Dynamic functional network connectivity in patients with a mismatch between white matter hyperintensity and cognitive function.

Objective: White matter hyperintensity (WMH) in patients with cerebral small vessel disease (CSVD) is strongly associated with cognitive impairment. However, the severity of WMH does not coincide fully with cognitive impairment. This study aims to explore the differences in the dynamic functional network connectivity (dFNC) of WMH with cognitively matched and mismatched patients, to better understand the underlying mechanisms from a quantitative perspective. Methods: The resting-state functional magnetic resonance imaging (rs-fMRI) and cognitive function scale assessment of the patients were acquired. Preprocessing of the rs-fMRI data was performed, and this was followed by dFNC analysis to obtain the dFNC metrics. Compared the dFNC and dFNC metrics within different states between mismatch and match group, we analyzed the correlation between dFNC metrics and cognitive function. Finally, to analyze the reasons for the differences between the mismatch and match groups, the CSVD imaging features of each patient were quantified with the assistance of the uAI Discover system. Results: The 149 CSVD patients included 20 cases of "Type I mismatch," 51 cases of Type I match, 38 cases of "Type II mismatch," and 40 cases of "Type II match." Using dFNC analysis, we found that the fraction time (FT) and mean dwell time (MDT) of State 2 differed significantly between "Type I match" and "Type I mismatch"; the FT of States 1 and 4 differed significantly between "Type II match" and "Type II mismatch." Correlation analysis revealed that dFNC metrics in CSVD patients correlated with executive function and information processing speed among the various cognitive functions. Through quantitative analysis, we found that the number of perivascular spaces and bilateral medial temporal lobe atrophy (MTA) scores differed significantly between "Type I match" and "Type I mismatch," while the left MTA score differed between "Type II match" and "Type II mismatch." Conclusion: Different mechanisms were implicated in these two types of mismatch: Type I affected higher-order networks, and may be related to the number of perivascular spaces and brain atrophy, whereas Type II affected the primary networks, and may be related to brain atrophy and the years of education.

Abnormal Functional Attributes of Central Executive Network in Patients with Mild Cognitive Impairment Associated with End-Stage Renal Disease.

RATIONALE AND OBJECTIVES: To assess changes in the central executive network (CEN) of patients with mild cognitive impairment (MCI) associated with end-stage renal disease (ESRD). METHODS: A total of 121 patients with ESRD and 66 healthy controls (HCs) were enrolled. Patients were divided into an MCI group (n = 67) and a cognitively unimpaired group (n = 54). All participants underwent resting-state functional magnetic resonance imaging and were evaluated using the Montreal Cognitive Assessment (MoCA). The functional attributes of the CEN were calculated using three methods of functional connectivity (FC) analysis. Relationships among imaging features, cognitive scale scores, and clinical data were assessed, and a model was constructed to diagnose MCI in patients with ESRD. RESULTS: The comparison of the three groups showed that there were significant differences in the FC values of five connection pairs within the CEN, and the CEN demonstrated significant differences in connectivity to ten brain regions. In patients with MCI associated with ESRD, the information transmission efficiency of the CEN was reduced, which demonstrates the characteristics of a random network to some extent. Significant correlations were observed among imaging parameters, cognitive scale scores, and clinical data. The diagnostic model constructed based on these results demonstrated excellent discrimination and calibration. CONCLUSION: Alterations in the function of the CEN provide relevant bases for revealing the neuropathological mechanism of MCI in patients with ESRD. The diagnostic model developed in this study may help to establish more reliable imaging markers for detecting early cognitive impairment in this patient population.

More widespread functionality of posterior language area in patients with brain tumors.

Damage to the posterior language area (PLA), or Wernicke's area causes cortical reorganization in the corresponding regions of the contralateral hemisphere. However, the details of reorganization within the ipsilateral hemisphere are not fully understood. In this context, direct electrical stimulation during awake surgery can provide valuable opportunities to investigate neuromodulation of the human brain in vivo, which is difficult through the non-invasive approaches. Thus, in this study, we aimed to investigate the characteristics of the cortical reorganization of the PLA within the ipsilateral hemisphere. Sixty-two patients with left hemispheric gliomas were divided into groups depending on whether the lesion extended to the PLA. All patients underwent direct cortical stimulation with a picture-naming task. We further performed functional connectivity analyses using resting-state functional magnetic resonance imaging (MRI) in a subset of patients and calculated betweenness centrality, an index of the network importance of brain areas. During direct cortical stimulation, the regions showing positive (impaired) responses in the non-PLA group were localized mainly in the posterior superior temporal gyrus (pSTG), whereas those in the PLA group were widely distributed from the pSTG to the posterior supramarginal gyrus (pSMG). Notably, the percentage of positive responses in the pSMG was significantly higher in the PLA group (47%) than in the non-PLA group (8%). In network analyses of functional connectivity, the pSMG was identified as a hub region with high betweenness centrality in both the groups. These findings suggest that the language area can spread beyond the PLA to the pSMG, a hub region, in patients with lesion progression to the pSTG. The change in the pattern of the language area may be a compensatory mechanism to maintain efficient brain networks.

Brain Responses Difference between Sexes for Strong Desire to Void: A Functional Magnetic Resonance Imaging Study in Adults Based on Graph Theory.

Background: The alternations of brain responses to a strong desire to void were unclear, and the gender differences under the strong desire to void remain controversial. The present study aims to identify the functional brain network's topologic property changes evoked by a strong desire to void in healthy male and female adults with synchronous urodynamics using a graph theory analysis. Methods: The bladders of eleven healthy males and eleven females were filled via a catheter using a specific infusion and withdrawal pattern. A resting-state functional magnetic resonance imaging (fMRI) was performed on the enrolled subjects, scanning under both the empty bladder and strong desire to void states. An automated anatomical labeling (AAL) atlas was used to identify the ninety cortical and subcortical regions. Pearson's correlation calculations were performed to establish a brain connection matrix. A paired t-test (p < 0.05) and Bonferroni correction were applied to identify the significant statistical differences in topological properties between the two states, including small-world network property parameters [gamma (γ) and lambda (λ)], characteristic path length (Lp), clustering coefficient (Cp), global efficiency (Eglob), local efficiency (Eloc), and regional nodal efficiency (Enodal). Results: The final data suggested that females and males had different brain response patterns to a strong desire to void, compared with an empty bladder state. Conclusions: More brain regions involving emotion, cognition, and social work were active in females, and males might obtain a better urinary continence via a compensatory mechanism.

Dynamic functional connectivity and gene expression correlates in temporal lobe epilepsy: insights from hidden markov models.

BACKGROUD: Temporal lobe epilepsy (TLE) is associated with abnormal dynamic functional connectivity patterns, but the dynamic changes in brain activity at each time point remain unclear, as does the potential molecular mechanisms associated with the dynamic temporal characteristics of TLE. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired for 84 TLE patients and 35 healthy controls (HCs). The data was then used to conduct HMM analysis on rs-fMRI data from TLE patients and an HC group in order to explore the intricate temporal dynamics of brain activity in TLE patients with cognitive impairment (TLE-CI). Additionally, we aim to examine the gene expression profiles associated with the dynamic modular characteristics in TLE patients using the Allen Human Brain Atlas (AHBA) database. RESULTS: Five HMM states were identified in this study. Compared with HCs, TLE and TLE-CI patients exhibited distinct changes in dynamics, including fractional occupancy, lifetimes, mean dwell time and switch rate. Furthermore, transition probability across HMM states were significantly different between TLE and TLE-CI patients (p < 0.05). The temporal reconfiguration of states in TLE and TLE-CI patients was associated with several brain networks (including the high-order default mode network (DMN), subcortical network (SCN), and cerebellum network (CN). Furthermore, a total of 1580 genes were revealed to be significantly associated with dynamic brain states of TLE, mainly enriched in neuronal signaling and synaptic function. CONCLUSIONS: This study provides new insights into characterizing dynamic neural activity in TLE. The brain network dynamics defined by HMM analysis may deepen our understanding of the neurobiological underpinnings of TLE and TLE-CI, indicating a linkage between neural configuration and gene expression in TLE.

The abnormalities of brain function in females with primary insomnia: a resting-state functional magnetic resonance imaging study.

Background: The neuropathologic mechanism of primary insomnia (PI) of females remains unclear. This study aims to investigate the features of amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) in females with PI using functional magnetic resonance imaging (fMRI), and then explore the abnormalities of functional connectivity (FC). Materials and methods: A total of 39 female PI patients and 31 female healthy controls (HC) were enrolled in the study. The sleep condition was assessed using the Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI), and their depressive symptom was evaluated using the Hamilton Depression Scale (HAMD-24). The rs-fMRI was once conducted for every subject. ReHo, ALFF, and ROI-based FC were used to analyze the changes of brain function. Results: ALFF values were increased in the Cerebelum_4_5_L, as well as decreased ALFF in the bilateral Frontal_Sup_Medial (SFGmed), Angular_L (ANG.L), Parietal_Inf_R (IPL.R), SupraMarginal_R (SMG.R), and Postcentral_R (PoCG.R). ReHo values were increased in the Temporal_Pole_Mid_R (TPOsup.R), as well as decreased ReHo in the Insula_R (INS.R), Frontal_Inf_Oper_R (ORBinf.R), Putamen_R (PUT.R), Rolandic_Oper_R (ROL.R), bilateral Cingulum_Post (PCG), bilateral Frontal_Sup_Medial (SFGmed), bilateral anterior cingulate and paracingulate gyri (ACG), and the bilateral precuneus (PCUN). Across the entire brain, there was a decline in the FC between Angular_R and Frontal_Sup_Medial_L. Conclusion: Alterations in brain regions of female patients with PI involved multiple functional networks, including the default mode network, the salience network, the central executive network, and the limbic network. Reduced coordination between functional networks may be an important mechanism for insomnia and may lead to reduced cognitive function and decision-making ability.

Exploring mechanisms of anhedonia in depression through neuroimaging and data-driven approaches.

BACKGROUND: Anhedonia is a core symptom of depression that is closely related to prognosis and treatment outcomes. However, accurate and efficient treatments for anhedonia are lacking, mandating a deeper understanding of the underlying mechanisms. METHODS: A total of 303 patients diagnosed with depression and anhedonia were assessed by the Snaith-Hamilton Pleasure Scale (SHAPS) and magnetic resonance imaging (MRI). The patients were categorized into a low-anhedonia group and a high-anhedonia group using the K-means algorithm. A data-driven approach was used to explore the differences in brain structure and function with different degrees of anhedonia based on MATLAB. A random forest model was used exploratorily to test the predictive ability of differences in brain structure and function on anhedonia in depression. RESULTS: Structural and functional differences were apparent in several brain regions of patients with depression and high-level anhedonia, including in the temporal lobe, paracingulate gyrus, superior frontal gyrus, inferior occipital gyrus, right insular gyrus, and superior parietal lobule. And changes in these brain regions were significantly correlated with scores of SHAPS. CONCLUSIONS: These brain regions may be useful as biomarkers that provide a more objective assessment of anhedonia in depression, laying the foundation for precision medicine in this treatment-resistant, relatively poor prognosis group.

Association of plasma metals with resting-state functional connectivity in ischemic stroke.

BACKGROUND: Metal exposure has long been considered a significant risk factor for ischemic stroke. However, existing data on the effects of metal exposure on brain function in ischemic stroke are limited. Therefore, this study aimed to explore the correlation between exposure to various metals and changes in resting-state functional connectivity (rs-FC) in ischemic stroke patients. METHODS: This study included 28 acute ischemic stroke patients with hemiplegia and 28 matched healthy controls (HCs). All participants underwent T1-weighted MRI and 3.0 T resting-state functional magnetic resonance imaging (fMRI). After MRI acquisition, the rs-FC between 137 cortical and subcortical regions was extracted and preprocessed. Plasma levels of 19 metals were measured using inductively coupled plasma mass spectrometry (ICP-MS). The Bayesian kernel machine regression (BKMR) model and the weighted quantile sum regression (WQS) model were used to assess the overall effect of metal mixture exposure. The severity of neurological deficits in each acute ischemic stroke patient was evaluated using the National Institutes of Health Stroke Scale (NIHSS). Additionally, the associations between exposure to various metals and modifications in brain functional connectivity were determined using Pearson or Spearman correlation analysis. RESULTS: Bilateral brain connectivity was significantly decreased compared to controls and was associated with neurological impairment in ischemic stroke. In patients with ischemic stroke, the plasma concentrations of Cr (p < 0.001), Cu (p = 0.004), As (p = 0.010), Cs (p = 0.046), Rb (p = 0.041), and Sb (p = 0.001) were significantly higher than those in the HCs, whereas the plasma Tl concentrations (p = 0.022) were significantly lower. The results of the BKMR and WQS models showed that combined exposure to metal mixtures was linked to a higher risk of ischemic stroke. Cr was positively correlated with the rs-FC between the left Rolandic_Oper and the left Supp_Motor_Area (r = 0.414, p = 0.029), while negatively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal (r = -0.398, p = 0.037). Cu was negatively correlated with the rs-FC between the left paracentral lobule and the left thalamus (r = -0.409, p = 0.031). Tl was positively correlated with the rs-FC between the right Parietal_Inf and the left supramarginal cortex (r = 0.590, p = 0.001). A negative correlation was observed between Cs and rs-FC between the right Cingulate_Mid and left Occipital_Sup (r = -0.429, p = 0.024). Sb was negatively correlated with the rs-FC between the left Parietal_Inf and the right SupraMarginal (r = -0.384, p = 0.044), the right Parietal_Inf and the left SupraMarginal (r = -0.583, p = 0.001), and the left SupraMarginal and the right SupraMarginal (r = -0.377, p = 0.048). CONCLUSION: Plasma levels of Cr, Cu, Tl, Cs, and Sb were associated with altered rs-FC in brain regions related to motor control, sensory integration, executive function, language processing, and emotional regulation in ischemic stroke patients with basal ganglia infarction.

Functional network reorganization after endovascular thrombectomy in patients with anterior circulation stroke.

BACKGROUND: Endovascular thrombectomy has been confirmed to be an effective therapy for acute ischemic stroke (AIS). However, how functional brain networks reorganize after restoration of blood supply in AIS patients, and whether the degree of reperfusion associates with functional network changes remains unclear. METHODS: Resting-state fMRI data were collected from 43 AIS patients with anterior circulation occlusion after thrombectomy and 37 healthy controls (HCs). Both static and dynamic functional connectivity (FC) within four advanced functional networks including dorsal attention network (DAN), ventral attention network (VAN), executive control network (ECN) and default mode network (DMN), were calculated and compared between post-thrombectomy patients and HCs, and between two subgroups of post-thrombectomy patients with different reperfusion conditions. RESULTS: As compared to HCs, patients showed significant differences in static FC of four functional networks, and in dynamic FC of DAN, ECN and DMN. Furthermore, patients with better reperfusion conditions exhibited increased static FC with precuneus, and altered dynamic FC within precuneus. Moreover, these alterations were associated with clinical assessments of stroke severity and functional recovery in post-thrombectomy patients. CONCLUSIONS: Collectively, these findings may provide the potential imaging markers for assessment of thrombectomy efficacy and help establish the specific rehabilitation treatments for post-thrombectomy patients.

Alterations of resting-state network dynamics in Alzheimer's disease based on leading eigenvector dynamics analysis.

Alzheimer's disease (AD) is a neurodegenerative disease, and mild cognitive impairment (MCI) is considered a transitional stage between healthy aging and dementia. Early detection of MCI can help slow down the progression of AD. At present, there are few studies exploring the characteristics of abnormal dynamic brain activity in AD. This article uses a method called Leading Eigenvector Dynamics Analysis (LEiDA) to study resting-state functional magnetic resonance imaging (rs-fMRI) data of AD, MCI, and cognitively normal (CN) participants. By identifying repetitive states of phase coherence, inter group differences in brain dynamic activity indicators are examined. And the neurobehavioral scales were used to assess the relationship between abnormal dynamic activities and cognitive function. The results showed that in the indicators of occurrence probability and lifetime, the globally synchronized state of the patient group decreased. The activity state of the limbic regions significantly detected the difference between AD and the other two groups. Compared to CN, AD and MCI have varying degrees of increase in default and visual regions activity states. In addition, in the analysis related to the cognitive scales, it was found that individuals with poorer cognitive abilities were less active in the globally synchronized state, and more active in limbic regions activity state and visual regions activity state. Taken together, these findings reveal abnormal dynamic activity of resting-state networks in patients with AD and MCI, provide new insights into the dynamic analysis of brain networks, and contribute to a deeper understanding of abnormal spatial dynamic patterns in AD patients.

The functional and structural alterations in brain regions related to the fear network model in panic disorder: A resting-state fMRI and T1-weighted imaging study.

Abnormal functional connectivity (FC) within the fear network model (FNM) has been identified in panic disorder (PD) patients, but the specific local structural and functional properties, as well as effective connectivity (EC), remain poorly understood in PD. The purpose of this study was to investigate the structural and functional patterns of the FNM in PD. Magnetic resonance imaging data were collected from 33 PD patients and 35 healthy controls (HCs). Gray matter volume (GMV), degree centrality (DC), regional homogeneity (ReHo), and amplitude of low-frequency fluctuation (ALFF) were used to identify the structural and functional characteristics of brain regions within the FNM in PD. Subsequently, FC and EC of abnormal regions, based on local structural and functional features, and their correlation with clinical features were further examined. PD patients exhibited preserved GMV, ReHo, and ALFF in the brain regions of the FNM compared with HCs. However, increased DC in the bilateral amygdala was observed in PD patients. The amygdala and its subnuclei exhibited altered EC with rolandic operculum, insula, medial superior frontal gyrus, supramarginal gyrus, opercular part of inferior frontal gyrus, and superior temporal gyrus. Additionally, Hamilton Anxiety Scale score was positively correlated with EC from left lateral nuclei (dorsal portion) of amygdala to right rolandic operculum and left superior temporal gyrus. Our findings revealed a reorganized functional network in PD involving brain regions regulating exteroceptive-interoceptive signals, mood, and somatic symptoms. These results enhance our understanding of the neurobiological underpinnings of PD, suggesting potential biomarkers for diagnosis and targets for therapeutic intervention.

Adolescent maturation of cortical excitation-inhibition balance based on individualized biophysical network modeling.

The balance of excitation and inhibition is a key functional property of cortical microcircuits which changes through the lifespan. Adolescence is considered a crucial period for the maturation of excitation-inhibition balance. This has been primarily observed in animal studies, yet human in vivo evidence on adolescent maturation of the excitation-inhibition balance at the individual level is limited. Here, we developed an individualized in vivo marker of regional excitation-inhibition balance in human adolescents, estimated using large-scale simulations of biophysical network models fitted to resting-state functional magnetic resonance imaging data from two independent cross-sectional (N = 752) and longitudinal (N = 149) cohorts. We found a widespread relative increase of inhibition in association cortices paralleled by a relative age-related increase of excitation, or lack of change, in sensorimotor areas across both datasets. This developmental pattern co-aligned with multiscale markers of sensorimotor-association differentiation. The spatial pattern of excitation-inhibition development in adolescence was robust to inter-individual variability of structural connectomes and modeling configurations. Notably, we found that alternative simulation-based markers of excitation-inhibition balance show a variable sensitivity to maturational change. Taken together, our study highlights an increase of inhibition during adolescence in association areas using cross sectional and longitudinal data, and provides a robust computational framework to estimate microcircuit maturation in vivo at the individual level.

Elucidating trauma-related and disease-related regional cortical activity in post-traumatic stress disorder.

Trauma exposure may precipitate a cascade of plastic modifications within the intrinsic activity of brain regions, but it remains unclear which regions could be responsible for the development of post-traumatic stress disorder based on intrinsic activity. To elucidate trauma-related and post-traumatic stress disorder-related alterations in cortical intrinsic activity at the whole-brain level, we recruited 47 survivors diagnosed with post-traumatic stress disorder, 64 trauma-exposed controls from a major earthquake, and 46 age- and sex-matched healthy controls. All subjects were scanned with an echo-planar imaging sequence, and 5 parameters including the amplitude of low-frequency fluctuations, fractional amplitude of low-frequency fluctuations, regional homogeneity, degree centrality, and voxel-mirrored homotopic connectivity were calculated. We found both post-traumatic stress disorder patients and trauma-exposed controls exhibited decreased amplitude of low-frequency fluctuations in the bilateral posterior cerebellum and inferior temporal gyrus, decreased fractional amplitude of low-frequency fluctuation and regional homogeneity in the bilateral anterior cerebellum, and decreased fractional amplitude of low-frequency fluctuation in the middle occipital gyrus and cuneus compared to healthy controls, and these impairments were more severe in post-traumatic stress disorder patients than in trauma-exposed controls. Additionally, fractional amplitude of low-frequency fluctuation in left cerebellum was positively correlated with Clinician-Administered PTSD Scale scores in post-traumatic stress disorder patients. We identified brain regions that might be responsible for the emergence of post-traumatic stress disorder, providing important information for the treatment of this disorder.

Linked patterns of symptoms and cognitive covariation with functional brain controllability in major depressive disorder.

BACKGROUND: Controllability analysis is an approach developed for evaluating the ability of a brain region to modulate function in other regions, which has been found to be altered in major depressive disorder (MDD). Both depressive symptoms and cognitive impairments are prominent features of MDD, but the case-control differences of controllability between MDD and controls can not fully interpret the contribution of both clinical symptoms and cognition to brain controllability and linked patterns among them in MDD. METHODS: Sparse canonical correlation analysis was used to investigate the associations between resting-state functional brain controllability at the network level and clinical symptoms and cognition in 99 first-episode medication-naïve patients with MDD. FINDINGS: Average controllability was significantly correlated with clinical features. The average controllability of the dorsal attention network (DAN) and visual network had the highest correlations with clinical variables. Among clinical variables, depressed mood, suicidal ideation and behaviour, impaired work and activities, and gastrointestinal symptoms were significantly negatively associated with average controllability, and reduced cognitive flexibility was associated with reduced average controllability. INTERPRETATION: These findings highlight the importance of brain regions in modulating activity across brain networks in MDD, given their associations with symptoms and cognitive impairments observed in our study. Disrupted control of brain reconfiguration of DAN and visual network during their state transitions may represent a core brain mechanism for the behavioural impairments observed in MDD. FUNDING: National Natural Science Foundation of China (82001795 and 82027808), National Key R&D Program (2022YFC2009900), and Sichuan Science and Technology Program (2024NSFSC0653).

ADSC-derived exosomes provide neuroprotection in sepsis-associated encephalopathy by regulating hippocampal pyroptosis.

AIMS: Adipose-derived stem cell (ADSC)-derived exosomes have been recognized for their neuroprotective effects in various neurological diseases. This study investigates the potential neuroprotective effects of ADSC-derived exosomes in sepsis-associated encephalopathy (SAE). METHODS: Behavioral cognitive functions were evaluated using the open field test, Y-maze test, and novel object recognition test. Brain activity was assessed through functional magnetic resonance imaging (fMRI). Pyroptosis was measured using immunofluorescence staining and western blotting. RESULTS: Our findings indicate that ADSC-derived exosomes mitigate cognitive impairment, improve survival rates, and prevent weight loss in SAE mice. Additionally, exosomes protect hippocampal function in SAE mice, as demonstrated by fMRI evaluations. Furthermore, SAE mice exhibit neuronal damage and infiltration of inflammatory cells in the hippocampus, conditions which are reversed by exosome treatment. Moreover, our study highlights the downstream regulatory role of the NLRP3/caspase-1/GSDMD signaling pathway as a crucial mechanism in alleviating hippocampal inflammation. CONCLUSION: ADSC-derived exosomes confer neuroprotection in SAE models by mediating the NLRP3/caspase-1/GSDMD pathway, thereby ameliorating cognitive impairment.

Aberrant baseline brain activity and disrupted functional connectivity in patients with vascular cognitive impairment due to cerebral small vessel disease.

Objective: This study aims to examine the alterations in aberrant brain activity and network connectivity between individuals with mild and major vascular cognitive impairment (VCI). Materials and methods: A total of 114 patients with cerebral small vessel disease (CSVD) were included in this study, comprising 61 individuals with mild VCI (mean age, 55.7 ± 6.9 years; male, 42.6%) and 53 cases with major VCI (mean age, 57.6 ± 5.5 years; male, 58.5%). Additionally, 53 age-, gender-, and education-matched healthy subjects were recruited as normal controls (NC) (mean age, 54.9 ± 7.9 years; male, 52.9%). All participants underwent neuropsychological assessments and magnetic resonance imaging scans. One-way analysis of variance was used to compare fractional amplitude of low-frequency fluctuation (fALFF) values among the three groups. Two-sample t-tests were conducted to assess functional connectivity matrices between different groups for each connection. Moreover, mediation analyses were performed to explore the mediating effect of aberrant brain activity on the relationship between cognitive impairment and CSVD total burden. Results: VCI patients exhibited aberrant brain activity in regions such as the right thalamus (THA_R), right cuneus (CUN_R), left postcentral gyrus (PoCG_L), right postcentral gyrus (PoCG_R), right median cingulate, paracingulate gyri (PCG_R), and left precuneus (PCUN_L). Reduced positive functional connectivity was predominantly observed among nodes including PCUN_L, CUN_R, PoCG_L, PoCG_R, right posterior cingulate (PCG_R), and left occipital gyrus (IOG_L) in VCI patients. The aberrant baseline brain activity and disrupted brain network were more pronounced with worsening cognitive function. Increased fALFF values in THA_R, CUN_R, and PoCG_L mediated cognitive impairment in CSVD patients. Conclusion: Abnormal brain activities in THA_R, CUN_R, and PoCG_L, along with their associated abnormal functional connections, play a significant role in VCI. The study revealed a progressive increase in aberrant brain activity and network connectivity with advancing stages of VCI.

Short-term antipsychotic treatment reduces functional connectivity of the striatum in first-episode drug-naïve early-onset schizophrenia.

BACKGROUND: The striatum is thought to play a critical role in the pathophysiology and antipsychotic treatment of schizophrenia. Previous studies have revealed abnormal functional connectivity (FC) of the striatum in early-onset schizophrenia (EOS) patients. However, no prior studies have examined post-treatment changes of striatal FC in EOS patients. METHODS: We recruited 49 first-episode drug-naïve EOS patients to have resting-state functional magnetic resonance imaging scans at baseline and after 8 weeks of treatment with antipsychotics, along with baseline scanning of 34 healthy controls (HCs) for comparison purposes. We examined the FC values between each seed in striatal subregion and the rest of the brain. The Positive and Negative Syndrome Scale (PANSS) was applied to measure psychiatric symptoms in patients. RESULTS: Compared with HCs at baseline, EOS patients exhibited weaker FC of striatal subregions with several brain regions of the salience network and default mode network. Meanwhile, FC between the dorsal caudal putamen (DCP) and left supplementary motor area, as well as between the DCP and right postcentral gyrus, was negatively correlated with PANSS negative scores. Furthermore, after 8 weeks of treatment, EOS patients showed decreased FC between subregions of the putamen and the triangular part of inferior frontal gyrus, middle frontal gyrus, supramarginal gyrus and inferior parietal lobule. CONCLUSIONS: Decreased striatal FC is evident, even in the early stages of schizophrenia, and enhance our understanding of the neurodevelopmental abnormalities in schizophrenia. The findings also demonstrate that reduced striatal FC occurs after antipsychotic therapy, indicating that antipsychotic effects need to be accounted for when considering striatal FC abnormalities in schizophrenia.

Global, interhemispheric and intrahemispheric functional connection patterns in male adults with alcohol use disorder.

A growing body of evidence indicates the existence of abnormal local and long-range functional connection patterns in patients with alcohol use disorder (AUD). However, it has yet to be established whether AUD is associated with abnormal interhemispheric and intrahemispheric functional connection patterns. In the present study, we analysed resting-state functional magnetic resonance imaging data from 55 individuals with AUD and 32 healthy nonalcohol users. For each subject, whole-brain functional connectivity density (FCD) was decomposed into ipsilateral and contralateral parts. Correlation analysis was performed between abnormal FCD and a range of clinical measurements in the AUD group. Compared with healthy controls, the AUD group exhibited a reduced global FCD in the anterior and middle cingulate gyri, prefrontal cortex and thalamus, along with an enhanced global FCD in the temporal, parietal and occipital cortices. Abnormal interhemispheric and intrahemispheric FCD patterns were also detected in the AUD group. Furthermore, abnormal global, contralateral and ipsilateral FCD data were correlated with the mean amount of pure alcohol and the severity of alcohol addiction in the AUD group. Collectively, our findings indicate that global, interhemispheric and intrahemispheric FCD may represent a robust method to detect abnormal functional connection patterns in AUD; this may help us to identify the neural substrates and therapeutic targets of AUD.

Sex differences of signal complexity at resting-state functional magnetic resonance imaging and their associations with the estrogen-signaling pathway in the brain.

Sex differences in the brain have been widely reported and may hold the key to elucidating sex differences in many medical conditions and drug response. However, the molecular correlates of these sex differences in structural and functional brain measures in the human brain remain unclear. Herein, we used sample entropy (SampEn) to quantify the signal complexity of resting-state functional magnetic resonance imaging (rsfMRI) in a large neuroimaging cohort (N = 1,642). The frontoparietal control network and the cingulo-opercular network had high signal complexity while the cerebellar and sensory motor networks had low signal complexity in both men and women. Compared with those in male brains, we found greater signal complexity in all functional brain networks in female brains with the default mode network exhibiting the largest sex difference. Using the gene expression data in brain tissues, we identified genes that were significantly associated with sex differences in brain signal complexity. The significant genes were enriched in the gene sets that were differentially expressed between the brain cortex and other tissues, the estrogen-signaling pathway, and the biological function of neural plasticity. In particular, the G-protein-coupled estrogen receptor 1 gene in the estrogen-signaling pathway was expressed more in brain regions with greater sex differences in SampEn. In conclusion, greater complexity in female brains may reflect the interactions between sex hormone fluctuations and neuromodulation of estrogen in women. Supplementary Information: The online version contains supplementary material available at 10.1007/s11571-023-09954-y.

The multiscale topological organization of the functional brain network in adolescent PTSD.

The experience of an extremely aversive event can produce enduring deleterious behavioral, and neural consequences, among which posttraumatic stress disorder (PTSD) is a representative example. Although adolescence is a period of great exposure to potentially traumatic events, the effects of trauma during adolescence remain understudied in clinical neuroscience. In this exploratory work, we aim to study the whole-cortex functional organization of 14 adolescents with PTSD using a data-driven method tailored to our population of interest. To do so, we built on the network neuroscience framework and specifically on multilayer (multisubject) community analysis to study the functional connectivity of the brain. We show, across different topological scales (the number of communities composing the cortex), a hyper-colocalization between regions belonging to occipital and pericentral regions and hypo-colocalization in middle temporal, posterior-anterior medial, and frontal cortices in the adolescent PTSD group compared to a nontrauma exposed group of adolescents. These preliminary results raise the question of an altered large-scale cortical organization in adolescent PTSD, opening an interesting line of research for future investigations.