癫痫患者默认网络的静息态功能磁共振成像研究

目的:分析癫痫患者静息态fMRI下默认网络及其潜在结构的变化.方法:对15名临床诊断为原发全身强直痉挛癫痫患者和20名正常志愿者静息态时的fMRI数据进行独立成分分析,依据空间最佳匹配原则挑选独立成分,研究正常被试和癫痫患者的默认网络差异,并选定默认网络中11个脑区构建功能连接网络,运用图论和聚类方法探讨其潜在结构的改变.结果:与正常对照组相比,患者组默认网络的脑区激活普遍下降,功能连接网络发生明显变化,且整个网络呈现出混乱的层次化结构.结论:静息态下癫痫患者的默认网络及潜在的层次化结构发生异常.     

遭受多重侵害高职高专女生静息态脑功能局部一致性的研究

目的:探讨遭受多重侵害的高职高专女生静息态脑功能磁共振特点。方法:15名遭受多重侵害无创伤后应激症状被试(PV无PTSS组)、15名多重侵害有创伤后应激症状被试(PV有PTSS组)和15名正常对照接受静息态脑功能扫描。采用SPM8和静息态功能磁共振数据处理工具包分别进行数据预处理和ReHo分析。结果:静息状态下,与对照组相比,PV无PTSS组左侧额下回、左右额内侧回、右侧中央后回、左侧梭状回、左右海马旁回、右侧扣带回、左右豆状核和右侧岛叶的ReHo值降低;左右额上回、左右额中回、左右额下回、左右顶下小叶、左右楔前叶、左右颞上回、左侧颞横回、左右颞中回、右侧舌回和右侧扣带后回的ReHo值升高。与PV有PTSS组相比,PV无PTSS组在右侧额中回和额下回、左侧楔前叶、左侧舌回、左右海马旁回、左侧扣带回和左侧豆状核ReHo值降低;在左右额上回、左右额中回、左侧额内侧回、右侧中央后回、左侧缘上回、左右顶下小叶、左侧梭状回和左侧尾状核ReHo值升高。结论:遭受多重侵害但无创伤后应激症状的高职高专女生在静息状态下脑默认网络以及岛叶、基底神经节、海马旁回存在局部一致性信号异常,这些脑区异常可能为遭受多重侵害导致精神障碍的发病机制提供重要线索。     

海洛因成瘾者前额叶内侧皮质的静息状态功能连接

目的:探讨海洛因成瘾者脑默认网络静息状态功能连接的异常。方法:对正在接受美沙酮维持治疗的15例海洛因依赖者和15例健康对照进行静息状态脑功能磁共振扫描,以独立成分分析法获取每一个体的默认网络,并比较两组默认网络的功能连接差异。结果:与健康对照相比,海洛因成瘾者双侧前额叶内侧皮质、左侧颞中回和颞下回、小脑的功能连接升高。结论:前额叶内侧皮质可能是物质成瘾的关键脑区,可为成瘾的生物学诊断和靶向治疗提供线索。     

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.     

Functional connectivity tracks clinical deterioration in Alzheimer's disease

While resting state functional connectivity has been shown to decrease in patients with mild and/or moderate Alzheimer's disease, it is not yet known how functional connectivity changes in patients as the disease progresses. Furthermore, it has been noted that the default mode network is not as homogenous as previously assumed and several fractionations of the network have been proposed. Here, we separately investigated the modulation of 3 default mode subnetworks, as identified with group independent component analysis, by comparing Alzheimer's disease patients to healthy controls and by assessing connectivity changes over time. Our results showed decreased connectivity at baseline in patients versus controls in the posterior default mode network, and increased connectivity in the anterior and ventral default mode networks. At follow-up, functional connectivity decreased across all default mode systems in patients. Our results suggest that earlier in the disease, regions of the posterior default mode network start to disengage whereas regions within the anterior and ventral networks enhance their connectivity. However, as the disease progresses, connectivity within all systems eventually deteriorates.     

EEG network connectivity changes in mild cognitive impairment — Preliminary results

Resting state EEGs were compared between patients with amnestic subtype of mild cognitive impairment (aMCI) and matched elderly controls at two times over a one year period. The study aimed at investigating the role of functional connectivity between and within different brain regions in relation to the progression of cognitive deficit in MCI. The EEG was recorded in two sessions during eyes closed and eyes open resting conditions. Functional brain connectivity was investigated based on the measurement of phase synchronization in different frequency bands. Delta and theta synchronization characteristics indicated decreased level of local and large-scale connectivity in the patients within the frontal, between the frontal and temporal, and frontal and parietal brain areas which was more pronounced 1 year later. As a consequence of opening the eyes connectivity in the alpha1 band within the parietal lobe decreased compared to the eyes closed condition but only in the control group. The lack of alpha1 band reactivity following eye opening could reliably differentiate patients from controls. Our preliminary results support the notion that the functional disconnection between distant brain areas is a characteristic feature of MCI, and may prove to be predictive in terms of the progression of this condition.     

Hippocampal and ventricular changes in Parkinson's disease mild cognitive impairment

We analyzed T1-weighted brain magnetic resonance imaging data of 100 cognitively normal elderly controls (NC), 127 cognitively normal Parkinson's disease (PD; PDCN) and 31 PD-associated mild cognitive impairment (PDMCI) subjects from the Norwegian ParkWest study. Using automated segmentation methods, followed by the radial distance technique and multiple linear regression we studied the effect of clinical diagnosis on hippocampal and ventricular radial distance while adjusting for age, education, and scanning site. PDCN subjects had significantly smaller bilateral hippocampal radial distance relative to NC. Nonamnestic PDMCI subjects showed smaller right hippocampal radial distance relative to NC. PDMCI subjects showed significant enlargement of all portions of the lateral ventricles relative to NC and significantly larger bilateral temporal and occipital and left frontal lateral ventricular expansion relative to PDCN subjects. Nonamnestic PDMCI subjects showed significant ventricular enlargement spanning all parts of the lateral ventricle while those with amnestic PDMCI showed changes localized to the left occipital horn. Hippocampal atrophy and lateral ventricular enlargement show promise as structural biomarkers for PD.     

Longitudinal 1H MRS changes in mild cognitive impairment and Alzheimer's disease

Magnetic resonance (MR)-based volume measurements of atrophy are potential markers of disease progression in patients with amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD). Longitudinal changes in (1)H MR spectroscopy ((1)H MRS) metabolite markers have not been characterized in MCI subjects. Our objective was to determine the longitudinal (1)H MRS metabolite changes in patients with MCI, and AD, and to compare (1)H MRS metabolite ratios and ventricular volumes in tracking clinical disease progression in AD. The neuronal integrity marker N-acetylaspartate/creatine ratio declined in MCI and AD patients compared to cognitively normal elderly. The change in (1)H MRS metabolite ratios correlated with clinical progression about as strongly as the rate of ventricular expansion, suggesting that (1)H MRS metabolite ratios may be useful markers for the progression of AD. Choline/creatine ratio declined in stable MCI, compared to converter MCI patients and cognitively normal elderly, which may be related to a compensatory mechanism in MCI patients who did not to progress to AD.     

Increased fMRI responses during encoding in mild cognitive impairment

Structural and functional magnetic resonance imaging (fMRI) was performed on 21 healthy elderly controls, 14 subjects with mild cognitive impairment (MCI) and 15 patients with mild Alzheimer's disease (AD) to investigate changes in fMRI activation in relation to underlying structural atrophy. The fMRI paradigm consisted of associative encoding of novel picture-word pairs. Structural analysis of the brain was performed using voxel-based morphometry (VBM) and hippocampal volumetry. Compared to controls, the MCI subjects exhibited increased fMRI responses in the posterior hippocampal, parahippocampal and fusiform regions, while VBM revealed more atrophy in MCI in the anterior parts of the left hippocampus. Furthermore, the hippocampal volume and parahippocampal activation were negatively correlated in MCI, but not in controls or in AD. We suggest that the increased fMRI activation in MCI in the posterior medial temporal and closely connected fusiform regions is compensatory due to the incipient atrophy in the anterior medial temporal lobe.     

Prediction of Alzheimer's disease in mild cognitive impairment: a prospective study in Taiwan

The relationship between apolipoprotein E (ApoE) and clinical manifestations of mild cognitive impairment (MCI) has not been investigated in non-Caucasian populations. This prospective study was conducted in an ethnic Chinese population to evaluate the correlations of ApoE genotype, cognitive performance, medial temporal structure volumes, and clinical outcome in amnestic MCI. Twenty normal elders, 58 MCI, and 20 mild Alzheimer's disease (AD) patients received neuropsychological, MRI, and ApoE genotype assessments at baseline. Patients with MCI had intermediate cognitive performance and hippocampal volumes between those in normal and AD groups. In each diagnostic group, 4 carriers (E4+) consistently had smaller hippocampal volume than non-carriers (E4−) did. Nineteen MCI subjects (32.7%) converted to AD during the 3-year study period. Compared with MCI non-converters and E4− MCI converters, E4+ MCI converters had the smallest hippocampal volume. However, 4 was not a predictor for AD. Both cognitive performance and hippocampal volume were predictive for progression to AD. However, stepwise Cox regression model integrating both neuropsychological and radiological variables showed that global cognitive performance was the only significant predictor for AD. A poor global cognitive score may be more crucial than a small hippocampal volume in the prediction of AD.     

Diagnostic power of default mode network resting state fMRI in the detection of Alzheimer's disease

Functional magnetic resonance imaging (fMRI) of default mode network (DMN) brain activity during resting is recently gaining attention as a potential noninvasive biomarker to diagnose incipient Alzheimer's disease. The aim of this study was to determine which method of data processing provides highest diagnostic power and to define metrics to further optimize the diagnostic value. fMRI was acquired in 21 healthy subjects, 17 subjects with mild cognitive impairment and 15 patients with Alzheimer's disease (AD) and data evaluated both with volumes of interest (VOI)-based signal time course evaluations and independent component analyses (ICA). The first approach determines the amount of DMN region interconnectivity (as expressed with correlation coefficients); the second method determines the magnitude of DMN coactivation. Apolipoprotein E (ApoE) genotyping was available in 41 of the subjects examined. Diagnostic power (expressed as accuracy) of data of a single DMN region in independent component analyses was 64%, that of a single correlation of time courses between 2 DMN regions was 71%, respectively. With multivariate analyses combining both methods of analysis and data from various regions, accuracy could be increased to 97% (sensitivity 100%, specificity 95%). In nondemented subjects, no significant differences in activity within DMN could be detected comparing ApoE ε4 allele carriers and ApoE ε4 allele noncarriers. However, there were some indications that fMRI might yield useful information given a larger sample. Time course correlation analyses seem to outperform independent component analyses in the identification of patients with Alzheimer's disease. However, multivariate analyses combining both methods of analysis by considering the activity of various parts of the DMN as well as the interconnectivity between these regions are required to achieve optimal and clinically acceptable diagnostic power.     

CSF cortisol in Alzheimer's disease and mild cognitive impairment

Hypercortisolaemia occurs in Alzheimer's disease (AD) and may be involved in the AD related neurodegenerative process. In order to determine whether brain structures are exposed to high cortisol concentrations early in AD, we measured cerebrospinal fluid (CSF) cortisol in 66 subjects with AD, 33 subjects with mild cognitive impairment (MCI) and 34 control subjects. CSF cortisol concentrations were higher in AD subjects compared to controls (p<0.001) and to MCI subjects (p=0.002). There was no significant increase of cortisol in MCI subjects compared with controls suggesting that the increase of CSF cortisol is not an early event in the course of AD.     

Fasting plasma insulin and the default mode network in women at risk for Alzheimer's disease

Brain imaging studies in Alzheimer's disease research have demonstrated structural and functional perturbations in the hippocampus and default mode network (DMN). Additional evidence suggests risk for pathological brain aging in association with insulin resistance (IR). This study piloted investigation of associations of IR with DMN-hippocampal functional connectivity among postmenopausal women at risk for Alzheimer's disease. Twenty middle-aged women underwent resting state functional magnetic resonance imaging. Subjects were dichotomized relative to fasting plasma insulin levels (i.e., > 8 μIU/mL [n = 10] and < 8 μIU/mL [n = 10]), and functional connectivity analysis contrasted their respective blood oxygen level-dependent signal correlation between DMN and hippocampal regions. Higher-insulin women had significantly reduced positive associations between the medial prefrontal cortex and bilateral parahippocampal regions extending to the right hippocampus, and conversely, between the left and right hippocampus and medial prefrontal cortex. Neuropsychological data (all within normal ranges) also showed significant differences with respect to executive functioning and global intelligence. The results provide further evidence of deleterious effects of IR on the hippocampus and cognition. Further imaging studies of the IR-related perturbations in DMN-hippocampal functional connectivity are needed.     

Olfaction in patients with mild cognitive impairment and Alzheimer's disease

Understanding of olfactory dysfunction in Alzheimer's disease (AD) remains limited. In particular, it is not known how early in the course of the disease olfactory deficits occur, and whether they are restricted to identification or involve other aspects of olfaction. We studied olfactory (odor detection thresholds, quality discrimination, and identification) and cognitive (attention, reasoning, memory, naming and fluency) functioning in patients with AD, with mild cognitive impairment (MCI), and in normal elderly control (NEC) participants. MCI patients were impaired in olfactory sensitivity and identification, while a discrimination deficit was accounted for by abnormal thresholds. AD patients were impaired in all three domains, and were worse than the MCI group. Odor discrimination (OD) and identification performance correlated more prominently than detection thresholds with performance on neuropsychological tests. We concluded that deficits in olfactory detection thresholds and identification occur early in AD, before clinical symptoms are fully developed, and decline further over the course of the disease. High detection thresholds, together with impaired identification, may be useful as an early indicator of AD.     

Hippocampal metabolic abnormalities in mild cognitive impairment and Alzheimer's disease

Mild cognitive impairment (MCI) defines a group of otherwise healthy elderly subjects with a markedly elevated risk of developing Alzheimer's disease (AD). In the search for biomarkers of MCI, we assessed whether MCI shares neurochemical abnormalities with AD in areas affected early in the course of the disease. As a secondary study aim, we tested to what extent neurochemical findings reflect neuropsychological deficits. Proton spectroscopy was performed in 19 MCI patients, 18 AD patients and 22 age and gender matched controls (CON) within the parietal gray and white matter (PWM and PGM) and the hippocampus (HIP). The cognitive test battery used included measures compiled by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The N-acetyl-aspartate to creatine ratio (NAA/Cr) was significantly reduced in the HIP of MCI and AD compared with CON (p < 0.05). Only AD patients showed parietal abnormalities, namely significantly elevated myoinositol (mI/Cr and mI/NAA) in PGM, reduced NAA/Cr and elevated mI/NAA in PWM. MCI subjects were significantly impaired in categorical verbal fluency (VF) (p < 0.001) and delayed verbal recall (DVR) (p < 0.001). VF was positively correlated with hippocampal NAA/Cr (p < 0.05) and parietal mI/NAA (p < 0.05). In summary, this study demonstrates shared neurobiological hippocampal abnormalities in MCI and AD, whereas parietal lobe neurochemical profiles and functions were normal in MCI. Thus, biological evidence is provided that MCI represents a precursor stage of AD. Moreover, multivoxel 1H MRS may enable an objective staging of the neurodegenerative process underlying the age-dependent cognitive deficits eventually leading to dementia.     

Decreased EEG synchronization in Alzheimer's disease and mild cognitive impairment

The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.     

Age effect on the default mode network,inner thoughts,and cognitive abilities

Age-related effects on the default mode network (DMN) connectivity as measured at rest using functional magnetic resonance imaging (fMRI) are now well described. Little is known however about the relationships between these changes and age-related effects on cognition or on the unconstrained thoughts which occur during the resting-state scan, called inner experience. Brain resting-state activity, inner experience, and cognitive ability measurements were obtained in 70 participants aged 19–80 years. The anterior-posterior disruption of DMN activity with age reported in previous studies was recovered here. A significant effect of age was also found on cognitive abilities but not on inner experience. Finally, age-related changes in DMN connectivity were found to correlate with cognitive abilities, and more specifically with autobiographical memory performance. These findings provide new information to fuel the debate on the role of the brain default mode and more specifically on the effect of age-related changes in resting-state activity as measured with fMRI.     

Quantitative electroencephalography in mild cognitive impairment: longitudinal changes and possible prediction of Alzheimer's disease

The present study evaluated the clinical course of patients with mild cognitive impairment (MCI), the pattern of electroencephalography (EEG) changes following cognitive deterioration, as well as the potential of neurophysiological measures in predicting dementia. Twenty-seven subjects with MCI were followed for a mean follow up period of 21 months. Fourteen subjects (52%) progressed (P MCI) to clinically manifest Alzheimer's disease (AD), and 13 (48%) remained stable (S MCI). The two MCI subgroups did not differ in baseline EEG measures between each other and the healthy controls (n = 16), but had significantly lower theta relative power at left temporal, temporo-occipital, centro-parietal, and right temporo-occipital derivation when compared to the reference AD group (n = 15). The P MCI baseline alpha band temporo-parietal coherence, alpha relative power values at left temporal and temporo-occipital derivations, theta relative power values at frontal derivations, and the mean frequency at centro-parietal and temporo-occipital derivations overlapped with those for AD and control groups. After the follow-up, the P MCI patients had significantly higher theta relative power and lower beta relative power and mean frequency at the temporal and temporo-occipital derivations. A logistic regression model of baseline EEG values adjusted for baseline Mini-Mental Test Examination showed that the important predictors were alpha and theta relative power and mean frequency from left temporo-occipital derivation (T5-O1), which classified 85% of MCI subjects correctly.     

Hippocampal synaptic loss in early Alzheimer's disease and mild cognitive impairment

One of the major neuropathological findings in the brains of individuals with Alzheimer's disease (AD) is a loss of synaptic contacts in both the neocortex and hippocampus. Here we report, for the first time, an estimate of the total number of synapses in the outer molecular layer (OML) of the human dentate gyrus, in individuals with early Alzheimer's disease (eAD), mild cognitive impairment (MCI), or no cognitive impairment (NCI). An unbiased stereologic sampling scheme coupled with transmission electron microscopy to directly visualize synaptic contacts, was used to estimate the total number of synapses in short postmortem autopsy tissue. Individuals with eAD had significantly fewer synapses than the other two diagnostic groups. Seventy-five percent of the individuals with MCI had synaptic values that were lower than the NCI group mean. The number of synapses showed a significant correlation with the subject's Mini-Mental State score and with cognitive tests involving delayed recall. Synaptic loss showed no relationship to Braak stage or to apoE genotype. The volume of the OML was significantly reduced in eAD compared to the other two diagnositic groups that were not different from each other. These data suggest that a loss of afferents from the entorhinal cortex underlie the synapse loss seen in eAD. This study supports the concept that synapse loss is an early event in the disease process and suggests that MCI may be a transition stage between eAD and NCI with synaptic loss a structural correlate involved in cognitive decline.