A Meta‐Analysis of fMRI Activation Differences during Episodic Memory in Alzheimer's Disease and Mild Cognitive Impairment

Functional MRI (fMRI) has the potential to be used as a tool to detect biomarkers related to classifying Alzheimer's disease (AD) and its prodromal stage, mild cognitive impairment (MCI). Previous meta‐analyses suggest that during episodic memory tasks, MCI patients exhibit hyperactivation in the medial temporal lobe (MTL) while AD patients exhibit hypoactivation, compared to healthy older adults (HOAs). However, these previous studies have methodological weaknesses that limit the generalizability of the results. This quantitative meta‐analysis re‐examines the activation associated with episodic memory in AD and MCI as compared to cognitively normal populations to assess these commonly cited activation differences. A whole‐brain activation likelihood estimation based meta‐analysis was conducted on fMRI studies that examined episodic memory in HOA (n = 200), MCI (n = 131), and AD populations (n = 89; total n = 409). Diffuse activation was exhibited in the HOA sample, while activation was more limited in the clinical populations. Additionally, the HOA sample showed more activation in the right hippocampus compared to the AD sample. The MCI studies showed greater activation in the cerebellum compared to the HOA sample, potentially indicating a compensatory mechanism for verbal encoding. MTL hypoactivation in the AD sample is consistent with previous studies, but more evidence of MCI hyperactivation is needed before considering MTL activation as an early biomarker for the AD disease process.     

Altered resting state networks in mild cognitive impairment and mild Alzheimer's disease: an fMRI study

Activity and reactivity of the default mode network in the brain was studied using functional magnetic resonance imaging (fMRI) in 28 nondemented individuals with mild cognitive impairment (MCI), 18 patients with mild Alzheimer's disease (AD), and 41 healthy elderly controls (HC). The default mode network was interrogated by means of decreases in brain activity, termed deactivations, during a visual encoding task and during a nonspatial working memory task. Deactivation was found in the default mode network involving the anterior frontal, precuneus, and posterior cingulate cortex. MCI patients showed less deactivation than HC, but more than AD. The most pronounced differences between MCI, HC, and AD occurred in the very early phase of deactivation, reflecting the reactivity and adaptation of the network. The default mode network response in the anterior frontal cortex significantly distinguished MCI from both HC (in the medial frontal) and AD (in the anterior cingulate cortex). The response in the precuneus could only distinguish between patients and HC, not between MCI and AD. These findings may be consistent with the notion that MCI is a transitional state between healthy aging and dementia and with the proposed early changes in MCI in the posterior cingulate cortex and precuneus. These findings suggest that altered activity in the default mode network may act as an early marker for AD pathology.     

Grab‐AD: Generalizability and reproducibility of altered brain activity and diagnostic classification in Alzheimer's Disease

Alzheimer's disease (AD) is associated with disruptions in brain activity and networks. However, there is substantial inconsistency among studies that have investigated functional brain alterations in AD; such contradictions have hindered efforts to elucidate the core disease mechanisms. In this study, we aim to comprehensively characterize AD‐associated functional brain alterations using one of the world's largest resting‐state functional MRI (fMRI) biobank for the disorder. The biobank includes fMRI data from six neuroimaging centers, with a total of 252 AD patients, 221 mild cognitive impairment (MCI) patients and 215 healthy comparison individuals. Meta‐analytic techniques were used to unveil reliable differences in brain function among the three groups. Relative to the healthy comparison group, AD was associated with significantly reduced functional connectivity and local activity in the default‐mode network, basal ganglia and cingulate gyrus, along with increased connectivity or local activity in the prefrontal lobe and hippocampus (p < .05, Bonferroni corrected). Moreover, these functional alterations were significantly correlated with the degree of cognitive impairment (AD and MCI groups) and amyloid‐β burden. Machine learning models were trained to recognize key fMRI features to predict individual diagnostic status and clinical score. Leave‐one‐site‐out cross‐validation established that diagnostic status (mean area under the receiver operating characteristic curve: 0.85) and clinical score (mean correlation coefficient between predicted and actual Mini‐Mental State Examination scores: 0.56, p < .0001) could be predicted with high accuracy. Collectively, our findings highlight the potential for a reproducible and generalizable functional brain imaging biomarker to aid the early diagnosis of AD and track its progression.     

Altered topological patterns of brain networks in mild cognitive impairment and Alzheimer's disease: a resting-state fMRI study

Recent studies have shown that cognitive and memory decline in patients with Alzheimer's disease (AD) is coupled with losses of small-world attributes. However, few studies have investigated the characteristics of the whole brain networks in individuals with mild cognitive impairment (MCI). In this functional magnetic resonance imaging (fMRI) study, we investigated the topological properties of the whole brain networks in 18 AD patients, 16 MCI patients, and 18 age-matched healthy subjects. Among the three groups, AD patients showed the longest characteristic path lengths and the largest clustering coefficients, while the small-world measures of MCI networks exhibited intermediate values. The finding was not surprising, given that MCI is considered to be the prodromal stage of AD. Compared with normal controls, MCI patients showed decreased nodal centrality mainly in the medial temporal lobe as well as increased nodal centrality in the occipital regions. In addition, we detected increased nodal centrality in the medial temporal lobe and frontal gyrus, and decreased nodal centrality mainly in the amygdala in MCI patients compared with AD patients. The results suggested a widespread rewiring in AD and MCI patients. These findings concerning AD and MCI may be an integrated reflection of reorganization of the brain networks accompanied with the cognitive decline that may lead to AD.     

A concise and persistent feature to study brain resting‐state network dynamics: Findings from the Alzheimer's Disease Neuroimaging Initiative

Alzheimer's disease (AD) is the most common type of dementia in the elderly with no effective treatment currently. Recent studies of noninvasive neuroimaging, resting‐state functional magnetic resonance imaging (rs‐fMRI) with graph theoretical analysis have shown that patients with AD and mild cognitive impairment (MCI) exhibit disrupted topological organization in large‐scale brain networks. In previous work, it is a common practice to threshold such networks. However, it is not only difficult to make a principled choice of threshold values, but also worse is the discard of potential important information. To address this issue, we propose a threshold‐free feature by integrating a prior persistent homology‐based topological feature (the zeroth Betti number) and a newly defined connected component aggregation cost feature to model brain networks over all possible scales. We show that the induced topological feature (Integrated Persistent Feature) follows a monotonically decreasing convergence function and further propose to use its slope as a concise and persistent brain network topological measure. We apply this measure to study rs‐fMRI data from the Alzheimer's Disease Neuroimaging Initiative and compare our approach with five other widely used graph measures across five parcellation schemes ranging from 90 to 1,024 region‐of‐interests. The experimental results demonstrate that the proposed network measure shows more statistical power and stronger robustness in group difference studies in that the absolute values of the proposed measure of AD are lower than MCI and much lower than normal controls, providing empirical evidence for decreased functional integration in AD dementia and MCI.     

Functional abnormalities of the medial temporal lobe memory system in mild cognitive impairment and Alzheimer's disease: insights from functional MRI studies

Functional MRI (fMRI) studies of mild cognitive impairment (MCI) and Alzheimer's disease (AD) have begun to reveal abnormalities in memory circuit function in humans suffering from memory disorders. Since the medial temporal lobe (MTL) memory system is a site of very early pathology in AD, a number of studies, reviewed here, have focused on this region of the brain. By the time individuals are diagnosed clinically with AD dementia, the substantial memory impairments appear to be associated with not only MTL atrophy but also hypoactivation during memory task performance. Prior to dementia, when individuals are beginning to manifest signs and symptoms of memory impairment, the hippocampal formation and other components of the MTL memory system exhibit substantial functional abnormalities during memory task performance. It appears that, early in the course of MCI when memory deficits and hippocampal atrophy are less prominent, there may be hyperactivation of MTL circuits, possibly representing inefficient compensatory activity. Later in the course of MCI, when considerable memory deficits are present, MTL regions are no longer able to activate during attempted learning, as is the case in AD dementia. Recent fMRI data in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in the MTL memory system and in functionally connected brain regions, such as the precuneus. As this work continues to mature, it will likely contribute to our understanding of fundamental memory processes in the human brain and how these are perturbed in memory disorders. We hope these insights will translate into the incorporation of measures of task-related brain function into diagnostic assessment or therapeutic monitoring, such as for use in clinical trials.     

Partial recovery of abnormal insula and dorsolateral prefrontal connectivity to cognitive networks in chronic low back pain after treatment

We previously reported that effective treatment of chronic low back pain (CLBP) reversed abnormal brain structure and functional MRI (fMRI) activity during cognitive task performance, particularly in the left dorsolateral prefrontal cortex (DLPFC). Here, we used resting‐state fMRI to examine how chronic pain affects connectivity of brain networks supporting cognitive functioning and the effect of treatment in 14 CLBP patients and 16 healthy, pain‐free controls (scans were acquired at baseline for all subjects and at 6‐months post‐treatment for patients and a matched time‐point for 10 controls). The main networks activated during cognitive task performance, task‐positive network (TPN) and task‐negative network (TNN) (aka default mode) network, were identified in subjects' task fMRI data and used to define matching networks in resting‐state data. The connectivity of these cognitive resting‐state networks was compared between groups, and before and after treatment. Our findings converged on the bilateral insula (INS) as the region of aberrant cognitive resting‐state connectivity in patients pretreatment versus controls. These findings were complemented by an independent, data‐driven approach showing altered global connectivity of the INS. Detailed investigation of the INS confirmed reduced connectivity to widespread TPN and TNN areas, which was partially restored post‐treatment. Furthermore, analysis of diffusion‐tensor imaging (DTI) data revealed structural changes in white matter supporting these findings. The left DLPFC also showed aberrant connectivity that was restored post‐treatment. Altogether, our findings implicate the bilateral INS and left DLPFC as key nodes of disrupted cognition‐related intrinsic connectivity in CLBP, and the resulting imbalance between TPN and TNN function is partially restored with treatment. Hum Brain Mapp 36:2075–2092, 2015. © 2015 Wiley Periodicals, Inc.     

Cognitive and default‐mode resting state networks: Do male and female brains “rest” differently?

Variability in human behavior related to sex is supported by neuroimaging studies showing differences in brain activation patterns during cognitive task performance. An emerging field is examining the human connectome, including networks of brain regions that are not only temporally‐correlated during different task conditions, but also networks that show highly correlated spontaneous activity during a task‐free state. Both task‐related and task‐free network activity has been associated with individual task performance and behavior under certain conditions. Therefore, our aim was to determine whether sex differences exist during a task‐free resting state for two networks associated with cognitive task performance (executive control network (ECN), salience network (SN)) and the default mode network (DMN). Forty‐nine healthy subjects (26 females, 23 males) underwent a 5‐min task‐free fMRI scan in a 3T MRI. An independent components analysis (ICA) was performed to identify the best‐fit IC for each network based on specific spatial nodes defined in previous studies. To determine the consistency of these networks across subjects we performed self‐organizing group‐level ICA analyses. There were no significant differences between sexes in the functional connectivity of the brain areas within the ECN, SN, or the DMN. These important findings highlight the robustness of intrinsic connectivity of these resting state networks and their similarity between sexes. Furthermore, our findings suggest that resting state fMRI studies do not need to be controlled for sex. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Reduced precuneus deactivation during object naming in patients with mild cognitive impairment, Alzheimer's disease, and frontotemporal lobar degeneration

The precuneus is part of the default network of the human brain, which exhibits a high level of activity during the resting state and lower activity during task-related behavior. Typically, the posterior midline areas show this characteristic response in functional magnetic resonance imaging (fMRI) studies. In Alzheimer's disease (AD) and mild cognitive impairment (MCI), subjects exhibit a lack of this typical deactivation. The interpretation of these findings, however, is obfuscated by the presence of local pathology and atrophy in AD. In contrast to AD, in patients with early frontotemporal lobar degeneration (FTLD), the precuneus is virtually free of local neuropathology. In this study, we demonstrate reduced fMRI signal in the precuneus in a group of patients with FTLD during a confrontation naming task. We show that this effect in FTLD patients was (1) similar to that observed in AD and MCI and (2) not related to the degree of gray matter atrophy in the precuneus. We hypothesize that reduced deactivation of the default network is not related to local pathology but to a lack of connectivity, which decreases in both FTLD and AD, the major cortical dementias.     

Functional connectivity in elderly controls and AD patients using resting state fMRI: a pilot study

Conventionally, Alzheimer's disease (AD) and other dementias are diagnosed using clinical assessment, neuropsychology and also structural neuroimaging, showing neuronal degeneration starting in the hippocampal regions. However, there is an increasing need for a new method that is more sensitive to early AD identification than currently possible. A new promising technique that may be used for this is to measure local brain activation using functional magnetic resonance imaging (fMRI), since functional loss predates structural loss of brain tissue. A new method to apply fMRI is to study connectivity between brain regions during a resting state without application of a task. Recent data suggest that connectivity within memory systems during such a resting state is associated with the level of memory function. Here we explain how we will study healthy elderly controls, patients with a mild cognitive impairment (MCI, considered to be a transitional stage between normal condition and AD), and AD patients using resting state connectivity fMRI. If resting state connectivity is sensitive to cognitive decline, this will be of great importance for noninvasive dementia research, offering a tool to easily study functional networks in the brain without the requirement of a memory task, and perhaps offering a tool sensitive for early diagnostics.     

Frontoparietal and salience network alterations in obsessive–compulsive disorder: insights from independent component and sliding time window analyses

BackgroundResting-state functional MRI (fMRI) studies commonly report alterations in 3 core networks in obsessive–compulsive disorder (OCD) — the frontoparietal network, the default mode network and the salience network — defined by functionally connected infra-slow oscillations in ongoing brain activity. However, most of these studies observed static functional connectivity in the brains of patients with OCD.MethodsTo investigate dynamic functional connectivity alterations and widen the evidence base toward the triple network model in OCD, we performed group-based independent component and sliding time window analyses in 49 patients with OCD and 41 healthy controls.ResultsThe traditional independent component analysis showed alterations in the left frontoparietal network as well as between the left and right frontoparietal networks in patients with OCD compared with healthy controls. For dynamic functional connectivity, the sliding time window approach revealed peak dysconnectivity between the left and right frontoparietal networks and between the left frontoparietal network and the salience network.Limitations: The number of independent components, noise in the resting-state fMRI images, the heterogeneity of the OCD sample, and comorbidities and medication status in the patients could have biased the results.ConclusionDisrupted modulation of these intrinsic brain networks may contribute to the pathophysiology of OCD.     

Putting age-related task activation into large-scale brain networks: A meta-analysis of 114 fMRI studies on healthy aging

Normal aging is associated with cognitive decline and underlying brain dysfunction. Previous studies concentrated less on brain network changes at a systems level. Our goal was to examine these age-related changes of fMRI-derived activation with a common network parcellation of the human brain function, offering a systems-neuroscience perspective of healthy aging. We conducted a series of meta-analyses on a total of 114 studies that included 2035 older adults and 1845 young adults. Voxels showing significant age-related changes in activation were then overlaid onto seven commonly referenced neuronal networks. Older adults present moderate cognitive decline in behavioral performance during fMRI scanning, and hypo-activate the visual network and hyper-activate both the frontoparietal control and default mode networks. The degree of increased activation in frontoparietal network was associated with behavioral performance in older adults. Age-related changes in activation present different network patterns across cognitive domains. The systems neuroscience approach used here may be useful for elucidating the underlying network mechanisms of various brain plasticity processes during healthy aging.     

Hippocampal dysfunction in patients with mild cognitive impairment: a functional neuroimaging study of a visuospatial paired associates learning task

Mild cognitive impairment (MCI) patients report memory problems greater than those normally expected with ageing, but do not fulfil criteria for clinically probable Alzheimer's disease. Accumulating evidence demonstrates that impaired performance on the Paired Associates Learning (PAL) test from the Cambridge Neuropsychological Test Automated Battery (CANTAB) may be sensitive and specific for early and differential diagnosis of Alzheimer's disease. We adapted the basic CANTAB PAL task for functional magnetic resonance imaging (fMRI) in order to examine the functional brain deficits, at encoding and retrieval separately, in patients with MCI compared to healthy matched volunteers. As well as investigating the main effects of encoding and retrieval, we characterized neural responses in the two groups to increasing memory load. We focused on changes in BOLD response in the hippocampus and related structures, as an a priori region of interest based on what is known about the neuropathology of the early stages of Alzheimer's disease and previous information on the neural substrates of the PAL task. We also used structural MRI in the same patients to assess accompanying structural brain abnormalities associated with MCI.In terms of the BOLD response, the bilateral hippocampal activation in the MCI and control groups depended upon load, the MCI patients activating significantly more than controls at low loads and significantly less at higher loads. There were no other differences between MCI patients and controls in terms of the neural networks activated during either encoding or retrieval of the PAL task, including the prefrontal, cingulate and temporal cortex. The functional deficit in hippocampal activation in the MCI patients was accompanied by structural differences in the same location, suggesting that the decrease in hippocampal activation may be caused by a decrease in the amount of grey matter. This is one of the first studies to have used both encoding and retrieval phases of a memory paradigm for fMRI in MCI patients, and to have shown that the BOLD response in MCI patients can show both hyperactivation and hypoactivation in the same individuals as a function of memory load and encoding/retrieval. The findings suggest that performance on PAL might be a useful cognitive biomarker for early detection of Alzheimer's disease, especially when used in conjunction with neuroimaging.     

Phenotypic regional functional imaging patterns during memory encoding in mild cognitive impairment and Alzheimer's disease

BackgroundReliable blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) phenotypic biomarkers of Alzheimer’s disease (AD) or mild cognitive impairment (MCI) are likely to emerge only from a systematic, quantitative, and aggregate examination of the functional neuroimaging research literature.MethodsA series of random-effects activation likelihood estimation (ALE) meta-analyses were conducted on studies of episodic memory encoding operations in AD and MCI samples relative to normal controls. ALE analyses were based on a thorough literature search for all task-based functional neuroimaging studies in AD and MCI published up to January 2010. Analyses covered 16 fMRI studies, which yielded 144 distinct foci for ALE meta-analysis.ResultsALE results indicated several regional task-based BOLD consistencies in MCI and AD patients relative to normal control subjects across the aggregate BOLD functional neuroimaging research literature. Patients with AD and those at significant risk (MCI) showed statistically significant consistent activation differences during episodic memory encoding in the medial temporal lobe, specifically parahippocampal gyrus, as well superior frontal gyrus, precuneus, and cuneus, relative to normal control subjects.ConclusionsALE consistencies broadly support the presence of frontal compensatory activity, medial temporal lobe activity alteration, and posterior midline “default mode” hyperactivation during episodic memory encoding attempts in the diseased or prospective predisease condition. Taken together, these robust commonalities may form the foundation for a task-based fMRI phenotype of memory encoding in AD.     

Hallucination‐ and speech‐specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task‐based fMRI data: An fBIRN study

Hypercoupling of activity in speech‐perception‐specific brain networks has been proposed to play a role in the generation of auditory‐verbal hallucinations (AVHs) in schizophrenia; however, it is unclear whether this hypercoupling extends to nonverbal auditory perception. We investigated this by comparing schizophrenia patients with and without AVHs, and healthy controls, on task‐based functional magnetic resonance imaging (fMRI) data combining verbal speech perception (SP), inner verbal thought generation (VTG), and nonverbal auditory oddball detection (AO). Data from two previously published fMRI studies were simultaneously analyzed using group constrained principal component analysis for fMRI (group fMRI‐CPCA), which allowed for comparison of task‐related functional brain networks across groups and tasks while holding the brain networks under study constant, leading to determination of the degree to which networks are common to verbal and nonverbal perception conditions, and which show coordinated hyperactivity in hallucinations. Three functional brain networks emerged: (a) auditory‐motor, (b) language processing, and (c) default‐mode (DMN) networks. Combining the AO and sentence tasks allowed the auditory‐motor and language networks to separately emerge, whereas they were aggregated when individual tasks were analyzed. AVH patients showed greater coordinated activity (deactivity for DMN regions) than non‐AVH patients during SP in all networks, but this did not extend to VTG or AO. This suggests that the hypercoupling in AVH patients in speech‐perception‐related brain networks is specific to perceived speech, and does not extend to perceived nonspeech or inner verbal thought generation.     

Attentional reorientation along the meridians of the visual field: Are there different neural mechanisms at play?

Hemispatial neglect, after unilateral lesions to parietal brain areas, is characterized by an inability to respond to unexpected stimuli in contralesional space. As the visual field's horizontal meridian is most severely affected, the brain networks controlling visuospatial processes might be tuned explicitly to this axis. We investigated such a potential directional tuning in the dorsal and ventral frontoparietal attention networks, with a particular focus on attentional reorientation. We used an orientation‐discrimination task where a spatial precue indicated the target position with 80% validity. Healthy participants (n = 29) performed this task in two runs and were required to (re‐)orient attention either only along the horizontal or the vertical meridian, while fMRI and behavioral measures were recorded. By using a general linear model for behavioral and fMRI data, dynamic causal modeling for effective connectivity, and other predictive approaches, we found strong statistical evidence for a reorientation effect for horizontal and vertical runs. However, neither neural nor behavioral measures differed between vertical and horizontal reorienting. Moreover, models from one run successfully predicted the cueing condition in the respective other run. Our results suggest that activations in the dorsal and ventral attention networks represent higher‐order cognitive processes related to spatial attentional (re‐)orientating that are independent of directional tuning and that unilateral attention deficits after brain damage are based on disrupted interactions between higher‐level attention networks and sensory areas.     

Meta‐analytic evidence for altered mesolimbic responses to reward in schizophrenia

Dysfunction of reward‐related neural circuitry in schizophrenia (SCZ) has been widely reported, and may provide insight into the motivational and cognitive disturbances that characterize the disorder. Although previous meta‐analyses of reward learning paradigms in SCZ have been performed, a meta‐analysis of whole‐brain coordinate maps in SCZ alone has not been conducted. In this study, we performed an activation likelihood estimate (ALE) meta‐analysis, and performed a follow‐up analysis of functional connectivity and functional decoding of identified regions. We report several salient findings that extend prior work in this area. First, an alteration in reward‐related activation was observed in the right ventral striatum, but this was not solely driven by hypoactivation in the SCZ group compared to healthy controls. Second, the region was characterized by functional connectivity primarily with the lateral prefrontal cortex and pre‐supplementary motor area (preSMA), as well as subcortical regions such as the thalamus which show structural deficits in SCZ. Finally, although the meta‐analysis showed no regions outside the ventral striatum to be significantly altered, regions with higher functional connectivity with the ventral striatum showed a greater number of subthreshold foci. Together, these findings confirm the alteration of ventral striatal function in SCZ, but suggest that a network‐based approach may assist future analysis of the functional underpinnings of the disorder.     

Reduced neuronal efficacy in progressive mild cognitive impairment: a prospective fMRI study on visuospatial processing

Mild cognitive impairment (MCI) often refers to the preclinical stage of dementia, where the majority develop Alzheimer's disease (AD). Given that neurodegenerative burden and compensatory mechanisms might exist before accepted clinical symptoms of AD are noticeable, the current prospective study aimed to investigate the functioning of brain regions in the visuospatial networks responsible for preclinical symptoms in AD using event-related functional magnetic resonance imaging (fMRI). Eighteen MCI patients were evaluated and clinically followed for approximately 3 years. Five progressed to AD (PMCI) and eight remained stable (SMCI). Thirteen age-, gender- and education-matched controls also participated. An angle discrimination task with varying task demands was used. Brain activation patterns as well as task demand-dependent and -independent signal changes between the groups were investigated by using an extended general linear model including individual performance (reaction time [RT]) of each single trial. Similar behavioral (RT and accuracy) responses were observed between MCI patients and controls. A network of bilateral activations, e.g. dorsal pathway, which increased linearly with increasing task demand, was engaged in all subjects. Compared with SMCI patients and controls, PMCI patients showed a stronger relation between task demand and brain activity in left superior parietal lobules (SPL) as well as a general task demand-independent increased activation in left precuneus. Altered brain function can be detected at a group level in individuals that progress to AD before changes occur at the behavioral level. Increased parietal activation in PMCI could reflect a reduced neuronal efficacy due to accumulating AD pathology and might predict future clinical decline in patients with MCI.     

Disruption of Resting Functional Connectivity in Alzheimer’s Patients and At-Risk Subjects

The resting brain exhibits continuous intrinsic activity, which is correlated between groups of regions forming resting state networks. Evaluating resting connectivity is a popular approach for studying brain diseases. Several hundred studies are now available that address integrity of resting connectivity in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), as well as preclinical at-risk subjects. Most studies focus on the default mode network, a system of specific brain areas showing strong connected resting activity that attenuates during goal-directed behavior. The extent of intrinsic brain activity tends to be strongly correlated with cognitive processes and is specifically disrupted in AD and MCI patients and at-risk subjects, with changes seeming to evolve during the transition between the disease stages. In this study, we review the current findings in default mode network and other resting state network studies in AD and MCI patients and at-risk subjects as assessed by resting state functional magnetic resonance imaging.     

Three subsystems of the inferior parietal cortex are differently affected in mild cognitive impairment

The Inferior parietal cortex (IPC), including the intraparietal sulcus (IPS), angular gyrus (AG), and supramarginal gyrus (SG), plays an important role in episodic memory, and is considered to be one of the specific neuroimaging markers in predicting the conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD). However, it is still unclear whether the connectivity of the IPC is impaired in MCI patients. In the present study, we used resting state fMRI to examine the functional connectivity of the three subdivisions of the IPC in MCI patients after controlling the impact of regional grey matter atrophy. It was found that, using IPS, AG, and SG as seeds of functional connectivity, three canonical functional networks could be correspondingly traced, i.e., executive control network (ECN), default mode network (DMN), and salience network (SN), and the three networks are differently altered in MCI patients. In contrast to the healthy controls, it was found that in MCI patients: 1) AG connectivity was significantly reduced within the DMN; 2) IPS showed decreased connectivity with the right inferior frontal gyrus while showing increased connectivity with the left frontal regions within the ECN; and 3) SG displayed decreased connectivity with a distribution of regions including the frontal and parietal regions, and increased connectivity with some sub-cortical areas within the SN. Moreover, the connectivity within the three networks was correlated with episodic memory and general cognitive impairment in MCI patients. These results extend well beyond the DMN, and further suggest that MCI is associated with alteration of large-scale functional brain networks.