Differentiation of somatosensory cortices by high-resolution fMRI at 7 T
Research highlights
►Single-digit somatotopic maps were identified in areas 3b and 1 of SI. ►Separation of digit representations was 1.6 times greater in area 3b than in area 1. ►Somatotopic maps acquired at 7 T have high spatial and temporal reproducibility.
Introduction
Functional magnetic resonance imaging (fMRI) based on measuring changes in blood oxygen level-dependent (BOLD) signals has been used extensively to study the functional architecture of somatosensory and other cortices in humans (Fox, 2009, Kayser et al., 2005, Moore et al., 2000, Nelson and Chen, 2008, Sasaki et al., 2005, Schweizer et al., 2008, Silver and Kastner, 2009, Tootell et al., 2008). Such studies provide important insights into not only the normal organization of sensory cortices but also potentially into how neural systems are affected by disease or damage and how they may change over time during remodeling and with interventions (Borsook et al., 1998, Fox, 2009, Schaechter et al., 2006). fMRI is uniquely suited to address such questions because it is non-invasive and relatively easy to implement, but for ultimate success it is essential that the spatial resolution and sensitivity of fMRI data are adequate for recording fine details in single subjects with adequate within-subject reliability and reproducibility in reasonably short acquisition times (Harel et al., 2006). To date, these criteria have not been satisfied, where previous studies typically have reported findings with insufficient spatial resolution, or have used average maps from multiple subjects, reflecting the practical current limits on sensitivity and image contrast to noise ratio (Francis et al., 2000, Gelnar et al., 1998, Krause et al., 2001, Kurth et al., 2000, Maldjian et al., 1999, Nelson and Chen, 2008). Theoretically, the use of ultra-high fields (7 T or above) for fMRI promises to provide greater sensitivity for detecting functional activations and to permit the use of higher spatial resolution acquisitions (Bandettini, 2009). Thus, the advent of commercial ultra-high field MRI systems operating at 7 T provides an opportunity to push the limits of performance of fMRI to examine anew whether single-subject high-resolution functional maps can be acquired in reasonable times in order to be useful for a variety of applications.
In general, throughout the history of MRI, each substantive increase in field strength has in time led to dramatic improvements in the quality of images obtainable, but each major increase in field has also introduced new technical challenges and problems (Bandettini, 2009). Image quality in MRI is always limited by the relative strengths of the available signal and the “noise”—those random fluctuations in images that are unavoidable but which obscure details and make the detection of small signal differences more difficult. In principle, the strength of MRI signals increase quadratically with field strength but in practice other factors are also important and affect the achieved signal to noise ratio (SNR). However, experiences to date have demonstrated that SNR increases when moving from 1.5 T or 3 T to 7 T, and the higher SNR can be used to make images with finer spatial resolution, or in less time, or in which small signal differences are easier to detect (Haacke et al., 1999, Stark and Bradley, 1999). In addition, differences in signal induced by functional activation via the BOLD effect will also be magnified at higher fields and therefore should be detected with greater sensitivity (Dula et al., 2010, Gati et al., 1997, Ogawa et al., 1993, van der Zwaag et al., 2009). To date, however, there have been few convincing demonstrations that fMRI at 7 T offers significant advantages over lower fields and few illustrations of where the higher spatial resolution provides additional information.
In 1937, Penfield and colleagues, using invasive electrophysiological techniques, successfully mapped body surface representations in the human primary somatosensory cortex, establishing the existence of a somatotopic map or homunculus of the body surface in the human brain (Penfield and Boldrey, 1937). In the subsequent 60 years, with the lack of non-invasive imaging techniques, little advancement was made in the understanding of somatosensory organization in human cortex. Following the first development of BOLD fMRI (Ogawa et al., 1990), human somatotopy has been studied extensively at varying field strengths (1.5, 3, and 4 T) (Blankenburg et al., 2003, Eickhoff et al., 2006, Francis et al., 2000, Gelnar et al., 1998, Hinkley et al., 2007, Kurth et al., 2000, Kurth et al., 1998, Maldjian et al., 1999, Overduin and Servos, 2004, Ruben et al., 2006, Schweizer et al., 2008, Weibull et al., 2008). Studies have revealed a topographical organization of digits in area 3b (Gelnar et al., 1998, Jack et al., 1994, Maldjian et al., 1999, Schweizer et al., 2008). In a major step forward, Nelson and Chen (2008) elegantly demonstrated the existences of topographically organized digit maps in both area 3b and area 1, findings that complement those found by other techniques in non-human primates (Chen et al., 2005, Chen et al., 2007, Friedman et al., 2008, Nelson and Chen, 2008, Sur et al., 1982). Taken together, the existing knowledge on the digit representation within the primary somatosensory cortex provides an excellent model for the evaluation of the performance of BOLD at ultra-high field (7 T). Specifically, in this study, we assess (1) whether fMRI at 7 T can reliably resolve the separation of adjacent single digits, (2) the across-run reproducibility of single-digit activation, and (3) the across-subject variation of digit separation in subregions of SI (areas 3b and 1). We demonstrate that fMRI at 7 T can provide millimeter-scale depictions of the fine-detail organization of SI in individual subjects reliably and with good reproducibility of activation and signal magnitude. The robustness of single-trial BOLD activation significantly reduces imaging acquisition duration, an advantage that is desirable for fine-scale mapping studies particularly in patients when only limited scan time is possible. Additionally, the fine-scale mapping capability of 7 T appears to be well suited for studies of differences between subjects and across time.
Section snippets
Stimulation protocol
Six healthy human subjects (5 men, 1 woman) gave informed consented for this study in accordance with a protocol approved by the Vanderbilt University Institutional Review Board. A hand and finger cast was connected to an air pressure generator via plastic tubing. Stretchable fabric was fitted across each opening in the cast, allowing for restricted skin displacement in response to an air puff. Air puffs were delivered to the glabrous skin of selected distal finger pads (Fig. 1B). The digits
Results
In individual subjects (n = 6), we detected single-digit activations in subregions (areas 3b and 1) of the primary somatosensory cortex (SI). Single-digit activation was robust in single runs, and the activation maps were reproducible across runs. Digit activations were organized topographically in areas 3b and 1 with apparent intersubject variation.
Differentiability of BOLD signal at ultra-high field (7 T)
The differentiability of BOLD signals is constrained by the imaging resolution employed in fMRI experiments. Typical functional imaging studies use “snapshot” imaging techniques of which echo-planar imaging (EPI) is a prime example, in which complete cross sectional images that are sensitive to BOLD effects are obtained in very short times, substantially less than one second. These functional images are of lower resolution than more conventional anatomic MR images, so that activation maps are
Conclusion
This study demonstrates that ultra-high field BOLD fMRI at 7 T is capable of resolving fine-scale digit topography within areas 3b and 1 of SI cortex. These maps are comparable to nonhuman primate somatotopic maps derived from high-resolution electrophysiological and intrinsic optical methods and are in agreement with human digit somatotopic maps derived from fMRI and intraoperative imaging studies. BOLD activation is robust and reproducible across runs, highlighting its potential application in
Acknowledgments
The authors thank Drs. Robert Barry and Baxter Rogers for their thoughtful comments and suggestions during the review process, Robin Avison for her technical assistance, and Lauren Holroyd for her assistance. This project was supported by NIH grant nos. IS10 RR17799 (NCRR), EB002326 (NIBIB), and EB000461 (NIBIB).
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