Clinical and radiological characteristics of pediatric COVID-19 before and after the Omicron outbreak: a multi-center study.

Introduction: The emergence of the Omicron variant has seen changes in the clinical and radiological presentations of COVID-19 in pediatric patients. We sought to compare these features between patients infected in the early phase of the pandemic and those during the Omicron outbreak. Methods: A retrospective study was conducted on 68 pediatric COVID-19 patients, of which 31 were infected with the original SARS-CoV-2 strain (original group) and 37 with the Omicron variant (Omicron group). Clinical symptoms and chest CT scans were examined to assess clinical characteristics, and the extent and severity of lung involvement. Results: Pediatric COVID-19 patients predominantly had normal or mild chest CT findings. The Omicron group demonstrated a significantly reduced CT severity score than the original group. Ground-glass opacities were the prevalent radiological findings in both sets. The Omicron group presented with fewer symptoms, had milder clinical manifestations, and recovered faster than the original group. Discussion: The clinical and radiological characteristics of pediatric COVID-19 patients have evolved with the advent of the Omicron variant. For children displaying severe symptoms warranting CT examinations, it is crucial to weigh the implications of ionizing radiation and employ customized scanning protocols and protective measures. This research offers insights into the shifting disease spectrum, aiding in the effective diagnosis and treatment of pediatric COVID-19 patients.

Altered functional connectivity pattern of hippocampal subfields in individuals with objectively-defined subtle cognitive decline and its association with cognition and cerebrospinal fluid biomarkers.

Recent studies have shown that in the preclinical phase of Alzheimer's disease (AD), subtle cognitive changes can be detected using sensitive neuropsychological measures, and have proposed the concept of objectively-defined subtle cognitive decline (Obj-SCD). We aimed to assess the functional alteration of hippocampal subfields in individuals with Obj-SCD and its association with cognition and pathological biomarkers. Forty-two participants with cognitively normal (CN), 29 with Obj-SCD, and 55 with mild cognitive impairment (MCI) were retrospectively collected from the ADNI database. Neuropsychological performance, functional MRI, and cerebrospinal fluid (CSF) data were obtained. We calculated the seed-based functional connectivity (FC) of hippocampal subfields (cornu ammonis1 [CA1], CA2/3/dentate gyrus [DG], and subiculum) with whole-brain voxels. Additionally, we analyzed the correlation between FC values of significantly altered regions and neuropsychological performance and CSF biomarkers. The Obj-SCD group showed lower FC between left CA1-CA2/3/DG and right thalamus and higher FC between right subiculum and right superior parietal gyrus (SPG) compared with the CN and MCI groups. In the Obj-SCD group, FC values between left CA2/3/DG and right thalamus were positively associated with Auditory Verbal Learning Test (AVLT) recognition (r = 0.395, p = 0.046) and CSF Aß1-42 levels (r = 0.466, p = 0.019), and FC values between left CA1 and right thalamus were positively correlated with CSF Aß1-42 levels (r = 0.530, p = 0.006). Taken together, dysfunction in CA1-CA2/3/DG subregions suggests subtle cognitive impairment and AD-specific pathological changes in individuals with Obj-SCD. Additionally, increased subiculum connectivity may indicate early functional compensation for subtle cognitive changes.

Interactions between cigarette smoking and cognitive status on functional connectivity of the cortico-striatal circuits in individuals without dementia: A resting-state functional MRI study.

AIMS: Cigarette smoking is a modifiable risk factor for Alzheimer's disease (AD), and controlling risk factors may curb the progression of AD. However, the underlying neural mechanisms of the effects of smoking on cognition remain largely unclear. Therefore, we aimed to explore the interaction effects of smoking × cognitive status on cortico-striatal circuits, which play a crucial role in addiction and cognition, in individuals without dementia. METHODS: We enrolled 304 cognitively normal (CN) non-smokers, 44 CN smokers, 130 mild cognitive impairment (MCI) non-smokers, and 33 MCI smokers. The mixed-effect analysis was performed to explore the interaction effects between smoking and cognitive status (CN vs. MCI) based on functional connectivity (FC) of the striatal subregions (caudate, putamen, and nucleus accumbens [NAc]). RESULTS: The significant interaction effects of smoking × cognitive status on FC of the striatal subregions were detected in the left inferior parietal lobule (IPL), bilateral cuneus, and bilateral anterior cingulate cortex (ACC). Specifically, increased FC of right caudate to left IPL was found in CN smokers compared with non-smokers. The MCI smokers showed decreased FC of right caudate to left IPL and of right putamen to bilateral cuneus and increased FC of bilateral NAc to bilateral ACC compared with CN smokers and MCI non-smokers. Furthermore, a positive correlation between FC of the NAc to ACC with language and memory was detected in MCI smokers. CONCLUSIONS: Cigarette smoking could affect the function of cortico-striatal circuits in patients with MCI. Our findings suggest that quitting smoking in the prodromal stage of AD may have the potential to prevent disease progression.

Effects of Cigarette Smoking on Resting-State Functional Connectivity of the Nucleus Basalis of Meynert in Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI) is the prodromal phase of Alzheimer's disease (AD) and has a high risk of progression to AD. Cigarette smoking is one of the important modifiable risk factors in AD progression. Cholinergic dysfunction, especially the nucleus basalis of Meynert (NBM), is the converging target connecting smoking and AD. However, how cigarette smoking affects NBM connectivity in MCI remains unclear. Objective: This study aimed to evaluate the interaction effects of condition (non-smoking vs. smoking) and diagnosis [cognitively normal (CN) vs. MCI] based on the resting-state functional connectivity (rsFC) of the NBM. Methods: After propensity score matching, we included 86 non-smoking CN, 44 smoking CN, 62 non-smoking MCI, and 32 smoking MCI. All subjects underwent structural and functional magnetic resonance imaging scans and neuropsychological tests. The seed-based rsFC of the NBM with the whole-brain voxel was calculated. Furthermore, the mixed effect analysis was performed to explore the interaction effects between condition and diagnosis on rsFC of the NBM. Results: The interaction effects of condition × diagnosis on rsFC of the NBM were observed in the bilateral prefrontal cortex (PFC), bilateral supplementary motor area (SMA), and right precuneus/middle occipital gyrus (MOG). Specifically, the smoking CN showed decreased rsFC between left NBM and PFC and increased rsFC between left NBM and SMA compared with non-smoking CN and smoking MCI. The smoking MCI showed reduced rsFC between right NBM and precuneus/MOG compared with non-smoking MCI. Additionally, rsFC between the NBM and SMA showed a significant negative correlation with Wechsler Memory Scale-Logical Memory (WMS-LM) immediate recall in smoking CN (r = -0.321, p = 0.041). Conclusion: Our findings indicate that chronic nicotine exposure through smoking may lead to functional connectivity disruption between the NBM and precuneus in MCI patients. The distinct alteration patterns on NBM connectivity in CN smokers and MCI smokers suggest that cigarette smoking has different influences on normal and impaired cognition.

An Illustrated Guide to the Imaging Evolution of COVID in Non-Epidemic Areas of Southeast China.

Purpose: By analyzing the CT manifestations and evolution of COVID in non-epidemic areas of southeast China, analyzing the developmental abnormalities and accompanying signs in the early and late stages of the disease, providing imaging evidence for clinical diagnosis and identification, and assisting in judging disease progression and monitoring prognosis. Methods: This retrospective and multicenter study included 1,648 chest CT examinations from 693 patients with laboratory-confirmed COVID-19 infection from 16 hospitals of southeast China between January 19 and March 27, 2020. Six trained radiologists analyzed and recorded the distribution and location of the lesions in the CT images of these patients. The accompanying signs include crazy-paving sign, bronchial wall thickening, microvascular thickening, bronchogram sign, fibrous lesions, halo and reverse-halo signs, nodules, atelectasis, and pleural effusion, and at the same time, they analyze the evolution of the abovementioned manifestations over time. Result: There were 1,500 positive findings in 1,648 CT examinations of 693 patients; the average age of the patients was 46 years, including 13 children; the proportion of women was 49%. Early CT manifestations are single or multiple nodular, patchy, or flaky ground-glass-like density shadows. The frequency of occurrence of ground-glass shadows (47.27%), fibrous lesions (42.60%), and microvascular thickening (40.60%) was significantly higher than that of other signs. Ground-glass shadows increase and expand 3-7 days after the onset of symptoms. The distribution and location of lesions were not significantly related to the appearance time. Ground-glass shadow is the most common lesion, with an average absorption time of 6.2 days, followed by consolidation, with an absorption time of about 6.3 days. It takes about 8 days for pure ground-glass lesions to absorb. Consolidation change into ground glass or pure ground glass takes 10-14 days. For ground-glass opacity to evolve into pure ground-glass lesions, it takes an average of 17 days. For ground-glass lesions to evolve into consolidation, it takes 7 days, pure ground-glass lesions need 8 days to evolve into ground-glass lesions. The average time for CT signs to improve is 10-15 days, and the first to improve is the crazy-paving sign and nodules; while the progression of the disease is 6-12 days, the earliest signs of progression are air bronchogram signs, bronchial wall thickening, and bronchiectasis. There is no severe patient in this study. Conclusion: This study depicts the CT manifestation and evolution of COVID in non-epidemic origin areas, and provides valuable first-hand information for clinical diagnosis and judgment of patient's disease evolution and prediction.

Quantitative and semi-quantitative CT assessments of lung lesion burden in COVID-19 pneumonia.

This study aimed to clarify and provide clinical evidence for which computed tomography (CT) assessment method can more appropriately reflect lung lesion burden of the COVID-19 pneumonia. A total of 244 COVID-19 patients were recruited from three local hospitals. All the patients were assigned to mild, common and severe types. Semi-quantitative assessment methods, e.g., lobar-, segmental-based CT scores and opacity-weighted score, and quantitative assessment method, i.e., lesion volume quantification, were applied to quantify the lung lesions. All four assessment methods had high inter-rater agreements. At the group level, the lesion load in severe type patients was consistently observed to be significantly higher than that in common type in the applications of four assessment methods (all the p < 0.001). In discriminating severe from common patients at the individual level, results for lobe-based, segment-based and opacity-weighted assessments had high true positives while the quantitative lesion volume had high true negatives. In conclusion, both semi-quantitative and quantitative methods have excellent repeatability in measuring inflammatory lesions, and can well distinguish between common type and severe type patients. Lobe-based CT score is fast, readily clinically available, and has a high sensitivity in identifying severe type patients. It is suggested to be a prioritized method for assessing the burden of lung lesions in COVID-19 patients.

Increased striatal functional connectivity is associated with improved smoking cessation outcomes: A preliminary study.

The striatum is the critical area of reward processing and has been repeatedly linked to nicotine addiction. However, it remains unclear whether different smoking cessation outcomes (relapse or not) are associated with different functional connectivity changes of the striatum during smoking cessation treatment. A total of 30 treatment-seeking smokers were recruited in the study and underwent magnetic resonance imaging (MRI) scans immediately before and after a 12-week treatment with varenicline. After the 12-week treatment with varenicline, 14 subjects relapsed to smoking (relapsers), whereas 16 not relapsed (nonrelapsers). Changes in resting-state functional connectivity (rsFC) across groups and visits were assessed using repeated measures analysis of covariance (ANCOVA). Significant interaction effects were detected: (1) between left nucleus accumbens (NAc) and left orbitofrontal cortex (OFC), insula, inferior frontal gyrus (IFG), and bilateral precuneus; (2) between right NAc and left insula, IFG, and bilateral dorsolateral prefrontal cortex (DLPFC); and (3) between bilateral putamen and left precuneus. Post hoc region-of-interest analyses in brain areas showing interaction effects indicated significantly decreased rsFC after treatment compared with before treatment in relapsers but opposite longitudinal changes in nonrelapers. These novel findings suggest that increased striatal rsFC is associated with improved smoking cessation outcomes. These striatal functional circuits may serve as potential therapeutic targets for more efficacious treatment of nicotine addiction.

Abnormal white matter tracts of insula in smokers.

Nicotine addiction is characterized as a neural circuit dysfunction, particularly with regard to the alterations in central reward pathways. The insula, a cortical region that is thought to play a central role in this reward circuitry, has been implicated in the maintenance of nicotine addiction. However, it remains largely unclear about the white matter (WM) microstructural alterations of insula in nicotine addiction and whether the WM alterations of insula could predict smoking cessation outcomes. In this study, 58 male nicotine-dependent smokers and 34 matched male nonsmoking controls were recruited. After a 12-week smoking cessation treatment with varenicline, 38 smokers relapsed, and 20 did not relapse. Diffusion tensor imaging and probabilistic tractography were used to investigate the differences of WM tracts of insula between smokers and nonsmokers. Relative to nonsmokers, in the left hemisphere, smokers showed lower fractional anisotropy (FA) in the fiber tracts of anterior insula cortex-to-nucleus accumbens and posterior insula cortex-to-nucleus accumbens; in the right hemisphere, smokers showed higher FA, and lower axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) in the fiber tracts of anterior insula cortex-to-medial orbitofrontal cortex, posterior insula cortex-to-medial orbitofrontal cortex, and posterior insula cortex-to-nucleus accumbens. However, there were no differences of WM diffusion properties between relapsers and nonrelapsers. This study is the first using probabilistic tractography to exclusively clarify the precise roles of insular WM tracts in smokers, which may provide new insights into the underlying neurobiology of nicotine addiction.

Increased thalamic volume and decreased thalamo-precuneus functional connectivity are associated with smoking relapse.

The thalamus, with the highest density of nicotinic acetylcholine receptor (nAChR) in the brain, plays a central role in thalamo-cortical circuits that are implicated in nicotine addiction. However, little is known about whether the thalamo-cortical circuits are potentially predictive of smoking relapse. In the current study, a total of 125 participants (84 treatment-seeking male smokers and 41 age-matched male nonsmokers) were recruited. Structural and functional magnetic resonance images (MRI) were acquired from all participants. After a 12-week smoking cessation treatment with varenicline, the smokers were then divided into relapsers (n = 54) and nonrelapsers (n = 30). Then, we compared thalamic volume and seed-based thalamo-cortical resting state functional connectivity (rsFC) prior to the cessation treatment among relapsers, nonrelapsers and nonsmokers to investigate the associations between thalamic structure/function and smoking relapse. Increased thalamic volume was detected in smokers relative to nonsmokers, and in relapsers relative to nonrelapsers, especially on the left side. Moreover, decreased left thalamo-precuneus rsFC was detected in relapsers relative to nonrelapsers. Additionally, a logistic regression analysis showed that the thalamic volume and thalamo-precuneus rsFC predicted smoking relapse with an accuracy of 75.7%. These novel findings indicate that increased thalamic volume and decreased thalamo-precuneus rsFC are associated with smoking relapse, and these thalamic measures may be used to predict treatment efficacy of nicotine addiction and serve as a potential biomarker for personalized medicine.

Temporal changes of COVID-19 pneumonia by mass evaluation using CT: a retrospective multi-center study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has widely spread worldwide and caused a pandemic. Chest CT has been found to play an important role in the diagnosis and management of COVID-19. However, quantitatively assessing temporal changes of COVID-19 pneumonia over time using CT has still not been fully elucidated. The purpose of this study was to perform a longitudinal study to quantitatively assess temporal changes of COVID-19 pneumonia. METHODS: This retrospective and multi-center study included patients with laboratory-confirmed COVID-19 infection from 16 hospitals between January 19 and March 27, 2020. Mass was used as an approach to quantitatively measure dynamic changes of pulmonary involvement in patients with COVID-19. Artificial intelligence (AI) was employed as image segmentation and analysis tool for calculating the mass of pulmonary involvement. RESULTS: A total of 581 confirmed patients with 1,309 chest CT examinations were included in this study. The median age was 46 years (IQR, 35-55; range, 4-87 years), and 311 (53.5%) patients were male. The mass of pulmonary involvement peaked on day 10 after the onset of initial symptoms. Furthermore, the mass of pulmonary involvement of older patients (>45 years) was significantly severer (P<0.001) and peaked later (day 11 vs. day 8) than that of younger patients (≤45 years). In addition, there were no significant differences in the peak time (day 10 vs. day 10) and median mass (P=0.679) of pulmonary involvement between male and female. CONCLUSIONS: Pulmonary involvement peaked on day 10 after the onset of initial symptoms in patients with COVID-19. Further, pulmonary involvement of older patients was severer and peaked later than that of younger patients. These findings suggest that AI-based quantitative mass evaluation of COVID-19 pneumonia hold great potential for monitoring the disease progression.

Initial chest CT findings in COVID-19: correlation with clinical features.

In December 2019, coronavirus disease 2019 (COVID-19), a new de novo infectious disease, was first identified in Wuhan, China and quickly spread across China and around the world. The etiology was a novel betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (Lu et al., 2020). On Mar. 11, 2020, World Health Organization (WHO) characterized COVID-19 as a global pandemic. As of Mar. 22, 2020, over 292 000 confirmed COVID-19 cases have been reported globally. To date, COVID-19, with its high infectivity, has killed more people than severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) combined (Wu and McGoogan, 2020).

Increased interregional functional connectivity of anterior insula is associated with improved smoking cessation outcome.

Damage to the insular cortex has been shown to disrupt smoking behavior. However, whether smoking cessation outcomes are associated with abnormal functions of insula and its subregions remains unclear. In this study, we investigated the relationship between insular functions (interregional functional connectivity and regional activity) and treatment outcomes of cigarette smoking. Thirty treatment-seeking smokers were recruited into the treatment study and underwent magnetic resonance imaging (MRI) scans immediately before and after the treatment. Sixteen participants remained abstinent from smoking (quitters), while 14 relapsed to smoking (relapers). Changes in resting-state functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) across groups and visits were assessed using repeated measures ANCOVA. Significant interaction effects were detected: 1) between the left anterior insula and left precuneus; and 2) between the right anterior insula and left precuneus and medial frontal gyrus. Post-hoc region-of-interest analyses in brain areas showing interaction effects indicated significantly increased functional connectivity after treatment compared with before treatment in quitters but opposite longitudinal changes in relapsers. However, no significant effects in fALFF were observed. These novel findings suggest that increased interregional functional connectivity of the anterior insula is associated with improved smoking cessation outcome: individuals with increased functional connectivity of the anterior insula during the treatment would more likely quit smoking successfully. These insular circuits may serve as therapeutic targets for more efficacious treatment of nicotine addiction.

Understanding the association between psychomotor processing speed and white matter hyperintensity: A comprehensive multi-modality MR imaging study.

Cognitive processing speed is crucial for human cognition and declines with aging. White matter hyperintensity (WMH), a common sign of WM vascular damage in the elderly, is closely related to slower psychomotor processing speed. In this study, we investigated the association between WMH and psychomotor speed changes through a comprehensive assessment of brain structural and functional features. Multi-modal MRIs were acquired from 60 elderly adults. Psychomotor processing speeds were assessed using the Trail Making Test Part A (TMT-A). Linear regression analyses were performed to assess the associations between TMT-A and brain features, including WMH volumes in five cerebral regions, diffusivity parameters in the major WM tracts, regional gray matter volume, and brain activities across the whole brain. Hierarchical regression analysis was used to demonstrate the contribution of each index to slower psychomotor processing speed. Linear regression analysis demonstrated that WMH volume in the occipital lobe and fractional anisotropy of the forceps major, an occipital association tract, were associated with TMT-A. Besides, resting-state brain activities in the visual cortex connected to the forceps major were associated with TMT-A. Hierarchical regression showed fractional anisotropy of the forceps major and regional brain activities were significant predictors of TMT-A. The occurrence of WMH, combined with the disruption of passing-through fiber integrity and altered functional activities in areas connected by this fiber, are associated with a decline of psychomotor processing speed. While the causal relationship of this WMH-Tract-Function-Behavior link requires further investigation, this study enhances our understanding of these complex mechanisms.

Brain Gray Matter Volume and Functional Connectivity Are Associated With Smoking Cessation Outcomes.

Smoking cessation is critical for reducing the risk of respiratory, cardiovascular diseases and cancers. However, most cessation attempts resulted in failure. In the present study, we aim to explore whether alterations of brain gray matter (GM) volume and functional connectivity (FC) are related to cessation outcomes, in hope of providing evidence for improving smoking cessation outcomes. Seventy-three smokers and 41 non-smokers were enrolled in the present study. All smokers participated in a 12-week smoking cessation treatment during which Varenicline was used to aid cessation. At the end of treatment, the smokers were divided into quitters and relapsers based on their abstinence performance. Structural magnetic resonance imaging (MRI) and voxel-based morphometry were applied to quantify the differences of regional brain volumes among the three groups at baseline. In addition, resting-state FC was used to investigate the related functional changes. In comparison with non-smokers, the smokers showed smaller GM volume in the left dorsal medial thalamus. Among the 73 smokers, 29 subjects successfully quitted smoking. The quitters showed greater GM volume than the relapsers in the right postcentral gyrus, right putamen\caudate nucleus and left orbitofrontal cortex (OFC). The GM volume in the left OFC was found to be negatively correlated with the pack years and daily smoking amount in the quitters. Furthermore, we found significantly reduced FC between left thalamus and left cerebellum in the relapsers. These findings extended our knowledge of the neural mechanism of smoking cessation, and suggested that brain structural and functional changes were related to smoking cessation outcomes.

Application of T1-/T2-Weighted Ratio Mapping to Elucidate Intracortical Demyelination Process in the Alzheimer's Disease Continuum.

Background The biological diagnosis criteria of the Alzheimer's disease (AD) suggests that previous work may misclassify the cognitive impairment caused by other factors into AD. Consequently, re-assessing the imaging profile of AD continuum is needed. Considering the high vulnerability of cortical association fibers, we aimed to elucidate the cortical demyelination process in the AD continuum biologically defined. Methods According to the biological diagnosis criteria, we determined the positive amyloid status (A+) as cerebrospinal fluid (CSF) amyloid1 - 42 < 192 pg/ml, Florbetapir Positron emission tomography (PET) composite standardized uptake value ratio (SUVR) >1.11. Also, the positive Tau status (T+) was determined as p-Tau181 > 23 pg/ml. Based on the cognitive characterization, we further categorized 252 subjects into 27 cognitively unimpaired with normal AD biomarkers (A-T-, controls), 49 preclinical AD (A+T+), 113 AD with mild cognitive impairment (MCI) (A+T+), and 63 AD dementia (A+T+). We estimated the intracortical myelin content used the T1- and T2-weighted (T1W/T2W) ratio mapping. To investigate the sensitivity of the ratio mapping, we also utilized well-validated AD imaging biomarkers as the reference, including gray matter volume and Fludeoxyglucose PET (FDG-PET). Based on the general linear model, we conducted the voxel-wise two-sample T-tests between the controls and each group in the AD continuum. Results Compared to the controls, the results showed that the preclinical AD patients exhibited decreased T1W/T2W ratio value in the right inferior parietal lobule (IPL); as the disease progresses, the prodromal AD patients demonstrated lower ratio value in bilateral IPL, with hippocampus (HP) atrophy. Lastly, the AD dementia patients exhibited decreased ratio value in bilateral IPL and hippocampus; also, we observed the bilateral temporal cortices atrophy and widespread decreased metabolism in the AD dementia patients. After corrected with gray volume, the results remained mostly unchanged. Conclusion Our study implied the decreased right IPL T1W/T2W ratio might represent early AD-related demyelination in disease continuum. Additionally, we demonstrated that the T1W/T2W ratio mapping is an easy-to-implement and sensitive metric to assess the intracortical myelin content in AD, particularly in the early stage.

Gray matter structural covariance networks changes along the Alzheimer's disease continuum.

Alzheimer's disease (AD) has a long neuropathological accumulation phase before the onset of dementia. Such AD neuropathological deposition between neurons impairs the synaptic communication, resulting in networks disorganization. Our study aimed to explore the evolution patterns of gray matter structural covariance networks (SCNs) along AD continuum. Based on the AT(N) (i.e., Amyloid/Tau/Neurodegeneration) pathological classification system, we classified subjects into four groups using cerebrospinal fluid amyloid-beta1-42 (A) and phosphorylated tau protein181 (T). We identified 101 subjects with normal AD biomarkers (A-T-), 40 subjects with Alzheimer's pathologic change (A + T-), 101 subjects with biological AD (A + T+) and 91 AD with dementia (demented subjects with A + T+). We used four regions of interest to anchor default mode network (DMN, medial temporal subsystem and midline core subsystem), salience network (SN) and executive control network (ECN). Finally, we used a multi-regression model-based linear-interaction analysis to assess the SCN changes. Along the disease progression, DMN and SN showed increased structural association at the early stage while decreased structural association at the late stage. Moreover, ECN showed progressively increased structural association as AD neuropathological profiles progress. In conclusion, this study found the dynamic trajectory of SCNs changes along the AD continuum and support the network disconnection hypothesis underlying AD neuropathological progression. Further, SCN may potentially serve as an effective AD biomarker.

The Ventral Intermediate Nucleus Differently Modulates Subtype-Related Networks in Parkinson's Disease.

Background: Posture instability gait difficulty-dominant (PIGD) and tremor-dominant (TD) are two subtypes of Parkinson's disease (PD). The thalamus is involved in the neural circuits of both subtypes. However, which subregion of the thalamus has an influence on the PD subtypes remains unclear. Objective: To explore the core subregion of the thalamus showing a significant influence on the PD subtypes and its directional interaction between the PD subtypes. Methods: A total of 79 PD patients (43 TD and 36 PIGD) and 31 normal controls (NC) were enrolled, and the gray matter volume and perfusion characteristics in the thalamus were compared between the three groups. The subregion of the thalamus with significantly different perfusion and volume among three groups was used as the seed of a Granger causality analysis (GCA) to compare the causal connectivity between different subtypes. Results: Perfusion with an increased gradient among the three groups (TD > PIGD > NC) in the bilateral ventral intermediate nucleus (Vim) was observed, which was positively correlated with the clinical tremor scores. The GCA revealed that TD patients had enhanced causal connectivity from the bilateral Vim to the bilateral paracentral gyrus, M1 and the cerebellum compared with the NC group, while the PIGD subtype revealed an increased causal connectivity from the bilateral Vim to the bilateral premotor cortex (preM) and putamen. Additionally, there were positive correlations between the tremor scores and a causal connectivity from the Vim to the cerebellum. The connectivity from the right Vim to the right preM and the right putamen was positively correlated with the PIGD scores. Conclusion: This multilevel analysis showed that the Vim had a significant influence on the PD subtypes and that it differentially mediated the TD and PIGD-related causal connectivity pattern in PD.

Altered effective connectivity anchored in the posterior cingulate cortex and the medial prefrontal cortex in cognitively intact elderly APOE ε4 carriers: a preliminary study.

The APOE ε4 allele is associated with impaired intrinsic functional connectivity in neural networks, especially in the default mode network (DMN). However, effective connectivity (EC) reflects the direct causal effects of one brain region to another, which has rarely been investigated. Recently, Granger causality analysis (GCA) proved suitable for the study of directionality in neuronal interactions. Using GCA, we examined the differences in the EC between the anterior medial prefrontal cortex/posterior cingulate cortex (aMPFC/PCC) and the whole brain in 17 ε4 carrying and 32 non-carrying cognitively intact elderly individuals. Furthermore, correlation analyses were performed between the abnormal EC and cognition/neuropathological indices. Compared with the non-carriers, the results showed that the ε4 carriers exhibited decreased EC from the PCC to the whole brain in the middle temporal gyrus (MTG), the anterior cingulate cortex (ACC), and the precuneus (PCu). Meanwhile, the ε4 carriers demonstrated increased EC from the whole brain to the aMPFC in the inferior parietal lobe (IPL) and the postcentral gyrus (PCG). The correlation analyses suggested that the EC from the IPL/PCG to the aMPFC was related to episodic memory in non-carriers, while the decreased EC from the PCC to the ACC was associated with increased levels of t-tau in the ε4 carriers. In ε4 carriers, a negative influence can be traced from the PCC to both the anterior and posterior DMN subsystems; meanwhile, the anterior DMN subsystem receives compensatory effects from the parietal cortex. Early increases in AD-related pathologies in the PCC may act as first factors during this pathological process.

Different patterns of gray matter density in early- and middle-late-onset Parkinson's disease: a voxel-based morphometry study.

Early-onset Parkinson's disease (EOPD) has a clinical course and characteristics distinct from middle-late-onset Parkinson's disease (M-LOPD). Although many studies have investigated these differences, the neural mechanisms of these characteristics remain unclear. This study aimed to investigate the morphological differences, and their related clinical significance, between EOPD and M-LOPD patients. We recruited two groups of patients, 28 EOPD patients and 37 M-LOPD patients, and two age- and sex-matched control groups (23 controls in each group). The voxel-based morphometry (VBM) technique was used to examine changes in gray matter (GM) density between patients and their corresponding controls. Compared with controls, EOPD patients had lower GM density in the left putamen, inferior frontal gyrus and insula, and higher GM density in the right occipital lobe and bilateral cerebellum posterior lobes. M-LOPD patients had lower GM density in the left cerebellum posterior lobe, occipital lobe and right supplementary motor area (SMA), and higher GM density in the left middle temporal gyrus. Correlation analyses showed that GM density values in the right cerebellum posterior lobe positively correlated with the Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and the Hoehn-Yahr stages in EOPD patients. Our results reveal different patterns of structural changes in EOPD and M-LOPD patients. A probable compensatory effect of the cerebellum was observed and may partly explain the slower decline of motor function in EOPD patients.