Low Frequency Systemic Hemodynamic “Noise” in Resting State BOLD fMRI: Characteristics, Causes, Implications, Mitigation Strategies, and Applications

• Published in: Frontiers in neuroscience Vol. 13; p. 787
• Main Authors: Tong, Yunjie, Hocke, Lia M., Frederick, Blaise B.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 14.08.2019; Frontiers Media S.A
• Subjects: Brain mapping; Brain research; cerebrovascular reactivity; denoising; Functional magnetic resonance imaging; low frequency oscillation; Mental disorders; Neural networks; Neuroscience; NMR; Noise; noise modeling; Nuclear magnetic resonance; physiological noise; Physiology; Respiration; Spectrum analysis; vascular mapping; United States > US; denoising; vascular mapping; noise modeling; physiological noise modeling; cerebrovascular reactivity; physiological noise; low frequency oscillation
• ISSN: 1662-453X; 1662-4548; 1662-453X
• DOI: 10.3389/fnins.2019.00787

Advances in functional magnetic resonance imaging (fMRI) acquisition have improved signal to noise to the point where the physiology of the subject is the dominant noise source in resting state fMRI data (rsfMRI). Among these systemic, non-neuronal physiological signals, respiration and to some degree cardiac fluctuations can be removed through modeling, or in the case of newer, faster acquisitions such as simultaneous multislice acquisition, simple spectral filtering. However, significant low frequency physiological oscillation (∼0.01-0.15 Hz) remains in the signal. This is problematic, as it is the precise frequency band occupied by the neuronally modulated hemodynamic responses used to study brain connectivity, precluding its removal by spectral filtering. The source of this signal, and its method of production and propagation in the body, have not been conclusively determined. Here, we summarize the defining characteristics of the systemic low frequency noise signal, and review some current theories about the signal source and the evidence supporting them. The strength and distribution of the systemic LFO signal make characterizing and removing it essential for accurate quantification, especially for resting state connectivity, when no stimulation can be compared with the signal. Widespread correlated non-neuronal signals obscure and distort the more localized patterns of neuronal correlations between interacting brain regions; they may even cause apparent connectivity between regions with no neuronal interaction. Here, we discuss a simple method we have developed to parse the global, moving, blood-borne signal from the stationary, neuronal connectivity signals, substantially reducing the negative correlations that result from global signal regression. Finally, we will discuss some of the uses to which the moving systemic low frequency oscillation can be put if we consider it a "signal" carrying information, rather than simply "noise" complicating the interpretation of resting state connectivity. Properly utilizing this signal may offer insights into subtle hemodynamic alterations that can be used as early indicators of circulatory dysfunction in a number of neuropsychiatric conditions, such as prodromal stroke, moyamoya, and Alzheimer's disease.