Most recent paper
A study of dynamic functional connectivity changes in flight trainees based on a triple network model
Sci Rep. 2025 Mar 6;15(1):7828. doi: 10.1038/s41598-025-89023-y.
ABSTRACT
The time-varying functional connectivity of the Central Executive Network (CEN), Default Mode Network (DMN), and Salience Network (SN) in flight trainees during a resting state was investigated using dynamic functional network connectivity (dFNC). The study included 39 flight trainees and 37 age- and sex-matched healthy controls. Resting-state fMRI data and behavioral test outcomes were obtained from both groups. Independent component analysis (ICA), sliding window, and K-means clustering approaches were utilized for evaluating functional network connectivity (FNC) and temporal metrics based on the triple networks. Correlation analyses were performed on the behavioral assessments and these metrics. The flight trainees demonstrated a significantly enhanced functional connection linking the CEN and DMN in state 2 (P < 0.05, FDR corrected). Additionally, flight trainees spent less time in state 5, while they exhibited a protracted mean dwell time and fractional windows in state 2, which were significantly correlated with accuracy on the Berg Card Sorting Test (BCST) and Change Detection Test (all P < 0.05). The improved connectivity of flight trainees between the CEN and DMN following the completion of rigorous flight training resulted in increased stability. This enhancement may be relevant to cognitive abilities such as decision-making, memory, and information integration. When multitasking, flight trainees displayed superior visual processing skills and enhanced cognitive flexibility. dFNC research provides a unique perspective on the sophisticated cognitive capabilities that are required in high-demand, high-stress occupations such as piloting, thereby providing significant insights into the intricate brain mechanisms that are inherent in these domains.
PMID:40050304 | DOI:10.1038/s41598-025-89023-y
The effects of intermittent theta burst stimulation (iTBS) on resting-state brain entropy (BEN)
Neurotherapeutics. 2025 Mar 5:e00556. doi: 10.1016/j.neurot.2025.e00556. Online ahead of print.
ABSTRACT
Intermittent theta burst stimulation (iTBS), a novel protocol within repetitive transcranial magnetic stimulation (rTMS), has shown superior therapeutic effects for depression compared to conventional high-frequency rTMS (HF-rTMS). However, the neural mechanisms underlying iTBS remain poorly understood. Brain entropy (BEN), a measure of the irregularity of brain activity, has recently emerged as a promising marker for regional brain function and has demonstrated sensitivity to depression and HF-rTMS. Given its potential, BEN may help elucidate the mechanisms of iTBS. In this study, we computed BEN using resting-state fMRI data from sixteen healthy participants obtained from OpenNeuro. Participants underwent iTBS over the left dorsolateral prefrontal cortex (L-DLPFC) at two different intensities (90 % and 120 % of resting motor threshold (rMT)) on separate days. We used a 2 × 2 repeated measures analysis of variance (ANOVA) to analyze the interaction between iTBS stimulation intensity and the pre- vs. post-stimulation effects on BEN and paired sample t-tests to examine the specific BEN effects of iTBS at different intensities. Additionally, spatial correlation analysis was conducted to determine whether iTBS altered the baseline coupling between BEN and neurotransmitter receptors/transporters, to investigate potential neurotransmitter changes induced by iTBS. Our results indicate that subthreshold iTBS (90 % rMT) reduced striatal BEN, while suprathreshold iTBS (120 % rMT) increased it. Subthreshold iTBS led to changes in the baseline coupling between BEN and several neurotransmitter receptor/transporter maps, primarily involving serotonin (5-HT), cannabinoid (CB), acetylcholine (ACh), and glutamate (Glu). Our findings suggest that BEN is sensitive to the effects of iTBS, with different stimulation intensities having distinct effects on neural activity. Notably, subthreshold iTBS may offer more effective stimulation. This research highlights the crucial role of stimulation intensity in modulating brain activity and lays the groundwork for future clinical studies focused on optimizing therapeutic outcomes through precise stimulation intensity.
PMID:40050146 | DOI:10.1016/j.neurot.2025.e00556
Effects of the KCNQ (Kv7) Channel Opener Ezogabine on Resting-State Functional Connectivity of Striatal Brain Reward Regions, Depression and Anhedonia in Major Depressive Disorder: Results from a Randomized Controlled Trial
Biol Psychiatry. 2025 Mar 4:S0006-3223(25)01011-X. doi: 10.1016/j.biopsych.2025.02.897. Online ahead of print.
ABSTRACT
BACKGROUND: Major depressive disorder (MDD) is a leading cause of disability worldwide, with available treatments often showing limited efficacy. Recent research suggests targeting specific subtypes of depression and understanding the underlying brain mechanisms can improve treatment outcomes. This study investigates the potential of the potassium KCNQ (Kv7) channel opener ezogabine to modulate the resting-state functional connectivity (RSFC) of the brain's reward circuitry and alleviate depressive symptoms, including anhedonia, a core feature of MDD.
METHODS: A double-blind, randomized, placebo-controlled clinical trial in individuals aged 18 to 65 with MDD compared daily dosing with ezogabine (n=19) to placebo (n=21) for five weeks. Functional magnetic resonance imaging (fMRI) assessed RSFC of the brain's key reward regions (ventral caudate, nucleus accumbens) at baseline and post-treatment. Clinical symptoms were measured using the Snaith-Hamilton Pleasure Scale (SHAPS), Montgomery-Åsberg Depression Rating Scale (MADRS), and other clinical symptom scales.
RESULTS: Ezogabine significantly reduced RSFC between the reward seeds and the posterior cingulate cortex (PCC)/precuneus compared to placebo, which was associated with a reduction in depression severity. Improvements in anhedonia (SHAPS) and depressive symptoms (MADRS) with ezogabine compared to placebo were also associated with decreased connectivity between the reward seeds and mid/posterior cingulate regions (MCC, PCC, precuneus).
CONCLUSIONS: The findings suggest that ezogabine's antidepressant effects are mediated through modulation of striatal-mid/posterior cingulate connectivity, indicating a potential therapeutic mechanism for KCNQ-targeted drugs for MDD and anhedonia. Future studies should validate these results in larger trials.
CLINICALTRIALS: gov identifier: NCT03043560.
PMID:40049579 | DOI:10.1016/j.biopsych.2025.02.897
Self-Organizing Dynamic Research Based on Phase Coherence Graph Autoencoders: Analysis of Brain Metastable States Across the Lifespan
Neuroimage. 2025 Mar 4:121119. doi: 10.1016/j.neuroimage.2025.121119. Online ahead of print.
ABSTRACT
The development of the human brain is a complex, lifelong process during which collective behaviors of neurons exhibit self-organizing dynamics. Metastable states play a crucial role in understanding the complex dynamical mechanisms of the brain, and analyzing them helps to reveal the mechanisms of functional changes in the brain throughout development and aging. Specifically, global metastable state provides a overall perspective on the flexibility of brain reorganization, while the evolution trajectories of transient functional patterns capture detailed changes in brain activity. The leading eigenvector dynamics analysis (LEiDA) method significantly reduces the dimensionality of data and is widely used to capture the temporal trajectory characteristics of transient functional patterns, i.e., metastable brain states. However, LEiDA's linear dimensionality reduction of high-dimensional raw brain data may overlook non-linear information and lose some relationships between features. We developed a framework based on Phase Coherence Graph Autoencoder (PCGAE) that employs graph autoencoders (GAE) for non-linear dimensionality reduction of phase coherence matrices. This approach clusters to identify more distinct metastable brain states and is applied to the analysis of resting-state functional magnetic resonance imaging (rs-fMRI) data across the human lifespan. This paper investigates age-related differences and continuity changes from different perspectives: metastable state indicators and state trajectory indicators (occurrence probability, lifetime, and state transition metrics). Global metastable state shows a linear decline with age, while both linear and quadratic effects of age-related changes are observed in detailed state metastable and state trajectory indicators. Finally, the proposed feature extraction scheme demonstrates good classification performance for categorizing brain age groups. These findings can help us understand the self-organizing reorganization characteristics associated with aging and their complex dynamic changes, providing new insights into brain development throughout the entire lifespan.
PMID:40049301 | DOI:10.1016/j.neuroimage.2025.121119
Centrality nearest-neighbor projected-distance regression (C-NPDR) feature selection for correlation-based predictors with application to resting-state fMRI study of major depressive disorder
PLoS One. 2025 Mar 6;20(3):e0319346. doi: 10.1371/journal.pone.0319346. eCollection 2025.
ABSTRACT
BACKGROUND: Nearest-neighbor projected-distance regression (NPDR) is a metric-based machine learning feature selection algorithm that uses distances between samples and projected differences between variables to identify variables or features that may interact to affect the prediction of complex outcomes. Typical tabular bioinformatics data consist of separate variables of interest, such as genes or proteins. In contrast, resting-state functional MRI (rs-fMRI) data are composed of time-series for brain regions of interest (ROIs) for each subject, and these within-brain time-series are typically transformed into correlations between pairs of ROIs. These pairs of variables of interest can then be used as inputs for feature selection or other machine learning methods. Straightforward feature selection would return the most significant pairs of ROIs; however, it would also be beneficial to know the importance of individual ROIs.
RESULTS: We extend NPDR to compute the importance of individual ROIs from correlation-based features. We introduce correlation-difference and centrality-based versions of NPDR. Centrality-based NPDR can be coupled with any centrality method and can be coupled with importance scores other than NPDR, such as random forest importance scores. We develop a new simulation method using random network theory to generate artificial correlation data predictors with variations in correlations that affect class prediction.
CONCLUSIONS: We compared feature selection methods based on detection of functional simulated ROIs, and we applied the new centrality NPDR approach to a resting-state fMRI study of major depressive disorder (MDD) participants and healthy controls. We determined that the areas of the brain that have the strongest network effect on MDD include the middle temporal gyrus, the inferior temporal gyrus, and the dorsal entorhinal cortex. The resulting feature selection and simulation approaches can be applied to other domains that use correlation-based features.
PMID:40048476 | DOI:10.1371/journal.pone.0319346
Alterations in brain function in patients with post-stroke cognitive impairment: a resting-state functional magnetic resonance imaging study
Front Aging Neurosci. 2025 Feb 19;17:1501082. doi: 10.3389/fnagi.2025.1501082. eCollection 2025.
ABSTRACT
BACKGROUND: Cognitive impairment is a common dysfunction following stroke, significantly affecting patients' quality of life. Studies suggest that post-stroke cognitive impairment (PSCI) may be related to neural activity in specific brain regions. However, the neural mechanisms remain to be further explored. This study aimed to investigate the alterations in brain function in patients with PSCI.
METHODS: This was a case-control study. Thirty patients with PSCI, thirty with non-PSCI (NPSCI), and thirty age- and gender-matched healthy controls (HCs) were selected in a 1:1:1 ratio. Resting-state functional magnetic resonance imaging (rs-fMRI) were acquired from all participants to study the potential neural mechanisms of PSCI patients by comparing the differences in fractional amplitude of low-frequency fluctuation (fALFF), Kendall's coefficient of concordance-regional homogeneity (KCC-ReHo), and seed-based functional connectivity (FC). Additionally, the Montreal Cognitive Assessment (MoCA) scores of PSCI patients were collected, and Pearson correlation was used to analyze the correlation between functional indicators and cognitive performance in PSCI patients.
RESULTS: fALFF analysis revealed that the PSCI group had decreased zfALFF values in the left caudate, right inferior temporal gyrus (ITG), anterior cingulate cortex (ACC), left putamen, and left superior temporal gyrus. In contrast, increased zfALFF values were observed in the right Cerebellum_6. KCC-ReHo analysis indicated that the PSCI group had decreased SzKCC-ReHo values in the right middle frontal gyrus (MFG) and left postcentral lobe, while increased SzKCC-ReHo values in the left cerebellum_ crus 1, and left cerebellum_4-5. Furthermore, seed-based FC analysis revealed decreased zFC values between brain regions in the PSCI group, especially between the angular gyrus and precuneus. Additionally, correlation analysis showed that the zfALFF value of ACC was positively correlated with MoCA scores in the PSCI group.
CONCLUSION: This study demonstrated significant changes in the spontaneous neural activity intensity, regional homogeneity, and FC of multiple cognition-related brain regions in PSCI patients, shedding light on the underlying neural mechanisms of brain function in PSCI.
PMID:40046780 | PMC:PMC11880027 | DOI:10.3389/fnagi.2025.1501082
Comparison of the social gene expression network and social brain network: a resting-state functional magnetic resonance imaging study
Brain Imaging Behav. 2025 Mar 6. doi: 10.1007/s11682-025-00993-z. Online ahead of print.
ABSTRACT
Numerous previous studies have classified brain regions related to social processing into the "social brain" regions. Recent genetic studies showed that gene expression has a crucial effect on both brain functions and behavioral social performance. However, studies still lack a clear understanding of the organization of the social gene expression (SocGene) network. This study aimed to distinguish the difference between the SocGene network and the social brain network (SBN) and further explored their deficits in schizophrenia (SCZ) patients. The SocGene network was constructed by generating the gene expression maps of six social neuropeptide receptors from the Allen Human Brain Atlas. Then, we recruited a general population sample of 37 participants and a clinical sample including 26 SCZ and 25 Healthy controls (HCs) successively to construct the resting-state SocGene and SBN at the individual level. The integration (global efficiency, GE) and segregation (local efficiency, LE) of these brain networks were calculated using the graphic analysis. Results showed that the GE and LE of the SocGene network were significantly higher than those of the SBN in both two cohorts. The SCZ patients showed significantly diminished LE of the two brain networks compared to HCs, especially in the SocGene network. These findings implied that the SocGene network strengthened the integration and segregation compared to the SBN. SCZ patients mainly exhibited deficits in the segregation of these two brain networks. The current findings provide a new perspective on combining genetic expression and brain function in understanding the psychopathology of social functioning.
PMID:40045109 | DOI:10.1007/s11682-025-00993-z
A brief review of MRI studies in patients with attention-deficit/hyperactivity disorder and future perspectives
Brain Dev. 2025 Mar 4;47(2):104340. doi: 10.1016/j.braindev.2025.104340. Online ahead of print.
ABSTRACT
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by persistent inattention, hyperactivity, and/or impulsivity that significantly affects academic, occupational, and social functioning. This review summarizes key findings of structural and functional magnetic resonance imaging (MRI) studies investigating the neural underpinnings of ADHD, focusing on T1-weighted structural MRI, diffusion tensor imaging (DTI), task-based functional MRI (task fMRI), and resting-state functional MRI (rs-fMRI). T1-weighted structural MRI studies have revealed reduced gray matter volume in regions implicated in executive function, particularly the frontal cortex, basal ganglia, and cerebellum, along with evidence of delayed cortical maturation. DTI findings highlighted abnormalities in white matter integrity, particularly in the fronto-striatal-cerebellar circuits and connections between the corpus callosum and cingulum. Task fMRI studies have demonstrated reduced activation of brain networks involved in cognitive control, timing, and reward processing, including fronto-striatal and fronto-parietal networks. Furthermore, rs-fMRI research has shown altered connectivity patterns within and between key brain networks, including the default mode, fronto-parietal, and salience networks. Despite these insights, inconsistencies across studies underscore the need for larger and more standardized research efforts. Future research should employ multimodal imaging techniques and advanced analytical methods such as machine learning to better subtype ADHD and customize interventions. Moreover, establishing harmonized imaging protocols across institutions, as exemplified by innovative strategies, such as the traveling-subject method, is crucial for mitigating intersite variability. Through collaborative efforts, neuroimaging studies in ADHD are anticipated to enhance our understanding of the disorder's heterogeneity while informing the development of precise clinical diagnoses and personalized therapeutic interventions.
PMID:40043540 | DOI:10.1016/j.braindev.2025.104340
The neuroprotective power of artificial liver therapy: reversing cognitive impairment in minimal hepatic encephalopathy
Brain Imaging Behav. 2025 Mar 5. doi: 10.1007/s11682-024-00947-x. Online ahead of print.
ABSTRACT
Alteration of functional connectivity in brain regions is one of the potential neuropathological mechanisms underlying cognitive impairment in patients with minimal hepatic encephalopathy (MHE). Artificial liver therapy has been shown to improve cognitive impairment in patients, suggesting a potential neuroprotective effect on the brain. This study investigates the impact of artificial liver therapy (AL) on cognitive impairment in patients with minimal hepatic encephalopathy (MHE) by examining alterations in brain functional connectivity. Resting-state functional magnetic resonance imaging (fMRI) data was collected from healthy controls and MHE patients before and after therapy. The MHEpost-AL group showed improved memory, reaction time, and executive function compared to the MHEpre-AL group. Functional connectivity analysis revealed increased connectivity in specific brain regions in the MHEpre-AL group compared to healthy controls, with subsequent decreased connectivity after therapy. Lower MoCA scores, higher blood ammonia levels, and lower cholinesterase levels were associated with higher functional connectivity in the MHEpre-AL group. The study suggests that artificial liver therapy improves cognitive impairment in MHE patients, with changes in blood biochemistry mediating the link between functional connectivity and cognitive function. Correcting blood biochemistry levels may reverse abnormal brain connectivity and enhance cognitive function in MHE patients.
PMID:40042700 | DOI:10.1007/s11682-024-00947-x
The Relations Among Anxiety, Movie-Watching, and in-Scanner Motion
Hum Brain Mapp. 2025 Mar;46(4):e70163. doi: 10.1002/hbm.70163.
ABSTRACT
Movie-watching fMRI has emerged as a theoretically viable platform for studying neurobiological substrates of affective states and emotional disorders such as pathological anxiety. However, using anxiety-inducing movie clips to probe relevant states impacted by psychopathology could risk exacerbating in-scanner movement, decreasing signal quality/quantity and thus statistical power. This could be especially problematic in target populations such as children who typically move more in the scanner. Consequently, we assessed: (1) the extent to which an anxiety-inducing movie clip altered in-scanner data quality (movement, censoring, and DVARS) in a pediatric sample with and without anxiety disorders (n = 78); and (2) investigated interactions between anxiety symptoms and movie-attenuated motion in a highly powered, transdiagnostic pediatric sample (n = 2058). Our results suggest anxiogenic movie-watching in fact reduces in-scanner movement compared to resting-state, increasing the quantity/quality of data. In one measure, pathological anxiety appeared to impact movie-attenuated motion, but the effect was small. Given potential boosts to data quality, future developmental neuroimaging studies of anxiety may benefit from the use of movie paradigms.
PMID:40042099 | DOI:10.1002/hbm.70163
Dynamic Temporal Alterations of the Cerebellum in Parkinson's Disease With Different Dominant-Affected Sides
J Neurosci Res. 2025 Mar;103(3):e70029. doi: 10.1002/jnr.70029.
ABSTRACT
Laterality of motor deficits is a hallmark of Parkinson's disease (PD), which is strongly correlated with disease progression. The cerebellum is an important node in the motor-related network in PD. However, the role of the cerebellum in PD lateralization remains unclear. This study enrolled 48 left-dominant-affected PD patients (LPD), 60 right-dominant-affected PD patients (RPD) and 92 age- and sex-matched healthy controls (HCs). We utilized dynamic functional connectivity and co-activation pattern analysis to investigate dynamic alterations of the cerebellum between PD patients and HCs by resting-state fMRI. Pearson partial correlation was used to measure brain-clinical correlations. We revealed two states and five co-activation patterns during the scans. Compared to HCs and RPD, LPD patients more frequently displayed State II and persisted in this state for a more extended period. The mean dwell time (MDT) in State II rose from HCs to RPD and to LPD. The MDT in State II was positively correlated with sleep disturbance in LPD patients. Regarding co-activation patterns (CAPs), LPD and RPD patients were less likely to exhibit CAP2. LPD patients were less likely to demonstrate CAP1 compared to HCs. The CAP1 metrics were positively associated with motor deficits in LPD patients. These results revealed the dynamic alterations of the cerebellum in different dominant-affected PD patients, which were related to motor deficits and sleep disturbances in PD patients. Our findings suggest that the dynamic cerebellar features may be significant factors in the lateralization of PD.
PMID:40041986 | DOI:10.1002/jnr.70029
Frequency-Dependent Changes in Wavelet-ALFF in Patients With Acute Basal Ganglia Ischemic Stroke: A Resting-State fMRI Study
Neural Plast. 2025 Feb 25;2025:8003718. doi: 10.1155/np/8003718. eCollection 2025.
ABSTRACT
Background and Purpose: Motor impairment is a common occurrence in patients with acute basal ganglia (BG) ischemic stroke (ABGIS). However, the underlying mechanisms of poststroke motor dysfunction remain incompletely elucidated. In this study, we employed multifrequency band wavelet transform-based amplitude of low-frequency fluctuations (Wavelet-ALFFs) to investigate the alterations of spontaneous regional neural activity in patients with ABGIS. Methods: A total of 39 ABGIS patients with motor dysfunction and 45 healthy controls (HCs) underwent resting-state functional magnetic resonance imaging. Wavelet-ALFF values were calculated in the conventional frequency band (0.01-0.08 Hz), slow-5 frequency band (0.01-0.027 Hz), and slow-4 frequency band (0.027-0.073 Hz). A two-sample t-test was performed to compare the Wavelet-ALFF values between the two groups with sex as a covariate and Gaussian random field (GRF) theory (voxel p < 0.001, cluster p < 0.05, two-tailed) was used for the multiple corrections. Furthermore, spearman correlation analysis was performed to assess the relationship between alterations in regional neural activity between Fugl-Meyer Assessment (FMA) and National Institutes of Health Stroke Scale (NIHSS) scores. Results: In comparison to HCs, patients with ABGIS showed significantly increased Wavelet-ALFF in the left middle temporal gyrus (MTG) and decreased Wavelet-ALFF in the right inferior frontal operculum (IFO) across all three frequency bands (conventional, slow-4, and slow-5). In the left superior occipital gyrus (SOG), Wavelet-ALFF was decreased in the conventional frequency band but increased in the slow-4 frequency band. Additionally, patients with ABGIS demonstrated reduced Wavelet-ALFF in the right superior temporal gyrus (STG) in the conventional and slow-4 frequency bands. In the slow-5 frequency band, increased Wavelet-ALFF was observed in the left calcarine cortex (CC), left middle frontal gyrus (MFG), left supramarginal gyrus (SMG), and left postcentral gyrus (PCG), while decreased Wavelet-ALFF was noted in the right precuneus (PCu). Correlation analysis revealed that increased Wavelet-ALFF in the left CC in the slow-5 frequency band was positively correlated with the FMA score. No other correlations were detected in the conventional and slow-4 frequency bands. Conclusions: The altered spontaneous neural activity was frequency-specific in patients with ABGIS, and the slow-5 frequency band exhibited better results. Furthermore, the relationship between spontaneous brain activity and clinical characteristics highlighted patterns of neural alterations associated with motor dysfunction. These findings may provide novel insights into the neural mechanisms underlying motor dysfunction in ABGIS.
PMID:40041455 | PMC:PMC11879565 | DOI:10.1155/np/8003718
Longitudinal functional brain connectivity maturation in premature newborn infants: Modulatory influence of early music enrichment
Imaging Neurosci (Camb). 2024 Nov 18;2:1-18. doi: 10.1162/imag_a_00373. eCollection 2024 Nov 1.
ABSTRACT
Premature birth affects brain maturation, illustrated by altered brain functional connectivity at term equivalent age (TEA) and alters neurobehavioral outcome. To correct early developmental differences and improve neurological outcome, music during the neonatal intensive care unit (NICU) stay has been proposed as an auditory enrichment with modulatory effects on functional and structural brain development, but longitudinal effects of such interventions have not been studied so far. We longitudinally investigated resting-state functional connectivity (RS-FC) maturation in preterm infants (n = 43). Data-driven Independent Component Analyses (ICA) were performed on scans obtained at 33- and 40-week gestational age (GA), determining the presence of distinct resting-state networks (RSNs). Connectome analysis "accordance measure" quantitively examined the RS-FC both at 33- and 40-week GA. Further comparing the internetwork RS-FC at 33- and 40-week GA provided a circuitry of interest (COI) for significant maturational changes in which the effects on the RS-FC of a music intervention were tested. The connectome analyses resulted in a COI of RS-FC connections significantly maturing from 33 to 40 weeks GA, namely between the thalamic/brainstem and prefrontal-limbic, salience, sensorimotor, auditory, and prefrontal cortical networks; between the prefrontal-limbic and cerebellar, visual and left hemispheric precuneus networks; between the salience and visual, and cerebellar networks; and between the sensorimotor and auditory, and posterior cingulate/precuneus networks. The infants exposed to music exhibited significantly increased maturation in RS-FC between the thalamic/brainstem and salience networks, compared with controls. This study exemplifies that preterm infant RS-FC maturation is modulated through NICU music exposure, highlighting the importance of environmental enrichment for neurodevelopment in premature newborns.
PMID:40041298 | PMC:PMC11873764 | DOI:10.1162/imag_a_00373
Effect of transcutaneous vagus nerve stimulation with electrical stimulation on generalized anxiety disorder: Study protocol for an assessor-participant blinded, randomized sham-controlled trial
Heliyon. 2025 Feb 6;11(4):e42469. doi: 10.1016/j.heliyon.2025.e42469. eCollection 2025 Feb 28.
ABSTRACT
BACKGROUND: Generalized anxiety disorder (GAD) is the most common type of anxiety disorder and can cause severe damage to patients and increase medical and social burdens. Vagus nerve stimulation (VNS) has been used for treating mental disorders, but the involvement of surgery, perioperative risks, and potentially significant side effects have limited this treatment. Anatomical studies have shown that the ear is the only area where the afferent vagus nerve is distributed on the skin. Recently, the safety and efficacy of transcutaneous auricular vagus nerve stimulation (t-VNS) with electrical stimulation for depression and epilepsy have been objectively evaluated. This trial is trying to evaluate the efficacy of t-VNS with electrical stimulation for the treatment of GAD and explore the potential underlying neural mechanism using fMRI.
METHODS: An assessor-participant blinded, randomized sham-controlled trial will be performed. Sixty participants with GAD will be randomly assigned to the t-VNS group or sham t-VNS group. The treatment will last for 8 weeks, once every 30 min and twice a day. Four clinical assessments will be conducted: before treatment, at 2 weeks, at 4 weeks, and posttreatment. The primary outcome parameter is the categorical classification of treatment response in the Hamilton Anxiety Rating Scale (HAMA) score. Functional magnetic resonance imaging (fMRI) scans will be applied, and the alterations in Amplitude of low-frequency fluctuations (ALFF) and functional connectivity (FC) on resting-state fMRI will be compared between the two groups before and after treatment. Moreover, the correlation between the changes in clinical symptoms and the changes in the altered ALFF and FC in the two groups will be analyzed.
DISCUSSION: This high-level evidence-based medical research is expected to evaluate the value of t-VNS in treating GAD and provide a preliminary explanation of its mechanism of action in brain functional imaging. In addition, the use of t-VNS devices has substantially decreased time and financial costs, potentially providing a promising option for complementary alternative medicine in the treatment of GAD, thereby advancing treatment decisions for this condition.
TRIAL REGISTRATION: International Traditional Medicine Clinical Trial Registry, ITMCTR2022000099. Registered on June 30, 2022.
PMID:40041000 | PMC:PMC11876880 | DOI:10.1016/j.heliyon.2025.e42469
A specific model of resting-state functional brain network in MRI-negative temporal lobe epilepsy
Heliyon. 2025 Feb 13;11(4):e42695. doi: 10.1016/j.heliyon.2025.e42695. eCollection 2025 Feb 28.
ABSTRACT
PURPOSE: Without any visible indicator on structure magnetic resonance imaging (MRI), the diagnosis of MRI-negative temporal lobe epilepsy (NTLE) gets harder. By considering healthy control (HC), a specific functional connectivity (FC) model was constructed in a network topology to improve FC computation to a high-level.
METHODS: MRI data of 20 NTLE patients and 60 HC were pre-processed. Relative to HC, a network-level specific FC model of each network index was built to score the network functions for each NTLE patient. The specific brain areas (regarded as ROIs) were extracted for NTLE by sensitivity analysis of scores. By considering scores of specific ROIs as feature vectors to input into a SVM respectively, a specific NTLE classifier was constructed. Both 10-fold cross validation and hold-out method were utilized to validate the classification and to evaluate the effectiveness of our specific FC models. Simultaneously, the specific FC model was compared to the conventional FC model of Pearson correlation.
RESULTS: By the constructed model for specific FC at a network-level, 11 specific ROIs, such as, frontal lobe, temporal lobe, parietal lobe, hippocampus, and occipital lobe, were extracted for NTLE. Accuracy of our specific NTLE classifier could reach up nearly 93 %, over 6 % greater than conventional FC model of Pearson correlation.
CONCLUSIONS: The network-level specific FC model might provide a new methodology for machine-aiding detection of functional abnormal lesions of NTLE by resting-state functional MRI.
PMID:40040985 | PMC:PMC11876875 | DOI:10.1016/j.heliyon.2025.e42695
A resting-state fMRI cross-sectional study of cardiorespiratory fitness decline after stroke
Front Neurol. 2025 Jan 28;16:1465467. doi: 10.3389/fneur.2025.1465467. eCollection 2025.
ABSTRACT
OBJECTIVE: The present study aimed to investigate alterations in neural activity and reorganization of functional networks within critical brain regions associated with reduced cardiorespiratory fitness (CRF) in stroke patients. By employing resting-state functional magnetic resonance imaging (fMRI), we sought to identify specific brain areas that may be implicated in CRF decline among this patient population.
METHODS: A total of 22 patients with stroke and 15 healthy subjects matched for age, gender, and body mass index were recruited. Rehabilitation assessments included peak oxygen uptake (VO2peak), peak work-rate, 10-meter walk test (10mWT), five times sit-to-stand test (FTSST), and 6-min walking distance (6MWD). Resting-state fMRI data were collected for the two groups, and correlation between changes in the amplitude of low-frequency fluctuations (ALFF) and CRF was analyzed to detect brain regions related to CRF and local neural activity in patients with stroke. On the basis of ALFF analysis, brain network analysis was performed, and the CRF-related brain regions in patients with stroke were selected as seed points. Functional connectivity (FC) analysis was the used to identify brain regions and networks potentially associated with CRF in patients with stroke.
RESULTS: Patients with stroke exhibited significantly lower VO2peak, peak work-rate, 10mWT, and 6MWD compared to healthy controls (p < 0.001). FTSST was significantly higher in patients with stroke than healthy controls (p < 0.001). ALFF analysis identified CRF-related brain regions in patients with stroke, including the ipsilesional superior temporal gyrus (r = 0.56947, p = 0.00036), middle frontal gyrus (r = 0.62446, p = 0.00006), and precentral gyrus (r = 0.56866, p = 0.00036). FC analysis revealed that the functional connectivity of brain regions related to CRF in patients with stroke involved the ipsilesional M1 to ipsilesional precentral gyrus and contralesional postcentral gyrus, and the correlation coefficients were r = 0.54802 (p = 0.00065) and r = 0.49511 (p = 0.0025), respectively. The correlation coefficients of ipsilesional middle frontal gyrus to contralesional middle frontal gyrus, angular gyrus and ipsilesional superior frontal gyrus were r = 0.58617 (p = 0.00022), r = 0.57735 (p = 0.00028), and r = -0.65229 (p = 0.00002), respectively.
CONCLUSION: This study observed that CRF levels were lower in stroke patients compared to those in healthy individuals. Resting fMRI analysis was applied to identify CRF-related brain regions (ipsilesional superior temporal, middle frontal, precentral gyri) and networks in patients with stroke.
CLINICAL TRIAL REGISTRATION: https://www.chictr.org.cn/showproj.html?proj=151095.
PMID:40040907 | PMC:PMC11877007 | DOI:10.3389/fneur.2025.1465467
Data-driven Discovery of the Central Autonomic Network: Dynamic Integration of HRV and Multivariate fMRI Connectivity
Annu Int Conf IEEE Eng Med Biol Soc. 2024 Jul;2024:1-5. doi: 10.1109/EMBC53108.2024.10782925.
ABSTRACT
INTRODUCTION: Although the interaction between the brain and the heart, through the autonomic nervous system, is an established phenomenon, multimodal studies that have explored their bidirectional interplay are still limited.
AIM: In this context, the objective of the present study was to investigate the coupling between sympathetic and vagal dynamics and brain functional connectivity during resting state, thanks to simultaneously acquired electrocardiogram and functional magnetic resonance imaging (fMRI) data.
METHODS: Twenty healthy controls (67.42 ± 10.81 years, 60% females) were included in the study. Unimodal fMRI and heart rate variability (HRV) results were integrated in a joint analysis framework. Trivariate dynamic functional connectivity (dFC) features were correlated with time-varying HRV parameters to identify brain regions involved in autonomic modulation.
RESULTS: In a data-driven approach, the present analysis allowed to extract triplets of brain regions whose dFC was coupled with both sympathetic and vagal activity dynamics. The identified brain regions often belonged to the central autonomic network, which is a network of brain structures that are involved in the regulation of autonomic processes at high central level.
CONCLUSION: The present multimodal HRV and fMRI dFC analysis provided new findings on the physiological brain-heart interactions, paving the way to explore the same mechanisms in disorders of the brain-heart axis.
PMID:40040234 | DOI:10.1109/EMBC53108.2024.10782925
Acute Stress Disorder Detection using Machine Learning based on resting-state fMRI
Annu Int Conf IEEE Eng Med Biol Soc. 2024 Jul;2024:1-4. doi: 10.1109/EMBC53108.2024.10782811.
ABSTRACT
Early diagnosis of Acute Stress Disorder (ASD) is important, given its potential progression to post-traumatic system disorder (PTSD). The current diagnostic tool has some degree of subjectiveness in assessing emotional responses to trauma and the severity of stress reactions. To this end, we proposed a new method to detect ASD using machine learning with resting-state functional magnetic resonance imaging (rs-fMRI) data. We used 48 subjects of rs-fMRI data and PTSD Check List - Civilian Version (PCL-C) questionnaire from Advancing Understanding of RecOvery afteR traumA (AURORA) dataset. We extracted five frequency-domain features from each blood-oxygen-level dependent (BOLD) signal from 48 cortical and 21 subcortical regions. We also extracted four graph features from sparse inverse covariance matrices of the BOLD signals. Eighteen features appeared to be significantly different (p<0.05). Using these features, multi-layer perceptron showed accuracy 91.7%, sensitivity 96.8%, and specificity 82.4% using the leave-one-subject-out cross validation scheme. We found that the Right Accumbens and Lingual Gyrus has high effect size and substantial impact within the machine learning model.
PMID:40040221 | DOI:10.1109/EMBC53108.2024.10782811
Investigation of the Effect of Physiological Artifacts on Task-based Functional Connectivity: A Simulation Study
Annu Int Conf IEEE Eng Med Biol Soc. 2024 Jul;2024:1-5. doi: 10.1109/EMBC53108.2024.10781953.
ABSTRACT
Functional connectivity is commonly used for studying functional interactions among brain regions. However, its results are affected by noise and/or physiological artifacts, especially when computed using blood-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) signals. In this study, we assessed the effect of these artifacts by simulating physiological and BOLD fMRI signals during resting and task conditions and quantifying the resulting functional connectivity results patterns by well established methods (full and partial correlation). Our results reveal that the regions with similar physiological response functions were adversely affected by physiological artifacts. Notably, functional connectivity values computed during task execution exhibited lower errors compared to those computed during the rest period. Furthermore, the results computed using the partial correlation method consistently yielded lower errors compared to those computed using full correlation. Overall, our findings quantitatively characterize the impact of physiological artifacts on functional connectivity patterns and emphasize the importance of method choice in mitigating the impact of artifacts.
PMID:40040207 | DOI:10.1109/EMBC53108.2024.10781953
Exploring Schizophrenia Classification in fMRI Data: A Common Spatial Patterns(CSP) Approach for Enhanced Feature Extraction and Classification
Annu Int Conf IEEE Eng Med Biol Soc. 2024 Jul;2024:1-4. doi: 10.1109/EMBC53108.2024.10782387.
ABSTRACT
In the exploration of dynamic changes in network connectivity within resting-state functional magnetic resonance imaging (rs-fMRI), the dominant focus has traditionally been on a holistic study of the entire brain. Various methodologies and analyses have been applied in prior research within this domain. This study takes a novel approach by delving into a comparative analysis of the similarities between electroencephalogram (EEG) signals with motor imagery tasks and rs-fMRI signal. Both data types collect time series data from their respective datasets. Drawing from the insights of previous research, the common spatial patterns (CSP) method, mostly used for its efficacy in handling EEG signals, was employed. Notably, CSP is a supervised learning transformation of signals, offering advantages over the implementation of deep learning models. this study pioneers the integration of the CSP method with fMRI datasets. Validation of this approach was conducted through a rs-fMRI study focused on schizophrenia, includes two primary classes: patients and controls. In addition to CSP, principal component analysis (PCA) was explored as an unsupervised dimensionality reduction technique, serving as a benchmark for comparison. The results revealed that CSP has better performance relative to PCA and other examined methods. This study contributes to the expanding landscape of understanding time-varying network connectivity, emphasizing the potential applicability of CSP beyond its traditional domain of EEG signals, and take benefit of its effectiveness in the context of rs-fMRI.
PMID:40040201 | DOI:10.1109/EMBC53108.2024.10782387