Compensation versus deterioration across functional networks in amnestic mild cognitive impairment subtypes.

Functional connectivity studies to detect neurophysiological correlates of amnestic mild cognitive impairment (aMCI), a prodromal stage of Alzheimer's disease, have generated contradictory results in terms of compensation and deterioration, as most of the studies did not distinguish between the different aMCI subtypes: single-domain aMCI (sd-aMCI) and multiple-domain aMCI (md-aMCI). The present study aimed to characterize the neurophysiological correlates of aMCI subtypes by using resting-state functional magnetic resonance imaging. The study included sd-aMCI (n = 29), md-aMCI (n = 26), and control (n = 30) participants. The data were subjected to independent component analysis (ICA) to explore the default mode network (DMN) and the fronto-parietal control network (FPCN). Additionally, seed-based and moderation analyses were conducted to investigate the connectivity of the medial temporal lobe and functional networks. aMCI subtypes presented differences in functional connectivity relative to the control group: sd-aMCI participants displayed increased FPCN connectivity and reduced connectivity between the posterior parahippocampal gyrus (PHG) and medial structures; md-aMCI participants exhibited lower FPCN connectivity, higher anterior PHG connectivity with frontal structures and lower posterior PHG connectivity with central-parietal and temporo-occipital areas. Additionally, md-aMCI participants showed higher posterior PHG connectivity with structures of the DMN than both control and sd-aMCI participants, potentially indicating more severe cognitive deficits. The results showed gradual and qualitative neurofunctional differences between the aMCI subgroups, suggesting the existence of compensatory (sd-aMCI) and deterioration (md-aMCI) mechanisms in functional networks, mainly originated in the DMN. The findings support consideration of the subgroups as different stages of MCI within the Alzheimer disease continuum.

Associations of Personal Hourly Exposures to Air Temperature and Pollution with Resting Heart Rate in Chronic Obstructive Pulmonary Disease.

Previous studies linked higher daily ambient air temperature and pollution with increased cardiorespiratory morbidity, but immediate effects of personal, hourly exposures on resting heart rate remained unclear. We followed 30 older former smokers with chronic obstructive pulmonary disease (COPD) in Massachusetts for four nonconsecutive 30-day periods over 12 months, collecting 54,487 hourly observations of personal air temperature, fine particulate matter (PM2.5), nitrogen dioxide (NO2), ozone (O3), and resting heart rate. We explored the single lag effects (0-71 h) and cumulative effects (0-5 h, the significant lag windows) of air temperature and pollution on resting heart rate using generalized additive mixed models with distributed lag nonlinear models. Single lag effects of higher air temperature and pollutants on higher resting heart rate were most pronounced at lag 0 to 5 h. Cumulative effects of higher air temperature, PM2.5, O3, and NO2 (each interquartile range increment) on higher resting heart rate at lag 0-5 h, show differences of (beats per minute [bpm], 95% CI) 1.46 (1.31-1.62), 0.35 (0.32-0.39), 2.32 (2.19-2.45), and 1.79 (1.66-1.92), respectively. In conclusion, higher personal hourly air temperature, PM2.5, O3, and NO2 exposures at lag 0-5 h are associated with higher resting heart rate in COPD patients.

Short- and medium-term cumulative effects of traffic-related air pollution on resting heart rate in the elderly: A wearable device study.

BACKGROUND: Epidemiological evidence regarding the association between air pollution and resting heart rate (RHR), a predictor of cardiovascular disease and mortality, is limited and inconsistent. OBJECTIVES: We used wearable devices and time-series analysis to assess the exposure-response relationship over an extended lag period. METHODS: Ninety-seven elderly individuals (>65 years) from the Taipei Basin participated from May to November 2020 and wore Garmin® smartwatches continuously until the end of 2021 for heart rate monitoring. RHR was defined as the daily average of the lowest 30-min heart rate. Air pollution exposure data, covering lag periods from 0 to 60 days, were obtained from nearby monitoring stations. We used distributed lag non-linear models and linear mixed-effect models to assess cumulative effects of air pollution. Principal component analysis was utilized to explore underlying patterns in air pollution exposure, and subgroup analyses with interaction terms were conducted to explore the modification effects of individual factors. RESULTS: After adjusting for co-pollutants in the models, an interquartile range increase of 0.18 ppm in carbon monoxide (CO) was consistently associated with increased RHR across lag periods of 0-1 day (0.31, 95 % confidence interval [CI]: 0.24-0.38), 0-7 days (0.68, 95 % CI: 0.57-0.79), and 0-50 days (1.02, 95 % CI: 0.82-1.21). Principal component analysis identified two factors, one primarily influenced by CO and nitrogen dioxide (NO2), indicative of traffic sources. Increases in the varimax-rotated traffic-related score were correlated with higher RHR over 0-1 day (0.36, 95 % CI: 0.25-0.47), 0-7 days (0.62, 95 % CI: 0.46-0.77), and 0-50 days (1.27, 95 % CI: 0.87-1.67) lag periods. Over a 0-7 day lag, RHR responses to traffic pollution were intensified by higher temperatures (ß = 0.80 vs. 0.29; interaction p-value [P_int] = 0.011). Males (ß = 0.66 vs. 0.60; P_int < 0.0001), hypertensive individuals (ß = 0.85 vs. 0.45; P_int = 0.028), diabetics (ß = 0.96 vs. 0.52; P_int = 0.042), and those with lower physical activity (ß = 0.70 vs. 0.54; P_int < 0.0001) also exhibited stronger responses. Over a 0-50 day lag, males (ß = 0.99 vs. 0.96; P_int < 0.0001), diabetics (ß = 1.66 vs. 0.69; P_int < 0.0001), individuals with lower physical activity (ß = 1.49 vs. 0.47; P_int = 0.0006), and those with fewer steps on lag day 1 (ß = 1.17 vs. 0.71; P_int = 0.029) showed amplified responses. CONCLUSIONS: Prolonged exposure to traffic-related air pollution results in cumulative cardiovascular risks, persisting for up to 50 days. These effects are more pronounced on warmer days and in individuals with chronic conditions or inactive lifestyles.

Exploring the late maturation of an intrinsic episodic memory network: A resting-state fMRI study.

Previous research suggests that episodic memory relies on functional neural networks,which are present even in the absence of an explicit task. The regions that integrate.these networks and the developmental changes in intrinsic functional connectivity.remain elusive. In the present study, we outlined an intrinsic episodic memory network.(iEMN) based on a systematic selection of functional connectivity studies, and.inspected network differences in resting-state fMRI between adolescents (13-17 years.old) and adults (23-27 years old) from the publicly available NKI-Rockland Sample.Through a review of brain regions commonly associated with episodic memory.networks, we identified a potential iEMN composed by 14 bilateral ROIs, distributed.across temporal, frontal and parietal lobes. Within this network, we found an increase.in resting-state connectivity from adolescents to adults between the right temporal pole.and two regions in the right lateral prefrontal cortex. We argue that the coordination of.these brain regions, connecting areas of semantic processing and areas of controlled.retrieval, arises as an important feature towards the full maturation of the episodic.memory system. The findings add to evidence suggesting that adolescence is a key.period in memory development and highlights the role of intrinsic functional.connectivity in such development.

Distinct Longitudinal Changes in EEG Measures Reflecting Functional Network Disruption in ALS Cognitive Phenotypes.

Amyotrophic lateral sclerosis (ALS) is characterised primarily by motor system degeneration, with clinical evidence of cognitive and behavioural change in up to 50% of cases. We have shown previously that resting-state EEG captures dysfunction in motor and cognitive networks in ALS. However, the longitudinal development of these dysfunctional patterns, especially in networks linked with cognitive-behavioural functions, remains unclear. Longitudinal studies on non-motor changes in ALS are essential to further develop our understanding of disease progression, improve care and enhance the evaluation of new treatments. To address this gap, we examined 124 ALS individuals with 128-channel resting-state EEG recordings, categorised by cognitive impairment (ALSci, n = 25), behavioural impairment (ALSbi, n = 58), or non-impaired (ALSncbi, n = 53), with 12 participants meeting the criteria for both ALSci and ALSbi. Using linear mixed-effects models, we characterised the general and phenotype-specific longitudinal changes in brain network, and their association with cognitive performance, behaviour changes, fine motor symptoms, and survival. Our findings revealed a significant decline in [Formula: see text]-band spectral power over time in the temporal region along with increased [Formula: see text]-band power in the fronto-temporal region in the ALS group. ALSncbi participants showed widespread ß-band synchrony decrease, while ALSci participants exhibited increased co-modulation correlated with verbal fluency decline. Longitudinal network-level changes were specific of ALS subgroups and correlated with motor, cognitive, and behavioural decline, as well as with survival. Spectral EEG measures can longitudinally track abnormal network patterns, serving as a candidate stratification tool for clinical trials and personalised treatments in ALS.

Brain Functional Alterations in Patients With Benign Paroxysmal Positional Vertigo Demonstrate the Visual-Vestibular Interaction and Integration.

OBJECTIVE: This study aimed to analyze the features of resting-state functional magnetic resonance imaging (rs-fMRI) and clinical relevance in patients with benign paroxysmal positional vertigo (BPPV) that have undergone repositioning maneuvers. METHODS: A total of 38 patients with BPPV who have received repositioning maneuvers and 38 matched healthy controls (HCs) were enrolled in the present study from March 2018 to August 2021. Imaging analysis software was employed for functional image preprocessing and indicator calculation, mainly including the amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), percent amplitude of fluctuation (PerAF), and seed-based functional connectivity (FC). Statistical analysis of the various functional indicators in patients with BPPV and HCs was also conducted, and correlation analysis with clinical data was performed. RESULTS: Patients with BPPV displayed decrease in ALFF, fALFF, and PerAF values, mainly in the bilateral occipital lobes in comparison with HCs. Additionally, their ALFF and fALFF values in the proximal vermis region of the cerebellum increased relative to HCs. The PerAF values in the bilateral paracentral lobules, the right supplementary motor area (SMA), and the left precuneus decreased in patients with BPPV and were negatively correlated with dizziness visual analog scale (VAS) scores 1 week after repositioning (W1). In addition, in the left fusiform gyrus and lingual gyrus, the PerAF values show a negative correlation with dizziness handicap inventory (DHI) scores at initial visit (W0). Seed-based FC analysis using the seeds from differential clusters of fALFF, ALFF, and PerAF showed reductions between the left precuneus and bilateral occipital lobe, the left precuneus and left paracentral lobule, and within the occipital lobes among patients with BPPV. CONCLUSION: The spontaneous activity of certain brain regions in the bilateral occipital and frontoparietal lobes of patients with BPPV was reduced, whereas the activity in the cerebellar vermis was increased. Additionally, there were reductions in FC between the precuneus and occipital cortex or paracentral lobule, as well as within the occipital cortex. The functional alterations in these brain regions may be associated with the inhibitory interaction and functional integration of visual, vestibular, and sensorimotor systems. The functional alterations observed in the visual cortex and precuneus may represent adaptive responses associated with residual dizziness.

Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders.

Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM). A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.

A comparative study of interhemispheric functional connectivity in patients with basal ganglia ischemic stroke.

Background: Voxel-mirrored homotopic connectivity (VMHC) is utilized to assess the functional connectivity of neural networks by quantifying the similarity between corresponding regions in the bilateral hemispheres of the brain. The exploration of VMHC abnormalities in basal ganglia ischemic stroke (BGIS) patients across different cerebral hemispheres has been limited. This study seeks to establish a foundation for understanding the functional connectivity status of both brain hemispheres in BGIS patients through the utilization of VMHC analysis utilizing resting-state functional magnetic resonance imaging (rs-fMRI). Methods: This study examined a total of 38 patients with left basal ganglia ischemic stroke (LBGIS), 44 patients with right basal ganglia ischemic stroke (RBGIS), and 41 individuals in a healthy control (HC) group. Rs-fMRI studies were performed on these patients, and the pre-processed rs-fMRI data were analyzed using VMHC method. Subsequently, the VMHC values were compared between three groups using a one-way ANOVA and post hoc analysis. Correlation analysis with clinical scales was also conducted. Results: The results indicated that compared to the HC group, significant differences were detected in postcentral gyrus, extending to precentral gyrus in both BGIS groups. Post hoc analysis showed that in the pairwise ROI-based comparison, individuals with LBGIS and RBGIS exhibited reduced VMHC values compared to HC groups. There was no significant difference between the LBGIS and RBGIS groups. In the LBGIS group, the VMHC value showed a negative correlation with NIHSS and a positive correlation with BI. Conclusion: The analysis of VMHC in rs-fMRI revealed a pattern of brain functional remodeling in patients with unilateral BGIS, marked by reduced synchronization and coordination between hemispheres. This may contribute to the understanding of the neurological mechanisms underlying motor dysfunction in these patients.

Exploring spontaneous brain activity changes in high-altitude smokers: Insights from ALFF/fALFF analysis.

INTRODUCTION: This study aims to explore the impact of smoking on intrinsic brain activity among high-altitude (HA) populations. Smoking is associated with various neural alterations, but it remains unclear whether smokers in HA environments exhibit specific neural characteristics. METHODS: We employed ALFF and fALFF methods across different frequency bands to investigate differences in brain functional activity between high-altitude smokers and non-smokers. 31 smokers and 31 non-smokers from HA regions participated, undergoing resting-state functional magnetic resonance imaging (rs-fMRI) scans. ALFF/fALFF values were compared between the two groups. Correlation analyses explored relationships between brain activity and clinical data. RESULTS: Smokers showed increased ALFF values in the right superior frontal gyrus (R-SFG), right middle frontal gyrus (R-MFG), right anterior cingulate cortex (R-ACC), right inferior frontal gyrus (R-IFG), right superior/medial frontal gyrus (R-MSFG), and left SFG compared to non-smokers in HA. In sub-frequency bands (0.01-0.027 Hz and 0.027-0.073 Hz), smokers showed increased ALFF values in R-SFG, R-MFG, right middle cingulate cortex (R-MCC), R-MSFG, Right precentral gyrus and L-SFG while decreased fALFF values were noted in the right postcentral and precentral gyrus in the 0.01-0.027 Hz band. Negative correlations were found between ALFF values in the R-SFG and smoking years. CONCLUSION: Our study reveals the neural characteristics of smokers in high-altitude environments, highlighting the potential impact of smoking on brain function. These results provide new insights into the neural mechanisms of high-altitude smoking addiction and may inform the development of relevant intervention measures.

Intrinsic functional networks for distinct sources of error in visual working memory.

Visual working memory (VWM) is a core cognitive function wherein visual information is stored and manipulated over short periods. Response errors in VWM tasks arise from the imprecise memory of target items, swaps between targets and nontargets, and random guesses. However, it remains unclear whether these types of errors are underpinned by distinct neural networks. To answer this question, we recruited 80 healthy adults to perform delayed estimation tasks and acquired their resting-state functional magnetic resonance imaging scans. The tasks required participants to reproduce the memorized visual feature along continuous scales, which, combined with mixture distribution modeling, allowed us to estimate the measures of memory precision, swap errors, and random guesses. Intrinsic functional connectivity within and between different networks, identified using a hierarchical clustering approach, was estimated for each participant. Our analyses revealed that higher memory precision was associated with increased connectivity within a frontal-opercular network, as well as between the dorsal attention network and an angular-gyrus-cerebellar network. We also found that coupling between the frontoparietal control network and the cingulo-opercular network contributes to both memory precision and random guesses. Our findings demonstrate that distinct sources of variability in VWM performance are underpinned by different yet partially overlapping intrinsic functional networks.

Neuroimaging studies of resting-state functional magnetic resonance imaging in eating disorders.

Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), binge-eating disorder (BED), and pica, are psychobehavioral conditions characterized by abnormal eating behaviors and an excessive preoccupation with weight and body shape. This review examines changes in brain regions and functional connectivity in ED patients over the past decade (2013-2023) using resting-state functional magnetic resonance imaging (rs-fMRI). Key findings highlight alterations in brain networks such as the default mode network (DMN), central executive network (CEN), and emotion regulation network (ERN). In individuals with AN, there is reduced functional connectivity in areas associated with facial information processing and social cognition, alongside increased connectivity in regions linked to sensory stimulation, aesthetic judgment, and social anxiety. Conversely, BED patients show diminished connectivity in the dorsal anterior cingulate cortex within the salience network and increased connectivity in the posterior cingulate cortex and medial prefrontal cortex within the DMN. These findings suggest that rs-fMRI could serve as a valuable biomarker for assessing brain function and predicting treatment outcomes in EDs, paving the way for personalized therapeutic strategies.

Resting state of human brain measured by fMRI experiment is governed more dominantly by essential mode as a global signal rather than default mode network.

Resting-state of the human brain has been described by a combination of various basis modes including the default mode network (DMN) identified by fMRI BOLD signals in human brains. Whether DMN is the most dominant representation of the resting-state has been under question. Here, we investigated the unexplored yet fundamental nature of the resting-state. In the absence of global signal regression for the analysis of brain-wide spatial activity pattern, the fMRI BOLD spatiotemporal signals during the rest were completely decomposed into time-invariant spatial-expression basis modes (SEBMs) and their time-evolution basis modes (TEBMs). Contrary to our conventional concept above, similarity clustering analysis of the SEBMs from 166 human brains revealed that the most dominant SEBM cluster is an asymmetric mode where the distribution of the sign of the components is skewed in one direction, for which we call essential mode (EM), whereas the second dominant SEBM cluster resembles the spatial pattern of DMN. Having removed the strong 1/f noise in the power spectrum of TEBMs, the genuine oscillatory behavior embedded in TEBMs of EM and DMN-like mode was uncovered around the low-frequency range below 0.2 Hz.

Abnormal resting-state functional connectivity of hippocampal subregions in type 2 diabetes mellitus-associated cognitive decline.

Objective: Type 2 diabetes mellitus (T2DM) over time predisposes to inflammatory responses and abnormalities in functional brain networks that damage learning, memory, or executive function. The hippocampus is a key region often reporting connectivity abnormalities in memory disorders. Here, we investigated peripheral inflammatory responses and resting-state functional connectivity (RSFC) changes characterized of hippocampal subregions in type 2 diabetes-associated cognitive decline (T2DACD). Methods: The study included 16 patients with T2DM, 16 patients with T2DACD and 25 healthy controls (HCs). Subjects were assessed for cognitive performance, tested for the expression of inflammatory factors IL-6, IL-10 and TNF-α in peripheral serum, underwent resting-state functional magnetic resonance imaging scans, and analyzed for RSFC using the hippocampal subregions as seeds. We also calculated the correlation between cognitive performance and RSFC of hippocampal subregion, and analyzed the significantly altered RSFC values of T2DACD for Receiver Operating Characteristic (ROC) analysis. Results: T2DACD patients showed a decline in their ability to complete cognitive assessment scales and experimental paradigms, and T2DM did not show abnormal cognitive performance. IL-6 expression was increased in peripheral serum in both T2DACD and T2DM. Compared with HCs, T2DACD showed abnormalities RSFC of the left anterior hippocampus with left precentral gyrus and left angular gyrus. T2DM showed abnormalities RSFC of the left middle hippocampus with right medial frontal gyrus, right anterior and middle hippocampus with left precuneus, left anterior hippocampus with right precuneus and right posterior middle temporal gyrus. Compared with T2DM, T2DACD showed abnormalities RSFC of the left posterior hippocampus and right middle hippocampus with left precuneus. In addition, RSFC in the left posterior hippocampus with left precuneus of T2DACD was positively correlated with Flanker conflict response time (r=0.766, P=0.001). In the ROC analysis, the significantly altered RSFC values of T2DACD achieved significant performance. Conclusions: T2DACD showed a significant decrease in attentional inhibition and working memory, peripheral pro-inflammatory response increased, and abnormalities RSFC of the hippocampal subregions with default mode network and sensory-motor network. T2DM did not show a significant cognitive decline, but peripheral pro-inflammatory response increased and abnormalities RSFC of the hippocampus subregions occurred in the brain. In addition, the left precuneus may be a key brain region in the conversion of T2DM to T2DACD. The results of this study may provide a basis for the preliminary diagnosis of T2DACD.

Comparing different motion correction approaches for resting-state functional connectivity analysis with functional near-infrared spectroscopy data.

Significance: Motion artifacts are a notorious challenge in the functional near-infrared spectroscopy (fNIRS) field. However, little is known about how to deal with them in resting-state data. Aim: We assessed the impact of motion artifact correction approaches on assessing functional connectivity, using semi-simulated datasets with different percentages and types of motion artifact contamination. Approach: Thirty-five healthy adults underwent a 15-min resting-state acquisition. Semi-simulated datasets were generated by adding spike-like and/or baseline-shift motion artifacts to the real dataset. Fifteen pipelines, employing various correction approaches, were applied to each dataset, and the group correlation matrix was computed. Three metrics were used to test the performance of each approach. Results: When motion artifact contamination was low, various correction approaches were effective. However, with increased contamination, only a few pipelines were reliable. For datasets mostly free of baseline-shift artifacts, discarding contaminated frames after pre-processing was optimal. Conversely, when both spike and baseline-shift artifacts were present, discarding contaminated frames before pre-processing yielded the best results. Conclusions: This study emphasizes the need for customized motion correction approaches as the effectiveness varies with the specific type and amount of motion artifacts present.

Divergent pattern of functional connectivity within the dorsal attention network differentiates schizophrenia and bipolar disorder patients.

Introduction: Schizophrenia (SZ) and bipolar disorder (BD) share common clinical features, symptoms, and neurocognitive deficits, which results in common misdiagnosis. Recently, it has been suggested that alterations within brain networks associated with perceptual organization yield potential to distinguish SZ and BD individuals. The aim of our study was to evaluate whether functional connectivity (FC) of the dorsal attention network (DAN) may differentiate both conditions. Methods: The study involved 90 participants: 30 remitted SZ patients, 30 euthymic BD patients, and 30 healthy controls (HC). Resting state functional magnetic resonance imaging was used to compare the groups in terms of the FC within the core nodes of the DAN involving frontal eye fields (FEF) and intraparietal sulcus (IPS). Results: BD patients presented weaker inter-hemispheric FC between right and left FEF than HC. While SZ did not differ from HC in terms of inter-FEF connectivity, they presented increased inter- and intra-hemispheric FC between FEF and IPS. When compared with BD, SZ patients showed increased FC between right FEF and other nodes of the network (bilateral IPS and left FEF). Conclusion: We have shown that altered resting state FC within DAN differentiates BD, SZ, and HC groups. Divergent pattern of FC within DAN, consisting of hypoconnectivity in BD and hyperconnectivity in SZ, might yield a candidate biomarker for differential diagnosis between both conditions. More highly powered studies are needed to confirm these possibilities.

Risk Factors Associated With Exaggerated Blood Pressure Response At The Time Of Exercise Treadmill Stress Test.

BACKGROUND: Exaggerated blood pressure response (EBPR) to exercise stress testing (EST) may be a marker of future hypertension and carry valuable information for the prediction of cardiovascular events. We sought to evaluate the clinical and resting EST parameters associated with increased likelihood to EBPR. METHODS: The records of 14073 patients (mean age: 55±11 years) without known cardiovascular disease who underwent a treadmill EST were analysed. RESULTS: The overall prevalence of arterial hypertension was 44%. A considerable proportion (24%) of patients exhibited EBPR. Multivariate analysis of the entire study population showed that middle-aged individuals (40-60 years old), resting systolic BP>130mmHg and/or diastolic BP>80 mmHg, known arterial hypertension, current cigarette smoking and family history of premature coronary artery disease are all independent risk factors for EBPR (all P<0.001). Although the presence of arterial hypertension increased the likelihood of EBPR in the analysis of the entire population, the relevant association in subjects above 60 years old is statistically non-significant (P=0.120). Notably, the pre-test systolic BP>130mmHg and/or diastolic BP>80 mmHg level increased significantly the likelihood to manifest EBPR in all age categories (<40, 40-60 and >60 years old) independent of hypertension presence and in all hypertensive patients independently of antihypertension treatment intake (all P<0.001). CONCLUSIONS: Considering the diagnostic and prognostic utility of EBPR during treadmill EST the clinical and resting haemodynamic parameters that increase the likelihood to EBPR are targets for interventions and preventive measures to modify lifestyle risk behaviours and reduce hypertension and cardiovascular risk factors in the early stages.

Mapping the Evidence for Measuring Energy Expenditure and Indicating Hypermetabolism in Motor Neuron Disease: A Scoping Review.

OBJECTIVE: To map the international methods used to measure energy expenditure of adults living with motor neuron disease (MND) and to highlight discrepancies when indicating hypermetabolism in the MND literature. BACKGROUND: A decline in the nutritional status of patients is associated with exacerbated weight loss and shortened survival. Assessments of energy expenditure, using a variety of methods, are important to ensure an adequate energy intake to prevent malnutrition-associated weight loss. Assessments of energy expenditure are also commonly used to indicate hypermetabolism in MND, although these approaches may not be optimal. METHODS: A protocol based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses extension for Scoping Reviews Guidelines was developed. Three electronic databases (Medline [Ovid], CINAHL [EBSCO], and Web of Science) were exhaustively searched. Identified publications were systematically screened according to predefined PICOS eligibility criteria. The primary outcome was the identification of methods used to measure energy expenditure in MND. The secondary outcome was the identification of applications of energy expenditure assessments to indicate hypermetabolism in MND. RESULTS: Thirty-two observational primary research publications were identified. Thirteen (40.6%) were longitudinal in design, with data on repeated measurements of energy expenditure presented in 3 (9.4%). Thirteen (40.6%) were case-control studies, of which 11 use a matched control group. Pulmonary function was used to assess eligibility in 10 publications. Energy expenditure was measured using indirect calorimetry (IC) in 31 studies. Discrepancies in the durations of fasted, measurement, and washout periods were observed. Of all included publications, 50% used assessments of resting energy expenditure to identify hypermetabolism. Bioelectrical impedance analysis was used to assess body composition alongside energy expenditure in 93.8% of publications. CONCLUSIONS: Resting energy expenditure is most frequently measured using an open-circuit IC system. However, there is a lack of a standardized, validated protocol for the conduct and reporting of IC and metabolic status in patients with MND.

Salience network segregation mediates the effect of tau pathology on mild behavioral impairment.

INTRODUCTION: A recently developed mild behavioral impairment (MBI) diagnostic framework standardizes the early characterization of neuropsychiatric symptoms in older adults. However, the joint contributions of Alzheimer's disease (AD) pathology and brain function to MBI remain unclear. METHODS: We test a novel model assessing direct relationships between AD biomarker status and MBI symptoms, as well as mediated effects through segregation of the salience and default-mode networks, using data from 128 participants with diagnosis of amnestic mild cognitive impairment or mild dementia-AD type. RESULTS: We identified a mediated effect of tau positivity on MBI through functional segregation of the salience network from the other high-level, association networks. There were no direct effects of AD biomarkers status on MBI. DISCUSSION: Our findings suggest that tau pathology contributes to MBI primarily by disrupting salience network function and emphasize the role of the salience network in mediating relationships between neuropathological changes and behavioral manifestations. HIGHLIGHTS: Network segregation mediates Alzheimer's disease (AD) pathology impact on mild behavioral impairment (MBI). The salience network is pivotal in linking tau pathology and MBI. This study used path analysis with AD biomarkers and network integrity. The study evaluated the roles of salience, default mode, and frontoparietal networks. This is the first study to integrate MBI with AD biomarkers and network functionality.

The neural plasticity and efficacy of acupuncture for post-stroke dysphagia: protocol for a randomized controlled trial with fMRI and DTI.

BACKGROUND: Dysphagia, a common complication of acute stroke, is associated with increased mortality and morbidity. Acupuncture, a widely used swallowing therapy in China, has been suggested as an effective therapy for treating Post-Stroke Dysphagia (PSD) by recent meta-analyses and guidelines. The use of resting-state functional Magnetic Resonance Imaging (rs-fMRI) and Diffusion Tensor Imaging (DTI) could explore the change of regional spontaneous neural activity, functional relationships between brain regions, and white matter connectivity patterns after acupuncture intervention for PSD. This trial aims to evaluate the efficacy of acupuncture treatment for PSD and explore its central mechanism by neuroimaging. METHODS/DESIGN: This randomized controlled trial will recruit 40 PSD patients. All patients will be randomized to either the Real Acupuncture (RA) or Sham Acupuncture (SA) group by a ratio of 1:1. All patients will receive immediate acupuncture treatment in the MRI scanning room, followed by four weeks of long-term acupuncture treatment. The primary outcomes are the rs-fMRI and DTI indicators, which will be evaluated after the immediate and long-term acupuncture treatment. The secondary outcomes are the scales that assess the efficacy, including the Functional Oral Intake Scale (FOIS), Water Swallowing Test (WST), Swallowing Quality Of Life Questionnaire (SWAL-QOL), and National Institute of Health Stroke Scale (NIHSS). The modified version of the Massachusetts General Hospital Acupuncture Sensation Scale (M-MASS) and fMRI sensation record table will also be evaluated. DISCUSSION: This protocol presents the design of a randomized, single-blind trial that will evaluate the efficacy and explore the neural plasticity of acupuncture treatment for PSD. This trial will deepen our insight into the clinical value of acupuncture for PSD and initially probe into the time-dosage-effect mechanism of acupuncture. TRIAL REGISTRATION NUMBERS: Chinese Clinical Trial Registry ( www.chictr.org.cn ) ChiCTR2300067480. This study was registered on 9th January 2023.

Mapping brain activity and neurotransmitters pre-cigarette smoking evolution: A study of male subjects.

BACKGROUND: The impact of tobacco smoking on global health persists and it is essential to understand the progression of addiction and the involvement of neurotransmitters. METHODS: This study assessed 47 participants with tobacco use disorder (TUD) categorized based on changes in Fagerström Test for Nicotine Dependence (FTND) scores over 6 years: progressive TUD (pTUD), regressive TUD (rTUD), and stable TUD (sTUD). Additionally, 35 healthy controls were included. Resting-state functional magnetic resonance imaging was used to evaluate brain regional homogeneity (ReHo) and correlations with neurotransmitter distributions using JuSpace. RESULTS: Significant differences in ReHo were observed among pTUD, rTUD, sTUD, and controls. After strict Bonferroni correction, rTUD exhibited increased ReHo in the dorsolateral superior frontal gyrus compared to sTUD (p < 0.001) and controls (p < 0.001). Both pTUD (p < 0.001) and rTUD (p < 0.001) showed decreased ReHo in the superior temporal gyrus compared to sTUD. sTUD had increased ReHo in the supramarginal gyrus compared to all other groups (p < 0.001, p < 0.001, p = 0.002, separately). The strongest association, which survived rigorous Bonferroni correction, was between the ReHo changes in rTUD compared to sTUD and neurotransmitter distribution. This includes 5-hydroxytryptamine receptor 2A (p = 0.001), gamma-aminobutyric acid type A receptor (p < 0.001), norepinephrine transporter (p < 0.001), and N-Methyl-D-Aspartate (p = 0.002). CONCLUSIONS: This study provides insights into how smoking behaviors correlate with alterations in brain activity and neurotransmitter function. By elucidating these neural links to tobacco use disorder progression, our findings contribute to a deeper understanding of smoking's neurological impact and potentially inform more targeted therapeutic strategies.