Evidence map›Paper›PMID 41993320›Full record

ArticlebioRxiv : the preprint server for biology2026

Global Signal Removal (GSR) as graph spatial filtering.

Fahimeh Arab, Benjamin S Sipes, Srikantan S Nagarajan, Ashish Raj

Abstract readPreprint
In one paragraph

Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Fahimeh ArabDepartment of Radiology and Biomedical Imaging, University of California San Francisco.ORCID 0000-0001-5868-0406
Benjamin S SipesDepartment of Radiology and Biomedical Imaging, University of California San Francisco.ORCID 0000-0002-8266-2213
Srikantan S NagarajanDepartment of Radiology and Biomedical Imaging, University of California San Francisco.ORCID 0000-0001-7209-3857
Ashish RajDepartment of Radiology and Biomedical Imaging, University of California San Francisco.ORCID 0000-0003-2414-2444

Funding

Mapping the Human Connectome: Structure, Function, and HeritabilityU54MH091657 · NIMH · WASHINGTON UNIVERSITY · PI UGURBIL, KAMIL, VAN ESSEN, DAVID C · 2010 to 2014
$34.7M
Understanding the dynamic interactions between tau pathology and microgliamediated inflammation in Alzheimer's DiseaseR01AG072753 · NIA · WEILL MEDICAL COLL OF CORNELL UNIV · PI BUTLER, TRACY A., GUPTA, AJAY · 2021 to 2025
$5.3M
Dynamic Brain Imaging of Speech in Primary Progressive AphasiaRF1NS100440 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GORNO TEMPINI, MARIA LUISA, HOUDE, JOHN FRANCIS · 2023 to 2023
$2.4M
Mathematical modeling of selective vulnerability of genes, cells and network in mouse tauopathyRF1AG087302 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI RAJ, ASHISH · 2024 to 2024
$2.1M
Exploring the differential spreading of distinct pathological conformers of AD/LBD-related proteins by combining mathematical modeling and functional studyR21AG087921 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI PENG, CHAO, RAJ, ASHISH · 2024 to 2025
$441k
NIA NIH HHS R01 AG072753NIA NIH HHS R21 AG087921NIA NIH HHS RF1 AG087302NIMH NIH HHS U54 MH091657NINDS NIH HHS RF1 NS100440
6 · The paper itself

Abstract

Global Signal Removal (GSR) is a widely applied step in functional magnetic resonance imaging (fMRI) preprocessing. Although GSR conventionally denotes 'Global Signal Regression,' we use 'Global Signal Removal' to encompass a broader family of spatial filtering operations. GSR in general remains controversial due to concerns about introducing spurious anticorrelations and removing neurally meaningful signals. In this paper, we provide a precise geometric characterization by formalizing GSR as graph spatial filtering. We demonstrate that the most common form of GSR, Regression-GSR, equates to a rank-1 deflation of the covariance matrix (i.e. functional connectivity) by the degree vector. Empirically, the degree vector is dominated by the first principal component of the functional connectivity matrix (correlation = 0.88 ± 0.12 in resting-state HCP data), making Regression-GSR an approximation to first eigenmode removal. This view of GSR as a spatial projection framework allows us to develop a family of GSR variants, each expressible in a unified spatial filter: Naive-GSR removes the uniform vector, PCA-GSR precisely removes the first eigenvector, and SC-GSR, a new variant we introduce that removes the first harmonic of the structural connectivity matrix. A key distinction emerges: while Naive, PCA, and SC-GSR are orthogonal projections, Regression-GSR is an oblique projection that computes regional weights proportional to the degree vector but removes a spatially uniform signal. All GSR variants induce numerical singularity in the covariance matrix, but they differ in their effects on task-state separability, which we examine empirically. In summary, we reframe GSR as a family of graph spatial filters that enable interpretability of its effects, with systematically varying effects on network connectivity across variants.

Indexed as

fMRI preprocessingfunctional connectivityglobal signal regressiongraph filteringresting-state networksspatial projection

Identifiers

PMID41993320
PMCPMC13081951

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.