Brain-wide ongoing activity is responsible for significant cross-trial BOLD variability.

Area of Science:

• Neuroimaging
• Systems Neuroscience
• Physiology

Background:

• Task-based functional magnetic resonance imaging (fMRI) suffers from significant cross-trial variability.
• The blood oxygenation level-dependent (BOLD) signal is modeled as a sum of stimulation-related and ongoing components.
• The spatiotemporal characteristics of ongoing BOLD activity and its impact on responses remain under-investigated.

Purpose of the Study:

• To investigate the spatiotemporal features of ongoing BOLD activity in the brain.
• To determine the effect of ongoing BOLD activity on cross-trial variability and stimulation-evoked responses.
• To develop a method for quantifying and removing ongoing BOLD activity to enhance fMRI reliability.

Main Methods:

• Measured fMRI responses to visual stimuli (light onset/offset) in awake rats.
• Simultaneously recorded neuronal activity using calcium-based fiber photometry.
• Analyzed brain-wide correlations of BOLD signals and quantified the impact of removing ongoing activity.

Main Results:

• BOLD signals across brain regions were highly correlated at zero time lag, indicating widespread ongoing activity.
• Removing ongoing activity reduced BOLD response variability by approximately 30% and increased coherence with neuronal signals.
• Ongoing BOLD activity influenced stimulation-evoked responses, including post-stimulation undershoots.

Conclusions:

• Brain-wide ongoing BOLD activity is a major source of cross-trial variability in fMRI.
• Quantifying and removing this ongoing component can significantly improve the reliability and sensitivity of fMRI.
• This method is generalizable across various fMRI experiments without altering stimulation paradigms.