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Jingyuan E. Chen. 1 Department of Radiology, Stanford University, Stanford, California. 2 Department of Electrical Engineering, Stanford University, Stanford, California.
Hesamoddin Jahanian. 1 Department of Radiology, Stanford University, Stanford, California.
Gary H. Glover. 1 Department of Radiology, Stanford University, Stanford, California.
Address correspondence to: Jingyuan Chen, Department of Radiology, Stanford University, Lucas MRI/S Center, MC 5488, 1201 Welch Road, Stanford, CA 94305-5488, E-mail: [email protected]
Introduction
Permitted by recent technical advances in magnetic resonance (MR) acquisition that provide accelerated temporal sampling rates, there has been growing interest in exploiting brain resting-state functional connectivity (RSFC) at frequencies beyond the conventional 0.1 Hz. These early investigations (Boubela et al., 2013; Boyacioglu et al., 2013; Chen and Glover, 2015; Gohel and Biswal, 2015; Lee et al., 2013; Lin et al., 2015; Niazy et al., 2011; Wu et al., 2008), although with disparate acquisition protocols, converge on similar conclusions that spontaneous activity persists at frequencies well above the typical upper limit of 0.1 Hz and shares partially overlapped functional information across frequencies. These intriguing findings have offered new biomarker opportunities for clinical and neuroscience research and have provoked emerging efforts to reexamine the frequency dependence of brain functional behaviors across broad mental states (Lin et al., 2015; Yuan et al., 2014), age (Smith-Collins et al., 2015), and clinical populations (Morgan et al., 2015; Sours et al., 2015; Wang et al., 2015).
The potential concern with these promising high-frequency (HF) network connectivity results is that the blood oxygenation level-dependent (BOLD) mechanism tracks neural activity in an indirect and very sluggish manner, which naturally confers an upper limit on the neural information's observable frequencies. Previously, we demonstrated BOLD-like components up to 0.5 Hz and simulated the RS hemodynamic response function (HRF) by deriving Buxton's balloon model in an equilibrium state, which extended the frequency response from roughly 0.3 Hz (the upper limit of a canonical HRF model in SPM8 [Wellcome Trust Centre for Neuroimaging, University College London, UK]) to ∼1 Hz (Chen and Glover, 2015). However, this extended response range is still not sufficiently high to explain the frequencies reported by some studies (e.g., 5 Hz in Lin et al., 2015). One possible explanation is that RSFC at such high frequencies derives from alternative neural activity-related changes that can be captured...