Most recent paper

Front Psychiatry. 2025 Jul 31;16:1591938. doi: 10.3389/fpsyt.2025.1591938. eCollection 2025.

ABSTRACT

INTRODUCTION: Exposure to trauma produces abnormal intrinsic brain activity, but its association to stress-related symptom severity is often elusive, and the relationships with co-occurring psychiatric and cognitive changes are poorly understood.

METHODS: This study investigated the neurobehavioral mechanisms of persistent disability in male combat-exposed military personnel and veterans with symptoms of post-traumatic stress disorder (CE-PTSD) (n=19) and trauma-exposed healthy controls with similar combat experiences (n=24). Disturbances in intrinsic activity during resting-state fMRI were identified using a whole-brain analytic approach that quantified regional homogeneity (ReHo) and fractional amplitude of low-frequency fluctuations (fALFF). To determine if functional abnormalities were related to changes in brain macrostructure, cortical thickness and gray/white-matter volume were measured. Regional abnormalities in CE-PTSD were identified by comparing measures of brain function and structure between the two groups. The behavioral relevance of regional abnormalities in the CE-PTSD group was then assessed by their correlations with stress and psychiatric symptom severity and cognitive functioning.

RESULTS: Despite the absence of changes in brain structure in CE-PTSD, fALFF was abnormally increased in the right anterior insula/temporal pole (aIn/TP), left aIn, and bilateral parahippocampus (PH), whereas ReHo was reduced in the right inferior temporal gyrus. Greater increases in right aIn/TP fALFF correlated with more severe hyperarousal and impulsivity in CE-PTSD, suggesting ruminative thoughts or negative feelings hamper emotion regulation. Conversely, greater right PH fALFF correlated with lower hyperarousal and depression, signifying an adaptive response to stress that promotes better affective processing. Importantly, regional abnormalities were detrimental for more complex executive functions, consistent with observations that stress impedes cognitive flexibility and inhibitory control due to a persistent reliance on hypervigilant behaviors.

DISCUSSION: An unbiased, efficient and computationally reliable imaging approach identified intrinsic dysfunction in brain regions that may be core features of CE-PTSD. Though larger samples are needed for verification, the preliminary results provide new insights into the associations between regional abnormalities and different facets of emotion regulation and cognition, which in turn may impact an individual's functional abilities in daily life and responsiveness to psychotherapy.

PMID:40821020 | PMC:PMC12352161 | DOI:10.3389/fpsyt.2025.1591938

Hum Brain Mapp. 2025 Aug 15;46(12):e70322. doi: 10.1002/hbm.70322.

ABSTRACT

Common measures of brain functional connectivity (FC) including covariance and correlation matrices are symmetry-positive definite (SPD) matrices residing on a cone-shaped Riemannian manifold. Despite its remarkable success for Euclidean-valued data generation, the use of standard generative adversarial networks (GANs) to generate manifold-valued FC data neglects its inherent SPD structure and hence the inter-relatedness of edges in real FC. We propose a novel graph-regularized manifold-aware conditional Wasserstein GAN (GR-SPD-GAN) for FC data generation on the SPD manifold that can preserve the global FC structure. Specifically, we optimize a generalized Wasserstein distance between the real and generated SPD data under adversarial training, conditioned on the class labels. The resulting generator can synthesize new SPD-valued FC matrices associated with different classes of brain networks, for example, brain disorder or healthy control. Furthermore, we introduce additional population graph-based regularization terms on both the SPD manifold and its tangent space to encourage the generator to respect the inter-subject similarity of FC patterns in the real data. This also helps in avoiding mode collapse and produces more stable GAN training. Evaluated on resting-state functional magnetic resonance imaging (fMRI) data of major depressive disorder (MDD), qualitative and quantitative results show that the proposed GR-SPD-GAN clearly outperforms several state-of-the-art GANs in generating more realistic fMRI-based FC samples. When applied to FC data augmentation for MDD identification, classification models trained on augmented data generated by our approach achieved the largest margin of improvement in classification accuracy among the competing GANs over baselines without data augmentation.

PMID:40820900 | PMC:PMC12358810 | DOI:10.1002/hbm.70322

Addict Biol. 2025 Aug;30(8):e70083. doi: 10.1111/adb.70083.

ABSTRACT

Adaptive stress coping is often impaired in individuals with alcohol use disorder (AUD). This process relies on neurocircuitry involved in emotional and behavioural regulation, particularly the ventromedial PFC (vmPFC) and orbitofrontal cortex (OFC), along with limbic and ventral striatal regions (e.g., amygdala, hippocampus and nucleus accumbens). These systems are highly sensitive to the neurotoxic effects of alcohol, which may disrupt their ability to flexibly adapt in response to acute stress. This study investigated state-dependent changes (termed 'flexibility') in vmPFC-limbic/striatal and OFC-limbic/striatal functional connectivity from rest to acute stress in individuals with AUD versus matched controls and examined associations with coping strategies. Twenty-four adults with AUD (agemean = 33, 11F) and 23 matched controls (agemean = 32, 11F) underwent fMRI during resting-state followed by the Montreal Imaging Stress Task (MIST) and completed the COPE Inventory. Functional connectivity between vmPFC-limbic/striatal and OFC-limbic/striatal regions was assessed during rest and stress (MIST) conditions. Group differences in state-dependent changes in functional connectivity were analysed using repeated-measures ANCOVA. Functional connectivity between the right OFC-right amygdala and right OFC-right hippocampus increased from resting-state to the MIST in the control group, but this shift was not present in the AUD group (group x condition, pFDR < 0.05). Although connectivity did not differ between groups during the MIST (p's > 0.2), the AUD group exhibited elevated connectivity between these regions at rest (p's < 0.05). Moreover, among controls, increased right OFC-right hippocampus connectivity from rest to MIST was associated with more adaptive versus maladaptive coping (p < 0.05). Compared to controls, individuals with AUD exhibited a pattern of inflexible OFC-amygdala and OFC-hippocampus functional connectivity under changing stress conditions. Diminished stress-related connectivity changes in AUD appeared to be driven by elevated functional connectivity at rest. Future studies should test whether this resting-state connectivity pattern reflects an allostatic state that constrains the system's capacity to flexibly respond to acute stress.

PMID:40820466 | PMC:PMC12358688 | DOI:10.1111/adb.70083

Sci Rep. 2025 Aug 17;15(1):30096. doi: 10.1038/s41598-025-14736-z.

ABSTRACT

The Insula is an area of the brain that plays a vital role in various functions, mainly several executive functions (EFs) during neurological development. Functional connectivity (FC) between the Frontal lobes and the Insula, the regions most commonly associated with EFs, is claimed to play an essential role in EFs. However, there is insufficient data on the relationship between the FC between the two brain regions and the EFs in childhood and adolescence. We investigate the relationship between the degree of functional connection between the Insula and the Frontal lobe and EFs in a sample of Korean children's and adolescent communities. Total 95 participants between the ages of 6 and 17 were recruited. An fMRI seed-based connectivity analysis was conducted with the Insula and all the Frontal lobe areas of interest. A partial correlation analysis of the Stroop and Children's Color Trails Test (CCTT) were performed to measure the overall EFs. One hundred eleven children and adolescents (average age 12.23) participated in the resting functional magnetic resonance imaging (rs-fMRI) study. The Stroop and CCTT tests found a strong positive correlation with the functional connection between the Insula and the Frontal lobes. In particular, this study confirmed that the solid functional connection between the Inferior front gyrus and the Insula is related to good linguistic ability and attention. The functional solid connection between the Prefrontal gyrus and the Insula is related to developed inhibition and cognitive flexibility.

PMID:40820084 | PMC:PMC12358560 | DOI:10.1038/s41598-025-14736-z

Brain Topogr. 2025 Aug 18;38(5):58. doi: 10.1007/s10548-025-01133-y.

ABSTRACT

Hemifacial spasm (HFS) is a chronic neurological disorder characterized by involuntary muscle contractions of the face, significantly impacting patients' quality of life. Although the facial nerve nucleus has been implicated in HFS pathogenesis, specific research on its functional connectivity within whole-brain networks remains limited. This study aimed to investigate alterations in whole-brain functional connectivity with the facial nerve nucleus as the region of interest (ROI) in HFS patients, before and after microvascular decompression (MVD), to uncover potential mechanisms underlying the disorder and the impact of surgical intervention. Resting-state functional magnetic resonance imaging (rs-fMRI) was conducted on 30 HFS patients and 30 matched healthy controls. Functional connectivity (FC) was analyzed using the facial nerve nucleus as the seed ROI. Demographic, clinical, and laboratory data were collected, including spasm severity, anxiety and depression scores, and preoperative biomarkers. Statistical analyses assessed differences in FC and its correlation with clinical parameters. HFS patients demonstrated significantly increased FC between the left facial nucleus and the right parahippocampal gyrus, as well as between the right facial nucleus and the right fusiform gyrus, compared to healthy controls. These patterns persisted postoperatively, with additional increased FC observed between the right facial nucleus and bilateral superior temporal gyri. Correlation analyses revealed that left facial nucleus-right parahippocampal gyrus FC was positively associated with spasm severity and fibrinogen levels, while right facial nucleus-right fusiform gyrus FC was negatively correlated with monoamine oxidase (MAO) levels. ReHo of both facial nucleus showed significant differences between preoperative HFS patients and healthy controls, whereas ALFF/fALFF and lateralisation of facial nucleus did not show significant between-group differences. This study highlights the role of altered FC between the facial nucleus and brain regions involved in memory, emotion, and visual processing in HFS pathogenesis. While MVD provides symptomatic relief, its short-term effects on FC appear limited, suggesting that functional connectivity changes are chronic and may serve as biomarkers for disease monitoring. These findings provide novel insights into the neural mechanisms of HFS and emphasize the need for further research on long-term brain network adaptations post-surgery.

PMID:40820044 | PMC:PMC12358327 | DOI:10.1007/s10548-025-01133-y

Neuroimage. 2025 Aug 15;318:121420. doi: 10.1016/j.neuroimage.2025.121420. Online ahead of print.

ABSTRACT

Evidence indicates that brain waste clearance happens more efficiently during sleep. Recent studies suggest that the correlation, i.e., coupling, between the cortical grey matter (gGM) blood oxygenation level-dependent signal and cerebrospinal fluid (CSF) signal in the foramen magnum, measured via resting-state functional MRI (fMRI), serves as a non-invasive measure of the ventricular CSF system. Sleep deprivation has been demonstrated to affect brain function and health. Our aim is to assess gGM-CSF coupling after partial sleep deprivation, hypothesizing a change in the coupling measure relative to normal sleep. To test this hypothesis, we analyzed resting-state fMRI data from 63 healthy participants in the "The Stockholm Sleepy Brain Study", grouped according to age: younger (20 - 29 years) and older (65 - 75 years) adults. We examined gGM-CSF coupling twice in each subject, in the evening following a night of normal sleep and after a night of partial sleep deprivation (≤ 3 h of sleep). Our results revealed significantly increased gGM-CSF coupling after sleep deprivation compared to normal sleep (mean r = -0.30 ± 0.19 vs. -0.25 ± 0.14; t(62) = 2.05, p = 0.045). A linear mixed model demonstrated a significant interaction of age with the sleep condition (β = 0.0031, t = 2.73, p = 0.0083), showing significant changes only in the younger subgroup (t(35) = 2.99, p = 0.0050). These findings indicate that gGM-CSF coupling increases after partial sleep deprivation in younger adults, which may reflect compensatory mechanisms in response to reduced sleep duration. Furthermore, the results suggest that this compensatory response could be diminished in older adults.

PMID:40819829 | DOI:10.1016/j.neuroimage.2025.121420

Brain Res Bull. 2025 Aug 15;230:111512. doi: 10.1016/j.brainresbull.2025.111512. Online ahead of print.

ABSTRACT

Propofol demonstrates dependence at subclinical anesthetic doses, however, the underlying neural mechanisms remain unclear. In this study, we established a self-administration model of propofol in Sprague-Dawley (SD) rats, used a combination of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) analysis approach of resting-state functional magnetic resonance imaging (rs-fMRI) to examine the local brain functional activity changes, Western Blot (WB) was used to detect the change of c-Fos protein expression in the prefrontal cortex and hippocampus. Results showed that the propofol-dependent rats exhibited enhanced seeking behaviour and decreased spontaneous locomotor activity compared to saline control group, while increased ALFF values in the bilateral prefrontal cortex and right hippocampus, and increased ReHo values in the left striatum and pons. c-Fos gene expression in the prefrontal cortex was significantly increased in propofol-dependent rats compared with controls. In conclusion, enhanced seeking behaviour and decreased spontaneous locomotor activity in propofol-dependent rats may lead to abnormal functional activity and upregulation of c-Fos expression in the prefrontal cortex. These findings may shed light on propofol-dependent brain dysfunction from the perspective of local brain activity, emphasizing the potential usefulness of combining functional MRI and c-Fos expression in elucidating the neuropathological mechanisms of propofol dependence and may ultimately inform future disease treatment of propofol addiction.

PMID:40819826 | DOI:10.1016/j.brainresbull.2025.111512

Brain Res Bull. 2025 Aug 15:111514. doi: 10.1016/j.brainresbull.2025.111514. Online ahead of print.

ABSTRACT

Charcot-Marie-Tooth disease (CMT), an inherited peripheral nervous system disorder, causes muscle weakness, sensory deficits, decreased or absent tendon reflexes, and skeletal deformities. Although primarily a peripheral disorder, some studies indicate central nervous system (CNS) involvement. This study systematically investigated the potential structural and functional brain alterations in patients with CMT without overt CNS symptoms using magnetic resonance imaging (MRI) techniques. In this prospective cross-sectional study, 14 patients with clinically and genetically confirmed CMT and 14 age- and sex-matched healthy controls (HCs) underwent 3T brain MRI. Gray/white matter volume, cortical thickness, amplitude of low-frequency fluctuations (ALFF), and regional homogeneity (ReHo) were compared between groups. Compared to HCs, patients with CMT exhibited increased gray matter volume in the left cerebellar lobules IV-VI and right orbital part of the inferior frontal gyrus. The CMT group demonstrated significantly higher ALFF in the bilateral cuneus regions and decreased ALFF values in the left middle frontal gyrus. Additionally, enhanced ReHo was observed in the right middle occipital and right fusiform gyri in patients with CMT compared to that in HCs. No significant differences were observed in global brain volume or cortical thickness. Patients with CMT exhibited a CNS remodeling pattern and functional hyperactivation of the visual cortex. This phenomenon potentially underlies the neural basis of patients' increased reliance on visual feedback to compensate for proprioceptive deficits. This study provides insights into CNS involvement and neuroplastic adaptations in CMT, highlighting the importance of neuroimaging for understanding the multimodal pathophysiological mechanisms of this disorder.

PMID:40819825 | DOI:10.1016/j.brainresbull.2025.111514

Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Aug 13:S2451-9022(25)00248-4. doi: 10.1016/j.bpsc.2025.07.013. Online ahead of print.

ABSTRACT

BACKGROUND: Negative symptom severity predicts functional outcome and quality of life in people with psychosis. However, negative symptoms are poorly responsive to medication, and existing literature has not converged on their neurobiological basis. Previous work in small schizophrenia samples has observed that lower cerebellar-dorsolateral prefrontal cortex (DLPFC) connectivity is associated with higher negative symptom severity and that increasing cerebellar-DLPFC connectivity with neuromodulation reduces negative symptoms. We extended this finding by testing associations between cerebellar-DLPFC connectivity, negative symptoms, and cognitive performance in a large sample of individuals with psychosis.

METHODS: Individuals with psychosis spectrum disorders (n=260) underwent resting-state fMRI and clinical characterization using the Positive and Negative Symptoms Scale and the Screen for Cognitive Impairment in Psychiatry. Using a previously identified cerebellar region as a seed, we measured connectivity to the DLPFC and regressed connectivity against negative symptom severity, covarying for age, sex, and scanner. We then tested if cognitive performance indirectly affected the relationship between connectivity and negative symptom severity.

RESULTS: Across the psychosis spectrum, higher cerebellar-DLPFC connectivity was associated with lower negative symptom severity (r=-0.17, p=.007). This connectivity-negative symptoms relationship was not affected by psychosis subtype or duration of illness. Better delayed verbal learning was associated with higher cerebellar-DLPFC connectivity (r=.13, p=.034) and had a significant indirect effect on the relationship between connectivity and negative symptoms.

CONCLUSIONS: Our results extend relationships between cerebellar-DLPFC connectivity, negative symptom severity, and cognitive performance across the psychosis spectrum. Larger neuromodulation studies should test if increasing cerebellar-DLPFC connectivity reduces negative symptoms in psychotic disorders.

PMID:40816655 | DOI:10.1016/j.bpsc.2025.07.013

Brain Stimul. 2025 Aug 13;18(5):1539-1550. doi: 10.1016/j.brs.2025.08.003. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory cranial-cervical dystonia (CCD or Meige syndrome). However, clinical responses vary substantially across individuals, likely due to differences in electrode placement and modulation of target neural circuits.

METHODS: We retrospectively analyzed 51 patients with CCD treated with STN-DBS at a single center. Pre- and postoperative imaging was used to reconstruct electrode locations and model patient-specific electric fields. We then performed (i) voxel-wise sweet spot mapping to identify optimal stimulation sites, (ii) fiber filtering using normative tractography to determine white matter pathways associated with clinical improvement, and (iii) network mapping based on resting-state fMRI to identify functional connectivity patterns predictive of DBS response.

RESULTS: Voxel-wise correlation analysis revealed that the optimal stimulation localized to the STN motor subregion (R = 0.52, p < 0.001). Normative structural connectivity analysis showed that symptom improvement correlated strongly with modulation of fibers projecting to the cranial and cervical regions of sensorimotor cortex (R = 0.52, p < 0.001) and sensorimotor-associated basal ganglia pathways (R = 0.62, p < 0.001). Functional network mapping further revealed connectivity to the sensorimotor cortex as significantly associated with clinical improvement (R = 0.43, p = 0.002).

CONCLUSION: These findings inform refinement of STN targeting strategies in DBS for CCD. The involvement of cranial and cervical sensorimotor regions highlights the importance of symptom-based dystonia classification for individualized neuromodulation approaches.

PMID:40816470 | DOI:10.1016/j.brs.2025.08.003

J Affect Disord. 2025 Aug 13:120063. doi: 10.1016/j.jad.2025.120063. Online ahead of print.

ABSTRACT

BACKGROUND: Studies have demonstrated an association between cognitive decline and body mass index (BMI). However, the neural mechanisms that underlie this association remain unclear. This study aimed to investigate the relationship between BMI, cognitive function, and brain structural-functional connectivity (SC-FC) coupling.

METHODS: This study included 490 healthy subjects undergoing resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) scans and cognitive function tests. Structural connectivity (SC) was constructed using DTI, and functional connectivity (FC) was constructed using rs-fMRI. The SC-FC coupling was constructed using Spearman's correlation between the SC and FC. Linear regression analyses were conducted to investigate the associations of BMI and SC-FC with cognitive function. Finally, mediation analysis was performed to test whether SC-FC coupling mediated the relationship between BMI and cognitive function.

RESULTS: BMI was positively correlated with Fluency, TMT-A, and WMS-III-SS, while showing negative associations with BACS-SC, BVMT-R, and NAB-Mazes (all p < 0.05). Higher BMI was linked to increased SC-FC in the right caudal hippocampus (cHipp; β = 0.19) and middle temporal gyrus (MTG; β = 0.19). Mediation analyses showed that the positive effect of BMI on the right cHipp SC-FC mediated its negative impact on Fluency (45.43 % mediated); the influence of BMI on right cHipp SC-FC mediated poorer performance on NAB-Mazes (85.25 % mediated); and the positive effect of BMI on right MTG SC-FC enhanced NAB-Mazes performance (69.12 % mediated).

CONCLUSIONS: BMI influences cognitive function through its effects on brain SC-FC coupling, with distinct regional SC-FC patterns mediating both detrimental and beneficial cognitive outcomes.

PMID:40816371 | DOI:10.1016/j.jad.2025.120063

Psychiatry Res Neuroimaging. 2025 Aug 10;352:112046. doi: 10.1016/j.pscychresns.2025.112046. Online ahead of print.

ABSTRACT

BACKGROUND: Emerging evidence suggests that alcohol use disrupts large-scale brain network interactions, particularly within the triple network model-comprising the Salience Network (SN), Default Mode Network (DMN), and Frontoparietal Network (FPN). However, few studies have examined how these connectivity alterations vary across the full spectrum of alcohol consumption, especially using ultra-high-field imaging and data-driven approaches. This study leverages 7 Tesla resting-state fMRI and multivariate pattern analysis (MVPA) to characterize distinct brain connectivity patterns across heavy, moderate, and non-drinking adults, aiming to identify neural signatures that differentiate alcohol use severity levels.

METHODS: We analyzed resting-state functional connectivity data from 69 adults (Mean age - 28.96; SD - 3.49; Range: 22-36) [41M, 28F] drawn from the Human Connectome Project. Participants were stratified into three matched groups (n=23 each): heavy alcohol users (HA), moderate users (MA), and non-users (NA). Alcohol consumption was quantified using the Achenbach Self-Report (ASR) and the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). Functional connectivity within and between the SN, DMN, and FPN was assessed using both traditional seed-based analyses and MVPA. Between-group differences (HA vs. MA, HA vs. NA, MA vs. NA) were evaluated using Bonferroni corrected statistical tests.

RESULTS: Compared to non-users, alcohol users showed widespread increases in both intra- and inter-network functional coupling. The most striking differences emerged between HA and MA groups, with MVPA revealing unique hyperconnectivity signatures that distinguished these subgroups. Notably, HA individuals demonstrated reduced connectivity between the superior lateral occipital cortex and the precuneus, and hypoconnectivity between the orbitofrontal cortex and language-related regions. No significant sex differences were observed.

CONCLUSIONS: This study provides the first evidence from 7T MRI and MVPA that distinct functional connectivity profiles can discriminate levels of alcohol use severity in adults. The observed triple network hyperconnectivity-particularly between heavy and moderate users-may reflect early neurofunctional reorganization or compensatory mechanisms preceding the onset of alcohol use disorder. These findings advance the search for neurobiological markers of risk and resilience along the continuum of alcohol use and underscore the utility of high-field neuroimaging coupled with machine learning in addiction neuroscience.

PMID:40816048 | DOI:10.1016/j.pscychresns.2025.112046

Neuroimage Clin. 2025 Aug 6;48:103862. doi: 10.1016/j.nicl.2025.103862. Online ahead of print.

ABSTRACT

BACKGROUND: High-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex (DLPFC) serves as an effective treatment for major depression and other psychiatric disorders. Despite its growing clinical application, the neural mechanisms by which prefrontal rTMS exerts its therapeutic effects remain incompletely understood. To address this gap, we investigated the immediate blood-oxygen-level-dependent (BOLD) activity during 600 stimuli of left DLPFC 10 Hz rTMS in healthy individuals using interleaved TMS-fMRI.

METHODS: In a crossover design, 17 healthy subjects received 10 Hz rTMS (60 trains with 9-second intertrain intervals) over the left DLPFC at 40 % and 80 % of their resting motor threshold (rMT) inside the MR scanner.

RESULTS: 10 Hz rTMS over the left DLPFC elicited BOLD responses in prefrontal regions, cingulate cortex, insula, striatum, thalamus, as well as auditory and somatosensory areas. Notably, our findings revealed that 10 Hz rTMS effects were lateralized towards the contralateral (right) DLPFC. Dose-response effects between 40 % vs. 80 % rMT were exclusively observed in the hippocampus.

CONCLUSIONS: The 10 Hz rTMS protocol used in this study induced distinct target engagement and propagation patterns in the prefrontal cortex. These patterns differ from our previous interleaved TMS-fMRI findings using 600 stimuli of left DLPFC intermittent theta burst stimulation (iTBS) at the same intensities. Thus, interleaved TMS-fMRI emerges as a valuable method for comparing clinical prefrontal rTMS protocols regarding their immediate effect on brain circuits in order to differentiate their action mechanisms and to potentially inform clinical applications.

PMID:40816029 | PMC:PMC12362399 | DOI:10.1016/j.nicl.2025.103862