Spatiotemporal characteristics and vascular sources of neural-specific and -nonspecific fMRI signals at submillimeter columnar resolution

Abstract

The neural specificity of hemodynamic-based functional magnetic resonance imaging (fMRI) signals are dependent on both the vascular regulation and the sensitivity of the applied fMRI technique to different types and sizes of blood vessels. In order to examine the specificity of MRI-detectable hemodynamic responses, submillimeter blood oxygenation-level dependent (BOLD) and cerebral blood volume (CBV) fMRI studies were performed in a well-established cat orientation column model at 9.4 Tesla. Neural-nonspecific and -specific signals were separated by comparing the fMRI responses of orthogonal orientation stimuli. The BOLD response was dominantly neural-nonspecific, mostly originating from pial and intracortical emerging veins, and thus was highly correlated with baseline blood volume. Uneven baseline CBV may displace or distort small functional domains in high-resolution BOLD maps. The CBV response in the parenchyma exhibited dual spatiotemporal characteristics, a fast and early neural-nonspecific response (with 4.3-s time constant) and a slightly slower and delayed neural-specific response (with 9.4-s time constant). The nonspecific CBV signal originates from early-responding arteries and arterioles, while the specific CBV response, which is not correlated with baseline blood volume, arises from late-responding microvessels including small pre-capillary arterioles and capillaries. Our data indicate that although the neural specificity of CBV fMRI signals is dependent on stimulation duration, high-resolution functional maps can be obtained from steady-state CBV studies.

Submillimeter-resolution fMRI

“…They discussed that while the CBV fMRI response originated from vessels of all sizes and with different time characteristics, the CBF fMRI response mostly emerges from the microvessels and surrounding tissue and, thus, its spatial specificity is only weakly time dependent. Better spatial localization of the CBV signal at a later time period was also found in the whisker barrel map with totalHb-weighted OIS (Berwick et al, 2008) and the orientation column maps with CBV fMRI (Moon et al, 2013). However, Sheth et al (2004) reported that totalHb-weighted OIS evoked by whisker stimulation was better localized to the active barrel at an earlier time point.…”

Quantitative separation of arterial and venous cerebral blood volume increases during voluntary locomotion

“…This suggests that spatial variation (Handwerker et al, 2004) in HRFs might be due to differences in arterial and venous contributions to the HRF. Since the spatial pattern of the arterial response is thought to be more closely related to the spatial pattern of neural activity (Moon et al, 2013), brief, temporally isolated stimuli will give a hemodynamic response that more precisely reflects the underlying neural activity. However, using impulse-like stimuli is not always possible, particularly when using ‘naturalistic’ stimuli, which have multiple time-scales (Kay et al, 2008; Ben-Yakov et al, 2012; Honey et al, 2012; Naselaris et al, 2011).…”

Deciphering laminar-specific neural inputs with line-scanning fMRI

“…These fMRI studies estimate connection strengths, based on signal-correlations, among brain regions, but do not reveal the specific neural circuitry underlying the fMRI signal. High field fMRI has pushed the spatial resolution of fMRI to the submillimeter range, which makes it possible to distinguish fMRI signals from a specific cortical column 4, 5 and identify specific features of laminar fMRI responses across the cortical thickness 6 . However, it remains challenging to use these laminar related fMRI signals to extract neural information about the underlying circuit.…”

“…Different temporal phases of the fMRI response may contain distinct information about the neural sources causing the hemodynamic signal 4, 7, 8 . The initial BOLD fMRI onset signal has been reported to be spatially associated with the neural activation event to a larger extent than the later phases 7, 9 .…”