Kuncheng Li

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

Previous studies have led to the proposal that patients with Alzheimers 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. Hum Brain Mapp 2006.

Brain anatomical network and intelligence

Intuitively, higher intelligence might be assumed to correspond to more efficient information transfer in the brain, but no direct evidence has been reported from the perspective of brain networks. In this study, we performed extensive analyses to test the hypothesis that individual differences in intelligence are associated with brain structural organization, and in particular that higher scores on intelligence tests are related to greater global efficiency of the brain anatomical network. We constructed binary and weighted brain anatomical networks in each of 79 healthy young adults utilizing diffusion tensor tractography and calculated topological properties of the networks using a graph theoretical method. Based on their IQ test scores, all subjects were divided into general and high intelligence groups and significantly higher global efficiencies were found in the networks of the latter group. Moreover, we showed significant correlations between IQ scores and network properties across all subjects while controlling for age and gender. Specifically, higher intelligence scores corresponded to a shorter characteristic path length and a higher global efficiency of the networks, indicating a more efficient parallel information transfer in the brain. The results were consistently observed not only in the binary but also in the weighted networks, which together provide convergent evidence for our hypothesis. Our findings suggest that the efficiency of brain structural organization may be an important biological basis for intelligence.

Regional coherence changes in the early stages of Alzheimer’s disease: A combined structural and resting-state functional MRI study

Recent functional imaging studies have indicated that the pathophysiology of Alzheimers disease (AD) can be associated with the changes in spontaneous low-frequency (<0.08 Hz) blood oxygenation level-dependent fluctuations (LFBF) measured during a resting state. The purpose of this study was to examine regional LFBF coherence patterns in early AD and the impact of regional brain atrophy on the functional results. Both structural MRI and resting-state functional MRI scans were collected from 14 AD subjects and 14 age-matched normal controls. We found significant regional coherence decreases in the posterior cingulate cortex/precuneus (PCC/PCu) in the AD patients when compared with the normal controls. Moreover, the decrease in the PCC/PCu coherence was correlated with the disease progression measured by the Mini-Mental State Exam scores. The changes in LFBF in the PCC/PCu may be related to the resting hypometabolism in this region commonly detected in previous positron emission tomography studies of early AD. When the regional PCC/PCu atrophy was controlled, these results still remained significant but with a decrease in the statistical power, suggesting that the LFBF results are at least partly explained by the regional atrophy. In addition, we also found increased LFBF coherence in the bilateral cuneus, right lingual gyrus and left fusiform gyrus in the AD patients. These regions are consistent with previous findings of AD-related increased activation during cognitive tasks explained in terms of a compensatory-recruitment hypothesis. Finally, our study indicated that regional brain atrophy could be an important consideration in functional imaging studies of neurodegenerative diseases.

DYNAMIC FUNCTIONAL REORGANIZATION OF THE MOTOR EXECUTION NETWORK AFTER STROKE

Numerous studies argue that cortical reorganization may contribute to the restoration of motor function following stroke. However, the evolution of changes during the post-stroke reorganization has been little studied. This study sought to identify dynamic changes in the functional organization, particularly topological characteristics, of the motor execution network during the stroke recovery process. Ten patients (nine male and one female) with subcortical infarctions were assessed by neurological examination and scanned with resting-state functional magnetic resonance imaging across five consecutive time points in a single year. The motor execution network of each subject was constructed using a functional connectivity matrix between 21 brain regions and subsequently analysed using graph theoretical approaches. Dynamic changes in topological configuration of the network during the process of recovery were evaluated by a mixed model. We found that the motor execution network gradually shifted towards a random mode during the recovery process, which suggests that a less optimized reorganization is involved in regaining function in the affected limbs. Significantly increased regional centralities within the network were observed in the ipsilesional primary motor area and contralesional cerebellum, whereas the ipsilesional cerebellum showed decreased regional centrality. Functional connectivity to these brain regions demonstrated consistent alterations over time. Notably, these measures correlated with different clinical variables, which provided support that the findings may reflect the adaptive reorganization of the motor execution network in stroke patients. In conclusion, the study expands our understanding of the spectrum of changes occurring in the brain after stroke and provides a new avenue for investigating lesion-induced network plasticity.

Regional Homogeneity Changes in Patients With Parkinson's Disease

Resting state brain activity in Parkinsons disease (PD) can give clues to the pathophysiology of the disorder, and might be helpful in diagnosis, but it has never been explored using functional MRI (fMRI). In the current study, we used a regional homogeneity (ReHo) method to investigate PD‐related modulations of neural activity in the resting state. FMRIs were acquired in 22 patients with PD at both before and after levodopa administration, as well as in 22 age‐ and sex‐matched normal controls. In the PD group compared with the healthy controls, we found ReHo decreased in extensive brain regions, including the putamen, thalamus, and supplementary motor area; and increased in some other areas, including the cerebellum, primary sensorimotor cortex, and premotor area. The ReHo off medication was negatively correlated with the Unified Parkinsons Disease Rating Scale (UPDRS) in the putamen and some other regions, and was positively correlated with the UPDRS in the cerebellum. Administration of levodopa relatively normalized ReHo. Our findings demonstrate that neural activity in the resting state is changed in patients with PD. This change is secondary to dopamine deficiency, and related to the severity of the disease. The different neuronal activity at the baseline state should be considered in explaining fMRI findings obtained during tasks. Hum Brain Mapp 2009.

Frequency-dependent changes in the amplitude of low-frequency fluctuations in amnestic mild cognitive impairment: a resting-state fMRI study.

Here we utilized resting-state functional magnetic resonance imaging (R-fMRI) to measure the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF) in 24 patients with amnestic mild cognitive impairment (aMCI) and 24 age- and sex-matched healthy controls. Two different frequency bands (slow-5: 0.01-0.027 Hz; slow-4: 0.027-0.073 Hz) were analyzed. We showed that there were widespread differences in ALFF/fALFF between the two bands in many brain regions, predominantly including the medial prefrontal cortex (MPFC), posterior cingulate cortex/precuneus (PCC/PCu), basal ganglia, and hippocampus/parahippocampal gyrus (PHG). Compared to controls, the aMCI patients had decreased ALFF/fALFF values in the PCC/PCu, MPFC, hippocampus/PHG, basal ganglia, and prefrontal regions, and increased ALFF/fALFF values mainly in several occipital and temporal regions. Specifically, we observed that the ALFF/fALFF abnormalities in the PCC/PCu, PHG, and several occipital regions were greater in the slow-5 band than in the slow-4 band. Finally, our results of functional analysis were not significantly influenced by the gray matter loss in the MCI patients, suggesting that the results reflect functional differences between groups. Together, our data suggest that aMCI patients have widespread abnormalities in intrinsic brain activity, and the abnormalities depend on the studied frequency bands of R-fMRI data.

Changes of functional connectivity of the motor network in the resting state in Parkinson's disease

We used functional MRI (fMRI) and a network model based on graph theory to measure functional connectivity of brain motor network in the resting state in patients with Parkinsons disease (PD). FMRIs were acquired in 22 PD patients before and after levodopa administration, and in age- and sex-matched normal controls. The total connectivity degree of each region within the motor network was calculated and compared between patients and controls. We found that PD patients at off state had significantly decreased functional connectivity in the supplementary motor area, left dorsal lateral prefrontal cortex and left putamen, and had increased functional connectivity in the left cerebellum, left primary motor cortex, and left parietal cortex compared to normal subjects. Administration of levodopa relatively normalized the pattern of functional connectivity in PD patients. The functional connectivity in most of regions in the motor network correlated with the Unified Parkinsons Disease Rating Scale motor score in the patients. Our findings demonstrate that the pattern of functional connectivity of the motor network in the resting state is disrupted in PD. This change is secondary to dopamine deficiency, and related to the severity of the disease. We postulate that this abnormal functional connectivity of motor network in the baseline state is possibly an important factor contributing to some motor deficits in PD, e.g. akinesia.

Impairment and compensation coexist in amnestic MCI default mode network.

Mild cognitive impairment (MCI) is the transitional, heterogeneous continuum from healthy elderly to Alzheimers disease (AD). Previous studies have shown that brain functional activity in the default mode network (DMN) is impaired in AD patients. However, altering DMN activity patterns in MCI patients remains largely unclear. The present study utilized resting-state functional magnetic resonance imaging (fMRI) and an independent component analysis (ICA) approach to investigate DMN activity in 14 amnestic MCI (aMCI) patients and 14 healthy elderly. Compared to the aMCI patients, the healthy elderly exhibited increased functional activity in the DMN regions, including the bilateral precuneus/posterior cingulate cortex, right inferior parietal lobule, and left fusiform gyrus, as well as a trend towards increased right medial temporal lobe activity. The aMCI patients exhibited increased activity in the left prefrontal cortex, inferior parietal lobule, and middle temporal gyrus compared to the healthy elderly. Increased frontal-parietal activity may indicate compensatory processes in the aMCI patients. These findings suggest that abnormal DMN activity could be useful as an imaging-based biomarker for the diagnosis and monitoring of aMCI patients.

Diffusion Tensor Tractography Reveals Disrupted Topological Efficiency in White Matter Structural Networks in Multiple Sclerosis

Little is currently known about the alterations in the topological organization of the white matter (WM) structural networks in patients with multiple sclerosis (MS). In the present study, we used diffusion tensor imaging and deterministic tractography to map the WM structural networks in 39 MS patients and 39 age- and gender-matched healthy controls. Graph theoretical methods were applied to investigate alterations in the network efficiency in these patients. The MS patients and the controls exhibited efficient small-world properties in their WM structural networks. However, the global and local network efficiencies were significantly decreased in the MS patients compared with the controls, with the most pronounced changes observed in the sensorimotor, visual, default-mode, and language areas. Furthermore, the decreased network efficiencies were significantly correlated with the expanded disability status scale scores, the disease durations, and the total WM lesion loads. Together, the results suggest a disrupted integrity in the large-scale brain systems in MS, thus providing new insights into the understanding of MS connectome. Our data also suggest that a topology-based brain network analysis can provide potential biomarkers for disease diagnosis and for monitoring the progression and treatment effects for patients with MS.

Spatial patterns of intrinsic brain activity in mild cognitive impairment and alzheimer's disease: A resting‐state functional MRI study

We used resting‐state functional MRI to investigate spatial patterns of spontaneous brain activity in 22 healthy elderly subjects, as well as 16 mild cognitive impairment (MCI) and 16 Alzheimers disease (AD) patients. The pattern of intrinsic brain activity was measured by examining the amplitude of low‐frequency fluctuations (ALFF) of blood oxygen level dependent signal during rest. There were widespread ALFF differences among the three groups throughout the frontal, temporal, and parietal cortices. Both AD and MCI patients showed decreased activity mainly in the medial parietal lobe region and lentiform nucleus, while there was increased activity in the lateral temporal regions and superior frontal and parietal regions as compared with controls. Compared with MCI, the AD patients showed decreased activity in the medial prefrontal cortex and increased activity in the superior frontal gyrus and inferior and superior temporal gyri. Specifically, the most significant ALFF differences among the groups appeared in the posterior cingulate cortex, with a reduced pattern of activity when comparing healthy controls, MCI, and AD patients. Additionally, we also showed that the regions with ALFF changes had significant correlations with the cognitive performance of patients as measured by mini‐mental state examination scores. Finally, while taking gray matter volume as covariates, the ALFF results were approximately consistent with those without gray matter correction, implying that the functional analysis could not be explained by regional atrophy. Together, our results demonstrate that there is a specific pattern of ALFF in AD and MCI, thus providing insights into biological mechanisms of the diseases. Hum Brain Mapp, 2010.