NEUROREPORTNEUROPHYSIOLOGY, BASIC AND CLINICAL

Serial activation of distinct cytoarchitectonic
areas of the human S1 cortex after
posterior tibial nerve stimulation
Isao Hashimoto,1,2,CA Kenji Sakuma,2 Tomoaki Kimura,3 Yoshinobu Iguchi4 and Kensuke Sekihara5
1

Human Information Systems Laboratory (Tokyo Of®ce), Kanazawa Institute of Technology, 6-7-8 Akasaka, Minato-ku, Tokyo
107-0052; 2 Department of Integrative Physiology, National Institute for Physiological Sciences, Okazaki; 3 Department of
Acupuncture, Tsukuba College of Technology, Tsukuba; 4 Department of Psychophysiology, Tokyo Institute of Psychiatry, Tokyo
Metropolitan Organization for Medical Research, Tokyo; 5 Department of Electronic Systems & Engineering, Tokyo Metropolitan
Institute of Technology, Tokyo, Japan
CA,1

Corresponding Author and Address

Received 6 April 2001; accepted 11 April 2001

MEG recordings visualized non-invasively a dynamic anterior±posterior activation in the pyramidal cell population of thehuman primary somatosensory cortex (S1) after posterior
tibial nerve stimulation. Somatosensory evoked ®elds (SEFs)
were recorded over the foot area in response to rightposterior tibial nerve stimulation at the ankle in six normal
subjects. A newly developed MEG vector beamformer technique applied to the SEFs revealed two distinct sources in themesial wall of the left hemisphere around the primary P37m
response typically separated by 1.3 cm. The ®rst source was
located in area 3b and oriented toward the contralateralhemisphere. The second source was assumed to be in an area

near the marginal sulcus and the source orientation was
directed posteriorly. The ®rst source began to be active during
the initial slope of the P37m. The second source was active
after the P37m peak and the signal intensities of the ®rst andsecond sources were equal at a mean latency of 2.6 ms after
the peak of P37m. Then the ®rst source became inactive andthe second source was dominant after about 5 ms post-P37m
peak. These ®ndings suggest that a single peaked posterior
tibial nerve P37m consists of partially overlapping two subcomponents generated in area 3b and an area near themarginal sulcus. NeuroReport 12:1857±1862 & 2001 Lippincott
Williams & Wilkins.

Key words: Area 3b; Marginal ramus of cingulate sulcus; MEG vector beamformer technique; P37m; Posterior tibial nerve; Somatosensory evoked®elds; Two distinct sources

INTRODUCTION

MEG signals measured outside the head are generated
primarily from cortical currents tangential to the scalp.
Since MEG signals mainly re¯ect intracellular current ¯owwithin the apical dendrites of the cortical pyramidal cells,
only activity of pyramidal neurons in the cortical ®ssures
can be detected. In other words, activity of a large area ofthe cortical gyri remains undetected due to its radialcurrent ¯ow. However, there is one exception to thisgeneral rule; in the mesial surface of the brain, intracellularcurrents in cortical ®ssures and gyri are both tangential to
the scalp and can be recorded. Thus, this cortical area ofparacentral lobule receiving projections mainly from thefoot is uniquely situated for the MEG study of earlysomatosensory information processing.
However, considerable interindividual anatomical variations have been documented for the superior end of thecentral sulcus; the central sulcus extends to the medialsurface in 64% of cases, just reaches the superior margin of
the hemisphere in 16%, and in 20 % it does not even reachthe superior margin [1]. These morphological variations of0959-4965 & Lippincott Williams & Wilkins

the foot area of somatosensory cortex have been further
substantiated by recordings of cortical somatosensory
evoked potentials (SEPs) after stimulation of the posterior
tibial nerve in which locations exhibiting maximum P37
amplitude distributed widely within the paracentral lobule[2]. By recording somatosensory evoked ®elds (SEFs) toposterior tibial and sural nerves, Huttunen et al. [3] observed the changing ®eld patterns with temporally shiftingorientations of the source currents during various components within 200 ms. Similar orientation changes werereported during P37m in which the ®eld patterns to theposterior tibial nerve stimulation appeared to rotate very
quickly (158/ms) as a function of time [4]. These orientation
changes were interpreted as successive activation of different cytoarchitectonic areas in the foot primary somatosensory cortex (S1) [4,5]. In the studies above, source currents
were modeled with a single moving dipole.
Hari et al. [6] examined in more detail activation
patterns of the human foot S1 cortex by application of a
two-dipole time-varying source model. The ®ndings suggested that areas 3b and 5 were sequentially activated.

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NEUROREPORTI. HASHIMOTO ET AL.

However, there has been no report in support of or against
the observed sequential activation for posterior tibial nerve
stimulation. The MEG vector beamformer technique recently developed by Sekihara et al. [7,8] provides us with aunique tool for the analysis of multiple sources locatednearby, which are activated simultaneously and/or successively. In the present study, the P37m component for
stimulation of posterior tibial nerve was characterized byapplying the beamformer technique. We found that two
distinct sources separated by about 1.3 cm were sequentially and simultaneously active during the P37m primary
response. The results using a single moving dipole model
were reported previously [9].

source moment magnitude at r and time t is de®ned as athree-dimensional vector s(r,t)  [sx (r,t),sy (r,t),sz (r,t)]. The
estimate of the source moment is denoted as ^s(r,t). We
de®ne lx j (r), ly j (r) and 1z j (r) as the jth sensor output when asingle source exists at r with the unit moment directed in
the x, y, and z directions, respectively. We then de®ne thelead ®eld matrix L(r) as a matrix whose jth row is equal to[lx j (r),ly j (r),z j (r)]; this lead ®eld matrix represents the sensitivity of the whole sensor array at r.
The vector beamformer technique reconstructs thesource moment by applying the following linear operation:

MATERIALS AND METHODS

where the matrix W(r) is a weight matrix de®ned as
W(r)  [wx (r),wy (r),wz (r)], and the weight vectors wx (r),wy (r) and wz (r) detect the x, y, and z components of thesource moment, respectively. Let us de®ne the measurement covariance matrix as D, and de®ne the three-dimensional unit column vector as fx , fy , and fz . The weightvectors in an intermediate stage are ®rst obtained using

Six healthy adults (three females, three males; age 25±30
years, mean 28) were studied. Informed consent was
obtained prior to the study. Brief electrical stimuli with
0.2 ms duration were delivered to the right posterior tibial
nerve at the ankle (cathode proximal) with a repetition rateof 4 Hz. The stimulus intensity was three times sensory
threshold and elicited a mild twitch of toe. Magnetic
recordings (bandpass 0.1±1200 Hz) were taken from thevertex centering at Cz of the international 10-20 systemwith a 37-channel SQUID gradiometer (BTi Magnes, San
Diego, CA) in a magnetically shielded room. The detection
coils of the gradiometer are arranged in a uniform,
concentric array on a spherical surface with a radius of
122 mm; each coil measures 20 mm in diameter. The
sensors are con®gured as ®rst-order axial gradiometerswith a baseline ofp50 mm. The ®eld sensitivities of thesensors were 10 fT/ Hz or better.
An epoch of 60 ms duration (10 ms pre- and 50 ms poststimulus) was digitized at a 4000 Hz/channel sampling
rate and 10 000 responses were averaged off-line. DC offset
was based on the pre-stimulus period.
The origin of the head-based co-ordinate system wasde®ned as the midpoint between the pre-auricular points.
The x-axis pointed from the origin to the nasion, the y-axis
to the left pre-auricular point, and the z-axis to the vertex
in a direction perpendicular to the x-y plane. Magnetic
resonance imaging (MRI) was acquired with spherical lipid
markers (5 mm diameter) placed on the MEG ®duciarypoints to allow for superposition of source locations onto
the MRI slices. A local spherical model was ®tted to thedigitized head shape over the recording area for eachsubject.
Data analysis: The MEG vector beamformer technique
was applied to localize sources from the P37m component.
The results of the analysis were shown as current-density
maps for transverse, coronal and sagittal sections of thegeneric head. Furthermore, the highest current sources forthe two activation areas were overlaid on the MRI slices.
The details of this vector beamformer technique havebeen reported elsewhere [7,8], so it is only brie¯y described
here. Let us de®ne the magnetic ®eld measured by the mth
sensor at time t as bm (t), and a column vectorb(t)  [b1 (t),...,bm (t)T as a set of measured data. Here M isthe total number of sensors and the superscript T indicatesthe matrix transpose. A spatial location (x,y,z) is represented by a three-dimensional vector r: r  (x,y,z). The

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Vol 12 No 9 3 July 2001

^s(r, t)  WT (r)b(t)wì (r) 

Dÿ1 L(r)[LT (r)Dÿ1 l(r)]fì
p T
f ì Ùfì

(1)(2)

where ì  x, y, or z, andÙ  [LT (r)Dÿ1 L(r)]ÿ1 LT (r)Dÿ2 L(r)[LT (r)Dÿ1 L(r)]ÿ1
Let us de®ne Es as a matrix whose columns consist of thesignal-level eigenvectors of D. Then, the ®nal form of theweight vectors are obtained by projecting the weight vector
eì onto the signal subspace of the measurement covariancematrix, i.e.
wì (r)  Es E Ts wì (r):(3)

Then the source moment at r is estimated using eqn (1)with the weight vectors obtained using eqns (2) and (3).
Note that when calculating the above weight vectors, thelocation r is a controllable parameter. Therefore, thesource-moment distribution can be reconstructed by scanning the beamformer output over the region of interest in acompletely post-processing manner. Because this reconstruction is performed at each instant in time, the spatiotemporal reconstruction of the source activities can beobtained.

RESULTS

Figure 1 illustrates P37m in an extended time scale (upper
traces) recorded over foot somatosensory region in the left
hemisphere. The magnetic signals start 30 ms after the rightposterior tibial nerve stimulation. The P37m peak occurs at
34 ms. The current±density maps produced by applicationof the beamformer technique to the MEG data revealed
initial activation in the anterior part of S1 foot area at
33.1 ms (a sampled point shown by a red dotted line on the
superimposed SEF traces at the top), followed by coactivation of the posterior part of S1 cortex at 36.2 ms(indicated by a green line; Fig. 1). At 1 ms later (37.2 ms),
the posterior activation became dominant (indicated by ablue line) and at about 2 ms thereafter (39.1 ms, black line),NEUROREPORTDYNAMIC ACTIVATION OF 2 AREAS DURING P37M PRIMARY RESPONSE

amplitude (fT)

100
0
2100
20

25

30

L

5

35
latency (ms)

40

12

12
L

8

(cm)

(cm)

(cm)

R
0

4
25

L

12

0

L

8

(cm)

(cm)

(cm)

12
R

25

8
36.2 ms

4

R

(cm)

12

0

R

12

L

8

(cm)

L

5
(cm)

33.1 ms

4

4

4
25

8
37.2 ms

4

R
L

5

12

12

0

L

8

(cm)

(cm)

R
(cm)

8

R

5

4
25

45

25

R
0

5
(cm)

10

210

8
39.1 ms

4
25

0
(cm)

5

25

0

5

10

(cm)

Fig. 1. Current±density maps during P37m for right posterior tibial nerve stimulation in one subject. Superimposed traces at the top of the ®gureillustrate P37m in an extended time. The contour maps show reconstructed source magnitude distributions at four different latencies. The
reconstruction grid spacing was set at 1 mm. The maximum intensity projections onto the axial (left column), coronal (middle column), and sagittal(right column) directions are shown. The letters L and R in the coronal views indicate the left and right hemispheres, respectively. The circles depicting
a human head show the projections of the sphere used for the forward modeling. The colors of contours represent the relative intensity of the source
magnitude; the relationship between the colors and relative intensities is indicated by the color bar. The current-density maps revealed initial activationin the anterior part of SI foot area at 33.1 ms (a sample point shown by a red dotted line on the SEF traces at the top), followed by co-activation of theposterior part of S1 cortex at 36.2 ms (indicated by a green line). At 1 ms later (37.2 ms), the posterior activation became dominant (indicated by a blueline) and at about 2 ms thereafter (39.1 ms, black line), the initial anterior activation completely disappeared.

the initial anterior activation completely disappeared (Fig.
1). In all subjects, anterior activation was followed byposterior activation. Thus, the intensities of the two sources
varied as a function of time. Figure 2 shows co-registrationof MEG sources and MRI in which the anterior source wasin area 3b and the posterior source was in an area near themarginal sulcus (marginal ramus of the cingulate sulcus).
The spatial and temporal relations between the twosources are summarized in Table 1. In order to facilitatecomparison between individual subjects with different
lengths of conduction pathways, the time origin was set atthe peak of P37m. Similarly, the spatial origin was set atthe location of the anterior source with the highest current
source density. With these normalization processes, large
interindividual anatomical variations documented for thecentral sulcus and the marginal sulcus with respect to thehead co-ordinate system can be minimized. The averagelatency ( s.d.) when the intensities of the two sourceswere equal was 2.6  2.4 ms after the peak of P37m. The
latency when the anterior source disappeared and only theposterior source was present was 5.0  3.1 ms following theP37m peak. Compared with the early anterior source, theVol 12 No 9 3 July 2001

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NEUROREPORTI. HASHIMOTO ET AL.

Fig. 2. Superimposition of P37m sources on MRI for the data presented in Fig. 1. The anterior source indicated by a solid circle was in area 3b, andthe posterior source indicated by a square was in an area near the marginal sulcus (marginal ramus of the cingulate sulcus). The bars originating fromthe source locations indicate the moment directions of these sources. From the left to right are axial, coronal and sagittal slices of the MRI. On thecoronal slice, left hemisphere is shown on the right as in Fig. 1.

Table 1. Spatial and temporal relationships between the anterior and posterior sources during P37m for posterior tibial nerve stimulation.
Subject

Latencya when the twosources are equal inintensity (ms)

Latencya when only the Äxb (mm)posterior source ispresent (ms)Äyb (mm)Äzb (mm)

Totalb distance
between the twosources (mm)

1
2
3
4
5
6
Mean
s.d.

2.90
2.40
ÿ0.30
2.50
0.94
6.70
2.57
2.37

5.10
4.00
3.30
4.90
1.94
11.0
5.04
3.14

ÿ1.7
6.7
ÿ0.8
1.7
3.6
3.8
2.2
3.1

2.0
ÿ1.5
2.3
6.7
2.1
1.0
2.1
2.7

6.9
10.1
12.1
10.5
15.8
19.4
12.5
4.5

a
b

ÿ6.3
ÿ7.6
ÿ10.7
ÿ8.0
ÿ15.3
ÿ19.0
ÿ11.2
5.0

The time origin was set at the peak of P37m.
The spatial origin was set at the location of the anterior source.

and that of the posterior source was toward contralateralposterior direction.

later posterior source was located 11.2  5.0 mm posterior,
2.2  3.1 mm lateral, and 2.1  2.7 mm higher. The mean
total distance between the two sources was 12.5  4.5 mm.
Table 2 shows orientations of the anterior and posteriorsources for all subjects. The mean orientation of theanterior source was directed toward the right hemisphereDISCUSSION

Previous MEG studies have shown a systematic rotation ofsource currents in the foot somatosensory cortex after

Table 2. The orientation of the anterior and posterior sources. The x, y, and z components of the normal vectors representing these orientations
are shown.
Subject

1
2
3
4
5
6
Mean
s.d.
a

Anterior source orientation
x

y

z

x

y

z

ÿ0.47
ÿ0.17
0.91
ÿ0.53
ÿ0.66
ÿ0.67
ÿ0.26
0.60

ÿ0.86
ÿ0.97
ÿ0.41
ÿ0.83
ÿ0.75
ÿ0.72
ÿ0.76
0.19

0.20
0.15
0.10
0.15
0.05
0.16
0.14
0.05

ÿ0.92
ÿ0.95
0.66
ÿ0.81
ÿ0.88
ÿ0.82
ÿ0.62
0.63

ÿ0.37
ÿ0.26
ÿ0.71
0.52
ÿ0.22
0.31
ÿ0.12
0.45

0.05
ÿ0.16
0.22
ÿ0.26
ÿ0.43
ÿ0.48
ÿ0.18
0.27

The angle between the two orientations.

1860

Anglea 8

Posterior source orientation

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41
67
23
92
44
75
57
25

DYNAMIC ACTIVATION OF 2 AREAS DURING P37M PRIMARY RESPONSE

posterior tibial nerve stimulation [4±6]. For the left posterior tibial nerve stimulation, the rotation was counter-clockwise starting approximately from 9 o'clock, and for theright stimulation it was clockwise beginning at 15 o'clock,suggesting initial activation at the mesial surface of thecortex. The present study supports the above ®ndings.
Such observations imply time-varying shifts in the centerof gravity of cortical activation in an enfolded corticalsurface.
Hari et al. [6] studied, posterior tibial nerve SEFs withapplication of the two-dipole time-varying source model inwhich the two dipoles with ®xed locations and orientations
were allowed to change their signal strengths as a functionof time. Our data seem to support the above two-dipole
assumption for SEFs for the posterior tibial nerve stimulation. However, it is also possible that the assumption of thetwo dipoles being ®xed in locations and orientations may
not always be physiologically valid. For example, it has
been shown recently that an equivalent current dipole(ECD) for N20m primary response to median nerve [10] orindex ®nger [11] stimulation moves serially from medial tolateral direction in area 3b.
Moreover, in general, it is not possible to detect these
two sources by using the two-dipole search method. The
prerequisite for the two-dipole method is that two sourcesmust exist at each time point, and this prerequisite was notalways met in the posterior-tibial SEFs as we have shownin the present study. For example, in Fig. 1, a single source
is present at the latency of 33.1 ms. When we applied thetwo-dipole search method for the ®eld data at this latency,
we obtained one dipole precisely at the location of the peakin the contour map and the other near the center of thesphere with the goodness of ®t greater than 0.99. When weapplied the two-dipole search method for the data at
36.2 ms, we could successfully obtain two dipoles exactly
at the two peak locations in the contour map with thegoodness of ®t greater than 0.99. However, this success isdue to the fact that we know a priori from the beamformer
analysis that the two sources exist at this time slice. Without this knowledge, we might set the number of dipoles
more than two and such a multi-dipole search would
surely give a false source con®guration with a high valueof goodness of ®t. We believe that the multi-dipole searchmethod is hardly an effective method because we must
know exactly the value of the model parameter (the number of dipoles), which is generally unknown. On the other
hand, the beamformer method can reconstruct the multiple
source activities without requiring such information andcan be effective in the situations where the multi-dipole
method fails.
The MEG vector beamformer technique can provide
information on temporal and spatial behavior of multiple
nearby sources simultaneously and sequentially active,
since this technique is basically free from the constraints ofthe dipole modeling. The present results are generally inline with the temporal activation patterns of the twosources described by Hari et al. [6]; anterior activation
precedes posterior activation. However, because of theassumption of ®xed dipoles, the relative distance of thetwo sources was left unknown.
The anatomical distance between the central sulcus andthe marginal sulcus is presumably about 1.5 cm [1]. Given

NEUROREPORT

that the anterior source is in area 3b, the mean distance of
1.3 cm between the anterior and posterior sources willplace the posterior source at or near the marginal sulcus in
the area of paracentral lobule. Since the ®eld patterns
rotated systematically in previous studies [4±6], it isreasonable to assume activation in a ®ssure located posterior to the central sulcus. Hari et al. [6] speculated that theactivation took place in area 5 in the anterior wall of themarginal sulcus. They also argue that area 3b in the mesial
wall extends very closely to the marginal sulcus, directly
abutting on area 5.
With similar types and density of mechanoreceptors
responding to tactile air-puff stimulation of foot [12], ascompared with those of the hand [13] and face [14], it ismore likely that the S1 area receiving projection from thefoot is organized in a similar manner as the hand and face
S1 cortex (see Brodmann's map [15] of the mesial wall of
the hemisphere). Thus, we suggest that foot S1 area
consists of 3a, 3b, 1, and 2, not unlike the hand and face S1.
Because the timing of activation of the two sources was
only a few ms apart, it is unlikely that somatosensory
association area 5 is the generator of the posterior source[16,17]. It is plausible that areas 1 and 2 may be locatedanterior to or at the marginal sulcus. Furthermore, therotation phenomenon of the ®eld patterns after posterior
tibial nerve stimulation can also be explained by theactivity in this sulcus. However, the cytoarchitectonic areasof the human foot S1 have been poorly delineated histologically, and thus the precise cytoarchitectonic area generating the posterior source is still an open question and needs
more detailed studies integrating anatomical and neurophysiological data.

CONCLUSION

The MEG vector beamformer technique applied to SEFs
after the posterior tibial nerve stimulation revealed two
distinct sources, one in area 3b and another near themarginal sulcus, which are sequentially and simultaneously active during P37m primary response. Because
cortical ®ssures and gyri in the mesial surface of the brain
are both tangential to the scalp, this cortical area ofparacentral lobule receiving projections mainly from thefoot is uniquely situated for the MEG study of earlysomatosensory processing.

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Acknowledgements: This research was supported by a Grant-in-Aid for Scienti®c Research from the Ministry of Education,
Science and Culture of Japan (09877185) and a Grant-in-Aid of the Japan Medical Association (1998). One of the authors (K.S.)
was supported by a research project `Mind Articulation' sponsored by Japan Science and Technology Corporation.

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