Search bioRxivSearch

bioRxiv · 10.1101/862730

Connectomic consistency: a systematic stability analysisof structural and functional connectivity

Abstract

Connectomics, the study of brain connectivity, has become an indispensable tool in neuroscientific research as it provides insights into brain organization. Connectomes are generated for different modalities such as using diffusion MRI to capture structural organization of the brain or using functional MRI to elaborate brains functional organization. Understanding links between structural and functional organizations is crucial in explaining how observed behavior emerges from the underlying neurobiological mechanisms. Many studies have investigated how these two organizations relate to each other; however, we still lack a proper understanding on how much variation should be expected on the two modalities, both between people cross-sectionally and within a single person longitudinally. Notably, connectomes of both modalities were shown to have significant differences depending on how they are generated. In this study, for both modalities, we systematically analyzed consistency of connectomes, that is the similarity between connectomes in terms of individual connections between brain regions or in terms of overall network topology. We present a comprehensive study of consistency in structural and resting-state functional connectomes both for a single subject examined longitudinally and across a large cohort of subjects cross-sectionally. We compared connectomes generated by different tracking algorithms, parcellations, edge weighting schemes, and edge pruning techniques. We evaluated consistency both at the levels of individual edges using correlation and at the level of network topology via graph matching accuracy. We also examined consistency of connectomes that are generated using most commonly applied communication schemes. Our results demonstrate varying degrees of consistency for the two modalities, with structural connectomes showing higher consistency than functional connectomes. Moreover, we observed a wide variation in consistency depending on how connectomes are generated. Our study sets a reference point for consistency of connectome types, which is especially important for structure-function coupling studies in evaluating mismatches between modalities.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Osmanlioglu, Y., Alappatt, J. A., Parker, D., Verma, R.. 2019-12-03. Connectomic consistency: a systematic stability analysisof structural and functional connectivity. https://doi.org/10.1101/862730

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