Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience

Abstract

Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, the increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here, we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues. This article is part of the themed issue ‘Interpreting BOLD: a dialogue between cognitive and cellular neuroscience’.

Identifying disease foci from static and dynamic effective connectivity networks: Illustration in soldiers with trauma

“…To this effect, it has been shown that deconvolution produces improved estimation of effective connectivity [David et al, ; Ryali et al, ]. In fact, a recent paper presenting the viewpoint of cellular neuroscience on BOLD fMRI [Hall et al, ] discussed about several caveats in interpreting fMRI findings that deserve careful consideration based on the underlying cellular mechanisms. One such chief issue pertains to neurovascular dynamics or HRF variability, about which they say as follows: “advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD.” They suggest the use of computational modeling (e.g., deconvolution) to mitigate the issue.…”

Hemodynamic response function (HRF) variability confounds resting‐state fMRI functional connectivity

“…It must be noted that all the entities in Eqns. (5)(6)(7)(8)(9) are absolute values. We varied the value of the off-diagonal elements of C (neural-FC) from 21 to 1 in steps of 0.25, to obtain the impact of HRF variability at different FC strengths.…”

“…A recent article debating cellular neuroscience's viewpoints on BOLD fMRI presented numerous caveats while interpreting fMRI results, which demands careful consideration based on the underlying cellular mechanisms. They comment on neurovascular dynamics or HRF variability, which is one such issue, as follows: “advances in cellular neuroscience, demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD.” They suggest the community use computational modeling (e.g., deconvolution) to mitigate the issue.…”

Combined fMRI-MRS acquires simultaneous glutamate and BOLD-fMRI signals in the human brain

“…BOLD-fMRI reflects a spectrum of energy and blood-flow dependent processes (Logothetis et al, 2001) which are not fully understood (Logothetis, 2008, Hall et al, 2016). 1 H-MRS is a non-invasive measure of absolute concentrations of neurochemicals and, particularly in the absence of any sensory stimulation, has been exploited to identify biomarkers of normal and pathological brain states (Oz et al, 2014).…”