Search bioRxiv⌕ Search

bioRxiv · 10.1101/2022.01.12.475422

A Precision Functional Atlas of Network Probabilities and Individual-Specific Network Topography

Abstract

The brain is organized into a broad set of functional neural networks. These networks and their various characteristics have been described and scrutinized through in vivo resting state functional magnetic resonance imaging (rs-fMRI). While the basic properties of networks are generally similar between healthy individuals, there is vast variability in the precise topography across the population. These individual differences are often lost in population studies due to population averaging which assumes topographical uniformity. We leveraged precision brain mapping methods to establish a new open-source, method-flexible set of precision functional network atlases: the Masonic Institute for the Developing Brain (MIDB) Precision Brain Atlas. Using participants from the Adolescent Brain Cognitive Development (ABCD) study, single subject precision network maps were generated with two supervised network-matching procedures (template matching and non-negative matrix factorization), an overlapping template matching method for identifying integration zones, as well as an unsupervised community detection algorithm (Infomap). From these individualized maps we also generated probabilistic network maps and integration zones for two demographically-matched groups of n[~]3000 each. We demonstrate high reproducibility between groups (Pearsons r >0.999) and between methods (r=0.96), revealing both regions of high invariance and high variability. Compared to using parcellations based on groups averages, the MIDB Precision Brain Atlas allowed us to derive a set of brain regions that are largely invariant in network topography across populations, which provides more reproducible statistical maps of executive function in brain-wide associations. We also explore an example use case for probabilistic maps, highlighting their potential for use in targeted neuromodulation. The MIDB Precision Brain Atlas is expandable to alternative datasets and methods and is provided open-source with an online web interface to encourage the scientific community to experiment with probabilistic atlases and individual-specific topographies to more precisely relate network phenomenon to functional organization of the human brain.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Hermosillo, R. J., Moore, L. A., Feczko, E. J., Pines, A. R., Dworetsky, A., Conan, G., Mooney, M. A., Randolph, A., Adeyemo, B., Earl, E., Perrone, A., Carrasco, C. M., Uriarte-Lopez, J., Snider, K., Doyle, O., Cordova, M., Nagel, B. J., Ewing, S. W. F., Satterthwaite, T. D., Dosenbach, N., Gratton, C., Petersen, S., Dominguez, O. M., Fair, D. A.. 2022-01-13. A Precision Functional Atlas of Network Probabilities and Individual-Specific Network Topography. https://doi.org/10.1101/2022.01.12.475422

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↗