Cerebellar Contributions to Language in Typical and Atypical Development: A Review

In this review, we present the growing literature suggesting, from a variety of angles, that the cerebellum contributes to higher-order cognitive functions, rather than simply sensorimotor functions, and more specifically to language and its development. The cerebellum’s association with language function is determined by the specific cortico-cerebellar connectivity to the right cerebellum from the left cortical hemisphere. The findings we review suggest that the cerebellum plays an important role as part of a broader language network, and also implies that the cerebellum may be a potential new therapeutic target to treat speech and language deficits, especially during development.     

fMRI of patients with social anxiety disorder during a social situation task

Previous functional neuroimaging studies found that the amygdala and other limbic regions may play a substantial role in social anxiety disorder (SAD). However, more widely distributed large-scale brain systems may be involved in cognitive processing in SAD patients when confronted with social situations. We employed functional MRI (fMRI) to investigate local brain activation of patients with SAD (n=6) and healthy controls (HC, n=9) during cognitive work. During fMRI scanning, subjects performed a social situation task using a block design paradigm in which the task and control trials were performed by turn. The patients with SAD showed higher anxiety levels during scanning in all social situations. The HC group showed greater common activation in the posterior cingulate cortex (PCC), cuneus, occipital gyrus, and cerebellum. Although the patients with SAD showed activation patterns similar to that of the HC group, they showed comparatively significant decreased activation in the left cerebellum, left precuneus, and bilateral PCC. The present study demonstrates that SAD may involve dysfunction of a broad neuronal network including the limbic system, parieto-posterior cortex and cerebellum. The findings contribute to previous findings that revealed abnormal activities of emotion-related regions including the amygdala and insular cortex during facial perception in SAD.     

Ipsilateral Alteration of Resting State Activity Suggests That Cortical Dysfunction Contributes to the Pathogenesis of Cluster Headache

The pathomechanism of cluster headache (CH) is not entirely understood, but central and peripheral components were suggested. A recent report showed that transcranial magnetic stimulation measured cortical excitability was increased in the hemisphere ipsilalteral to the pain. In the current study we set out to investigate the amplitude of resting brain fMRI activity to find signatures of the increased excitability. High resolution T1 weighted and resting state functional MRI images were acquired from seventeen patients with CH in pain free period and from twenty-six healthy volunteers. Patients’ data were normalized (e.g. inverted along the midsagittal axis) according to the headache side. Independent component analysis and a modified dual regression approach were used to reveal the differences between the resting state networks. Furthermore, the timecourses were decomposed into five frequency bands by discrete wavelet decomposition and were also re-regressed to the original data to reveal frequency specific resting activity maps. Two of the identified resting state networks showed alterations in CH. When the data were inverted to have patients’ headaches on the left, the ipsilateral attention network showed increased connectivity in 0.08–0.04 Hz frequency band in the in CH group. In the same dataset, cerebellar network showed higher functional connectivity in 0.02–0.01 Hz range in the ipsilateral cerebellum. When the data of patients having headache on the left were inverted to the right, similar increased signal was found in the ipsilateral attention network in 0.08–0.04 Hz band. The cerebellar network showed increased connectivity in the cerebellum in 0.02–0.01 Hz band in patients. The Fourier analysis of these area revealed increased power in CH at all cases. Our results showed alterations of brain functional networks in CH. The alterations of resting state activity were found in the hemisphere ipsilateral to the pain, signifying the altered cortical processing in the pathomechanism of CH.     

Divergent brain network connectivity in amyotrophic lateral sclerosis

Using resting state (RS) functional magnetic resonance imaging and independent component analysis, the integrity of brain networks related to cognition and behavior was investigated in 20 nondemented patients with amyotrophic lateral sclerosis (ALS). The association between RS functional connectivity and executive functions was assessed in 16 patients with neuropsychological assessment. ALS patients compared with control subjects showed a decreased connectivity of the right orbitofrontal cortex, and an enhanced connectivity of the left precuneus in the default mode network; a decreased connectivity of the left inferior frontal cortex, and an increased connectivity of the right angular gyrus in the right frontoparietal network; and an increased connectivity of the parietal cortex in the left frontoparietal network. The enhanced parietal connectivity was associated with the clinical and cognitive deficits of the patients. In ALS, an alteration of large-scale functional brain networks associated with cognition does occur, even in the absence of overt dementia. The increased parietal connectivity may have a role in an attempt to maintain cognitive efficiency in the presence of structural frontotemporal injury.     

Functional and Structural Alterations in Temporal Lobe Tumor Patients: Evidence of Functional Compensation in the Human Brain

Patients with temporal lobe tumor are frequently accompanied by cognitive impairments. This study aims to combine diffusion tensor imaging(DTI) with resting-state functional magnetic resonance image(fMRI) to explore the underlying cognitive alternation and functional reorganization in patients with temporal lobe tumor.Twenty patients with right temporal lobe tumor and seventeen healthy volunteers were recruited in this study. Independent component analysis(ICA) was utilized to divide the whole brain into six sub functional networks, and DTI combined with graph-based topological analysis was used to calculate the structural properties of whole-brain and sub functional networks. Besides, the rich hubs in both patients and healthy controls(HCs)were identified and a further analysis of their internal functional and structural connectivity was also conducted. The E_(global) in self-referential network(SRN) of patients is higher than HCs, while decreased E_(global) of dorsal attention network(DAN) and default mode network(DMN) were found in patients. For the patients, brain regions with increased nodal efficiency(E_(nodal)) were located in the frontal lobe(corresponding to SRN). Six identical hubs were found in two groups. Compared patients with HCs, significant between-group differences in both functional and structural connectivity were observed between right insula(INS.R) and right lenticular nucleus, putamen(PUT.R). The findings provide evidence that impaired cognition are closely related to functional and structural abnormalities and the compensatory roles of frontal lobe were also identified in patients.The proposed combination of DTI and f MRI promises a widespread utilization in clinical research on the mechanisms of neurological diseases.     

老年人轻度认知障碍部分定向相干脑网络分析

近年的研究表明,轻度认知障碍(MCI)患者的认知加工呈现脑连通性缺失特征,但各脑区间如何影响,因果特性不明。本研究的目的在于分析MCI患者在认知任务下的有向脑网络特征。采集了30位老人在信息冲突颜色认知作业下的头皮脑电,包括21位正常人和9位MCI患者。选取刺激呈现后的脑电计算其部分定向相干值,依此构建脑网络,并着重分析了不同脑区的入度差异。研究发现：在beta段,MCI患者右前额区信息流入缺失,左中央区的信息流入异常增强;在患者组和正常组中前脑区的入度要远高于后脑区;正常人在匹配和不匹配刺激下右脑区的入度要高于左脑区;但是在患者组中左右脑区的入度却没有明显差别。在特定阈值下：正常人在匹配刺激下左脑区（阈值0.14）的入度要低于MCI患者（F=3.780,P=0.040）;正常人在不匹配刺激下左脑区（阈值0.26）的入度要低于MCI患者（F=3.780,P=0.040）;正常人在匹配刺激下右脑区（阈值0.18）的入度要高于MCI患者（F=3.941,P=0.021）。文章从入度为脑网络特征验证了MCI患者在颜色认知任务下右脑的功能缺损。     

Multivariable network associated with cognitive decline and dementia

Data mining of a large data base from the population longitudinal study named "The Conselice Study" has been the focus of the present investigation. Initially, 65 years old or older participants were interviewed, underwent medical and cognitive examination, and were followed up for 5 years: 937 subjects completed the follow-up. Relationships of 35 genetic and/or phenotypic factors with incident cognitive decline and dementia were investigated. The new mathematical approach, called the Auto Contractive Map (AutoCM), was able to show the differential importance of each variables. This new variable processing created a semantic connectivity map that: (a) preserved non-linear associations; (b) showed connection schemes; (c) captured the complex dynamics of adaptive interactions. This method, based on an artificial adaptive system, was able to define the association strength of each variable with all the others. Few variables resulted to be aggregation points and were considered as major biological hubs. Three hubs were identified in the hydroxyl-methyl-gutaryl-CoA reductase (HMGCR) enzyme, plasma cholesterol levels and age. Gene variants and cognate phenotypic variables showed differential degrees of relevance to brain aging and dementia. This data analysis method was compared with another mathematical model called mutual information relevance network and results are presented and discussed.     

Association Between the Basal Ganglia and Large-Scale Brain Networks in Epilepsy

Epilepsy may affect connectivity between the putamen and cortex even during the resting state. Putamen is part of the basal ganglia resting state network (BG-RSN) which is anti-correlated with the default mode network (DMN) in healthy subjects. Therefore, we aimed at studying the functional brain connectivity (FC) of the putamen with the cortical areas engaged in the DMN as well as with the primary somatomotor cortex which is a cortical region engaged in the BG-RSN. We compared the data obtained in patients with epilepsy with that in healthy controls (HC). Functional magnetic resonance imaging (fMRI) was performed in 10 HC and 24 patients with epilepsy: 14 patients with extratemporal epilepsy (PE) and 10 patients with temporal epilepsy (PT). Resting state fMRI data was obtained using the 1.5 T Siemens Symphony scanner. The Group ICA of fMRI Toolbox (GIFT) program was used for independent component analysis. The component representing the DMN was chosen according to a spatial correlation with a mask typical for DMN. The FC between the putamen and the primary somatomotor cortex was studied to assess the connectivity of the putamen within the BG-RSN. A second-level analysis was calculated to evaluate differences among the groups using SPM software. In patients with epilepsy as compared to HC, the magnitude of anti-correlation between the putamen and brain regions engaged in the DMN was significantly lower. In fact, the correlation changed the connectivity direction from negative in HC to positive in PE and PT. The disturbed FC of the BG in patients with epilepsy as compared with HC was further illustrated by a significant decrease in connectivity between the left/right putamen and the left/right somatomotor cortex, i.e. between regions that are engaged in the BG-RSN. The FC between the putamen and the cortex is disturbed in patients with epilepsy. This may reflect an altered function of the BG in epilepsy.     

Disrupted brain connectome in semantic variant of primary progressive aphasia

Using resting-state functional magnetic resonance imaging and graph analysis, the topological organization of the functional brain network connectivity was explored in patients with left-sided onset semantic variant (SV) of primary progressive aphasia relative to healthy controls. Functional brain networks in SV patients were characterized by a significantly lower mean network degree, clustering coefficient, and global efficiency, longer characteristic path length and higher assortativity compared with controls. SV patients showed also a strongly left-lateralized loss of hubs, and reduced nodal degree in the inferior and ventral temporal regions and occipital cortices. In SV, the decreased nodal degree extended into the medial and ventral frontal cortex bilaterally, left amygdala and/or hippocampus, and left caudate nucleus. These findings provide evidence that the focal structural degeneration of the inferior temporal, and perysilvian language regions in SV patients ultimately results in a distributed pattern of functional connectivity abnormalities. The local network analysis shows that SV is associated with a functional degradation in the “pan-modal” inferior and/or ventral temporal regions, and the “modality-specific” visual cortical origin of the ventral processing pathway.     

Impairment of movement-associated brain deactivation in multiple sclerosis: further evidence for a functional pathology of interhemispheric neuronal inhibition

Motor control demands coordinated excitation and inhibition across distributed brain neuronal networks. Recent work has suggested that multiple sclerosis (MS) may be associated with impairments of neuronal inhibition as part of more general progressive impairments of connectivity. Here, we report results from a prospective, multi-centre fMRI study designed to characterise the changes in patients relative to healthy controls during a simple cued hand movement task. This study was conducted at eight European sites using 1.5 Tesla scanners. Brain deactivation during right hand movement was assessed in 56 right-handed patients with relapsing-remitting or secondary progressive MS without clinically evident hand impairment and in 60 age-matched, healthy subjects. The MS patients showed reduced task-associated deactivation relative to healthy controls in the pre- and postcentral gyri of the ipsilateral hemisphere in the region functionally specialised for hand movement control. We hypothesise that this impairment of deactivation is related to deficits of transcallosal connectivity and GABAergic neurotransmission occurring with the progression of pathology in the MS patients. This study has substantially extended previous observations with a well-powered, multicentre study. The clinical significance of these deactivation changes is still uncertain, but the functional anatomy of the affected region suggests that they could contribute to impairments of motor control.     

Alterations in Normal Aging Revealed by Cortical Brain Network Constructed Using IBASPM

Normal aging has been linked with the decline of cognitive functions, such as memory and executive skills. One of the prominent approaches to investigate the age-related alterations in the brain is by examining the cortical brain connectome. IBASPM is a toolkit to realize individual atlas-based volume measurement. Hence, this study seeks to determine what further alterations can be revealed by cortical brain networks formed by IBASPM-extracted regional gray matter volumes. We found the reduced strength of connections between the superior temporal pole and middle temporal pole in the right hemisphere, global hubs as the left fusiform gyrus and right Rolandic operculum in the young and aging groups, respectively, and significantly reduced inter-module connection of one module in the aging group. These new findings are consistent with the phenomenon of normal aging mentioned in previous studies and suggest that brain network built with the IBASPM could provide supplementary information to some extent. The individualization of morphometric features extraction deserved to be given more attention in future cortical brain network research.     

Functional connectivity in the prefrontal cortex measured by near-infrared spectroscopy during ultrarapid object recognition

Near-infrared spectroscopy (NIRS) is a developing technology for low-cost noninvasive functional brain imaging. With multichannel optical instruments, it becomes possible to measure not only local changes in hemoglobin concentrations but also temporal correlations of those changes in different brain regions which gives an optical analog of functional connectivity traditionally measured by fMRI. We recorded hemodynamic activity during the Go-NoGo task from 11 right-handed subjects with probes placed bilaterally over prefrontal areas. Subjects were detecting animals as targets in natural scenes pressing a mouse button. Data were low-pass filtered<1 Hz and cardiac∕respiration∕superficial layers artifacts were removed using Independent Component Analysis. Fisher's transformed correlations of poststimulus responses (30 s) were averaged over groups of channels unilaterally in each hemisphere (intrahemispheric connectivity) and the corresponding channels between hemispheres (interhemispheric connectivity). The hemodynamic response showed task-related activation (an increase∕decrease in oxygenated∕deoxygenated hemoglobin, respectively) greater in the right versus left hemisphere. Intra- and interhemispheric functional connectivity was also significantly stronger during the task compared to baseline. Functional connectivity between the inferior and the middle frontal regions was significantly stronger in the right hemisphere. Our results demonstrate that optical methods can be used to detect transient changes in functional connectivity during rapid cognitive processes.     

结合表型信息的阿尔兹海默症图卷积神经网络分类方法研究

阿尔兹海默症(AD)的早期检测与发现具有重要的临床和社会意义.由于AD患者的功能性脑网络拓扑性质存在异常变化,并且不同表型类型人群中阿尔兹海默症的患病率也存在着较大差异,因此将脑网络特征和表型信息结合构建训练特征,用于阿尔兹海默症不同阶段的分类.同时,图卷积神经网络(GCN)分类方法被证明是目前对图数据学习任务的最佳选...     

Hypothesis for the pathophysiology of delirium: role of baseline brain network connectivity and changes in inhibitory tone

Normal brain function is facilitated by a highly organized and interconnected structure allowing complex integration of sensory information and motor responses. The acute confusional state of delirium is characterized by a fluctuating disturbance in consciousness, arousal level and cognition-memory; as such, delirium represents a failure in the integration and appropriate processing of information. The pathogenesis of this cognitive disintegration is unclear; herein a hypothesis is proposed that delirium results from an acute breakdown in network connectivity within the brain. The hypothesis predicts that the extent to which the network connectivity breaks down is dependent on two factors: (i) the baseline connectivity within the brain and (ii) the level of inhibitory tone. Baseline connectivity is the connectivity of neural networks within the brain before the precipitating insult provoking delirium. Many non-modifiable risk factors for delirium influence baseline connectivity such as age, cognitive impairment, dementia and depression. Precipitant events that provoke delirium (modifiable risk factors) are hypothesized to further, and acutely, breakdown network connectivity by increasing inhibitory tone within the brain. Modifiable risk factors include inflammation, metabolic abnormalities, sleep deprivation and medication such as benzodiazepines. An important role for GABAergic neurotransmission is implicated in increasing the inhibitory tone to produce delirium. This theory accounts for the various forms of delirium, hypoactive, hyperactive and mixed. The form of delirium that ensues will depend upon how and which networks breakdown (dependent on both the individual’s baseline network connectivity and the degree change in inhibitory tone produced).     

Emotional faces and the default mode network

The default-mode network (DMN) of the human brain has become a central topic of cognitive neuroscience research. Although alterations in its resting state activity and in its recruitment during tasks have been reported for several mental and neurodegenerative disorders, its role in emotion processing has received relatively little attention. We investigated brain responses to different categories of emotional faces with functional magnetic resonance imaging (fMRI) and found deactivation in ventromedial prefrontal cortex (VMPFC), posterior cingulate gyrus (PC) and cuneus. This deactivation was modulated by emotional category and was less prominent for happy than for sad faces. These deactivated areas along the midline conformed to areas of the DMN. We also observed emotion-dependent deactivation of the left middle frontal gyrus, which is not a classical component of the DMN. Conversely, several areas in a fronto-parietal network commonly linked with attention were differentially activated by emotion categories. Functional connectivity patterns, as obtained by correlation of activation levels, also varied between emotions. VMPFC, PC or cuneus served as hubs between the DMN-type areas and the fronto-parietal network. These data support recent suggestions that the DMN is not a unitary system but differentiates according to task and even type of stimulus. The emotion-specific differential pattern of DMN deactivation may be explored further in patients with mood disorder, where the quest for biological markers of emotional biases is still ongoing.     

rTMS联合运动训练对静息态脑网络影响的研究

重复经颅磁刺激(rTMS)联合运动训练可以提高肢体运动能力,在脑卒中后的运动康复中有重要的应用价值。探讨rTMS联合运动训练对静息态脑网络的影响。招募10名健康受试者,使用1 Hz rTMS刺激优势半球,结束后非利手立即执行运动训练,以提高非利手的运动能力,rTMS联合运动训练共持续14天。采集rTMS联合运动训练前后闭目静息态的脑电(EEG)信号,使用相位延迟指数(PLI)进行功能连接性分析,并以PLI值为边的权重计算依据来建立有权无向脑网络,计算网络节点的最短路径长度和节点效率,使用非参数符号秩和检验进行统计学分析。结果发现,rTMS联合运动训练使EEG低频段(theta和alpha)脑功能区间的连接显著增加、高频段(beta、gamma₁和gamma₂)显著降低,对脑功能区内的连接影响较小。特别地,采取rTMS联合运动训练,使alpha频段非优势侧中央区与优势侧额叶区(训练前0.141 4±0.102 5,训练后0.217 2±0.134 7,P<0.05)、非优势侧额叶区(训练前0.141 0±0.109 9,训练后0.205 9±0.136 1,P <0.05)的功能连接性显著增加。网络特征结果显示,节点效率在低频段增加、高频段降低,而节点最短路径长度表现出相反的结果,其中gamma₂频段在双侧中央区的节点效率(左中央区,实验前0.060 0±0.000 3,实验后0.042 9±0.001 3,P <0.05;右中央区,实验前0.060 7±0.002 3,实验后0.041 9±0.002 4,P <0.05)和最短路径长度(左中央区,实验前18.539 0±0.457 1,实验后28.585 8±1.001 4,P<0.05;右中央区,实验前18.650 8±0.438 6,实验后28.853 0±1.652 6,P <0.05)发生显著性的改变。通过该项研究,加深对rTMS联合运动训练促进运动能力神经机制的理解,为未来探究其对脑卒中、脑损伤患者脑活动的影响提供帮助。     

Aberrant spontaneous low-frequency brain activity in amnestic mild cognitive impairment: A meta-analysis of resting-state fMRI studies

Recent resting-state functional magnetic resonance imaging (rs-fMRI) studies have provided strong evidence of abnormal spontaneous brain activity in amnestic mild cognitive impairment (aMCI). However, the conclusions have been inconsistent. A meta-analysis of whole-brain rs-fMRI studies that measured differences in the amplitude of low-frequency fluctuations (ALFF) between aMCI patients and healthy controls was conducted using the Seed-based d Mapping software package. Twelve studies reporting 14 datasets were included in the meta-analysis. Compared to healthy controls, patients with aMCI showed decreased ALFFs in the bilateral precuneus/posterior cingulate cortices, bilateral frontoinsular cortices, left occipitotemporal cortex, and right supramarginal gyrus and increased ALFFs in the right lingual gyrus, left middle occipital gyrus, left hippocampus, and left inferior temporal gyrus. A meta-regression analysis demonstrated that the increased severity of cognitive impairment in aMCI patients was associated with greater decreases in ALFFs in the cuneus/precuneus cortices. Our comprehensive meta-analysis suggests that aMCI is associated with widespread aberrant regional spontaneous brain activity, predominantly involving the default mode, salience, and visual networks, which contributes to understanding its pathophysiology.     

Scalp acupuncture enhances local brain regions functional activities and functional connections between cerebral hemispheres in acute ischemic stroke patients

This study aimed to explore the changes in functional connections between cerebral hemispheres and local brain regions functional activities in patients with acute ischemic stroke (AIS) treated with International Standard Scalp Acupuncture (ISSA). Thirty patients with middle cerebral artery AIS in the dominant hemisphere were selected and randomly divided into two groups such as the control group and the scalp acupuncture group, with 15 patients in each group. Patients in the control group were treated with conventional Western medicine, while patients in the scalp acupuncture group received ISSA (acupuncture at the parietal midline [MS5], acupuncture at the left anterior parietotemporal oblique line [MS6] and acupuncture at the left posterior parietotemporal oblique line [MS7]) for one course of treatment. All patients were evaluated for treatment efficacy and received whole brain resting state functional magnetic resonance imaging (Rs-fMRI) scan before and after treatment. The observational indicators included: (a) the National Institutes of Health Stroke Scale (NIHSS) scores and the simplified Fugl-Meyer Assessment (SFMA) scores; (b) analyses of the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and voxel-mirrored homotopic connectivity (VMHC). The results showed a significant difference in the NIHSS scores before and after treatment in the scalp acupuncture group compared with the control group (p < .05), indicating that patients improved better after scalp acupuncture treatment. Compared with the control group, the VMHC, ALFF and ReHo values in the scalp acupuncture group increased after treatment. The VMHC values increased in the brain regions dominated by bilateral BA6 and BA8; the ALFF values increased in the left BA39 and the adjacent superior temporal gyrus and middle temporal gyrus; and the ReHo values increased in the brain regions extending from left middle temporal gyrus (including BA21) to BA37, and the brain regions extending from the left BA40 and angular gyrus to BA7. The present study indicated that scalp acupuncture can specifically strengthen the functional activities of the brain regions related to sensory integration, language processing and motor coordination in the middle aged and elderly patients with AIS of the dominant cerebral hemisphere, and can strengthen bilateral frontal lobe motor control. This study may provide a scientific basis for the clinical application of ISSA treatment in patients with AIS, and may also provide a preliminary research basis for further animal experiments.     

Structural and functional neural correlates of visuospatial information processing in normal aging and amnestic mild cognitive impairment

Our understanding of cognitive changes related to human aging and their underlying neural processes is challenged by the distinction between normal and pathological aging. In our study, the neural correlates of visuospatial working memory (VSWM) in young persons (YC), healthy older adults (HC) and patients with amnestic mild cognitive impairment (aMCI) were investigated. Effects of the genetic risk factor apolipoprotein E (ApoE) ε4 on a VSWM task were analyzed for HC and aMCI patients. Higher cortical activation in extrastriate occipital regions and significantly decreased brain volumes in frontoparietal areas were observed in HC compared with young persons. Also, reduced cortical activation in the right middle frontal gyrus and superior frontal gyrus was observed in aMCI-patients compared with HC. Thus, attenuated cortical activation during VSWM tasks is related to the formation of aMCI and may serve as an early marker for cognitive decline. In contrast to previous studies, no significant apolipoprotein E-linked differences were found between HC and aMCI groups.     

Language and the aging brain: patterns of neural compensation revealed by functional brain imaging

Human aging brings with it declines in sensory function, both in vision and in hearing, as well as a general slowing in a variety of perceptual and cognitive operations. Yet in spite of these declines, language comprehension typically remains well preserved in normal aging. We review data from functional magnetic resonance imaging (fMRI) to describe a two-component model of sentence comprehension: a core sentence-processing area located in the perisylvian region of the left cerebral hemisphere and an associated network of brain regions that support the working memory and other resources needed for comprehension of long or syntactically complex sentences. We use this two-component model to describe the nature of compensatory recruitment of novel brain regions observed when healthy older adults show the same success at comprehending sentences as their younger adult counterparts. We suggest that this plasticity in neural recruitment contributes to the stability of language comprehension in the aging brain.