Cerebrovascular stressors, such as breath holding or CO2 inhalation, cause global magnetic resonance imaging (MRI) signal changes. In this study, we show that intrathoracic pressure changes cause rapid MRI signal alterations that have similar spatial patterns to the changes associated with breath holding or CO2 inhalation. Nine subjects performed the Valsalva maneuver during functional MRI data collection. Expiratory pressures ranged from 10 to 40 mm Hg. Breath holds ending on either inhalation or exhalation were also collected. The maximal and minimal functional MRI (fMRI) signal scaled with thoracic pressure load, and the overall amplitude of responses to the Valsalva varied, depending on brain tissue. Additionally, a Valsalva effort as short as 5 seconds yielded signal changes similar in spatial distribution and magnitude to a 20-second breath hold, suggesting potential applications of the Valsalva maneuver for calibrated fMRI experiments.

Head motion can be estimated at any point of fMRI image processing. Processing steps involving temporal interpolation (e.g., slice time correction or outlier replacement) often precede motion estimation in the literature. From first principles it can be anticipated that temporal interpolation will alter head motion in a scan. Here we demonstrate this effect and its consequences in five large fMRI datasets. Estimated head motion was reduced by 10-50% or more following temporal interpolation, and reductions were often visible to the naked eye. Such reductions make the data seem to be of improved quality. Such reductions also degrade the sensitivity of analyses aimed at detecting motion-related artifact and can cause a dataset with artifact to falsely appear artifact-free. These reduced motion estimates will be particularly problematic for studies needing estimates of motion in time, such as studies of dynamics. Based on these findings, it is sensible to obtain motion estimates prior to any image processing (regardless of subsequent processing steps and the actual timing of motion correction procedures, which need not be changed). We also find that outlier replacement procedures change signals almost entirely during times of motion and therefore have notable similarities to motion-targeting censoring strategies (which withhold or replace signals entirely during times of motion).

The recent introduction of simultaneous multi-slice (SMS) acquisitions has enabled the acquisition of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) data with significantly higher temporal sampling rates. In a parallel development, the use of multi-echo fMRI acquisitions in conjunction with a multi-echo independent component analysis (ME-ICA) approach has been introduced as a means to automatically distinguish functionally-related BOLD signal components from signal artifacts, with significant gains in sensitivity, statistical power, and specificity. In this work, we examine the gains that can be achieved with a combined approach in which data obtained with a multi-echo simultaneous multi-slice (MESMS) acquisition are analyzed with ME-ICA. We find that ME-ICA identifies significantly more BOLD-like components in the MESMS data as compared to data acquired with a conventional multi-echo single-slice acquisition. We demonstrate that the improved performance of MESMS derives from both an increase in the number of temporal samples and the enhanced ability to filter out high-frequency artifacts.

Functional connectivity techniques are commonplace tools for studying brain organization. A critical element of these analyses is to distinguish variance due to neurobiological signals from variance due to nonneurobiological signals. Multiecho fMRI techniques are a promising means for making such distinctions based on signal decay properties. Here, we report that multiecho fMRI techniques enable excellent removal of certain kinds of artifactual variance, namely, spatially focal artifacts due to motion. By removing these artifacts, multiecho techniques reveal frequent, large-amplitude blood oxygen level-dependent (BOLD) signal changes present across all gray matter that are also linked to motion. These whole-brain BOLD signals could reflect widespread neural processes or other processes, such as alterations in blood partial pressure of carbon dioxide (pCO2) due to ventilation changes. By acquiring multiecho data while monitoring breathing, we demonstrate that whole-brain BOLD signals in the resting state are often caused by changes in breathing that co-occur with head motion. These widespread respiratory fMRI signals cannot be isolated from neurobiological signals by multiecho techniques because they occur via the same BOLD mechanism. Respiratory signals must therefore be removed by some other technique to isolate neurobiological covariance in fMRI time series. Several methods for removing global artifacts are demonstrated and compared, and were found to yield fMRI time series essentially free of motion-related influences. These results identify two kinds of motion-associated fMRI variance, with different physical mechanisms and spatial profiles, each of which strongly and differentially influences functional connectivity patterns. Distance-dependent patterns in covariance are nearly entirely attributable to non-BOLD artifacts.

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative has focused scientific attention on the necessary tools to understand the human brain and mind. Here, we outline our collective vision for what we can achieve within a decade with properly targeted efforts and discuss likely technological deliverables and neuroscience progress.