# The biological role of local and global fMRI BOLD signal variability in multiscale human brain organization

**Authors:** Giulia Baracchini, Yigu Zhou, Jason da Silva Castanheira, Justine Y. Hansen, Can Fenerci, Roni Setton, Jenny R. Rieck, Gary R. Turner, Cheryl L. Grady, Bratislav Misic, Jason S. Nomi, Lucina Q. Uddin, R. Nathan Spreng

PMC · DOI: 10.1038/s41467-026-68700-0 · 2026-01-30

## TL;DR

The study shows that variability in fMRI brain signals reflects meaningful biological processes across different scales of brain organization.

## Contribution

The paper establishes that BOLD signal variability is a biologically relevant feature of multi-scale brain function.

## Key findings

- BOLD signal variability is spatially heterogeneous and distinct from noise.
- The variability reflects multi-scale and multi-modal brain organization.
- It integrates with histology, transcriptomics, and other neurobiological data.

## Abstract

Variability drives the organization and behavior of complex systems, including the human brain. Understanding the variability of brain signals is thus necessary to broaden our window into brain function and behavior. Few empirical investigations of macroscale brain signal variability have been undertaken, given the difficulty in separating biological sources of variance from artefactual noise. Here, we characterize the temporal variability of the most predominant macroscale brain signal, the fMRI BOLD signal, and systematically investigate its statistical, topographical, and neurobiological properties. We contrast fMRI acquisition protocols, and integrate across histology, microstructure, transcriptomics, neurotransmitter receptor and metabolic data, fMRI static connectivity, and empirical and simulated magnetoencephalography data. We show that BOLD signal variability represents a spatially heterogeneous, central property of multi-scale multi-modal brain organization, distinct from noise. Our work establishes the biological relevance of BOLD signal variability and provides a lens on brain stochasticity across spatial and temporal scales.

Baracchini et al. reveal that temporal variability in fMRI brain signals encodes biologically meaningful information across spatial and temporal scales, highlighting its role in healthy brain function and systems-level organization.

## Full-text entities

- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12960827/full.md

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Source: https://tomesphere.com/paper/PMC12960827