Ultra-slow oscillations in fMRI and resting-state connectivity: Neuronal and vascular contributions and technical confounds

Ultra-slow, ~0.1-Hz variations in the oxygenation level of brain blood are widely used as an fMRI-based surrogate of ‘‘resting-state’’ neuronal activity. The temporal correlations among these fluctuations across the brain are interpreted as ‘‘functional connections’’ for maps and neurological diagnostics. Ultra-slow variations in oxygenation follow a cascade. First, they closely track changes in arteriole diameter. Second, interpretable functional connections arise when the ultra-slow changes in amplitude of g-band neuronal oscillations, which are shared across even far-flung but synaptically connected brain regions, entrain the ~0.1-Hz vasomotor oscillation in diameter of local arterioles. Significant confounds to estimates of functional connectivity arise from residual vasomotor activity as well as arteriole dynamics driven by self-generated movements and subcortical common modulatory inputs. Last, methodological limitations of fMRI can lead to spurious functional connections. The neu...