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High-resolution fMRI maps of columnar organization in human primary somatosensory cortex

Jiajia Yang^1,2, Laurentius Huber², Yinghua Yu^1,2,3, Yuhui Chai², Arman Khojandi², and Peter A Bandettini^2,4

¹Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, Japan, ²Section on Functional Imaging Methods, National Institute of Mental Health, Bethesda, MD, United States, ³The Japan Society for the Promotion of Science, Tokyo, Japan, ⁴Functional MRI Core Facility, National Institute of Mental Health, Bethesda, MD, United States

Synopsis

More than half a century ago, animal studies revealed that area 3b of the primary somatosensory cortex (S1) receives cutaneous input from slow-adapting (SA) and rapidly adapting (RA) cutaneous receptors in a columnar manner. However, there have been no direct observations of columnar origination in the human SI. Here, for the first time, we investigate the columnar organization in the human S1 by using advanced high-resolution (0.7mm) fMRI at 7T. We find that the human area 3b is columnar organized with alternating SA and RA columnar preferences. We find that SA selective stimulation evokes activity in the middle layers only.

INTRODUCTION

There are four primary tactile mechanoreceptors located in the skin. Each receptor plays a different functional role in the resulting refined sense of touch. Specifically, the slow-adapting (SA) precipitators of Merkel’s disks and Ruffini endings respond to light touch and flutter (<10Hz). In contrast, Meissner’s corpuscles and Pacinian corpuscle are rapidly adapting (RA) receptors that sense high-frequency (30 ~ 200 Hz) vibration¹. Early animal studies^2,3,4 confirmed the homogeneity of SA and RA inputs within a vertical column pattern in S1 (i.e., area 3b) (as indicated in Figure 1(a)), however, there have been no direct observations of columnar organization in the human S1. In the present study, we employ advanced high-resolution (0.7mm) fMRI at 7T^5,6to investigate the columnar origination in the human S1 by means of a sophisticated roughness stimulation setup.

METHODS

Five participants were asked to undergo one or two 26 min fMRI experiments at a 7T Siemens scanner, equipped with a 32-channel NOVA Medical head coil and SC72 body gradient. Data acquisition procedures were used as described in our previous study^5,6. In short: We used a multi-contrast VASO⁷-BOLD sequence with slices positioned to be approximately perpendicular to the cortex of the central sulcus (Figure 2(a)). (Nominal in-plane resolution = 0.71mm, TI1/TI2/TR = 1.1/2.6/3.4s, twelve slices with FLASH GRAPPA-2, matrix 46x138, 3D-EPI readout⁸, FOV 32.7x97.9x10.8mm³).To selectively simulate SA and RA receptors, we used a unique surface roughness estimation paradigm as shown in Figure 1(b). Three 3D printed stimuli (dot spacing: 2, 3 and 4mm) and acustom-designed device (Figure 1(c) and (d)) were used in the present study. The hemispheroidal raised dots were elevated by 1.5mm from the surface and were 1.0mm in diameter. The dot patterns were printed on the flat surface with a 40×50mm square base. In each functional run, three surfaces in random order were moved under participants’ index or middle fingers in each task block (37.4 s) and each task block was followed by a 26.2s rest. To generate low and high frequency “vibration”, the motion speed of 12 blocks was 8mm/s (i.e., 2~4Hz) and other 12 blocks was 80mm/s (i.e., 20~40Hz). The participants were asked to estimate the roughness of three surfaces of each block and indicated which one is the roughest of three surfaces by pressing a response key at the end of each block (Figure 1(b)). Layer and columnar analyses were done in the software suite LAYNII (https://github.com/layerfMRI/LAYNII).

RESULTS

Initially, we confirmed that the roughness estimation tasks (relative to the baseline) activated contra-lateral areas in 3b and 2 (Figure 2(d)). When we directly compared the activation maps of high and low frequency conditions, we find that the activation of the high frequency condition occupied the whole index finger area in the 3b region. However, the low frequency condition activated the middle part in the same region only (Figure 2(e)), as expected from previous invasive animal studies. Furthermore, when we extracted the fMRI signal across an orthogonal coordinate system of ‘layers’ x ‘columns’ (Figure 3(a) and (c)), we clearly confirmed the double sides RA columns and middle SA column in area 3b (activation profiles are shown in Figure 3(d)). The layer profiles of each column (Figure 3(b)) are also consistent with previous results in animals. Namely, SA receptors predominantly activate the middle layer of area 3b, while RA receptors activated all layers in area 3b.

DISCUSSION

In the present study, we used sub-millimeter BOLD and blood-volume-sensitive (VASO) fMRI^5,6at 7T to demonstrate that area 3b of human is divided into alternating SA and RA columns. Furthermore, the use of VASO fMRI, which is specific and sensitive enough to reveal functional laminar activity, allowed us to find both SA and RA selective stimulation evoked activity in the middle layers of the 3b. RA selective stimulation, on the other hand, activates the superficial and deep layers as well. We regard these observations as an important step towards the understanding of the columnar organization of the human somatosensory system.

CONCLUSION

To explore columnar organization in human area 3b, we use advanced high-resolution fMRI at 7T with a unique surface roughness estimation paradigm.This study suggests that the cutaneous input projected to area 3b is divided into alternating columns of neurons preferentially sensitive to the SA and RA receptors. These results are the first clear findings confirming the columnar organization of the human somatosensory cortex. This study provides a new starting point for non-invasive investigations of columnar organization in the human somatosensory system.

Acknowledgements

We thank Benedikt Poser and Dimo Ivanov for the 3D-EPI readout that is used in the VASO sequence used here. We thank Kenny Chung for administrative support of human volunteer scanning. This research is supported by the NIMH Intramural Research Program (#ZIA-MH002783), JSPS KAKENHI Grant Numbers JP17J40084, JP18K15339, JP18H05009, JP17K18855 and Japan-U.S. Science and Technology Cooperation Program (Brain Research). The study was approved under NIH Combined Neuroscience Institutional Review Board protocol #93-M-0170 (ClinicalTrials.gov identifier: NCT00001360).

References

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Figures

Figure 1. Proposed SA and RA columnar model in human area 3b from animal studies. (a) SA receptors are sensitive to low frequency stimulation (<10 Hz) which predominantly projected the sensory information into the middle layer. RA receptors are sensitive to high frequency stimulation (> 20 Hz) which are considered to activate all layers. (b) For each condition, three raised dots surfaces were moved under participants’ index or middle fingers. They were asked to indicate which one is the roughest of three surfaces. (c) and (d) The stimulation device is custom-designed. It is manually operated inside the scanner room.

Figure 2. Acquisition methods and activity maps (z statistical maps). (a) The imaging slice is aligned perpendicular to the cortical layers of the left hand representation in the right area 3b. Right panel showed average BOLD and VASO images across one scan session. (b) & (c) Finger representations in area 3b. (d) BOLD activation maps of D1 and D2 for the high frequency conditions. (e) BOLD activation maps of D1 high and low frequency conditions.

Figure 3. Columnar structure in human area 3b. (a) SA and RA columnar color maps (BOLD & VASO) of one participant. (b) Shows the average cortical layer profiles in SA and RA columns. (c) Illustration of SA and RA columns of middle and upper layers. (d) Shows the average columnar profiles in SA and RA columns. Blue and red arrows refer to columns of SA and RA preferences, respectively. Error bars refer to SEM across data points of each layer/column.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)

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