Functional magnetic resonance imaging (fMRI) is now routinely used to map the topographic organization of human visual cortex. Mapping the detailed topography of somatosensory cortex, however, has proven to be more difficult. Here we used the increased blood-oxygen-level-dependent contrast-to-noise ratio at ultra-high field (7 Tesla) to measure the topographic representation of the digits in human somatosensory cortex at 1 mm isotropic resolution in individual subjects. A "traveling wave" paradigm was used to locate regions of cortex responding to periodic tactile stimulation of each distal phalangeal digit. Tactile stimulation was applied sequentially to each digit of the left hand from thumb to little finger (and in the reverse order). In all subjects, we found an orderly map of the digits on the posterior bank of the central sulcus (postcentral gyrus). Additionally, we measured event-related responses to brief stimuli for comparison with the topographic mapping data and related the fMRI responses to anatomical images obtained with an inversion-recovery sequence. Our results have important implications for the study of human somatosensory cortex and underscore the practical utility of ultra-high field functional imaging with 1 mm isotropic resolution for neuroscience experiments. First, topographic mapping of somatosensory cortex can be achieved in 20 min, allowing time for further experiments in the same session. Second, the maps are of sufficiently high resolution to resolve the representations of all five digits and third, the measurements are robust and can be made in an individual subject. These combined advantages will allow somatotopic fMRI to be used to measure the representation of digits in patients undergoing rehabilitation or plastic changes after peripheral nerve damage as well as tracking changes in normal subjects undergoing perceptual learning.

The primary somatosensory cortex (S1) can be subdivided cytoarchitectonically into four distinct Brodmann areas (3a, 3b, 1, and 2), but these areas have never been successfully delineated in vivo in single human subjects. Here, we demonstrate the functional parcellation of four areas of S1 in individual human subjects based on high-resolution functional MRI measurements made at 7 T using vibrotactile stimulation. By stimulating four sites along the length of the index finger, we were able to identify and locate map reversals of the base to tip representation of the index finger in S1. We suggest that these reversals correspond to the areal borders between the mirrored representations in the four Brodmann areas, as predicted from electrophysiology measurements in nonhuman primates. In all subjects, maps were highly reproducible across scanning sessions and stable over weeks. In four of the six subjects scanned, four, mirrored, within-finger somatotopic maps defining the extent of the Brodmann areas could be directly observed on the cortical surface. In addition, by using multivariate classification analysis, the location of stimulation on the index finger (four distinct sites) could be decoded with a mean accuracy of 65% across subjects. Our measurements thus show that within-finger topography is present at the millimeter scale in the cortex and is highly reproducible. The ability to identify functional areas of S1 in vivo in individual subjects will provide a framework for investigating more complex aspects of tactile representation in S1.

Using ultra-high field 7 Tesla (7T) functional magnetic resonance imaging (fMRI), we map the cortical and perceptual responses elicited by intraneural microstimulation (INMS) of single mechanoreceptive afferent units in the median nerve, in humans. Activations are compared to those produced by applying vibrotactile stimulation to the unit’s receptive field, and unit-type perceptual reports are analyzed. We show that INMS and vibrotactile stimulation engage overlapping areas within the topographically appropriate digit representation in the primary somatosensory cortex. Additional brain regions in bilateral secondary somatosensory cortex, premotor cortex, primary motor cortex, insula and posterior parietal cortex, as well as in contralateral prefrontal cortex are also shown to be activated in response to INMS. The combination of INMS and 7T fMRI opens up an unprecedented opportunity to bridge the gap between first-order mechanoreceptive afferent input codes and their spatial, dynamic and perceptual representations in human cortex.DOI: http://dx.doi.org/10.7554/eLife.12812.001

Previous functional magnetic resonance imaging (fMRI) studies have demonstrated digit somatotopy in primary somatosensory cortex (SI), and even shown that at high spatial resolution it is possible to resolve within-digit somatotopy. However, fMRI studies have failed to resolve the spatial organisation of digit representations in secondary somatosensory cortex (SII). One of the major limitations of high spatial resolution fMRI studies of the somatosensory system has been the long acquisition time needed to acquire slices spanning both SI and SII. Here, we exploit the increased blood oxygenation level dependent contrast of ultra-high-field (7 Tesla) fMRI and the use of multiband imaging to study the topographic organisation in SI and SII with high spatial resolution at the individual subject level. A total of n = 6 subjects underwent vibrotactile stimulation of their face, hand digits and foot (body imaging) and their individual hand digits (digit mapping) for each left and right sides of the body. In addition, n = 2 subjects participated only in the body imaging experiment on both their left and right sides. We show an orderly representation of the face, hand digits and foot in contralateral primary cortex in each individual subject. In SII, there is clear separation of the body areas of the face, hand and foot but the spatial organisation varies across individual subjects. However, separate representation of the individual digits of the hand in SII could not be resolved, even at the spatial resolution of 1.5 mm due to largely overlapping representations.

The increased blood oxygenation level-dependent contrast-to-noise ratio at ultrahigh field (7 T) has been exploited in a comparison of the spatial location and strength of activation in high-resolution (1.5  mm isotropic) gradient echo (GE) and spin echo (SE), echo planar imaging data acquired during the execution of a simple motor task in five subjects. SE data were acquired at six echo times from 30 to 55  ms. Excellent fat suppression was achieved in the SE echo planar images using slice-selective gradient reversal. Threshold-free cluster enhancement was used to define regions of interest (ROIs) containing voxels showing significant stimulus-locked signal changes from the GE and average SE data. These were used to compare the signal changes and spatial locations of activated regions in SE and GE data. T(2) and T(2)* values were measured, with means of 48.3 ± 1.1  ms and 36.5 ± 3.4  ms in the SE ROI. In addition, we identified a dark band in SE images of the motor cortex corresponding to a region in which T(2) and T(2)* were significantly lower than in the surrounding grey matter. The fractional SE signal change in the ROI was found to vary linearly as a function of TE, with a slope that was dependent on the particular ROI assessed: the mean ΔR(2) value was found to be 0.85 ± 0.11  s(-1) for the SE ROI and -0.37 ± 0.05  s(-1) for the GE ROI. The fractional signal change relative to the shortest TE revealed that the largest signal change occurred at a TE of 45  ms outside of the dark band. At this TE, the ratio of the fractional signal change in GE and SE data was found to be 0.48 ± 0.05. Phase maps produced from high-resolution GE images spanning the right motor cortex were used to identify veins. The GE ROI was found to contain 18% more voxels overlying the venous mask than the SE ROI.

With the advent of ultra-high field (7T), high spatial resolution functional MRI (fMRI) has allowed the differentiation of the cortical representations of each of the digits at an individual-subject level in human primary somatosensory cortex (S1). Here we generate a probabilistic atlas of the contralateral SI representations of the digits of both the left and right hand in a group of 22 right-handed individuals. The atlas is generated in both volume and surface standardised spaces from somatotopic maps obtained by delivering vibrotactile stimulation to each distal phalangeal digit using a travelling wave paradigm. Metrics quantify the likelihood of a given position being assigned to a digit (full probability map) and the most probable digit for a given spatial location (maximum probability map). The atlas is validated using a leave-one-out cross validation procedure. Anatomical variance across the somatotopic map is also assessed to investigate whether the functional variability across subjects is coupled to structural differences. This probabilistic atlas quantifies the variability in digit representations in healthy subjects, finding some quantifiable separability between digits 2, 3 and 4, a complex overlapping relationship between digits 1 and 2, and little agreement of digit 5 across subjects. The atlas and constituent subject maps are available online for use as a reference in future neuroimaging studies.

The sensation of touch in the glabrous skin of the human hand is conveyed by thousands of fast-conducting mechanoreceptive afferents, which can be categorised into four distinct types. The spiking properties of these afferents in the periphery in response to varied tactile stimuli are well-characterised, but relatively little is known about the spatiotemporal properties of the neural representations of these different receptor types in the human cortex. Here, we use the novel methodological combination of single-unit intraneural microstimulation (INMS) with magnetoencephalography (MEG) to localise cortical representations of individual touch afferents in humans, by measuring the extracranial magnetic fields from neural currents. We found that by assessing the modulation of the beta (13–30 Hz) rhythm during single-unit INMS, significant changes in oscillatory amplitude occur in the contralateral primary somatosensory cortex within and across a group of fast adapting type I mechanoreceptive afferents, which corresponded well to the induced response from matched vibrotactile stimulation. Combining the spatiotemporal specificity of MEG with the selective single-unit stimulation of INMS enables the interrogation of the central representations of different aspects of tactile afferent signalling within the human cortices. The fundamental finding that single-unit INMS ERD responses are robust and consistent with natural somatosensory stimuli will permit us to more dynamically probe the central nervous system responses in humans, to address questions about the processing of touch from the different classes of mechanoreceptive afferents and the effects of varying the stimulus frequency and patterning.

An efficient multi-slice inversion–recovery EPI (MS-IR-EPI) sequence for fast, high spatial resolution, quantitative T 1 mapping is presented, using a segmented simultaneous multi-slice acquisition, combined with slice order shifting across multiple acquisitions. The segmented acquisition minimises the effective TE and readout duration compared to a single-shot EPI scheme, reducing geometric distortions to provide high quality T 1 maps with a narrow point-spread function. The precision and repeatability of MS-IR-EPI T 1 measurements are assessed using both T 1 -calibrated and T 2 -calibrated ISMRM/NIST phantom spheres at 3 and 7 T and compared with single slice IR and MP2RAGE methods. Magnetization transfer (MT) effects of the spectrally-selective fat-suppression (FS) pulses required for in vivo imaging are shown to shorten the measured in-vivo T 1 values. We model the effect of these fat suppression pulses on T 1 measurements and show that the model can remove their MT contribution from the measured T 1 , thus providing accurate T 1 quantification. High spatial resolution T 1 maps of the human brain generated with MS-IR-EPI at 7 T are compared with those generated with the widely implemented MP2RAGE sequence. Our MS-IR-EPI sequence provides high SNR per unit time and sharper T 1 maps than MP2RAGE, demonstrating the potential for ultra-high resolution T 1 mapping and the improved discrimination of functionally relevant cortical areas in the human brain.