to investigate anesthetic risks, including difficult airway, hypo- and hyperthermia, blood loss, and pain, in connection with patient, anesthetic, and surgical factors. METHODS: Both descriptive and inferential statistics were employed to study the anesthetic risks and their predictors. Data of 252 surgeries for 132 Chinese osteogenesis imperfecta patients aged 18 or below were retrieved from the authors' hospital between 2015 and 2019. RESULTS: Two thirds of the cohort were Sillence type IV patients, with types I, III, and V accounting for 7.6%, 14.4%, and 11.4%, respectively. Video and direct laryngoscopy were used. No case of difficult airway was identified. Due to a careful management strategy, intraoperative temperature varied on average between -0.38°C and +0.89°C from the initial temperature. Fifty-two and 18 cases of hyper- and hypothermia were encountered, respectively. The use of sevoflurane for maintenance resulted in a mean increase of +0.24°C [95% CI 0.05 ~ 0.42] in the maximum temperature. Massive blood losses (>20% of estimated total blood volume) were observed in 18.3% of the cases. Neither intraoperative temperature changes nor blood loss was found to be related to Sillence classification. Regional anesthesia techniques were applied to 72.6% of the cases. Ultrasound guidance was used per the judgment of anesthesiologists or when in case of difficult landmarks. The incidence of difficult regional anesthesia was low (4 out of 252). For postoperative analgesia, 154 neuraxial blocks (including 77 caudal and 77 lumbar epidural) and 29 peripheral nerve blocks were performed. CONCLUSION: Anesthesia for children with osteogenesis imperfecta undergoing complex orthopedic procedures was challenging. Proper anesthesia planning was essential for both intraoperative management and postoperative analgesia. Age, surgical duration, and use of sevoflurane for maintenance impacted the intraoperative temperature most, and massive blood loss was not uncommon. The risks for airway or regional anesthesia difficulties were low. Pain scores could be controlled to be ≤3 via multiple techniques.

White-matter functional networks changes in patients with schizophrenia.

Resting-state functional MRI (rsfMRI) is a useful technique for investigating the functional organization of human gray-matter in neuroscience and neuropsychiatry. Nevertheless, most studies have demonstrated the functional connectivity and/or task-related functional activity in the gray-matter. White-matter functional networks have been investigated in healthy subjects. Schizophrenia has been hypothesized to be a brain disorder involving insufficient or ineffective communication associated with white-matter abnormalities. However, previous studies have mainly examined the structural architecture of white-matter using MRI or diffusion tensor imaging and failed to uncover any dysfunctional connectivity within the white-matter on rsfMRI. The current study used rsfMRI to evaluate white-matter functional connectivity in a large cohort of ninety-seven schizophrenia patients and 126 healthy controls. Ten large-scale white-matter networks were identified by a cluster analysis of voxel-based white-matter functional connectivity and classified into superficial, middle and deep layers of networks. Evaluation of the spontaneous oscillation of white-matter networks and the functional connectivity between them showed that patients with schizophrenia had decreased amplitudes of low-frequency oscillation and increased functional connectivity in the superficial perception-motor networks. Additionally, we examined the interactions between white-matter and gray-matter networks. The superficial perception-motor white-matter network had decreased functional connectivity with the cortical perception-motor gray-matter networks. In contrast, the middle and deep white-matter networks had increased functional connectivity with the superficial perception-motor white-matter network and the cortical perception-motor gray-matter network. Thus, we presumed that the disrupted association between the gray-matter and white-matter networks in the perception-motor system may be compensated for through the middle-deep white-matter networks, which may be the foundation of the extensively disrupted connections in schizophrenia.

BOLD-fMRI reveals the association between renal oxygenation and functional connectivity in the aging brain.

Aging is accompanied by a decline in physical and cognitive function. Vascular aging may provide a major influence on these measures. The purpose of this study was to explore the relationship between renal oxygenation and functional connectivity of the aging brain because of the anatomic and hemodynamic similarities between cerebral and renal vessels. Fifty-two healthy older adults were recruited to undergo a BOLD-fMRI scan of the brain and kidneys, and forty-four healthy younger subjects were recruited as the control group. First, cerebral functional connectivity density (FCD) was used to evaluate functional connectivity. Renal medullary and cortical R2* values were extracted respectively, and the ratio of medullary and cortical R2* values (MCR) was calculated. Then, the association between brain FCD and renal MCR was analyzed. Compared with younger adults, the elderly group showed higher renal medullary R2* and MCR, which might reflect a slight abnormality of renal oxygenation with aging. The older subjects also showed enhanced FCD in bilateral motor-related regions and decreased FCD in regions of the default mode network (DMN). The findings indicated that the functional connectivity in the DMN and motor cortices was vulnerable to aging. Moreover, the altered brain FCD values in the watershed regions, DMN and motor cortices were significantly correlated with the renal MCR value in the elderly group. The association between renal oxygenation abnormalities and spontaneous activity in the brain might reflect vascular aging and its influence on the kidney and brain during aging to some extent. This study provided a new perspective for understanding the relationship between tissue oxygenation and brain functional connectivity.

Brain activation and connection across resting and motor-task states in patients with generalized tonic-clonic seizures.

AIMS: Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. METHODS: Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups. RESULTS: All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients. CONCLUSION: Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.

Striatum- and Cerebellum-Modulated Epileptic Networks Varying Across States with and without Interictal Epileptic Discharges.

Idiopathic generalized epilepsy (IGE) is characterized by cryptogenic etiology and the striatum and cerebellum are recognized as modulators of epileptic network. We collected simultaneous electroencephalogram and functional magnetic resonance imaging data from 145 patients with IGE, 34 of whom recorded interictal epileptic discharges (IEDs) during scanning. In states without IEDs, hierarchical connectivity was performed to search core cortical regions which might be potentially modulated by striatum and cerebellum. Node-node and edge-edge moderation models were constructed to depict direct and indirect moderation effects in states with and without IEDs. Patients showed increased hierarchical connectivity with sensorimotor cortices (SMC) and decreased connectivity with regions in the default mode network (DMN). In the state without IEDs, striatum, cerebellum, and thalamus were linked to weaken the interactions of regions in the salience network (SN) with DMN and SMC. In periods with IEDs, overall increased moderation effects on the interaction between regions in SN and DMN, and between regions in DMN and SMC were observed. The thalamus and striatum were implicated in weakening interactions between regions in SN and SMC. The striatum and cerebellum moderated the cortical interaction among DMN, SN, and SMC in alliance with the thalamus, contributing to the dysfunction in states with and without IEDs in IGE. The current work revealed state-specific modulation effects of striatum and cerebellum on thalamocortical circuits and uncovered the potential core cortical targets which might contribute to develop new clinical neuromodulation techniques.

Atypical Hierarchical Connectivity Revealed by Stepwise Functional Connectivity in Aging.

Hierarchical functional structure plays a crucial role in brain function. We aimed to investigate how aging affects hierarchical functional structure and to evaluate the relationship between such effects and molecular, microvascular, and cognitive features. We used resting-state functional magnetic resonance imaging (fMRI) data from 95 older adults (66.94 ± 7.23 years) and 44 younger adults (21.8 ± 2.53 years) and employed an innovative graph-theory-based analysis (stepwise functional connectivity (SFC)) to reveal the effects of aging on hierarchical functional structure in the brain. In the older group, an SFC pattern converged on the primary sensory-motor network (PSN) rather than the default mode network (DMN). Moreover, SFC decreased in the DMN and increased in the PSN at longer link-steps in aging, indicating a reconfiguration of brain hub systems during aging. Subsequent correlation analyses were performed between SFC values and molecular, microvascular features, and behavioral performance. Altered SFC patterns were associated with dopamine and serotonin, suggesting that altered hierarchical functional structure in aging is linked to the molecular fundament with dopamine and serotonin. Furthermore, increased SFC in the PSN, decreased SFC in the DMN, and accelerated convergence rate were all linked to poorer microvascular features and lower executive function. Finally, a mediation analysis among SFC features, microvascular features, and behavioral performance indicated that the microvascular state may influence executive function through SFC features, highlighting the interactive effects of SFC features and microvascular state on cognition.

Intergenerational Transmission of Violence Among Substance-Abusing Chinese Parents: Roles of Detachment and Social Support.

Despite a large population of registered people with drug addiction, child protection in substance-abusing families is a neglected issue in China. The present study aims to investigate the association between parents' childhood abuse history and the risk of abusing their own children in substance-abusing Chinese families and also to examine the mediating role of detachment and moderating role of social support during the intergenerational transmission of abuse. A total of 173 men and 116 women were selected using cluster sampling from two compulsory drug rehabilitation centers in Jiangsu Province. Results indicated that one's childhood abuse history was positively associated with the current perpetration of child abuse for both fathers and mothers. Detachment mediated the linkage between a history of childhood maltreatment and perpetration of child abuse in all types of abuse for both men and women except for women's sexual abuse. Social support from family members buffered the intergenerational transmission of child abuse for fathers but not for mothers. Child maltreatment in substance-abusing families is an urgent issue that needs measures to prevent the intergenerational transmission of violence in China. Intervention programs could involve helping parents cope with their childhood abuse history through rebuilding secure attachment and facilitating social support for their parenting practices, especially for fathers.

Voxel-wise Functional Connectivity of the Default Mode Network in Epilepsies: A Systematic Review and Meta-Analysis.

BACKGROUND: Default Mode Network (DMN) is recognized to be involved in the generation and propagation of epileptic activities in various epilepsies. Converging evidence has suggested disturbed Functional Connectivity (FC) in epilepsies, which was inferred to be related to underlying pathological mechanisms. However, abnormal changes of FC in DMN revealed by different studies are controversial, which obscures the role of DMN in distinct epilepsies. OBJECTIVE: The present work aims to investigate the voxel-wise FC in DMN across epilepsies Methods: A systematic review was conducted on 22 published articles before October 2020, indexed in PubMed and Web of Science. A meta-analysis with a random-effect model was performed using the effect-size signed differential mapping approach. Subgroup analyses were performed in three groups: Idiopathic Generalized Epilepsy (IGE), mixed Temporal Lobe Epilepsy (TLE), and mixed Focal Epilepsy (FE) with different foci. RESULTS: The meta-analysis suggested commonly decreased FC in mesial prefrontal cortices across different epilepsies. Additionally decreased FC in posterior DMN was observed in IGE. The TLE showed decreased FC in temporal lobe regions and increased FC in the dorsal posterior cingulate cortex. Interestingly, an opposite finding in the ventral and dorsal middle frontal gyrus was observed in TLE. The FE demonstrated increased FC in the cuneus. CONCLUSION: The current findings revealed both common and specific alterations of FC in DMN across different epilepsies, highlighting the contribution of these dysfunctions to epileptic activities and cognitive behaviors in patients. Furthermore, the current study provided powerful evidence to support DMN as a potential candidate for effective intervention in epilepsy.

Effects of transcranial direct current stimulation on brain changes and relation to cognition in patients with schizophrenia: a fMRI study.

We studied brain changes during an N-back task before and after 10 sessions of transcranial direct current stimulation (tDCS) and its relation to cognitive changes. This was a double-blind, sham-controlled, randomized study of tDCS in 27 patients with schizophrenia. They performed an N-back task in a 3 T scanner before and after receiving the 10 tDCS sessions. Cognitive performance outside the fMRI session was assessed using the MATRICS Consensus Cognitive Battery and other tests at baseline and several time points after 10 sessions of tDCS. During the N-back task performed during fMRI scans, comparing the 0-back vs. the 2-back task, the active tDCS group demonstrated a significantly increased activation in the right fusiform, left middle frontal, left inferior frontal gyrus (opercular part) and right inferior frontal gyrus (triangular part) and reduced activation in the left posterior cingulum gyrus with most of these results primarily due to increases in activation during the 0-back rather than 2-back task. There were also significant positive or negative correlations between some of the brain changes and cognitive performance. tDCS modulated prefrontal activation at low working memory load or attention mode, but default mode network at higher working memory load. Changes in brain activation measured during the N-back task were correlated with some dimensions of cognitive function immediately after 10 tDCS sessions and at follow-up times. The results support tDCS could offer a potential novel approach for modulating cortical activity and its relation to cognitive function.

Reconfiguration of Functional Dynamics in Cortico-Thalamo-Cerebellar Circuit in Schizophrenia Following High-Frequency Repeated Transcranial Magnetic Stimulation.

Schizophrenia is a serious mental illness characterized by a disconnection between brain regions. Transcranial magnetic stimulation is a non-invasive brain intervention technique that can be used as a new and safe treatment option for patients with schizophrenia with drug-refractory symptoms, such as negative symptoms and cognitive impairment. However, the therapeutic effects of transcranial magnetic stimulation remain unclear and would be investigated using non-invasive tools, such as functional connectivity (FC). A longitudinal design was adopted to investigate the alteration in FC dynamics using a dynamic functional connectivity (dFC) approach in patients with schizophrenia following high-frequency repeated transcranial magnetic stimulation (rTMS) with the target at the left dorsolateral prefrontal cortex (DLPFC). Two groups of schizophrenia inpatients were recruited. One group received a 4-week high-frequency rTMS together with antipsychotic drugs (TSZ, n = 27), while the other group only received antipsychotic drugs (DSZ, n = 26). Resting-state functional magnetic resonance imaging (fMRI) and psychiatric symptoms were obtained from the patients with schizophrenia twice at baseline (t1) and after 4-week treatment (t2). The dynamics was evaluated using voxel- and region-wise FC temporal variability resulting from fMRI data. The pattern classification technique was used to verify the clinical application value of FC temporal variability. For the voxel-wise FC temporary variability, the repeated measures ANCOVA analysis showed significant treatment × time interaction effects on the FC temporary variability between the left DLPFC and several regions, including the thalamus, cerebellum, precuneus, and precentral gyrus, which are mainly located within the cortico-thalamo-cerebellar circuit (CTCC). For the ROI-wise FC temporary variability, our results found a significant interaction effect on the FC among CTCC. rTMS intervention led to a reduced FC temporary variability. In addition, higher alteration in FC temporal variability between left DLPFC and right posterior parietal thalamus predicted a higher remission ratio of negative symptom scores, indicating that the decrease of FC temporal variability between the brain regions was associated with the remission of schizophrenia severity. The support vector regression (SVR) results suggested that the baseline pattern of FC temporary variability between the regions in CTCC could predict the efficacy of high-frequency rTMS intervention on negative symptoms in schizophrenia. These findings confirm the potential relationship between the reduction in whole-brain functional dynamics induced by high-frequency rTMS and the improvement in psychiatric scores, suggesting that high-frequency rTMS affects psychiatric symptoms by coordinating the heterogeneity of activity between the brain regions. Future studies would examine the clinical utility of using functional dynamics patterns between specific brain regions as a biomarker to predict the treatment response of high-frequency rTMS.

Connective profiles and antagonism between dynamic and static connectivity underlying generalized epilepsy.

This study aims to characterize the connective profiles and the coupling relationship between dynamic and static functional connectivity (dFC and sFC) in large-scale brain networks in patients with generalized epilepsy (GE). Functional, structural and diffuse MRI data were collected from 83 patients with GE and 106 matched healthy controls (HC). Resting-state BOLD time course was deconvolved to neural time course using a blind hemodynamic deconvolution method. Then, five connective profiles, including the structural connectivity (SC) and BOLD/neural time course-derived sFC/dFC networks, were constructed based on the proposed whole brain atlas. Network-level weighted correlation probability (NWCP) were proposed to evaluate the association between dFC and sFC. Both the BOLD signal and neural time course showed highly concordant findings and the present study emphasized the consistent findings between two functional approaches. The patients with GE showed hypervariability and enhancement of FC, and notably decreased SC in the subcortical network. Besides, increased dFC, weaker anatomic links, and complex alterations of sFC were observed in the default mode network of GE. Moreover, significantly increased SC and predominantly increased sFC were found in the frontoparietal network. Remarkably, antagonism between dFC and sFC was observed in large-scale networks in HC, while patients with GE showed significantly decreased antagonism in core epileptic networks. In sum, our study revealed distinct connective profiles in different epileptic networks and provided new clues to the brain network mechanism of epilepsy from the perspective of antagonism between dynamic and static functional connectivity.

Different Modulatory Effects of Cognitive Training and Aerobic Exercise on Resting State Functional Connectivity of Entorhinal Cortex in Community-Dwelling Older Adults.

The entorhinal cortex (EC) plays an essential role in age-related cognitive decline. However, the effect of functional connectivity (FC) changes between EC and other cerebral cortices on cognitive function remains unclear. The aim of this study was to explore the modulation of two interventions (cognitive training and aerobic exercise) on EC-FC in community-dwelling older adults. In total, 94 healthy older adults aged between 65 and 75 years were assigned to either the cognitive training or aerobic exercise group to receive 24 sessions over 12 weeks, or to a control group. Resting-state functional magnetic resonance imaging was performed at both baseline and 12-month follow-up. Compared to the cognitive training group, the aerobic exercise group showed greater EC-FC in the bilateral middle temporal gyrus, right supramarginal gyrus, left angular gyrus, and right postcentral gyrus. Compared to the control group, the cognitive training group had a decreased EC-FC in the right hippocampus, right middle temporal gyrus, left angular gyrus, and right postcentral gyrus and an increased EC-FC in the bilateral pallidum, while the aerobic exercise group showed increased EC-FC between the right medial prefrontal cortex(mPFC), bilateral pallidum, and right precuneus. Baseline EC-FC in the mPFC was positively correlated with the visuospatial/constructional index score of the Repeatable Battery for the Assessment of Neuropsychological Status. In the cognitive training group, EC-FC value changes in the right hippocampus were negatively correlated with changes in the RBANS delayed memory index score, while in the aerobic exercise group, EC-FC value changes in the left angular gyrus were positively correlated with changes in the RBANS attention index score. These findings support the hypothesis that both cognitive training and aerobic exercise can modulate EC-FC in aging populations but through different neural pathways.

Detecting the Information of Functional Connectivity Networks in Normal Aging Using Deep Learning From a Big Data Perspective.

A resting-state functional connectivity (rsFC)-constructed functional network (FN) derived from functional magnetic resonance imaging (fMRI) data can effectively mine alterations in brain function during aging due to the non-invasive and effective advantages of fMRI. With global health research focusing on aging, several open fMRI datasets have been made available that combine deep learning with big data and are a new, promising trend and open issue for brain information detection in fMRI studies of brain aging. In this study, we proposed a new method based on deep learning from the perspective of big data, named Deep neural network (DNN) with Autoencoder (AE) pretrained Functional connectivity Analysis (DAFA), to deeply mine the important functional connectivity changes in fMRI during brain aging. First, using resting-state fMRI data from 421 subjects from the CamCAN dataset, functional connectivities were calculated using sliding window method, and the complex functional patterns were mined by an AE. Then, to increase the statistical power and reliability of the results, we used an AE-pretrained DNN to relabel the functional connectivities of each subject to classify them as belonging to the attributes of young or old individuals. A method called search-back analysis was performed to find alterations in brain function during aging according to the relabeled functional connectivities. Finally, behavioral data regarding fluid intelligence and response time were used to verify the revealed functional changes. Compared to traditional methods, DAFA revealed additional, important aged-related changes in FC patterns [e.g., FC connections within the default mode (DMN) and the sensorimotor and cingulo-opercular networks, as well as connections between the frontoparietal and cingulo-opercular networks, between the DMN and the frontoparietal/cingulo-opercular/sensorimotor/occipital/cerebellum networks, and between the sensorimotor and frontoparietal/cingulo-opercular networks], which were correlated to behavioral data. These findings demonstrated that the proposed DAFA method was superior to traditional FC-determining methods in discovering changes in brain functional connectivity during aging. In addition, it may be a promising method for exploring important information in other fMRI studies.

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PURPOSE: The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). METHOD: Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. KEY FINDINGS: Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. SIGNIFICANCE: Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.