In addition to memory deficits, attentional impairment is a common manifestation of Alzheimer's disease (AD). The present study examines the abnormalities of attention-related functional networks in AD using resting functional MRI (fMRI) technique and evaluates the sensitivity and specificity of these networks as potential biomarkers compared to the default mode network (DMN). Group independent component analysis (Group ICA) was applied to fMRI data from 15 AD patients and 16 normal healthy elderly controls (NC) to derive the dorsal attention network (DAN) and the ventral attention network (VAN) which are respectively responsible for the endogenous attention orienting ("top-down") process and the exogenous attention re-orienting ("bottom-up") process. Receiver operating characteristic (ROC) curve analysis was performed for activity in core regions within each of these networks. Functional connectivity analysis revealed disrupted DAN and preserved (less impaired) VAN in AD patients compared with NC, which might indicate impairment of a "top-down" and intact "bottom-up" attentional processing mechanisms in AD. ROC curve analysis suggested that activity in the left intraparietal sulcus and left frontal eye field from DAN as well as the posterior cingulate cortex from the DMN could serve as sensitive and specific biomarkers distinguishing AD from NC.

The current findings provide evidence confirming the lack of connection in the fronto-limbic circuitry at the early stages of the schizophrenia. Because the coordinates reported in the primary literature were highly variable, future investigations with large samples would be required to support the identified white matter changes in FES.

Depression is the most common psychiatric disorder observed in Parkinson’s disease (PD) patients, however the neural contribution to the high rate of depression in the PD group is still unclear. In this study, we used resting-state functional magnetic resonance imaging (fMRI) to investigate the underlying neural mechanisms of depression in PD patients. Twenty-one healthy individuals and thirty-three patients with idiopathic PD, seventeen of whom were diagnosed with major depressive disorder, were recruited. An analysis of amplitude of low-frequency fluctuations (ALFF) was performed on the whole brain of all subjects. Our results showed that depressed PD patients had significantly decreased ALFF in the dorsolateral prefrontal cortex (DLPFC), the ventromedial prefrontal cortex (vMPFC) and the rostral anterior cingulated cortex (rACC) compared with non-depressed PD patients. A significant positive correlation was found between Hamilton Depression Rating Scale (HDRS) and ALFF in the DLPFC. The findings of changed ALFF in these brain regions implied depression in PD patients may be associated with abnormal activities of prefrontal-limbic network.

Although previous studies have reported deficits in the gray matter volume of schizophrenic patients, it remains unclear whether these deficits occur at the onset of the disease, before treatment, and whether they are progressive over the duration of untreated disease. Furthermore, the gray matter volume represents the combinations of cortical thickness and surface area; these features are believed to be influenced by different genetic factors. However, cortical thickness and surface area in antipsychotic-naive first-episode schizophrenic patients have seldom been investigated. Here, the cortical thicknesses and surface areas of 128 antipsychotic-naive first-episode schizophrenic patients were compared with 128 healthy controls. The patients exhibited significantly lower cortical thickness, primarily in the bilateral prefrontal and parietal cortex, and increased thickness in the bilateral anterior temporal lobes, left medial orbitofrontal cortex, and left cuneus. Furthermore, decreased cortical thickness was related to positive schizophrenia symptoms but not to the severity of negative symptoms and the untreated disease duration. No significant difference of surface area was observed between the 2 groups. Thus, without the confounding factors of medication and illness progression, this study provides further evidence to support anatomical deficits in the prefrontal and parietal cortex early in course of the illness. The increased thicknesses of the bilateral anterior temporal lobes may represent a compensatory factor or may be an early-course neuronal pathology caused by preapoptotic osmotic changes or hypertrophy. Furthermore, these anatomical deficits are crucial to the pathogenesis of positive symptoms and relatively stable instead of progressing during the early stages of the disease.

Background Schizophrenia (SCZ) and psychotic bipolar disorder (PBD) share considerable overlap in clinical features, genetic risk factors and co-occurrence among relatives. The common and unique functional cerebral deficits in these disorders, and in unaffected relatives, remain to be identified. Method A total of 59 healthy controls, 37 SCZ and 57 PBD probands and their unaffected first-degree relatives (38 and 28, respectively) were studied using resting-state functional magnetic resonance imaging (rfMRI). Regional cerebral function was evaluated by measuring the amplitude of low-frequency fluctuations (ALFF). Areas with ALFF alterations were used as seeds in whole-brain functional connectivity analysis. We then tested whether abnormalities identified in probands were present in unaffected relatives. Results SCZ and PBD probands both demonstrated regional hypoactivity in the orbital frontal cortex and cingulate gyrus, as well as abnormal connectivity within striatal-thalamo-cortical networks. SCZ probands showed greater and more widely distributed ALFF alterations including the thalamus and bilateral parahippocampal gyri. Increased parahippocampal ALFF was related to positive symptoms and cognitive deficit. PBD patients showed uniquely increased functional connectivity between the thalamus and bilateral insula. Only PBD relatives showed abnormal connectivity within striatal-thalamo-cortical networks seen in both proband groups. Conclusions The present findings reveal a common pattern of deficits in frontostriatal circuitry across SCZ and PBD, and unique regional and functional connectivity abnormalities that distinguish them. The abnormal network connectivity in PBD relatives that was present in both proband groups may reflect genetic susceptibility associated with risk for psychosis, but within-family associations of this measure were not high.

IMPORTANCE Accumulating evidence supports the hypothesis that cerebral white matter abnormalities are involved in the pathophysiology of schizophrenia; however, findings from in vivo neuroimaging studies have been inconsistent. Besides confounding factors, including age, illness duration, and medication effects, an additional cause for the inconsistent results may be heterogeneity in the nature of white matter alterations associated with the disorder.OBJECTIVE To investigate whether different patterns of white matter abnormalities exist in a large cohort of medication-naive patients with first-episode schizophrenia and the relationship between such patterns and clinical parameters. DESIGN, SETTING, AND PARTICIPANTSA cross-sectional diffusion tensor imaging study of 113 medication-naive patients with first-episode schizophrenia and 110 demographically matched healthy control individuals. The study was conducted in the mental health center of West

While the past decade has seen great progress in mapping loci for common diseases, studying how these risk alleles lead to pathology remains a challenge. Age-related macular degeneration (AMD) affects 9 million older Americans, and is characterized by the loss of the retinal pigment epithelium (RPE). Although the closely linked genome-wide association studies ARMS2/HTRA1 genes, located at the chromosome 10q26 locus, are strongly associated with the risk of AMD, their downstream targets are unknown. Low population frequencies of risk alleles in tissue banks make it impractical to study their function in cells derived from autopsied tissue. Moreover, autopsy eyes from end-stage AMD patients, where age-related RPE atrophy and fibrosis are already present, cannot be used to determine how abnormal ARMS2/HTRA1 expression can initiate RPE pathology. Instead, induced pluripotent stem (iPS) cell-derived RPE from patients provides us with earlier stage AMD patient-specific cells and allows us to analyze the underlying mechanisms at this critical time point. An unbiased proteome screen of A2E-aged patient-specific iPS-derived RPE cell lines identified superoxide dismutase 2 (SOD2)-mediated antioxidative defense in the genetic allele's susceptibility of AMD. The AMD-associated risk haplotype (T-in/del-A) impairs the ability of the RPE to defend against aging-related oxidative stress. SOD2 defense is impaired in RPE homozygous for the risk haplotype (T-in/del-A; T-in/del-A), while the effect was less pronounced in RPE homozygous for the protective haplotype (G-Wt-G; G-Wt-G). ARMS2/HTRA1 risk alleles decrease SOD2 defense, making RPE more susceptible to oxidative damage and thereby contributing to AMD pathogenesis.

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