Structural and Functional Changes in Subcortical Vascular Mild Cognitive Impairment: A Combined Voxel-Based Morphometry and Resting-State fMRI Study

The present study aimed to investigate changes in structural gray matter (GM) volume and functional amplitude of spontaneous low-frequency oscillations (LFO) and functional connectivity density in patients with subcortical vascular mild cognitive impairment (svMCI). Structural MRI and resting-sate functional MRI data were collected from 26 svMCI patients and 28 age- and gender-matched healthy controls. Structurally, widespread GM atrophy was found in the svMCI patients that resided primarily in frontal (e.g., the superior and middle frontal gyri and medial prefrontal cortex) and temporal (the superior and inferior temporal gyri) brain regions as well as several subcortical brain sites (e.g., the thalamus and the caudate). Functionally, svMCI-related changes were predominantly found in the default mode network (DMN). Compared with the healthy controls, the svMCI patients exhibited decreased LFO amplitudes in the anterior part of the DMN (e.g., the medial prefrontal cortex), whereas increased LFO amplitudes in the posterior part of the DMN (e.g., the posterior cingulate/precuneus). As for functional connectivity density, the DMN regions (e.g., the posterior cingulate/precuneus, the medial prefrontal cortex and the middle temporal gyrus) consistently exhibited decreased functional connectivity. Finally, the overall patterns of functional alterations in LFO amplitudes and functional connectivity density remained little changed after controlling for structural GM volume losses, which suggests that functional abnormalities can be only partly explained by morphological GM volume changes. Together, our results indicate that svMCI patients exhibit widespread abnormalities in both structural GM volume and functional intrinsic brain activity, which have important implications in understanding the pathophysiological mechanism of svMCI.     

Functional Neural Correlates of Attentional Deficits in Amnestic Mild Cognitive Impairment

Although amnestic mild cognitive impairment (aMCI; often considered a prodromal phase of Alzheimer’s disease, AD) is most recognized by its implications for decline in memory function, research suggests that deficits in attention are present early in aMCI and may be predictive of progression to AD. The present study used functional magnetic resonance imaging to examine differences in the brain during the attention network test between 8 individuals with aMCI and 8 neurologically healthy, demographically matched controls. While there were no significant behavioral differences between groups for the alerting and orienting functions, patients with aMCI showed more activity in neural regions typically associated with the networks subserving these functions (e.g., temporoparietal junction and posterior parietal regions, respectively). More importantly, there were both behavioral (i.e., greater conflict effect) and corresponding neural deficits in executive control (e.g., less activation in the prefrontal and anterior cingulate cortices). Although based on a small number of patients, our findings suggest that deficits of attention, especially the executive control of attention, may significantly contribute to the behavioral and cognitive deficits of aMCI.     

Gray and White Matter Changes in Subjective Cognitive Impairment,Amnestic Mild Cognitive Impairment and Alzheimer's Disease: A Voxel-Based Analysis Study

Subjective cognitive impairment may be a very early at-risk period of the continuum of dementia. However, it is difficult to discriminate at-risk states from normal aging. Thus, detection of the early pathological changes in the subjective cognitive impairment period is needed. To elucidate these changes, we employed diffusion tensor imaging and volumetry analysis, and compared subjective cognitive impairment with normal, mild cognitive impairment and Alzheimer''s disease. The subjects in this study were 39 Alzheimer''s disease, 43 mild cognitive impairment, 28 subjective cognitive impairment and 41 normal controls. There were no statistically significant differences between the normal control and subjective cognitive impairment groups in all measures. Alzheimer''s disease and mild cognitive impairment had the same extent of brain atrophy and diffusion changes. These results are consistent with the hypothetical model of the dynamic biomarkers of Alzheimer''s disease.     

Microstructural White Matter Changes,Not Hippocampal Atrophy,Detect Early Amnestic Mild Cognitive Impairment

Background

Alzheimer’s disease (AD) is generally considered to be characterized by pathology in gray matter of the brain, but convergent evidence suggests that white matter degradation also plays a vital role in its pathogenesis. The evolution of white matter deterioration and its relationship with gray matter atrophy remains elusive in amnestic mild cognitive impairment (aMCI), a prodromal stage of AD.

Methods

We studied 155 cognitively normal (CN) and 27 ‘late’ aMCI individuals with stable diagnosis over 2 years, and 39 ‘early’ aMCI individuals who had converted from CN to aMCI at 2-year follow up. Diffusion tensor imaging (DTI) tractography was used to reconstruct six white matter tracts three limbic tracts critical for episodic memory function - the fornix, the parahippocampal cingulum, and the uncinate fasciculus; two cortico-cortical association fiber tracts - superior longitudinal fasciculus and inferior longitudinal fasciculus; and one projection fiber tract - corticospinal tract. Microstructural integrity as measured by fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) was assessed for these tracts.

Results

Compared with CN, late aMCI had lower white matter integrity in the fornix, the parahippocampal cingulum, and the uncinate fasciculus, while early aMCI showed white matter damage in the fornix. In addition, fornical measures were correlated with hippocampal atrophy in late aMCI, whereas abnormality of the fornix in early aMCI occurred in the absence of hippocampal atrophy and did not correlate with hippocampal volumes.

Conclusions

Limbic white matter tracts are preferentially affected in the early stages of cognitive dysfunction. Microstructural degradation of the fornix preceding hippocampal atrophy may serve as a novel imaging marker for aMCI at an early stage.     

轻度认知损伤患者的联系记忆损伤特征

遗忘型轻度认知损伤患者(aMCI)在项目记忆和联系记忆上都有损伤．本文通过临床记忆量表中的项目记忆和联系记忆测验,研究aMCI的联系记忆是否比项目记忆有更显著的损伤．另外,通过分析配对联想学习测验,进一步研究aMCI联系记忆损伤的特点．25名aMCI和28名健康老人参与了两个联系记忆测验(配对联想学习测验和联想回忆测验)和两个项目记忆测验(图像自由回忆和无意义图形再认),aMCI患者在联系记忆测验上表现出了更显著的损伤,即使控制了项目记忆的损伤,aMCI的联系记忆仍然比健康老人显著降低．另外,ROC分析表明联系记忆测验比项目记忆测验对aMCI病人有更高的区分度．对配对联想学习测验的分析表明,相对于健康老人,aMCI患者在记忆有语言联系的词对要比记忆无语义联系的词对更为困难．本研究进一步表明aMCI患者的联系记忆比项目记忆有更大的损伤．相对于健康老人,aMCI患者不仅难以在两个无关项目间创建记忆连接,而且在有效利用项目间本身的语义联系方面存在更大的损伤．联系记忆测验比项目记忆测验对aMCI患者有更高的区分度．在神经心理评估中增加联系记忆测验,能更加有效地识别aMCI患者．     

Famous Landmark Identification in Amnestic Mild Cognitive Impairment and Alzheimer's Disease

Background

Identification of famous landmarks (FLI), famous faces (FFI) and recognition of facial emotions (FER) is affected early in the course of Alzheimer''s disease (AD). FFI, FER and FLI may represent domain specific tasks relying on activation of distinct regions of the medial temporal lobe, which are affected successively during the course of AD. However, the data on FFI and FER in MCI are controversial and FLI domain remains almost unexplored.

Objectives

To determine whether and how are these three specific domains impaired in head to head comparison of patients with amnestic MCI (aMCI) single domain (SD-aMCI) and multiple domain (MD-aMCI). We propose that FLI might be most reliable in differentiating SD-aMCI, which is considered to be an earlier stage of AD pathology spread out, from the controls.

Patients and Methods

A total of 114 patients, 13 with single domain (SD–aMCI) and 30 with multiple domains (MD–aMCI), 29 with mild AD and 42 controls underwent standard neurological and neuropsychological evaluations as well as tests of FLI, FER and FFI.

Results

Compared to the control group, AD subjects performed worse on FFI (p = 0.020), FER (p<0.001) and FLI (p<0.001), MD-aMCI group had significantly worse scores only on FLI (p = 0.002) and approached statistical significance on FER (0.053). SD-aMCI group performed significantly worse only on FLI (p = 0.028) compared to controls.

Conclusions

Patients with SD-aMCI had an isolated impairment restricted to FLI, while patients with MD–aMCI showed impairment in FLI as well as in FER. Patients with mild dementia due to AD have more extensive impairment of higher visual perception. The results suggest that FLI testing may contribute to identification of patients at risk of AD. We hypothesize that clinical examination of all three domains might reflect the spread of the disease from transentorhinal cortex, over amygdala to fusiform gyrus.     

White Matter Changes in Patients with Amnestic Mild Cognitive Impairment Detected by Diffusion Tensor Imaging

Compared to normal aging adults, individuals with amnestic mild cognitive impairment (aMCI) have significantly increased risk for progressing into Alzheimer’s disease (AD). Autopsy studies found that most of the brains of aMCI cases showed anatomical features associated with AD pathology. The recent development of non-invasive neuroimaging technique, such as diffusion tensor imaging (DTI), makes it possible to investigate the microstructures of the cerebral white matter in vivo. We hypothesized that disrupted white matter (WM) integrity existed in aMCI. So we used DTI technique, by measuring fractional anisotropy (FA) and mean diffusivity (MD), to test the brain structures involved in patients with aMCI. DTI scans were collected from 40 patients with aMCI, and 28 normal controls (NC). Tract-based spatial statistics (TBSS) analyses of whole-brain FA and MD images in each individual and group comparisons were carried out. Compared to NC, aMCI patients showed significant FA reduction bilaterally, in the association and projection fibers of frontal, parietal, and temporal lobes, corpus callosum, bilateral corona radiation, right posterior thalamic radiation and right sagittal stratum. aMCI patients also showed significantly increased MD widespreadly in the association and projection fibers of frontal, parietal and temporal lobes, and corpus callosum. Assessment of the WM integrity of the frontal, parietal, temporal lobes, and corpus callosum by using DTI measures may aid early diagnosis of aMCI.     

Electrophysiological Correlates of Amnestic Mild Cognitive Impairment in a Simon Task

Amnestic mild cognitive impairment (aMCI) represents a prodromal stage of Alzheimer`s disease (AD), especially when additional cognitive domains are affected (Petersen et al., 2009). Thus, single-domain amnestic MCI (sdaMCI) and multiple-domain-amnestic MCI (mdaMCI) biomarkers are important for enabling early interventions to help slow down progression of the disease. Recording event-related potentials (ERPs) is a non-invasive and inexpensive measure of brain activity associated with cognitive processes, and it is of interest from a clinical point of view. The ERP technique may also be useful for obtaining early sdaMCI and mdaMCI biomarkers because ERPs are sensitive to impairment in processes that are not manifested at behavioral or clinical levels. In the present study, EEG activity was recorded in 25 healthy participants and 30 amnestic MCI patients (17 sdaMCI and 13 mdaMCI) while they performed a Simon task. The ERPs associated with visuospatial (N2 posterior-contralateral – N2pc -) and motor (lateralized readiness potential – LRP –) processes were examined. The N2pc amplitude was smaller in participants with mdaMCI than in healthy participants, which indicated a decline in the correlates of allocation of attentional resources to the target stimulus. In addition, N2pc amplitude proved to be a moderately good biomarker of mdaMCI subtype (0.77 sensitivity, 0.76 specificity). However, the LRP amplitude was smaller in the two MCI groups (sdaMCI and mdaMCI) than in healthy participants, revealing a reduction in the motor resources available to execute the response in sdaMCI and mdaMCI patients. Furthermore, the LRP amplitude proved to be a valid biomarker (0.80 sensitivity, 0.92 specificity) of both amnestic MCI subtypes.     

Disrupted Brain Functional Network in Internet Addiction Disorder: A Resting-State Functional Magnetic Resonance Imaging Study

Internet addiction disorder (IAD) is increasingly recognized as a mental health disorder, particularly among adolescents. The pathogenesis associated with IAD, however, remains unclear. In this study, we aim to explore the encephalic functional characteristics of IAD adolescents at rest using functional magnetic resonance imaging data. We adopted a graph-theoretic approach to investigate possible disruptions of functional connectivity in terms of network properties including small-worldness, efficiency, and nodal centrality on 17 adolescents with IAD and 16 socio-demographically matched healthy controls. False discovery rate-corrected parametric tests were performed to evaluate the statistical significance of group-level network topological differences. In addition, a correlation analysis was performed to assess the relationships between functional connectivity and clinical measures in the IAD group. Our results demonstrate that there is significant disruption in the functional connectome of IAD patients, particularly between regions located in the frontal, occipital, and parietal lobes. The affected connections are long-range and inter-hemispheric connections. Although significant alterations are observed for regional nodal metrics, there is no difference in global network topology between IAD and healthy groups. In addition, correlation analysis demonstrates that the observed regional abnormalities are correlated with the IAD severity and behavioral clinical assessments. Our findings, which are relatively consistent between anatomically and functionally defined atlases, suggest that IAD causes disruptions of functional connectivity and, importantly, that such disruptions might link to behavioral impairments.     

A Longitudinal Study of Atrophy in Amnestic Mild Cognitive Impairment and Normal Aging Revealed by Cortical Thickness

In recent years, amnestic mild cognitive impairment (aMCI) has attracted significant attention as an indicator of high risk for Alzheimer''s disease. An understanding of the pathology of aMCI may benefit the development of effective clinical treatments for dementia. In this work, we measured the cortical thickness of 109 aMCI subjects and 99 normal controls (NC) twice over two years. The longitudinal changes and the cross-sectional differences between the two types of participants were explored using the vertex thickness values. The thickness of the cortex in aMCI was found significantly reduced in both longitudinal and between-group comparisons, mainly in the temporal lobe, superolateral parietal lobe and some regions of the frontal cortices. Compared to NC, the aMCI showed a significantly high atrophy rate in the left lateral temporal lobe and left parahippocampal gyrus over two years. Additionally, a significant positive correlation between brain atrophy and the decline of Mini-Mental State Examination (MMSE) scores was also found in the left superior and left middle temporal gyrus in aMCI. These findings demonstrated specific longitudinal spatial patterns of cortical atrophy in aMCI and NC. The higher atrophy rate in aMCI might be responsible for the accelerated functional decline in the aMCI progression process.     

Abnormal Spontaneous Neural Activity in Obsessive-Compulsive Disorder: A Resting-State Functional Magnetic Resonance Imaging Study

Neuroimaging studies of obsessive-compulsive disorder have found abnormalities in orbitofronto-striato-thalamic circuitry, including the orbitofrontal cortex, anterior cingulate cortex, caudate, and thalamus, but few studies have explored abnormal intrinsic or spontaneous brain activity in the resting state. We investigated both intra- and inter-regional synchronized activity in twenty patients with obsessive-compulsive disorder and 20 healthy controls using resting-state functional magnetic resonance imaging. Regional homogeneity (ReHo) and functional connectivity methods were used to analyze the intra- and inter-regional synchronized activity, respectively. Compared with healthy controls, patients with obsessive-compulsive disorder showed significantly increased ReHo in the orbitofrontal cortex, cerebellum, and insula, and decreased ReHo in the ventral anterior cingulate cortex, caudate, and inferior occipital cortex. Based on ReHo results, we determined functional connectivity differences between the orbitofrontal cortex and other brain regions in both patients with obsessive-compulsive disorder and controls. We found abnormal functional connectivity between the orbitofrontal cortex and ventral anterior cingulate cortex in patients with obsessive-compulsive disorder compared with healthy controls. Moreover, ReHo in the orbitofrontal cortex was correlated with the duration of obsessive-compulsive disorder. These findings suggest that increased intra- and inter-regional synchronized activity in the orbitofrontal cortex may have a key role in the pathology of obsessive-compulsive disorder. In addition to orbitofronto-striato-thalamic circuitry, brain regions such as the insula and cerebellum may also be involved in the pathophysiology of obsessive-compulsive disorder.     

A Resting-State Functional Magnetic Resonance Imaging Study of Acute Carbon Monoxide Poisoning in Humans

The objective of this study was to evaluate the brain function characteristics of carbon monoxide poisoning patients using resting-state functional magnetic resonance imaging (fMRI) method. For this purpose, 12 carbon monoxide poisoning patients and healthy controls were subjected to resting-state fMRI scans separately. A regional homogeneity (ReHo) approach was used to analyze the brain function in carbon monoxide poisoning patients. Compared with control group, the value of ReHo in carbon monoxide poisoning group showed distinct decrease in bilateral superior frontal gyrus, middle frontal gyrus, right cuneus, left middle temporal gyrus, right insula, and cerebellum. Therefore, it was concluded that the brain functions in carbon monoxide poisoning patients were abnormal under the resting-state. The cuneate lobe function may indicate the degree of brain hypoxia and strengthening the cerebellar function training may promote the rehabilitation process.     

Changes of Functional and Effective Connectivity in Smoking Replenishment on Deprived Heavy Smokers: A Resting-State fMRI Study

Previous researches have explored the changes of functional connectivity caused by smoking with the aid of fMRI. This study considers not only functional connectivity but also effective connectivity regarding both brain networks and brain regions by using a novel analysis framework that combines independent component analysis (ICA) and Granger causality analysis (GCA). We conducted a resting-state fMRI experiment in which twenty-one heavy smokers were scanned in two sessions of different conditions: smoking abstinence followed by smoking satiety. In our framework, group ICA was firstly adopted to obtain the spatial patterns of the default-mode network (DMN), executive-control network (ECN), and salience network (SN). Their associated time courses were analyzed using GCA, showing that the effective connectivity from SN to DMN was reduced and that from ECN/DMN to SN was enhanced after smoking replenishment. A paired t-test on ICA spatial patterns revealed functional connectivity variation in regions such as the insula, parahippocampus, precuneus, anterior cingulate cortex, supplementary motor area, and ventromedial/dorsolateral prefrontal cortex. These regions were later selected as the regions of interest (ROIs), and their effective connectivity was investigated subsequently using GCA. In smoking abstinence, the insula showed the increased effective connectivity with the other ROIs; while in smoking satiety, the parahippocampus had the enhanced inter-area effective connectivity. These results demonstrate our hypothesis that for deprived heavy smokers, smoking replenishment takes effect on both functional and effective connectivity. Moreover, our analysis framework could be applied in a range of neuroscience studies.     

Regional Expression of Key Cell Cycle Proteins in Brain from Subjects with Amnestic Mild Cognitive Impairment

Mild cognitive impairment (MCI) is regarded as a transition stage between the cognitive changes of normal aging and the more serious problems caused by Alzheimer’s disease (AD). Previous studies had demonstrated increased expression of cell cycle proteins in AD brain. In the present study, we have analyzed the expression of the cell cycle proteins, CDK2, CDK5 and cyclin G1 in hippocampus and inferior parietal lobule (IPL) in subjects with amnestic mild cognitive impairment and control using Western blot analysis. The expression of CDK2, CDK5 and cyclin G1 were found to be significantly increased in MCI hippocampus as well as in IPL compared to control brain. These results suggest that some cells may have re-entered the cell cycle. However, the expression of CDK2 and CDK5 is greater in MCI hippocampus compared to those of MCI IPL, and hippocampus is a region that is severely affected by AD pathology. Since these proteins are involved directly or indirectly in microtubule destabilization and hyperphosphorylation of tau, and also in APP processing we hypothesize that cell cycle disturbance may be important contributor in the pathogenesis of AD. Special issue dedicated to Dr. John P. Blass.     

Regional Homogeneity within the Default Mode Network in Bipolar Depression: A Resting-State Functional Magnetic Resonance Imaging Study

Aim

We sought to use a regional homogeneity (ReHo) approach as an index in resting-state functional magnetic resonance imaging (fMRI) to investigate the features of spontaneous brain activity within the default mode network (DMN) in patients suffering from bipolar depression (BD).

Methods

Twenty-six patients with BD and 26 gender-, age-, and education-matched healthy subjects participated in the resting-state fMRI scans. We compared the differences in ReHo between the two groups within the DMN and investigated the relationships between sex, age, years of education, disease duration, the Hamilton Rating Scale for Depression (HAMD) total score, and ReHo in regions with significant group differences.

Results

Our results revealed that bipolar depressed patients had increased ReHo in the left medial frontal gyrus and left inferior parietal lobe compared to healthy controls. No correlations were found between regional ReHo values and sex, age, and clinical features within the BD group.

Conclusions

Our findings indicate that abnormal brain activity is mainly distributed within prefrontal-limbic circuits, which are believed to be involved in the pathophysiological mechanisms underlying bipolar depression.     

Factors Predicting Reversion from Mild Cognitive Impairment to Normal Cognitive Functioning: A Population-Based Study

Introduction

Mild cognitive impairment (MCI) is associated with an increased risk of developing dementia. However, many individuals diagnosed with MCI are found to have reverted to normal cognition on follow-up. This study investigated factors predicting or associated with reversion from MCI to normal cognition.

Methods

Our analyses considered 223 participants (48.9% male) aged 71–89 years, drawn from the prospective, population-based Sydney Memory and Ageing Study. All were diagnosed with MCI at baseline and subsequently classified with either normal cognition or repeat diagnosis of MCI after two years (a further 11 participants who progressed from MCI to dementia were excluded). Associations with reversion were investigated for (1) baseline factors that included diagnostic features, personality, neuroimaging, sociodemographics, lifestyle, and physical and mental health; (2) longitudinal change in potentially modifiable factors.

Results

There were 66 reverters to normal cognition and 157 non-reverters (stable MCI). Regression analyses identified diagnostic features as most predictive of prognosis, with reversion less likely in participants with multiple-domain MCI (p = 0.011), a moderately or severely impaired cognitive domain (p = 0.002 and p = 0.006), or an informant-based memory complaint (p = 0.031). Reversion was also less likely for participants with arthritis (p = 0.037), but more likely for participants with higher complex mental activity (p = 0.003), greater openness to experience (p = 0.041), better vision (p = 0.014), better smelling ability (p = 0.040), or larger combined volume of the left hippocampus and left amygdala (p<0.040). Reversion was also associated with a larger drop in diastolic blood pressure between baseline and follow-up (p = 0.026).

Discussion

Numerous factors are associated with reversion from MCI to normal cognition. Assessing these factors could facilitate more accurate prognosis of individuals with MCI. Participation in cognitively enriching activities and efforts to lower blood pressure might promote reversion.     

Resting-State Network Disruption and APOE Genotype in Alzheimer's Disease: A lagged Functional Connectivity Study

Background

The apolipoprotein E epsilon 4 (APOE-4) is associated with a genetic vulnerability to Alzheimer''s disease (AD) and with AD-related abnormalities in cortical rhythms. However, it is unclear whether APOE-4 is linked to a specific pattern of intrinsic functional disintegration of the brain after the development of the disease or during its different stages. This study aimed at identifying spatial patterns and effects of APOE genotype on resting-state oscillations and functional connectivity in patients with AD, using a physiological connectivity index called “lagged phase synchronization”.

Methodology/Principal Findings

Resting EEG was recorded during awake, eyes-closed state in 125 patients with AD and 60 elderly controls. Source current density and functional connectivity were determined using eLORETA. Patients with AD exhibited reduced parieto-occipital alpha oscillations compared with controls, and those carrying the APOE-4 allele had reduced alpha activity in the left inferior parietal and temporo-occipital cortex relative to noncarriers. There was a decreased alpha2 connectivity pattern in AD, involving the left temporal and bilateral parietal cortex. Several brain regions exhibited increased lagged phase synchronization in low frequencies, specifically in the theta band, across and within hemispheres, where temporal lobe connections were particularly compromised. Areas with abnormal theta connectivity correlated with cognitive scores. In patients with early AD, we found an APOE-4-related decrease in interhemispheric alpha connectivity in frontal and parieto-temporal regions.

Conclusions/Significance

In addition to regional cortical dysfunction, as indicated by abnormal alpha oscillations, there are patterns of functional network disruption affecting theta and alpha bands in AD that associate with the level of cognitive disturbance or with the APOE genotype. These functional patterns of nonlinear connectivity may potentially represent neurophysiological or phenotypic markers of AD, and aid in early detection of the disorder.     

The Selective Impairment of Resting-State Functional Connectivity of the Lateral Subregion of the Frontal Pole in Schizophrenia

Objective

Although extensive resting-state functional connectivity (rsFC) changes have been reported in schizophrenia, rsFC changes of the frontal pole (FP) remain unclear. The FP contains several subregions with different connection patterns; however, it is unknown whether the FP subregions are differentially affected in schizophrenia. To explore this possibility, we compared rsFC differences of the FP subregions between schizophrenia patients and healthy controls.

Method

One hundred healthy controls and 91 patients with schizophrenia underwent resting-state functional MRI with a sensitivity-encoded spiral-in (SENSE-SPIRAL) imaging sequence to reduced susceptibility-induced signal loss and distortion. The FP was subdivided into the orbital (FPo), medial (FPm), and lateral (FPl) subregions. Mean fMRI time series were extracted for each FP subregion and entered into a seed-based rsFC analysis.

Results

The FP subregions exhibited differential rsFC patterns in both healthy controls and schizophrenia patients. Direct comparison between groups revealed reduced rsFCs between the bilateral FPl and several cognitive-related regions, including the dorsolateral prefrontal cortex, medial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex/precuneus, temporal cortex and inferior parietal lobule in schizophrenia. Although the FPl exhibited obvious atrophy, rsFC changes were unrelated to volumetric atrophy in the FPl, to duration of illness, and to antipsychotic medication dosage. No significant differences were observed in the rsFCs of other FP subregions.

Conclusion

These findings suggest a selective (the lateral subregion) functional disconnection of the FP subregions in schizophrenia.     

Protein Levels and Activity of Some Antioxidant Enzymes in Hippocampus of Subjects with Amnestic Mild Cognitive Impairment

Mild cognitive impairment (MCI) is generally referred to the transitional zone between normal cognitive aging and early dementia or clinically probable Alzheimer’s disease (AD). Most individuals with amnestic MCI eventually develop AD, which suggests that MCI may be the earliest phase of AD. Oxidative stress is observed in brain from subjects with both AD and MCI. Among others, two possibilities for elevated oxidataive stress are decreased activity or elevated expression of antioxidant enzymes, the latter as a response to the former. Accordingly, in the current study, the protein levels and activity of some antioxidant enzymes in the hippocampus of control and MCI brain were measured using Western blot analysis and spectrophotometric methods, respectively. Alterations in the levels and activity of a number of antioxidant enzymes in MCI brain compared to age-matched controls were found. These results are consistent with the hypothesis that oxidative stress may be an early event in the progression of amnestic MCI to AD. Special issue article in honor of Dr. Anna Maria Giuffrida-Stella.