Associations between differential connectivity patterns of executive control networks and APOE ɛ4 in the Alzheimer continuum.

The APOE ɛ4 allele and age are risk factors for Alzheimer's disease (AD) and contribute to decreased executive function. However, the influence of APOE ɛ4 on the executive control network (ECN) in the AD continuum is still unclear. This study included 269 participants aged between 50 and 95 years old, based on ADNI data, including 104 cognitively normal (CN) individuals, 72 individuals with early mild cognitive impairment (EMCI), 55 individuals with late mild cognitive impairment (LMCI), and 38 AD patients. Within each disease group, participants were subdivided into APOE ɛ4 carriers and non-carriers. We explored brain regions within the ECN affected by the interactions between genes and disease states by resting-state functional magnetic resonance imaging (fMRI) and voxel-based two-way analysis of variance (ANOVA). Subsequently, functional connectivity (FC) between seeds and peak clusters were extracted and correlated with the cognitive performance. We found that the damages of carrying APOE ɛ4 in ECNs mainly distributed in the fronto-parietal and parietal-temporal systems. Functional network intergroup differences indicated increased intrafrontal and fronto-parietal connectivity at the early stage of AD and increased connectivity between the parietal lobe and related regions at late disease in these APOE ɛ4 carriers. Our conclusion is that the functional connectivity in the ECN exhibits different distinguishably patterns of impairment in the AD continuum under the influence of the APOE ɛ4 allele. Patients with different genotypes showed heterogeneity in functional network changes in the early stages of disease, which may be a potential biomarker for early AD.

Distinguishable neural circuit mechanisms associated with the clinical efficacy of rTMS in aMCI patients.

Repetitive transcranial magnetic stimulation is used in early-stage Alzheimer's disease to slow progression, but heterogeneity in response results in different treatment outcomes. The mechanisms underlying this heterogeneity are unclear. This study used resting-state neuroimaging to investigate the variability in episodic memory improvement from angular gyrus repetitive transcranial magnetic stimulation and tracked the neural circuits involved. Thirty-four amnestic mild cognitive impairment patients underwent angular gyrus repetitive transcranial magnetic stimulation (4 weeks, 20 Hz, 100% resting motor threshold) and were divided into high-response and low-response groups based on minimal clinically important differences in auditory verbal learning test scores. Baseline and pre/post-treatment neural circuit activities were compared. Results indicated that the orbital middle frontal gyrus in the orbitofrontal cortex network and the precuneus in the default mode network had higher local activity in the low-response group. After treatment, changes in local and remote connectivity within brain regions of the orbitofrontal cortex, default mode network, visual network, and sensorimotor network showed opposite trends and were related to treatment effects. This suggests that the activity states of brain regions within the orbitofrontal cortex and default mode network could serve as imaging markers for early cognitive compensation in amnestic mild cognitive impairment patients and predict the aftereffects of repetitive transcranial magnetic stimulation response.

The gonadal niche safeguards human fetal germline cell development following maternal SARS-CoV-2 infection.

During pregnancy, germline development is vital for maintaining the continuation of species. Recent studies have shown increased pregnancy risks in COVID-19 patients at the perinatal stage. However, the potential consequence of infection for reproductive quality in developing fetuses remains unclear. Here, we analyze the transcriptome and DNA methylome of the fetal germline following maternal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We find that infection at early gestational age, a critical period of human primordial germ cell specification and epigenetic reprogramming, trivially affects fetal germ cell (FGC) development. Additionally, FGC-niche communications are not compromised by maternal infection. Strikingly, both general and SARS-CoV-2-specific immune pathways are greatly activated in gonadal niche cells to protect FGCs from maternal infection. Notably, there occurs an "in advance" development tendency in FGCs after maternal infection. Our study provides insights into the impacts of maternal SARS-CoV-2 infection on fetal germline development and serves as potential clinical guidance for future pandemics.

Personality traits influence the effectiveness of hypomania checklist-32 in screening for bipolar disorder.

Background: It is clinically challenging to distinguish bipolar disorder (BD) from major depressive disorder (MDD) in the early stages. While the hypomania checklist-32 (HCL-32) is a proper auxiliary tool that is useful to differentiate between BD and MDD, there is currently no standard cut-off value. The variations in HCL-32 cut-off values could potentially be influenced by personality traits. Therefore, the aim of this study is to explore the effect of personality traits on the screening performance of HCL-32. Methods: In this retrospective cross-sectional study, 168 patients with BD or MDD were evaluated with the Eysenck Personality Questionnaire (EPQ) and HCL-32. The associations between demographic data, diagnosis and clinical rating scales were analyzed. Results: Diagnosis was not associated with extraversion but was related to neuroticism. HCL-32 scores in typical extraverted patients were higher in contrast to atypical extraverted patients. The best cut-off value for BD recognition of typical and atypical extraversion groups were 15 and 12.5, respectively. In patients with MDD, HCL-32 score of typical neuroticism was higher than the atypical type, but there was no difference in patients with BD. In typical neuroticism, there was no difference in HCL-32 scores between patients with MDD and BD. But among atypical neurotic patients, HCL-32 scores of BD were higher compared to MDD, with a cut-off value of 14.5. Limitations: This study had a small sample size. Conclusion: HCL-32 scores were affected by personality traits, with higher scores for typical extraversion and neuroticism. Clinicians should also consider the patients' personality traits when referring to HCL-32 scores, so as to increase the recognition rate of BD and eliminate false positives.