Altered resting-state functional connectivity of the cerebellum in schizophrenia

Structural and functional abnormalities of the cerebellum in schizophrenia have been reported. Most previous studies investigating resting-state functional connectivity (rsFC) have relied on a priori restrictions on seed regions or specific networks, which may bias observations. In this study, we aimed to elicit the connectivity alterations of the cerebellum in schizophrenia in a hypothesis-free approach. Ninety-five schizophrenia patients and 93 sex- and age-matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI). A voxel-wise data-driven method, resting-state functional connectivity density (rsFCD), was used to investigate cerebellar connectivity changes in schizophrenia patients. Regions with altered rsFCD were chosen as seeds to perform seed-based resting-state functional connectivity (rsFC) analyses. We found that schizophrenia patients exhibited decreased rsFCD in the right hemispheric VI; moreover, this cerebellar region showed increased rsFC with the prefrontal cortex and subcortical nuclei and decreased rsFC with the visual cortex and sensorimotor cortex. In addition, some rsFC changes were associated with positive symptoms. These findings suggest that abnormalities of the cerebellar hub and cerebellar-subcortical-cortical loop may be the underlying mechanisms of schizophrenia.     

Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks.     

Altered self-referential network in resting-state amnestic type mild cognitive impairment

IntroductionImpaired capacity for self-reference has been observed in amnestic mild cognitive impairment (aMCI) subjects who are thought to be the likely to develop into clinical Alzheimer’s disease (AD). The altered pattern of self-referencing network (SRN) is not yet well understood in aMCI subjects particularly in resting state, and little is known about the relationship between SRN and other resting-state networks in aMCI subjects.MethodsThe study was designed to administer longitudinal resting-state functional magnetic resonance imaging (fMRI) scanning to 26 aMCI subjects and 18 matched healthy controls. Independent component analysis was used to separate SRN, and a further cross-correlation approach was recruited to explore the relationship between SRN and other resting-state networks.ResultsCompared to controls, selective changes of SRN regarding to the increased functional connectivity between ventromedial prefrontal cortex/medial orbital prefrontal cortex/gyrus rectus and the mean time series of SRN at baseline in aMCI, while these functional connections were associated with more extent of longitudinal diminish after follow up in the same subjects. In addition, greater decreased connectivity relationship between SRN and default mode network was observed in aMCI subjects.ConclusionsAltered patterns of resting-state SRN were firstly explored in aMCI subjects, and it could help guide subsequent investigations designed to specify the precise functional implications of SRN in the progression of aMCI.     

早发精神分裂症静息态脑功能低频振幅研究

目的通过静息态功能磁共振研究早发未用药精神分裂症患者局部脑功能低频振幅(amplitude of low-frequency fluctuation,ALFF)的变化,探讨其静息态下功能异常的脑区。方法收集20例早发未用药精神分裂症患者与20名性别、年龄、受教育年限相匹配的正常对照,分别对其进行全脑静息态功能磁共振扫描,计算ALFF值。结果与对照组相比,患者组左侧额上回、左侧楔前叶、左侧扣带回、左侧枕叶、左侧海马旁回、左侧距状沟ALFF值增高(P0.05,Alpha Sim校正),右侧颞上回和右侧小脑后叶ALFF值降低(P0.05,Alpha Sim校正)。结论早发精神分裂症患者在静息态下有多处脑区ALFF值改变,提示其在静息态下存在脑功能异常。     

Altered resting-state functional connectivity of the dentate nucleus in Parkinson's disease

We used functional magnetic resonance imaging (fMRI) to measure functional connectivity of the dentate nucleus (DN) between patients with Parkinson's disease (PD) and normal controls who were studied in a resting state. Images were acquired in 18 PD patients and in age- and sex-matched normal controls. Connectivity of the bilateral DN was calculated and compared between patients and controls, connectivity of the bilateral DN within the cerebellum was compared between rigidity and bradykinesia-dominant patients (PD_AR) and tremor-dominant patients (PD_T), and correlation analysis was performed between the connectivity strength and behavioral measures within the cerebellum. Some regions in the cerebellum showed enhanced connectivity with the bilateral DN in PD patients, and decreased connectivity of the DN with the bilateral cerebellar posterior lobe was observed in PD_T as compared to PD_AR. A set of regions consistent with the default mode network showed disrupted connectivity with the DN. Decreased connectivity between the inferior parietal lobule and the DN was also observed in PD patients. Additional analyses did not show any significant correlations between functional connectivity within the cerebellum and Unified Parkinson's Disease Rating Scale-III scores. Our findings suggest that connectivity of the DN in the resting state is disrupted in PD, and there may be a compensatory cerebellar connectivity mechanism in the resting state in PD. Further study of the cerebellum may clarify the pathophysiology of PD.     

Abnormal baseline brain activity in low-grade hepatic encephalopathy: a resting-state fMRI study

Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neuropsychiatric diseases, but rarely in low-grade hepatic encephalopathy (HE), a common neuropsychiatric complication of liver cirrhosis. We conducted a resting-state fMRI in 19 healthy controls, 18 cirrhotic patients without HE, and 22 cirrhotic patients with low-grade HE. The amplitude of low-frequency fluctuations (ALFF) of fMRI signal was computed to measure the spontaneous neuronal activity. Several regions showing significant ALFF differences among three groups were the precuneus, occipital lobe, left frontal lobe and anterior/middle cingulate cortex, and left cerebellum posterior lobe. Compared to controls or patients without HE, patients with low-grade HE showed decreased ALFF in the precuneus and adjacent cuneus, visual cortex, and left cerebellum posterior lobe. Compared to controls, patients with low-grade HE showed higher ALFF in both cortical and subcortical regions, including the right middle cingulate gyrus, and left anterior/middle cingulate gyrus, inferior frontal gyrus, insula lobe, parahippocampal gyrus, middle temporal gyrus and lentiform nucleus; compared to patients without HE, patients with low-grade HE showed higher ALFF in the left medial frontal gyrus and anterior cingulate gyrus, bilateral superior frontal gyrus, and right middle frontal gyrus. Moreover, correlations between ALFF changes and poor neurocognitive performances were found in patients with low-grade HE. These results suggested the existence of aberrant brain activity at the baseline state in low-grade HE, which may be implicated in the neurological pathophysiology underlying HE.     

Cerebellar Neural Circuits Involving Executive Control Network Predict Response to Group Cognitive Behavior Therapy in Social Anxiety Disorder

Some intrinsic connectivity networks including the default mode network (DMN) and executive control network (ECN) may underlie social anxiety disorder (SAD). Although the cerebellum has been implicated in the pathophysiology of SAD and several networks relevant to higher-order cognition, it remains unknown whether cerebellar areas involved in DMN and ECN exhibit altered resting-state functional connectivity (rsFC) with cortical networks in SAD. Forty-six patients with SAD and 64 healthy controls (HC) were included and submitted to the baseline resting-state functional magnetic resonance imaging (fMRI). Seventeen SAD patients who completed post-treatment clinical assessments were included after group cognitive behavior therapy (CBT). RsFC of three cerebellar subregions in both groups was assessed respectively in a voxel-wise way, and these rsFC maps were compared by two-sample t tests between groups. Whole-brain voxel-wise regression was performed to examine whether cerebellar connectivity networks can predict response to CBT. Lower rsFC circuits of cerebellar subregions compared with HC at baseline (p < 0.05, corrected by false discovery rate) were revealed. The left Crus I rsFC with dorsal medial prefrontal cortex was negatively correlated with symptom severity. The clinical assessments in SAD patients were significantly decreased after CBT. Higher pretreatment cerebellar rsFC with angular gyrus and dorsal lateral frontal cortex corresponded with greater symptom improvement following CBT. Cerebellar rsFC circuits involving DMN and ECN are possible neuropathologic mechanisms of SAD. Stronger pretreatment cerebellar rsFC circuits involving ECN suggest potential neural markers to predict CBT response.     

The apolipoprotein E gene affects the three-year trajectories of compensatory neural processes in the left-lateralized hippocampal network

Previous cross-sectional studies that investigated the effects of apolipoprotein E (ApoE) ε4 status on hippocampal networks have shown inconsistent results. Aging is a well-known risk factor for Alzheimer’s disease (AD) and could strongly interact with ApoE-related vulnerabilities to affect AD risk. However, no longitudinal data have been published regarding the interaction of the ApoE genotype and aging on hippocampal networks. Fifty-one patients with amnestic-type mild cognitive impairment (aMCI) and 64 matched cognitively normal elderly subjects underwent resting-state fMRI scans and neuropsychological tests at baseline and at a 35-month follow-up. Hippocampal resting-state functional connectivity (FC) data were analyzed utilizing a mixed analysis of covariance with ApoE genotype, time points and disease as fixed factors, controlling for age, sex and years of education. The notable finding was that the FC between the left hippocampus and right frontal regions for ε4 carriers longitudinally increased in the normal subjects, but decreased in aMCI patients, whereas the FC for non-carriers was maintained in normal subjects but increased in aMCI patients. Specifically, the longitudinal increases in hippocampal FC with the right inferior frontal gyrus were positively correlated with the changes in episodic memory test scores in non-carriers with aMCI. The interaction between the ApoE genotype, aging and disease suggested that aging should be considered a key regulator of the impact of the ApoE genotype on the phenotypic variants of AD. These findings also demonstrated that compensatory neural processes were accelerated in genetically high risk individuals, but could be subsequently exhausted with the onset of cognitive impairment.     

The cerebellum in mild cognitive impairment and Alzheimer's disease - a structural MRI study

Neuropathological research consistently revealed the cerebellum to undergo degenerative changes in Alzheimer's disease (AD). Whether these alterations affect cerebellar morphology in vivo has not yet been investigated in a comprehensive way. Magnetic resonance imaging was performed in 20 patients with AD, 20 with mild cognitive impairment (MCI), and 20 healthy controls. By manual tracing the cerebellum was divided in four substructures (anterior lobe, superior posterior lobe, inferior posterior lobe and corpus medullare, respectively) on each hemisphere. Posterior cerebellar lobes were significantly smaller in AD patients when compared to healthy controls. In the AD group, atrophy of the posterior cerebellar regions was associated with poorer cognitive performance. Our findings lend further support for cerebellar involvement in AD.     

抑郁症首次发病患者静息态脑功能局部一致性的研究

目的 利用功能磁共振(fMRI)和局部一致性(regional homogeneity,ReHo)探讨抑郁症首次发病(以下简称首发)患者在静息态脑功能是否存在异常及异常部位.方法 对34例符合美国精神疾病诊断与统计手册第4版诊断标准的首发抑郁症患者(抑郁症组)和34名性别、年龄、文化程度匹配的健康志愿者(对照组)进行静息态fMRI扫描.结果 抑郁症组静息态脑血氧水平依赖信号的ReHo高于对照组的脑区有左侧额叶眶回、顶下小叶、颞上回,右侧额内侧回、顶下小叶、小脑后叶;低于对照组的脑区有左颞下回、右颞上同和胼胝体、双侧后扣带回(P＜0.005,K≥10).结论首发抑郁症患者在静息态存在多个腩区功能活动的异常,并可能和抑郁症的病理机制有关.     

Sensorimotor network rewiring in mild cognitive impairment and Alzheimer's disease

This study aimed at elucidating whether (a) brain areas associated with motor function show a change in functional magnetic resonance imaging (fMRI) signal in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD), (b) such change is linear over the course of the disease, and (c) fMRI changes in aMCI and AD are driven by hippocampal atrophy, or, conversely, reflect a nonspecific neuronal network rewiring generically associated to brain tissue damage. FMRI during the performance of a simple motor task with the dominant right‐hand, and structural MRI (i.e., dual‐echo, 3D T1‐weighted, and diffusion tensor [DT] MRI sequences) were acquired from 10 AD patients, 15 aMCI patients, and 11 healthy controls. During the simple‐motor task, aMCI patients had decreased recruitment of the left (L) inferior frontal gyrus compared to controls, while they showed increased recruitment of L postcentral gyrus and head of L caudate nucleus, and decreased activation of the cingulum compared with AD patients. Effective connectivity was altered between primary sensorimotor cortices (SMC) in aMCI patients vs. controls, and between L SMC, head of L caudate nucleus, and cingulum in AD vs. aMCI patients. Altered fMRI activations and connections were correlated with the hippocampal atrophy in aMCI and with the overall GM microstructural damage in AD. Motor‐associated functional cortical changes in aMCI and AD mirror fMRI changes of the cognitive network, suggesting the occurrence of a widespread brain rewiring with increasing structural damage rather than a specific response of cognitive network. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.     

Altered functional brain networks in amnestic mild cognitive impairment: a resting-state fMRI study

Amnestic mild cognitive impairment MCI (aMCI) has a high progression to Alzheimer’s disease (AD). Recently, resting-state functional MRI (RS-fMRI) has been increasingly utilized in studying the pathogenesis of aMCI, especially in resting-state networks (RSNs). In the current study, we aimed to explore abnormal RSNs related to memory deficits in aMCI patients compared to the aged-matched healthy control group using RS-fMRI techniques. Firstly, we used ALFF (amplitude of low-frequency fluctuation) method to define the regions of interest (ROIs) which exhibited significant changes in aMCI compared with the control group. Then, we divided these ROIs into different networks in line with prior studies. The aim of this study is to explore the functional connectivity between these ROIs within networks and also to investigate the connectivity between networks. Comparing aMCI to the control group, our results showed that 1) the hippocampus (HIPP) had decreased FC with the medial prefrontal cortex (mPFC) and inferior parietal lobe (IPL), and the mPFC showed increased connectivity to IPL in the default mode network; 2) the thalamus showed decreased FC with the putamen and HIPP, and the HIPP showed increased connectivity to the putamen in the limbic system; 3) the supplementary motor area had decreased FC with the middle temporal gyrus and increased FC with the superior parietal lobe in the sensorimotor network; 4) increased connectivity between the lingual gyrus and middle occipital gyrus in the visual network; and 5) the DMN has reduced inter-network connectivities with the SMN and VN. These findings indicated that functional brain networks involved in cognition such as episodic memory, sensorimotor and visual cognition in aMCI were altered, and provided a new sight in understanding the important subtype of aMCI.     

静息状态功能磁共振成像观察轻度阿尔茨海默病后扣带回功能连通性的变化

目的 利用静息状态功能磁共振成像(fMRI)研究阿尔茨海默病(AD)早期后扣带回相关的静息脑网络连通性是如何变化的.方法 运用fMRI研究了16例轻度AD患者和16名健康对照者在静息状态后扣带回的功能连通性.与后扣带回有功能连通性的脑区是通过检测低频波动信号的时程相关性获得的.应用通用的SPM2图像统计软件计算组间和组内连通性差异,激活区阈值设置:P<0.01(校正),像素范围>5.利用SPM2软件随机效应分析t检验(经校正P<0.01,t=2.47,像素范围>5),比较患者组和对照组连通性激活的脑区.结果 与后扣带回有功能连通性减弱的脑区包括前额叶中线区、楔前叶、双侧视皮质、双侧颞下回、左侧海马、右侧丘脑、右侧额叶背外侧区;偏左侧化的连通性增高的脑区包括前额叶中线区、左侧颞下回、左侧基底节区、双侧额叶背外侧区及左侧中央前区.结论 与后扣带回相关的静息状态脑网络连通性减低与AD早期情节记忆损害和高级视觉功能损害有关系,轻度AD保留着功能连接的重塑性以便维持脑功能.静息fMRI是一种探索AD脑功能机制的适宜方法.     

不同亚型轻度认知障碍患者静息态脑功能局部一致性研究

目的探讨遗忘型和非遗忘型轻度认知障碍(mild cognition impairment,MCI)患者局部自发脑活动特点。方法纳入遗忘型MCI(amnesicMCI,aMCI)患者25例,非遗忘型MCI(non-amnesticMCI,naMCI)患者21例和正常对照(normal control,NC)15名进行静息态功能磁共振扫描,通过计算每个给定体素与其最邻近26个体素时间序列的相似性获得全脑局部一致性(regional homogeneity,ReHo)图,比较三组被试全脑ReHo差异。结果 aMCI组右侧额叶ReHo值低于NC组,左侧颞中回和左侧小脑ReHo值高于NC组(P0.05,Alphasim校正);naMCI组前扣带回和右侧额中回ReHo值低于NC组,右侧海马旁回、右侧颞中回和右侧楔前叶ReHo值高于NC组(P0.05,Alphasim校正);aMCI左侧前额叶和左侧颞中回ReHo值高于naMCI组,右侧小脑ReHo值低于naMCI组(P0.05,Alphasim校正)。结论 aMCI和naMCI患者左侧前额叶、左侧颞中回及右侧小脑自发脑功能活动存在差异,这为区别aMCI和naMCI两者脑功能活动特点提供了初步影像学依据。     

Impaired perceptual networks in temporal lobe epilepsy revealed by resting fMRI

Viewed as a neural network disorder, mesial temporal lobe epilepsy (mTLE) may cause widespread deficits in human brain functions. Impairments in cognitive functions such as memory and language have been well addressed, but perceptual deficits have only been considered in terms of behavioral data. Little imaging research on perceptual deficits in mTLE has been reported. The present study is expected to reveal impairments in the perceptual networks in patients with mTLE using fMRI. The fMRI-based independent component analysis (ICA) was applied to 33 patients with mTLE and 33 matched healthy controls. In light of the resting-state networks (RSNs) corresponding to the basal functions of visual, auditory, and sensorimotor systems, the ICA data of functional connectivity within these RSNs were compared between the patients and controls. Compared with the controls, the mTLE patients presented decreased functional connectivity within the regions of the auditory and sensorimotor networks, as well increased functional connectivity in the primary visual cortex and decreased functional connectivity in the bilateral MT+ areas of the visual network. Our neuroimaging results are in agreement with the previous findings that specific perceptual functions are impaired in mTLE. Furthermore, our findings in the visual network support the belief that the primary visual function is not impaired and that there may be deficits in the high-order visual function in mTLE. Our fMRI study may contribute to the understanding of neuropathophysiological mechanisms underlying perceptual impairments in mTLE.     

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.     

Functional connectivity networks are disrupted in left temporal lobe epilepsy

OBJECTIVE: Functional connectivity maps the distributed network of brain regions fluctuating synchronously during a continuous brain state. This study sought to investigate whether patients with left temporal lobe epilepsy (TLE) differ from controls in their resting-state functional connectivity between typical language regions. METHODS: We studied 17 patients with left TLE, together with eight healthy controls, using seeded functional connectivity. Seed regions were defined using the regions of maximal activation and deactivation during a language functional magnetic resonance imaging (fMRI) task in a separate cohort of 30 controls. RESULTS: Language fMRI produced the expected activation pattern, which was not different between patients and controls. However, functional connectivity between language areas during rest was markedly different; whereas controls showed connectivity between each of the seed areas and the majority of the language areas, patients showed connectivity only with a few areas, particularly the seed area itself. This difference was significant in the direct comparison of patients and control connectivity maps. INTERPRETATION: We suggest that this reduced connectivity in left temporal lobe epilepsy may reflect a disturbance of the language network during resting state in patients and may be related to subtle language difficulties in this patient population.     

Cerebellar-parietal dysfunctions in multiple sclerosis patients with cerebellar signs

Consistent findings have shown that the cerebellum is critically implicated in a broad range of cognitive processes including executive functions. Of note, cerebellar symptoms and a number of cognitive deficits have been widely reported in patients with multiple sclerosis (MS). This study investigated for the first time the role of cerebellar symptoms in modulating the neural networks associated with a cognitive task broadly used in MS patients (Paced Visual Serial Addition Test (PVSAT)). Twelve relapsing-remitting (RR) MS patients with prevalent cerebellar signs and symptoms (RR-MSc), 15 RR-MS patients without cerebellar manifestation (RR-MSnc) and 16 matched-healthy controls were examined during functional magnetic resonance imaging (fMRI). We tested whether the RR-MSc patients displayed abnormal activations within "cognitive" cerebellar regions and other areas typically engaged in working memory and tightly connected with the cerebellum. Despite similar behavioral performances during fMRI, RR-MSc patients displayed, relatively to both RR-MSnc patients and controls, significantly greater responses in the left cerebellar Crus I/Lobule VI. RR-MSc patients also displayed reduced functional connectivity between the left cerebellar Crus I and the right superior parietal lobule (FWE<.05). These results demonstrated that the presence of the cerebellar signs drastically impacts on the neurofunctional networks underlying working memory in MS. The altered communication between the cerebellum and a cortical area implicated in short-term buffering and storage of relevant information, offer new insights into the pathophysiological mechanisms of cognition in MS.     

Altered baseline brain activity in children with ADHD revealed by resting-state functional MRI

In children with attention deficit hyperactivity disorder (ADHD), functional neuroimaging studies have revealed abnormalities in various brain regions, including prefrontal-striatal circuit, cerebellum, and brainstem. In the current study, we used a new marker of functional magnetic resonance imaging (fMRI), amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to investigate the baseline brain function of this disorder. Thirteen boys with ADHD (13.0+/-1.4 years) were examined by resting-state fMRI and compared with age-matched controls. As a result, we found that patients with ADHD had decreased ALFF in the right inferior frontal cortex, left sensorimotor cortex, and bilateral cerebellum and the vermis as well as increased ALFF in the right anterior cingulated cortex, left sensorimotor cortex, and bilateral brainstem. This resting-state fMRI study suggests that the changed spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology in children with ADHD.     

Detection of PCC functional connectivity characteristics in resting-state fMRI in mild Alzheimer's disease

Resting-state networks dissociate in the early stage of Alzheimer's disease (AD). The posterior cingulate cortex (PCC) in AD brain is vulnerable to isolation from the rest of brain. However, it remains unclear how this functional connectivity is related to PCC changes. We employed resting-state functional MRI (fMRI) to examine brain regions with a functional connection to PCC in a mild AD group compared with matched control subjects. PCC connectivity was gathered by investigating synchronic low frequency fMRI signal fluctuations with a temporal correlation method. We found asymmetric PCC-left hippocampus, right dorsal-lateral prefrontal cortex and right thalamus connectivity disruption. In addition, some other regions such as the bilateral visual cortex, the infero-temporal cortex, the posterior orbital frontal cortex, the ventral medial prefrontal cortex and the precuneus showed decreased functional connectivity to the PCC. There were also some regions, primarily in the left frontal-parietal cortices, that showed increased connectivity. These regions included the medial prefrontal cortex, bilateral dorsal-lateral prefrontal cortex, the left basal ganglia and the left primary motor cortex. Impairments to memory, high vision-related functions and olfaction in AD can be explained by a disruption to the functional connection of resting-state networks. The results of increased connectivity may support the compensatory-recruitment hypothesis. Our findings suggest that the characteristics of resting-state functional connectivity could plausibly provide an early imaging biomarker for AD.