Clinical Neurophysiology 132 (2021) 382–391

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Clinical Neurophysiology
journal homepage: www.elsevier.com/locate/clinph

Noninvasive measurement of sensory action currents in the cervical cordby magnetospinography
Miho Akaza a, Shigenori Kawabata b,⇑, Isamu Ozaki c, Yuki Miyano d, Taishi Watanabe d, Yoshiaki Adachi e,
Kensuke Sekihara b, Yuki Sumi a, Takanori Yokota faRespiratory and Nervous System Science, Biomedical Laboratory Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45
Yushima, Bunkyo-ku, Tokyo 113-8519, Japanb
Department of Advanced Technology in Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku,
Tokyo 113-8519, Japanc
Department of Physical Therapy, Faculty of Health Sciences, Aomori University of Health and Welfare, 58-1 Mase, Hamadate, Aomori 030-8505, Japand
Healthcare Business Group, RICOH Company, Ltd., 2-3-10 Kandasurugadai Chiyoda-ku, Tokyo 101-0062, Japane
Applied Electronics Laboratory, Kanazawa Institute of Technology, 7-1 Ogigaoka, Nonoichi, Ishikawa 921-8501, Japanf
Department of Neurology and Neurological Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku,
Tokyo 113-8519, Japana r t i c l e

i n f oArticle history:
Accepted 6 November 2020
Available online 19 December 2020
Keywords:
Magnetospinography
Superconducting quantum interference
device (SQUID)
Evoked magnetic fieldDorsal column
Dorsal horn
Somatosensory evoked potential

h i g h l i g h t s
 Neural activity in the cervical cord and root evoked by median nerve wrist stimulation can be visual-ized by magnetospinography.
 Dorsal horn excitatory postsynaptic activity can also be identified by magnetospinography.
 Magnetospinography provides useful information for the functional electrophysiological diagnosis ofsomatosensory pathways.

a b s t r a c t
Objective: To obtain magnetic recordings of electrical activities in the cervical cord and visualize sensory
action currents of the dorsal column, intervertebral foramen, and dorsal horn.
Methods: Neuromagnetic fields were measured at the neck surface upon median nerve stimulation at thewrist using a magnetospinography system with high-sensitivity superconducting quantum interference
device sensors. Somatosensory evoked potentials (SEPs) were also recorded. Evoked electrical currents
were reconstructed by recursive null-steering beamformer and superimposed on cervical X-ray images.
Results: Estimated electrical currents perpendicular to the cervical cord ascended sequentially. Theirpeak latency at C5 and N11 peak latency of SEP were well-correlated in all 16 participants (r = 0.94,
p < 0.0001). Trailing axonal currents in the intervertebral foramens were estimated in 10 participants.
Estimated dorsal–ventral electrical currents were obtained within the spinal canal at C5. Current density
peak latency significantly correlated with cervical N13–P13 peak latency of SEPs in 13 participants(r = 0.97, p < 0.0001).
Conclusions: Magnetospinography shows excellent spatial and temporal resolution after median nerve
stimulation and can identify the spinal root entry level, calculate the dorsal column conduction velocity,
and analyze segmental dorsal horn activity.
Significance: This approach is useful for functional electrophysiological diagnosis of somatosensory
pathways.
Ó 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. This is an open
access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Abbreviations: SCEF, spinal cord evoked magnetic fields; SEP, somatosensory evoked potential; MSG, magnetospinography; SQUID, superconducting quantum interference
device; DSSP, dual signal subspace projection; UGRENS, unit gain constraint recursively applied null-steering spatial filtering.
⇑ Corresponding author at: Department of Advanced Technology in Medicine, Graduate School of Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo
113-8510, Japan.
E-mail addresses: m-akaza.nuro@tmd.ac.jp (M. Akaza), kawabata.orth@tmd.ac.jp (S. Kawabata), isamu_ozaki@icloud.com (I. Ozaki), yuki.yh.hasegawa@jp.ricoh.com(Y. Miyano), taishi.watanabe@jp.ricoh.com (T. Watanabe), k-sekihara@nifty.com (K. Sekihara), ysumi.pulm@tmd.ac.jp (Y. Sumi), tak-yokota.nuro@tmd.ac.jp (T. Yok.
https://doi.org/10.1016/j.clinph.2020.11.029
1388-2457/Ó 2020 International Federation of Clinical Neurophysiology. Published by Elsevier B.V.
This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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M. Akaza, S. Kawabata, I. Ozaki et al.

1. Introduction

permits evaluation of the dorsal column volley, dorsal horn excitatory postsynaptic activity, and action potentials at the dorsal root
entry zone.
Therefore, in the present study, we attempted to measure themagnetic field at the neck in response to electrical stimulation of
the median nerve at the wrist and reconstructed the chronologicalcurrent distribution in the cervical cord to visualize the ascending
volley along the dorsal column, dorsal horn excitatory postsynaptic
activity, and action potentials at the dorsal root entry zone. We
also recorded conventional SEPs at the skin surface of the anterior
and posterior neck regions with a non-cephalic montage to determine the relationship between the cervical N11 potential and thedorsal column activity reconstructed from magnetic fields or
between dorsal horn activity, including the posterior neck N13
potential and anterior neck P13 potential, and its magnetic counterpart that may be localized within the spinal cord.

Paresthesia and sensory deficit of the hands are some of themost common symptoms of both cervical spinal cord diseases
and peripheral neuropathies. Although conventional noninvasive
electrophysiological techniques such as somatosensory evoked
potentials (SEPs) are useful for detecting functional abnormalitiesof the somatosensory pathways, they are incapable of assessing
the exact site of conduction failure in the dorsal column. The
ascending dorsal column activity after median nerve stimulation
at the wrist can be detected as a small positive potential (P11) thatis recorded from the scalp with reference to the hand, shoulder, or
clavicle contralateral to the stimulation (a non-cephalic montage)
and that culminates at around 11 ms after the stimulus (Craccoand Cracco, 1976; Cruccu et al., 2008; Desmedt and Cheron,1980). This activity corresponds to a small negative potential(N11) that is recorded at the skin surface of the posterior neck witha non-cephalic montage (Desmedt and Cheron, 1980; Desmedt andNguyen, 1984). However, this near-field N11 potential is often illdefined because it appears during the transition from a positive
potential of the brachial plexus origin (P9) to a negative potentialof the dorsal horn origin (cervical N13). Furthermore, the P11
potential is reported to be indiscernible in about one-third ofhealthy individuals (Ozaki et al., 1994; Tanosaki et al., 1999), probably because the electrophysiological heterogeneity of the surrounding vertebral bones and soft tissues may distort theextracellular current distribution of the action potential.
In contrast to potential recording, magnetic recordings are notinfluenced by the bone and skin (Hashimoto et al., 1991; Trahms
et al., 1989). This results in magnetic distributions with a smaller
spatial extent. Since 1999, our group has been working on magnetospinography (MSG) to noninvasively assess spinal cord and deep
nerve dysfunction. There have since been several reports on animal
experiments concerning neuromagnetic fields of the cervical spinal
cord after stimulation of the lower thoracic cord, called cervicalspinal cord evoked magnetic fields (cervical SCEFs), which demonstrate propagation of ascending volleys along the spinal cord andconduction block at the experimental cord lesion in cats
(Kawabata et al., 2002) and rabbits (Tomori et al., 2010). Ascending
volleys and synaptic activity in the lumbar spinal cord have also
been distinguished by analyzing SCEFs after stimulation of the sciatic nerve in rabbits (Tomizawa et al., 2008). In addition, Sumiya
et al. (2017) successfully recorded cervical SCEFs at the body surface in humans after stimulation of the lower thoracic cord with
an epidural electrode to estimate the current constitution of thenerve impulse that travels along the cervical cord. Moreover, theresults of cervical SCEFs in a patient with cervical spondylotic
myelopathy that were overlaid on the patient’s cervical X-ray
image showed that the site of the impulse travel failure coincidedwith the site of cervical spinal stenosis, demonstrating that MSG
can be clinically applied to spinal cord functional tests (Sumiya
et al., 2017).
However, to expand the clinical application of cervical SCEFs, anoninvasive procedure would be preferred, particularly one thatavoids the need for epidural electrode insertion. For examinationof upper limb stimulation, electrical stimulation at the elbow
might be more useful than stimulation at the wrist for recording
sufficiently large signals of cervical SCEFs. Thus, in their study,
Sumiya et al. (2017) attempted to record cervical SCEFs after electrical stimulation of the median nerve at the elbow in healthy individuals and were able to delineate the ascending volley along thedorsal column and action potentials at the dorsal root entry zone
as chronological current constitution maps that were estimatedfrom the cervical SCEFs. However, it remains to be determined
whether median nerve stimulation at the wrist in healthy individuals can evoke cervical SCEFs with a high signal-to-noise ratio that

2. Methods
2.1. Standard protocol approvals, registration, and patient consent
This study was approved by the Ethics Committee of Tokyo
Medical and Dental University of Medicine (#M2000-1229). All
participants provided written informed consent.
2.2. MSG system
All recordings were performed using a multichannel superconducting quantum interference device (SQUID) biomagnetometersystem developed by the Applied Electronics Laboratory, Kanazawa Institute of Technology (Adachi et al., 2017). The device isequipped with an array of 44 SQUID magnetometers arranged in
an area of 180 mm  130 mm (Fig. 1A) along the cylindrical surface
with a 200-mm radius, as shown in Fig. 1B. Vector-type SQUID
magnetometers, which simultaneously detect three orthogonalcomponents of magnetic fields (Fig. 1D), were applied to extract
as much magnetic field information from the observation area as
possible. The sensors positioned at the four corners of the sensor
array marked in gray-filled circles in Fig. 1a detected only the Zcomponent of the measurements from some of the participants
due to the limit in the number of data acquisition channels. The
noise level in the white noise region was typically less than
4 fT/Hz0.5.
A cryostat was specifically designed to maintain the SQUID sensors in their superconducting state (Fig. 1C). It has a cylindricalmain body to store liquid helium and a protrusion from its sidesurface. The sensor array was installed along the upper surface ofthe protrusion and oriented upward to detect the biomagnetic fieldalong the back surface of participants in the supine position. In thisarticle, the x-, y-, and z-directions were considered to be oriented
from the left to right, from the caudal to cranial, and from the ventral to dorsal side of the body, respectively.
2.3. Signal processing
Although artifacts due to the electrical stimulation during themeasurement often make it difficult to analyze the signal in theearly latency period after stimulation, the artifact-removal methoddual signal subspace projection (DSSP) (Sekihara et al., 2016) wasable to effectively suppress artifacts. Unit gain constraint recursively applied null-steering spatial filtering (UGRENS) (Kumihashi
and Sekihara, 2010; Sekihara and Nagarajan, 2015) was adapted
to the acquired magnetic field data to reconstruct the spatial distribution of the current density around the spinal cord. The reconstructed current distribution obtained was superimposed on an383

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Clinical Neurophysiology 132 (2021) 382–391

Fig. 1. Appearance and structure of the magnetospinography system. (A, B) The device is equipped with an array of 44 superconducting quantum interference device(SQUID) magnetometers arranged in an area of 180 mm  130 mm along the cylindrical surface with a 200-mm radius. The sensors positioned at the four corners of thesensor array marked using gray-filled circles detected only the Z-component during the measurement of some of the participants due to the limit on the number of dataacquisition channels. The noise level in the white noise region is typically less than 4 fT/Hz0.5. (C, D) The cryostat to maintain the SQUID sensors in their superconducting state
has uniquely designed vector-type SQUID magnetometers, which simultaneously detect three orthogonal components of the magnetic fields and are applied to extract the
maximum possible amount of magnetic field information from the observation area. It has a cylindrical main body to store liquid helium and a protrusion from its sidesurface. The sensor array is installed along the upper surface of the protrusion oriented upward to observe the biomagnetic field along the back surface of participants in thesupine position. (E, F) X-ray images in the frontal view (E) and lateral view (F) show the relationship between the sensors and the participant in Experiment 1. (G, H) X-ray
images in the frontal view (G) and lateral view (H) show the relationship between the sensors and the participant in Experiment 2.

2019; Watanabe et al., 2019; Sasaki et al., 2020). Two thousand
responses from 5 to 30 ms after the stimulation were averaged
to improve the signal-to-noise ratio and the evoked action currents
were reconstructed by the above-mentioned spatial filter—a recursive null-steering (RENS) beamformer—and superimposed on an Xray image of each participant’s cervical spine.

X-ray image for coregistration with morphological information.
The position of the spinal cord relative to the sensor array wasdetermined based on the lateral X-ray image. The depth of thesource was estimated using the distance between the midpointof the spinal canal and the center of the sensor array. The reconstructed current can be obtained from the magnetic field distribution at each measured time point. According to this method, it ispossible to display a temporal change in the current intensity at
any location, such as the spinal canal or the foramen, in a specifictime domain as a waveform as if a virtual electrode was placed
there.

2.5. Experiment 2. Recording of the magnetic field from the right sideof the neck in response to electrical supramaximal median nerve
stimulation at the wrist
Thirteen healthy volunteers aged 25–42 years (mean ± SD, 33.2 ±5.5 years) and measuring 156–178 cm in height (mean ± SD, 168.4 ± 6.
4 cm) participated in Experiment 2. Because the dorsal horn excitatory postsynaptic activity runs from dorsal to ventral, recordings
were performed with the participants in the right lateral decubitus
position. The relationship between the sensors and the participant
is shown in Fig. 1G and H. The distance between the sensors andthe cervical cord was minimized. Neuromagnetic fields were measured at the surface of the right-side neck in response to electricalsupramaximal stimulation (duration, 0.3 ms at 2–5 Hz) of the rightside median nerve at the wrist. Evoked responses were acquired ata sampling rate of 40 kHz with 10 Hz to 5 kHz analog band-pass filtering. In contrast to Experiment 1, the high-frequency band-pass filter
was set to 10 Hz to evaluate the dorsal horn excitatory postsynaptic
activity. Two thousand responses from 5 to 30 ms after the
stimulation were averaged, and evoked action currents were reconstructed by a spatial filter—a RENS beamformer—and superimposedon a lateral X-ray image of each participant’s cervical spine, as inExperiment 1.

2.4. Experiment 1. Recording of the magnetic field from the surface ofthe posterior neck in response to electrical supramaximal median
nerve stimulation at the wrist
Sixteen healthy volunteers aged 25–42 years (mean ± SD, 33.5
± 5.5 years) and measuring 156–182 cm in height (mean ± SD,
169.2 ± 7.0 cm) participated in Experiment 1. Recordings were performed with the participants in the supine position. The relationship between the sensors and the participant is shown in Fig. 1E
and F. The distance between the sensors and the cervical cord
was minimized. Neuromagnetic fields in response to electricalsupramaximal stimulation (duration, 0.3 ms at 2–5 Hz) of theright-side median nerve at the wrist were measured at the surfaceof the posterior neck using the above-mentioned MSG system.
Evoked responses synchronized with the stimulation wereacquired at a sampling rate of 40 kHz with 100 Hz to 5 kHz analog
band-pass filtering. The high-frequency band-pass filter was set to
100 Hz to eliminate artifacts and evaluate axonal electrical activity
in the dorsal column. Our group previously reported that, with thissetting, intra-axonal currents and inward volume currents at the
depolarization site could be evaluated in the cervical cord andperipheral nerves in the cauda equina, brachial plexus, and median
nerve around the carpal tunnel (Sumiya et al., 2017; Ushio et al.,2.6. SEP recording
Immediately before each magnetic field measurement, a conventional SEP with the same stimulus setting was also recorded384

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M. Akaza, S. Kawabata, I. Ozaki et al.

in the supine position for reference. The SEP recording electrodes(impedance, <5 kX; filter bandpass, 20–2000 Hz) were set at theright–left Erb’s point, C5 posterior (C5S)–left Erb’s point, and C5
posterior–anterior cervical (AC) derivation. In three participants,
a C30 (2 cm posterior to C3)–Fz montage, C30 –left Erb’s point montage, and Fz–left Erb’s point montage were also recorded. Morethan 300 responses were averaged, and the SEP measurement
was repeated at least twice to confirm reproducibility. An
MEB2300 neuropack device (Nihon Kohden, Tokyo, Japan) wasused to record SEPs and stimulate the nerve for the MSG and SEP
measurement.

3. Results
3.1. Experiment 1. Recording of the magnetic field from the surface ofthe posterior neck in response to electrical supramaximal median
nerve stimulation at the wrist
SCEFs were successfully recorded in all 16 healthy participants.
The SCEFs indicated two to four phasic waveforms and Fig. 3 shows
the three-directional magnetic fields recorded by each sensor in a
representative participant (HC1, a 34-year-old man). The reconstructed current distribution is displayed as a pseudocolor map
superimposed on an X-ray image of the participant’s cervical spine.
Fig. 4 shows a representative case (HC1); at a latency of 9.7 ms,
leading axonal currents flowed into the C5 to C7 intervertebral
foramen. At 10.3 ms, the leading axonal currents flowed into thespinal canal. Then, at 12.7 ms, trailing axonal currents, which were
caudally directed, appeared in the intervertebral foramen. Following the leading axonal currents, currents flowing perpendicular tothe spinal cord, indicating an inward volume current at the depolarization site in the dorsal column fibers, appeared at around theC7 level and propagated toward the cranium from 11.5 ms to12.1 ms after the stimulus. The current waveforms were retrieved
from the virtual electrodes at each vertebral level at the midline of
the cervical spinal canal and the 2-cm lateral line. In Fig. 5 (HC1),
the upper black traces represent SEP waveforms recorded with a
C30 –Fz montage, C30 –left Erb’s point montage, Fz–left Erb’s pointmontage, and C5S–left Erb’s point montage. A waveform recordedwith a C5 posterior–left Erb’s point montage showed a small N11
potential during the transition from the P9 potential of the brachial
plexus origin to the cervical N13 potential of the dorsal horn origin.
The lower waveforms represent the currents flowing perpendicular
to the spinal cord, with the inward volume current at the depolarization site in the dorsal column at each positioned marked by virtual electrode. The shifts in the peak latencies of the waveforms
indicated that the estimated reconstructed inward volume currents at the depolarization site in the dorsal column ascended
sequentially along the spinal canal. The peak latency of the reconstructed electrical current C5 (solid red arrowhead) was almost thesame as that of the N11 potential of the SEPs. Moreover, the peaklatency of the reconstructed electrical current at C5 and the peaklatency of the N11 SEP component recorded with a C5S–left Erb’s
point montage were well-correlated in all 16 participants(r = 0.94, p < 0.0001) (Fig. 6). Whereas the conduction velocity of
the ascending volley could not be obtained from conventional
SEP analyses, the conduction velocity of the ascending volley calculated from the peak latency of the reconstructed electrical current
at the C5–6 virtual electrode could be evaluated and ranged from
53.9 to 75.9 m/s (n = 10; average, 63.1 ± 7.5 m/s).
In 10 of the 16 participants, the electrical activities in the intervertebral foramens (C4/5 to T1/2) were also evaluated with a trailing current because the inward volume currents at the
depolarization site spread centripetally in the intervertebral foramen and because confronting currents produce magnetic fields
that cancel each other out; the leading current can even pass at
the clipped point, according to our previous findings (Fukuoka
et al., 2004). Reconstructed currents at the adjacent intervertebral
foramen (C4/5 to T1/2) are shown in Fig. 7A (from a representative
case: HC2, a 39-year-old woman). The trailing axonal currents in
the intervertebral foramens were estimated in all 10 of the participants. Each individual variation in the peak trailing axonal current
density flowing into the intervertebral foramens is shown in Fig. 7B(HC2–11). The currents were largest at the C6/7 intervertebral
foramen (outlet of root C7) or the C7/T1 intervertebral foramen(outlet of root C8) in most participants.

2.7. Analysis
When a nerve is electrically stimulated, transmembrane ioniccurrents are generated at the depolarization site in the nerve.
Accordingly, intra-axonal and inward volume currents at the depolarization site are derived from the voltage difference between the
depolarization site and surrounding tissue (Fig. 2). These intraaxonal and inward volume currents are the origin of magnetic
fields. Their intensity and direction are based on Ampère’s circuitallaw. In this article, we define the forward intra-axonal current as
the leading current and the backward intra-axonal current as thetrailing current.
Based on previous work (Fukuoka et al., 2002, 2004), the negative peak of the action potential in the nerve is equivalent to theinward volume current at the depolarization site. Therefore, tocompare dorsal column current activity estimated from magnetic
field measurement and the cervical N11 in SEPs, the timing of
the inward volume current at the depolarization site flowing perpendicular to the spinal cord was compared with the SEP N11 negative peak in the C5S–left Erb’s point derivation. The posteroanterior electrical current estimated from magnetic recordings
was compared with the peak latency of the cervical N13 potential
in the C5S–AC derivation. Electrical activity in the intervertebral
foramen was evaluated using the trailing current because theinward volume currents at the depolarization site spread centripetally in the intervertebral foramen and because confronting
currents produce magnetic fields that cancel each other out; theleading current can pass, even at the clipped point, according toour previous findings (Fukuoka et al., 2004).
Linear regression analysis was performed to confirm the correlation between the estimated electrical current and the SEP.
P values less than 0.05 were considered significant. All statistical analyses were performed using GraphPad Prism 5.0 for Windows (GraphPad Software, San Diego, CA).

Fig. 2. Schema of the electrical currents during nerve conduction.

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Clinical Neurophysiology 132 (2021) 382–391

Fig. 3. Magnetic fields measured from the surface of the posterior neck in response to electrical supramaximal median nerve stimulation at the wrist. (A) Positions of
the sensors superimposed on an X-ray image of a participant. (B) The three-directional magnetic fields recorded by each sensor (a representative case: HC1, a 34-year-oldman). The black traces are magnetic fields in the ventral–dorsal direction relative to the cervical spinal cord (ventral is upward in the graphs). The red traces are magnetic
fields in the left–right direction (right is upward). The green traces are magnetic fields parallel to the spinal cord (cranial is upward). Some malfunctioning pickup coils show aflat line. The red signals, mainly generated from intra-axonal currents, are highest above the spinal cord. The polarity of the black and green signals is reversed on each side of
the spinal cord. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 4. Reconstructed currents estimated from the magnetic field measured from the surface of the posterior neck in response to electrical supramaximal median
nerve stimulation at the wrist. Reconstructed current map (a representative case: HC1, a 34-year-old man). Currents at the level of the spinal canal are reconstructed by arecursive null-steering beamformer and superimposed on an X-ray image. The current intensity is shown by a color scale (where red is high). Small white arrows indicate
current vectors. The leading component of the currents (large upward-pointing red arrow) appears 9.7 ms after stimulation and propagates cranially along the spinal canal. At
12.7 ms, the trailing component (downward-pointing red arrow) appears on the caudal side. Perpendicular currents (blue arrows) flowing toward the spine between theleading and trailing components are also observed on both sides. (For interpretation of the references to colour in this figure legend, the reader is referred to the web versionof this article.)

structed current distribution in a representative participant(HC1) 13.2 ms after stimulation is displayed as a pseudocolor
map superimposed on an X-ray image of the cervical spine. The virtual electrodes, C5 posterior (C5S) electrode, and AC electrode aredisplayed on the lateral X-ray images of the participant. The upper
traces are SEPs recorded with a C5S–AC montage that show thecervical N13–P13 potential generated by an excitatory postsynaptic potential at the dorsal horn. The lower waveforms show the

3.2. Experiment 2. Recording of the magnetic field from the surface of
the unilateral neck in response to electrical supramaximal median
nerve stimulation at the wrist
SCEFs were successfully recorded in all 13 healthy participants.
The magnetic fields indicated two to four phasic waveforms andFig. 8 shows the three-directional magnetic fields recorded by eachsensor in a representative participant (HC1). In Fig. 9, the recon386

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M. Akaza, S. Kawabata, I. Ozaki et al.

Fig. 5. Waveforms of somatosensory evoked potentials and reconstructed currents at ‘‘virtual electrodes”. In a representative case (HC1, a 34-year-old man), the upper
black traces represent somatosensory evoked potential (SEP) waveforms recorded with a C30 –Fz montage, C30 –left Erb’s point montage, Fz–left Erb’s point montage, and C5
posterior (C5S)–left Erb’s point montage. The waveforms with a C5S–left Erb’s point montage show a small N11 potential during the transition from the P9 potential of thebrachial plexus origin to the cervical N13 potential of the dorsal horn origin. The lower waveforms represent the currents that flow perpendicular to the spinal cord, with theinward volume current at the depolarization site in the dorsal column at each position marked by a virtual electrode. The shifts in the peak latencies of the waveforms
indicate that the estimated reconstructed inward volume currents at the depolarization site in the dorsal column ascend sequentially along the spinal canal. Moreover, thepeak latency of the reconstructed electrical current at C5 is almost the same as that of the N11 potential of the SEPs.

reconstituted dorsal–ventral direction currents at each virtualelectrode centered around the C5 level spinal canal in the X axis
(virtual electrodes X  30, X  15, 0, X + 15, and X + 30) and Y axis
(virtual electrodes Y  15, 0, Y + 15, and Y + 30). The estimatedelectrical current intensity was larger in the spinal canal at the
C5 level. Moreover, the culmination of the postero-anterior electrical current estimated from the magnetic recordings coincided withthe peak of the cervical N13–P13 and the volume-conducted posterior cervical negative and anterior cervical positive SEP responses
in all of the 13 participants; the current peak latency was significantly correlated with the cervical N13–P13 peak latency of the
SEPs (r = 0.97, p < 0.0001) (Fig. 10).

4. Discussion
In this study, we succeeded in recording SCEFs with a highsignal-to-noise ratio after median nerve stimulation at the wrist.
This approach permitted the visualization of complex neural activities generated from the nerve roots and the cervical spinal cordfrom about 9 to 13 ms after stimulation. Reconstruction of the spatial distribution of the current density around the cervical cord by
UGRENS showed that median nerve SCEFs comprise three components: action currents at the dorsal root entry zone, action currents
traveling along the dorsal column, and intracellular currents of theneurons within the dorsal horn.
First, we discuss the action currents at the dorsal root entry
zone. The conventional electrophysiological method is inferior
when evaluating the electrical activity in the intervertebral foramen. In the present study, the electrical activity in the interverte-

Fig. 6. Correlation between the peak latencies of the estimated electricalcurrents and somatosensory evoked potentials. The peak latency of the estimatedelectrical current perpendicular to the spinal cord at C5, which indicates theestimated inward volume current in the dorsal column at C5, and the N11 peaklatency of somatosensory evoked potentials (SEPs) recorded with a C5 posterior(C5S)–contralateral Erb’s point montage are well-correlated in all 16 participants(r = 0.94, p < 0.0001).
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Clinical Neurophysiology 132 (2021) 382–391

Fig. 7. Reconstructed currents estimated from the magnetic field measured at the adjacent intervertebral foramina in response to electrical supramaximal median
nerve stimulation at the wrist. (A) Reconstructed currents at the adjacent intervertebral foramen (a representative case: HC2, a 39-year-old woman). (B) Each individual
variation in the peak trailing axonal current density flowing into the intervertebral foramens (HC2–11). The currents are largest at the C6/7 intervertebral foramen (outlet ofroot C7) or the C7/T1 intervertebral foramen (outlet of root C8) in most participants. Currents passing through the C4/5 intervertebral foramen (outlet of root C5) are observedin 2 of the 10 participants, HC6 and HC11.

Fig. 8. Magnetic field measured from the surface of the unilateral neck in response to electrical supramaximal median nerve stimulation at the wrist. (A) Positions of
the sensors superimposed on an X-ray image of a participant. (B) The three-directional magnetic fields recorded by each sensor (a representative case: HC1, a 34-year-oldman). The black traces are magnetic fields in the left-right direction relative to the cervical spinal cord (left is upward in the graphs). The red traces are magnetic fields in thedorsal-ventral direction (ventral is upward). The green traces are magnetic fields parallel to the spinal cord (cranial is upward). Some malfunctioning pickup coils show a flatline. The red signals, mainly generated from intra-axonal currents, are highest above the spinal cord. The polarity of the black and green signals is reversed on each side of the
spinal cord. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

ble to easily determine individual differences in innervation. Then,by comparing the evoked magnetic fields on the affected and nonaffected sides of the intervertebral foramens, it will be possible toelectrophysiologically diagnose the level of the radiculopathy inthe cervical spine. However, further studies are needed, including
animal experiments, because the accuracy of the signal source estimation of the spatial filtering method may not be sufficient. A
next-generation algorithm that has higher spatial resolution thanthe current one should be considered. Moreover, because median
nerve electrical stimulation at the wrist activates mainly C7 andbral foramen could be evaluated by MSG. Anatomically, the median
nerve is usually innervated from C6–T1 but less often from C5(Netter, 2014). Consistent with the typical innervation pattern,
the currents were largest at the C6/7 intervertebral foramen (outletof root C7) or the C7/T1 intervertebral foramen (outlet of root C8)
in most participants and currents passing through the C4/5 intervertebral foramen (outlet of root C5) were observed in 2 of the
10 participants: HC6 and HC11. Many individual differences havebeen reported in the dermatome in the upper limb (Kimura,
2001; Willbourn and Aminoff, 1988). Using MSG, it may be possi388

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M. Akaza, S. Kawabata, I. Ozaki et al.

Fig. 9. Waveforms of somatosensory evoked potentials and reconstructed postero-anterior currents at a ‘‘virtual electrode”. The reconstructed current distribution
13.2 ms after stimulation in a representative participant (HC1, a 34-year-old man) is displayed as a pseudocolor map superimposed on an X-ray image of the cervical spine.
The virtual electrodes, C5 posterior (C5S) electrode, and anterior cervical (AC) electrode are displayed on the lateral X-ray images of the participant. The upper waves:somatosensory evoked potentials (SEPs) recorded at a C5S–AC montage. The lower waveforms: the reconstituted currents at each virtual electrode centered on the C5 level
spinal canal in the X axis (virtual electrodes X  30, X  15, 0, X + 15, and X + 30) and Y axis (virtual electrodes Y  15, 0, Y + 15, and Y + 30). The estimated electrical current
intensity was larger in the spinal canal at the C5 level. The culmination of the estimated dorsal–ventral electrical current coincides with the peak of the cervical N13–P13 in
the SEP.

evaluation was also possible of currents flowing perpendicular tothe long axis of the spinal canal that may originate from the inward
volume current at the depolarization site of the dorsal column.
Fukuoka et al. (2002, 2004) found that the negative peak of theaction potential in the nerve is equivalent to the inward volume
current at the depolarization site. Our group also previously
reported that the peak latency of the inward volume current at
the depolarization site flowing perpendicular to the brachial plexus
corresponded to the peak latency of the compound nerve action
potential at Erb’s point (Watanabe et al., 2019). In the present
study, the good correlation between the peak latency of the current
flowing perpendicular to the spinal canal at C5 and that of the N11of the SEPs indicates that the inward volume current activity at the
depolarization site in the dorsal column was successfully recorded
by MSG.
Moreover, the reconstructed electrical current that flowed perpendicular to the spinal cord ascended sequentially along the
spinal canal and its conduction velocity in the dorsal column could

C8 innervated sensory and motor nerves, our previous method canevaluate radiculopathy in C7 and C8, but is less suitable for evaluating electrical nerve activity in the C4/5 and C5/6 intervertebral
foramens. Other types of nerve electrical stimulation, such as thatof the superficial radial nerve and lateral antebrachial cutaneous
nerve, should be considered.
The action potential propagation along the dorsal column isrecorded as a small negative notch in P9 to cervical N13 waveforms
with a C5S–NC derivation in the SEPs. It can also be recorded as a
P11 potential with a cephalic–NC montage in about two-thirds ofindividuals. There is a consensus that prolonged latency ordecreased amplitude of the N11 or P11 potential may indicate dorsal column dysfunction (El Negamy and Sedgwick, 1979; Restuccia
et al., 1992). However, it is impossible to observe the ascending
impulses and to measure the conduction velocity in SEPs. In thepresent study, we demonstrated using MSG that leading currents
followed by trailing currents travel rostrally in the spinal canal.
Between the leading axonal currents and trailing axonal currents,389

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Clinical Neurophysiology 132 (2021) 382–391

Moreover, the peak intensity latency of the reconstructed current significantly correlated with the cervical N13–P13 peaklatency of the SEPs in 13 healthy participants. Vertebral skin andesophageal recordings (Desmedt and Cheron, 1981; Desmedt andNguyen, 1984; Mauguière, 1987) have revealed that the cervical
N13–P13 potential is due to static transverse dipolar sources thatare presumably generated from the spinal cord gray matter anddorsal horn, as evidenced by the disappearance of the cervical
N13–P13 potential in patients diagnosed with syringomyelia(Urasaki et al., 1988). The equivalent current dipole of the cervical
N13–P13 potential is presumably located at about the medullary
C5 segments (Desmedt, 1989; Hallström et al., 1989; Jeanmonod
et al., 1989). Collaterals of ascending or descending branches fromlarge-diameter cutaneous afferents penetrate the dorsal horn
through its medio-dorsal aspect and form the bushy arborizationsof Cajal in cytoarchitectonic layer III (Cajal, 1995). These arborizations form dense synapses on the dendrites of interneurons, withsome located in layers IV–V and with dendrites extending in parallel arrays into layer III (Brown et al., 1980; for a review, see Abrairaand Ginty, 2013).
After stimulation of large-diameter cutaneous afferents in themonkey, intraspinal mapping of the lumbar spinal cord withmicroelectrodes located a focal excitatory postsynaptic potential
negativity in the dorsal horn and positivity in the ventral cord
(Beall et al., 1977). We demonstrate that, in addition to the ascending action volley along the dorsal column corresponding to the N11
or P11 potential of SEPs, MSG can evaluate stable neural activities
within the dorsal horn corresponding to the cervical N13–P13
potential of SEPs. It is difficult to detect the spread of longitudinal
neural activity in the spinal cord by SEP. Due to the influence of thebone and its high electrical impedance, the cervical N13 is widelydistributed between C3 and T1, similar to how the cerebral N20 is
widely distributed in the contralateral parietal region on the scalp.
However, MSG can detect longitudinal neural activity in the spinal
cord while recording the intracellular electrical current. MSG
makes it possible to noninvasively measure dorsal horn activity
in humans, which was previously only reported in an animal
experiment (Abraira and Ginty, 2013).

Fig. 10. Correlation between the peak latencies of the estimated electricalcurrents and somatosensory evoked potentials. The current density peak latencyof the estimated electrical current in the posterior–anterior (dorsal–ventral)direction obtained within the spinal canal at C5 is significantly correlated withthe cervical N13–P13 peak latency of the somatosensory evoked potentials (SEPs)(r = 0.97, p < 0.0001).

be evaluated. Sumiya et al. (2017) reported a conduction velocityof 64.3 m/s for reconstructed currents in response to stimulationof the lower thoracic cord. We found that the conduction velocity
calculated from the peak latency at C5–6 ranged from 53.9 to75.9 m/s (n = 10; average, 63.1 ± 7.5 m/s), which is compatible withthe result of Sumiya et al. These findings indicate that magnetic
field measurement with excellent spatial resolution can be applied
for the detailed evaluation of the electrical activity of the dorsal
column. It was reported that the evoked potential sensitivity ofthe detection of small lesions in multiple sclerosis was inferior tothat of magnetic resonance imaging (Filippini et al., 1994). However, our results suggest that MSG might be able to identify clinically silent lesions by detecting focal slow conduction and be amore useful electrophysiological method compared with the conventional method.
One important anatomical finding is often overlooked: after
spinal entry, large-diameter cutaneous afferents from mechanoreceptors such as Merkel and Meissner receptors bifurcate in the dorsal column into an ascending branch that reaches the
cuneate/gracile nucleus and a shorter descending branch, as documented with horseradish peroxidase injections in the cat (Brown
et al., 1980; for a review, see Abraira and Ginty, 2013). However,in the present study, as well as in all of the previous studies on
MSG, descending volleys along the dorsal column could not be
detected. Perhaps magnetic fields produced by the descending volleys did not persist and were cancelled out by those produced by
the ascending volleys in the opposite direction that lasted longer.
Instead, a not traveling but stable current source in the posterior
to anterior direction could be estimated within the spinal canalat around 13 ms after the stimulus. As shown in Fig. 9, the reconstructed current source around C5 ran in the dorsal to ventral
direction and its waveform was very similar to the SEPs recordedwith a C5S–AC montage. This result is consistent with the resultsof a previous study on magnetic recording using a single-channel
SQUID system by Curio et al. (1989).

5. Conclusions
We successfully and separately visualized the activities of thedorsal column, dorsal horn, and root in response to electrical median nerve stimulation at the wrist by measuring the magnetic fieldat the neck and reconstructing their respective currents. In contrast
to the conventional electrophysiological method, MSG, due to its
excellent spatial and temporal resolution after median nerve stimulation, enables us to identify the level of spinal root entry, calculate the conduction velocity of the dorsal column, and analyze
segmental dorsal horn activity in detail. This approach thereby
provides useful information for the functional electrophysiologicaldiagnosis of somatosensory pathways.
Funding
This research was supported by the RICOH Company Grand
Number 1250000125012A210. The funding body played no rolein study design, data collection and analysis, preparation of themanuscript, or the decision to publish.
Author Contributions
M.A., S.K., I.O., and T.Y. took part in the conception and design ofthe project; M.A., S.K., I.O., and Y.M. were involved in its execution;and M.A., I.O., S.K, Y.M., T.W., Y. A., K.S., and Y.S. performed analysis
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and interpretation of data. All authors have approved the submission of this manuscript.

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Declaration of Competing Interest
None of the authors have potential conflicts of interest to bedisclosed.
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