Alterations of spontaneous brain activity in systematic lupus erythematosus patients without neuropsychiatric symptoms: A resting-functional MRI study

Purpose To explore the alterations of spontaneous neuronal activity using amplitude of low-frequency fluctuation (ALFF), fractional amplitude of low-frequency fluctuation (fALFF), and regional homogeneity (ReHo) in non-NPSLE patients and their relationship with the anxiety and depression statuses. Methods Twenty-three non-NPSLE patients and 28 healthy controls were enrolled in this study. Resting-state functional magnetic resonance imaging was firstly analyzed by ALFF, fALFF, and ReHo. The relationships between ALFF/fALFF/ReHo values of abnormal regions and anxiety/depression rating scales, including Self-Rating Anxiety (SAS) and Self-Rating Depression (SDS), were also analyzed. Results Compared with HC, non-NPSLE had decreased ALFF values in the bilateral postcentral gyrus, while increased ALFF values in the bilateral inferior temporal gyrus, left putamen, and bilateral precuneus. Non-NPSLE showed reduced fALFF values in the left lingual gyrus, left middle occipital gyrus, right postcentral gyrus, and left superior parietal gyrus, while increased fALFF values were in the left inferior temporal gyrus, right hippocampus, bilateral precuneus, and bilateral superior frontal gyrus. Reduced ReHo values were in the bilateral postcentral gyrus and higher ReHo values were in the left inferior temporal gyrus, left putamen, and bilateral superior frontal gyrus. In the non-NPSLE group, the mean ALFF values of bilateral precuneus were positively correlated with the SAS rating scales (R = 0.5519, p = 0.0176); either were the mean ALFF values of right inferior temporal gyrus and SAS rating scales (R = 0.5380, p = 0.0213). The mean fALFF values of left inferior temporal gyrus were positively correlated with SAS rating scales (R = 0.5700, p = 0.0135). And the mean ReHo values of left putamen were positively correlated with SDS (R = 0.5477, p = 0.0186). Conclusion Non-NPSLE exhibited abnormal spontaneous neural activity and coherence in several brain regions mainly associated with cognitive and emotional functions. The ALFF values of bilateral PCUN, the right ITG, the fALFF values of left ITG, and the ReHo values of left PUT may be complementary biomarkers for assessing the psychiatric symptoms.

Increased MANF Expression in the Inferior Temporal Gyrus in Patients With Alzheimer Disease

Alzheimer disease (AD) is an aging-related disorder linked to endoplasmic reticulum (ER) stress. The main pathologic feature of AD is the presence of extracellular senile plaques and intraneuronal neurofibrillary tangles (NFTs) in the brain. In neurodegenerative diseases, the unfolded protein response (UPR) induced by ER stress ensures cell survival. Mesencephalic astrocyte-derived neurotrophic factor (MANF) protects against ER stress and has been implicated in the pathogenesis of AD. MANF is expressed in neurons of the brain and spinal cord. However, there have been no investigations on MANF expression in the brain of AD patients. This was addressed in the present study by immunohistochemistry, western blotting, and quantitative analyses of postmortem brain specimens. We examined the localization and expression levels of MANF in the inferior temporal gyrus of the cortex (ITGC) in AD patients (n = 5), preclinical (pre-)AD patients (n = 5), and age-matched non-dementia controls (n = 5) by double immunofluorescence labeling with antibodies against the neuron-specific nuclear protein neuronal nuclei (NeuN), ER chaperone protein 78-kDa glucose-regulated protein (GRP78), and MANF. The results showed that MANF was mainly expressed in neurons of the ITGC in all 3 groups; However, the number of MANF-positive neurons was significantly higher in pre-AD (Braak stage III/IV) and AD (Braak stage V/VI) patients than that in the control group. Thus, MANF is overexpressed in AD and pre-AD, suggesting that it can serve as a diagnostic marker for early stage disease.

Abnormal Default-Mode Network Homogeneity in Melancholic and Nonmelancholic Major Depressive Disorder at Rest

Background. Melancholic depression has been assumed as a severe type of major depressive disorder (MDD). We aimed to explore if there were some distinctive alterations in melancholic MDD and whether the alterations could be used to discriminate the melancholic MDD and nonmelancholic MDD. Methods. Thirty-one outpatients with melancholic MDD, thirty-three outpatients with nonmelancholic MDD, and thirty-two age- and gender-matched healthy controls were recruited. All participants were scanned by resting-state functional magnetic resonance imaging (fMRI). Imaging data were analyzed with the network homogeneity (NH) and support vector machine (SVM) methods. Results. Both patient groups exhibited increased NH in the right PCC/precuneus and right angular gyrus and decreased NH in the right middle temporal gyrus compared with healthy controls. Compared with nonmelancholic patients and healthy controls, melancholic patients exhibited significantly increased NH in the bilateral superior medial frontal gyrus and decreased NH in the left inferior temporal gyrus. But merely for melancholic patients, the NH of the right middle temporal gyrus was negatively correlated with TEPS total and contextual anticipatory scores. SVM analysis showed that a combination of NH values in the left superior medial frontal gyrus and left inferior temporal gyrus could distinguish melancholic patients from nonmelancholic patients with accuracy, sensitivity, and specificity of 79.66% (47/59), 70.97% (22/31), and 89.29%(25/28), respectively. Conclusion. Our findings showed distinctive network homogeneity alterations in melancholic MDD which may be potential imaging markers to distinguish melancholic MDD and nonmelancholic MDD.

Altered regional homogeneity and functional brain networks in Type 2 diabetes with and without mild cognitive impairment

Patients with Type-2 Diabetes Mellitus (T2DM) have a considerably higher risk of developing mild cognitive impairment (MCI) and dementia. The initial symptoms are very insidious at onset. We investigated the alterations in spontaneous brain activity and network connectivity through regional homogeneity (ReHo) and graph theoretical network analyses, respectively, of resting-state functional Magnetic Resonance Imaging (rs-fMRI) in T2DM patients with and without MCI, so as to facilitate early diagnose. Twenty-five T2DM patients with MCI (DM-MCI), 25 T2DM patients with normal cognition (DM-NC), 27 healthy controls were enrolled. Whole-brain ReHo values were calculated and topological properties of functional networks were analyzed. The DM-MCI group exhibited decreased ReHo in the left inferior/middle occipital gyrus and right inferior temporal gyrus, and increased ReHo in frontal gyrus compared to the DM-NCs. Significant correlations were found between ReHo values and clinical measurements. The DM-MCI group illustrated greater clustering coefficient/local efficiency and altered nodal characteristics (efficiency, degree and betweenness), which increased in certain occipital, temporal and parietal regions but decreased in the right inferior temporal gyrus, compared to the DM-NCs. The altered ReHo and impaired network organization may underlie the impaired cognitive functions in T2DM and suggesting a compensation mechanism. These rs-fMRI measures have the potential as biomarkers of disease progression in diabetic encephalopathy.