High-Field fMRI for Human Applications: An Overview of Spatial Resolution and Signal Specificity

In the last decade, dozens of 7 Tesla scanners have been purchased or installed around the world, while 3 Tesla systems have become a standard. This increased interest in higher field strengths is driven by a demonstrated advantage of high fields for available signal-to-noise ratio (SNR) in the magnetic resonance signal. Functional imaging studies have additional advantages of increases in both the contrast and the spatial specificity of the susceptibility based BOLD signal. One use of this resultant increase in the contrast to noise ratio (CNR) for functional MRI studies at high field is increased image resolution. However, there are many factors to consider in predicting exactly what kind of resolution gains might be made at high fields, and what the opportunity costs might be. The first part of this article discusses both hardware and image quality considerations for higher resolution functional imaging. The second part draws distinctions between image resolution, spatial specificity, and functional specificity of the fMRI signals that can be acquired at high fields, suggesting practical limitations for attainable resolutions of fMRI experiments at a given field, given the current state of the art in imaging techniques. Finally, practical resolution limitations and pulse sequence options for studies in human subjects are considered

What multiplexing means for the interpretation of functional MRI data

Despite technology advances that have enabled routine acquisition of functional MRI data with sub-millimeter resolution, the inferences that cognitive neuroscientists must make to link fMRI data to behavior are complicated. Thus, a single dataset subjected to different analyses can be interpreted in different ways. This article presents two optical analogies that can be useful for framing fMRI analyses in a way that allows for multiple interpretations of fMRI data to be valid simultaneously without undermining each other. The first is reflection: when an object is reflected in a mirrored surface, it appears as if the reflected object is sharing space with the mirrored object, but of course it is not. This analogy can be a good guide for interpreting the fMRI signal, since even at sub-millimeter resolutions the signal is determined by a mixture of local and long-range neural computations. The second is refraction. If we view an object through a multi-faceted prism or gemstone, our view will change–sometimes dramatically–depending on our viewing angle. In the same way, interpretation of fMRI data (inference of underlying neuronal activity) can and should be different depending on the analysis approach. Rather than representing a weakness of the methodology, or the superiority of one approach over the other (for example, simple regression analysis versus multi-voxel pattern analysis), this is an expected consequence of how information is multiplexed in the neural networks of the brain: multiple streams of information are simultaneously present in each location. The fact that any one analysis typically shows only one view of the data also puts some parentheses around fMRI practitioners’ constant search for ground truth against which to compare their data. By holding our interpretations lightly and understanding that many interpretations of the data can all be true at the same time, we do a better job of preparing ourselves to appreciate, and eventually understand, the complexity of the brain and the behavior it produces

Consequences of polar form coherence for fMRI responses in human visual cortex

AbstractRelevant features in the visual image are often spatially extensive and have complex orientation structure. Our perceptual sensitivity to such spatial form is demonstrated by polar Glass patterns, in which an array of randomly-positioned dot pairs that are each aligned with a particular polar displacement (rotation, for example) yield a salient impression of spatial structure. Such patterns are typically considered to be processed in two main stages: local spatial filtering in low-level visual cortex followed by spatial pooling and complex form selectivity in mid-level visual cortex. However, it remains unclear both whether reciprocal interactions within the cortical hierarchy are involved in polar Glass pattern processing and which mid-level areas identify and communicate polar Glass pattern structure. Here, we used functional magnetic resonance imaging (fMRI) at 7T to infer the magnitude of neural response within human low-level and mid-level visual cortex to polar Glass patterns of varying coherence (proportion of signal elements). The activity within low-level visual areas V1 and V2 was not significantly modulated by polar Glass pattern coherence, while the low-level area V3, dorsal and ventral mid-level areas, and the human MT complex each showed a positive linear coherence response functions. The cortical processing of polar Glass patterns thus appears to involve primarily feedforward communication of local signals from V1 and V2, with initial polar form selectivity reached in V3 and distributed to multiple pathways in mid-level visual cortex

Distortion and Signal Loss in Medial Temporal Lobe

Background: The medial temporal lobe (MTL) contains subregions that are subject to severe distortion and signal loss in functional MRI. Air/tissue and bone/tissue interfaces in the vicinity of the MTL distort the local magnetic field due to differences in magnetic susceptibility. Fast image acquisition and thin slices can reduce the amount of distortion and signal loss, but at the cost of image signal-to-noise ratio (SNR). Methodology/Principal Findings: In this paper, we quantify the severity of distortion and signal loss in MTL subregions for three different echo planar imaging (EPI) acquisitions at 3 Tesla: a conventional moderate-resolution EPI (36363 mm), a conventional high-resolution EPI (1.561.562 mm), and a zoomed high-resolution EPI. We also demonstrate the advantage of reversing the phase encode direction to control the direction of distortion and to maximize efficacy of distortion compensation during data post-processing. With the high-resolution zoomed acquisition, distortion is not significant and signal loss is present only in the most anterior regions of the parahippocampal gyrus. Furthermore, we find that the severity of signal loss is variable across subjects, with some subjects showing negligible loss and others showing more dramatic loss. Conclusions/Significance: Although both distortion and signal loss are minimized in a zoomed field of view acquisition with thin slices, this improvement in accuracy comes at the cost of reduced SNR. We quantify this trade-off between distortion and SNR in order to provide a decision tree for design of high-resolution experiments investigating the functio

Hemifield columns co-opt ocular dominance column structure in human achiasma

In the absence of an optic chiasm, visual input to the right eye is represented in primary visual cortex (V1) in the right hemisphere, while visual input to the left eye activates V1 in the left hemisphere. Retinotopic mapping In V1 reveals that in each hemisphere left and right visual hemifield representations are overlaid (Hoffmann et al., 2012). To explain how overlapping hemifield representations in V1 do not impair vision, we tested the hypothesis that visual projections from nasal and temporal retina create interdigitated left and right visual hemifield representations in V1, similar to the ocular dominance columns observed in neurotypical subjects (Victor et al., 2000). We used high-resolution fMRI at 7 T to measure the spatial distribution of responses to left- and right-hemifield stimulation in one achiasmic subject. T_2-weighted 2D Spin Echo images were acquired at 0.8 mm isotropic resolution. The left eye was occluded. To the right eye, a presentation of flickering checkerboards alternated between the left and right visual fields in a blocked stimulus design. The participant performed a demanding orientation-discrimination task at fixation. A general linear model was used to estimate the preference of voxels in V1 to left- and right-hemifield stimulation. The spatial distribution of voxels with significant preference for each hemifield showed interdigitated clusters which densely packed V1 in the right hemisphere. The spatial distribution of hemifield-preference voxels in the achiasmic subject was stable between two days of testing and comparable in scale to that of human ocular dominance columns. These results are the first in vivo evidence showing that visual hemifield representations interdigitate in achiasmic V1 following a similar developmental course to that of ocular dominance columns in V1 with intact optic chiasm

Layer-Specific fMRI Reflects Different Neuronal Computations at Different Depths in Human V1

Recent work has established that cerebral blood flow is regulated at a spatial scale that can be resolved by high field fMRI to show cortical columns in humans. While cortical columns represent a cluster of neurons with similar response properties (spanning from the pial surface to the white matter), important information regarding neuronal interactions and computational processes is also contained within a single column, distributed across the six cortical lamina. A basic understanding of underlying neuronal circuitry or computations may be revealed through investigations of the distribution of neural responses at different cortical depths. In this study, we used T2-weighted imaging with 0.7 mm (isotropic) resolution to measure fMRI responses at different depths in the gray matter while human subjects observed images with either recognizable or scrambled (physically impossible) objects. Intact and scrambled images were partially occluded, resulting in clusters of activity distributed across primary visual cortex. A subset of the identified clusters of voxels showed a preference for scrambled objects over intact; in these clusters, the fMRI response in middle layers was stronger during the presentation of scrambled objects than during the presentation of intact objects. A second experiment, using stimuli targeted at either the magnocellular or the parvocellular visual pathway, shows that laminar profiles in response to parvocellular-targeted stimuli peak in more superficial layers. These findings provide new evidence for the differential sensitivity of high-field fMRI to modulations of the neural responses at different cortical depths

Downregulation of FIP200 Induces Apoptosis of Glioblastoma Cells and Microvascular Endothelial Cells by Enhancing Pyk2 Activity

The expression of focal adhesion kinase family interacting protein of 200-kDa (FIP200) in normal brain is limited to some neurons and glial cells. On immunohistochemical analysis of biopsies of glioblastoma tumors, we detected FIP200 in the tumor cells, tumor-associated endothelial cells, and occasional glial cells. Human glioblastoma tumor cell lines and immortalized human astrocytes cultured in complete media also expressed FIP200 as did primary human brain microvessel endothelial cells (MvEC), which proliferate in culture and resemble reactive endothelial cells. Downregulation of endogenous expression of FIP200 using small interfering RNA resulted in induction of apoptosis in the human glioblastoma tumor cells, immortalized human astrocytes, and primary human brain MvEC. It has been shown by other investigators using cells from other tissues that FIP200 can interact directly with, and inhibit, proline-rich tyrosine kinase 2 (Pyk2) and focal adhesion kinase (FAK). In the human glioblastoma tumor cells, immortalized human astrocytes, and primary human brain MvEC, we found that downregulation of FIP200 increased the activity of Pyk2 without increasing its expression, but did not affect the activity or expression of FAK. Coimmunoprecipitation and colocalization studies indicated that the endogenous FIP200 was largely associated with Pyk2, rather than FAK, in the glioblastoma tumor cells and brain MvEC. Moreover, the pro-apoptotic effect of FIP200 downregulation was inhibited significantly by a TAT-Pyk2-fusion protein containing the Pyk2 autophosphorylation site in these cells. In summary, downregulation of endogenous FIP200 protein in glioblastoma tumor cells, astrocytes, and brain MvECs promotes apoptosis, most likely due to the removal of a direct interaction of FIP200 with Pyk2 that inhibits Pyk2 activation, suggesting that FIP200 expression may be required for the survival of all three cell types found in glioblastoma tumors