B lymphocytes ameliorate Alzheimer's disease-like neuropathology via interleukin-35.

Increasing evidence supports the involvement of the peripheral immune system in the pathogenesis of Alzheimer's disease (AD). In the present study, we found that B lymphocytes could mitigate beta-Amyloid (Aß) pathology and memory impairments in a transgenic AD mouse model. Specifically, in young 5 × FAD mice, we evidenced increased B cells in the frontal cortex and meningeal tissues; depletion of mature B cells aggravated these mice's Aß load and memory deficits. The increased B cells produced more interleukin-35 (IL-35) in the front cortex. We further found IL-35 neutralization exacerbated Aß pathology, while injecting IL-35 mitigated Aß load and cognitive dysfunction in 5 × FAD mice with or without mature B cell deficiency. Mechanistically, IL-35 inhibited neuronal BACE1 transcription through modulating the SOCS1/STAT1 pathway, and reduced Aß production accordingly. Reanalysis of the single-cell RNA sequencing data from blood samples of AD patients suggested an increased population of IL-35-producing B cells. Together, the present study revealed a novel effect of B lymphocyte-derived IL-35 on inhibiting Aß production in the frontal cortex, which may serve as a potential target for future AD treatment.

The application of MDT model for calciphylaxis management in patients with end-stage renal disease.

This study focuses on the application of nurse-led multidisciplinary collaborative therapy (MDT) management model for calciphylaxis prevention of patients with terminal renal disease. Through the establishment of a multidisciplinary management team spanning nephrology department, blood purification center, dermatology department, burn and plastic surgery department, infection department, stem cell platform, nutrition department, pain department, cardiology department, hydrotherapy group, dermatology group, and outpatient treatment room, the distribution of duties among team members were clarified to bring out the best advantages of a multidisciplinary teamwork during treatment and nursing. For patients with calciphylaxis symptoms in terminal renal disease, a case-by-case management model was carried out with the focus on personalised problem. We emphasised on personalised wound care, precise medication care, active pain management, psychological intervention and palliative care, the amelioration of calcium and phosphorus metabolism disorder, nutritional supplementation, and the therapeutic intervention based on human amniotic mesenchymal stem cell regeneration. The MDT model effectively compensates for traditional nursing mode and could serve as a novel clinical management modality for calciphylaxis prevention in patients with terminal renal disease.

Microglial AIM2 alleviates antiviral-related neuro-inflammation in mouse models of Parkinson's disease.

Inflammasome involvement in Parkinson's disease (PD) has been intensively investigated. Absent in melanoma 2 (AIM2) is an essential inflammasome protein known to contribute to the development of several neurological diseases. However, a specific role for AIM2 in PD has not been reported. In this study, we investigated the effect of AIM2 in the N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD model by use of various knockout and bone marrow chimeric mice. The mechanism of action for AIM2 in PD was assessed by RNA-sequencing and in vitro primary microglial transfection. Results were validated in the A30P transgenic mouse model of PD. In the MPTP mouse model, AIM2 activation was found to negatively regulate neuro-inflammation independent of the inflammasome. Microglial AIM2 deficiency exacerbated behavioral and pathological features of both MPTP-induced and transgenic PD mouse models. Mechanistically, AIM2 reduced cyclic GMP-AMP synthase (cGAS)-mediated antiviral-related inflammation by inhibition of AKT-interferon regulatory factor 3 (IRF3) phosphorylation. These results demonstrate microglial AIM2 to inhibit the antiviral-related neuro-inflammation associated with PD and provide for a foundation upon which to identify new therapeutic targets for treatment of the disease.

Miconazole Promotes Cooperative Ability of a Mouse Model of Alzheimer Disease.

BACKGROUND: Cooperative defect is 1 of the earliest manifestations of disease patients with Alzheimer disease (AD) exhibit, but the underlying mechanism remains unclear. METHODS: We evaluated the cooperative function of APP/PS1 transgenic AD model mice at ages 2, 5, and 8 months by using a cooperative drinking task. We examined neuropathologic changes in the medial prefrontal cortex (mPFC). Another experiment was designed to observe whether miconazole, which has a repairing effect on myelin sheath, could promote the cooperative ability of APP/PS1 mice in the early AD-like stage. We also investigated the protective effects of miconazole on cultured mouse cortical oligodendrocytes exposed to human amyloid ß peptide (Aß1-42). RESULTS: We observed an age-dependent impairment of cooperative water drinking behavior in APP/PS1 mice. The AD mice with cooperative dysfunction showed decreases in myelin sheath thickness, oligodendrocyte nuclear heterochromatin percentage, and myelin basic protein expression levels in the mPFC. The cooperative ability was significantly improved in APP/PS1 mice treated with miconazole. Miconazole treatment increased oligodendrocyte maturation and myelin sheath thickness without reducing Aß plaque deposition, reactive gliosis, and inflammatory factor levels in the mPFC. Miconazole also protected cultured oligodendrocytes from the toxicity of Aß1-42. CONCLUSIONS: These results demonstrate that mPFC hypomyelination is involved in the cooperative deficits of APP/PS1 mice. Improving myelination through miconazole therapy may offer a potential therapeutic approach for early intervention in AD.

Drainage of senescent astrocytes from brain via meningeal lymphatic routes.

Recent progress on the central lymphatic system has greatly increased our understanding of how the brain maintains its own waste homeostasis. Here, we showed that perivascular spaces and meningeal lymphatic vessels form a functional route for clearance of senescent astrocytes from the aging brain. Blocking meningeal lymphatic drainage by ligation of the deep cervical lymph nodes impaired clearance of senescent astrocytes from brain parenchyma, subsequently increasing neuroinflammation in aged mice. By contrast, enhancing meningeal lymphatic vessel diameter by a recombinant adeno-associated virus encoding mouse vascular endothelial growth factor-C (VEGF-C) improved clearance of senescent astrocytes and mitigated neuroinflammation. Mechanistically, VEGF-C was highly expressed in senescent astrocytes, contributing themselves to migrate across lymphatic vessels along C-C motif chemokine ligand 21 (CCL21) gradient by interacting with VEGF receptor 3. Moreover, intra-cisternal injection of antibody against CCL21 hampered senescent astrocytes into the lymphatic vessels and exacerbated short memory defects of aged mice. Together, these findings reveal a new perspective for the meningeal lymphatics in the removal of senescent astrocytes, thus offering a valuable target for therapeutic intervention.

IL-37 Represses the Autoimmunity in Myasthenia Gravis via Directly Targeting Follicular Th and B Cells.

IL-37 is a newly identified immune-suppressive factor; however, the function, cellular sources, and mechanism of IL-37 in humoral immunity and Myasthenia gravis (MG) are still unclear. In this study, we found IL-37 were substantially downregulated in the serum and PBMCs of MG patients compared with healthy controls. The lower IL-37 was associated with severer disease (quantitative MG score) and higher follicular Th (Tfh)/Tfh17 and B cell numbers. Flow cytometry analysis revealed that IL-37 was mainly produced by CD4+ T cells without overlapping with Th1, Th17, and Tfh subsets in MG patients. Regulatory IL-37+ T cell rarely expressed Foxp3 and CD25 but produced numerous IL-4. Tfh and B cell expressed high levels of SIGIRR, the receptor of IL-37, in MG patients. Mechanically, IL-37 directly bond to SIGIRR, repressed the proliferation, cytokine production of Tfh and B cells, and the secretion of autoantibody via inhibition of STAT3 signaling in Tfh and B cells.

Endoscope-Assisted Minimally Invasive Surgery for the Treatment of Glandular Gynecomastia.

BACKGROUND: Gynecomastia (GYN) is the most common benign disease in males. A vacuum-assisted biopsy is a minimally invasive surgical technique for GYN treatment that achieves satisfactory aesthetic results. However, due to the operation under non-direct vision, it is difficult to localize the bleeding points and assess the residual glandular tissue. Endoscopy was applied to observe the operative field after subcutaneous mastectomy. The present study aimed to recommend our initial experience in glandular GYN with endoscope-assisted minimally invasive subcutaneous mastectomy. METHODS: A total of 34 patients diagnosed with glandular GYN (50 breasts), treated with endoscope-assisted minimally invasive surgery at The First Affiliated Hospital with Nanjing Medical University between June 2018 and June 2020, were enrolled in this study. According to Simon's classification of the breast, 10 was grade I, 25 was grade IIA, and 15 was grade IIB. The characteristics of patients, operative data, postoperative complications, cosmetic outcome, and patient satisfaction were recorded. RESULTS: Endoscope-assisted minimally invasive mastectomy was performed successfully in all cases. The operative duration of the operation was 55-120 min/side. The total weight of the resected tissue of the 50 breasts was 55-350 g, and the blood loss was 10-105 mL/breast. Endoscopy detected five breasts with bleeding and three with residual glandular during the operation. Postoperative bleeding occurred in 1 breast, subcutaneous seroma in 3 breasts, dysesthesia of the nipple-areolar complex in 2 breasts, and skin redundancy in a bilateral patient. None of the patients experienced severe pain, infection, nipple necrosis, and nipple retraction, a saucer-like deformity. With a median follow-up of 21 months, all patients were satisfied with their cosmetic outcome (100%), and no recurrence occurred. CONCLUSION: Endoscope-assisted minimally invasive mastectomy could be used as a feasible technique for the treatment of glandular GYN. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online. Instructions to Authors www.springer.com/00266 .

Altered effective connectivity in migraine patients during emotional stimuli: a multi-frequency magnetoencephalography study.

BACKGROUND: Migraine is a common and disabling primary headache, which is associated with a wide range of psychiatric comorbidities. However, the mechanisms of emotion processing in migraine are not fully understood yet. The present study aimed to investigate the neural network during neutral, positive, and negative emotional stimuli in the migraine patients. METHODS: A total of 24 migraine patients and 24 age- and sex-matching healthy controls were enrolled in this study. Neuromagnetic brain activity was recorded using a whole-head magnetoencephalography (MEG) system upon exposure to human facial expression stimuli. MEG data were analyzed in multi-frequency ranges from 1 to 100 Hz. RESULTS: The migraine patients exhibited a significant enhancement in the effective connectivity from the prefrontal lobe to the temporal cortex during the negative emotional stimuli in the gamma frequency (30-90 Hz). Graph theory analysis revealed that the migraine patients had an increased degree and clustering coefficient of connectivity in the delta frequency range (1-4 Hz) upon exposure to positive emotional stimuli and an increased degree of connectivity in the delta frequency range (1-4 Hz) upon exposure to negative emotional stimuli. Clinical correlation analysis showed that the history, attack frequency, duration, and neuropsychological scales of the migraine patients had a negative correlation with the network parameters in certain frequency ranges. CONCLUSIONS: The results suggested that the individuals with migraine showed deviant effective connectivity in viewing the human facial expressions in multi-frequencies. The prefrontal-temporal pathway might be related to the altered negative emotional modulation in migraine. These findings suggested that migraine might be characterized by more universal altered cerebral processing of negative stimuli. Since the significant result in this study was frequency-specific, more independent replicative studies are needed to confirm these results, and to elucidate the neurocircuitry underlying the association between migraine and emotional conditions.

Systemic inflammasome activation and pyroptosis associate with the progression of amnestic mild cognitive impairment and Alzheimer's disease.

BACKGROUND: Growing evidence indicates that inflammasome-mediated inflammation plays important roles in the pathophysiology of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD). Pyroptosis induced by inflammasome, and Gasdermin D (GSDMD) is involved in several neurodegenerative disorders. However, it is not clear whether peripheral inflammasome and pyroptosis are activated in aMCI and AD patients, influencing on neuroinflammation. The aim of this study was to examine the association between systemic inflammasome-induced pyroptosis and clinical features in aMCI and AD. METHODS: A total of 86 participants, including 33 subjects with aMCI, 33 subjects with AD, and 20 cognitively normal controls, in this study. The Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) scale were used for cognitive assessment. Levels of inflammasome-related genes/proteins in peripheral blood mononuclear cells (PBMCs) were determined using quantitative polymerase chain reaction and Western blotting. The levels of IL-1ß, Aß1-42, Aß1-40, p-tau, and t-tau in cerebrospinal fluid (CSF), as well as the plasma IL-1ß level, were measured by enzyme-linked immunosorbent assay. Finally, lipopolysaccharides (LPS) were used to investigate the effects of systemic inflammasome-induced pyroptosis in an AD mice model. RESULTS: Several genes involved in the inflammatory response were enriched in PBMCs of AD patients. The mRNA and protein levels of NLRP3, caspase-1, GSDMD, and IL-1ß were increased in PBMCs of aMCI and AD patients. The IL-1ß level in plasma and CSF of aMCI and AD patients was significantly higher than that in controls and negatively correlated with the CSF Aß1-42 level, as well as MMSE and MoCA scores. Furthermore, there was a positive correlation between the IL-1ß level in plasma and CSF of aMCI or AD patients. In vivo experiments showed that systemic inflammasome-induced pyroptosis aggravated neuroinflammation in 5 × FAD mice. CONCLUSIONS: Our findings showed that canonical inflammasome signaling and GSDMD-induced pyroptosis were activated in PBMCs of aMCI and AD patients. In addition, the proinflammatory cytokine IL-1ß was strongly associated with the pathophysiology of aMCI and AD. As such, targeting inflammasome-induced pyroptosis may be a new approach to inhibit neuroinflammation in aMCI and AD patients.

Baicalein Attenuates Neuroinflammation by Inhibiting NLRP3/caspase-1/GSDMD Pathway in MPTP Induced Mice Model of Parkinson's Disease.

BACKGROUND: Inflammasome-induced neuroinflammation is a major pathogenic mechanism underlying the degeneration of nigral dopaminergic neurons in Parkinson's disease (PD). Baicalein is a flavonoid isolated from the traditional Chinese medicinal herbal Scutellaria baicalensis Georgi with known anti-inflammatory and neuroprotective efficacy in models of neurodegenerative diseases, including PD. However, its effects on inflammasome-induced neuroinflammation during PD remain unclear. METHODS: We used N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD-like pathology in mice. Behavioral assessments including the pole test, rotarod test and open filed test were conducted to evaluate the effects of baicalein on MPTP-induced motor dysfunction. The efficacies of baicalein against MPTP-induced dopaminergic neuron loss and glial cell activation in the substantia nigra compact (SNc) were examined by immunohistochemistry, effects on proinflammatory cytokines by qPCR and enzyme-linked immunosorbent assay (ELISA), effects on inflammasome pathway activation by immunoblotting and flow cytometry. RESULTS: Administration of baicalein reversed MPTP-induced motor dysfunction, loss of dopaminergic neurons, and pro-inflammatory cytokine elevation. Baicalein also inhibited NLRP3 and caspase-1 activation and suppressed gasdermin D (GSDMD)-dependent pyroptosis. Additionally, baicalein inhibited the activation and proliferation of disease-associated proinflammatory microglia. CONCLUSIONS: These findings suggest that baicalein can reverse MPTP-induced neuroinflammation in mice by suppressing NLRP3/caspase-1/GSDMD pathway. Our study provides potential insight of baicalein in PD therapy.

Brain astrocytoma misdiagnosed as anti-NMDAR encephalitis: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, which is the most common type of autoimmune encephalitis, is caused by the production of autoantibodies against NMDA receptor. Anti-NMDAR encephalitis patients present with various non-specific symptoms, such as abnormal psychiatric or behaviour, speech dysfunction, cognitive dysfunction, seizures, movement disorders, decreased level of consciousness, and central hypoventilation or autonomic dysfunction. CASE PRESENTATION: A 67-year-old man presented with new-onset focal seizures. The brain magnetic resonance imaging (MRI) plain scan and enhanced scan showed abnormal signal on the proximal midline frontoparietal junction region. Anti-NMDAR antibody was detected in cerebrospinal fluid (CSF) and serum using a commercial kit (Euroimmune, Germany) by indirect immunofluorescence testing (IIFT) according to the manufacturer's instructions for twice. Both of the test results were positive in CSF and serum. The patient was diagnosed as anti-NMDAR encephalitis and then was treated repeatedly with large dose of intravenous corticosteroids and gamma globulin. Accordingly, the refractory nature of seizures in this case may be attributed to NMDAR autoantibodies. When the patient presented at the hospital for the third time, the brain MRI revealed an increase in the size of the frontal parietal lesion and one new lesion in the left basal ganglia. The patient underwent a surgical biopsy and astrocytoma was confirmed by histopathology. CONCLUSIONS: Although the sensitivity and specificity of anti-NMDAR-IgG antibodies in CSF to diagnose anti-NMDAR encephalitis are close to 100%, it is not absolute. Anti-NMDAR antibodies were positive, which might make the diagnosis more complex. The diagnosis of atypical presentation of anti-NMDAR encephalitis requires reasonable exclusion of other disorders.

Abnormal functional connectivity under somatosensory stimulation in migraine: a multi-frequency magnetoencephalography study.

BACKGROUND: Although altered neural networks have been demonstrated in recent MEG (magnetoencephalography) research in migraine patients during resting state, it is unknown whether this alteration can be detected in task-related networks. The present study aimed to investigate the abnormalities of the frequency-specific somatosensory-related network in migraine patients by using MEG. METHODS: Twenty-two migraineurs in the interictal phase and twenty-two sex- and age-matched healthy volunteers were studied using a whole-head magnetoencephalography (MEG) system. Electrical stimuli were delivered alternately to the median nerve on the right wrists of all subjects. MEG data were analyzed in a frequency range of 1-1000 Hz in multiple bands. RESULTS: The brain network patterns revealed that the patients with migraine exhibited remarkably increased functional connectivity in the high-frequency (250-1000 Hz) band between the sensory cortex and the frontal lobe. The results of quantitative analysis of graph theory showed that the patients had (1) an increased degree of connectivity in the theta (4-8 Hz), beta (13-30 Hz) and gamma (30-80 Hz) bands; (2) an increased connectivity strength in the beta (13-30 Hz) and gamma (30-80 Hz) bands; (3) an increased path length in the beta (13-30 Hz), gamma (30-80 Hz) and ripple (80-250 Hz) bands; and (4) an increased clustering coefficient in the theta (4-8 Hz), beta (13-30 Hz) and gamma (30-80 Hz) bands. CONCLUSIONS: The results indicate that migraine is associated with aberrant connections from the somatosensory cortex to the frontal lobe. The frequency-specific increases in connectivity in terms of strength, path length and clustering coefficients support the notion that migraineurs have elevated cortical networks. This alteration in functional connectivity may be involved in somatosensory processing in migraine patients and may contribute to understanding migraine pathophysiology and to providing convincing evidence for a spatially targeted migraine therapy.

Prognostic value of age in neurological cancer: an analysis of 22,393 cases from the SEER database.

Although the risk of neurological cancer (NC) is age-dependent, few studies have evaluated the prognostic value of age in determining NC survival in a large population. The aim of this retrospective study was to compare the long-term survival of young and elderly NC patients. We searched the Surveillance, Epidemiology, and End-Results database and identified 22,393 patients who were diagnosed with NC between 1988 and 2003 and were treated with surgery. Patients were categorized as young (≤40 years old) or elderly (>40 years old), and 5-year NC-specific survival (NCSS) data were obtained for each patient. A Kaplan-Meier survival analysis and the Cox proportional hazards model were used to analyze long-term survival outcomes and risk factors. The two groups differed significantly in terms of pathological grade, histological type, stage, and tumor size (P < 0.001). A difference in 5-year NCSS rates (63.8 and 19.0% in young and elderly patients, respectively) was detected by uni- and multivariate analyses. A stratified analysis of age on cancer survival revealed significant differences at T1-T4 stages. Age has prognostic value for determining NC risk. NCSS is higher in young than in elderly NC patients.

Formation control of fixed-wing UAVs with communication delay.

Fixed-wing unmanned aerial vehicles (UAVs) possess high speed and non-hovering capabilities, rendering them uniquely advantages for reconnaissance and detection. The focus of this paper is to addressing the problem of formation control for fixed-wing UAVs in the presence of communication delay. To tackle this problem, for the non-holonomic kinematic model, we propose an intuitive and practical control law based on the leader-follower method to ensure that UAVs maintain a predetermined geometric formation. The stability analysis of the system with communication delay is conducted by constructing a strict Lyapunov-Krasovskii function. Furthermore, we consider the impact of communication delay on formation accuracy and present a prediction algorithm capable of forecasting the actual position of each UAV. To validate our theoretical findings, both digital simulation and hardware-in-loop experiment are conducted.

Dimensionality Reduction Hybrid U-Net for Brain Extraction in Magnetic Resonance Imaging.

In various applications, such as disease diagnosis, surgical navigation, human brain atlas analysis, and other neuroimage processing scenarios, brain extraction is typically regarded as the initial stage in MRI image processing. Whole-brain semantic segmentation algorithms, such as U-Net, have demonstrated the ability to achieve relatively satisfactory results even with a limited number of training samples. In order to enhance the precision of brain semantic segmentation, various frameworks have been developed, including 3D U-Net, slice U-Net, and auto-context U-Net. However, the processing methods employed in these models are relatively complex when applied to 3D data models. In this article, we aim to reduce the complexity of the model while maintaining appropriate performance. As an initial step to enhance segmentation accuracy, the preprocessing extraction of full-scale information from magnetic resonance images is performed with a cluster tool. Subsequently, three multi-input hybrid U-Net model frameworks are tested and compared. Finally, we propose utilizing a fusion of two-dimensional segmentation outcomes from different planes to attain improved results. The performance of the proposed framework was tested using publicly accessible benchmark datasets, namely LPBA40, in which we obtained Dice overlap coefficients of 98.05%. Improvement was achieved via our algorithm against several previous studies.

Robust control strategy for multi-UAVs system using MPC combined with Kalman-consensus filter and disturbance observer.

The stability of formation flight is not only sensitive to external disturbances but also to data observed and transferred between sensors and unmanned aerial vehicles (UAVs). A multi-constrained model predictive control (MPC) strategy, combined with Kalman-consensus filter (KCF) and fixed-time disturbance observer (FTDOB) is developed for the formation control of multiple quadrotors here Firstly, KCF is used to effectively fuse the data shared in the formation with noise and uncertainty, which improves the applicability and robustness of the formation in complex environments. Secondly, FTDOB is able to estimate the external disturbances suffered by the quadrotor in a fixed time and provides real-time compensation for the controller. On this basis, an improved MPC (IMPC) is designed for each UAV of the formation, which improves the computational efficiency while ensuring the asymptotic stability of the system. Eventually, the capability and effectiveness of the proposed strategy are verified by simulation in terms of disturbance rejection and noise suppression, as well as good trajectory tracking of the formation.

Effects of Repetitive Transcranial Magnetic Stimulation at the Cerebellum on Working Memory.

Transcranial magnetic stimulation is a widely used brain intervention technique in clinical settings. In recent years, the role of the cerebellum in learning and memory has become one of the hotspots in the field of cognitive neuroscience. In this study, we recruited 36 healthy college or graduate students as subjects and divided them into groups, with 10 to 14 subjects in each group. We performed 5 Hz and 20 Hz repeated transcranial magnetic stimulation and sham stimulation on the Crus II subregion of the cerebellum in different groups, then let them complete the 2-back working memory task before and after the stimulation. We simultaneously recorded the electroencephalogram in the experiment and analyzed the data. We found that after repeated transcranial magnetic stimulation of the cerebellum at 5 Hz and 20 Hz, the N170 and P300 event-related potential components in the prefrontal cortex showed significant differences compared to those in the sham stimulation group. Using phase-locked values to construct brain networks and conduct further analysis, we discovered that stimulation frequencies of 5 Hz and 20 Hz had significant effects on the local and global efficiency of brain networks in comparison to the sham stimulation group. The results showed that repeated transcranial magnetic stimulation on cerebellar targets can effectively affect the subjects' working memory tasks. Repeated transcranial magnetic stimulation at 5 Hz and 20 Hz could enhance the excitatory responses of the frontal lobes. After stimulation at 5 Hz and 20 Hz, the efficiency of the brain network significantly improved.

Features of event-related potentials during retrieval of episodic memory in patients with mild cognitive impairment due to Alzheimer's disease.

Objective: To provide a rigorous comparison between patients with mild cognitive impairment due to Alzheimer's disease (MCI-AD) and healthy elderly, as well as to assess the value of electroencephalography (EEG) in terms of early diagnosis, we conducted a neutral image recognition memory task involving individuals with positive biomarkers including ß amyloid deposition, pathologic tau or neurodegeneration. Methods: The task involving study and test blocks was designed to evaluate participants' recognition memory. Electroencephalogram was recorded synchronously to elicit event-related potentials in patients with MCI-AD and healthy control subjects. We further analyzed differences between groups or conditions in terms of behavioral performance, time domain, and time-frequency domain. Results: The MCI-AD cohort showed a slower response time to old/new images and had low accuracy regarding behavioral performance. The amplitude of the late positive complex for the old/new effects was significantly suppressed in the MCI-AD cohort when compared with that in the HC cohort. The amplitude of the late old/new effects was correlated with the Auditory Verbal Learning Test recognition score in all participants. The time-frequency domain analysis revealed that correct recognition of old items elicited a decrease in beta power, mainly limited to the HC cohort. Moreover, the combination of behavioral (processing speed and accuracy) and electrophysiological (average amplitude and relative power of delta band) measures contributes to classifying patients with MCI-AD from healthy elderly people. Conclusion: Changes of old/new effects, accuracy and response time are sensitive to the impairment of recognition memory in patients with MCI-AD and have moderate value in predicting the incipient stage of AD.

Differences and Changes in Cerebellar Functional Connectivity of Parkinson's Patients with Visual Hallucinations.

Recent studies have discovered that functional connections are impaired in patients with Parkinson's disease (PD) accompanied by hallucinations (PD-H), even at the preclinical stage. The cerebellum has been implicated in playing a role in cognitive processes. However, the functional connectivity (FC) between the cognitive sub-regions of the cerebellum in PD patients with hallucinations needs further clarification. Resting-state functional magnetic resonance imaging (rs-fMRI) data were collected from three groups (17 PD-H patients, 13 patients with Parkinson's disease not accompanied by hallucinations (PD-NH), and 26 healthy controls (HC)). The data were collected in this study to investigate the impact of cerebellar FC changes on cognitive performance. Additionally, we define cerebellar FC as a training feature for classifying all subjects using Support Vector Machines (SVMs). We found that in the PD-H patients, there was an increase in FC within the left side of the precuneus (PCUN) compared to the HC. Additionally, there was an increase in FC within the bilateral opercular part of the inferior frontal gyrus (IFGoprec) and triangular part of the inferior frontal gyrus (IFCtriang), as well as the left side of the postcentral gyrus (PoCG), inferior parietal lobe (IPL), and PCUN compared to the PD-NH patients. In the machine learning training results, cerebellar FC has also been proven to be an effective biomarker feature, achieving a recognition rate of over 90% for PD-H. These findings indicate that the cortico-cerebellar FC in PD-H and PD-NH patients was significantly disrupted, with different patterns of distribution. The proposed pipeline offers a promising, low-cost alternative for diagnosing preclinical PD-H and may also be beneficial for other degenerative brain disorders.