Search bioRxiv⌕ Search

bioRxiv · 10.1101/2023.04.15.537017

Tuning Minimum-Norm regularization parameters for optimal MEG connectivity estimation

Abstract

The accurate characterization of cortical functional connectivity from Magnetoencephalography (MEG) data remains a challenging problem due to the subjective nature of the analysis, which requires several decisions at each step of the analysis pipeline, such as the choice of a source estimation algorithm, a connectivity metric and a cortical parcellation, to name but a few. Recent studies have emphasized the importance of selecting the regularization parameter in minimum norm estimates with caution, as variations in its value can result in significant differences in connectivity estimates. In particular, the amount of regularization that is optimal for MEG source estimation can actually be suboptimal for coherence-based MEG connectivity analysis. In this study, we expand upon previous work by examining a broader range of commonly used connectivity metrics, including the imaginary part of coherence, corrected imaginary part of Phase Locking Value, and weighted Phase Lag Index, within a larger and more realistic simulation scenario. Our results show that the best estimate of connectivity is achieved using a regularization parameter that is 1 or 2 orders of magnitude smaller than the one that yields the best source estimation. This remarkable difference may imply that previous work assessing source-space connectivity using minimum-norm may have benefited from using less regularization, as this may have helped reduce false positives. Importantly, we provide the code for MEG data simulation and analysis, offering the research community a valuable open source tool for informed selections of the regularization parameter when using minimum-norm for source space connectivity analyses. HighlightsO_LIThe regularization parameter of the Minimum Norm Estimate of neural activity impacts connectivity estimation C_LIO_LIWe study empirically the optimal parameter for connectivity estimation using realistic synthetic datasets C_LIO_LIWe find the optimal parameter for connectivity estimation is systematically smaller than the optimal parameter for source imaging; different connectivity metrics yield the same result C_LIO_LICode and data are available open source. C_LI

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Vallarino, E., Hincapie, A. S., Jerbi, K., Leahyf, R., Pascarella, A., Sorrentino, A., Sommariva, S.. 2023-04-16. Tuning Minimum-Norm regularization parameters for optimal MEG connectivity estimation. https://doi.org/10.1101/2023.04.15.537017

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗