bioRxiv ScienceSearch

bioRxiv · 10.1101/446856

Atlas-based classification algorithms for identification of informative brain regions in fMRI data

Abstract

Multi-voxel pattern analysis (MVPA) has been successfully applied to neuroimaging data due to its larger sensitivity compared to univariate traditional techniques. Searchlight is the most widely employed approach to assign functional value to different regions of the brain. However, its performance depends on the size of the sphere, which can overestimate the region of activation when a large sphere size is employed\n\nIn the current study, we examined the validity of two different alternatives to Searchlight: an atlas-based local averaging method (ABLA, Schrouff et al., 2013a) and a Multi-Kernel Learning (MKL, Rakotomamonjy et al., 2008) approach, in a scenario where the goal is to find the informative brain regions that support certain mental operations. These methods employ weights to measure the informativeness of a brain region and highly reduce the large computational cost that Searchlight entails. We evaluated their performance in two different scenarios where the differential BOLD activation between experimental conditions was large vs. small, and employed nine different atlases to assess the influence of diverse brain parcellations.\n\nResults show that both methods were able to localize informative regions when differences between conditions were large, demonstrating a large sensitivity and stability in the identification of regions across atlases. Moreover, the sign of the weights reported by these methods provided the directionality of univariate approaches. However, when differences were small, only ABLA localized informative regions. Thus, our results show that atlas-based methods are useful alternatives to Searchlight, but that the nature of the classification to perform should be taken into account when choosing the specific method to implement.

Source connections

Explore related subjects

Keep this discovery

BibTeXRIS

Arco, J. E., Diaz-Gutierrez, P., Ramirez, J., Ruz, M.. 2018-10-18. Atlas-based classification algorithms for identification of informative brain regions in fMRI data. https://doi.org/10.1101/446856

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