Most recent paper
A comprehensive analysis of brain network complexity in task-based fMRI using entropy: systematic review
Brain Imaging Behav. 2026 Mar 26;20(2):61. doi: 10.1007/s11682-026-01124-y.
ABSTRACT
Entropy-based analysis is increasingly used in task-based functional magnetic resonance imaging (fMRI) to quantify neural signal complexity and information dynamics, but variation in entropy definitions, parameter choices, and analytic scope can limit cross-study comparability. To systematically review how entropy measures are implemented, parameterized, and interpreted in task-based fMRI studies in healthy human subjects, focusing on methodological practice. Web of Science was searched using the keywords “fMRI” and “entropy” for the period 2000–2023, restricted to journal articles, proceedings papers, review articles, meeting abstracts, and book chapters. Included studies used task-based fMRI, applied entropy-based quantitative measures, involved healthy human participants, and reported original empirical findings or methodological applications. Non-human, clinical, and resting-state studies were excluded. Records were screened by verifying whether “fMRI” and “entropy” appeared in the title, keywords, Keywords Plus, or abstract. Extracted items included entropy type, analytic scope (regional/voxel-wise, network-level, connectivity-based), parameter and reporting details, task types, and preprocessing context where available. Data were synthesized using structured narrative methods because meta-analysis was not appropriate given differences in entropy definitions, parameterization, task types, and outcome metrics. Risk of bias was assessed with an adapted Joanna Briggs Institute (JBI) checklist (Joanna Briggs Institute, 2017). Database searches yielded 1,313 records. 274 were screened and 234 full texts assessed. 92 studies met inclusion criteria. Exclusions at full-text were primarily resting-state studies (n = 81), clinical populations (n = 42), and non-human studies (n = 19). Across the 92 included studies, Shannon entropy predominated (78.3%), followed by sample entropy (9.78%), transfer entropy (4.35%), multiscale entropy (3.26%), approximate entropy (3.26%), and multiple-entropy approaches (1.09%). Entropy measures were found to be matched with distinct methodological roles. Approximate and sample entropy were commonly used for regional or voxel-wise signal regularity, multiscale entropy for multi–time scale complexity (often at the network level), transfer entropy for directed connectivity, and Shannon entropy for broad applications including machine-learning feature and validation use. Evidence synthesis was constrained by inconsistency in entropy formulations, parameter reporting, preprocessing decisions, and outcome metrics. Formal heterogeneity testing, subgroup analyses, and sensitivity analyses were not conducted, and results were summarized descriptively. Task-based fMRI entropy research is methodologically diverse but consistently demonstrates the feasibility of using entropy to characterize task-related brain complexity across different analytic levels. The prevalent use of Shannon entropy and inconsistent parameter/reporting practices underscore the need for clearer, standardized reporting and reproducible implementation guidance to improve comparability across studies.
PMID:41886027 | PMC:PMC13021814 | DOI:10.1007/s11682-026-01124-y
Temporal Dynamics of Parkinson's Disease Tremor: Clinical and Neuroimaging Insights
Mov Disord. 2026 Mar 26. doi: 10.1002/mds.70268. Online ahead of print.
ABSTRACT
BACKGROUND: Parkinson's disease (PD) is a progressive neurodegenerative disorder clinically defined by three cardinal motor symptoms: bradykinesia, rigidity, and tremor. Although the natural history of bradykinesia and rigidity is well described, the evolution of tremor as the disease progresses remains controversial.
OBJECTIVES: The goal was to clinically characterize long-term trajectories of rest, postural, and action tremor in PD and examine their neural network correlates using longitudinal resting-state functional magnetic resonance imaging (rs-fMRI).
METHODS: In this retrospective longitudinal cohort study, we analyzed 93 tremor-positive PD patients (mean disease duration: 3.6 years), each with up to six clinical assessments over 4.2 years. Linear mixed-effects models assessed temporal change in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and Fahn-Tolosa-Marín Tremor Rating Scale (FTM-TRS) scores. Rs-fMRI data from 30 tremor-affected patients (mean interval, 3.35 years) were analyzed for seed-to-whole-brain connectivity and connectivity between predefined brain regions.
RESULTS: Bradykinesia (β = +0.09, P < 0.001) and rigidity (β = +0.06, P < 0.001) worsened, whereas total FTM-TRS scores declined by 0.49 points/year (P = 0.037), driven by reductions in postural (P < 0.001) and action tremor (P = 0.033); resting tremor remained stable. Rs-fMRI revealed longitudinal changes in cerebellar- and thalamic-seed-to-whole-brain connectivity.
CONCLUSIONS: Tremor in PD evolves along distinct clinical courses, often stabilizing or improving as other motor features worsen. These findings are consistent with partially adaptive reorganization within tremor-related networks and underscore the importance of identifying patient subtypes with divergent trajectories to inform prognosis and optimize therapy. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PMID:41885037 | DOI:10.1002/mds.70268
Decreased BOLD Signal Variability in Middle-Aged and Older Adults on the Autism Spectrum
Autism Res. 2026 Mar 26:e70208. doi: 10.1002/aur.70208. Online ahead of print.
ABSTRACT
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Preliminary evidence suggests an increased risk for early-onset cognitive and neurological decline in ASD. While brain development in children, adolescents, and young adults with ASD diverges from neurotypical (NT) peers, it remains unclear in older adults with ASD. Understanding age-related changes of brain function in ASD is crucial to establish best practices for cognitive and health screenings and develop interventions that might reduce the risk of accelerated decline. Decreases in blood-oxygenation-level-dependent (BOLD) signal variability (BSV) in typical aging have been shown across multiple studies and are associated with poorer cognitive performance. We hypothesized that adults with ASD would show reduced BSV compared to the NT group, with steeper negative age associations in the ASD than NT group. The study assessed BSV during resting state fMRI in adults (40-70 years), 28 with ASD and 39 age-matched NT. General linear models tested diagnostic group, age, and group-by-age interactions, controlling for motion. Significant group-by-age interactions were observed for the right insular, left temporal occipital fusiform, right frontal orbital, and right inferior lateral occipital cortex, with BSV showing strong negative associations with age in the ASD but not NT adults. These findings suggest that BSV decreases may occur earlier in adults with ASD compared to their NT peers. This would be consistent with accelerated aging; however, additional longitudinal analyses are necessary to determine if the results presented truly reflect accelerated aging or arise from lifelong persistent differences in brain function.
PMID:41885009 | DOI:10.1002/aur.70208
A Multimodal Dataset to Investigate Task-Evoked Negative BOLD Response and Neurodegeneration
Sci Data. 2026 Mar 25. doi: 10.1038/s41597-026-07081-x. Online ahead of print.
ABSTRACT
The Quantitative Neuroimaging Laboratory Dataset provides magnetic resonance imaging (MRI) modalities and two resting-state and twelve task-based functional MRI (fMRI) tapping into four cognitive domains (episodic memory, fluid reasoning, processing speed, and crystallized memory). It also includes three positron emission tomography (PET) scans ([18 F]Fluorodeoxyglucose (FDG), Florbetaben, and MK-6240), plus neuropsychological assessments, and vital signs. Currently, 356 participants consented (97 young: 20 ~ 40 years; and 259 elderly: 60 ~ 80 years), while 259 completed at least one scan. We uploaded 4688 MRI/fMRI and 719 PET scans (232 Florbetaben, 251 FDG, and 236 MK-6240). 189 participants completed all scan modalities. All imaging underwent an in-house, pre-processing pipeline developed for each modality. This dataset aims to characterize the spatial and temporal properties of the brain's hemodynamic response in the opposite direction (i.e., brain deactivation), its task dependency, and its interaction with the brain's large-scale functional connectivity networks. Ultimately, this will enable the translation of neuroimaging findings into personalized medicine approaches that better characterize and predict individual pathologies in neuropsychiatric diseases.
PMID:41882039 | DOI:10.1038/s41597-026-07081-x
Sex Difference in Brain Responses During Short Abstinence in People With Internet Gaming Disorder
Addict Biol. 2026 Apr;31(4):e70145. doi: 10.1111/adb.70145.
ABSTRACT
Withdrawal or the adverse response to abstinence is a significant marker of addiction; however, the neural features of internet gaming disorder (IGD), especially the effects of sex under abstinence, have rarely been examined. This study aimed to examine brain reactions in IGD patients after short-term abstinence and the differences between the sexes. Thirty males and 30 females with IGDs and 30 males and 30 females recreational game users (RGUs) were recruited. Resting-state fMRI data were collected after 1.5 h without gaming. In the IGD and RGU groups, we found atypical brain areas with concurrent degree centrality (DC) and regional homogeneity (ReHo) changes. We then performed functional connectivity (FC) analysis and two-factor ANOVA on these regions to compare IGD and RGU and test for sex differences. Compared with RGUs, IGD subjects presented abnormal cerebral areas with concurrent DC and ReHo abnormalities. After short-term abstinence, IGD and RGU patients presented abnormal prefrontal lobe and insula FC values. Subsequent sex difference analyses focused on the superior frontal gyrus (SFG), middle frontal gyrus (MFG), inferior frontal gyrus (IFG) and insula. ANOVA followed by FDR-corrected post hoc comparisons revealed that IGD males exhibited significantly greater prefrontal and insula FC than females after short-term abstinence. Specifically, males showed markedly enhanced FC in multiple prefrontal regions and the insula, with effect sizes (Cohen's d) ranging from medium to large, confirming both the efficacy and reliability of the observed differences. Compared with RGUs, IGD patients presented FC changes in executive control and reward processing brain regions. With respect to sex differences, short-term abstinence may have altered cognitive control functions more in males than in females and increased internet gaming severity in males. These findings suggest that males are more susceptible to IGD.
PMID:41881684 | DOI:10.1111/adb.70145
Altered brain network topology in adolescents with major depressive disorder and bipolar disorder: A resting-state fMRI graph-theoretical and machine learning study
J Affect Disord. 2026 Mar 23:121670. doi: 10.1016/j.jad.2026.121670. Online ahead of print.
ABSTRACT
BACKGROUND: Adolescents with major depressive disorder (MDD) and bipolar disorder (BD) share substantial clinical overlap and elevated suicide risk, yet the neurobiological distinctions between these disorders and their associations with suicidality remain incompletely understood. This study investigated functional connectome differences between adolescent MDD and BD and examined associations with suicide attempts (SA).
METHODS: Resting-state fMRI data were acquired from 125 adolescents aged 12-19 years (48 MDD, 36 BD, 41 healthy controls). We used graph-theoretical analysis to investigate group differences in functional brain networks, and machine learning models were applied to functional network data to distinguish between MDD and BD.
RESULTS: Compared with MDD and healthy controls, adolescents with BD exhibited a global shift toward network randomization, characterized by a lower clustering coefficient and widespread reductions in nodal centrality across hubs of the DMN, SN, and CEN. In contrast, MDD was characterized by preserved global topology but focal nodal alterations. Within the MDD group, greater suicidal-ideation severity was associated with lower nodal efficiency in the insula and supramarginal gyrus. A support vector machine classifier distinguished MDD from BD with 88.24% (p < 0.001) accuracy, with features from the insula and cingulate gyrus being highly informative.
CONCLUSIONS: Adolescent MDD and BD showed distinct patterns of functional network disruption, with BD showing global network disorganization and MDD showing more localized disruptions. Alterations involving the insula and supramarginal gyrus may be relevant to suicidality in adolescent MDD, and network-based features may aid in distinguishing MDD from BD.
PMID:41881121 | DOI:10.1016/j.jad.2026.121670
Disrupted cerebello-cerebral functional integration of triple core networks in major depressive disorder: A resting-state fMRI study
J Affect Disord. 2026 Mar 23:121665. doi: 10.1016/j.jad.2026.121665. Online ahead of print.
ABSTRACT
BACKGROUND: Emerging evidence has highlighted the cerebellum's role in emotion and cognition through cerebello-cerebral interactions. However, the manner in which the cerebellum integrates with the cerebral triple core networks, the default mode network (DMN), central executive network (CEN), and salience network (SN), in Major Depressive Disorder (MDD) remains unclear.
METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 119 patients with MDD and 106 healthy control (HC) subjects. Voxel-wise functional connectivity (FC) between the cerebral cortex and cerebellum was subsequently constructed. To evaluate cerebello-cerebral functional integration based on voxel-wise FC, functional gradient analysis and independent component analysis (ICA) were performed.
RESULTS: The cerebral triple core network components were found to map onto cerebellar motor and cognitive functional modules. In patients with MDD, reduced mapping of the cerebral DMN and SN components to the cerebellum was observed. Additionally, patients exhibited compression of the cerebello-cerebral functional gradient within both motor and cognitive modules. The triple core networks showed increased contributions to cerebellar cognitive modules, whereas the DMN demonstrated decreased contributions to cerebellar motor modules in MDD. These cerebello-cerebral interaction patterns were significantly correlated with clinical assessment measures, including scores on the Trail Making Test (TMT) and the Emotion Regulation Questionnaire (ERQ).
CONCLUSIONS: These findings indicate disrupted functional integration between the cerebral triple core networks and the cerebellum in MDD. The results further support the cerebellum's involvement in disease pathogenesis and suggest potential neurobiological markers for diagnosis and intervention.
PMID:41881114 | DOI:10.1016/j.jad.2026.121665
Abnormal functional connectivity patterns in temporal lobe epilepsy-An international ENIGMA-epilepsy study
Epilepsia Open. 2026 Mar 25. doi: 10.1002/epi4.70209. Online ahead of print.
ABSTRACT
OBJECTIVES: Temporal lobe epilepsy (TLE) impacts multiple brain networks. Aberrant functional connectivity has been demonstrated in resting-state networks (RSNs) that mediate higher brain functions in TLE. This study aimed to identify the reproducible patterns of altered functional connectivity in TLE in a large, international cohort through ENIGMA-Epilepsy.
METHODS: Resting-state functional MRI datasets from nine centers across North America, South America, Europe and South Africa, including 442 people with TLE and 387 healthy adults, were analyzed. We examined group differences in whole-brain connectivity in patients compared to controls in seven major RSNs. We also investigated whole-brain connectivity maps for key nodes within the default mode network (DMN). Furthermore, the associations between connectivity patterns and clinical variables were assessed.
RESULTS: We found lower within-network connectivity scores (13.6% on average) and higher between-network connectivity scores (129% on average) in non-limbic RSN in TLE. This pattern was reproducible across all seven sites and most robust for DMN and visual networks. Patterns of connectivity were not associated with age of seizure onset or disease duration and were mostly similar in patients with left and right TLE with a few exceptions; isolated regions of high connectivity in left TLE and lower connectivity in right TLE compared to controls.
SIGNIFICANCE: We show strong evidence of lower connectivity within most RSNs and higher connectivity outside of these networks that was highly consistent across geographically diverse sites, demonstrating the robustness and generalizability of our findings. The findings demonstrate a consistent disruption of network organization in TLE that may underlie cognitive co-morbidities and seizure propagation patterns observed in this patient population.
PLAIN LANGUAGE SUMMARY: In this international ENIGMA-Epilepsy study, resting-state fMRI data from 442 individuals with TLE showed reduced connectivity within major resting-state networks (about 14% lower) and markedly increased connectivity between networks (about 129% higher), compared to 387 healthy controls. These patterns were highly reproducible across sites. Connectivity alterations were not related to age of onset or disease duration and were largely similar across left and right TLE, aside from small, region-specific differences. Overall, the study demonstrates a robust, widespread reorganization of brain network connectivity in TLE, which may help explain associated cognitive difficulties and seizure spread.
PMID:41880651 | DOI:10.1002/epi4.70209
Altered temporal dynamics of intrinsic brain activity in mild cognitive impairment with olfactory dysfunction
J Alzheimers Dis. 2026 Mar 25:13872877261431797. doi: 10.1177/13872877261431797. Online ahead of print.
ABSTRACT
BackgroundOdor identification (OI) impairment in mild cognitive impairment (MCI) elevates the risk for Alzheimer's disease (AD). The present study was designed to clarify the underlying neural mechanisms by investigating brain network aberrations in MCI patients with OI impairment using dynamic resting-state functional magnetic resonance imaging (rs-fMRI).ObjectiveThis study aimed to delineate the profile of dynamic intrinsic brain activity in MCI patients with and without OI impairment. It further aimed to establish the clinical relevance of these dynamic neural signatures by linking them to cognitive and olfactory function.MethodsIn 194 participants (97 MCI and 97 healthy controls [HC]), we analyzed dynamic metrics including dynamic fractional Amplitude of Low-Frequency Fluctuations (dfALFF), dynamic Amplitude of Low-Frequency Fluctuations (dALFF), dynamic Degree Centrality (dDC), and dynamic Regional Homogeneity (dReHo), and their correlation with cognitive performance and OI.ResultsThe MCI with OI impairment (MCI-OII) group (n = 22) performed worse across all cognitive domains than both HC and the MCI without OI impairment (MCI-NOII) group (n = 75, p < 0.001). These patients exhibited elevated dALFF, dfALFF, dDC, and dReHo variability in regions including the fusiform gyrus, insula, precuneus, and cingulate cortex (p < 0.001). These dynamic metrics correlated with olfactory and cognitive scores (p < 0.05). Additionally, dReHo in the right precuneus partially mediated the relationship between olfactory function and delayed recall memory.ConclusionsThis study demonstrates that MCI patients with OI impairment exhibit widespread disruptions in dynamic brain activity. These alterations correlate with clinical deficits, and precuneus dReHo may partially link olfactory and cognitive decline in MCI.
PMID:41879263 | DOI:10.1177/13872877261431797
The motion sensitivity and predictive utility of different estimates of interregional functional coupling in resting-state functional MRI
Netw Neurosci. 2026 Mar 20;10(1):221-243. doi: 10.1162/NETN.a.534. eCollection 2026.
ABSTRACT
Numerous methods exist for quantifying statistical dependencies, termed "functional coupling" (FC), between regional brain activity recorded with resting-state functional magnetic resonance imaging (rs-fMRI). However, their efficacy in mitigating the effects of known sources of noise, such as those induced by participant head motion, and in augmenting effect sizes for brain-wide association studies (BWAS), remains unclear. Here we compared 10 different measures of FC, including correlations, partial correlations, coherence, mutual information, and partial information decomposition, and one measure of effective connectivity (EC; regression dynamic causal modeling), across two independent datasets comprising a total of 1,797 participants (867 males). Each method was evaluated for its ability to mitigate motion-related confounds in FC/EC estimates (assessed via framewise-displacement - edgewise FC correlations) and for its utility in predicting 94 behavioral measures (assessed via cross-validated kernel ridge regression). Our analyses showed that EC was most resistant to motion artifacts but had the weakest behavioral predictions. Conversely, traditional correlation-based methods showed the highest sensitivity to motion, but offered the strongest behavioral prediction across most domains and datasets. Nonetheless, relative differences in predictive accuracies were small, indicating that the use of different FC or EC metrics in rs-fMRI does not significantly impact BWAS effect sizes.
PMID:41878612 | PMC:PMC13008380 | DOI:10.1162/NETN.a.534
A Hybrid RF Coil for Whole-Brain Imaging in Non-Human Primates at 7 T
Magn Reson Med. 2026 Mar 24. doi: 10.1002/mrm.70361. Online ahead of print.
ABSTRACT
PURPOSE: Ultra-high field MRI (≥ 7 T) offers unprecedented potential for mapping non-human primate (NHP) brain function. However, complex electromagnetic systems are required to meet the challenges of UHF imaging and the mechanical demands of awake NHP studies. To address these challenges, we developed a hybrid RF coil system optimized for whole-brain fMRI of macaques at 7 T.
METHODS: The hybrid coil system combines a 6-channel preamplifier-decoupled transceive dipole array with a 16-channel loop receive array, housed in a compact structure designed for awake imaging that maintains open visual fields. Key design features include compatibility with sphinx-position monkey chairs and head fixation systems required for awake experiments. Electromagnetic simulations guided dipole design to optimize uniform transmit performance and deep penetration. Phantom and in vivo experiments validated these predictions using anesthetized macaques and evaluated the system's readiness for awake imaging.
RESULTS: The hybrid coil demonstrated uniform B 1 + $$ {B}_1^{+} $$ distribution with phase-shimmed transmission across the brain. It supported robust parallel imaging, enabling up to R = 3 × 2 acceleration factors for high-resolution acquisitions. The achieved whole-brain tSNR in fMRI is comparable to that of an existing 8-TX/24-RX coil designed for imaging anesthetized macaques. Critically, submillimeter (0.75 mm isotropic) resting-state fMRI revealed clear default-mode network connectivity, confirming the system's capability for high-quality functional imaging.
CONCLUSION: By effectively addressing both the technical challenges of ultra-high field MRI and the mechanical constraints associated with visual stimulation in awake NHPs, this hybrid coil system provides a powerful tool for advancing our understanding of primate brain function.
PMID:41876923 | DOI:10.1002/mrm.70361
Thalamic organization differentially contributes to clinical conditions in epilepsy
Commun Med (Lond). 2026 Mar 24. doi: 10.1038/s43856-026-01530-9. Online ahead of print.
ABSTRACT
BACKGROUND: The thalamus plays an important role in key clinical conditions of focal temporal lobe epilepsy (TLE), but no investigation has examined whether the same thalamic local and connectome properties shape a patient's status across these different conditions.
METHODS: This retrospective longitudinal MRI study used resting-state fMRI and structural imaging to identify whole-brain focal/regional and connectome-level features associated with six binary clinical conditions of TLE (pre/post-surgery, seizure and neurocognitive outcomes, pathology, seizure subtype, and SOZ lateralization) in 91 patients across two centers (age range: 15-65 years) and 85 matched healthy participants (age range: 18-60 years).
RESULTS: Across conditions, relative to all other brain regions, thalamic features exert the strongest influence. Specifically, thalamic focal and connectome intrinsic activity and gray matter volume are robustly associated with post-surgical reorganization. Pre-surgical thalamic hyperconnectivity predicts poorer seizure control, whereas post-surgical reorganization is not associated with either seizure outcome. Neuropsychological outcomes are subsequently examined and show associations with local ipsilateral thalamic properties. Namely, pre-surgical organization of the ipsilateral thalamus is associated with better preservation of cognitive performance, whereas post-surgical organization is associated with greater cognitive decline.
CONCLUSIONS: Our results expand and refine our understanding of the thalamus as a region showing robust and recurrent associations across multiple clinical conditions of TLE. Importantly, we distinguish its role in pre- versus post-surgical brain organization with respect to seizure and neuropsychological outcomes, highlighting its importance for planning and prognosis in epilepsy surgery.
PMID:41876841 | DOI:10.1038/s43856-026-01530-9
Brain network functional connectivity changes induced by music-induced analgesia in fibromyalgia patients
Sci Rep. 2026 Mar 24. doi: 10.1038/s41598-026-45376-6. Online ahead of print.
ABSTRACT
Music can liberate positive power of pain management in fibromyalgia (FM) patients through multiple neural modulation. However, traditional brain research preferred to investigate the neural characteristics of music-induced analgesia (MIA) based on the seed points of functional activation, which limits the understanding of the connection states of the whole-brain functional synchronization network involved in FM's music listening. The current study aimed to investigate the whole-brain network functional connectivity (FC) differences of resting-state functional magnetic resonance imaging (RS-fMRI) before and after music listening in FM patients using a data-driven analysis approach. Using a publicly available dataset, the RS-fMRI data from 20 FM patients were analyzed. A network-based FC approach was applied to compare intra- and inter-network FC changes across the visual network (VN), somatosensory network (SMN), ventral attention network (VAN), default mode network (DMN), and subcortical network (SC). After music listening, FM patients exhibited significant reduction in evaluation of pain intensity (PI), and also exhibited changed intra-network FC within the VAN and VN; changed inter-network FC between the VAN and DMN, between the VN and SMN or DMN, between the SMN and DMN, and between the VN and SMN or DMN, respectively. What's more, correlations were found between post-pre changes in subjective pain ratings and post-pre changes in network FC. Positive correlations were found between PI's reduction and the increase of inter-network FC between the right fusiform (VN) and left middle insula (SMN), and also found between the reduction of pain unpleasantness (PU) and the increase of inter-network FC between the left middle insula (SMN) and left posterior occipital cortex (DMN). The network FC results here provided new evidence to the inter/intra-networks in VN, SMN, VAN, DMN, and subcortical network, explaining that FM patients may generate cognitive processing from bottom to top and emotion regulation from top to down to realize their MIA.
PMID:41876765 | DOI:10.1038/s41598-026-45376-6
Dynamic brain connectivity patterns induced by oxytocin: An fMRI Co-Activation pattern analysis study
Mol Psychiatry. 2026 Mar 24. doi: 10.1038/s41380-026-03549-9. Online ahead of print.
ABSTRACT
Oxytocin (OT) is a neuropeptide widely implicated in emotional regulation and social cognition. However, its effects on dynamic brain connectivity remain poorly understood. In this study, we applied co-activation pattern (CAP) analysis to resting-state fMRI data to examine how a single intranasal dose of OT modulates whole-brain functional dynamics. Participants included healthy young (18-31 years) and older (63-81 years) adults, with analyses conducted at both the group level and across age subgroups. OT significantly altered temporal properties of brain states, including increased frequency, in-degree, and out-degree in multiple CAPs, indicating enhanced network flexibility and switching. Notably, OT modulated states involving the amygdala, medial prefrontal cortex, and salience network, regions critical for emotion regulation, and increased self-transition probabilities, suggesting greater within-state stability. Age-stratified analysis revealed differential sensitivity: young adults exhibited more pronounced modulation and greater dynamic flexibility, while older adults showed more sustained engagement with emotion-related states. Importantly, only in the elderly OT and combined young subgroups did time spent in these states significantly correlate with cognitive performance on the Digit Symbol Substitution Test, suggesting that OT-enhanced engagement in these networks supports compensatory mechanisms during aging. No such correlations were found in young participants or in either age group under placebo, highlighting the specificity of oxytocin's functional relevance in older adults. Meta-analytic decoding using Neurosynth confirmed that OT-modulated regions are closely associated with emotion, memory, and social cognition. These findings demonstrate that OT shapes transient brain dynamics in age- and function-specific ways. CAP analysis provides a powerful approach for capturing such neuromodulatory effects.
PMID:41876708 | DOI:10.1038/s41380-026-03549-9
Effects of CBT-I in modulating neuroplasticity in brain regions associated with insomnia disorder and serum 27-OHC levels
Prog Neuropsychopharmacol Biol Psychiatry. 2026 Mar 22:111678. doi: 10.1016/j.pnpbp.2026.111678. Online ahead of print.
ABSTRACT
Insomnia disorder (ID) is often accompanied by cognitive deficits and disturbances in brain networks and metabolism. As a potential marker of central metabolism and oxidative stress, the role of 27-hydroxycholesterol (27-OHC) in ID pathophysiology and dCBT-I-induced neuroplasticity remains unclear. This study investigated the relationships among alterations in brain function, 27-OHC levels, and the therapeutic effects of dCBT-I. We collected resting-state fMRI data and serum samples from 32 ID patients (at baseline and after six weeks of dCBT-I) and 32 healthy controls. We compared group differences in spontaneous anterior cingulate cortex (ACC) activity and resting-state functional connectivity (rsFC), and assessed whether changes in brain function and 27-OHC levels were associated with dCBT-I effects. Results showed that ID patients exhibited decreased spontaneous activity in the right ACC and enhanced rsFC within the sensorimotor network. Serum 27-OHC concentrations were significantly elevated and positively correlated with rsFC strength of the supplementary motor area. After dCBT-I, 27-OHC levels significantly decreased, and the treatment reversed aberrant activity in several brain regions. Post-treatment changes in dysfunctional beliefs about sleep were closely associated with normalized activity in the left putamen and left middle temporal gyrus. In summary, elevated serum 27-OHC and its aberrant coupling with the sensorimotor network jointly constitute an important biological basis for hyperarousal in ID. dCBT-I not only alleviates peripheral metabolic stress but also reshapes patients' cognition by inducing neuroplasticity within the striatum (especially the putamen and caudate).
PMID:41875969 | DOI:10.1016/j.pnpbp.2026.111678
Subclinical anxiety is associated with reduced self-distancing and enhanced self-blame-related connectivity between anterior temporal and subgenual cingulate cortices
Prog Neuropsychopharmacol Biol Psychiatry. 2026 Mar 22:111679. doi: 10.1016/j.pnpbp.2026.111679. Online ahead of print.
ABSTRACT
Excessive self-blaming emotions are commonly observed in anxiety disorders, with qualitatively similar symptomatology reported in subclinical populations. Interpretation of moral information requires assessing the social conceptual information, a process overseen by the superior anterior temporal lobe (sATL). Feelings of self-blame evoke interactions of sATL and socio-affective regions, and previous research shows that subclinical anxiety modulates the organisation of the self-blame circuitry. This study aimed to extend these findings by exploring links of trait-anxiety with (i) self-blaming emotions and associated behaviours in an experimental task, and (ii) self-blame-dependent neural activity and connectivity, as observed during reliving of autobiographical guilt memories. We also explored the role of resting-state fMRI in linking these phenomena. Increased anxiety was linked to stronger self-blaming emotions, and more pronounced self-attacking and hiding. When experiencing negative emotions about themselves (i.e. shame and self-anger), anxious individuals were also less likely to disengage from self-focused thoughts. These behavioural findings were paralleled by enhanced self-blame-related connectivity between the left sATL and bilateral posterior subgenual cingulate cortex. Distinct patterns of activity and connectivity within the ATL-related circuitry were furthermore linked to individual differences in intensity of the self-blaming emotions and approach-avoidance motivation towards the guilt memories. As such, the results of the current study link stronger self-blaming emotions in anxious individuals with specific maladaptive patterns of behaviour. Furthermore, the work provides robust evidence for the important role of ATL-related circuitry in self-blame processing, supporting its broader involvement in social conceptual processing and its alterations in subclinical anxiety.
PMID:41875966 | DOI:10.1016/j.pnpbp.2026.111679
Temporal interference stimulation (TIS) for major depressive disorder: right lingual gyrus as a predictor
J Affect Disord. 2026 Mar 21:121660. doi: 10.1016/j.jad.2026.121660. Online ahead of print.
ABSTRACT
BACKGROUND: Temporal interference stimulation (TIS) enables selective modulation of deep-brain targets without cortical activation, yet its therapeutic utility in major depressive disorder (MDD) remains unknown. Therefore, this multicenter, randomized controlled trial evaluated right-amygdala targeted TIS for MDD and identified predictors of treatment response.
METHODS: This study was a secondary analysis of a multicenter, randomized, double-blind, sham-controlled trial. Seventy-six MDD patients were enrolled across Tianjin Anding Hospital and Shanghai Ruijin Hospital and randomly assigned in a 1:1 ratio to active or sham groups. Resting-state functional MRI (rs-fMRI) and 17-item Hamilton Depression Rating Scale (HDRS-17) assessments were obtained at baseline, and clinical outcomes were evaluated at weeks 3 and 8. Within the active group, patients were categorized as responders or nonresponders based on week-8 HDRS-17 outcomes. Baseline amplitude of low-frequency fluctuations (ALFF) was compared between groups using two-sample t-tests. Associations between the identified regions and symptom improvement were examined using partial correlations. Logistic regression and ROC analyses were used to evaluate the predictive value of baseline ALFF measures for treatment response. The study was registered with ClinicalTrials.gov, NCT06477276.
RESULTS: 14 patients (44%) responded to active TIS. Responders showed significantly lower baseline ALFF in the right lingual gyrus (GRF voxel p < 0.001, cluster p < 0.05, one-tailed). Right lingual gyrus ALFF was negatively correlated with HDRS-17 improvement (r = -0.696, p < 0.001). Logistic regression confirmed its predictive value (Model 1: OR = 0.016, 95% CI = 0.000 to 0.915, p = 0.045; Model 2 adjusted for age: OR = 0.000, 95% CI = 0.000 to 0.125, p = 0.011). ROC analysis yielded an AUC of 0.714 (p = 0.040, 95% CI = 0.550 to 0.893).
CONCLUSION: Right-amygdala TIS improves depressive symptoms, and lower baseline right lingual gyrus ALFF emerged as a promising biomarker for predicting response.
PMID:41871633 | DOI:10.1016/j.jad.2026.121660
An exploratory study of altered regional homogeneity in Parkinson's disease with depression
Front Psychiatry. 2026 Mar 5;17:1771679. doi: 10.3389/fpsyt.2026.1771679. eCollection 2026.
ABSTRACT
BACKGROUND: Depression is a prevalent non-motor symptom in Parkinson's disease (PD), yet its pathogenesis is unclear and biomarkers are lacking. This rs-fMRI study used Regional Homogeneity (ReHo) to explore neural correlates in PD with depression (DPD).
METHODS: We included 23 DPD, 24 non-depressed PD (NDPD), and 20 healthy controls (HC). ReHo analysis was applied to identify regional brain activity differences. Correlations between ReHo values and depression severity (HAMD scores) were examined. ROC analysis assessed the diagnostic utility of ReHo changes.
RESULTS: Compared to NDPD, DPD showed increased ReHo in the left inferior temporal gyrus (ITG) and decreased ReHo in the right middle frontal gyrus (MFG), left insula, and left hippocampus. ReHo in left ITG positively correlated with HAMD scores (r = 0.4347, P = 0.0023), while right MFG (r = -0.5262, P = 0.0001), left insula, and left hippocampus (r = -0.4049, P = 0.0048) showed negative correlations. ROC analysis indicated that ReHo in the left insula and hippocampus could distinguish DPD (AUC = 0.8062).
CONCLUSION: DPD is associated with distinct ReHo alterations. Abnormalities in the left ITG, right MFG, left insula, and left hippocampus may reflect the neural basis of DPD. Our exploratory analyses suggest that altered ReHo in the left insula and left hippocampus may hold potential as neuroimaging biomarkers.
PMID:41868838 | PMC:PMC12999784 | DOI:10.3389/fpsyt.2026.1771679
A novel virtual reality-integrated multi-modal intervention for community-dwelling older adults with mild cognitive impairment: protocol for a randomized controlled trial
Front Aging Neurosci. 2026 Mar 5;18:1721346. doi: 10.3389/fnagi.2026.1721346. eCollection 2026.
ABSTRACT
BACKGROUND: Emerging research suggests virtual reality (VR) techniques hold promise for mitigating cognitive decline in patients with mild cognitive impairment (MCI). Furthermore, accumulating evidence indicates that gut dysbiosis is a key factor associated with cognitive impairment. This study aims to determine whether a novel virtual reality-integrated multi-modal intervention can beneficially modulate the brain-gut axis in individuals with MCI.
METHODS: This study is a randomized single-blind controlled trial that will include 66 older adults with MCI from the community. Eligible participants will be randomly assigned in a 1:1 ratio to the intervention group or the waitlist group. The intervention group will complete 36 sessions (three sessions per week for 12 weeks) consisting of virtual reality cognitive training (VRCT), traditional cognitive training (TCT), and physical exercise (PE). The control group will not receive any intervention during the study period. The primary outcome is the change in a memory-weighted cognitive composite score. Exploratory outcomes: mechanistic changes along the brain-gut axis, including: (1) Changes in gut microbiota alpha/beta diversity and composition assessed by 16S rRNA gene sequencing, (2) Changes in resting-state brain activity and functional connectivity assessed by fMRI. Outcome measures will be assessed at three or four time points: baseline, mid-intervention (Week 6), post-intervention (Week 12), and at a 12-week follow-up (Week 24).
EXPECTED OUTCOMES: We hypothesize that, relative to the waitlist control, the intervention group will demonstrate concurrent improvements in cognitive performance and a shift in gut microbiota composition toward a more favorable profile, thereby providing preliminary evidence for modulation of the brain-gut axis.
CLINICAL TRIAL REGISTRATION: [www.chictr.org.cn], identifier [ChiCTR2400093397].
PMID:41868429 | PMC:PMC12999948 | DOI:10.3389/fnagi.2026.1721346
A Large-scale Neural Model Inversion Framework for Effective Connectivity Estimation
Med Image Comput Comput Assist Interv. 2026;15961:3-12. doi: 10.1007/978-3-032-04937-7_1. Epub 2025 Sep 20.
ABSTRACT
The development of a computational framework that can infer large-scale brain-wide effective connectivity (EC) based on resting-state functional MRI (rs-fMRI) represents a grand challenge to computational neuroimaging. Towards the goal of estimating full-scale, whole-brain EC, we developed a new computational framework termed Large-scale nEural Model Inversion (LEMI) by utilizing a linear neural mass model with an efficient Kalman-filter based gradient descent algorithm. Key advantages of LEMI include fast estimation of both intra-regional and inter-regional connection strengths for large-scale networks, allowing exploration of both intrinsic and external mechanisms in neuroscience problems. Using ground-truth simulations, we demonstrated that LEMI can accurately and efficiently recover model parameters in a large network (100 regions) within 90 minutes. We then applied the LEMI model to an empirical rs-fMRI dataset from the ADNI database and identified widespread reduced excitation-inhibition (E-I) ratio in patients with Alzheimer's disease (AD). Overall, LEMI provides an efficient and accurate computational framework to estimate large-scale EC and whole-brain E-I balance based on non-invasive neuroimaging data.
PMID:41867361 | PMC:PMC13004605 | DOI:10.1007/978-3-032-04937-7_1