Most recent paper
Influence of binge drinking on the resting state functional connectivity of university Students: A follow-up study
Addict Behav Rep. 2025 Jan 10;21:100585. doi: 10.1016/j.abrep.2025.100585. eCollection 2025 Jun.
ABSTRACT
Binge Drinking (BD) is characterized by consuming large amounts of alcohol on one occasion, posing risks to brain function. Nonetheless, it remains the most prevalent consumption pattern among students. Cross-sectional studies have explored the relationship between BD and anomalies in resting-state functional connectivity (RS-FC), but the medium/long-term consequences of BD on RS-FC during developmental periods remain relatively unexplored. In this two-year follow-up study, the impact of sustained BD on RS-FC was investigated in 44 college students (16 binge-drinkers) via two fMRI sessions at ages 18-19 and 20-21. Using a seed-to-voxel approach, RS-FC differences were examined in nodes of the main brain functional networks vulnerable to alcohol misuse, according to previous studies. Group differences in RS-FC were observed in four of the explored brain regions. Binge drinkers, compared to the control group, exhibited, at the second assessment, decreased connectivity between the right SFG (executive control network) and right precentral gyrus, the ACC (salience network) and right postcentral gyrus, and the left amygdala (emotional network) and medial frontal gyrus/dorsal ACC. Conversely, binge drinkers showed increased connectivity between the right Nacc (reward network) and four clusters comprising bilateral middle frontal gyrus (MFG), right middle cingulate cortex, and right MFG extending to SFG. Maintaining a BD pattern during critical neurodevelopmental years impacts RS-FC, indicating mid-to-long-term alterations in functional brain organization. This study provides new insights into the neurotoxic effects of adolescent alcohol misuse, emphasizing the need for longitudinal studies addressing the lasting consequences on brain functional connectivity.
PMID:39898113 | PMC:PMC11787028 | DOI:10.1016/j.abrep.2025.100585
Default mode network-basal ganglia network connectivity predicts the transition to postherpetic neuralgia
IBRO Neurosci Rep. 2025 Jan 13;18:135-141. doi: 10.1016/j.ibneur.2025.01.009. eCollection 2025 Jun.
ABSTRACT
BACKGROUND: Neuroimaging studies have revealed aberrant network functional connectivity in postherpetic neuralgia (PHN) patients. However, there is a lack of knowledge regarding the relationship between the brain network connectivity during the acute period and disease prognosis.
OBJECTIVE: The purpose of this study was to detect characteristic network connectivity in the process of herpes zoster (HZ) pain chronification and to identify whether abnormal network connectivity in the acute period can predict the outcome of patients with HZ.
METHODS: In this cross-sectional study, 31 patients with PHN, 33 with recuperation from herpes zoster (RHZ), and 28 with acute herpes zoster (AHZ) were recruited and underwent resting-state functional magnetic resonance imaging (fMRI). We investigated the differences in the connectivity of four resting-state networks (RSN) among the three groups. Receiver operating characteristic (ROC) curve analysis was performed to identify whether abnormal network connectivity in the acute period could predict the outcome of patients with HZ.
RESULTS: First, we found within-basal ganglia network (BGN) and default mode network (DMN)-BGN connectivity differences, with PHN patients showing increased DMN-BGN connectivity compared to AHZ and RHZ patients, while RHZ patients showing increased within-BGN connectivity compared to AHZ and PHN patients. Moreover, DMN-BGN connectivity was associated with the ID pain score in patients with AHZ. Finally, the DMN-BGN connectivity of AHZ patients could predict the outcome of HZ patients with sensitivity and specificity of 77.8 % and 63.2 %, respectively.
CONCLUSIONS: Our results provide evidence that DMN-BGN connectivity during the acute period confers a risk for the development of chronic pain and can act as a neuroimaging biomarker to predict the outcome of patients with HZ.
PMID:39896717 | PMC:PMC11783054 | DOI:10.1016/j.ibneur.2025.01.009
Simultaneous Confidence Regions for Image Excursion Sets: a Validation Study with Applications in fMRI
bioRxiv [Preprint]. 2025 Jan 25:2025.01.24.634784. doi: 10.1101/2025.01.24.634784.
ABSTRACT
Functional Magnetic Resonance Imaging (fMRI) is commonly used to localize brain regions activated during a task. Methods have been developed for constructing confidence regions of image excursion sets, allowing inference on brain regions exceeding non-zero activation thresholds. However, these methods have been limited to a single predefined threshold and brain volume data, overlooking more sensitive cortical surface analyses. We present an approach that constructs simultaneous confidence regions (SCRs) which are valid for all possible activation thresholds and are applicable to both volume and surface data. This approach is based on a recent method that constructs SCRs from simultaneous confidence bands (SCBs), obtained by using the bootstrap on 1D and 2D images. To extend this method to fMRI studies, we evaluate the validity of the bootstrap with fMRI data through extensive 2D simulations. Six bootstrap variants, including the nonparametric bootstrap and multiplier bootstrap are compared. The Rademacher multiplier bootstrap-t performs the best, achieving a coverage rate close to the nominal level with sample sizes as low as 20. We further validate our approach using realistic noise simulations obtained by resampling resting-state 3D fMRI data, a technique that has become the gold standard in the field. Moreover, our implementation handles data of any dimension and is equipped with interactive visualization tools designed for fMRI analysis. We apply our approach to task fMRI volume data and surface data from the Human Connectome Project, showcasing the method's utility.
PMID:39896511 | PMC:PMC11785249 | DOI:10.1101/2025.01.24.634784
Data-driven denoising in spinal cord fMRI with principal component analysis
bioRxiv [Preprint]. 2025 Jan 23:2025.01.23.634596. doi: 10.1101/2025.01.23.634596.
ABSTRACT
Numerous approaches have been used to denoise spinal cord functional magnetic resonance imaging (fMRI) data. Principal component analysis (PCA)-based techniques, which derive regressors from a noise region of interest (ROI), have been used in both brain (e.g., CompCor) and spinal cord fMRI. However, spinal cord fMRI denoising methods have yet to be systematically evaluated. Here, we formalize and evaluate a PCA-based technique for deriving nuisance regressors for spinal cord fMRI analysis (SpinalCompCor). In this method, regressors are derived with PCA from a noise ROI, an area defined outside of the spinal cord and cerebrospinal fluid. A parallel analysis is used to systematically determine how many components to retain as regressors for modeling; this designated a median of 11 regressors across three fMRI datasets: motor task (n=26), breathing task (n=27), and resting state (n=10). First-level fMRI modeling demonstrated that principal component regressors did fit noise (e.g., physiological noise from blood vessels), particularly in the resting state fMRI dataset. However, group-level motor task activation maps themselves did not show a clear benefit from including SpinalCompCor regressors over our original denoising model. The potential for collinearity of principal component regressors with the task may be a concern, and this should be considered in future implementations for which task-correlated noise is anticipated.
PMID:39896462 | PMC:PMC11785179 | DOI:10.1101/2025.01.23.634596
Depthwise cortical iron relates to functional connectivity and fluid cognition in healthy aging
Neurobiol Aging. 2025 Jan 28;148:27-40. doi: 10.1016/j.neurobiolaging.2025.01.006. Online ahead of print.
ABSTRACT
Age-related differences in fluid cognition have been associated with both the merging of functional brain networks, defined from resting-state functional magnetic resonance imaging (rsfMRI), and with elevated cortical iron, assessed by quantitative susceptibility mapping (QSM). Limited information is available, however, regarding the depthwise profile of cortical iron and its potential relation to functional connectivity. Here, using an adult lifespan sample (n = 138; 18-80 years), we assessed relations among graph theoretical measures of functional connectivity, column-based depthwise measures of cortical iron, and fluid cognition (i.e., tests of memory, perceptual-motor speed, executive function). Increased age was related both to less segregated functional networks and to increased cortical iron, especially for superficial depths. Functional network segregation mediated age-related differences in memory, whereas depthwise iron mediated age-related differences in general fluid cognition. Lastly, higher mean parietal iron predicted lower network segregation for adults younger than 45 years of age. These findings suggest that functional connectivity and depthwise cortical iron have distinct, complementary roles in the relation between age and fluid cognition in healthy adults.
PMID:39893877 | DOI:10.1016/j.neurobiolaging.2025.01.006
Functionally specialized spectral organization of the resting human cortex
Neural Netw. 2025 Jan 27;185:107195. doi: 10.1016/j.neunet.2025.107195. Online ahead of print.
ABSTRACT
Ample studies across various neuroimaging modalities have suggested that the human cortex at rest is hierarchically organized along the spectral and functional axes. However, the relationship between the spectral and functional organizations of the human cortex remains largely unexplored. Here, we reveal the confluence of functional and spectral cortical organizations by examining the functional specialization in spectral gradients of the cortex. These spectral gradients, derived from functional magnetic resonance imaging data at rest using our temporal de-correlation method to enhance spectral resolution, demonstrate regional frequency biases. The grading of spectral gradients across the cortex - aligns with many existing brain maps - is found to be highly functionally specialized through discovered frequency-specific resting-state functional networks, functionally distinctive spectral profiles, and an intrinsic coordinate system that is functionally specialized. By demonstrating the functionally specialized spectral gradients of the cortex, we shed light on the close relation between functional and spectral organizations of the resting human cortex.
PMID:39893804 | DOI:10.1016/j.neunet.2025.107195
Dynamic alterations in spontaneous neural activity in patients with attention-deficit/hyperactivity disorder: a resting-state fMRI study
Brain Res Bull. 2025 Jan 30:111230. doi: 10.1016/j.brainresbull.2025.111230. Online ahead of print.
ABSTRACT
BACKGROUND: To investigate the change of dynamic amplitude of low-frequency fluctuation (dALFF) and dynamic fractional amplitude of low-frequency fluctuation (dfALFF) in patients with attention-deficit/hyperactivity disorder (ADHD), and to explore whether dALFF/dfALFF can be used to distinguish ADHD from health controls (HCs).
METHODS: Forty-eight cases of clinically confirmed ADHD and forty-four cases of HCs were included in the present study. It was compared to the amplitude of low-frequency fluctuations (ALFF) and fractional ALFF (fALFF), as well as the dynamic indicators dALFF and dfALFF. We investigated the relationship between clinical and dynamic indicators, and additionally performed voxel-based functional connectivity (FC) analysis. Finally, we developed an auxiliary diagnosis model.
RESULTS: Brain regions with increased dALFF variability of ADHD were located in right middle frontal gyrus (MFG), left inferior parietal lobe (IPL) and superior parietal gyrus (SPG) compared with HCs. Meanwhile, increased dfALFF variability was also observed in left lingual gyrus (LING), right MFG and left middle occipital gyrus (MOG) in ADHD compared to HCs. Neuropsychological scale scores correlated with some dALFF and dfALFF indicators. Reduced FC was found between the left IPL and right cerebellum crus II in ADHD compared with HCs. With dALFF and dfALFF variability as features, we achieved a good area under the curve and an accurate classification.
CONCLUSION: This study offers new valuable insights into the cerebral dysfunction associated with ADHD from the standpoint of dynamic local brain activity. The understanding of dALFF/dfALFF variability can contribute to the comprehension of neurophysiological mechanisms and potentially aid in the diagnosis of ADHD.
PMID:39892580 | DOI:10.1016/j.brainresbull.2025.111230
Reduced connection strength leads to enhancement of working memory capacity in cognitive training
Neuroimage. 2025 Jan 30:121055. doi: 10.1016/j.neuroimage.2025.121055. Online ahead of print.
ABSTRACT
It has been widely observed that cognitive training can enhance the working memory capacity (WMC) of participants, yet the underlying mechanisms remain unexplained. Previous research has confirmed that abacus-based mental calculation (AMC) training can enhance the WMC of subjects and suggested its possible association with changes in functional connectivity. With fMRI data, we construct whole brain resting state connectivity of subjects who underwent long-term AMC training and other subjects from a control group. Their working memory capacity is simulated based on their whole brain resting state connectivity and reservoir computing. It is found that the AMC group has higher WMC than the control group, and especially the WMC involved in the frontoparietal network (FPN), visual network (VIS) and sensorimotor network (SMN) associated with the AMC training is even higher in the AMC group. However, the advantage of the AMC group disappears if the connection strengths between brain regions are neglected. The effects on WMC from the connection strength differences between the AMC and control groups are evaluated. The results show that the WMC of the control group is enhanced and achieved consistency with or even better than that the AMC group if the connection strength of the control group are weakened. And the advantage of FPN, VIS and SMN is reproduced too. In conclusion, our work reveals a correlation between reduction in functional connection strength and enhancements in the WMC of subjects undergoing cognitive training.
PMID:39892528 | DOI:10.1016/j.neuroimage.2025.121055
DSAM: A deep learning framework for analyzing temporal and spatial dynamics in brain networks
Med Image Anal. 2025 Jan 29;101:103462. doi: 10.1016/j.media.2025.103462. Online ahead of print.
ABSTRACT
Resting-state functional magnetic resonance imaging (rs-fMRI) is a noninvasive technique pivotal for understanding human neural mechanisms of intricate cognitive processes. Most rs-fMRI studies compute a single static functional connectivity matrix across brain regions of interest, or dynamic functional connectivity matrices with a sliding window approach. These approaches are at risk of oversimplifying brain dynamics and lack proper consideration of the goal at hand. While deep learning has gained substantial popularity for modeling complex relational data, its application to uncovering the spatiotemporal dynamics of the brain is still limited. In this study we propose a novel interpretable deep learning framework that learns goal-specific functional connectivity matrix directly from time series and employs a specialized graph neural network for the final classification. Our model, DSAM, leverages temporal causal convolutional networks to capture the temporal dynamics in both low- and high-level feature representations, a temporal attention unit to identify important time points, a self-attention unit to construct the goal-specific connectivity matrix, and a novel variant of graph neural network to capture the spatial dynamics for downstream classification. To validate our approach, we conducted experiments on the Human Connectome Project dataset with 1075 samples to build and interpret the model for the classification of sex group, and the Adolescent Brain Cognitive Development Dataset with 8520 samples for independent testing. Compared our proposed framework with other state-of-art models, results suggested this novel approach goes beyond the assumption of a fixed connectivity matrix, and provides evidence of goal-specific brain connectivity patterns, which opens up potential to gain deeper insights into how the human brain adapts its functional connectivity specific to the task at hand. Our implementation can be found on https://github.com/bishalth01/DSAM.
PMID:39892220 | DOI:10.1016/j.media.2025.103462
A Statistical Characterization of Dynamic Brain Functional Connectivity
Hum Brain Mapp. 2025 Feb 1;46(2):e70145. doi: 10.1002/hbm.70145.
ABSTRACT
This study examined the statistical underpinnings of dynamic functional connectivity in mental disorders, using resting-state fMRI signals. Notably, there has been an absence of research demonstrating the non-stationarity of the empirical probability distribution of functional connectivity. This gap has prompted debate on the existence of dynamic functional connectivity, leading skeptics to question its relevance and the reliability of research findings. Our aim was to fill this gap by conducting a comprehensive empirical distribution analysis of functional connectivity, using Pearson's correlation as a measure. We conducted our analysis on a set of preprocessed resting-state fMRI samples obtained from 186 subjects selected from the UCLA Consortium for Neuropsychiatric Phenomics dataset. Departing from conventional methods that aggregated signals over voxels within a region of interest, our approach leveraged individual voxel signals. Specifically, our approach offered a precise characterization of the empirical probability distribution of resting-state fMRI signals by evaluating the temporal variations and non-stationarity in dynamic functional connectivity, as measured by Pearson's correlation. Our study investigated functional connectivity patterns across 49 regions of interest, comparing healthy control subjects with patients diagnosed with ADHD, bipolar disorder, and schizophrenia. Our analysis revealed that (1) the empirical distribution of the correlation coefficient exhibited non-stationarity, (2) the beta distribution was an accurate approximation of the exact correlation coefficient distribution, and (3) the empirical distribution of means derived from the fitted beta distributions, unraveled distinctive dynamic functional connectivity patterns with potential as biomarkers associated with different mental disorders. A key contribution of our study was the presentation of the first comprehensive empirical distribution analysis of dynamic functional connectivity, thus providing compelling evidence for its existence. Overall, our study presented an innovative statistical approach that advances our understanding of the dynamic nature of functional connectivity patterns derived from resting-state fMRI. Our examination of the empirical distribution of dynamic functional connectivity provided solid evidence supporting its existence. The distinctive dynamic functional connectivity patterns we identified across various mental disorders hold promise as potential biomarkers for further development.
PMID:39891569 | DOI:10.1002/hbm.70145
Abnormal local cortical functional connectivity due to interneuron dysmaturation after neonatal intermittent hypoxia
J Neurosci. 2025 Jan 31:e1449242024. doi: 10.1523/JNEUROSCI.1449-24.2024. Online ahead of print.
ABSTRACT
Prematurely born infants often experience frequent hypoxic episodes due to immaturity of respiratory control resulting in disturbances of cortical development and long-term cognitive and behavioral abnormalities. We hypothesize that neonatal intermittent hypoxia alters maturation of cortical excitatory and inhibitory circuits that can be detected early with functional MRI. C57BL/6 mouse male and female pups were exposed to an intermittent hypoxia (IH) regimen from P3 to P7, corresponding to pre-term humans. Adult mice after neonatal IH exhibited motor hyperactivity and impaired motor learning in complex wheel tests. Patch clamp and evoked field potential recordings revealed increased glutamatergic synaptic transmission. To investigate the role of GABAergic inhibition on glutamatergic transmission during the developmental, we applied a selective GABAA receptor inhibitor picrotoxin. A decreased synaptic inhibitory drive in the motor cortex was evidenced by miniature IPSC frequency on pyramidal cells, multi-unit activity recording in vivo with picrotoxin injection, and decreased interneuron density. There was also an increased tonic depolarizing effect of picrotoxin after IH on Betz cells' membrane potential on patch clamp and direct current potential in extracellular recordings. The amplitude of low-frequency fluctuation on resting-state fMRI was larger, with a larger increase in regional homogeneity index after picrotoxin injection in the IH group.The increased glutamatergic transmission, decreased numbers, and activity of inhibitory interneurons after neonatal IH may affect the maturation of connectivity in cortical networks, resulting in long-term cognitive and behavioral changes. Functional MRI reveals increased intrinsic connectivity in the sensorimotor cortex, suggesting neuronal dysfunction in cortical maturation after neonatal IH.Significance Statement The study demonstrates that perinatal hypoxic brain injury disrupts the balance between excitatory and inhibitory neurotransmission in developing cortical networks. This disruption, potentially caused by functional deficiencies in GABAergic interneurons alongside increased glutamatergic transmission, may contribute to altered brain connectivity and the observed behavioral deficits, including hyperactivity and cognitive difficulties. This research provides insights into how perinatal brain injury disrupts the balance of neural excitation and inhibition, which can be detected as altered local resting-state fMRI connectivity. These findings contribute to our understanding of possible cellular underpinning of clinical fMRI findings after perinatal brain injury.
PMID:39890465 | DOI:10.1523/JNEUROSCI.1449-24.2024
Functional connectivity of the scene processing network at rest does not reliably predict human behaviour on scene processing tasks
eNeuro. 2025 Jan 31:ENEURO.0375-24.2024. doi: 10.1523/ENEURO.0375-24.2024. Online ahead of print.
ABSTRACT
The perception of scenes is associated with processing in a network of scene-selective regions in the human brain. Prior research has identified a posterior-anterior bias within this network. Posterior scene regions exhibit preferential connectivity with early visual and posterior parietal regions, indicating a role in representing egocentric visual features. In contrast, anterior scene regions demonstrate stronger connectivity with frontoparietal control and default mode networks, suggesting a role in mnemonic processing of locations. Despite these findings, evidence linking connectivity in these regions to cognitive scene processing remains limited. In this preregistered study, we obtained cognitive behavioural measures alongside resting-state fMRI data from a large-scale public dataset to investigate interindividual variation in scene processing abilities relative to the functional connectivity of the scene network. Our results revealed substantial individual differences in scene recognition, spatial memory, and navigational abilities. Resting-state functional connectivity reproduced the posterior-anterior bias within the scene network. However, contrary to our preregistered hypothesis, we did not observe any consistent associations between interindividual variation in this connectivity and behavioural performance. These findings highlight the need for further research to clarify the role of these connections in scene processing, potentially through assessments of functional connectivity during scene-relevant tasks or in naturalistic conditions.Significance Statement Our ability to process scenes is crucial for interacting with our environment as it allows us to extract spatial, contextual, and navigational information. However, the mechanisms by which the scene network in the human brain supports these abilities remain poorly understood. To investigate this, we compared behavioural measures of scene processing with resting-state functional connectivity within the scene network. Extensive individual variability was evident in scene recognition, spatial memory, and navigational abilities. However, contrary to our preregistered hypothesis, we did not observe any consistent associations between task performance and the resting-state functional connectivity of the scene network. These results suggest that future research employing task-related or naturalistic designs may be necessary for elucidating the neural basis of scene perception.
PMID:39890456 | DOI:10.1523/ENEURO.0375-24.2024
Lesion in the path of current flow to target pericavitational and perilesional brain areas: Acute network-level tDCS findings in chronic aphasia using concurrent tDCS/fMRI
Brain Stimul. 2025 Jan 29:S1935-861X(25)00030-0. doi: 10.1016/j.brs.2025.01.024. Online ahead of print.
NO ABSTRACT
PMID:39889819 | DOI:10.1016/j.brs.2025.01.024
Altered local spontaneous activity and functional connectivity density in major depressive disorder patients with anhedonia
Asian J Psychiatr. 2025 Jan 25;104:104380. doi: 10.1016/j.ajp.2025.104380. Online ahead of print.
ABSTRACT
OBJECTIVE: The purpose of this study was to investigate the alterations of intrinsic brain function in major depressive disorder (MDD) patients with and without anhedonia based on whole-brain level by using two novel measures, four-dimensional spatial-temporal consistency of local neural activity (FOCA) and local functional connectivity density (lFCD).
METHODS: A total of 26 MDD patients with anhedonia (MDD-WA), 29 MDD patients without anhedonia (MDD-WoA), and 30 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and intrinsic brain function was explored by FOCA and lFCD. A two-sample t-test was conducted to explore FOCA and lFCD differences between MDD patients and HCs, then analysis of covariance (ANCOVA) and post hoc tests were performed to obtain brain regions with significant differences among three groups. Finally, the diagnostic performance of FOCA and lFCD values with significant inter-group difference was evaluated using receiver operating characteristic (ROC) curves.
RESULTS: Compared to HCs, MDD patients showed decreased FOCA in the right cuneus (CUN) and left postcentral gyrus (PoCG), as well as diminished lFCD in the right CUN and left calcarine fissure and surrounding cortex (CAL). Interestingly, the MDD-WA group was more likely to exhibit decreased FOCA in the left PoCG and reduced lFCD in the left CAL after consideration for the effect of anhedonia in MDD patients. The MDD-WA group further showed increased FOCA in the bilateral caudate (CAU) and right ventral anterior nucleus (VA) when comparing to HCs. Additionally, as compared with MDD-WoA group, the MDD-WA group presented decreased FOCA in the right middle occipital gyrus (MOG), which was also negatively associated with the severity of anhedonia in MDD patients. Finally, FOCA values of the right MOG exhibited excellent discriminant validity in differentiating MDD-WA from MDD-WoA, and the other individual or combined indices of FOCA or lFCD values in the aforementioned distinct brain regions presented significant utility in distinguishing between MDD or MDD-WA and HCs.
CONCLUSIONS: The present findings suggest that aberrant intrinsic brain function in the left CAL, left PoCG, bilateral CAU, right VA, and, especially the right MOG may be associated with anhedonia in patients with MDD. Altered FOCA in the right MOG may have the potential to be a diagnostic neuroimaging biomarker for MDD patients with anhedonia.
PMID:39889674 | DOI:10.1016/j.ajp.2025.104380
Association of Plasma Biomarkers of Alzheimer Disease and Neurodegeneration With Longitudinal Intra-Network Functional Brain Connectivity
Neurology. 2025 Feb 25;104(4):e210271. doi: 10.1212/WNL.0000000000210271. Epub 2025 Jan 31.
ABSTRACT
BACKGROUND AND OBJECTIVES: Alzheimer disease (AD) is defined by cortical β-amyloid (Aβ), tau, and neurodegeneration, which contribute to cognitive decline, in part, by altering large-scale functional brain networks. While cortical Aβ and tau have been associated with changes in functional brain connectivity, it is unknown whether plasma biomarkers relate to such changes. In a healthy community sample of cognitively unimpaired adults free from major CNS disease from the Baltimore Longitudinal Study of Aging, we examined whether plasma biomarkers of AD pathology (Aβ42/40, phosphorylated tau [pTau-181]), astrogliosis (glial fibrillary acidic protein [GFAP]), and neuronal injury (neurofilament light chain [NfL]) were associated with longitudinal changes in functional connectivity and whether changes in functional connectivity were related to longitudinal cognition.
METHODS: Plasma biomarkers were measured using the Quanterix SIMOA assays. Intranetwork connectivity (3T resting-state fMRI) from 7 functional networks was derived using a predefined cortical parcellation mask for each participant visit. Cognitive performance was assessed concurrently with fMRI scan. Covariate-adjusted linear mixed-effect models were used to determine (1) whether plasma biomarkers were associated with longitudinal changes in connectivity, (2) whether the magnitude of the biomarker-connectivity relationships differed by amyloid status, and (3) whether changes in connectivity co-occurred with longitudinal changes in cognition.
RESULTS: Our primary findings (n = 486; age = 65.5 ± 16.2 years; 54% female; mean follow-up time = 4.3 ± 1.7 years) showed that higher baseline GFAP was associated with faster declines in somatomotor (β = -0.04, p = 0.01, 95% CI -0.06 to -0.01), limbic (β = -0.03, p = 0.02, 95% CI -0.06 to -0.005), and frontoparietal (β = -0.04, p = 0.02, 95% CI -0.07 to -0.01) network connectivity. Amyloid status moderated several biomarker-connectivity associations. For instance, higher baseline NfL was related to faster declines in visual and limbic network connectivity, but only among amyloid-positive participants. Among 421 participants with ≥2 fMRI visits (age = 71.7 ± 11.4 years; 55% female; follow-up time = 3.9 ± 1.6 years), longitudinal changes in connectivity were associated with concurrent declines in cognition; however, these results did not survive multiple comparison correction.
DISCUSSION: Among cognitively unimpaired participants, plasma biomarkers of amyloidosis, astrogliosis, and neuronal injury are associated with declines in network connectivity, particularly among amyloid-positive participants. Major limitations include the lack of inclusion of the sensitive pTau-217 and pTau-231 isoforms and comparative PET biomarkers.
PMID:39889254 | DOI:10.1212/WNL.0000000000210271
Developmental functional brain network abnormalities in autism spectrum disorder comorbid with attention deficit hyperactivity disorder
Eur J Pediatr. 2025 Jan 31;184(2):166. doi: 10.1007/s00431-025-05989-x.
ABSTRACT
Autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often co-occur. Developmental stages significantly influence the variations in brain alterations. However, whether ASD comorbid with ADHD (ASD + ADHD) represents a unique neural characteristic from ASD without comorbid ADHD (ASD-alone), or instead manifests a shared neural correlate associated with ASD across diverse age cohorts remain unclear. This study examined topological properties and functional connectivity (FC) patterns through resting-state functional magnetic resonance imaging data from the Autism Brain Imaging Data Exchange II. Participants were divided into two age cohorts: childhood (under 12 years) and adolescence (12-18 years), consisting of 171 ASD pediatric patients and 111 typically developing (TD) controls. These cohorts were further classified into subgroups of ASD + ADHD, ASD-alone, and TD controls to compare across the age categories. The age, intelligence quotient, and gender of participants across three groups were matched within childhood and adolescence stages. We constructed functional brain networks, conducted graph-theory analysis, and analysed FC for both age cohorts. The findings revealed that both ASD + ADHD and ASD-alone shared some FC dysfunctions in the Default Mode Network (DMN) and atypical global metrics. Additionally, each group demonstrated unique neural FC and topological profiles that evolved with development.
CONCLUSIONS: This study highlights the neural profiles of ASD + ADHD from a developmental perspective and suggests age-considerate approaches in clinical treatments.
WHAT IS KNOWN: • ASD + ADHD shared some neural correlate associated with ASD-alone and also had specific neurobiological mechanisms which were different from ASD-alone. • Developmental stages significantly influence the variations in brain alterations observed in ASD or ADHD.
WHAT IS NEW: • Both ASD + ADHD and ASD-alone shared some FC dysfunctions in the Default Mode Network and atypical global metrics. • ASD + ADHD and ASD-alone demonstrated unique neural FC and topological profiles that evolved with development.
PMID:39888443 | DOI:10.1007/s00431-025-05989-x
TR(Acking) Individuals Down: Exploring the Effect of Temporal Resolution in Resting-State Functional MRI Fingerprinting
Hum Brain Mapp. 2025 Feb 1;46(2):e70125. doi: 10.1002/hbm.70125.
ABSTRACT
Functional brain fingerprinting has emerged as an influential tool to quantify reliability in neuroimaging studies and to identify cognitive biomarkers in both healthy and clinical populations. Recent studies have revealed that brain fingerprints reside in the timescale-specific functional connectivity of particular brain regions. However, the impact of the acquisition's temporal resolution on fingerprinting remains unclear. In this study, we examine for the first time the reliability of functional fingerprinting derived from resting-state functional MRI (rs-fMRI) with different whole-brain temporal resolutions (TR = 0.5, 0.7, 1, 2, and 3 s) in a cohort of 20 healthy volunteers. Our findings indicate that subject identifiability within a fixed TR is successful across different temporal resolutions, with the highest identifiability observed at TR 0.5 and 3 s (TR(s)/identifiability(%): 0.5/64; 0.7/47; 1/44; 2/44; 3/56). We discuss this observation in terms of protocol-specific effects of physiological noise aliasing. We further show that, irrespective of TR, associative brain areas make an higher contribution to subject identifiability (functional connections with highest mean ICC: within subcortical network [SUB; ICC = 0.0387], within default mode network [DMN; ICC = 0.0058]; between DMN and somato-motor [SM] network [ICC = 0.0013]; between ventral attention network [VA] and DMN [ICC = 0.0008]; between VA and SM [ICC = 0.0007]), whereas sensory-motor regions become more influential when integrating data from different TRs (functional connections with highest mean ICC: within fronto-parietal network [ICC = 0.382], within dorsal attention network [DA; ICC = 0.373]; within SUB [ICC = 0.367]; between visual network [VIS] and DA [ICC = 0.362]; within VIS [ICC = 0.358]). We conclude that functional connectivity fingerprinting derived from rs-fMRI holds significant potential for multicentric studies also employing protocols with different temporal resolutions. However, it remains crucial to consider fMRI signal's sampling rate differences in subject identifiability between data samples, in order to improve reliability and generalizability of both whole-brain and specific functional networks' results. These findings contribute to a better understanding of the practical application of functional connectivity fingerprinting, and its implications for future neuroimaging research.
PMID:39887794 | DOI:10.1002/hbm.70125
Predicting individual traits from models of brain dynamics accurately and reliably using the Fisher kernel
Elife. 2025 Jan 31;13:RP95125. doi: 10.7554/eLife.95125.
ABSTRACT
Predicting an individual's cognitive traits or clinical condition using brain signals is a central goal in modern neuroscience. This is commonly done using either structural aspects, such as structural connectivity or cortical thickness, or aggregated measures of brain activity that average over time. But these approaches are missing a central aspect of brain function: the unique ways in which an individual's brain activity unfolds over time. One reason why these dynamic patterns are not usually considered is that they have to be described by complex, high-dimensional models; and it is unclear how best to use these models for prediction. We here propose an approach that describes dynamic functional connectivity and amplitude patterns using a Hidden Markov model (HMM) and combines it with the Fisher kernel, which can be used to predict individual traits. The Fisher kernel is constructed from the HMM in a mathematically principled manner, thereby preserving the structure of the underlying model. We show here, in fMRI data, that the HMM-Fisher kernel approach is accurate and reliable. We compare the Fisher kernel to other prediction methods, both time-varying and time-averaged functional connectivity-based models. Our approach leverages information about an individual's time-varying amplitude and functional connectivity for prediction and has broad applications in cognitive neuroscience and personalised medicine.
PMID:39887179 | DOI:10.7554/eLife.95125
Association of player position and functional connectivity alterations in collegiate American football players: an fMRI study
Front Neurol. 2025 Jan 7;15:1511915. doi: 10.3389/fneur.2024.1511915. eCollection 2024.
ABSTRACT
INTRODUCTION: Resting state-fMRI, provides a sensitive method for detecting changes in brain functional integrity, both with respect to regional oxygenated blood flow and whole network connectivity. The primary goal of this report was to examine alterations in functional connectivity in collegiate American football players after a season of repetitive head impact exposure.
METHODS: Collegiate football players completed a rs-fMRI at pre-season and 1 week into post-season. A seed-based functional connectivity method, isolating the posterior cingulate cortex (PCC), was utilized to create individual functional connectivity maps. During group analysis, first, voxel-wise paired sample t-tests identified significant changes in connectivity from pre- to post-season, by player, and previous concussion history. Second, 10 DMN ROIs were constructed by overlaying an anatomical map over regions of positive correlation from one-sample t-tests of pre-season and post-season. These ROIs, plus the LpCun, were included in linear mix-effect modeling, with position or concussion history as covariates.
RESULTS: 66 players were included (mean age 20.6 years; 100% male; 34 (51.5%) non-speed position players). The 10 DMN ROIs showed no alterations from pre-season to post-season. By concussion history, the right temporal ROI demonstrated a significant effect on baseline functional connectivity (p = 0.03). Speed players, but not non-speed players, demonstrated a significant decrease in functional connectivity in the precuneus from pre- to post-season (p < 0.001).
DISCUSSION: There are region-specific differences functional connectivity related to both position and concussion history in American collegiate football players. Player position affected functional connectivity across a season of football. Position-specific differences in head impact exposure rate and magnitude plays a crucial role in functional connectivity alterations.
PMID:39882371 | PMC:PMC11776490 | DOI:10.3389/fneur.2024.1511915
Static and dynamic brain functional connectivity patterns in patients with unilateral moderate-to-severe asymptomatic carotid stenosis
Front Aging Neurosci. 2025 Jan 15;16:1497874. doi: 10.3389/fnagi.2024.1497874. eCollection 2024.
ABSTRACT
BACKGROUND AND PURPOSE: Asymptomatic carotid stenosis (ACS) is an independent risk factor for ischemic stroke and vascular cognitive impairment, affecting cognitive function across multiple domains. This study aimed to explore differences in static and dynamic intrinsic functional connectivity and temporal dynamics between patients with ACS and those without carotid stenosis.
METHODS: We recruited 30 patients with unilateral moderate-to-severe (stenosis ≥ 50%) ACS and 30 demographically-matched healthy controls. All participants underwent neuropsychological testing and 3.0T brain MRI scans. Resting-state functional MRI (rs-fMRI) was used to calculate both static and dynamic functional connectivity. Dynamic independent component analysis (dICA) was employed to extract independent circuits/networks and to detect time-frequency modulation at the circuit level. Further imaging-behavior associations identified static and dynamic functional connectivity patterns that reflect cognitive decline.
RESULTS: ACS patients showed altered functional connectivity in multiple brain regions and networks compared to controls. Increased connectivity was observed in the inferior parietal lobule, frontal lobe, and temporal lobe. dICA further revealed changes in the temporal frequency of connectivity in the salience network. Significant differences in the temporal variability of connectivity were found in the fronto-parietal network, dorsal attention network, sensory-motor network, language network, and visual network. The temporal parameters of these brain networks were also related to overall cognition and memory.
CONCLUSIONS: These results suggest that ACS involves not only changes in the static large-scale brain network connectivity but also dynamic temporal variations, which parallel overall cognition and memory recall.
PMID:39881682 | PMC:PMC11774917 | DOI:10.3389/fnagi.2024.1497874