Biology subjects

Stam, C. J.

Publications and source records attributed to Stam, C. J..

6 recordsLinked to original sources

bioRxiv2025

Connectome-guided personalization of optimal tDCS intervention selection in Alzheimers disease

Transcranial direct current stimulation (tDCS) is being investigated as a clinical intervention in Alzheimers disease (AD) with the goal of reducing its neurophysiological effects (i.e. oscillatory slowing and loss of functional connectivity). However, progress is hampered by variable outcomes across studies, likely related to both methodological and individual differences. We recently described a virtual brain network simulation method for optimizing tDCS interventions and now propose a novel methodology for further personalizing this approach. While the general model of the AD brain we used for our previous study was based on an average human connectome and brain anatomy, we now created new personalized models for 10 biomarker-confirmed AD patients. We used individual, amplitude envelope correlation (AEC)-based connectivity matrices extracted from magnetoencephalography (MEG) scans and implemented individual structural MRI data for current flow modeling of the tDCS effects. We then assessed a set of previously established stimulation strategies based on their ability to restore relevant neurophysiological outcome parameters in each personalized model, while undergoing AD damage. Personalized tDCS strategies were able to delay neurophysiological deterioration, but in dissimilar ways compared to our previous results. While the general model favored posterior anodal stimulation targeting the precuneus region, the personalized models favored frontal anodal stimulation targeting the dorsolateral prefrontal cortex (dlPFC) region in 90% of the cases. This may be explained by higher connectivity levels of frontal regions in the personalized connectivity matrices, as anodal stimulation of highly connected regions produced more beneficial effects. In this methodological study we propose several ways to improve personalized computational tDCS stimulation prediction modeling. We conclude that connectome-guided personalization of tDCS effects lead to different strategies with potentially better intervention outcomes. For external validation of this model-guided tDCS approach, personalized and general model predictions are currently being tested and compared in a clinical tDCS-MEG trial in AD patients.

neuroscience↗

bioRxiv2023

Emergence of High-Order Functional Hubs in the Human Brain

Network theory is often based on pairwise relationships between nodes, which is not necessarily realistic for modeling complex systems. Importantly, it does not accurately capture non-pairwise interactions in the human brain, often considered one of the most complex systems. In this work, we develop a multivariate signal processing pipeline to build high-order networks from time series and apply it to resting-state functional magnetic resonance imaging (fMRI) signals to characterize high-order communication between brain regions. We also propose connectivity and signal processing rules for building uniform hypergraphs and argue that each multivariate interdependence metric could define weights in a hypergraph. As a proof of concept, we investigate the most relevant three-point interactions in the human brain by searching for high-order "hubs" in a cohort of 100 individuals from the Human Connectome Project. We find that, for each choice of multivariate interdependence, the high-order hubs are compatible with distinct systems in the brain. Additionally, the high-order functional brain networks exhibit simultaneous integration and segregation patterns qualitatively observable from their high-order hubs. Our work hereby introduces a promising heuristic route for hypergraph representation of brain activity and opens up exciting avenues for further research in high-order network neuroscience and complex systems.

neuroscience↗

bioRxiv2021

Multimodal multilayer network centrality relates to executive functioning

Executive functioning is a higher-order cognitive process that is thought to depend on a brain network organization facilitating network integration across specialized subnetworks. The frontoparietal network (FPN), a subnetwork that has diverse connections to other brain modules, seems pivotal to this integration, and a more central role of regions in the FPN has been related to better executive functioning. Brain networks can be constructed using different modalities: diffusion MRI (dMRI) can be used to reconstruct structural networks, while resting-state fMRI (rsfMRI) and magnetoencephalography (MEG) yield functional networks. These networks are often studied in a unimodal way, which cannot capture potential complementary or synergistic modal information. The multilayer framework is a relatively new approach that allows for the integration of different modalities into one network of networks. It has already yielded promising results in the field of neuroscience, having been related to e.g. cognitive dysfunction in Alzheimers disease. Multilayer analyses thus have the potential to help us better understand the relation between brain network organization and executive functioning. Here, we hypothesized a positive association between centrality of the FPN and executive functioning, and we expected that multimodal multilayer centrality would supersede unilayer centrality in explaining executive functioning. We used dMRI, rsfMRI, MEG, and neuropsychological data obtained from 33 healthy adults (age range 22-70 years) to construct eight modality-specific unilayer networks (dMRI, fMRI, and six MEG frequency bands), as well as a multilayer network comprising all unilayer networks. Interlayer links in the multilayer network were present only between a nodes counterpart across layers. We then computed and averaged eigenvector centrality of the nodes within the FPN for every uni- and multilayer network and used multiple regression models to examine the relation between uni- or multilayer centrality and executive functioning. We found that higher multilayer FPN centrality, but not unilayer FPN centrality, was related to better executive functioning. To further validate multilayer FPN centrality as a relevant measure, we assessed its relation with age. Network organization has been shown to change across the life span, becoming increasingly efficient up to middle age and regressing to a more segregated topology at higher age. Indeed, the relation between age and multilayer centrality followed an inverted-U shape. These results show the importance of FPN integration for executive functioning as well as the value of a multilayer framework in network analyses of the brain. Multilayer network analysis may particularly advance our understanding of the interplay between different brain network aspects in clinical populations, where network alterations differ across modalities. HighlightsO_LIMultimodal neuroimaging and neurophysiology data were collected in healthy adults C_LIO_LIMultilayer frontoparietal centrality was positively associated with executive functioning C_LIO_LIUnilayer (unimodal) centralities were not associated with executive functioning C_LIO_LIThere was an inverted-U relationship between multilayer centrality and age C_LI

neuroscience↗

bioRxiv2021

Neuronal morphology and physiology, functional brain networks and memory in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) patients are at risk of memory deficits, which have been linked to functional network disturbances, particularly of integration of the default mode network (DMN). However, the cellular substrates of functional network integration are unknown. We leverage a unique cross-scale dataset of therapy-resistant TLE patients, who underwent fMRI, MEG and/or neuropsychological testing before neurosurgery. fMRI and MEG underwent atlas-based connectivity analyses. Functional network centrality of the lateral middle temporal gyrus, part of the DMN, was used as a measure of local network integration. Subsequently, non-pathological cortical tissue from this region was used for single cell morphological and electrophysiological patch-clamp analysis, assessing integration in terms of total dendritic length and action potential rise speed. As could be hypothesized, greater network centrality related to better memory performance. Moreover, greater network centrality correlated with more integrative properties at the cellular level across patients. We conclude that individual differences in cognitively relevant functional network integration of a DMN region are mirrored by differences in cellular integrative properties of this region in TLE patients. These findings connect previously separate scales of investigation, increasing translational insight into focal pathology and large-scale network disturbances in TLE.

neuroscience↗

bioRxiv2018

Topological phase transitions in functional brain networks

Functional brain networks are often constructed by quantifying correlations among brain regions. Their topological structure includes nodes, edges, triangles and even higher-dimensional objects. Topological data analysis (TDA) is the emerging framework to process datasets under this perspective. In parallel, topology has proven essential for understanding fundamental questions in physics. Here we report the discovery of topological phase transitions in functional brain networks by merging concepts from TDA, topology, geometry, physics, and network theory. We show that topological phase transitions occur when the Euler entropy has a singularity, which remarkably coincides with the emergence of multidimensional topological holes in the brain network. Our results suggest that a major alteration in the pattern of brain correlations can modify the signature of such transitions, and may point to suboptimal brain functioning. Due to the universal character of phase transitions and noise robustness of TDA, our findings open perspectives towards establishing reliable topological and geometrical biomarkers of individual and group differences in functional brain network organization.

neuroscience↗

bioRxiv2018

Topological segregation of functional networks increases in developing brains

A growing literature conceptualises human brain development from a network perspective, but it remains unknown how functional brain networks are refined during the preschool years. The extant literature diverges in its characterisation of functional network development, with little agreement between haemodynamic- and electrophysiology-based measures. In children aged from 4 to 12 years, as well as adults, age appropriate magnetoencephalography was used to estimate unbiased network topology, using minimum spanning tree (MST) constructed from phase synchrony between beamformer-reconstructed time-series. During childhood, network topology becomes increasingly segregated, while cortical regions decrease in centrality. We propose a heuristic MST model, in which a clear developmental trajectory for the emergence of complex brain networks is delineated. Our results resolve topological reorganisation of functional networks across temporal and special scales in youth and fill a gap in the literature regarding neurophysiological mechanisms of functional brain maturation during the preschool years.

neuroscience↗