Most recent paper

Psychiatry Res. 2026 Jul 28;364:117349. doi: 10.1016/j.psychres.2026.117349. Online ahead of print.

ABSTRACT

BACKGROUND: Transcranial magnetic stimulation (TMS) offers a noninvasive alternative to pharmacotherapy for treatment-resistant depression (TRD). A new fMRI-guided accelerated TMS protocol demonstrates rapid clinical efficacy, although predictive biomarkers of response have not yet been established. This study examines the efficacy of the new TMS protocol in a unique clinical setting and explores a biomarker for predicting antidepressant response to accelerated intermittent theta burst stimulation (iTBS).

METHODS: We conducted a retrospective chart review of 29 patients (ages 18-74) who received accelerated iTBS targeting the left dorsolateral prefrontal cortex (DLPFC). Patients received 10 iTBS sessions per day for 5 consecutive days, totaling 50 sessions. Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) throughout the treatment. Resting-state fMRI data was used to conduct correlational analysis between the mesolimbic pathway and clinical improvement.

RESULTS: Patients exhibited a rapid and significant reduction in MADRS scores, with response and remission rates of 72.41% and 65.52%, respectively, by Day 5. Suicidality significantly improved from baseline to Day 5, with 86% of patients having a resolution of suicidality by Day 5. Resting state functional connectivity (RSFC) between the right NAcc and left VTA was significantly associated with greater percent reduction in depressive symptoms.

DISCUSSION: Our findings suggest that accelerated iTBS yields rapid antidepressant effects and robust reductions in suicidality in treating TRD. Moreover, RSFC within the mesolimbic pathway may serve as a potential biomarker for predicting treatment response. Future work should conduct double-blind, sham-controlled trials with larger samples.

PMID:42537324 | DOI:10.1016/j.psychres.2026.117349

Front Aging Neurosci. 2026 Jul 16;18:1862635. doi: 10.3389/fnagi.2026.1862635. eCollection 2026.

ABSTRACT

BACKGROUND: Pisa syndrome (PS) is a disabling postural complication of Parkinson's disease (PD), but its functional network basis remains insufficiently defined. The aim of this study is to determine whether PD with PS is associated with multilevel resting-state functional network abnormalities beyond differences in motor severity.

METHODS: We studied 31 patients with PD and PS and 42 patients with PD without PS using resting-state fMRI. Analyses included seed-based functional connectivity, regional homogeneity, fractional amplitude of low-frequency fluctuations, and graph-theoretical metrics of whole-brain topology. Group comparisons adjusted for age, sex, education, Hoehn and Yahr (H&Y) stage, and levodopa equivalent daily dose (LEDD); sensitivity analyses further adjusted for the Movement Disorder Society-Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III).

RESULTS: Compared with PD without PS, PD-PS showed reduced connectivity between the pedunculopontine nucleus (PPN) and the left supplementary motor area (SMA) and right cerebellar Crus I, reduced interoccipital connectivity, increased connectivity between the right anterior insula and posterior cingulate/medial prefrontal cortex, lower occipital and postcentral fALFF, lower right superior parietal ReHo, and disrupted whole-brain topology with lower small-worldness and efficiency and longer path length. PPN-SMA connectivity correlated inversely with MDS-UPDRS-III and positively with visuospatial/executive performance, but not with lateral flexion angle; global efficiency correlated with Hoehn and Yahr stage and lateral flexion angle. PPN-related findings reflect connectivity involving a PPN-centered brainstem region rather than the PPN nucleus per se. Findings remained significant after additional adjustment for MDS-UPDRS-III.

CONCLUSION: PS in PD is associated with convergent abnormalities involving brainstem-sensorimotor coupling, visual-parietal integration, salience-default mode interactions, and global network organization. These findings demonstrate group differences in functional network organization between PD patients with and without PS. They support a multilevel network model, but further studies are needed to determine whether these alterations are specifically related to PS severity or pathophysiology.

PMID:42534898 | PMC:PMC13422441 | DOI:10.3389/fnagi.2026.1862635

Front Public Health. 2026 Jul 16;14:1805995. doi: 10.3389/fpubh.2026.1805995. eCollection 2026.

ABSTRACT

BACKGROUND: Diminished ovarian reserve (DOR) is a condition that severely impacts female fertility, and there are currently no effective treatment strategies for DOR. Moxibustion may offer a non-invasive, low-risk intervention. This study aims to assess the clinical efficacy of moxibustion in improving ovarian reserve in women with DOR and to explore its underlying central neural mechanisms using resting-state functional magnetic resonance imaging.

METHODS: This prospective, single-center, parallel-group randomized controlled trial will be conducted at the Hubei Provincial Hospital of Traditional Chinese Medicine. Participants diagnosed with DOR will be randomly assigned in a 1:1 ratio to either an intervention group or a control group. They will both receive a lifestyle intervention. In addition, the intervention group will receive 16-week Yin-Yang Regulating Moxibustion. The primary outcome include changes in antral follicle count. Secondary outcomes include serum levels of anti-Müllerian hormone, follicle-stimulating hormone, and luteinizing hormonechanges in menopausal symptoms, anxiety, depression, and quality of life. Rs-fMRI will be used to investigate the brain's central neural mechanisms.

DISCUSSION: The results of this study will provide new insights into the adjunctive treatment of DOR and elucidate its potential mechanisms through neuroimaging.

CLINICAL TRIAL REGISTRATION: https://itmctr.ccebtcm.org.cn/, identifier ITMCTR2025001808.

PMID:42534888 | PMC:PMC13422477 | DOI:10.3389/fpubh.2026.1805995

Front Hum Neurosci. 2026 Jul 16;20:1860966. doi: 10.3389/fnhum.2026.1860966. eCollection 2026.

ABSTRACT

BACKGROUND: Many patients with IDH-mutated gliomas struggle with cognitive dysfunction and mental fatigue at long-term follow-up. Here, we investigate the relationship between functional network re-organization and long-term cognitive outcomes in patients treated for IDH mutated glioma.

METHODS: We examined 61 patients at 5-21 years post-surgery using resting-state fMRI and neuropsychological testing. Individual-level network maps were obtained by regressing each patient's resting-state time series against reference template networks via dual regression, and network integrity was quantified as the spatial correspondence between these maps and the corresponding healthy templates. The Mental Fatigue Scale and Hospital Anxiety and Depression Scale were used to assess fatigue, depression and anxiety.

RESULTS: Tests of executive function, processing speed/attention, and language showed significant associations with auditory, executive control, and frontoparietal network-template similarity. Memory domains displayed distinct patterns: visual memory correlated with network-template similarity of the default mode network, and verbal memory with the auditory network. Mental fatigue correlated with executive function, processing speed/attention, and language performance. Three cognition-fatigue profiles emerged, distinguished by depression/anxiety levels and auditory/sensorimotor network integrity.

CONCLUSION: In patients with IDH mutated gliomas at long-term follow-up, preserved cognitive performance is associated with functional network organization resembling healthy brain templates. For patients with cognitive impairment, different networks were linked to distinct cognitive domains. Patients with a combination of mental fatigue and executive impairment were characterized by most pronounced network re-organization and highest symptoms of anxiety and depression. These findings suggest network-specific rehabilitation approaches targeting the interplay between fatigue, mood, and executive control may improve patient outcomes.

PMID:42534736 | PMC:PMC13422171 | DOI:10.3389/fnhum.2026.1860966

J Mil Veteran Fam Health. 2023 Dec 12;9(5):38-55. doi: 10.3138/jmvfh-2023-0014. eCollection 2023 Dec 1.

ABSTRACT

INTRODUCTION: In recent clinical trials, psychedelic-assisted psychotherapy (PAP) led to symptomatic improvement among people with several psychiatric conditions. PAP has three distinct phases: preparation, support during psychedelic administration, and integration. The purpose of this scoping review was to identify randomized controlled trials that used PAP and synthesize the research base related to neuronal networks and neural function as measured with neuroimaging during the integration period and to link these findings to psychological changes after PAP.

METHODS: PubMed and ProQuest databases were searched using key words. Inclusion and exclusion criteria were used to determine whether an article would be reviewed. The authors specifically focused on articles that used neuroimaging or reported a psychological outcome one day or more after psychedelic administration.

RESULTS: Most articles used functional magnetic resonance imaging (fMRI) and, in particular, resting-state fMRI to assess functional connectivity. Results generally reported changes in higher-order networks, although the direction of change in strength of connectivity was variable. Themes related to psychological findings were linked to increases in psychological and cognitive flexibility, increased openness, and decreased neuroticism after psychedelic treatment.

DISCUSSION: In general, more consistent methodology across the field should be applied to make progress in understanding network-based changes underlying clinical improvements after PAP. Limited evidence suggests that changes in the executive control network, and in its integration with other networks, may result in greater cognitive flexibility during the integration period.

PMID:42533988 | PMC:PMC13293224 | DOI:10.3138/jmvfh-2023-0014

Sci Data. 2026 Jul 30;13(1):1107. doi: 10.1038/s41597-026-07746-7.

ABSTRACT

Trajectories of age-related neurocognitive decline are nonuniform, and are impacted by numerous environmental and physiological factors. Earlier life phases set the stage for later life neurocognitive function, with midlife marking a critical transition characterized by increasing variability in cognitive, affective, and physiological functioning. Despite its importance, this turbulent period remains underrepresented in open neuroimaging data resources. To address this gap, the Nathan Kline Institute - Rockland Sample (NKI-RS) created 'Mapping Interindividual Variation in the Aging Connectome' (MIVAC), an openly shared, multimodal dataset designed to map brain aging trajectories beginning in midlife and assess the influence of key modifiable factors linked to dementia prevention such as cardiorespiratory fitness, sleep, and mood. This longitudinal investigation includes 348 community-ascertained participants aged 38 to 71 years at baseline, with 219 participants completing 3 annual timepoints. Data collection incorporated deep phenotyping, including detailed assessment of cognitive, behavioral, medical, and cardiorespiratory fitness domains, to compliment multimodal neuroimaging (resting-state fMRI, diffusion MRI, morphometric MRI, and arterial spin labeling) and biospecimen collection. The protocol harmonizes with prior NKI-RS sub studies, enabling lifespan cross-sectional or longitudinal questions, while incorporating age-specific considerations for cognitive and neural aging. The full dataset is openly available.

PMID:42532989 | DOI:10.1038/s41597-026-07746-7

Sleep Med. 2026 Jul 28;147:109167. doi: 10.1016/j.sleep.2026.109167. Online ahead of print.

ABSTRACT

OBJECTIVE: Idiopathic REM sleep behavior disorder (iRBD) is a well-established prodromal manifestation of α-synucleinopathies, and patients without hyposmia may represent an early stage of the "body-first" Parkinson's disease (PD) subtype. This study aimed to investigate brain functional network alterations in hyposmia-free iRBD patients and validate the hypothesis of early cortical compensatory mechanisms.

METHODS: Data were retrieved from the Parkinson's Progression Markers Initiative (PPMI) database. Thirty-seven hyposmia-free iRBD patients and 37 demographically matched healthy controls (HCs) were included. Degree centrality (DC) analysis to identify functional hub alterations, and seed-based functional connectivity (FC) analysis using differentially expressed DC regions as regions of interest.

RESULTS: Compared with HCs, iRBD patients exhibited significantly increased DC values in the left superior frontal gyrus. Seed-based FC analysis revealed enhanced connectivity between the Frontal_Sup_2_L and multiple cortical regions, including prefrontal subregions, temporal gyri, and sensorimotor areas. Within the iRBD group, the mean FC strength between the Frontal_Sup_2_L and its differentially connected brain regions was negatively correlated with RBDSQ scores (r = -0.360, p = 0.029).

CONCLUSIONS: Our findings suggest that hyposmia-free iRBD patients exhibit compensatory reorganization of brain functional networks centered on the left superior frontal gyrus, supporting the early cortical compensation hypothesis in the "body-first" α-synucleinopathy subtype. Stratification by both the presence and timing of hyposmia relative to RBD onset is critical for reconciling inconsistent rs-fMRI findings in iRBD.The DC value of the left Frontal_Sup_2_L and its FC with extensive cortical regions represent candidate imaging indicators for prodromal α-synucleinopathies, whose clinical utility requires prospective validation in larger independent cohorts with longitudinal designs.

PMID:42531839 | DOI:10.1016/j.sleep.2026.109167

Andrology. 2026 Jul 30. doi: 10.1111/andr.70333. Online ahead of print.

ABSTRACT

INTRODUCTION: Dapoxetine, a short-acting selective serotonin reuptake inhibitor (SSRI), is commonly prescribed to treat premature ejaculation (PE). Functional connectivity (FC) between dorsolateral prefrontal cortex (DLPFC) and subcallosal cingulate cortex (SCC) has been found to serve as neuroimaging biomarker for predicting SSRI treatment response. Despite the fact that altered FC has been observed in PE patients, the neural mechanisms underlying the rapid-acting effects on brain of immediate-term dapoxetine administration remain unknown. This study aimed to explore the mechanisms underlying this therapeutic effect based on DLPFC and SCC, which are involved in the regulation of ejaculatory reflex.

METHODS: Resting-state functional magnetic resonance imaging and structural MRI data were acquired from a sample of 40 PE patients before and after immediate-term dapoxetine administration, as well as 40 healthy controls (HCs). Seed-based voxel-wise FC analysis was performed, and whole-brain FC values in regions of interest (ROIs) (bilateral SCC and DLPFC: spheres with 6 mm radius) were calculated. FC values of bilateral DLPFC and SCC were compared between PE patients before and after dapoxetine administration and HCs.

RESULTS: Using SCC as ROIs, treatment-naïve PE patients showed decreased FC within the default mode network (p < 0.005) but increased FC with the attention network (p < 0.005) compared to HCs. Following dapoxetine administration, the pattern of alterations compared to HCs changed, now additionally featuring decreased FC between the SCC and the visual network (p < 0.005). Crucially, within-patient comparisons revealed that dapoxetine administration significantly decreased FC between the SCC and both the attention network (p < 0.005) and the visual network (p < 0.005). In contrast, using DLPFC as ROIs revealed widespread hypocomnectivity in patients, which remained unchanged following acute administration.

CONCLUSION: The therapeutic effects of immediate-term dapoxetine administration may act by downregulating FC of SCC and related circuits (promotional factors for PE), but do not enhance FC of DLPFC and related circuits (inhibition factors for PE). The latter may be achieved by long-term dapoxetine administration or other long-acting SSRI treatments.

PMID:42530223 | DOI:10.1111/andr.70333

J Integr Neurosci. 2026 Jul 27;25(7):51891. doi: 10.31083/JIN51891.

ABSTRACT

BACKGROUND: Frailty is a common geriatric syndrome characterized by a progressive decline in physical function and an increased susceptibility to adverse outcomes, including falls. Although diminished postural stability is a hallmark of frailty, the neural correlates associated with balance impairments throughout the progression of the syndrome remain unclear. This study aims to elucidate the brain functional activity of older adults with varying degrees of frailty during a resting state, as well as the relationship between this activity and postural stability.

METHODS: Sixty-eight older adults were divided into non-frail (n = 23), pre-frail (n = 30), and frail (n = 15) groups based on the Fried frailty phenotype. Postural stability was assessed using the Huber®360 neuromuscular control training and assessment system. Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired on a 3.0 T scanner, and the amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were utilized as indicators of brain functional activity. Spearman correlation analysis was employed to examine the correlations between the brain functional activity and the postural stability.

RESULTS: Compared to the non-frail group, the frail and pre-frail groups were significantly older and exhibited poorer performance in grip strength, Short Physical Performance Battery (SPPB) scores, and Timed Up and Go Test (TUGT) results, as well as a greater burden of comorbidities-such as depressive symptoms and sleep disturbances (all p < 0.05). Significant inter-group differences were observed across all postural stability parameters. Relative to the non-frail group, the pre-frail group exhibited significantly decreased ALFF in the left inferior frontal gyrus (pars opercularis) extending to the insula, while the frail group demonstrated reduced ALFF in bilateral posterior cerebellum; additionally, the frail group showed decreased ReHo in the left posterior cerebellum/pons and increased ReHo in the right middle temporal/occipital gyrus. ALFF was significantly correlated with right single-leg sway area, the limits of stability, SPPB score, and TUGT completion time, whereas ReHo was significantly correlated only with SPPB score and TUGT completion time (all p < 0.05).

CONCLUSIONS: Resting-state brain function exhibits significant differences among older adults in varying states of frailty, primarily involving spontaneous activity and local synchronization within the cerebellum-pons circuitry and cognition-related brain regions. These functional brain abnormalities are closely associated with diminished postural stability, suggesting that alterations in central nervous system function may represent a significant neural correlate of impaired balance in frail older adults. This study provides neuroimaging evidence to support the early screening of frailty and balance-related interventions in older adults, while also laying a foundation for future longitudinal and multimodal investigations.

PMID:42530043 | DOI:10.31083/JIN51891

CNS Neurosci Ther. 2026 Aug;32(8):e71066. doi: 10.1002/cns.71066.

ABSTRACT

BACKGROUND: Insomnia disorder (ID) is characterized by hyperarousal, yet the relationship between cortical excitability and large-scale network dynamics remains incompletely understood. While fMRI studies indicate network alterations in ID, high-temporal-resolution characterization of these dynamics across the sleep-wake cycle is lacking.

METHODS: Twenty-six patients with ID and 29 healthy controls underwent eyes-closed resting-state OPM-MEG recordings during evening (pre-sleep) and morning (post-awakening) sessions. We analyzed the aperiodic spectral exponent to index cortical excitability and employed microstate analysis to quantify fast network dynamics. A mediation analysis was conducted to explore the associations between electrophysiological features and sleep quality.

RESULTS: Compared to controls, patients with ID exhibited a significantly flatter aperiodic power spectrum in the evening, suggesting elevated cortical excitability. Microstate analysis revealed distinct spatiotemporal alterations: (1) an evening-specific increase in the coverage of a putative temporal-limbic microstate, and (2) a sustained elevation of a putative sensorimotor microstate observed in both evening and morning sessions. Mediation analysis indicated that the altered evening limbic microstate dynamics statistically mediated the association between the aperiodic exponent and subjective sleep disturbance measures.

CONCLUSIONS: These findings indicate that ID involves concurrent disruptions in aperiodic neural activity and microstate temporal organization. The study highlights distinct diurnal profiles for putative sensorimotor and limbic network alterations, suggesting that OPM-MEG can effectively capture the multifaceted electrophysiological signatures of the insomnia phenotype.

PMID:42529863 | DOI:10.1002/cns.71066

Netw Neurosci. 2026 Jul 20;10(3):567-593. doi: 10.1162/NETN.a.551. eCollection 2026.

ABSTRACT

Fine-scale spatial dynamics within functional brain networks manifest as high spatial-frequency variations that conventional independent component analysis (ICA) methods fail to capture. These subtle changes may carry critical information about transient connectivity and disordered brain function. We developed NeuroMark-DyFICA (dynamic frequency-informed ICA), a novel framework to enhance detection of spatiotemporal variability in fMRI data. It integrates three stages: dynamic NeuroMark ICA across sliding windows to estimate time-varying, spatially constrained networks; high-pass spatial filtering to emphasize fine-scale spatial features; and group-level ICA to extract refined dynamic components with subject-specific mixing weights. Unlike prior NeuroMark applications or conventional dynamic ICA, NeuroMark-DyFICA establishes a reproducible latent space of high-frequency dynamics, uniquely capturing transient, fine-scale reconfigurations of network topography. Validation using a controlled 2D simulation demonstrated reliable detection of subtle spatial shifts mimicking pathology, which conventional ICA failed to recover. Applying to resting-state fMRI from schizophrenia patients and healthy controls, multiple networks were estimated. We highlight six representative systems (thalamus, auditory, visual/fusiform, middle frontal, default mode, cerebellum). Results revealed two complementary abnormalities in schizophrenia: an imbalance between inactive and hyper-engaged states and altered convergence among dynamic states. NeuroMark-DyFICA reveals fine-grained spatiotemporal disruptions in brain networks, offering mechanistic insights and potential biomarkers for psychiatric disorders.

PMID:42529646 | PMC:PMC13418253 | DOI:10.1162/NETN.a.551

Psychoradiology. 2026 Jul 27;6:kkag024. doi: 10.1093/psyrad/kkag024. eCollection 2026.

ABSTRACT

BACKGROUND: Transcranial Magnetic Stimulation targeting the dorsolateral prefrontal cortex (DLPFC) is a therapeutic approach for treating depressive disorder. However, traditional anatomical methods often fail to localize a treatment target. The functional connectivity method represented by the Stanford Neuromodulation Therapy (SNT) has been proposed and demonstrated efficacy. A step of SNT is to achieve DLPFC target localization using resting-state functional magnetic resonance imaging (rs-fMRI) data, based on measurement of the negative correlation coefficient between the functional connectivity of DLPFC and the subgenual anterior cingulate cortex (sgACC).

METHODS: This study has three goals. Firstly, to apply the SNT protocol to investigate variability in target localization in four groups (Human Connectome Project [HCP], China Human Connectome Project [CHCP], major depressive disorder [MDD] from Huaxi Depression Imaging Cohort Study [HX-DICS], and healthy controls [HC] from HX-DICS) from three databases. Secondly, to investigate potential differences in how the DPABI and FSL rs-fMRI pre-processing pipelines, particularly the spatial smoothing, denoising, and temporal filtering steps, affect the localization of individualized DLPFC targets. Thirdly, to assess the effect of rs-fMRI scan duration (ranging from 6 to 30 min) on target localization.

RESULTS: Significant inter-subject variability in DLPFC coordinates was found, emphasizing the necessity of individualized targeting. DPABI and FSL pre-processing produced significant differences in target coordinates, which exceeded 1 cm, with mean Euclidean distances ranging from 1.45 to 3.82 cm across cohorts, and individual maximum deviations reaching 6.14 cm. FSL pipeline consistently produced higher negative correlation coefficients than DPABI. Scan duration analysis indicated that after 12 min, the stability of individual target positions no longer improved significantly with prolonged scanning time, suggesting that approximately 12 min may provide sufficiently reliable data for target computation.

CONCLUSION: Taken together, findings demonstrate that advancing precision neuromodulation therapy requires optimized data acquisition, standardized workflows, software-specific validation, and optimum scan duration.

PMID:42529453 | PMC:PMC13418188 | DOI:10.1093/psyrad/kkag024

Front Immunol. 2026 Jul 14;17:1803497. doi: 10.3389/fimmu.2026.1803497. eCollection 2026.

ABSTRACT

BACKGROUND: DNA methylation of the ELOVL2 (Elongation of Very Long Chain Fatty Acids Protein 2) promoter is one of the most robust molecular biomarkers for chronological age; however, whether ELOVL2 plays a functional role in brain aging and immunosenescence, and whether the APOE genotype modulates these effects, has not been fully explored. This study investigated the associations among ELOVL2 methylation, APOE genotype, and neurophysiological changes in the brain, as well as indicators of immunosenescence of peripheral blood T cells during aging.

METHODS: We examined 72 non-demented volunteers aged 20-88 years, stratified by APOE genotype (41 APOE-, 31 APOE+). ELOVL2 methylation levels were measured via bisulfite conversion and pyrosequencing. Participants underwent cognitive screening, auditory P3 event-related potential (ERP) recordings, and resting-state MRI functional connectivity (rsFC) assessments. In a subgroup of 18 healthy subjects, we examined peripheral blood T-cell subsets and analyzed the association of CD3+HLA-DR+ T cells with ELOVL2 methylation and neurophysiological characteristics.

RESULTS: ELOVL2 CpG promoter methylation (chr 6:11044880. GRCh37) was associated with P3 ERP latency in both the overall sample and APOE4+ carriers, remaining significant even after adjusting for age; however, this association was not significant in APOE4- individuals. DNA methylation of ELOVL2 was inversely correlated with fMRI rsFC in the salience-, and memory-related, and central autonomic networks, indicating disrupted connectivity within these networks. An increased proportion of CD3+ cells expressing the immune activation marker HLA-DR was correlated with elevated ELOVL2 methylation level and with decreased fMRI rsFC in brain networks, including circuits related to the DMN medial prefrontal cortex, amygdala, and cerebellum.

CONCLUSION: The results imply a close link between ELOVL2 methylation, inflammaging and brain dysfunction, which is modulated by APOE4+ genotype.

PMID:42523772 | PMC:PMC13407353 | DOI:10.3389/fimmu.2026.1803497

Res Sq [Preprint]. 2026 Jul 16:rs.3.rs-10240247. doi: 10.21203/rs.3.rs-10240247/v1.

ABSTRACT

(248/250 words) The rostromedial tegmental nucleus (RMTg) has been shown to inhibit midbrain dopaminergic centers through its GABAergic projections, and to be critical for regulating responses to aversive and rewarding stimuli. This nucleus has primarily been evaluated in rodents and non-human primates, while recent postmortem analysis of human brainstem tissue localized GABergic cell clusters in the putative RMTg. The objectives of this preliminary investigation in healthy controls (HC) were to (i) define RMTg function during evoked thermal stimulation and the resting-state using 7T functional magnetic resonance imaging (fMRI), and (ii) explore the expression of putative RMTg markers, µ-opioid receptors (OPMR1), nociceptin receptors (NOPR), and FOXP1 as well as tyrosine hydroxylase (TH) in the midbrain tegmentum. Relative to 40°C stimuli, greater responses to 46°C (normally noxious) in the putative RMTg as well as raphe nuclei, locus coeruleus, substantia nigra, thalamus, putamen, and anterior cingulate were observed. Resting-state 7T fMRI showed robust RMTg functional connectivity with components of mesocorticolimbic and nigrostriatal circuitry, thalamus, hippocampus, and cerebellar subdivision. In postmortem analyses, neurons immunolabeled for OPMR1, NOPR, and FOXP1 were detected in an area adjacent to the decussation of the superior cerebellar peduncle. These immune-positive neurons in the area of the putative RMTg were adjacent to intense TH immunoreactivity. This investigation provides novel evidence of activation of a distinct area within the human midbrain tegmentum, putatively identified as the RMTg, particularly during nociceptive processing in addition to its resting-state connectivity with the broader central nervous system. Further exploration of the human RMTg is warranted.

PMID:42523566 | PMC:PMC13405508 | DOI:10.21203/rs.3.rs-10240247/v1

bioRxiv [Preprint]. 2026 Jul 18:2026.07.06.736898. doi: 10.64898/2026.07.06.736898.

ABSTRACT

The hippocampus and amygdala are neighboring medial temporal lobe structures linked to memory and affect, yet how their subregions are jointly embedded within distributed isocortical systems remains unclear. Using resting-state fMRI from 722 Human Connectome Project Young Adult participants, we mapped hippocampal and amygdalar subregions within a unified cortex-wide framework, quantifying subregion-to-cortex connectivity via Pearson correlation (broad co-fluctuation) and GLASSO partial correlation (relatively more direct functional association). We introduced two count-based metrics: dominance (relative hippocampal vs. amygdalar representation) and sharedness (balanced co-representation). Direct associations showed both structures sharing coupling with paralimbic areas and, more modestly, default mode regions, while broader co-fluctuations extended into somatomotor and paralimbic networks. Divergence patterns depended on the estimator: hippocampal subregions preferentially coupled with default-mode and visual networks under direct association, while amygdalar nuclei favored ventral attention and limbic networks; broader co-fluctuations additionally implicated somatomotor cortex for amygdala and visual cortex for hippocampus. These principles held at the subfield/nucleus level, varying along the hippocampal long axis and identifying the paralaminar nucleus as the most hippocampus-like amygdalar subregion. Data-driven connectivity gradients confirmed both systems' separation and fine-scale interdigitation. Hippocampal and amygdalar subregions are thus embedded in cortex not as discrete systems, but through structured, spatially organized co-representation.

PMID:42523343 | PMC:PMC13405180 | DOI:10.64898/2026.07.06.736898

bioRxiv [Preprint]. 2026 Jul 13:2026.07.08.737282. doi: 10.64898/2026.07.08.737282.

ABSTRACT

Functional MRI studies have traditionally focused on gray matter, whereas white-matter BOLD signals have often been treated as weak or artifactual. Recent work suggests that white-matter BOLD fluctuations contain reproducible functional information, but most gray-to-white matter analyses rely on marginal functional connectivity, which cannot separate pairwise coupling from shared variance among distributed cortical systems. Here, we used a multivariate cortical encoding framework to test whether spontaneous white-matter BOLD activity can be predicted from distributed cortical gray-matter activity and whether this predictive structure reveals organization beyond marginal connectivity. Resting-state fMRI data from 81 Human Connectome Project young adult participants were analyzed using a strict white-matter mask with no overlap with cortical predictors. For each white-matter voxel, time series from 400 Schaefer cortical parcels were used to predict held-out white-matter BOLD signals with nested leave-one-run-out ridge regression. Cortical activity modestly but reliably predicted white-matter BOLD dynamics, demonstrating consistent cross-validated prediction accuracy across a broad spatial extent of the white matter. Ridge beta fingerprints strongly recapitulated marginal functional connectivity fingerprints, indicating a shared functional backbone, but their first gradients diverged reproducibly. This beta-FC divergence axis organized FC-adjusted prediction residuals and remained robust after controlling for gray-matter proximity, mask-boundary distance, white-matter prevalence, temporal signal variability, spatial coordinates, and spatial autocorrelation. The high-divergence end showed relatively low marginal FC but high FC-adjusted prediction residuals and was enriched for posterior thalamic/optic-radiation and posterior corona-radiata anatomy. These findings suggest that multivariate cortical encoding reveals a tract-organized dimension of white-matter functional coupling not captured by pairwise connectivity alone.

PMID:42523274 | PMC:PMC13404838 | DOI:10.64898/2026.07.08.737282

Eur Psychiatry. 2026 Jul 29:1-39. doi: 10.1192/j.eurpsy.2026.12246. Online ahead of print.

NO ABSTRACT

PMID:42522874 | DOI:10.1192/j.eurpsy.2026.12246

Psychiatry Clin Neurosci. 2026 Jul 29. doi: 10.1111/pcn.70109. Online ahead of print.

ABSTRACT

BACKGROUND: Childhood neglect is a potent risk factor for major depressive disorder (MDD), yet its underlying neural mechanisms linking neglect to depression remain poorly understood. This study aimed to investigate brain network alterations and task-rest functional connectivity (FC) similarity associated with childhood neglect and to clarify their mechanistic roles in depression.

METHODS: Participants included MDD patients with childhood neglect (n = 42), MDD patients without childhood trauma (n = 23), and healthy controls without childhood trauma (n = 66). All participants completed clinical scales and underwent both resting-state and task-based fMRI during a Go/No-Go response inhibition task.

RESULTS: (1) A distinct subnetwork comprising 207 edges across 170 nodes (P < 0.05) exhibited hyperconnectivity in the MDD-Neglect group compared to both the MDD-No Trauma group (P < 0.001) and healthy controls (P < 0.001), with prominent involvement of the default mode network and dorsal attention network. (2) The connectivity strength of the significant subnetwork positively predicted depressive symptom severity (β = 0.438, P < 0.001) and significantly mediated the relationship between childhood neglect and depressive symptoms. (3) The task-rest FC similarity of the significant subnetwork also positively predicted depressive symptom severity (β = 0.328, P < 0.001) and mediated the relationship between childhood neglect and depressive symptoms.

CONCLUSION: Childhood neglect may exacerbate depression through two complementary neurofunctional mechanisms: heightened static connectivity within a cognitive control subnetwork and diminished dynamic flexibility in brain network reconfiguration. These complementary network-level features advance a network-based understanding of how early adversity confers lasting depression risk.

SIGNIFICANT OUTCOMES: Patients with major depressive disorder and a history of childhood neglect exhibited a distinct pattern of hyperconnectivity within a large-scale brain subnetwork (primarily involving the DMN, DAN, and SAN) during response inhibition. Both increased functional connectivity strength and higher task-rest FC similarity within the network independently mediated the relationship between childhood neglect and depressive symptom severity.

LIMITATIONS: The cross-sectional design of this study limits causal inferences about the directional relationships among childhood neglect, brain network alterations, and depressive symptoms. Childhood neglect was assessed retrospectively via self-report, which may be subject to recall bias. The study is specific to the domain of response inhibition and functional connectivity measures, limiting generalization to other cognitive or emotional processes and to multimodal neural mechanisms.

PMID:42522354 | DOI:10.1111/pcn.70109

Psychol Med. 2026 Jul 29;56:e243. doi: 10.1017/S0033291726105352.

ABSTRACT

BACKGROUND: Psychological adaptability hinges on the dynamic balance between cognitive regulation (self-control) and emotional reactivity (impulsivity, reward/punishment sensitivity). However, traditional variable-centered approaches often fail to capture how these traits holistically co-occur, and the neural architectures predicting their longitudinal transitions in early adulthood remain under-explored.

METHODS: This longitudinal study (N = 1,229 baseline; N = 432 2-year follow-up) integrated a person-centered behavioral approach with resting-state fMRI. We employed Latent Profile Analysis (LPA) to identify trait configurations based on self-control, impulsivity, and sensitivity to reward/punishment. Network-Based Statistic (NBS) analysis with family-wise error (FWE) correction was utilized to evaluate functional connectivity differences among groups. Finally, hierarchical regression and formal interaction models were conducted to test the prospective predictive validity of the identified neural circuits.

RESULTS: LPA delineated three distinct baseline profiles: Adaptive, Moderate, and Maladaptive. NBS analysis revealed that the 'Adaptive' profile is underpinned by robust cortico-striatal functional connectivity, integrating the medial prefrontal cortex and striatum. Longitudinally, initial regression models demonstrated that the baseline integrity of this circuit prospectively predicted behavioral adaptation at the 2-year follow-up. Furthermore, hierarchical regression and formal interaction analyses confirmed that this cortico-striatal circuit provided significant incremental predictive validity - above and beyond massive baseline behavioral stability - specifically in males.

CONCLUSIONS: These findings highlight cortico-striatal integration as a significant, gender-specific prospective predictor of longitudinal adaptation. By bridging person-centered profiling with network neuroscience, this study elucidates the neural correlates supporting future adaptive functioning and psychological resilience during the early adult transition.

PMID:42522230 | DOI:10.1017/S0033291726105352

Brain Imaging Behav. 2026 Jul 29;20(4):114. doi: 10.1007/s11682-026-01182-2.

ABSTRACT

Borderline personality disorder (BPD) is a mental disorder characterized by extreme instability in mood, interpersonal relationships, self-image, and behavioral patterns. Its core symptoms include intense mood swings, strained interpersonal relationships, disturbed self-identity, impulsive behaviors, and cognitive and perceptual abnormalities. The etiology of BPD is complex, involving genetic, neurobiological, and psychosocial factors. Among neurobiological factors, neuroimaging studies have consistently reported inconsistent findings regarding amygdala volume in BPD patients-some MRI studies demonstrate a 15% increase, while others show a reduction. Such discrepancies may reflect the impact of heterogeneous patient populations, comorbidities, or differences in imaging protocols. Notably, structural and functional abnormalities in BPD are not limited to the amygdala but also involve multiple brain regions, including the prefrontal cortex, hippocampus, anterior cingulate cortex, and insula, which collectively contribute to impaired emotion regulation, interpersonal dysfunction, and other core symptoms. A systematic search was conducted on studies investigating brain neuroimaging differences between BPD patients and healthy controls (HC). Studies meeting the inclusion criteria were selected, and coordinate-based meta-analysis (CBMA) of brain structural and functional changes was performed using seed-based d mapping (SDM) software to explore potential abnormal brain structures and functions in BPD patients. After screening, a total of 26 studies were included. By integrating meta-analytic findings from four neuroimaging modalities-diffusion tensor imaging (DTI), structural magnetic resonance imaging (sMRI), functional magnetic resonance imaging (fMRI), and resting-state functional magnetic resonance imaging (rs-fMRI)-this study systematically summarized the characteristic changes in brain structure and function in BPD patients. Study results demonstrated that the neurobiological basis of BPD primarily involves structural and functional dysregulation of the frontolimbic system, particularly in brain regions linked to core mental functions like emotion regulation, self-cognition, and impulse control.

PMID:42521870 | DOI:10.1007/s11682-026-01182-2