Most recent paper

J Psychopharmacol. 2025 Aug 21:2698811251360745. doi: 10.1177/02698811251360745. Online ahead of print.

ABSTRACT

BACKGROUND: Cannabis constituents, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), show distinct pharmacological profiles with therapeutic relevance for neurological and psychiatric conditions. THC exerts euphoric effects primarily via CB1 receptor activation, while CBD displays non-euphoric properties affecting various pathways.

AIMS: This study evaluated the effects of THC, CBD, and their combination on brain functional connectivity (FC) and cerebral blood flow (CBF) using multimodal neuroimaging.

METHODS: Adult male Sprague Dawley rats received intraperitoneal doses of 10 mg/kg THC, 150 mg/kg CBD, 10.8:10 mg/kg THC:CBD, or vehicle. Resting-state blood oxygenation level dependent magnetic resonance imaging and arterial spin labelling assessed FC and CBF, approximately 2 h after drug administration. Graph-theory metrics and seed-based analyses identified connectivity and perfusion alterations, while plasma analyses determined cannabinoid concentrations.

RESULTS: THC increased whole-brain FC and clustering coefficient, with elevated CBF in cortical and subcortical regions. CBD decreased FC metrics without affecting CBF, while THC:CBD induced moderate increases in both. Seed-based analysis revealed THC-driven increases in cortical-hippocampal and cortical-striatal connectivity, attenuated in the THC:CBD group. A multivariate combined analysis of FC and CBF revealed a divergent pattern of changes induced by each drug.

CONCLUSIONS: In conclusion, we show that THC and CBD induce distinct neurophysiological profiles in rats, with THC increasing both connectivity and perfusion, moderated by CBD when combined. These findings corroborate existing knowledge about the effects of cannabinoids on the brain, while also supporting the potential of preclinical functional neuroimaging to delineate cannabinoid-induced endophenotypes, offering insights for therapeutic development.

PMID:40838351 | DOI:10.1177/02698811251360745

Hum Brain Mapp. 2025 Aug 15;46(12):e70304. doi: 10.1002/hbm.70304.

ABSTRACT

Numerous studies have emphasized the time-varying modular architecture of functional brain networks and its relevance to cognitive functions in healthy participants. However, how modular dynamics of resting-state functional networks change in schizophrenia and how these alterations relate to neurotransmitter and transcriptomic signatures have not been well elucidated. We harmonized resting-state fMRI data from a multi-site sample including 223 patients and 279 healthy controls and applied the multilayer network method to estimate the regional module switching rate (flexibility) of functional brain connectomes. We examined aberrant flexibility in patients relative to controls and explored its relations to neurotransmitter systems and postmortem gene expression. Compared with controls, patients with schizophrenia had significantly higher flexibility in the somatomotor and right visual regions, and lower flexibility in the left parahippocampal gyrus, right supramarginal gyrus, right frontal-operculum-insula, bilateral precuneus, posterior cingulate cortex, and bilateral inferior parietal gyrus. These alterations were associated with multiple neurotransmitter systems and weighted gene transcriptomic profiles. The most relevant genes were preferentially enriched for biological processes of transmembrane transport and brain development, specific cell types, and previously identified schizophrenia-related genes. This study reveals aberrant modular dynamics in schizophrenia and its relations to neurotransmitter systems and schizophrenia-related transcriptomic profiles, providing insights into the understanding of the pathophysiology underlying schizophrenia.

PMID:40838333 | PMC:PMC12368516 | DOI:10.1002/hbm.70304

Front Physiol. 2025 Aug 5;16:1633028. doi: 10.3389/fphys.2025.1633028. eCollection 2025.

ABSTRACT

INTRODUCTION: Trigeminal neuralgia (TN) is a chronic neuropathic pain disorder characterized by spontaneous or triggered electric shock-like facial pain. Microvascular decompression (MVD) is the most effective surgical intervention for classical TN that is refractory to medication. Recent advances in neuroimaging have enhanced visualization of the trigeminal nerve's vascular anatomy, deepening insights into TN pathophysiology and paving the way for improved diagnostics and therapies. Resting-state functional magnetic resonance imaging (rs-fMRI) has been extensively applied in studies of TN, uncovering alterations in brain activity, functional connectivity, cortical thickness and neural networks.

METHODS: Independent component analysis (ICA) presents a powerful alternative for analyzing fMRI data, offering several advantages over traditional region of interests (ROIs) approaches. The sensorimotor network playing a key role in pain modulation, identifying neuroimaging differences in the sensorimotor network is crucial for detecting and intervening in TN, Forty TN patients underwent MVD surgery, with follow-up assessments conducted 6 months postoperatively and twenty-five healthy controls (HC) were recruited and scanned with resting state fMRI (rs-fMRI). Group ICA was used to identify ROIs and assessed inter-group differences in neural activity using false discovery rate (FDR) correction.

RESULTS: Compared to the HC, increased activity was observed in the right frontal operculum cortex, right insular cortex, right inferior frontal gyrus (pars opercularis), and right frontal pole in TN patients. Conversely, decreased activity was found in the right cerebellum (lobule IX) and left cerebellum (lobules VIII and IX). Compared to the pre-surgery, increased activity was found in the right precentral gyrus in the post-surgery group. Compared to the HC, long-term increased activity was still present in the right frontal operculum cortex, right insular cortex, right inferior frontal gyrus (pars opercularis), and right frontal pole despite the effectiveness of MVD surgery. In contrast, MVD significantly reduced the area of aberrant activation regions, particularly in the operculo-insular cortex, and also normalized cerebellar abnormalities.

DISCUSSION: Our study demonstrates that ICA can effectively identify distinct patterns of functional connectivity in the sensorimotor network associated with TN and MVD surgery. These regions are involved in altered pain processing, including nociceptive stimulus integration, subjective pain perception, pain chronification, and pain-related empathy. Our findings suggest promising biomarkers for TN and provide insights for developing targeted treatments.

PMID:40837096 | PMC:PMC12361157 | DOI:10.3389/fphys.2025.1633028

Sci Rep. 2025 Aug 20;15(1):30537. doi: 10.1038/s41598-025-15842-8.

ABSTRACT

Recent studies have highlighted the intricate relationship between cerebrospinal fluid (CSF) dynamics and global brain activity, suggesting a role in neurovascular coupling and brain waste clearance. The lateral ventricles are believed to play a key role in linking global BOLD (gBOLD) signals to CSF inflow (CSFin) to the fourth ventricle. In this study, we developed a method to reliably quantify lateral ventricle volume (LVV) in fMRI data. Using three independent datasets, including resting-state and task-based fMRI, we assessed dynamic changes in LVV and their associations with gBOLD and CSFin. Our findings reveal a strong anti-correlation between LVV and gBOLD across all datasets, with an average gBOLD lag of approximately 1 s. The derivative of the LVV time series were positively correlated with CSFin, with CSFin lagging LVV changes by 1.4-2.4 s. A moderate negative correlation was also observed between CSFin and gBOLD, consistent with prior research. These results support the hypothesis that LVV fluctuations, driven by global cerebral blood volume oscillations, regulate CSF movement into and out of the fourth ventricle. Our findings provide a foundation for further investigations into the role of LVV dynamics in aging and neurological disorders.

PMID:40835878 | PMC:PMC12368167 | DOI:10.1038/s41598-025-15842-8

Cogn Affect Behav Neurosci. 2025 Aug 20. doi: 10.3758/s13415-025-01328-7. Online ahead of print.

ABSTRACT

Impaired breathing-related interoceptive abilities have been associated with adverse outcomes, including higher levels of anxiety. However, brain connectivity patterns related to poor interoception, and how these may be modulated by anxiety, are poorly understood. This exploratory study investigated connectivity profiles associated with breathing-related interoceptive abilities in 65 volunteers who underwent ultrahigh-field (7 Tesla) "resting-state" magnetic resonance imaging (rs-fMRI), as well as completed a breathing-related interoceptive task and an anxiety questionnaire. The breathing task measured four aspects of interoceptive ability (sensitivity, decision bias, metacognitive bias, and insight), which served alongside anxiety to explain amygdala connectivity in the rs-fMRI data. We observed that connectivity between bilateral amygdala and insula cortex was linked to the level of confidence ascribed to respiratory-related interoceptive judgements (metacognitive bias), while left-lateralised connectivity between amygdala and insula cortex was associated with a worsened ability to detect inspiratory resistances (interoceptive sensitivity). Both reductions in confidence and sensitivity correlated weakly with heightened anxiety levels at a behavioural level. By contrast, the connectivity differences across levels of metacognitive bias and interoceptive sensitivity were not accounted for by anxiety. Our findings could suggest that, in the general population, connectivity between amygdala and insula cortex is linked to breathing-related interoceptive processes in a manner that is largely independent of anxiety.

PMID:40835808 | DOI:10.3758/s13415-025-01328-7

J Neurovirol. 2025 Aug 20. doi: 10.1007/s13365-025-01270-x. Online ahead of print.

ABSTRACT

Sleep disturbances are frequently reported in persons with HIV and have been associated with the use of certain integrase strand transfer inhibitors (INSTIs), such as dolutegravir. This exploratory study assessed changes in cerebral function parameters in individuals with insomnia switching INSTIs. Individuals with an insomnia severity index (ISI) above 8 and virologically suppressed on a dolutegravir-containing ART regimen (DTG-ART) were randomised 1:1 to either continue DTG-ART or switch to bictegravir/emtricitabine/tenofovir alafenamide (BIC-ART) for 120 days. Cerebral function parameters were measured longitudinally at baseline (D0) and day 120 (D120) and included: (1) patient-reported outcomes (PROs) assessing sleep, quality of life (QoL) and symptoms related to ART, (2) resting-state functional cerebral MRI (fMRI), examining functional connectivity networks previously associated with DTG use or sleep and (3) plasma soluble inflammatory biomarkers associated with neuroinflammation or HIV disease progression (Neopterin, CXCL10 and IL-6). Functional connectivity analyses were performed using Seed-Based Correlations (SBC), and correlations between connectivity changes, PRO measures and biomarker concentrations determined. Of 19 individuals (12 DTG-ART, 7 BIC-ART), median age was 55 years (range 28-83), all were male and 17 of white ethnicity. Over 120 days, improvements in sleep and QoL in those randomised to BIC-ART vs. DTG-ART were observed. Median change in Insomnia Severity Index (ISI) score - 9 (-14 to -2) vs. -1 (-10 to -4), p = 0.030, Epworth Sleepiness Scale (ESS) -3.0 (-6 to -1) vs. 2 (-3 to 6), p = 0.007 and Short Form-36 Physical Function (SF36-PF) -5 (-40 to 5) vs. 0 (-5 to 15), p = 0.026) for BIC- vs. DTG- ART, respectively. BIC-ART was also associated with increased functional connectivity in the Default Mode and Salience Networks (both p < 0.05), which correlated with improvements in PRO measures (ESS and SF36-PF, both p < 0.05). No significant changes in soluble biomarkers were observed. Individuals with insomnia switching to BIC-ART had improvements in self-reported sleep, QoL and resting state fMRI networks associated with sleep, when compared to those continued on DTG-ART.

PMID:40835806 | DOI:10.1007/s13365-025-01270-x

J Affect Disord. 2025 Aug 18;391:120074. doi: 10.1016/j.jad.2025.120074. Online ahead of print.

ABSTRACT

Suicide, which involves a decision-making process biased toward a lethal option that may result in the loss of one's own life, remains a major public health concern, particularly among young adults with major depressive disorder (MDD). This study investigates whether impaired decision-making in the context of loss distinguishes young adults with MDD and suicidal ideation (MDSI) from those without suicidal ideation (MDNSI) and healthy controls (HC), and explores the underlying neurocomputational mechanisms. A total of 110 young adults (23 MDSI, 31 MDNSI, and 56 HC) underwent resting-state functional magnetic resonance imaging (fMRI) and completed a two-armed bandit decision-making task designed to separate loss and reward contexts. Accuracy and computational parameters reflecting decision impulsivity were compared among groups using analysis of covariance. Logistic regression was performed to identify features predicting MDSI among MDD patients. Response time modeling was conducted to differentiate loss-related impulsivity from indecisiveness. Functional connectivity analyses focused on the ventral tegmental area (VTA) and habenula networks to identify alterations mediating loss-decision impulsivity in MDSI. MDSI patients uniquely exhibited premature, value-insensitive impulsive decisions in the loss context, distinguishing them from MDNSI patients independent of depression severity. These decision abnormalities were not attributable to indecisiveness. In contrast, reward-based decision impairments were shared across both MDD subgroups. Disruptions in resting-state functional connectivity within the VTA-orbitofrontal and habenula-default mode networks in MDSI fully mediated their loss-specific impulsivity. These findings highlight loss-specific decision impulsivity and associated neural dysconnectivity as potential early markers of suicide risk, offering novel insights into targeted intervention strategies.

PMID:40835190 | DOI:10.1016/j.jad.2025.120074

Brain Lang. 2025 Aug 19;270:105634. doi: 10.1016/j.bandl.2025.105634. Online ahead of print.

ABSTRACT

Previous studies have revealed the involvement of the bilateral ventral occipitotemporal cortex (vOT) in word reading, especially in Chinese character reading. However, the interhemispheric communication mechanisms of the bilateral vOT and how they work in Chinese character reading have not been fully investigated. Two experiments were conducted in this study to address those questions using resting-state and task-based fMRI. Experiment 1 revealed stronger interhemispheric resting-state functional connectivity (rsFC) in the posterior vOT subregion compared to the middle and anterior subregions and a significant positive correlation with Chinese reading efficiency in the posterior subregion. Experiment 2 further explored the effective connectivity in the Chinese rhythm and semantic judgment tasks using dynamic causal model analysis. Results showed significant interhemispheric intrinsic connections similar to those in the resting state in the posterior subregion and right-to-left modulatory connections in the middle and anterior subregions. In addition, stronger right-to-left modulatory connectivity in the anterior subregion was associated with better behavioral performance in the semantic judgment task. These convergent findings highlight the importance of interhemispheric communication of the bilateral vOT in Chinese character reading.

PMID:40834679 | DOI:10.1016/j.bandl.2025.105634

medRxiv [Preprint]. 2025 Aug 15:2025.08.13.25333244. doi: 10.1101/2025.08.13.25333244.

ABSTRACT

OBJECTIVE: Emotional dysfunction is a common consequence of severe traumatic brain injury (TBI), yet the mechanisms underlying these symptoms remain poorly understood. This study investigated whether brain network and autonomic mechanisms involved in emotional processing are abnormal in TBI.

METHODS: We conducted a cross-sectional study of chronic severe TBI (n=26) and healthy control participants (n=15). We analysed functional MRI (fMRI) data to assess brain processing of emotionally salient music (joyful and fearful stimuli; n=15 TBI, n=15 controls), and resting-state fMRI (rsfMRI) to measure the functional connectivity of relevant intrinsic brain networks (limbic, salience, and default mode networks; n=16 TBI, n=15 controls). We additionally measured the pupillary light reflect (PLR) to assess parasympathetic and sympathetic function (n=14 TBI, n=11 controls).

RESULTS: Individuals with severe TBI did not demonstrate the left insula activation elicited by joyful versus fearful musical stimuli seen in healthy controls. rsfMRI revealed decreased connectivity between the salience network, caudate and hippocampus in severe TBI compared to controls. Exploratory analyses identified reduced connectivity between default mode (bilateral medial prefrontal cortex) and limbic (bilateral amygdala) nodes in TBI compared to controls. PLR measurements revealed blunted dark-adaptation responses in individuals with severe TBI compared to controls (F(1,24)=27.4, p<0.001).

INTERPRETATION: Individuals with chronic severe TBI show reduced insula activation during emotional stimuli processing, resting connectivity abnormalities in salience, limbic and default mode networks, and evidence of sympathetic dysfunction. Brain network and autonomic alterations may be potential neural mechanisms of post-TBI emotional dysregulation.

PMID:40832426 | PMC:PMC12363739 | DOI:10.1101/2025.08.13.25333244

bioRxiv [Preprint]. 2025 Aug 11:2025.08.07.669216. doi: 10.1101/2025.08.07.669216.

ABSTRACT

The amplitude of low-frequency fluctuations (ALFF) and its related measure, fractional ALFF (fALFF), are widely used resting-state fMRI techniques for quantifying spontaneous neural activity within specific frequency bands. However, inconsistencies in the definition and implementation of ALFF have led to confusion in the field. In this study, we provide a mathematical clarification of ALFF and fALFF by introducing two variants: the arithmetic mean-defined ALFF/fALFF (amALFF/amfALFF) and the quadratic mean-defined ALFF/fALFF (qmALFF/qmfALFF). We examine the relationships between mean BOLD intensity (MBI), amALFF, and qmALFF across both subjects and voxels using two independent datasets mapped onto different brain templates. Additionally, we investigate the impact of z -scoring the original BOLD signal on ALFF and fALFF metrics. Our key findings include: (1) MBI is positively correlated with both amALFF and qmALFF, highlighting the need for normalization to subject-level means; (2) normalized qmALFF and qmfALFF are highly correlated with normalized amALFF and amfALFF, respectively, at both the subject and voxel levels; (3) z -scoring the BOLD signal does not affect amfALFF or qmfALFF, but it substantially alters amALFF and qmALFF. Based on these findings, we present a comprehensive flowchart of the (f)ALFF algorithm implemented in the temporal domain. The full procedure is implemented in R, and the corresponding script is available at: https://github.com/lejianhuang/ALFF .

PMID:40832169 | PMC:PMC12363799 | DOI:10.1101/2025.08.07.669216

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