Most recent paper
Predicting repetitive negative thinking in daily life: Insights from the brain-based graph-theoretical predictive modeling
Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Sep 30:S2451-9022(25)00298-8. doi: 10.1016/j.bpsc.2025.09.020. Online ahead of print.
ABSTRACT
BACKGROUND: Abnormalities in the functional connectivity of large-scale brain networks, including the default mode (DMN), salience (SN), fronto-parietal (FPN), and limbic networks, have been implicated in repetitive negative thinking (RNT), a construct characterized by persistent and intrusive thoughts. However, the potential of these large-scale network abnormalities for predicting RNT in daily life remains underexplored.
METHODS: We leveraged the brain-based graph-theoretical predictive modeling (GPM) to predict daily-life RNT in 54 individuals. Functional MRI data were acquired during: (i) resting-state and (ii) an RNT-induced state. RNT severity and its momentary fluctuations were assessed using ecological momentary assessments (EMA).
RESULTS: The GPM identified key functional organizational properties of the DMN, FPN, and limbic networks that differentially predicted the severity and fluctuations of RNT and its specific clinical features (intrusiveness, repetitiveness, RNT-related anxiety). Specifically, the centrality of the medial prefrontal cortex (DMN) predicted EMA fluctuations of intrusiveness and severity of anxiety. Conversely, the strength and centrality of the orbitofrontal cortex (part of the limbic network) predicted EMA fluctuations of repetitiveness, and the segregation of the temporal pole (limbic network) predicted overall severity of RNT. Last, fluctuations in total RNT were predicted from the strength of the orbitofrontal cortex (limbic network) and segregation of the posterior mid-cingulate cortex (FPN). Notably, RNT was better predicted from daily-life prospective assessments than from lab-assessed clinical questionnaires.
CONCLUSIONS: These findings highlight the utility of the GPM for predicting the emergence of daily-life RNT and suggest specific network-level attributes (e.g., centrality, segregation) underlying RNT and its clinical features.
PMID:41038317 | DOI:10.1016/j.bpsc.2025.09.020
A sequential dual-site repetitive transcranial magnetic stimulation for major depressive disorder: A randomized clinical trial
Cell Rep Med. 2025 Oct 1:102402. doi: 10.1016/j.xcrm.2025.102402. Online ahead of print.
ABSTRACT
Repetitive transcranial magnetic stimulation (rTMS) is approved for major depressive disorder (MDD), but it is limited by variable efficacy. Here, we examine antidepressant effects of our sequential dorsolateral prefrontal cortex (dlPFC)-dorsomedial prefrontal cortex (dmPFC) accelerated rTMS protocol, which includes a 4-day treatment with 4 sessions per day. At week 4, the Montgomery-Åsberg Depression Rating Scale (MADRS) reduction is significantly larger in the active group, and critical, significant differences were apparent on day 4. For active and sham-controlled groups, respectively, response rates are 57.69% and 23.08%, and remission rates are 38.46% and 15.38%. Of responders, over 85% remain in remission over 6 months. Resting-state fMRI shows dissociable symptom improvement associated with increased dlPFC-frontoparietal and decreased dmPFC-amygdalo-subcallosal cingulate functional connectivity. We highlight a cost-efficient generalizable rTMS approach targeting differential networks in MDD, which shows rapid and sustained antidepressant effects with a relatively small number of pulses and minimal treatment duration. The study is registered with ChiCTR (ChiCTR2100046042).
PMID:41038161 | DOI:10.1016/j.xcrm.2025.102402
The Use of Repetitive Transcranial Magnetic Stimulation to Improve Cognitive Impairment in Patients With Stroke Based on rs-fMRI Findings: Protocol for a Meta-Analysis
JMIR Res Protoc. 2025 Oct 2;14:e77931. doi: 10.2196/77931.
ABSTRACT
BACKGROUND: Poststroke cognitive impairment (PSCI) is a chronic form of poststroke cognitive dysfunction that affects approximately one-third of the survivors of stroke. PSCI significantly increases the rates of mortality and functional disabilities, such as limitations in motor function, speech, and activities of daily living. Therefore, effective treatments are needed for patients with PSCI. Repetitive transcranial magnetic stimulation (rTMS) has been shown to exert beneficial behavioral effects in patients with PSCI. More importantly, a limited number of neuroimaging studies with small sample sizes have reported the beneficial effects of rTMS on brain plasticity and its reciprocal influence on cognitive and behavioral performance. Resting-state functional magnetic resonance imaging (rs-fMRI) has been widely used to study changes in brain activity, but there is no consensus regarding which brain regions play pivotal roles in rTMS for patients with PSCI.
OBJECTIVE: This study aims to explore the therapeutic effects of rTMS on changes in the brain activity of patients with PSCI, thereby providing robust evidence to elucidate its neuroimaging mechanisms.
METHODS: In this meta-analysis, we will systematically search the PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine, and China National Knowledge Infrastructure databases, VIP Chinese Science and Technology Periodical Database, and the China WanFang Database up to December 2024 to identify randomized controlled trials comparing active rTMS with sham stimulation conditions or conventional control conditions in patients with PSCI. The primary outcomes will include the amplitude of low-frequency fluctuation, fractional amplitude of low-frequency fluctuation, regional homogeneity, and functional connectivity across the whole brain. The secondary outcomes will include the Montreal Cognitive Assessment and Mini-Mental State Examination scores. Statistical analyses will be conducted via Review Manager (version 5.4), Seed-based d Mapping with Permutation of Subject Images (version 6.23), and Stata (version 18.0) software to assess study quality, evaluate the risk of bias, and analyze the outcome measures.
RESULTS: The study will offer a comprehensive analysis of the available evidence on the use of rTMS to improve cognitive impairment in patients with stroke based on rs-fMRI findings. The meta-analysis will be conducted from July 2024 to April 2026, following this predefined protocol. The process encompasses database searching and study screening (to be concluded by October 2025), data extraction and synthesis (to be completed by December 2025), and subsequent manuscript preparation and submission (anticipated by April 2026).
CONCLUSIONS: This meta-analysis will provide insights into the therapeutic potential of rTMS to improve cognitive impairment in patients with stroke. It will also highlight the strengths and limitations of the existing literature and suggest directions for future research. Ultimately, our study may aid future clinical decision-making concerning PSCI rehabilitation programs and provide evidence-based medical insights into the neuroimaging mechanisms of rTMS treatment for PSCI.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/77931.
PMID:41037808 | DOI:10.2196/77931
Meditation, psychedelics, and brain connectivity: A randomized controlled resting-state fMRI study of N,N-dimethyltryptamine and harmine in a meditation retreat
Imaging Neurosci (Camb). 2025 Sep 29;3:IMAG.a.907. doi: 10.1162/IMAG.a.907. eCollection 2025.
ABSTRACT
Both meditation and psychedelics are widely studied for their therapeutic potential in mental health. Recent research suggests potential synergies between mindfulness practice and psychedelics, though empirical studies have primarily focused on psilocybin. This study investigates the distinct and combined effects of mindfulness practice and an ayahuasca-inspired formulation containing N,N-dimethyltryptamine (DMT) and harmine on brain functional connectivity (FC), with implications for advancing clinical interventions. In this double-blind, placebo-controlled pharmaco-functional magnetic resonance imaging (fMRI) study, 40 meditation practitioners participated in a 3-day meditation retreat. They were randomized to receive either placebo or buccal DMT-harmine (120 mg each) and underwent fMRI scans 2 days before and after administration. Neural changes were assessed using multiple connectivity metrics, including within- and between-network connectivity, network and global connectivity, and cortical gradient analyses. Within-group changes showed that meditators in the placebo group exhibited increased network segregation across several resting-state networks, while the DMT-harmine group showed increased FC within the visual network (VIS) and between VIS and attention networks. Between-group differences similarly showed increased FC between VIS and the salience network (SAL) in the DMT-harmine group compared with placebo post-retreat. No evidence of prolonged cortical gradient disruption, which is characteristic of acute psychedelic action, was observed. This suggests a return to typical brain organization shortly after the experience. These findings reveal distinct neural mechanisms underlying meditation and psychedelic-augmented meditation. While meditation alone reduced FC between networks, DMT-harmine increased within- and between-network connectivity. Given the potential of meditation and psychedelics for improving mental health, further exploration of their synergistic potential in clinical contexts is warranted. This study advances the understanding of how psychedelics and mindfulness practice shape brain function, offering insights into their complementary roles in emotional and psychological well-being.
PMID:41035622 | PMC:PMC12479382 | DOI:10.1162/IMAG.a.907
Slow wave dynamics of scalp EEG can be explained by simple statistical models of long-range connections
Neuroimage. 2025 Sep 29:121418. doi: 10.1016/j.neuroimage.2025.121418. Online ahead of print.
ABSTRACT
Scalp-recorded electroencephalography (EEG) is thought to be driven by both local and global oscillations dependent on the cognitive state and task of the individual. However, many EEG studies assume that the activity is local, especially when inverse modeling EEG activity. In this work, we show that a simple model of purely macroscopic connections derived from biologically plausible distributions of long-range axon delays can drive many of the traditional features of scalp-recorded EEG dynamics. All that is required is a simple linear model of time delays in a linear vector autoregressive framework with a few parameters. We make several simplifying modeling assumptions in the model: only long-range excitatory connections are included, local activity is treated as stochastic noise, and nonlinear synaptic dynamics are omitted. As a proof of concept, we restrict the model to five broad brain regions (frontal, parietal, occipital, temporal, thalamic) and model resting state EEG with no external input. We show how this simple connection model is derived from theoretical principles of synaptic activity. The model is able to replicate many features of real EEG data, including resting-state alpha power and coherence (8-13 Hz). We show that model parameters can also be informed by empirical work on structural connectivity, axon diameter estimation, and functional connectivity of fMRI BOLD measures. However, some features of the macroscopic simulations are not ideal as a model for all features of resting EEG, such as high coherence in low-frequencies in the simulation as opposed to real data. Overall, the results support the explanation of many classical EEG findings in terms of macroscopic network behavior as opposed to local activity.
PMID:41033379 | DOI:10.1016/j.neuroimage.2025.121418
Efficacy and Neural Mechanisms of Robotic-Assisted Therapy in Upper Extremity Rehabilitation for Stroke Survivors: A Resting-State fMRI Study
IEEE Trans Neural Syst Rehabil Eng. 2025 Oct 1;PP. doi: 10.1109/TNSRE.2025.3616524. Online ahead of print.
ABSTRACT
Robotic-assisted therapy (RAT) represents a promising adjunctive rehabilitation technology, however, its underlying neuroplastic mechanisms remain incompletely characterized. We aimed to elucidate the neuroplastic reorganization induced by RAT that mediates motor functional improvements in stroke survivors. Thirteen stroke survivors in the RAT group and 13 demographically/clinically matched in the conventional rehabilitation therapy (CRT) group underwent a 4-week rehabilitation intervention. Motor function was assessed using the Fugl-Meyer Assessment upper and lower extremity subscale (FMA-UE, FMA-LE) and modified Barthel Index (MBI) at pre- and post-intervention timepoints. Concurrently, resting-state functional MRI (rs-fMRI) data were acquired for amplitude of low-frequency fluctuation (ALFF) computation and seed-based functional connectivity (FC) analysis. Repeated measures ANOVA showed significant Group × Time interactions for both FMA-UE and FMA-LE (F(1,24) = 4.913, p<0.05; F(1,24) = 4.778, p< 0.05). All motor outcomes displayed strong main effects of Time (all p < 0.001). Post hoc simple effects tests revealed significant within group gains in FMA UE for both RAT and CRT and in FMA LE for RAT only, with no between group differences at any single time point. Neuroimaging showed that increases in ALFF within the ipsilesional precentral gyrus correlated with improvements in both FMA-UE and FMA-LE. Compared with CRT, RAT strengthened interhemispheric functional connectivity between the precentral and postcentral gyri and between the precentral and supramarginal gyri. Together, these findings indicate that RAT promotes motor recovery by up regulating activity in the ipsilesional motor cortex and enhancing cross hemispheric sensorimotor integration, providing the direct evidence for mechanism of post stroke neural restitution.
PMID:41032542 | DOI:10.1109/TNSRE.2025.3616524
Advances in Neuroimaging of Breast Cancer Pain: An Overview
J Pain Res. 2025 Sep 24;18:4975-4988. doi: 10.2147/JPR.S540502. eCollection 2025.
ABSTRACT
Breast cancer is currently the most common malignant tumor, primarily affecting women, and it frequently leads to chronic pain that significantly impairs physical and mental health. Neuroimaging studies have demonstrated that breast cancer-related pain is associated with specific brain alterations, including changes in activation, connectivity, and structure of pain-processing regions. This review synthesizes findings on functional and structural brain changes related to chronic pain in breast cancer and compares them with non-cancer chronic pain patterns. By integrating recent evidence, it proposes a conceptual framework to advance the understanding of pain mechanisms and supports personalized pain management strategies to improve quality of life.
PMID:41030773 | PMC:PMC12477286 | DOI:10.2147/JPR.S540502
Long-Term Efficacy and Resting-State Functional Magnetic Resonance Imaging Changes of Deep Brain Stimulation in the Lateral Habenula Nucleus for Treatment-Resistant Bipolar Disorder
Brain Behav. 2025 Oct;15(10):e70899. doi: 10.1002/brb3.70899.
ABSTRACT
BACKGROUND: To explore the long-term efficacy and resting-state functional magnetic resonance imaging (fMRI) changes of lateral habenula nucleus (LHb) deep brain stimulation (DBS; LHb-DBS) for treatment-resistant bipolar disorder (TRBD).
METHODS: An 18-year-old woman with TRBD received bilateral LHb-DBS. We assessed changes in Hamilton Depression Scale-17 (HDRS-17), Bech-Rafaelsen Melancholia Scale (BRMS), Hamilton Anxiety Scale (HAMA), and Pittsburgh Sleep Quality Scale (PSQI) scores from preoperative baseline to postoperative continuous 24-month follow-up. Brain activity and resting-state functional connectivity (rsFC) were examined off-stimulation at 0.6 and 15 months post-LHb-DBS. Overall improvement and adverse events were analyzed.
RESULTS: Continuous 24-month follow-up showed average improvements from baseline of 65.33%, 54.90%, 63.33%, and 48.72% for HDRS-17, BRMS, HAMA, and PSQI scores, respectively. At the final follow-up, improvement was 96.00%, 88.24%, 84.85%, and 69.23%, respectively. Resting-state fMRI results revealed an increase in fractional amplitude of low-frequency fluctuations (fALFF) within the putamen, ventral tegmental area (VTA), and substantia nigra pars compacta (SNc) over 15 months of continuous bilateral LHb stimulation when DBS was off. From baseline to 15 months, fALFF in the putamen, VTA, and SNc increased by 1.68%, 6.36%, and 1.10%, respectively. Consistently reduction in rsFC was observed between the left nucleus accumbens (NAcc) and left hippocampus. Over the 15 months of continuous stimulation, rsFC decreased by 72% from baseline.
CONCLUSIONS: Long-term LHb-DBS can control symptoms and improve the quality of life in patients with TRBD. This may be attributed to an increase in fALFF in the putamen, VTA, and SNc, and a reduction in rsFC between the left NAcc and left hippocampus.
PMID:41030103 | PMC:PMC12484712 | DOI:10.1002/brb3.70899
Impaired neural activity and functional connectivity in the hippocampus of adolescents with non-suicidal self-injury addiction
BMC Psychiatry. 2025 Sep 30;25(1):895. doi: 10.1186/s12888-025-07331-z.
ABSTRACT
BACKGROUND: Non-suicidal self-injury (NSSI) addiction is prevalent among adolescents, but its underlying neural mechanisms remain unclear. This study aims to investigate the neural activity and functional connectivity characteristics associated with NSSI addiction using resting-state functional magnetic resonance imaging (rs-fMRI).
METHODS: A prospective collection of 62 adolescents was completed for this study, including 33 adolescents with self-injury behaviors and 29 age-, gender-, and education-matched healthy controls. The addiction component of the Ottawa Self-Injury Inventory (OSI) was used to assess the degree of NSSI addiction. Amplitude of low-frequency fluctuation (ALFF) analysis was employed to detect changes in local neural activity. Differential brain regions were considered regions of interests (ROIs). Whole-brain functional connectivity (FC) analysis based on ALFF was used to further explore potential changes in functional connections between ROIs and other brain areas in the NSSI group, and to analyze the relationship between these neural changes and addiction characteristics.
RESULTS: ALFF analysis revealed decreased ALFF values in the bilateral hippocampus and increased ALFF values in the right supplementary motor area of NSSI adolescents compared to healthy controls. Significantly reduced FC values was observed between the left hippocampus and the left precuneus, right middle temporal gyrus, and right inferior temporal gyrus, and between the right hippocampus and the right middle temporal gyrus. Additionally, increased FC values was observed between the left hippocampus and the left thalamus. Furthermore, ALFF values in the bilateral hippocampus were negatively correlated with the total score of addiction characteristics in NSSI adolescents.
CONCLUSIONS: This study highlights reduced local neural activity and functional connectivity in the bilateral hippocampus of NSSI adolescents, and demonstrates that these alterations are associated with heightened addictive features in self-injuring individuals.
TRIAL REGISTRATION: A study of positive psychological group interventions in adolescents with non-suicidal self-injury (registration date: 03/01/2024; registration number: ChiCTR2400079412).
PMID:41029257 | PMC:PMC12486709 | DOI:10.1186/s12888-025-07331-z
Approach bias modification training reduces gaming severity and improves brain network topology in internet gaming disorder
Addict Behav. 2025 Sep 12;172:108494. doi: 10.1016/j.addbeh.2025.108494. Online ahead of print.
ABSTRACT
BACKGROUND: Patients with internet gaming disorder (IGD) suffer from an imbalance of over-integrated and weakly dissociated functional brain networks. Approach bias modification training (ApBMt) has been used to correct patients' automatic approach biases to addictive stimuli; however, research exploring changes in brain network topology is limited.
METHODS: Seventy subjects were randomly assigned to the approach-avoidance task (AAT) group or the sham-AAT group, and 57 subjects (AAT, 30; sham-AAT, 27) completed the entire procedure, which included pretests, AAT/sham-AAT interventions, and posttests. Behavioral and resting-state fMRI data were collected before and after the tests. This study aimed to investigate the effects of ApBMt on topological changes in resting functional brain networks in patients with IGD and explore the relationship between these network changes and behavioral indicators of addiction severity.
RESULTS: Repeated-measures ANOVA of the behavioral data showed that the AAT group had significant score reductions after ApBMt. Imaging data revealed significant decreases in brain network over-integration and increases in segregation of the fronto-parietal network (FPN) and the cingulo-opercular network (CON). Additionally, a positive correlation was found between the post-pre difference in DSM-5 scores and the post-pre difference in nodal efficiency (Ne) in the anterior prefrontal cortex (aPFC).
CONCLUSIONS: The findings of this study demonstrate that ApBMt effectively reduces the severity of IGD, along with associated changes in brain network topology, such as enhanced segregation and decreased over-integration. However, it is important to highlight that the neurobiological changes observed are correlated with the reduction in IGD severity, but causality cannot be established. Further research is necessary to better understand the clinical potential of ApBMt in treating IGD, either as a stand-alone intervention or in combination with other therapeutic approaches.
PMID:41027144 | DOI:10.1016/j.addbeh.2025.108494
Altered cerebral blood flow and functional connectivity in sickle cell disease
J Sick Cell Dis. 2025 Sep 18;2(1):yoaf031. doi: 10.1093/jscdis/yoaf031. eCollection 2025.
ABSTRACT
BACKGROUND: Adults with sickle cell disease (SCD) often experience cognitive deficits and chronic pain, but the cerebral mechanisms underlying these symptoms remain unclear. Elevated cerebral blood flow (CBF) is a compensatory response to anemia, yet its impact on brain function and perception is not well understood.
OBJECTIVE: To examine alterations in cerebral perfusion and resting-state brain function in adults with SCD and their associations with cognition and pain sensitivity.
METHODS: Seven adults with SCD and 3 healthy controls underwent arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI). Metrics included global/regional CBF, resting-state functional connectivity (rsFC), and amplitude of low-frequency fluctuations (ALFF). Participants completed NIH Toolbox fluid cognition tests and the Pain Sensitivity Questionnaire (PSQ).
RESULTS: SCD patients exhibited significantly higher global CBF (72.1 vs. 47.2 mL/100g/min; P = .04), reduced cortical zALFF (P = .0013), and elevated white-matter zALFF (P = .0023). They also showed resting-state network hyperconnectivity, with diminished anti-correlations between the default mode and salience networks. SCD participants scored lower on processing speed (P = .02) and reported higher pain sensitivity (PSQ total, P = .0040). Higher CBF was associated with slower cognitive performance but not directly with pain sensitivity. Exploratory mediation models suggested that altered brain activity may partially mediate this relationship.
CONCLUSIONS: Adults with SCD demonstrate cerebral hyperperfusion, disrupted functional connectivity, and altered spontaneous brain activity, which may contribute to cognitive slowing and heightened pain sensitivity. These findings highlight the need for further research into brain-targeted therapies in SCD.
PMID:41024864 | PMC:PMC12476913 | DOI:10.1093/jscdis/yoaf031
Motion impact score for detecting spurious brain-behavior associations
Nat Commun. 2025 Sep 29;16(1):8614. doi: 10.1038/s41467-025-63661-2.
ABSTRACT
In-scanner head motion introduces systematic bias to resting-state fMRI functional connectivity (FC) not completely removed by denoising algorithms. Researchers studying traits associated with motion (e.g. psychiatric disorders) need to know if their trait-FC relationships are impacted by residual motion to avoid reporting false positive results. We devised Split Half Analysis of Motion Associated Networks (SHAMAN) to assign a motion impact score to specific trait-FC relationships. SHAMAN distinguishes between motion causing overestimation or underestimation of trait-FC effects. We assessed 45 traits from n = 7270 participants in the Adolescent Brain Cognitive Development (ABCD) Study. After standard denoising with ABCD-BIDS and without motion censoring, 42% (19/45) of traits had significant (p < 0.05) motion overestimation scores and 38% (17/45) had significant underestimation scores. Censoring at framewise displacement (FD) < 0.2 mm reduced significant overestimation to 2% (1/45) of traits but did not decrease the number of traits with significant motion underestimation scores.
PMID:41022827 | PMC:PMC12479937 | DOI:10.1038/s41467-025-63661-2
Immediate and sustained effects of acupuncture on the default mode network
Braz J Psychiatry. 2025 Sep 29. doi: 10.47626/1516-4446-2025-4202. Online ahead of print.
ABSTRACT
OBJECTIVE: Functional magnetic resonance imaging (fMRI) techniques were conducted to investigate the immediate and sustained effects of acupuncture, as well as its impact on the functional connectivity (FC) within the default mode network (DMN) and the external FC.
METHODS: Thirty healthy participants received acupuncture needle stimulation at Baihui (GV20) and Yintang (GV29), and underwent resting-state fMRI scans in three phases: pre-needle insertion, during needle retention, and post-needle removal. Each phase lasted for 20 minutes.
RESULTS: In terms of the within-network connectivity of the DMN, post-needle removal scans showed a decrease in FC between the medial prefrontal cortex (mPFC) and the angular gyrus (ANG) compared to pre-needle insertion scans. The FC analysis from seed points to whole-brain voxels showed the following changes: compared to pre-needle insertion scans, acupuncture needle insertion increased the FC between the posterior cingulate cortex/precuneus (PCC/PCU) and Cerebellum_8_L, acupuncture needle withdrawal increased the FC between the PCC/PCU and Cerebellum_8_L; acupuncture needle insertion decreased the FC between ANG and Frontal_Sup_Medial_L, and acupuncture needle withdrawal decreased the FC between ANG and Frontal_Sup_Medial_L.
CONCLUSIONS: These results suggested that acupuncture has an impact on the DMN, and acupuncture exhibits sustained effects, not just immediate effects.
PMID:41022570 | DOI:10.47626/1516-4446-2025-4202
Association between brain connectivity and renal pathophysiology: a multi-trait Mendelian randomization analysis
Brain Struct Funct. 2025 Sep 29;230(8):151. doi: 10.1007/s00429-025-03014-3.
ABSTRACT
To investigate the potential bidirectional causal relationships between resting-state functional brain activity and major kidney diseases. We accessed genome-wide association study (GWAS) summary data of 191 resting-state fMRI (rs-fMRI) phenotypes. Summary-level GWAS data for seven kidney diseases-diabetic nephropathy, chronic kidney disease, glomerulonephritis, nephrotic syndrome, cystic kidney disease, IgA nephropathy, and kidney cyst-were obtained from the FinnGen consortium or the Kiryluk Lab, all based on European ancestry (sample sizes ranging up to 11,265 cases and 436,208 controls). We employed inverse variance weighted (IVW) analysis as the primary MR approach, supplemented by MR-Egger, Weighted Median, Weighted Mode, and Robust Adjusted Profile Score (RAPS) to evaluate pleiotropy and heterogeneity. Forward MR demonstrated that certain brain networks, such as the central executive network, default mode network, limbic network, and other interconnected circuits, appear to influence susceptibility to various kidney diseases. Reverse MR indicated that disrupted kidney function, particularly CKD, may adversely affect key brain functional networks, including those responsible for sensory-motor processing and cognitive integration. Although the observed effect sizes were modest, our results provide evidence that kidney diseases and brain functional activity may be interlinked, aligning with clinical observations of neurological-urinary system correlations and emerging data on cortical structural changes in chronic kidney disease. The "kidney-brain axis" could be relevant to both renal and neurological pathophysiology.
PMID:41020910 | DOI:10.1007/s00429-025-03014-3
Relationships Between Intra-Spinal Resting-State Functional Connectivity and Electrophysiology Following Spinal Cord Injury
Hum Brain Mapp. 2025 Oct 1;46(14):e70370. doi: 10.1002/hbm.70370.
ABSTRACT
We previously reported that a unilateral dorsal column lesion (DCL) at the cervical C4 level primarily reduces inter-horn resting-state functional connectivity (rsFC) measured by functional Magnetic Resonance Imaging (fMRI) in segments below the lesion. This study compares changes in rsFC from fMRI with changes in local field potential (LFP) coherence over an extended post-injury period. High-resolution fMRI and LFP data were acquired bilaterally in healthy monkeys and at 3- and 6-months post-lesion. At 3 months post-injury, tactile-stimulus-evoked LFP power in the dorsal horn was significantly weaker than in the healthy cord and non-lesion side. LFP coherences increased on the lesion side for the dorsal-to-intermediate zone (D-IGM) and dorsal-to-ventral (D-V) pairs but decreased for the non-lesion side D-IGM. By 6 months, stimulus-evoked LFP power on the lesion side remained low. LFP coherences between dorsal-to-dorsal (D-D), ventral-to-ventral (V-V), and D-V pairs on both the lesion and non-lesion sides were significantly reduced relative to the healthy cord. Low-frequency (delta, theta, and alpha) D-IGM coherences on the lesion side, and high-frequency (beta and gamma) coherences on the non-lesion side, were also significantly weakened. Across specific inter-horn pairs and time points, changes in LFP coherences and rsFC measures were weakly correlated. Measurements of inter-horn correlations two segments caudal to the lesion level at C7 revealed distance-dependent intraspinal connectivity changes following DCL. Post-mortem histology confirmed a complete DCL in most animals (7/9). The extent of the disruption of ascending sensory afferents, as assessed histologically, did not appear to correlate with the degree of LFP power reduction or rsFC changes at post-injury time points. In summary, we observed temporally and spatially heterogeneous changes of fMRI correlations and LFP coherences within intraspinal circuits. fMRI rsFC and LFP coherences were not always concordant, with discrepancies depending on specific gray-matter horns and intermediate-zone pairs.
PMID:41020550 | PMC:PMC12477704 | DOI:10.1002/hbm.70370
Regularized partial correlation provides reliable functional connectivity estimates while correcting for widespread confounding
Imaging Neurosci (Camb). 2025 Sep 24;3:IMAG.a.162. doi: 10.1162/IMAG.a.162. eCollection 2025.
ABSTRACT
Functional connectivity (FC) has been invaluable for understanding the brain's communication network, with strong potential for enhanced FC approaches to yield additional insights. Unlike with the fMRI field-standard method of pairwise correlation, theory suggests that partial correlation can estimate FC without confounded and indirect connections. However, partial correlation FC can also display low repeat reliability, impairing the accuracy of individual estimates. We hypothesized that reliability would be increased by adding regularization, which can reduce overfitting to noise in regression-based approaches like partial correlation. We therefore tested several regularized alternatives-graphical lasso, graphical ridge, and principal component regression-against unregularized partial and pairwise correlation, applying them to empirical resting-state fMRI and simulated data. As hypothesized, regularization vastly improved reliability, quantified using between-session similarity and intraclass correlation. This enhanced reliability then granted substantially more accurate individual FC estimates when validated against structural connectivity (empirical data) and ground truth networks (simulations). Graphical lasso showed especially high accuracy among regularized approaches, seemingly by maintaining more valid underlying network structures. We additionally found graphical lasso to be robust to noise levels, data quantity, and subject motion-common fMRI error sources. Lastly, we demonstrated that resting-state graphical lasso FC can effectively predict fMRI task activations and individual differences in behavior, further establishing its reliability, external validity, and ability to characterize task-related functionality. We recommend graphical lasso or similar regularized methods for calculating FC, as they can yield more valid estimates of unconfounded connectivity than field-standard pairwise correlation, while overcoming the poor reliability of unregularized partial correlation.
PMID:41019970 | PMC:PMC12461088 | DOI:10.1162/IMAG.a.162
Changes in functional connectivity are associated with functional independence in the early postoperative period following awake surgical resection of language-eloquent glioma
Neurooncol Adv. 2025 Sep 2;7(1):vdaf192. doi: 10.1093/noajnl/vdaf192. eCollection 2025 Jan-Dec.
ABSTRACT
BACKGROUND: Neurocognitive decline in patients with primary brain tumors is associated with alterations in the functional connectome and reduced independence in daily living. This study explores postoperative connectomic changes associated with functional independence outcomes in patients with eloquent glioma, and how these associations differ from neurocognitive-connetcomic relationships.
METHODS: Fifteen patients with left perisylvian glioma underwent resting-state functional magnetic resonance imaging (fMRI) and neuropsychological evaluation within 2 weeks before and on average 1 month after resection. Functional independence was measured with the Physical Self-Maintenance Scale (PSMS) and the Instrumental Activities of Daily Living scale (IADL). Graph theoretical analysis quantified functional brain network properties.
RESULTS: Postoperative need for assistance in at least 1 activity on the IADL increased in 80% of patients with Total scores significantly increasing at the group level (Mdn change = 4.0, P = .006). In contrast, need for assistance on the PSMS increased in less than 30% of patients and Total scores were unchanged. Connectomic changes in Local Efficiency, Clustering Coefficient, Path Length, and Betweenness Centrality showed significant associations with need for assistance on the IADL (ρ = 0.63 to.72, all P < .01) but few activities on the PSMS. Functional independence ratings were not associated with Karnofsky Performance Status, manual dexterity, tumor volume, or extent of resection.
CONCLUSIONS: Alterations in functional connectomic properties after eloquent glioma resection are associated with early postoperative need for assistance in instrumental activities. Changes in connectomics are also associated with cognitive outcome in this population, though properties most involved appear to differ from those underlying changes in independence.
PMID:41019665 | PMC:PMC12461250 | DOI:10.1093/noajnl/vdaf192
Aberrant static and dynamic brain functional topological organization in the differentiation of myelin oligodendrocyte glycoprotein antibody-seropositive optic neuritis from seronegative optic neuritis
Front Neurosci. 2025 Sep 12;19:1627269. doi: 10.3389/fnins.2025.1627269. eCollection 2025.
ABSTRACT
OBJECTIVE: An early and accurate diagnosis of myelin oligodendrocyte glycoprotein antibody seropositive optic neuritis (MOG-ON) versus seronegative-ON is critical for optimal management. We aimed to explore alterations in static and dynamic functional networks for differentiation by resting-state functional magnetic resonance imaging (RS-fMRI) with the graph theory method.
METHODS: RS-fMRI was performed on 53 patients (23 with MOG-ON and 30 with seronegative-ON) and 26 healthy controls (HCs). Graph theory analysis was used to investigate the topological properties of the functional networks. Receiver operating characteristic (ROC) curve analysis was also performed to determine their effectiveness in differential diagnosis.
RESULTS: With respect to static properties, the MOG-ON and seronegative-ON groups presented a spectrum of abnormalities in global and nodal properties compared with the HC group. Furthermore, compared with the seronegative-ON group, the MOG-ON group also presented with abnormal properties mostly located in the visual network (VN). With respect to dynamic properties, the MOG-ON and seronegative-ON groups presented with greater variances of global and nodal properties compared with the HC group. Importantly, the variances in several global and nodal properties were greater in the MOG-ON group. Compared with that in HCs, the subnetwork (24 nodes and 28 edges) in the MOG-ON patients was enhanced. For ROC analysis, the optimal diagnostic performance was obtained by combining static and dynamic approaches.
CONCLUSION: In conclusion, abnormal topological organization of static and dynamic brain functional networks may help explore the neural mechanisms of ON in different phenotypes and serve as biomarkers for differentiation.
PMID:41017978 | PMC:PMC12463965 | DOI:10.3389/fnins.2025.1627269
SCN1A rs3812718 polymorphism modulates structural and functional brain networks in TLE: A multimodal imaging-genomics study
Epilepsy Behav. 2025 Sep 27;172:110725. doi: 10.1016/j.yebeh.2025.110725. Online ahead of print.
ABSTRACT
OBJECTIVE: To investigate the impact of the SCN1A rs3812718 polymorphism on gray matter volume (GMV) and resting-state functional network topology in temporal lobe epilepsy (TLE) patients.
METHODS: 60 TLE patients and 28 healthy controls (HCs) underwent genotyping and MRI (3D-T1, rs-fMRI). Participants were grouped by genotype (AA/AGvs.GG) and disease status (TLEvs.HC). Voxel-based morphometry assessed GMV; graph theory analyzed functional network topology. 2x2 ANCOVA tested genotype and disease main effects and their interaction.
RESULTS: AA/AG genotype frequency was higher in (TLE vs.HCs). GMV: Significant genotype main effect (AA/AGvs.GG): reduced GMV in right temporal regions/hippocampus/left SMG; increased in left MTG/right precuneus. Significant disease main effect (TLEvs.HC): widespread GMV reductions, especially in mesiotemporal/neocortical areas. Significant genotype-by-disease interaction: TLE patients with AA/AG genotype showed the most extensive GMV reductions (bilateral ITG, fusiform gyri, right hippocampus/precuneus/occipital, left caudate/rectus).
FUNCTIONAL NETWORKS: Significant disease main effect: reduced degree centrality in left dorsolateral prefrontal cortex (SFGdor/MFG) in TLEvs.HC. No significant interaction effects on global/nodal topology.
CORRELATIONS: In AA/AG TLE patients, left MTG GMV negatively correlated with epilepsy duration.
CONCLUSION: The SCN1A rs3812718AA/AG genotype is a TLE risk factor. It independently and interactively (with disease status) is associated with structural brain alterations (GMV) in TLE and is linked to disease-related functional network changes (DC) in cognitive regions. These genetic-neuroimaging signatures offer potential biomarkers for TLE precision medicine.
PMID:41016120 | DOI:10.1016/j.yebeh.2025.110725
Functional Connectivity of the Dorsal and Ventral Attention Network and Its Role in Attentional Disengagement
Brain Behav. 2025 Oct;15(10):e70868. doi: 10.1002/brb3.70868.
ABSTRACT
BACKGROUND: The interplay between the ventral attention network (VAN) and dorsal attention network (DAN) is crucial for attentional control, particularly in disengagement processes. While task-based fMRI studies have extensively characterized their roles, less is known about whether intrinsic connectivity patterns during rest within these networks predict individual differences in attentional disengagement. This study investigates the relationship between resting-state functional VAN-DAN connectivity and disengagement efficiency.
METHODS: An initial sample of 85 healthy participants completed a spatial cueing task, assessing attentional disengagement through reaction time differences between valid and invalid cue trials. Resting-state fMRI data were collected and analyzed using seed-based connectivity methods. Functional connectivity between key VAN and DAN regions-frontal eye fields (FEF), intraparietal sulcus (IPS), inferior frontal gyrus (IFG), and supramarginal gyrus (SMG)-was examined in relation to a disengagement index, representing cue validity effects.
RESULTS: Participants exhibited slower responses to invalidly cued targets, with a greater disengagement cost in the left visual field. Functional connectivity analyses revealed that VAN regions, particularly the right IFG and SMG, showed stronger associations with attentional disengagement than DAN regions. Increased FC with occipito-temporal areas correlated with heightened validity effects in the left hemifield, while greater connectivity with medial parietal and cingulate regions was linked to reduced disengagement asymmetry. Interhemispheric connectivity also played a modulatory role in attentional control.
CONCLUSION: These findings underscore the role of VAN over DAN in attentional disengagement, emphasizing the right IFG and SMG in reorienting attention. Greater connectivity with occipito-temporal regions may hinder disengagement, while enhanced functional connectivity with medial cortical areas facilitates adaptive shifts in attention. This study highlights the importance of intrinsic VAN-DAN interactions in shaping attentional control and provides insights into the neural mechanisms underlying disengagement efficiency.
PMID:41016017 | PMC:PMC12476866 | DOI:10.1002/brb3.70868