Most recent paper

Imaging Neurosci (Camb). 2025 Aug 14;3:IMAG.a.112. doi: 10.1162/IMAG.a.112. eCollection 2025.

ABSTRACT

Mental transformations, such as mental rotation, rely on motor representations and engage neural processes similarly to physical actions. Neuroimaging studies reveal that mental rotation activates the occipito-parietal cortex and motor-related areas, with differences based on whether stimuli are bodily or non-bodily. These findings emphasize the role of frontoparietal networks in mental rotation, similar to those used in motor planning. This study investigated whether resting-state functional connectivity of the left lateral prefrontal cortex (lPFC), a region linked to motor planning, and other functional brain networks predicts mental rotation performance. Fifty-nine healthy individuals underwent functional magnetic resonance imaging (fMRI) to capture resting-state blood oxygenation level dependent (BOLD) activity and completed mental rotation tasks using bodily (hands) and non-bodily (letters) stimuli. Performance in both mental rotation tasks exhibited the expected peak of difficulty with completely inverted stimuli, which require a mental transformation of 180 degrees. At the functional level, mental rotation error rates correlated with lPFC connectivity to the default mode network (DMN). However, this relationship was negative and much stronger for the hands task, indicating that lPFC-DMN interactions were associated with poorer mental rotation performance. These results indicate that effective mental rotation relies on the functional disconnection of the DMN from motor planning networks. The findings highlight the significance of studying resting-state functional connectivity to understand how brain networks contribute to cognitive functions and how their interactions can enhance or impair performance. This work advances our understanding of the neural mechanisms underlying mental rotation, emphasizing the interplay between motor cognition and resting-state dynamics.

PMID:40831904 | PMC:PMC12358948 | DOI:10.1162/IMAG.a.112

Res Sq [Preprint]. 2025 Aug 11:rs.3.rs-7158945. doi: 10.21203/rs.3.rs-7158945/v1.

ABSTRACT

Here we employed interleaved single-pulse transcranial magnetic stimulation with functional MRI (spTMS/fMRI) to generate causal activation maps targeting the left hemisphere according to two sets of personalized resting connectivity targeting approaches in over 80 participants. Voxelwise event-related fMRI BOLD maps quantified TMS-evoked brain responses to each stimulation site. Group-level maps controlled for head motion, scalp discomfort, and somatosensory effects, ensuring specificity of the intended brain responses to stimulation. Stimulation of frontal regions targeting the subgenual anterior cingulate cortex (sgACC) induced BOLD responses in the sgACC and modulated distributed cortical and subcortical regions. Similarly, ventrolateral targets led to an average negative BOLD response in the amygdala target and numerous other distributed brain regions. ROI-based analyses revealed no significant group differences (depressed vs. healthy control) in evoked responses within the sgACC or amygdala. These results validate that image-guided TMS can causally engage distributed brain regions, supporting its utility for circuit and network-based neuromodulation. The publicly available causal connectivity maps might be used to guide future research linking cortical circuit maps with fMRI and/or behavioral outcomes.

PMID:40831497 | PMC:PMC12363917 | DOI:10.21203/rs.3.rs-7158945/v1

Psychol Med. 2025 Aug 20;55:e240. doi: 10.1017/S0033291725101177.

ABSTRACT

BACKGROUND: Schizophrenia (SCZ) and genetic high-risk (GHR) individuals exhibit deficits in brain functional networks and cognitive function, potentially impacted by SCZ risk genes. This study aims to delineate these impairments in SCZ and GHR individuals, and further explore how risk genes affect brain networks and executive function.

METHODS: A total sample size of 292 participants (100 SCZ, 68 GHR, and 124 healthy controls [HCs]) in the study. The Wisconsin Card Sorting Test (WCST) and resting-state functional magnetic resonance imaging (rs-fMRI) are utilized to evaluate executive function and brain network topology. SCZ-related polygenic risk scores (SCZ-PRS) were used to evaluate genetic risk levels. WCST and PRS were not applied to all participants.

RESULTS: Significant reductions in nodal efficiency and degree centrality (Dnodal) were observed within the right median cingulate and paracingulate gyri (MCPG_R) in both SCZ and GHR groups, compared to HCs. There were significant correlations between SCZ-PRS, Dnodal in MCPG_R, and WCST scores. Moreover, Dnodal in MCPG_R completely mediated the relationship between SCZ-PRS and executive function. The enrichment analysis of these risk genes indicates their involvement in biological processes of signal transduction and synaptic transmission.

CONCLUSIONS: This study highlights the pivotal role of impaired cingulate function in mediating the effects of genetic risks on executive deficits, offering new insights into the genetic-neuro-cognitive nexus in schizophrenia and potential targets for clinical interventions.

PMID:40831310 | DOI:10.1017/S0033291725101177

Alzheimers Res Ther. 2025 Aug 19;17(1):192. doi: 10.1186/s13195-025-01800-z.

ABSTRACT

BACKGROUND AND OBJECTIVES: The two variants of primary progressive aphasia (PPA) with Frontotemporal dementia pathology- semantic (svPPA) and non-fluent (nfvPPA) exhibit both shared and distinct features. The phenotypic heterogeneity stems from alterations in underlying brain networks. Investigating the common network (CN) and variant-specific unique network (UN) is critical to understanding the pathology of these conditions. Additionally, examining the evolution of these networks is key to elucidating disease progression.

METHOD: We applied algebraic-topology to explore the CN and UN using individualised resting-state fMRI data from 31 patients with nfvPPA, 32 with svPPA, and 38 age- and sex-matched controls (scanned at first visit). Using persistent homology, we identified the networks that differentiated (p < 0.01) each patient group from healthy controls. Since the subset of these subjects was scanned at the 6th and 12th months, the longitudinal changes in the rsfMRI networks were evaluated at each interval. Network features were correlated with clinical behaviours, and the longitudinal impact of the changes in these networks on behaviours was evaluated over the 12-month period. To validate the rsfMRI networks and the longitudinal changes, we evaluated the grey matter (GM) volume, GM atrophy and the rate-of-atrophy of the brain areas. To corroborate the findings, we applied persistent homology on the structural networks derived from diffusion tensor images.

RESULT: We found the existence of a left lateralised functional network identical in both PPA groups. This CN, comprising regions associated with language and cognition, remained stable over time (12 months period) and was associated with the severity of dementia. Conversely, the right-dominant UN in both variants showed progressive disintegration annually. In svPPA, cerebellar disassociation led to a decline in daily life activities, while parietal lobe degradation in nfvPPA impaired naming abilities. The CN and UN with similar regions were also found in the structural connectivity and the longitudinal changes in UN aligned with accelerated GM atrophy in the affected regions.

DISCUSSION: Given the limited availability of pharmacological treatments, rehabilitation in PPA has primarily focused on modulating the left hemisphere using brain stimulation techniques. However, our findings indicate that while the disintegrated left hemispheric CN remained relatively stable, dysconnectivity progressed in the right hemisphere. These observations, along with the phylogenetic organization of brain networks and the variant-specific patterns of progression, highlight the need to incorporate right hemispheric rehabilitation strategies alongside the conventional left-hemispheric approaches in PPA.

PMID:40830901 | PMC:PMC12362973 | DOI:10.1186/s13195-025-01800-z

Eur Arch Psychiatry Clin Neurosci. 2025 Aug 19. doi: 10.1007/s00406-025-02079-9. Online ahead of print.

ABSTRACT

BACKGROUND: Deficits in the hippocampus are a consistent finding in schizophrenia and have also been demonstrated in early-stage psychosis. Moreover, alterations in hippocampal anatomy and connectivity have been implicated in aberrant functional interactions in subcortical and cortical networks. However, the nature and extent of these alterations and their association with frontal and subcortical regions remain unclear.

METHODS: To address these questions, we analysed resting state fMRI functional connectivity and graph properties in n = 93 individuals at clinical high-risk for psychosis (CHR-P), n = 26 patients with first-episode psychosis (FEP), n = 31 individuals with affective disorders and substance abuse as well as n = 58 healthy controls. We used novel denoising techniques and individually optimised functional connectivity matrices, which were compared across clinical groups. Finally, the centrality of the hippocampus as well as network segregation and integration were assessed using graph-based analysis.

RESULTS: Both the FEP and CHR-P groups were characterised by reduced functional connectivity between the hippocampus and inferior frontal cortex albeit the differences in CHR-P individuals did not survive corrections for multiple comparisons. Compared to CHR-P, FEP show lower centrality of the hippocampus but increased network segregation.

CONCLUSIONS: Our findings show lower connectivity between the hippocampus and frontal cortex in early-stage psychosis, with FEP patients showing stronger decreases in connectivity compared to CHR-Ps. Furthermore, network-based analyses highlight reduced centrality in FEPs compared to CHR-Ps, indicating reduced influence on the wider network. Thus, altered connectivity along the hippocampal-frontal axis could be a potential marker of illness stage in early-stage psychosis.

PMID:40828422 | DOI:10.1007/s00406-025-02079-9

Eur Arch Psychiatry Clin Neurosci. 2025 Aug 19. doi: 10.1007/s00406-025-02090-0. Online ahead of print.

ABSTRACT

BACKGROUND: Schizophrenia is marked by disruptions in functional connectivity; however, findings on the specific brain regions involved and the direction of connectivity changes remain inconsistent. Therefore, a more comprehensive framework that evaluates whole-brain functional connectivity is needed to better understand brain dysfunction and its relationship to symptoms. This study aims to investigate whether the primary gradient in schizophrenia patients differs significantly from that in healthy controls using recently developed gradient-based analysis.

METHODS: We applied a gradient analysis to resting-state fMRI data to characterize the sensorimotor-to-transmodal functional cortical organization in schizophrenia patients (n = 32) and healthy controls (n = 27). We also used correlation analysis to examine the relationship between primary gradient organization and PANSS positive, negative, general subscale scores and total scores of SANS in schizophrenia patients.

RESULTS: The gradient analysis demonstrated that, compared with the healthy controls, schizophrenia exhibited reduced sensorimotor-to-transmodal differentiation in which there is increased gradient values from the sensorimotor systems of the cortical organizations such as visual network and decreased gradient values from the higher-level systems such as salience network and frontoparietal network. Alterations in primary gradient organization were significantly associated with PANSS positive and negative subscales, and total scores of SANS in schizophrenia.

CONCLUSION: The results indicate that schizophrenia exhibits disrupted cortical functional organization, and this arises from the reduced differentiation within the sensorimotor-to-transmodal gradient. These alterations in the sensorimotor-to-transmodal gradient explains variability in some of the clinical symptoms of schizophrenia.

PMID:40828421 | DOI:10.1007/s00406-025-02090-0

Brain Struct Funct. 2025 Aug 19;230(7):137. doi: 10.1007/s00429-025-02996-4.

ABSTRACT

Monoaminergic systems, including serotonin, dopamine, and norepinephrine, are essential for regulating brain activity and facilitating behavioral flexibility. These systems originate from brainstem nuclei and project widely to modulate functions such as mood, attention, memory, and adaptability. Using resting-state functional MRI (rs-fMRI), this study aimed to investigate the connectivity networks of key monoaminergic nuclei in 193 healthy adults and explore their correspondence with molecular imaging maps of neurotransmitter-specific biochemical markers. Functional connectivity (FC) was assessed using seed-based rs-fMRI analyses with seeds placed in the dorsal raphe nucleus (DRN), nucleus centralis superior (NCS), ventral tegmental area (VTA), substantia nigra pars compacta (SNc), and locus coeruleus (LC). Cross-modal analyses using molecular imaging data were performed to correlate these rs-FC maps with the distribution of neurotransmitter-related receptors, transporters, and synthesis enzymes, providing insights into the molecular architecture underlying the FC of monoaminergic systems. Whole-brain FC maps revealed distinct patterns for each nucleus. DRN projections were extensive, connecting to subcortical regions such as the hippocampus and amygdala and cortical areas including the precuneus, cingulate, and medial frontal cortex. NCS projections overlapped partially but uniquely targeted the orbitofrontal and insular cortices. Dopaminergic pathways exhibited connectivity with the striatum, thalamus, and prefrontal cortex, while noradrenergic LC projections displayed lateralized connectivity to occipital, temporal, and frontal regions. Cross-modal correlations with molecular imaging demonstrated significant spatial associations between rs-FC maps and neurotransmitter-specific markers, including 5HTT, DAT, and FDOPA. This study enhances our understanding of neurotransmitter networks, highlighting their relevance in brain function and potential as biomarkers for neuropsychiatric conditions.

PMID:40828212 | PMC:PMC12364969 | DOI:10.1007/s00429-025-02996-4

Psychopharmacology (Berl). 2025 Aug 19. doi: 10.1007/s00213-025-06881-0. Online ahead of print.

ABSTRACT

RATIONALE: Alcohol use disorder (AUD) is a common mental health disorder affecting many individuals and their families in the United States. The effects of alcohol are not fully understood, particularly the effect of alcohol on baseline brain activity.

OBJECTIVES: We aimed to assess whether chronic ethanol exposure alters resting state functional connectivity between regions of interest (ROIs) previously associated with addiction in male rats. We also aimed to assess whether inhibition of histone deacetylases (HDAC) reduced or blocked the effects of chronic ethanol exposure. Finally, we aimed to investigate whether chronic ethanol exposure altered regional homogeneity (ReHo) and whether HDAC inhibition blocked the effects of ethanol on ReHo.

METHODS: Male rats were administered water or ethanol (5 g/kg, 25% v/v) via intragastric gavage once daily during the light cycle for 14 days and allowed to withdraw for 24 h. Rats were additionally injected with either the HDAC inhibitor trichostatin A (TSA) (2 mg/kg, i.p.) or vehicle (10% DMSO in 0.9% saline) on the last two days of gavage and on the last day of withdrawal. Rats were scanned with magnetic resonance imaging (MRI) to obtain an anatomical scan as well as resting state functional connectivity (rs-fMRI).

RESULTS: We found that chronic ethanol exposure decreased rs-fMRI in the following pairs of ROIs: caudate putamen-prelimbic cortex, caudate putamen-infralimbic cortex, caudate putamen-nucleus accumbens core as well as caudate putamen-insula, insula-prelimbic cortex, and insula-infralimbic cortex. Chronic ethanol exposure also decreased ReHo, particularly in the dorsal striatum. We did not find significant effects of inhibition of HDACs on rs-fMRI of ROIs or ReHo.

CONCLUSIONS: Chronic alcohol exposure and withdrawal decreases baseline functional connectivity and local synchrony in male rats which is not affected by HDAC inhibition. Future studies should examine the effects of alcohol on resting state connectivity in female rats as well as in voluntary alcohol consumption paradigms. Understanding baseline differences may open new therapeutic avenues in alcohol abuse and AUD to restore typical resting state connectivity.

PMID:40828173 | DOI:10.1007/s00213-025-06881-0

Transl Psychiatry. 2025 Aug 18;15(1):293. doi: 10.1038/s41398-025-03524-y.

ABSTRACT

Amygdala-hippocampal connectivity is a promising area of study for an understanding of the neurobiological mechanisms of depression. In this study, we examined the association between amygdala-hippocampal connectivity and depressive symptoms in children with a specific focus on the subnuclei level. We then examined whether self-concept mediated brain-behavior associations. Resting-state functional magnetic resonance imaging (fMRI) was performed at age 7.5 years (N = 319), followed by self-reported depressive symptoms and self-concept between ages 8.5 and 10.5 years, using the Children's Depression Inventory (CDI-2) and Piers-Harris Children's Self-Concept Scale (PHCSC) respectively. We conducted multiple regression analyses to examine the associations between the amygdala-hippocampus resting-state functional connectivity (RSFC) and CDI scores, first at the whole-region level and subsequently at the subnuclear level. Mediation analyses were then performed to explore the mediating role of self-concept in these brain-behavior associations. We observed a significant association between left amygdala-anterior hippocampus connectivity and CDI total scores, primarily driven by the left superficial amygdala. Further exploration at sub-symptomatic levels highlighted an association with negative cognition. Finally, self-concept mediated the association between left amygdala-anterior hippocampus connectivity and depressive symptoms in children. This study provided valuable insights into the associations among amygdala-hippocampal subnuclei connectivity, childhood depressive symptoms, and self-concept. Diminished left superficial amygdala-anterior hippocampus connectivity may serve as an early biomarker to identify depressive symptoms, particularly in children with negative cognition problems.

PMID:40825774 | PMC:PMC12361540 | DOI:10.1038/s41398-025-03524-y

Biol Psychiatry Cogn Neurosci Neuroimaging. 2025 Aug 16:S2451-9022(25)00249-6. doi: 10.1016/j.bpsc.2025.08.001. Online ahead of print.

ABSTRACT

BACKGROUND: Moral injury (MI) is a condition that may emerge following a violation of an individual's moral code. MI leads to significant functional impairment in many trauma-exposed civilians with rumination proposed as a mechanism of action. Little is known about the neuropathophysiology of different MI dimensions, including MI related to transgressions caused by the self or others. We examined links between facets of MI, resting-state amplitude of low frequency fluctuations (ALFF) and rumination in trauma-exposed civilians.

METHODS: Sixty adults (18-65 years, 51 female) completed measures of moral injury (Moral Injury Exposure and Symptom Scale for Civilians, MIESS-C), rumination (Response Styles Questionnaire, RSQ), and resting-state fMRI. Voxel-wise linear regression on ALFF was performed with rumination and MIESS-C-derived self, other, and betrayal-related MI as regressors.

RESULTS: Betrayal-related MI associated with higher ALFF in the bilateral precuneus and left medial prefrontal cortex. Other-related MI associated with lower ALFF in the left dorsolateral prefrontal cortex and insula (voxel-wise p<.001, cluster false discovery rate-corrected p<.05). Rumination severity was positively associated with betrayal-related ALFF clusters in the bilateral precuneus r =0.32, p =0.012, and left medial prefrontal cortex, r =0.31, p =0.017.

CONCLUSIONS: Results reveal distinct neural signatures of MI, with betrayal-related MI associated with greater ALFF in default mode network regions, and this activation related to rumination severity. Other-related MI linked with diminished activation in cognitive control and interoceptive network regions, which may reflect physiological withdrawal. These signatures are attractive candidate neuromodulatory targets.

PMID:40825519 | DOI:10.1016/j.bpsc.2025.08.001

Proc Natl Acad Sci U S A. 2025 Aug 26;122(34):e2505294122. doi: 10.1073/pnas.2505294122. Epub 2025 Aug 18.

ABSTRACT

Functional connectivity (FC), a statistical correlation of pair-wise brain signals from resting-state (RS) functional MRI (fMRI), is a widely used concept for mapping large-scale functional networks in both humans and animals. However, its underlying causal mechanism remains poorly understood, particularly for strong interhemispheric connectivity (e.g., homotopic connections) consistently observed in FC. In this study, we investigated the neural basis of RS FC in mice using fMRI with anatomically defined patterned optogenetic activation and inhibition of excitatory neurons in six cortical regions. Unlike commonly used optogenetic activation, optogenetic silencing suppresses spontaneous neural activity in a localized region, reducing RS synaptic inputs to downstream networked areas. Consequently, fMRI can track spontaneous functional connections without the neural perturbations associated with excitation. While conventional optogenetic activation of excitatory neurons in the targeted cortical areas predominantly elicited their ipsilateral functional responses in both cortical and subcortical regions, optogenetic silencing induced both intra- and interhemispheric cortical responses, which were stronger than cortical-subcortical connections. These effects more closely resembled statistically defined RS FC patterns, providing insight into the underlying mechanisms of intrinsic FC. By modeling synaptic path length-dependent connectivity patterns based on structural connectivity (SC), we found that spontaneous functional connections can be explained by polysynaptic propagation, whereas evoked activity is largely restricted to monosynaptic pathways. These findings highlight the critical role of polysynaptic pathways in shaping spontaneous connectivity, suggesting that RS FC arises from causal interactions of spontaneous ongoing neural activity.

PMID:40825135 | DOI:10.1073/pnas.2505294122

Parkinsons Dis. 2025 Aug 7;2025:6870215. doi: 10.1155/padi/6870215. eCollection 2025.

ABSTRACT

Background: Parkinson's disease (PD), a progressive neurodegenerative disorder marked by motor and nonmotor symptoms, with resting-state fMRI (rsfMRI) proving pivotal in identifying neural circuit abnormalities and functional connectivity patterns, paving the way for a more personalized, precision medicine approach to PD diagnosis and treatment. Methods: Given its significance, this study conducted a bibliometric analysis to systematically map the intellectual landscape of rsfMRI applications in PD research. Relevant publications were sourced from the Web of Science Core Collection database from January 1, 2009, to July 18, 2024, and restricted to English-language articles and review articles. Utilizing VOSviewer and CiteSpace software, the analysis covered publication distributions across countries, institutions, and authors, along with co-citation patterns among co-authors and journals, keyword co-occurrence, and burst detection. Results: A total of 658 publications from January 1, 2009, to July 18, 2024, were identified, showing a gradual increase in annual publication and citation volume in earlier years. Notably, a decline emerged in 2023, highlighting the need for research paradigm shift to drive further progress. Among 45 countries and 865 institutions, China, led in publication and citation counts at both the institutional and author levels, with neuroscience-related journals playing a key role in advancing this field. Keyword analysis identified emerging research frontiers, including disease heterogeneity, early detection, symptom-specific mechanism exploration, and treatment evaluation. Conclusions: Results from this bibliometric analysis systematically elucidates the historical development, research progress over the years, and current research hotspots in rsfMRI studies of PD, thereby offering valuable guidance for future research endeavors in this field.

PMID:40822039 | PMC:PMC12352997 | DOI:10.1155/padi/6870215

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