Most recent paper

A low-variance subspace underlies individual differences in resting state fMRI

Mon, 02/09/2026 - 19:00

bioRxiv [Preprint]. 2026 Jan 27:2026.01.25.701594. doi: 10.64898/2026.01.25.701594.

ABSTRACT

People differ remarkably from one another, yet isolating individual differences in their brain activity remains challenging. Non-invasive whole-brain recordings of human brain activity, such as those from resting state fMRI (rs-fMRI), are complex and noisy, making it difficult to isolate stable dimensions of individual differences. Ideally, we want to find a few core dimensions that vary across people but have high test-retest reliability, giving the same value each time they are measured in the same person. However, it is still unknown whether any such reliable dimensions exist, and if they do, what could drive this reliability. Here, we show that there is a low-dimensional linear subspace of highly-reliable rs-fMRI activity. These dimensions form personal fingerprints, allowing participants to be identified with high accuracy despite fingerprints explaining only a fraction of the total variance. Many of these dimensions inherit their reliability from a single morphological, demographic, or behavioral property, and most dimensions can be predicted from the anatomical layout of cortical regions. These dimensions were identified using reliability component analysis (RCA), a new dimensionality reduction technique similar to principal component analysis (PCA) but which maximizes reliability instead of explained variance. Together, our findings suggest that stable individual signatures can be isolated from rs-fMRI. These signatures reflect persistent anatomical and physiological differences, and provide a principled low-dimensional basis for biomarker discovery.

PMID:41659684 | PMC:PMC12873822 | DOI:10.64898/2026.01.25.701594

Abnormal functional activity in the cerebellar crus can distinguish patients with migraine with comorbid insomnia

Mon, 02/09/2026 - 19:00

Front Neurosci. 2026 Jan 22;20:1745862. doi: 10.3389/fnins.2026.1745862. eCollection 2026.

ABSTRACT

BACKGROUND: Migraine is a prevalent neurological disorder that is frequently observed in clinical practice and is commonly comorbid with insomnia. Insomnia can exacerbate and precipitate migraine attacks, with both conditions exerting a reciprocal influence on one another. The cerebellar crus is significantly associated with the pathophysiology of migraine and insomnia. The relationship between cerebellar crus functional alterations and migraine-associated insomnia remains unclear. This study utilizes resting-state functional magnetic resonance imaging (rs-fMRI) to examine functional alterations in the cerebellar crus of patients with migraine and concurrent insomnia.

METHODS: Participants underwent resting-state functional magnetic resonance imaging. Subsequently, the disparity in amplitude of low-frequency fluctuations (ALFF) values among groups was analyzed, followed by functional connectivity (FC) investigations employing the cerebellum crus as seed regions.

RESULTS: Migraine patients frequently experience neuropsychological disorders and insomnia, which are interconnected. Both migraine with insomnia (MwI) and migraine without insomnia (MwoI) groups demonstrated elevated amplitude of low-frequency fluctuations (ALFF) in the left Crus I and II compared to the healthy controls (HC) group, with the MwI group exhibiting more pronounced alterations. Additionally, both patient groups showed decreased FC between the left Crus I and the right middle temporal gyrus (MTG) and inferior temporal gyrus (ITG) relative to the HC group. The MwoI group showed significantly lower FC compared to both the HC and MwI groups. A significant negative correlation was observed between ALFF in the left Crus I/II and Pittsburgh Sleep Quality Index (PSQI) scores in the MwoI group. Conversely, in the combined migraine cohort, FC between the left Crus I and the right MTG/ITG showed a positive correlation with PSQI scores.

CONCLUSION: This study identified a correlation between aberrant functional activity in the left Crus I/II and migraine comorbidity with insomnia. These findings provide fresh perspectives on the neural mechanisms underlying the migraine-insomnia relationship, thereby facilitating the identification of potential neuroimaging biomarkers and the exploration of targeted interventions for this patient subgroup.

PMID:41658941 | PMC:PMC12872798 | DOI:10.3389/fnins.2026.1745862

Mapping high-amplitude fMRI edge time series events across space and time

Mon, 02/09/2026 - 19:00

Imaging Neurosci (Camb). 2026 Feb 5;4:IMAG.a.1126. doi: 10.1162/IMAG.a.1126. eCollection 2026.

ABSTRACT

Resting-state fMRI time series are punctuated by spontaneous moments of high-amplitude activity lasting mere seconds. Previous research has demonstrated that such moments may contain a disproportionate amount of information and can be used to recapitulate maps of distributed brain activity or to recreate spatial functional connectivity patterns. Ultimately, this body of work has established that modeling neurovascular activity as a succession of spontaneous, punctuated moments is an effective approach for understanding cortex-wide brain activity. Here, we expand on this line of work by focusing our attention on the spatiotemporal properties of such punctuated moments, particularly on their duration. For this, we turn to an edge time series approach to resolve the dynamics of functional connectivity, identify moments of prominent synchrony, and record their duration. This procedure allows us to differentiate such punctuated moments by the time scales at which they unfold. By mapping moment duration to the cortex, we find that connectivity emanating from brain's primary sensory areas transpires with the longest durations. We further construct spatial patterns of connectivity unfolding over distinct durations, demonstrating how time scales differentially relate to traditionally constructed functional connectivity. Finally, we show how the longest connectivity moments could convey information about fluctuations in subjects' vigilance. Overall, the information that we have gleaned about prominent connectivity moments and their duration would otherwise be largely obscured when using other prevalent methods. Here we highlight an additional feature of functional connectivity to further our characterization of the brain's spatiotemporal organization.

PMID:41658341 | PMC:PMC12878659 | DOI:10.1162/IMAG.a.1126

Altered frequency architecture of spontaneous brain activity in asymptomatic carotid stenosis: a wavelet-based resting-state fMRI study

Mon, 02/09/2026 - 19:00

Front Neurol. 2026 Jan 22;17:1683526. doi: 10.3389/fneur.2026.1683526. eCollection 2026.

ABSTRACT

The intrinsic brain activity measured by resting-state fMRI (rs-fMRI) consists of synchronized neural oscillations across a broad range of low frequencies. Although previous studies have linked frequency-specific changes to cognitive function and impairment, the alterations of these frequency-specific spatiotemporal patterns in chronic occlusive cerebrovascular disease remain unclear. In this study, we investigated the cross-frequency structure underlying cognitive impairment in patients with severe asymptomatic carotid stenosis (SACS) using wavelet-transformed amplitude of low-frequency fluctuation (wavelet-ALFF) of rs-fMRI. We found that, in healthy controls, frequency-specific wavelet-ALFF exhibited a spatial distribution from lower to higher frequencies, aligned with the functional hierarchy extending from the default mode network (DMN) to primary somatomotor and subcortical regions. In contrast, SACS patients exhibited frequency-dependent changes, including significantly decreased wavelet-ALFF in the anteromedial DMN at lower frequencies and the posteromedial DMN at higher frequencies. Further spatiotemporal decomposition analysis revealed that SACS patients exhibited abnormal cross-frequency coupling in the DMN. Our findings suggest that frequency-specific changes underlying cognitive impairment in SACS arise from spatiotemporally abnormal cross-frequency interplay within the DMN. These insights may contribute to a better understanding of other major brain diseases.

PMID:41657414 | PMC:PMC12872527 | DOI:10.3389/fneur.2026.1683526

Neural basis of cognitive-perceptual and negative affect: the linking role of ventral anterior insula connectivity

Sun, 02/08/2026 - 19:00

Neurosci Lett. 2026 Feb 6:138537. doi: 10.1016/j.neulet.2026.138537. Online ahead of print.

ABSTRACT

BACKGROUND: Schizotypal personality (SP) is characterized by cognitive-perceptual disturbances, interpersonal difficulties, and disorganized behavior. We examined associations between SP traits and affect, and insula-centered neural mechanisms underlying this link.

METHODS: One hundred sixty-one university students completed the Schizotypal Personality Questionnaire-Brief and the Positive and Negative Affect Schedule and underwent resting-state fMRI. Seed-based whole-brain functional connectivity (FC) analyses used bilateral ventral anterior, dorsal anterior, and posterior insula seeds. Pearson correlations and mediation analyses tested associations among SP traits, Negative Affect, and FC.

RESULTS: Cognitive-Perceptual traits correlated positively with Negative Affect (r = 0.36, p < 0.001). FC between the right inferior parietal lobule (IPL.R) and the left ventral anterior insula (vAI.L) was positively correlated with Cognitive-Perceptual traits (r = 0.33, p < 0.001), whereas FC between the right cerebellar Crus I and the vAI.L was negatively correlated (r = -0.37, p < 0.001). FC between the right ventral anterior insula (vAI.R) and the Left Calcarine Gyrus (CAL.L) was also negative (r = -0.30, p < 0.001). vAI.L-IPL.R FC partially mediated the Cognitive-Perceptual traits-Negative Affect association (indirect effect = 0.1883, 95% bootstrap CI [0.0246, 0.4022]).

CONCLUSION: vAI.L-IPL.R FC partially accounts for the link between Cognitive-Perceptual traits and Negative Affect, highlighting a potential neural pathway underlying affective vulnerability in SP.

PMID:41655807 | DOI:10.1016/j.neulet.2026.138537

Emergent Language Symbolic Autoencoder (ELSA) with weak supervision to model hierarchical brain networks

Sun, 02/08/2026 - 19:00

Comput Biol Med. 2026 Feb 7;204:111533. doi: 10.1016/j.compbiomed.2026.111533. Online ahead of print.

ABSTRACT

Brain networks display hierarchical organization, a complexity that is challenging for deep learning models that are often flat classifiers and lack interpretability. To address this, we propose a novel architecture called the Emergent Language Symbolic Autoencoder (ELSA), a hierarchical symbolic autoencoder informed by weak supervision and an Emergent Language framework that learns to represent brain networks as interpretable symbolic sentences while simultaneously reconstructing the original data. Our framework's primary innovations are a set of hierarchically-aware loss functions and their application to modeling resting-state fMRI networks. By combining weak supervision from Independent Component Analysis (ICA) order with novel Progressive, Strict, and Containing Bias losses, we explicitly enforce a coarse-to-fine structure on the emergent language without requiring extensive manual labeling. We evaluated ELSA on data from the publicly available 1000 Functional Connectomes Project. The model generated sentences with clear hierarchical organization, where early symbols corresponded to broad parent networks and later symbols specified finer sub-networks. With the use of our proposed Progressive Strict loss function and containing bias penalty, the model's hierarchical consistency drastically improves compared to baseline, achieving near-perfect consistency at higher ICA orders and 43.5% at the challenging lowest order. The model also produces qualitatively superior visual progressions of the network reconstructions. By replacing opaque feature vectors with an interpretable symbolic language, ELSA provides a transparent, multi-level description of functional brain organization and offers a general framework for studying other hierarchically structured biomedical data.

PMID:41655479 | DOI:10.1016/j.compbiomed.2026.111533

Spatial amyloid-informed multimodal brain age as an early marker of Alzheimer's-related vulnerability and risk stratification

Sat, 02/07/2026 - 19:00

J Prev Alzheimers Dis. 2026 Feb 6;13(4):100501. doi: 10.1016/j.tjpad.2026.100501. Online ahead of print.

ABSTRACT

BACKGROUND: Brain age gap (BAG)-the difference between predicted and chronological age-captures neurobiological aging, but MRI-only models insufficiently reflect Alzheimer's disease (AD) pathology. Whether incorporating regional amyloid-β (Aβ) positron emission tomography (PET) improves sensitivity to early AD processes remains unknown.

OBJECTIVES: To develop an amyloid-informed multimodal BAG model and examine its associations with cognition, plasma biomarkers, and functional connectivity across the AD continuum.

DESIGN: Cross-sectional analysis using integrated machine-learning models.

SETTING: Chinese Preclinical Alzheimer's Disease Study (CPAS), a cohort recruited from community settings and memory clinics.

PARTICIPANTS: Nine hundred ninety community-dwelling adults spanning normal cognition, subjective cognitive decline (SCD), mild cognitive impairment (MCI), and dementia.

MEASUREMENTS: Regional Aβ-PET and structural MRI informed BAG estimation. Cognitive tests, plasma biomarkers (p-tau217, p-tau181, neurofilament light [NfL], glial fibrillary acidic protein [GFAP], Aβ42/40), and hippocampus-default mode network (DMN) connectivity from resting-state fMRI were assessed.

RESULTS: Higher BAG was associated with greater odds of SCD, MCI, or dementia across the cohort, with stronger effects in Aβ-positive individuals. BAG explained more cognitive variance than global Aβ burden and was linked to multidomain cognitive deficits. Elevated BAG corresponded to higher p-tau217, p-tau181, NfL, and GFAP and lower Aβ42/40, indicating early biomarker alterations. BAG was also associated with reduced hippocampus-DMN connectivity.

CONCLUSIONS: An amyloid-informed multimodal BAG model captures convergent AD-related pathology, biomarker alterations, and cognitive vulnerability beyond amyloid burden alone, supporting its value for individualized risk s2tratification and prevention-focused assessment.

PMID:41653882 | DOI:10.1016/j.tjpad.2026.100501

Establishing the link between post-concussive symptoms and brain network dysfunction: A systematic scoping review of neuroimaging evidence

Sat, 02/07/2026 - 19:00

Neuroimage Clin. 2026 Jan 26;49:103956. doi: 10.1016/j.nicl.2026.103956. Online ahead of print.

ABSTRACT

Mild traumatic brain injury (mTBI) is a prevalent condition with symptoms spanning physical, psychological, cognitive, and sleep domains. Altered functional brain networks have been implicated in mTBI, but the relationship between these network changes and post-concussive symptoms remains poorly understood. This study is a systematic scoping review, adhering to PRISMA-ScR guidelines, assessing current literature on the association between brain network dysfunction and mTBI-related symptoms. Searches across ProQuest, Web of Science, and PubMed yielded 41 studies for full review, with most (n = 39) employing resting-state functional magnetic resonance imaging (rs-fMRI) to examine brain networks. The default mode network (DMN) was a primary focus, with studies reporting heterogeneous findings of increased and decreased connectivity both within and outside this network. Over 85% of studies used mTBI-specific symptom measures, and 50% employed detailed questionnaires for emotional and physical symptom assessment. Of these, 23 studies identified significant correlations between symptom scores and network connectivity. However, methodological inconsistencies, including variable analytic approaches, highlight the need for standardization in this field. Key areas for future research include incorporating multimodal imaging techniques, conducting longitudinal studies or extending recruitment time points, and stratifying analyses by sex to optimise identification of connectivity changes. Addressing these gaps is crucial for advancing our understanding of functional network alterations in mTBI and their clinical implications, ultimately supporting improved diagnostic and therapeutic strategies.

PMID:41653507 | DOI:10.1016/j.nicl.2026.103956

Frequency-specific resting state fMRI features in gliomas

Sat, 02/07/2026 - 19:00

J Neurooncol. 2026 Feb 7;176(3):198. doi: 10.1007/s11060-026-05443-4.

NO ABSTRACT

PMID:41653232 | DOI:10.1007/s11060-026-05443-4

Brain network dysfunction and treatment-induced network reorganization in major depressive disorder

Sat, 02/07/2026 - 19:00

Brain Imaging Behav. 2026 Feb 7;20(1):5. doi: 10.1007/s11682-026-01076-3.

ABSTRACT

The present study aimed to investigate the characteristics of abnormal resting-state brain-network connectivity and the reorganization effects of antidepressant drug escitalopram oxalate treatment in patients with major depressive disorder (MDD), and to explore spatial correlations between brain network alterations and gene expression profiles. We employed a longitudinal study design to recruit 113 patients with MDD and 114 healthy controls (HCs) between November 2020 and October 2022. Clinical symptoms were assessed using the 17-item Hamilton Depression Scale (HAMD-17). Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired using a Siemens 3.0 T MRI scanner. At baseline, patients with MDD exhibited significantly reduced functional connectivity (FC) within the default mode network (DMN) compared to HCs, along with significantly increased FC between the sensorimotor network (SMN) and both the frontoparietal network (FPN) and the salience network (SN) (False Discovery Rate, FDR-corrected, p < 0.05). Following treatment with escitalopram oxalate, MDD patients showed a significant enhancement in intra-DMN connectivity, as well as a significant reduction in SMN-FPN and SMN-SN connectivity (FDR-corrected, p < 0.05). Notably, the degree of increase in intra-DMN connectivity was significantly and negatively correlated with improvement in core depressive symptoms (r = - 0.305, p = 0.026), while the reduction in SMN-DMN connectivity was positively correlated with the alleviation of somatic symptoms (r = 0.362, p = 0.008). Further neuroimaging-guided transcriptomics analysis indicated that these alterations in brain network connectivity were linked to biological pathways, such as the Wnt signaling. In conclusion, our findings demonstrate a multidimensional imbalance in brain network connectivity in MDD and show that antidepressant treatment can partially ameliorate aberrant connectivity patterns. These neural changes are closely associated with symptomatic improvements, offering valuable imaging-based evidence for understanding the neurobiological mechanisms of MDD and informing the development of personalized treatment strategies.

PMID:41653205 | DOI:10.1007/s11682-026-01076-3

Target variability and stability of neuroimaging-guided transcranial magnetic stimulation of the amygdala circuitry for posttraumatic stress disorder

Fri, 02/06/2026 - 19:00

Res Sq [Preprint]. 2026 Jan 26:rs.3.rs-8321466. doi: 10.21203/rs.3.rs-8321466/v2.

ABSTRACT

BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation therapy that is applied across psychiatric conditions to modulate specific neural circuits and improve clinical symptoms. While functional magnetic resonance imaging (fMRI)-guided personalized TMS targets are increasingly used, there are critical unresolved methodological, neurobiological, and clinical questions. Addressing topographic variability, stability, and associations with clinical outcomes is essential for advancing clinical development and scalable precision neuromodulation.

METHODS: A precision neurocircuitry-based fMRI-guided TMS approach was developed to treat disorders of the amygdala. In a randomized clinical trial for posttraumatic stress disorder (PTSD; n=50), topographic variability and stability of patient-specific right dorsolateral prefrontal cortex (rDLPFC) targets with the strongest functional connectivity to the right amygdala were analyzed.

RESULTS: There was significant target variability between participants and between targeting methods, but target stability was observed after engaging the amygdala circuitry with behavioral threat-related tasks. Target topography did not change after 20 sessions of sham TMS. However, after active TMS (1Hz, 36,000 pulses) target topography was significantly different. A larger change in the medial-anterior direction correlated with greater PTSD symptom improvement.

CONCLUSIONS: Target variability and stability for fMRI-guided TMS of the amygdala circuitry is demonstrated, supporting the use of patient-specific targeting strategies for TMS. A clinical change in PTSD symptoms was associated with greater change in target topography, which suggests neuroplastic adaptations in the targeted networks and a possible treatment-dependent shift towards more medial prefrontal control over amygdala regulation. These findings are important for fMRI-guided precision neuromodulation therapy development, particularly for the amygdala circuitry.

PMID:41646285 | PMC:PMC12869549 | DOI:10.21203/rs.3.rs-8321466/v2

Similar minds age alike: an MRI similarity approach for predicting age-related cognitive decline

Fri, 02/06/2026 - 19:00

NPJ Aging. 2026 Feb 6. doi: 10.1038/s41514-026-00345-1. Online ahead of print.

ABSTRACT

As individuals age, cortical alterations in brain structure contribute to cognitive decline. However, the specific patterns of age-related changes and their impact on cognition remain poorly understood. This study assessed the effects of aging on individual gray matter similarity networks and compared them to anatomical and functional connectivity networks derived from diffusion-weighted imaging and resting-state fMRI, respectively. Our results showed that gray matter similarity networks outperformed anatomical and functional connectivity in predicting age and cognition, showing the earliest age-related changes across the adult lifespan. These networks also demonstrated greater robustness to individual differences in cognition, behavior, and sex. Notably, age-related changes in gray matter similarity were associated with the brain's underlying cytoarchitecture, being strongest in brain regions from cortical layers II and III. These findings provide a new biological insight into the neural mechanisms of cognitive aging and highlight the potential of individual morphological similarity for capturing complex brain changes across the lifespan.

PMID:41651845 | DOI:10.1038/s41514-026-00345-1

The characteristics of fraction amplitude of low frequency fluctuation among first-episode and drug-naive individuals with depressive disorder combined with internet addiction

Fri, 02/06/2026 - 19:00

J Affect Disord. 2026 Feb 4:121346. doi: 10.1016/j.jad.2026.121346. Online ahead of print.

ABSTRACT

BACKGROUND: Major depressive disorder (MDD) and Internet addiction (IA) are common and cause significant impairment, yet their relationship remains unclear. This study aims to explore the neurobiological mechanisms of comorbid MDD and IA and to inform clinical interventions.

METHODS: This study recruited 141 first-episode, drug-naïve MDD patients (72 with IA, 69 without) and 61 healthy controls (HC). Clinical assessments included the Hamilton Depression Rating Scale (HAMD) and Internet Addiction Test (IAT). Resting-state fMRI data were acquired using a 3 T Siemens scanner, and fractional amplitude of low-frequency fluctuations (fALFF) was computed with the Data Processing Assistant for Resting-State fMRI (DPARSF) software. Statistical analyses involved ANOVA, MANCOVA, and partial correlation, with multiple comparisons corrected using the FDR and Bonferroni methods.

RESULTS: Compared to HC group, both MDD + IA and MDD groups exhibited common elevations in fALFF within the left superior medial frontal gyrus and right superior frontal gyrus, alongside reductions in the right middle occipital gyrus. Concurrently, group-specific alterations were identified: MDD + IA had higher fALFF in the right inferior frontal gyrus triangular region, while MDD exhibited lower fALFF in the right postcentral gyrus and left inferior temporal gyrus. MDD + IA had significantly higher fALFF in the left inferior parietal lobule than MDD. Furthermore, fALFF in this region was positively correlated with IAT scores.

CONCLUSIONS: MDD with IA is associated with distinct neurological alterations in frontal and parietal regions. The left inferior parietal lobule may serve as a potential neurobiological marker for MDD comorbid with IA, providing a target for future interventions.

PMID:41651243 | DOI:10.1016/j.jad.2026.121346

Reactive astrocytes and network functional connectivity underlying cognitive symptoms in schizophrenia: a PET and fMRI study

Fri, 02/06/2026 - 19:00

Biol Psychiatry Cogn Neurosci Neuroimaging. 2026 Feb 4:S2451-9022(26)00027-3. doi: 10.1016/j.bpsc.2026.01.009. Online ahead of print.

ABSTRACT

BACKGROUND: Cognitive symptoms are among the core features of schizophrenia, but their underlying mechanisms remain unclear. Current hypotheses suggest that alterations in the frontal cortex cause network dysfunction, contributing to cognitive symptoms. Growing evidence links reactive astrocytes with cognitive function and the pathophysiology of schizophrenia. We aimed to investigate in vivo reactive astrocyte signals in the dysconnected networks underlying cognitive symptoms in patients with schizophrenia.

METHODS: [18F]THK5351 positron emission tomography (PET) and resting-state functional MRI data were obtained from 32 patients with schizophrenia and 32 age- and sex-matched healthy controls. [18F]THK5351 PET was used to measure monoamine oxidase B, a marker of reactive astrocytes. We performed network analysis to identify dysconnected subnetworks related to cognitive symptoms and examined reactive astrocyte signals in these subnetwork regions.

RESULTS: Patients showed impaired verbal learning (F = 18.97, p < 0.001) and memory (F = 24.31, p <0.001). In patients, reduced left medial orbitofrontal cortex (mOFC)-left dorsolateral prefrontal cortex and left mOFC-right dorsal anterior cingulate cortex connectivity predicted impaired verbal learning (β = 0.45, p = 0.011) and memory (β = 0.56, p = 0.001), respectively. The PET standardized uptake value ratio was greater in the left mOFC in patients than in controls (t = -2.61, p = 0.011).

CONCLUSIONS: We found evidence of increased reactive astrocyte activity in the key region of the dysconnected network underlying cognitive impairments in schizophrenia. These results suggest a potential link between reactive astrocytes in the mOFC and the pathophysiology underlying cognitive symptoms in schizophrenia.

PMID:41651218 | DOI:10.1016/j.bpsc.2026.01.009

Toward a Better Measure of Functional Laterality: Comparing and Refining Laterality Indices in Resting-State Functional Connectivity

Fri, 02/06/2026 - 19:00

Neuroimage. 2026 Feb 4:121782. doi: 10.1016/j.neuroimage.2026.121782. Online ahead of print.

ABSTRACT

Systematic investigations into the lateralized human brain have revealed a bivariate functional architecture that underpins distinct cognitive processes. This architecture manifests through inter- and intra-hemispheric lateralization, captured respectively by neural integration and segregation. In this study, we conducted a comprehensive evaluation of multiple quantitative laterality metrics in resting-state fMRI connectivity, using conceptual models to illustrate how inter- and intra-hemispheric correlations shape functional lateralization. We further highlight the critical influence of factors such as correlation sign, correlation coefficient distribution, and statistical thresholding methodology on the interpretation of functional connectivity-based laterality indices. Our findings show that, in our dataset, laterality metrics based on positive-only functional connectivity with a lenient connection-level threshold most consistently capture established relationships between functional brain lateralization and performance in language and visuospatial domains.

PMID:41651090 | DOI:10.1016/j.neuroimage.2026.121782

Imaging of Brain Tumor Connectivity

Fri, 02/06/2026 - 19:00

Rofo. 2026 Feb 6. doi: 10.1055/a-2779-7718. Online ahead of print.

ABSTRACT

Brain tumors, especially glioblastomas, remain among the tumor diseases with the worst prognosis. Recent findings in brain tumor research show that neuronal and glial integration of tumors, as well as the formation of glioma cell networks, promote tumor progression and therapy resistance. This highlights the need for innovative imaging techniques that conceptualize brain tumors as systemic central nervous system (CNS) diseases that are deeply integrated in the brain's network architecture.This review presents current imaging methods for analyzing tumor-associated functional and structural connectivity with a focus on resting-state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI).Functional connectivity changes in glioma patients can be detected and quantified using fMRI. These changes are associated with tumor biology, as well as prognosis and cognitive performance. Rs-fMRI parameters may support prognostic assessment and the development of new therapeutic strategies. Quantitative structural connectivity analysis at the individual patient level can provide further insight into tumor integration in the brain's connectional architecture. DTI-based tractography is especially relevant in neurosurgical planning, as it maps the spatial relationship between the tumor and white matter tracts.Imaging analysis of tumor-associated network alterations provides deeper insight into brain tumor biology and may support the development of network-targeted therapeutic approaches. Connectivity-based imaging methods, particularly rs-fMRI and DTI, hold great potential to further enhance preoperative planning, prognostic assessment, and personalized treatment strategies for patients with brain tumors. · Glioma cells form networks beyond macroscopic tumor boundaries and promote therapy resistance.. · Glioma cells form synapses with neurons and exploit neural signals for growth.. · Network alterations can be visualized and quantified using rs-fMRI and DTI.. · Tumor-associated network alterations in imaging correlate with tumor biology and prognosis.. · Imaging markers optimize patient management and support development of new therapeutic strategies.. · Suvak S, Wunderlich S, Stoecklein V et al. Imaging of Brain Tumor Connectivity. Rofo 2026; DOI 10.1055/a-2779-7718.

PMID:41650981 | DOI:10.1055/a-2779-7718

Resting-state functional magnetic resonance imaging study of voxel-mirrored homotopy connections in patients with schizophrenia

Fri, 02/06/2026 - 19:00

Psychiatry Res Neuroimaging. 2026 Jan 15;358:112143. doi: 10.1016/j.pscychresns.2026.112143. Online ahead of print.

ABSTRACT

BACKGROUND: This resting-state functional magnetic resonance imaging (rs-fMRI) study investigated alterations in voxel-mirrored homotopic connectivity between schizophrenia patients and healthy controls. It further explored the associations between these neural alterations and clinical profiles. The findings aim to enhance the understanding of interhemispheric dysconnectivity in schizophrenia and may offer clues for identifying potential neurobiological substrates of the disorder.

METHODS: A total of 38 schizophrenic individuals who attended the psychiatric department were recruited as the experimental group, and 35 healthy volunteers from the medical examination centre were enrolled as the control group during the same time period. Scanning of the subject's entire brain using 3.0T MRI. we finally analysed the correlation between voxel-mirrored homotopic connectivity (VMHC) values and disease severity, disease duration and cognitive function.

RESULTS: (1) VMHC values were significantly lower in the bilateral lingual gyrus in the case group compared to the control group(p<0.05). (2)After applying rigorous False Discovery Rate (FDR) correction for multiple comparisons, the reduction in lingual gyrus VMHC remained specifically and positively correlated with poorer performance in delayed memory (p<0.05,Cohen's d = -1.09). Nominal associations with illness duration and overall symptom severity did not survive this statistical correction. (3) The VMHC values were positively correlated with the total cognitive scale score and the delayed memory factor score (p<0.05, q< 0.015).

CONCLUSIONS: This study identifies a robust reduction in interhemispheric functional connectivity within the lingual gyrus of chronic, medicated schizophrenia patients. Critically, the extent of this reduction is specifically linked to the severity of memory impairment, rather than to general symptom profiles. These findings highlight the role of aberrant homotopic connectivity in visual association cortex in the cognitive pathophysiology of schizophrenia and provide a focused neurobiological correlate for future mechanistic and longitudinal investigations.

PMID:41650581 | DOI:10.1016/j.pscychresns.2026.112143

Unveiling Resting-State Functional Connectivity Patterns in Patients With Migraine: A REFORM Study

Fri, 02/06/2026 - 19:00

Neurology. 2026 Mar 10;106(5):e214656. doi: 10.1212/WNL.0000000000214656. Epub 2026 Feb 6.

ABSTRACT

BACKGROUND AND OBJECTIVES: fMRI has proven useful in dissecting the neurobiological underpinnings of migraine. However, the existing evidence is limited by small samples, use of suboptimal statistical thresholds, and different methods of clinical data acquisition. Given these limitations, we hypothesized that a large, well-characterized sample would allow a clearer distinction between resting-state functional connectivity (rs-FC) alterations specific to migraine and those related to migraine subtypes.

METHODS: Adults with migraine and age-matched and sex-matched healthy controls (HCs) underwent a single 3T rs-fMRI scan. We compared rs-FC between migraine and HCs, and across migraine subtypes, using multi-voxel pattern and seed-based analysis. General linear models and analysis of covariance tests with Bonferroni-adjusted cluster-wise family-wise error correction (pFWE-Bonferroni ≤0.001) were applied. rs-FC measures, expressed as Z scores, were also compared across migraine subtypes using general linear models (pBonferroni < 0.05).

RESULTS: We analyzed rs-fMRI data from 264 participants with migraine (mean age 42 ± 12 years, 234 women) and 151 HCs (mean age 41 ± 11 years, 130 women). The multi-voxel pattern analysis identified significant rs-FC differences in a cluster within the bilateral middle cingulate cortex when comparing participants with migraine to HCs (pFWE-Bonferroni <0.001). The seed-based analysis revealed that participants with migraine had increased rs-FC between the cluster in the bilateral middle cingulate cortex and both the right lateral occipital cortex and bilateral occipital pole (both pFWE-Bonferroni <0.001), compared with HCs. Furthermore, increased rs-FC was identified between the limbic lobe and the right occipital pole (pFWE-Bonferroni = 0.0014) and precuneus (pFWE-Bonferroni <0.001). The cingulate-occipital rs-FC was consistently increased in participants with migraine, irrespective of the migraine subtype (pBonferroni <0.001). In addition, ictal participants who were scanned during attacks exhibited an increased hypothalamic rs-FC with the bilateral precuneus, compared with HCs (pBonferroni <0.001). No significant associations emerged between rs-FC and clinical features in migraine.

DISCUSSION: The identified rs-FC alterations between the middle cingulate cortex and occipital regions might represent a migraine-specific trait, suggesting an integration of nociceptive and visual processing. This discovery provides novel insights into the neurobiological underpinnings of migraine and proposes that altered cingulate-occipital rs-FC might serve as a potential biomarker for migraine.

PMID:41650361 | DOI:10.1212/WNL.0000000000214656

Systematic fMRI signal differences across cohorts alter lifespan connectome trajectories

Fri, 02/06/2026 - 19:00

bioRxiv [Preprint]. 2026 Jan 16:2026.01.15.699580. doi: 10.64898/2026.01.15.699580.

ABSTRACT

Large-scale lifespan neuroimaging studies increasingly integrate data across distinct cohorts to characterize trajectories of brain development and aging. However, systematic differences in acquisition protocols and hardware across cohorts can alter signal characteristics in ways that bias downstream analyses. Here we examine three cohorts from the Human Connectome Project (HCP), spanning development (HCP-D), young adulthood (HCP-YA) and aging samples (HCP-A), to illustrate this issue and evaluate existing strategies to mitigate it. HCP has set standards for open, deeply phenotyped, high-resolution human neuroimaging, which are frequently used as high-quality reference datasets in tool validation, replication studies, and cross-cohort meta-analyses. Because of HCP's widespread usage, even modest protocol differences between cohorts-and their downstream effects-can have outsized impacts on the field of neuroscience research. Our analysis reveals that the HCP-YA cohort exhibits systematically weaker temporal signal-to-noise-ratio (tSNR) relative to HCP-D/A. These signal quality discrepancies propagate to downstream analyses, leading to differences in overall resting-state functional correlations, and whole-brain and node-level measures of resting-state network organization (e.g., system segregation, modularity, participation coefficient). Consistent with protocol-driven signal differences, resting-state network measures derived from HCP-YA depart from expected lifespan trajectories, as confirmed by examination of two other lifespan datasets. Harmonization approaches accounting for protocol and scanner-model differences alleviate some of the artifactual differences in brain network measurement. Our findings underscore that signal differences do not merely introduce noise, but can qualitatively alter estimated lifespan trajectories of functional network organization, including partially inverting expected lifespan patterns. Without appropriate harmonization, analyses that combine HCP cohorts can therefore result in biologically misleading inferences about development and aging. We demonstrate how small acquisition differences bias resting-state-derived network metrics, and how these effects can be mitigated. This work advances best practices for valid inferences in multi-cohort lifespan neuroscience research.

PMID:41648495 | PMC:PMC12871149 | DOI:10.64898/2026.01.15.699580

Δ <sup>9</sup> -Tetrahydrocannabinol-induced enhancement of reward responsivity via mesocorticolimbic modulation in squirrel monkeys

Fri, 02/06/2026 - 19:00

bioRxiv [Preprint]. 2026 Jan 24:2026.01.22.701118. doi: 10.64898/2026.01.22.701118.

ABSTRACT

Δ 9 -tetrahydrocannabinol (THC)-containing products are widely used recreationally, partly due to THC's ability to enhance the appetitive (i.e., rewarding) properties of diverse stimuli. However, the neural mechanisms through which THC modulates reward-related processing remain poorly understood. Here, we used a Pavlovian paradigm in adult squirrel monkeys (3males, 1female) to associate a visual conditioned stimulus (CS + ) with appetitive food delivery. The modulatory effects of acute THC (1-10μg/kg, i.m.) on behavioral and brain responses to CS + were evaluated. Event-related functional MRI (fMRI) was employed to characterize the neural correlates of conditioned responding to the CS + , both in the absence and presence of THC treatment, with preconditioning scans serving as control. Behaviorally, THC (3μg/kg) selectively enhanced conditioned responding to the CS + without altering responses to the control stimulus (CS - ) or increasing baseline consummatory responding, underscoring the specificity of THC's action on reward-associated processes. Consistently, fMRI analyses revealed that THC amplified CS + -evoked activation within mesocorticolimbic regions, including the anterior cingulate cortex (ACC), striatum, hippocampus, and substantia nigra-ventral tegmental area (SN-VTA), without affecting activity in visual and motor cortices. This finding underscores the selectivity of THC's neuromodulatory effects on reward-related circuitry. Independent of CS exposure, resting-state functional connectivity analyses indicate that THC enhanced mesocorticolimbic network integration, as evident in strengthened SN-VTA-centered connectivity with the ACC, striatum, and hippocampus. Collectively, these findings demonstrate that THC enhances the responses to appetitive stimuli, through selective modulation of mesocorticolimbic circuitry, highlighting the SN-VTA as a pivotal hub for cannabinoid-mediated regulation of incentive salience and motivational drive toward reward-associated stimuli.

ONE-SENTENCE SUMMARIES: THC enhances behavioral and neural responses to rewards through mesocorticolimbic modulation centered on the SN-VTA.

PMID:41648305 | PMC:PMC12871707 | DOI:10.64898/2026.01.22.701118