Neural Interpretation of Blood Oxygenation Level-Dependent fMRI Maps at Submillimeter Columnar Resolution

Abstract

Whether conventional gradient-echo (GE) blood oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) is able to map submillimeter-scale functional columns remains debatable mainly because of the spatially nonspecific large vessel contribution, poor sensitivity and reproducibility, and lack of independent evaluation. Furthermore, if the results from optical imaging of intrinsic signals are directly applicable, regions with the highest BOLD signals may indicate neurally inactive domains rather than active columns when multiple columns are activated. To examine these issues, we performed BOLD fMRI at a magnetic field of 9.4 tesla to map orientation-selective columns of isoflurane-anesthetized cats. We could not convincingly map orientation columns using conventional block-design stimulation and differential analysis method because of large fluctuations of signals. However, we successfully obtained GE BOLD iso-orientation maps with high reproducibility (r ϭ 0.74) using temporally encoded continuous cyclic orientation stimulation with Fourier data analysis, which reduces orientation-nonselective signals such as draining artifacts and is less sensitive to signal fluctuations. We further reduced large vessel contribution using the improved spin-echo (SE) BOLD method but with overall decreased sensitivity. Both GE and SE BOLD iso-orientation maps excluding large pial vascular regions were significantly correlated to maps with a known neural interpretation, which were obtained in contrast agent-aided cerebral blood volume fMRI and total hemoglobin-based optical imaging of intrinsic signals at a hemoglobin iso-sbestic point (570 nm). These results suggest that, unlike the expectation from deoxyhemoglobin-based optical imaging studies, the highest BOLD signals are localized to the sites of increased neural activity when column-nonselective signals are suppressed.

Spatiotemporal precision and hemodynamic mechanism of optical point spreads in alert primates

“…This interpretation is not supported by fMRI. The BOLD mapping signal shows a tuned increase in activated columns, indicating a spatially specific decrease of [HbR], during the rebound (24). The observed orientation-tuned decrease in [HbR] suggests that the prolonged mapping signal is not caused by deoxygenation and, by extension, also raises doubts about the standard interpretation of the initial dip.…”

Lessons from fMRI about Mapping Cortical Columns

“…Thus, the highest orientation-selective BOLD signals indicate the sites of increased neural activity. In other words, the magnitude of BOLD response to preferred stimulation should be larger than the magnitude of response to non-preferred stimulation (Moon et al, 2007).…”

“…Thus, it is critical to examine whether fMRI can pinpoint sub-millimeter functional sites. This outstanding issue motivates us to study reproducibility, specificity and confirmation of fMRI columnar maps (Fukuda et al, 2006a;Moon et al, 2007). To do this, we selected a well-established orientation column model in cats, which has been extensively investigated by single-unit recordings, 2-DG autoradiography and optical imaging of intrinsic (OIS) signals (Payne and Peters, 2002).…”

New Pictures of the Structure and Plasticity of Orientation Columns in the Visual Cortex

“…To compare simulated results with the feature representation in the cat visual cortex, highresolution fMRI was performed on cat visual cortex at 9.4 T (Fukuda et al, 2006;Moon et al, 2007). The cat was anesthetized with isoflurane (0.8 -1.0%) and immobilized with pancuronium bromide (0.2 mg kg -1 hr -1 , i.v.).…”