This publication introduces a novel, publicly available dataset designed to support the development and evaluation of advanced algorithms and processing workflows for complex multi-echo functional magnetic resonance imaging (fMRI) data. The dataset comprises multi-echo fMRI and electrophysiological recordings collected from 83 healthy, right-handed adult participants. Data was acquired with two 3 T MR scanners and is available on OpenNeuro under the title “Complex multi-echo fMRI dataset: New strategies in processing of multi-echo data”.
Alterations in mitochondrial DNA (mtDNA) have been associated with worse cognitive abilities in older adults and premature epigenetic aging in young adulthood. However, it is not clear how mitochondrial dysfunction affects brain function in young adulthood and whether cognition-related networks might be most affected. We tested whether mtDNA functional impact (FI) score might map onto specific patterns of between-network functional connectivity in young adults from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). We also tested whether these relationships might be mediated by accelerated epigenetic aging, calculated using Horvath's epigenetic clock, CheekAge clock, and AltumAge clock. General connectivity method was used as a reliable marker of individual differences in brain function. We showed that a greater mtDNA FI score was associated with lower connectivity between the dorsal attention and language networks (beta = -0.41, p = 0.0007, AdjR2 = 0.15) and that there was suggestive evidence that this relationship might be mediated by accelerated epigenetic aging calculated using Horvath's epigenetic clock in young adulthood (ab = -0.061, SE = 0.04, 95% CI [-0.163; 0.001], 90% CI [-0.142; -0.002]). These findings were independent of sex, current BMI, and current substance use. Overall, we conclude that individuals with a greater mtDNA FI score might be at greater risk of experiencing worse attention to relevant linguistic inputs, greater difficulties with speech comprehension, and verbal working memory.
Premature epigenetic aging has been linked to poorer cognitive performance, but the neuroanatomical pathways underlying this association remain unclear. Therefore, we tested whether premature epigenetic aging predicts deviations from normative brain development and cognition in young adulthood. We followed 254 young adults from the ELSPAC prenatal birth cohort. Epigenetic aging was estimated using Horvath’s DNA methylation clock, CheekAge, and AltumAge. Structural MRI was processed with FreeSurfer to derive cortical thickness and surface area in 68 Desikan–Killiany regions and subcortical volumes in 14 Aseg regions. CentileBrain normative models trained on 37,407 MRI scans from individuals aged 3–90 years were used to quantify age- and sex-specific deviations from normative brain development. Cognitive performance was assessed using the WAIS-IV. Premature epigenetic aging estimated using Horvath’s clock was associated with more negative deviations from normative volume of the putamen and caudate, but not with other subcortical volumes, cortical thickness, or surface area. In women, this premature epigenetic aging was also associated with lower full-scale IQ and performance IQ, and moderated mediation analyses indicated that the deviations in putamen volume mediated the relationship between premature epigenetic aging and cognitive performance. In men, the relationship between premature epigenetic aging and cognitive performance was quadratic (U-shaped). No similar effects were observed when using CheekAge or AltumAge.Premature epigenetic aging estimated using Horvath’s clock and the associated deviations in development of the dorsal striatum in young adulthood may represent an early marker of poorer cognitive performance long before clinical symptoms might emerge.
The coupling between electroencephalography (EEG) and blood-oxygen-level-dependent (BOLD) signals has been investigated across numerous studies, but its neurobiological underpinnings remain poorly understood. Resting-state EEG alpha-BOLD coupling follows a characteristic spatial pattern, shifting from negative correlations in sensory regions to positive correlations in association cortices. In this study, we examined neurobiological correlates of resting-state alpha-BOLD coupling. We compared the spatial pattern of the alpha-BOLD coupling map to 82 cortical feature maps, including gene expression profiles of different cell types and receptor subunits as well as structural MRI measures. We identified three statistically significant ( q < 0.05 FDR-corrected) maps: the layer 6 VIP interneuron marker, excitatory layer-5 marker, and NMDA receptor subunit GRIN2C. The three significant gene maps, combined in a multiple linear regression model, explained R 2 = 0.312 of the spatial variance in alpha-BOLD coupling. Analysis of the spatial mismatch between cortical maps and the alpha-BOLD coupling map revealed that the early auditory cortex is the region that consistently diverges from predictions across gene expression and T1/T2 maps. The spatial correspondence between alpha-BOLD coupling and gene expression profiles of specific receptor subunits, neuronal types, and layer-specific populations identifies these as concrete candidates for future computational and experimental studies of alpha-BOLD coupling.
High-contrast striped patterns near 3 cycles per degree are well established as a cause of visual discomfort and perceptual distortions, which in clinical populations can manifest as symptoms such as migraines or seizures. This sensitivity has been linked to cortical hyperexcitability, characterized by abnormally increased neural responses to visual input. Although gamma-band oscillations in visual cortex are known to reflect excitatory-inhibitory dynamics associated with pattern sensitivity, the contribution of higher-frequency neural activity and large-scale network interactions has received limited direct investigation. Using intracranial EEG recordings from patients with non-photosensitive epilepsy, we examined how aversive gratings modulate local field potential activity across frequencies ranging from 55 to 1000 Hz. Analyses focused on visual cortex as well as higher-order parietal, temporal, insular, and limbic regions, assessing frequency-specific power changes and their relationship to self-reported visual discomfort. At the group level, aversive patterns elicited significantly greater high-gamma power than control patterns in extrastriate regions (BA 18 and, at later latencies, BA 19), while primary visual cortex (BA 17) showed no consistent condition-dependent modulation. At the individual level, patients with higher visual discomfort scores exhibited stronger and more sustained post-stimulus increases in high-frequency activity in BA 18 across multiple frequency bands, accompanied by moderate-to-large effect sizes. Beyond the occipital cortex, aversive patterns engaged lateral temporal regions, predominantly in the middle and superior temporal gyri, with sustained responses emerging approximately one second after stimulus onset. Parietal responses were brief and variable across frequency bands, and insular and limbic regions showed no consistent condition-specific modulation. Ripple-band activity mirrored the high-gamma pattern in occipital and temporal cortex, whereas fast ripple and very fast ripple responses were weaker, spatially sparse, and directionally heterogeneous. Together, these results indicate that visual discomfort reflects individual differences in extrastriate cortical excitability expressed through frequency-specific network dynamics, and identify high-frequency activity in BA 18/V2 as a candidate neural correlate of susceptibility to aversive visual stimuli.
Although Parkinson’s disease (PD) is primarily defined by motor symptoms, non-motor manifestations—including deficits in social cognition—are increasingly recognized for their impact on daily functioning. Emotion recognition impairment is one such deficit, but prior research has mainly focused on facial expressions, neglecting other socially relevant cues such as body postures. This study examined recognition of emotions from both faces and bodies and their cognitive and neuroanatomical correlates in non-demented patients with PD. We enrolled 25 individuals with mild to moderate PD and 24 age-matched healthy controls. Emotion recognition was assessed with validated facial (ER-40) and bodily (BR-40) tasks. Cognitive function was evaluated with the Montreal Cognitive Assessment, Dementia Rating Scale-2 and Frontal Assessment Battery. Motor symptoms were rated using the MDS-UPDRS Part III. Structural MRI data were analyzed with FreeSurfer. Compared with controls, patients with PD showed a specific impairment in recognizing emotions from body postures, despite comparable overall performance to controls. Within the PD group, poorer recognition was associated with greater cognitive impairment and higher bradykinesia subscores. MRI volumetry linked emotion recognition performance to the volumes of the cerebellar white matter, hippocampus, and left nucleus accumbens. In addition to these structures, facial emotion recognition was specifically related to cerebellar cortical volume, whereas body posture recognition showed associations with the rightputamen, and right amygdala. These findings highlight modality-specific social cognitive deficits in PD, related to both cognition and structural brain changes.
BACKGROUND:Maternal mental health during pregnancy is important for optimal brain development in offspring. Exposure to maternal depression in utero has been shown to be associated with accelerated global cortical brain aging in young adulthood. However, it is not clear whether maternal antenatal depression (MAD) also predicts region-specific deviations from normative development of cortical thickness, surface area, and subcortical volume in offspring or whether the region-specific deviations remain stable throughout the third decade of life. METHODS:Two neuroimaging follow-ups of a prenatal birth cohort in young adulthood tested whether MAD was associated with deviations from normative brain development in the offspring in their early and late 20s, as modeled using 37,407 magnetic resonance images from individuals 3 to 90 years of age (CentileBrain). RESULTS:MAD predicted deviations from normative development of thalamus and nucleus accumbens but not other subcortical volumes, surface area, or cortical thickness. Women exposed to greater MAD showed a smaller thalamus and nucleus accumbens in both the early and late 20s than expected based on age- and sex-normative means. In contrast, men exposed to greater MAD showed no deviations from the development of the thalamus but did show a larger nucleus accumbens in their late 20s than expected based on age- and sex-normative means. CONCLUSIONS:Given the importance of the thalamus in the pathogenesis of major depressive disorder and the critical role of the nucleus accumbens in reward and motivation, the altered development of these subcortical structures may contribute to a higher risk of depression.
The analysis of EEG microstates offers a valuable approach for investigating large-scale brain networks and dynamics. Beyond the commonly reported "canonical microstates," prior literature has identified another distinct topography: the vertical topography (VT). This VT is characterized by a prominent straight line dividing positive and negative values, extending from the nasion to the inion. Notably, our own simultaneous EEG/fMRI and shielded cabin EEG data, collected from 77 participants, also revealed the presence of this topography. Based on our subsequent analyses of both human and phantom data, we conclude that VT partly represents artifacts arising from unspecified movements of the EEG cap and its metallic components. This conclusion is strongly supported by our evaluation of VT's spatiotemporal characteristics, derived from EEG recorded under diverse conditions. Specifically, we found a significant correlation between framewise displacement (obtained from human EEG/fMRI) and VT's temporal characteristics. Therefore, we advocate for a prudent interpretation of VT when it appears in data. Its mere existence as a resulting topography can impact the spatiotemporal parameters of other microstates and even distort the shapes of the other topographies.
Accelerated epigenetic aging has been associated with changes in cognition. However, due to the lack of neuroimaging epigenetics studies, it is still unclear whether accelerated epigenetic. Aging in young adulthood might underlie the relationship between altered brain dynamics and cognitive functioning. We conducted neuroimaging epigenetics follow-up of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort in young adulthood and tested the possible mediatory role of accelerated epigenetic aging in the relationship between dynamic functional connectivity (DFC) and worse cognition. A total of 240 young adults (51% men; 28-30 years, all of European ancestry) participated in the neuroimaging epigenetics follow-up. Buccal swabs were collected to assess DNA methylation and calculate epigenetic aging using Horvath's epigenetic clock. Full-scale IQ was assessed using the Wechsler adult intelligence scale (WAIS). Resting-state functional magnetic resonance imaging (rs-fMRI) was acquired using a 3T Siemens Prisma MRI scanner, and DFC was assessed using mixture factor analysis, revealing information about the coverage of different DFC states. In women (but not men), lower coverage of DFC state 4 and thus lower frequency of epochs with high connectivity within the default mode network and between default mode, fronto-parietal, and visual networks was associated with lower full-scale IQ (AdjR2 = 0.05, std. beta = 0.245, p = 0.008). This relationship was mediated by accelerated epigenetic aging (ab = 7.660, SE = 4.829, 95% CI [0.473, 19.264]). In women, accelerated epigenetic aging in young adulthood mediates the relationship between altered brain dynamics and cognitive functioning. Prevention of cognitive decline should target women already in young adulthood.
Perception is a multi-faceted, dynamical process that can be tackled empirically through measures of stimulus detectability and confidence. We recorded stereo-electroencephalographic data of 29 participants partaking in three pre-registered experiments to assess if evidence accumulation, a form of sequential sampling of sensory evidence, can explain perception. In an immediate-response experiment, high-gamma activity from individual channels and decoded multivariate latent variables in the visual, inferior frontal, and anterior insular cortices display a correlation between the slope of their increase and reaction times. In two further experiments, this signal in the ventral visual cortex differentiates between (1) stimuli reported as seen vs. unseen in delayed detection, (2) high and low intensity stimuli during passive viewing, and (3) levels of confidence when stimuli were detected. A computational model of leaky evidence accumulation can successfully reproduce both behavioral and neural data. Overall, we show that evidence accumulation explains subjective aspects of visual perception.
To identify the neurocognitive mechanisms underpinning the social difficulties that characterize autism, we performed functional magnetic resonance imaging on pairs of autistic and non-autistic adults simultaneously whilst they interacted with one another on the iterated Ultimatum Game (iUG)-an interactive task that emulates the reciprocal characteristic of naturalistic interpersonal exchanges. Two age-matched sets of male-male dyads were investigated: 16 comprised an autistic Responder and a non-autistic Proposer, and 19 comprised non-autistic pairs of Responder and Proposer. Players' round-by-round behavior on the iUG was modeled as reciprocal choices, and dynamic functional connectivity (dFC) was measured to identify the neural mechanisms underpinning reciprocal behaviors. Behavioral expressions of reciprocity were significantly reduced in autistic compared with non-autistic Responders, yet no such differences were observed between the non-autistic Proposers in either set of dyads. Furthermore, we identified latent dFC states with temporal properties associated with reciprocity. Autistic interactants spent less time in brain states characterized by dynamic inter-network integration and segregation among the Default Mode Network and cognitive control networks, suggesting that their reduced expressions of social-emotional reciprocity reflect less efficient reconfigurations among brain networks supporting flexible cognition and behavior. These findings advance our mechanistic understanding of the social difficulties characterizing autism.
Maternal diet during pregnancy has been associated with brain development and cognitive function in offspring, but the mechanisms mediating these relationships remain poorly understood. We conducted a longitudinal neuroimaging follow-up of a prenatal birth cohort and used Food Frequency Questionnaires completed by the mother in mid-pregnancy to calculate prenatal Dietary Inflammatory Index (DII) and tested its relationship with brain gyrification, an index of early brain development, and IQ in young adults (n = 179, age 28-30). The longitudinal gyrification data were available for a subset of these individuals (n = 77, age 23-24). A higher maternal pro-inflammatory diet during pregnancy, as represented by higher DII, was associated with worse verbal IQ but not performance IQ in young adulthood. These findings were independent of sex and remained significant after adjusting for maternal education, maternal stressful life events during pregnancy, maternal smoking during pregnancy, prenatal supplements (e.g. folic acid, iron, zinc, calcium, vitamins), and maternal age at birth. Moreover, higher DII was associated with altered cortical gyrification in the early as well as the late 20, particularly in men. Gyrification of the anterior middle and inferior frontal gyrus mediated the relationship between prenatal DII and verbal IQ in young adulthood. These findings support the use of cortical gyrification as a proxy marker of early brain development and suggest it may underlie the relationship between maternal diet during pregnancy and its long-term impact on cognitive skills in offspring. They also have important implications for pregnant women who might be able to optimize the brain development and verbal IQ of their children through an anti-inflammatory diet.
This study aimed to directly compare electroencephalography (EEG) whole-brain patterns of neural dynamics with concurrently measured fMRI BOLD data. To achieve this, we aim to derive EEG patterns based on a spatio-spectral decomposition of band-limited EEG power in the source-reconstructed space. In a large dataset of 72 subjects undergoing resting-state hdEEG-fMRI, we demonstrated that the proposed approach is reliable in terms of both the extracted patterns as well as their spatial BOLD signatures. The five most robust EEG spatio-spectral patterns not only include the well-known occipital alpha power dynamics, ensuring consistency with established findings, but also reveal additional patterns, uncovering new insights into brain activity. We report and interpret the most reproducible source-space EEG-fMRI patterns, along with the corresponding EEG electrode-space patterns, which are better known from the literature. The EEG spatio-spectral patterns show weak, yet statistically significant spatial similarity to their functional magnetic resonance imaging (fMRI) blood oxygenation level-dependent (BOLD) signatures, particularly in the patterns that exhibit stronger temporal synchronization with BOLD. However, we did not observe a statistically significant relationship between the EEG spatio-spectral patterns and the classical fMRI BOLD resting-state networks (as identified through independent component analysis), tested as the similarity between their temporal synchronization and spatial overlap. This provides evidence that both EEG (frequency-specific) power and the BOLD signal capture reproducible spatio-temporal patterns of neural dynamics. Instead of being mutually redundant, these only partially overlap, providing largely complementary information regarding the underlying low-frequency dynamics.
Background Maternal perinatal mental health is essential for optimal brain development and mental health of the offspring. We evaluated whether maternal depression during the perinatal period and early life of the offspring might be selectively associated with altered brain function during emotion regulation and whether those may further correlate with physiological responses and the typical use of emotion regulation strategies.Methods Participants included 163 young adults (49% female, 28-30 years) from the ELSPAC prenatal birth cohort who took part in its neuroimaging follow-up and had complete mental health data from the perinatal period and early life. Maternal depressive symptoms were measured mid-pregnancy, 2 weeks, 6 months, and 18 months after birth. Regulation of negative affect was studied using functional magnetic resonance imaging, concurrent skin conductance response (SCR) and heart rate variability (HRV), and assessment of typical emotion regulation strategy.Results Maternal depression 2 weeks after birth interacted with sex and showed a relationship with greater brain response during emotion regulation in a right frontal cluster in women. Moreover, this brain response mediated the relationship between greater maternal depression 2 weeks after birth and greater suppression of emotions in young adult women (ab = 0.11, SE = 0.05, 95% CI [0.016; 0.226]). The altered brain response during emotion regulation and the typical emotion regulation strategy were also as sociated with SCR and HRV.Conclusions These findings suggest that maternal depression 2 weeks after birth predisposes female offspring to maladaptive emotion regulation skills and particularly to emotion suppression in young adulthood.
The analysis of EEG microstates is a useful method for exploring large-scale networks and brain dynamics. In addition to the often-reported microstates, or so-called 'canonical microstates', another topography has been reported in the literature - topography with a prominent straight line separating positive and negative values that extends from the nasion to the inion (vertical topography - VT). This topography was also revealed in our simultaneous EEG/fMRI and shielded cabin EEG data collected from 77 participants. Following analyses based on human and phantom data, we conclude that VT partially reflects artifacts caused by unspecified movements of the EEG cap and its metallic components. Our conclusion is supported by evaluation of spatiotemporal characteristics of VT estimated from EEG acquired under various conditions, especially by significant correlation between the framewise displacement (obtained from human EEG/fMRI) and the temporal characteristics of VT. We recommend cautious interpretation of VT when revealed in the data. Its very presence as a resulting topography may affect the spatiotemporal parameters of the other microstates and distorts the shapes of the other topographies. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the Czech Health Research Council, project no. NU21-04-00254. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee of Masaryk University gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Due to institutional and ethical restrictions, the datasets used in the current study are only made available via a request to the corresponding author.
In this work, we aimed to directly compare and integrate EEG whole-brain patterns of neural dynamics with concurrently measured fMRI BOLD data. For that purpose, we set out to derive EEG patterns based on a spatio-spectral decomposition of band-limited EEG power in the source-reconstructed space. On a large data set of 72 subjects resting-state hdEEG-fMRI we showed that the proposed approach is reliable both in terms of the extracted patterns as well as their spatial BOLD signatures. The five most robust EEG spatio-spectral patterns include, but go beyond, the well-known occipital alpha power dynamics. The EEG spatial-spectral patterns show relatively weak, yet statistically significant spatial similarity to their fMRI BOLD signatures, particularly the patterns that show stronger temporal synchronization with BOLD. However, we observed an insignificant relation between the temporal synchronization and spatial overlap of the EEG spatio-spectral patterns and the classical fMRI BOLD resting state networks (as obtained by independent component analysis). This provides evidence that both EEG (frequency-specific) power and BOLD signal capture reproducible spatiotemporal patterns of neural dynamics. Rather than being mutually redundant, these are only partially overlapping, carrying to a large extent complementary information concerning the underlying low-frequency dynamics. Finally, we report and interpret the most stable source space EEG-fMRI patterns, along with the corresponding EEG electrode space patterns better known from the literature. ### Competing Interest Statement The authors have declared no competing interest.
White matter (WM) development has been studied extensively, but most studies used cross-sectional data, and to the best of our knowledge, none of them considered the possible effects of biological (vs. chronological) age. Therefore, we conducted a longitudinal multimodal study of WM development and studied changes in fractional anisotropy (FA) in the different WM tracts and their relationship with cortical thickness-based measures of brain aging in young adulthood. A total of 105 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort underwent magnetic resonance imaging (MRI) at the age of 23-24, and the age of 28-30 years. At both time points, FA in the different WM tracts was extracted using the JHU atlas, and brain age gap estimate (BrainAGE) was calculated using the Neuroanatomical Age Prediction using R (NAPR) model based on cortical thickness maps. Changes in FA and the speed of cortical brain aging were calculated as the difference between the respective variables in the late vs. early 20s. We demonstrated tract-specific increases as well as decreases in FA, which indicate that the WM microstructure continues to develop in the third decade of life. Moreover, the significant interaction between the speed of cortical brain aging, tract, and sex on mean FA revealed that a greater speed of cortical brain aging in young adulthood predicted greater decreases in FA in the bilateral cingulum and left superior longitudinal fasciculus in young adult men. Overall, these changes in FA in the WM tracts in young adulthood point out the protracted development of WM microstructure, particularly in men.
IntroductionAltered subjective visual sensitivity manifests as feelings of discomfort or overload elicited by intense and irritative visual stimuli. This can result in a host of visual aberrations including visual distortions, elementary visual hallucinations and visceral responses like dizziness and nausea, collectively referred to as “pattern glare.” Current knowledge of the underlying neural mechanisms has focused on overall excitability of the visual cortex, but the individual contribution of excitatory and inhibitory systems has not yet been quantified.MethodsIn this study, we focus on the role of glutamate and γ-aminobutyric acid (GABA) as potential mediators of individual differences in subjective visual sensitivity, measured by a computerized Pattern Glare Test—a series of monochromatic square-wave gratings with three different spatial frequencies, while controlling for psychological variables related to sensory sensitivity with multiple questionnaires. Resting neurotransmitter concentrations in primary visual cortex (V1) and right anterior insula were studied in 160 healthy participants using magnetic resonance spectroscopy.ResultsData showed significant differences in the perception of visual distortions (VD) and comfort scores between men and women, with women generally reporting more VD, and therefore the modulatory effect of sex was considered in a further examination. A general linear model analysis showed a negative effect of occipital glutamate on a number of reported visual distortions, but also a significant role of several background psychological traits. When assessing comfort scores in women, an important intervening variable was the menstrual cycle.DiscussionOur findings do not support that baseline neurotransmitter levels have a significant role in overreactivity to aversive stimuli in neurotypical population. However, we demonstrated that biological sex can have a significant impact on subjective responses. Based on this additional finding, we suggest that future studies investigate aversive visual stimuli while examining the role of biological sex.