ORIGINAL RESEARCH
Dipole Orientation of Receptive Fields in the Somatosensory Cortex After Stimulation of the Posterior Tibial Nerve in Humans Kazuyoshi Nakanishi,* Ken Inoue,† Hikmat Hadoush,‡§ Toru Sunagawa,‡ and Mitsuo Ochi*
Summary: The origins of the earliest evoked potentials and magnetic fields after tibial nerve electrical stimulation are still controversial. We focused on the initial activity from the gyrus area and analyzed the components for the coronal and sagittal planes. In 12 healthy right-handed subjects, electrical stimuli were delivered to the left posterior tibial nerve at the ankle. The cortical somatosensory evoked fields were recorded, and the equivalent current dipoles were calculated and separated into the sagittal plane (y-components) and coronal plane (x-components) components. In nine subjects, we observed two deflections (y1 and y2) in the y-component waveform and two deflections (x1 and x2) in the x-component waveform over 60 milliseconds; y1 was directed anteriorly, y2 posteriorly, x1 to the left, and x2 to the right. The y1 was originated in the anterior wall of the central sulcus. By focusing on the y-component, we elucidated the existence of the posteroanterior component, which may originate from the area 3b (gyrus) in tibial nerve somatosensory evoked fields and has the same quality as N20m for median nerve somatosensory evoked fields. This is the first report to suggest that the posteroanterior component in the tibial nerve is analogous to N20m in the median nerve using magnetoencephalography. Key Words: Left posterior tibial nerve, Electrical stimulation, Evoked potentials, Somatosensory evoked fields, Gyrus, Central sulcus. (J Clin Neurophysiol 2014;31: 236–240)
he first recordings of somatosensory evoked fields (SEFs) after lower limb stimulation (Hari et al., 1984; Okada et al., 1984) confirmed the source location as the mesial wall of the hemisphere. Tibial and sural nerve SEFs were characterized more in detail (Huttunen et al., 1987), and the signal patterns were in agreement with a mesial wall origin, with temporally changing orientations of the source currents. Later, the origins of somatosensory evoked potentials (SEPs) for the tibial nerve were studied, and it was shown that the initial component, N35, is probably equivalent to the first cortical potential of N20 in median nerve SEPs (Yamada et al., 1996). However, regarding stimulation of the lower extremities, the origins of the evoked potentials and fields are still controversial
T
From the *Department of Orthopaedic Surgery, Programs for Applied Biomedicine, Division of Clinical Medical Science, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; †Department of Neurology, Hiroshima Prefectural Hospital, Hiroshima, Japan; ‡Graduate School of Health Science, Hiroshima University, Hiroshima, Japan; and §Faculty of Applied Medical Sciences, Jordan University of Science & Technology, Irbid, Jordan. Supported by the Grants-in-Aid for Scientific Research (Scientific Research C, Research Project No.: 24592198) from Japan Society for the Promotion of Science, Ministry of Health, Labor, and Welfare. Address correspondence and reprint requests to Kazuyoshi Nakanishi, MD, PhD, Department of Orthopaedic Surgery, Programs for Applied Biomedicine, Division of Clinical Medical Science, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima 734-8551, Japan; e-mail: [email protected]. Copyright Ó 2014 by the American Clinical Neurophysiology Society
ISSN: 0736-0258/14/3103-0236
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(Allison et al., 1996; Baumgartner et al., 1998; Beric and Prevec, 1981; Desmedt and Bourguet, 1985; Hauck et al., 2006). The responses from the fissural part of the cortex should demonstrate the transverse orientation (coronal plane), whereas those from the gyral part should demonstrate the longitudinal orientation (sagittal plane). The activity from the crown area usually projects tangentially and cannot project longitudinally. We considered that focusing on the y-axis would be an important strategy to elucidate the existence of the initial activity from the gyrus area. Therefore, we analyzed the components in the coronal and sagittal planes by measuring the values of the x- and y-axes, respectively.
MATERIALS AND METHODS Subjects
Twelve healthy right-handed male subjects (age, 32 6 3.5 [mean 6 SD] [range, 25–37 years]; height, 171 6 6.5 [range, 160–180 cm]) participated in this study. The evoked fields in the lower extremity were examined. The instruments used in this study were approved by the Japanese Ministry of Health, Labor, and Welfare. This study was approved by the ethics committees of Hiroshima University, and written informed consent was obtained from all subjects. During the experiment, both the subject and the examiner looked at an image of a clock projected on a screen in front of them in a magnetically shielded room. This setting prevented subjects from looking at their hands or moving their eyes.
Stimuli and Device Electrical stimuli were delivered to the left posterior tibial nerve at the ankle. The analysis period of 350 milliseconds started at 50 milliseconds before stimulation. Constant current square-wave pulses of 0.2 milliseconds in duration and a stimulus intensity of 12.3 6 3.3 (mean 6 SD) (range, 6.0–15.4) mA, which was three times larger than the sensory threshold intensity of the posterior tibial nerve and higher than the motor threshold, were delivered at 400 milliseconds interstimulus intervals. The cortical SEFs were recorded using a whole-head 306channel planar gradiometer system (Vector View Elekta Neuromag, Helsinki, Finland). Mutually orthogonal tangential magnetic field gradients were simultaneously obtained at 102 recording sites. The recording band-pass was 0.1 to 260 Hz, and the signals were digitized at 600 Hz. One thousand evoked fields were averaged. For source identification, the head was assumed to be a sphere, the dimensions of which were determined on the basis of individual magnetic resonance images obtained with a GE Yokogawa SIGNA 1.5 Tesla device (slice thickness, 2 mm; 3D-SPGR). The two coordinate systems (magnetoencephalography and MRI) were aligned by applying markers to magnetic resonance images and by identifying these landmarks with a 3D digitizer (Isotrack; Polhemus
Journal of Clinical Neurophysiology Volume 31, Number 3, June 2014
Journal of Clinical Neurophysiology Volume 31, Number 3, June 2014
Navigation Sciences, Colchester, VT) before magnetoencephalography. All source analysis was based on signals that were high-pass filtered at 4 Hz to eliminate baseline fluctuations and low-pass filtered at 100 Hz.
Data Analysis The sources of the evoked responses were modeled as single current dipoles. The magnetic field patterns were first visually examined in 1-millisecond step between 0 and 100 milliseconds to identify all local and stable “dipolar field patterns,” i.e., all field distributions resembling those produced by a single current dipole. Then, the equivalent current dipole (ECD) that best described the most dominant source during the strongest signals of each dipolar field pattern was identified by a least-square search using a subset of 20 to 30 channels over the source area. Thereafter, the position and direction of the ECDs were fixed, and their strength was calculated over time. The origin of the head-based coordinate system was defined as the midpoint between the preauricular points. The x-axis indicated that the origin was toward the right preauricular point, with a positive value toward the right preauricular point, the y-axis indicated that the origin was toward the nasion, with a positive value in the anterior direction, whereas the z-axis indicated that the origin was toward the vertex in a direction perpendicular to the x-y plane, with a positive value toward the upper side. The signal-to-noise ratio was sufficiently good during this period. The ECDs were superimposed on a high-resolution T1-weighted magnetic resonance image of the brain for each subject and were depicted with the coordination system on the
Dipole Orientation of Posterior Tibial Nerve SEF
magnetic resonance image. Significant sources were defined when the goodness of fit (GOF) was .90%. The source current of each ECD was separated into the sagittal plane (y-components) and coronal plane (x-components) components, and the peak latency and amplitude of deflection of the waveforms were investigated. A 50-millisecond prestimulus recording was used as the baseline for amplitude determination.
Statistical Analysis Bonferroni multiple comparison test was used to compare the strength and the response latency of each ECD component (P , 0.05).
RESULTS In all subjects, the ECDs for N40m were located in the foot somatosensory region, with dominance over the right hemisphere. The signal started at 32 to 34 milliseconds, and the earliest peak occurred at 38 milliseconds. Fig. 1 shows the location of the ECDs in the same subject to left posterior tibial nerve stimuli at several successive latencies. The direction of the source currents emerged at 38 milliseconds, and the dipole rotated counterclockwise during the next 5 milliseconds. Fig. 2 shows the earlier dipoles observed in the same subject as shown in Fig. 1. At 32 milliseconds, source currents toward the anterior were observed that turned to the left side at 34 milliseconds. This earlier signal was detected in nine subjects, and it originated in the anterior wall of the central sulcus. The locations of the single dipoles, indicated by the arrows over the
FIG. 1. Location of the equivalent current dipole at 38 (A), 40 (B), and 43 milliseconds (C) after left posterior tibial nerve stimuli in the same subject. Copyright Ó 2014 by the American Clinical Neurophysiology Society
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FIG. 2. Earlier dipole location at 32 (A) and 34 (B) milliseconds in the same subject as shown in Fig. 1. maps, varied by only a few millimeters during the first 70 milliseconds. In these nine subjects, two deflections (the first deflection was defined as y1 and the second as y2) were observed during 60 milliseconds in the y-component waveform; y1 was directed anteriorly and y2 posteriorly. In the x-component waveforms, two deflections (the first deflection was defined as x1 and the second as x2) were observed during 60 milliseconds; x1 was directed to the left and x2 to the right. Fig. 3 shows the waveforms of the x- and y-components in the same subject as shown in Fig. 1.
Table 1 shows the latency, amplitude, and goodness of fit for each deflection of the waveform. The latency of the x1/x2 and y1/y2 peaks was 39.4 6 1.9/48.6 6 3.2 and 35.4 6 1.7/47.1 6 4.5 milliseconds (mean 6 SD), respectively. The latency of y1 differed significantly from that of the x1 (P , 0.001), y2 (P , 0.001), and x2 peaks (P , 0.001). The latency of x1 also differed significantly from that of the y2 (P ¼ 0.002) and x2 (P , 0.001) peaks. No significant difference was detected in the latency between the y2 and x2 peaks (P ¼ 1.000). The amplitude of the x1/x2 and y1/y2 peaks was 14.3 6 6.2/6.5 6 6.4 and 5.0 6 4.4/10.7 6 5.3 nAm, respectively. The y1 amplitude was significantly smaller than the x1 (P ¼ 0.012) or y2 (P ¼ 0.009) amplitude. Although the ECDs for the y1 component were small and they were not observed in three subjects, the component of the peak ECDs in the anterior direction was determined with a goodness of fit of .90% in nine subjects.
DISCUSSION
FIG. 3. Waveforms of the x- and y-components in the same subject as shown in Fig. 1 (black line: y-components, gray line: x-components). The arrows indicate each peak and latency. The arrows indicate the deflections of x1, x2, y1, y2, and their peak latencies (milliseconds). 238
In this study, we observed single dipole movements obtained by tibial nerve SEFs over time. The time-varying orientation of the single dipole started from the posterior to the anterior, then from the right to the left, and persisted in the anterior to posterior direction in the contralateral hemisphere. Earlier studies of SEPs after electrical stimulation of the tibial nerve reported the presence of the first negative peak, which was variably named as N31, N32, N33, N34, or N37 (Kakigi et al., 1982; Lastimosa et al., 1982; Riffel and Stohr, 1982; Seyal et al., 1983; Tsuji et al., 1984; Vera et al., 1983; Yamada et al., 1982). Using Copyright Ó 2014 by the American Clinical Neurophysiology Society
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TABLE 1.
Dipole Orientation of Posterior Tibial Nerve SEF
Latencies and Amplitudes of Each Deflections in x- and y-Component Waveforms*† Latency, ms
P
Amplitude, nAm
P
Goodness of Fit, %
y1
35.4 6 1.7 (33–39)
5.0 6 4.4 (0.1–12.2)
39.4 6 1.9 (37–43)
y2 x2
47.1 6 4.5 (43–55) 48.6 6 3.2 (43–55)
0.012 vs. x1§ 0.009 vs. y2k 1.000 vs. x2 0.505 vs. y2 ,0.001 vs. x2‡ 0.162 vs. x2
92.4 6 1.8 (91.0–95.4)
x1
,0.001 vs. x1‡ ,0.001 vs. y2‡ ,0.001 vs. x2‡ 0.002 vs. y2k ,0.001 vs. x2‡ 1.000 vs. x2
Components
14.3 6 6.2 (5.9–23.7) 10.7 6 5.3 (2.8–18.5) 6.5 6 6.4 (0.3–18.5)
93.9 6 2.5 (91.1–97.6) 94.6 6 3.0 (91.7–98.6) 95.6 6 2.6 (91.7–98.1)
*n ¼ 9. †Mean 6 SD (range). ‡P , 0.001. kP , 0.01. §P , 0.05.
topographical mapping of SEPs, it has been indicated that the vector of N35 is directed vertically toward the contralateral surface, whereas P40 is directed transversely toward the ipsilateral hemisphere, and it was also concluded that N35 of tibial nerve SEPs is analogous to N20 (Yamada et al., 1996). Moreover, the amplitude of N35 was reported to be too small to be measured reliably. In this study, the recorded amplitude of the initial component of the y-axis was small and was estimated to originate in the anterior wall of the central sulcus, directed to the anterior. In contrast, the initial component of the x-axis was recorded with a larger amplitude than the y1 component. Moreover, even though the amplitude of the evoked magnetic fields of the x1 component was large in the channels on the ipsilateral left parietal region and in those on the contralateral side using a whole-head 306-channel planar gradiometer system, the ECDs of the x1 component were estimated in the contralateral right mesial wall and directed to the left in this study. This finding seems quite similar to the “paradoxically lateralized P40” in the topographic study reported by Yamada et al. As seen from the above, the initial component of the y-axis in this study is quite similar to N35, whereas that of the x-axis is also similar to P40. Therefore, our results strongly support the view of Yamada et al. that SEF examinations can be used to detect cortical activity with quite high precision. The second components of the x- and y-axis did not differ significantly in their latency. Thus, these two components may originate from an identical cortical response. The response seems to be the same as the N45m-P45m reported by Kakigi et al. because their latency and ECD direction are similar (Kakigi et al., 1995). It has been reported that the area 3b, which is located on the posterior bank of the central sulcus, was the source of N20 in SEPs (Allison et al., 1989a; Allison et al., 1989b) and of N20m in SEFs (Hari et al., 1984; Kakigi, 1994; Wood et al., 1985) after median nerve electrical stimulation. Our results suggest the existence and activity of the cortical area 3b, which is analogous to N20m in the SEFs observed after electrical stimulation of the median nerve. Consequently, this is the first report to suggest that the y1 component in the tibial nerve should be analogous to N20m in the median nerve using magnetoencephalography (Fig. 4). However, because the gyrus area for the lower extremities is much smaller than that for the upper extremities, our weak components were not observed in three individuals. In accord with median nerve SEPs/SEFs, the main portions of these evoked fields after tibial nerve stimulation were considered to originate from the areas 3b and 1 of the somatosensory cortices (Kakigi et al., 1995). Conversely, the initial transverse activation was reported to originate in the area 3b, facing the interhemispheric Copyright Ó 2014 by the American Clinical Neurophysiology Society
fissure, and the latter source, because of the systematic rotation of the field patterns, is assumed to reflect the activation of area 5 in the anterior wall of the marginal ramus of the cingulate sulcus (Hari et al., 1996). Hashimoto et al. detected a single peaked posterior tibial nerve P37m response that consists of two partially overlapping subcomponents, similar to those reported by Hari et al., and they concluded that those components were generated in area 3 and an area near the marginal sulcus (Hashimoto et al., 2001). The initial components in these two reports were directed transversely toward the ipsilateral hemisphere, and they are similar to the x1 component in our study. Therefore, our findings suggest that the y1 component exists with a shorter latency than the transverse x1 component. More recently, Terada et al. studied the generators of the initial components using subdural electrodes, and their results suggested that the initial response has at least three independent generators: a radial dipole on the primary motor area, a tangential dipole on the primary sensory area, and a dipole on the supplementary sensorimotor areas
FIG. 4. Scheme of cortical activation during the early somatosensory responses. A cross section of the right hemisphere viewed from the top. The top of the scheme represents the anterior direction. 239
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that was oriented perpendicularly to the mesial hemispheric surface (Terada et al., 2009). The latency and amplitude of the radial dipole are similar to our y1 component, except the ECD of our y1 component was estimated in the anterior wall of the central sulcus. These observations were not compatible with previous findings; however, it seems that similar components from the posterior to the anterior were actually detected before the transverse components in subjects 3, 5, or 8 in the study of Hari et al. (1996). The earliest response may have been difficult to detect because the amplitude of the response was small, the large x1 response was generated immediately after the y1 response, or these responses temporarily overlapped with each other. By focusing on the y-component in our study, we elucidated the existence of the posteroanterior component, which may originate from the area 3b (gyrus) in tibial nerve SEFs and is analogous to N20m of median nerve SEFs. Our results support the previous hypothesis that the component for the anterior direction is essentially equal to N20/N20m of median nerve SEPs/SEFs, and this activity for the tibial nerves varies in individuals. REFERENCES Allison T, McCarthy G, Wood CC, et al. Human cortical potentials evoked by stimulation of the median nerve. I. Cytoarchitectonic areas generating shortlatency activity. J Neurophysiol 1989a;62:694–710. Allison T, McCarthy G, Wood CC, et al. Human cortical potentials evoked by stimulation of the median nerve. II. Cytoarchitectonic areas generating longlatency activity. J Neurophysiol 1989b;62:711–722. Allison T, McCarthy G, Luby M, et al. Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation. Electroencephalogr Clin Neurophysiol 1996;100:126–140. Baumgartner U, Vogel H, Ellrich J, et al. Brain electrical source analysis of primary cortical components of the tibial nerve somatosensory evoked potential using regional sources. Electroencephalogr Clin Neurophysiol 1998;108:588–599. Beric A, Prevec TS. The early negative potential evoked by stimulation of the tibial nerve in man. J Neurol Sci 1981;50:299–306. Desmedt JE, Bourguet M. Color imaging of parietal and frontal somatosensory potential fields evoked by stimulation of median or posterior tibial nerve in man. Electroencephalogr Clin Neurophysiol 1985;62:1–17. Hari R, Reinikainen K, Kaukoranta E, et al. Somatosensory evoked cerebral magnetic fields from SI and SII in man. Electroencephalogr Clin Neurophysiol 1984;57:254–263. Hari R, Nagamine T, Nishitani N, et al. Time-varying activation of different cytoarchitectonic areas of the human SI cortex after tibial nerve stimulation. Neuroimage 1996;4:111–118.
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Hashimoto I, Sakuma K, Kimura T, et al. Serial activation of distinct cytoarchitectonic areas of the human S1 cortex after posterior tibial nerve stimulation. Neuroreport 2001;12:1857–1862. Hauck M, Baumgartner U, Hille E, et al. Evidence for early activation of primary motor cortex and SMA after electrical lower limb stimulation using EEG source reconstruction. Brain Res 2006;1125:17–25. Huttunen J, Hari R, Leinonen L. Cerebral magnetic responses to stimulation of ulnar and median nerves. Electroencephalogr Clin Neurophysiol 1987;66: 391–400. Kakigi R. Somatosensory evoked magnetic fields following median nerve stimulation. Neurosci Res 1994;20:165–174. Kakigi R, Shibasaki H, Hashizume A, et al. Short latency somatosensory evoked spinal and scalp-recorded potentials following posterior tibial nerve stimulation in man. Electroencephalogr Clin Neurophysiol 1982;53:602–611. Kakigi R, Koyama S, Hoshiyama M, et al. Topography of somatosensory evoked magnetic fields following posterior tibial nerve stimulation. Electroencephalogr Clin Neurophysiol 1995;95:127–134. Lastimosa AC, Bass NH, Stanback K, et al. Lumbar spinal cord and early cortical evoked potentials after tibial nerve stimulation: effects of stature on normative data. Electroencephalogr Clin Neurophysiol 1982;54:499–507. Okada YC, Tanenbaum R, Williamson SJ, et al. Somatotopic organization of the human somatosensory cortex revealed by neuromagnetic measurements. Exp Brain Res 1984;56:197–205. Riffel B, Stohr M. [Spinal and subcortical somatosensory evoked potentials after stimulation of the tibial nerve [in German]. Arch Psychiatr Nervenkr 1982;232:251–263. Seyal M, Emerson RG, Pedley TA. Spinal and early scalp-recorded components of the somatosensory evoked potential following stimulation of the posterior tibial nerve. Electroencephalogr Clin Neurophysiol 1983;55: 320–330. Terada K, Umeoka S, Baba K, et al. Generators of tibial nerve somatosensory evoked potential: recorded from the mesial surface of the human brain using subdural electrodes. J Clin Neurophysiol 2009;26:13–16. Tsuji S, Luders H, Lesser RP, et al. Subcortical and cortical somatosensory potentials evoked by posterior tibial nerve stimulation: normative values. Electroencephalogr Clin Neurophysiol 1984;59:214–228. Vera CL, Perot PL Jr, Fountain EL. Scalp recorded somatosensory evoked potentials to posterior tibial nerve stimulation in humans. Electroencephalogr Clin Neurophysiol 1983;56:159–168. Wood CC, Cohen D, Cuffin BN, et al. Electrical sources in human somatosensory cortex: identification by combined magnetic and potential recordings. Science 1985;227:1051–1053. Yamada T, Machida M, Kimura J. Far-field somatosensory evoked potentials after stimulation of the tibial nerve. Neurology 1982;32:1151–1158. Yamada T, Matsubara M, Shiraishi G, et al. Topographic analyses of somatosensory evoked potentials following stimulation of tibial, sural and lateral femoral cutaneous nerves. Electroencephalogr Clin Neurophysiol 1996;100: 33–43.
Copyright Ó 2014 by the American Clinical Neurophysiology Society
Dipole Orientation of Receptive Fields in the Somatosensory Cortex After Stimulation of the Posterior Tibial Nerve in Humans Kazuyoshi Nakanishi,* Ken Inoue,† Hikmat Hadoush,‡§ Toru Sunagawa,‡ and Mitsuo Ochi*
Summary: The origins of the earliest evoked potentials and magnetic fields after tibial nerve electrical stimulation are still controversial. We focused on the initial activity from the gyrus area and analyzed the components for the coronal and sagittal planes. In 12 healthy right-handed subjects, electrical stimuli were delivered to the left posterior tibial nerve at the ankle. The cortical somatosensory evoked fields were recorded, and the equivalent current dipoles were calculated and separated into the sagittal plane (y-components) and coronal plane (x-components) components. In nine subjects, we observed two deflections (y1 and y2) in the y-component waveform and two deflections (x1 and x2) in the x-component waveform over 60 milliseconds; y1 was directed anteriorly, y2 posteriorly, x1 to the left, and x2 to the right. The y1 was originated in the anterior wall of the central sulcus. By focusing on the y-component, we elucidated the existence of the posteroanterior component, which may originate from the area 3b (gyrus) in tibial nerve somatosensory evoked fields and has the same quality as N20m for median nerve somatosensory evoked fields. This is the first report to suggest that the posteroanterior component in the tibial nerve is analogous to N20m in the median nerve using magnetoencephalography. Key Words: Left posterior tibial nerve, Electrical stimulation, Evoked potentials, Somatosensory evoked fields, Gyrus, Central sulcus. (J Clin Neurophysiol 2014;31: 236–240)
he first recordings of somatosensory evoked fields (SEFs) after lower limb stimulation (Hari et al., 1984; Okada et al., 1984) confirmed the source location as the mesial wall of the hemisphere. Tibial and sural nerve SEFs were characterized more in detail (Huttunen et al., 1987), and the signal patterns were in agreement with a mesial wall origin, with temporally changing orientations of the source currents. Later, the origins of somatosensory evoked potentials (SEPs) for the tibial nerve were studied, and it was shown that the initial component, N35, is probably equivalent to the first cortical potential of N20 in median nerve SEPs (Yamada et al., 1996). However, regarding stimulation of the lower extremities, the origins of the evoked potentials and fields are still controversial
T
From the *Department of Orthopaedic Surgery, Programs for Applied Biomedicine, Division of Clinical Medical Science, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan; †Department of Neurology, Hiroshima Prefectural Hospital, Hiroshima, Japan; ‡Graduate School of Health Science, Hiroshima University, Hiroshima, Japan; and §Faculty of Applied Medical Sciences, Jordan University of Science & Technology, Irbid, Jordan. Supported by the Grants-in-Aid for Scientific Research (Scientific Research C, Research Project No.: 24592198) from Japan Society for the Promotion of Science, Ministry of Health, Labor, and Welfare. Address correspondence and reprint requests to Kazuyoshi Nakanishi, MD, PhD, Department of Orthopaedic Surgery, Programs for Applied Biomedicine, Division of Clinical Medical Science, Graduate School of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima 734-8551, Japan; e-mail: [email protected]. Copyright Ó 2014 by the American Clinical Neurophysiology Society
ISSN: 0736-0258/14/3103-0236
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(Allison et al., 1996; Baumgartner et al., 1998; Beric and Prevec, 1981; Desmedt and Bourguet, 1985; Hauck et al., 2006). The responses from the fissural part of the cortex should demonstrate the transverse orientation (coronal plane), whereas those from the gyral part should demonstrate the longitudinal orientation (sagittal plane). The activity from the crown area usually projects tangentially and cannot project longitudinally. We considered that focusing on the y-axis would be an important strategy to elucidate the existence of the initial activity from the gyrus area. Therefore, we analyzed the components in the coronal and sagittal planes by measuring the values of the x- and y-axes, respectively.
MATERIALS AND METHODS Subjects
Twelve healthy right-handed male subjects (age, 32 6 3.5 [mean 6 SD] [range, 25–37 years]; height, 171 6 6.5 [range, 160–180 cm]) participated in this study. The evoked fields in the lower extremity were examined. The instruments used in this study were approved by the Japanese Ministry of Health, Labor, and Welfare. This study was approved by the ethics committees of Hiroshima University, and written informed consent was obtained from all subjects. During the experiment, both the subject and the examiner looked at an image of a clock projected on a screen in front of them in a magnetically shielded room. This setting prevented subjects from looking at their hands or moving their eyes.
Stimuli and Device Electrical stimuli were delivered to the left posterior tibial nerve at the ankle. The analysis period of 350 milliseconds started at 50 milliseconds before stimulation. Constant current square-wave pulses of 0.2 milliseconds in duration and a stimulus intensity of 12.3 6 3.3 (mean 6 SD) (range, 6.0–15.4) mA, which was three times larger than the sensory threshold intensity of the posterior tibial nerve and higher than the motor threshold, were delivered at 400 milliseconds interstimulus intervals. The cortical SEFs were recorded using a whole-head 306channel planar gradiometer system (Vector View Elekta Neuromag, Helsinki, Finland). Mutually orthogonal tangential magnetic field gradients were simultaneously obtained at 102 recording sites. The recording band-pass was 0.1 to 260 Hz, and the signals were digitized at 600 Hz. One thousand evoked fields were averaged. For source identification, the head was assumed to be a sphere, the dimensions of which were determined on the basis of individual magnetic resonance images obtained with a GE Yokogawa SIGNA 1.5 Tesla device (slice thickness, 2 mm; 3D-SPGR). The two coordinate systems (magnetoencephalography and MRI) were aligned by applying markers to magnetic resonance images and by identifying these landmarks with a 3D digitizer (Isotrack; Polhemus
Journal of Clinical Neurophysiology Volume 31, Number 3, June 2014
Journal of Clinical Neurophysiology Volume 31, Number 3, June 2014
Navigation Sciences, Colchester, VT) before magnetoencephalography. All source analysis was based on signals that were high-pass filtered at 4 Hz to eliminate baseline fluctuations and low-pass filtered at 100 Hz.
Data Analysis The sources of the evoked responses were modeled as single current dipoles. The magnetic field patterns were first visually examined in 1-millisecond step between 0 and 100 milliseconds to identify all local and stable “dipolar field patterns,” i.e., all field distributions resembling those produced by a single current dipole. Then, the equivalent current dipole (ECD) that best described the most dominant source during the strongest signals of each dipolar field pattern was identified by a least-square search using a subset of 20 to 30 channels over the source area. Thereafter, the position and direction of the ECDs were fixed, and their strength was calculated over time. The origin of the head-based coordinate system was defined as the midpoint between the preauricular points. The x-axis indicated that the origin was toward the right preauricular point, with a positive value toward the right preauricular point, the y-axis indicated that the origin was toward the nasion, with a positive value in the anterior direction, whereas the z-axis indicated that the origin was toward the vertex in a direction perpendicular to the x-y plane, with a positive value toward the upper side. The signal-to-noise ratio was sufficiently good during this period. The ECDs were superimposed on a high-resolution T1-weighted magnetic resonance image of the brain for each subject and were depicted with the coordination system on the
Dipole Orientation of Posterior Tibial Nerve SEF
magnetic resonance image. Significant sources were defined when the goodness of fit (GOF) was .90%. The source current of each ECD was separated into the sagittal plane (y-components) and coronal plane (x-components) components, and the peak latency and amplitude of deflection of the waveforms were investigated. A 50-millisecond prestimulus recording was used as the baseline for amplitude determination.
Statistical Analysis Bonferroni multiple comparison test was used to compare the strength and the response latency of each ECD component (P , 0.05).
RESULTS In all subjects, the ECDs for N40m were located in the foot somatosensory region, with dominance over the right hemisphere. The signal started at 32 to 34 milliseconds, and the earliest peak occurred at 38 milliseconds. Fig. 1 shows the location of the ECDs in the same subject to left posterior tibial nerve stimuli at several successive latencies. The direction of the source currents emerged at 38 milliseconds, and the dipole rotated counterclockwise during the next 5 milliseconds. Fig. 2 shows the earlier dipoles observed in the same subject as shown in Fig. 1. At 32 milliseconds, source currents toward the anterior were observed that turned to the left side at 34 milliseconds. This earlier signal was detected in nine subjects, and it originated in the anterior wall of the central sulcus. The locations of the single dipoles, indicated by the arrows over the
FIG. 1. Location of the equivalent current dipole at 38 (A), 40 (B), and 43 milliseconds (C) after left posterior tibial nerve stimuli in the same subject. Copyright Ó 2014 by the American Clinical Neurophysiology Society
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FIG. 2. Earlier dipole location at 32 (A) and 34 (B) milliseconds in the same subject as shown in Fig. 1. maps, varied by only a few millimeters during the first 70 milliseconds. In these nine subjects, two deflections (the first deflection was defined as y1 and the second as y2) were observed during 60 milliseconds in the y-component waveform; y1 was directed anteriorly and y2 posteriorly. In the x-component waveforms, two deflections (the first deflection was defined as x1 and the second as x2) were observed during 60 milliseconds; x1 was directed to the left and x2 to the right. Fig. 3 shows the waveforms of the x- and y-components in the same subject as shown in Fig. 1.
Table 1 shows the latency, amplitude, and goodness of fit for each deflection of the waveform. The latency of the x1/x2 and y1/y2 peaks was 39.4 6 1.9/48.6 6 3.2 and 35.4 6 1.7/47.1 6 4.5 milliseconds (mean 6 SD), respectively. The latency of y1 differed significantly from that of the x1 (P , 0.001), y2 (P , 0.001), and x2 peaks (P , 0.001). The latency of x1 also differed significantly from that of the y2 (P ¼ 0.002) and x2 (P , 0.001) peaks. No significant difference was detected in the latency between the y2 and x2 peaks (P ¼ 1.000). The amplitude of the x1/x2 and y1/y2 peaks was 14.3 6 6.2/6.5 6 6.4 and 5.0 6 4.4/10.7 6 5.3 nAm, respectively. The y1 amplitude was significantly smaller than the x1 (P ¼ 0.012) or y2 (P ¼ 0.009) amplitude. Although the ECDs for the y1 component were small and they were not observed in three subjects, the component of the peak ECDs in the anterior direction was determined with a goodness of fit of .90% in nine subjects.
DISCUSSION
FIG. 3. Waveforms of the x- and y-components in the same subject as shown in Fig. 1 (black line: y-components, gray line: x-components). The arrows indicate each peak and latency. The arrows indicate the deflections of x1, x2, y1, y2, and their peak latencies (milliseconds). 238
In this study, we observed single dipole movements obtained by tibial nerve SEFs over time. The time-varying orientation of the single dipole started from the posterior to the anterior, then from the right to the left, and persisted in the anterior to posterior direction in the contralateral hemisphere. Earlier studies of SEPs after electrical stimulation of the tibial nerve reported the presence of the first negative peak, which was variably named as N31, N32, N33, N34, or N37 (Kakigi et al., 1982; Lastimosa et al., 1982; Riffel and Stohr, 1982; Seyal et al., 1983; Tsuji et al., 1984; Vera et al., 1983; Yamada et al., 1982). Using Copyright Ó 2014 by the American Clinical Neurophysiology Society
Journal of Clinical Neurophysiology Volume 31, Number 3, June 2014
TABLE 1.
Dipole Orientation of Posterior Tibial Nerve SEF
Latencies and Amplitudes of Each Deflections in x- and y-Component Waveforms*† Latency, ms
P
Amplitude, nAm
P
Goodness of Fit, %
y1
35.4 6 1.7 (33–39)
5.0 6 4.4 (0.1–12.2)
39.4 6 1.9 (37–43)
y2 x2
47.1 6 4.5 (43–55) 48.6 6 3.2 (43–55)
0.012 vs. x1§ 0.009 vs. y2k 1.000 vs. x2 0.505 vs. y2 ,0.001 vs. x2‡ 0.162 vs. x2
92.4 6 1.8 (91.0–95.4)
x1
,0.001 vs. x1‡ ,0.001 vs. y2‡ ,0.001 vs. x2‡ 0.002 vs. y2k ,0.001 vs. x2‡ 1.000 vs. x2
Components
14.3 6 6.2 (5.9–23.7) 10.7 6 5.3 (2.8–18.5) 6.5 6 6.4 (0.3–18.5)
93.9 6 2.5 (91.1–97.6) 94.6 6 3.0 (91.7–98.6) 95.6 6 2.6 (91.7–98.1)
*n ¼ 9. †Mean 6 SD (range). ‡P , 0.001. kP , 0.01. §P , 0.05.
topographical mapping of SEPs, it has been indicated that the vector of N35 is directed vertically toward the contralateral surface, whereas P40 is directed transversely toward the ipsilateral hemisphere, and it was also concluded that N35 of tibial nerve SEPs is analogous to N20 (Yamada et al., 1996). Moreover, the amplitude of N35 was reported to be too small to be measured reliably. In this study, the recorded amplitude of the initial component of the y-axis was small and was estimated to originate in the anterior wall of the central sulcus, directed to the anterior. In contrast, the initial component of the x-axis was recorded with a larger amplitude than the y1 component. Moreover, even though the amplitude of the evoked magnetic fields of the x1 component was large in the channels on the ipsilateral left parietal region and in those on the contralateral side using a whole-head 306-channel planar gradiometer system, the ECDs of the x1 component were estimated in the contralateral right mesial wall and directed to the left in this study. This finding seems quite similar to the “paradoxically lateralized P40” in the topographic study reported by Yamada et al. As seen from the above, the initial component of the y-axis in this study is quite similar to N35, whereas that of the x-axis is also similar to P40. Therefore, our results strongly support the view of Yamada et al. that SEF examinations can be used to detect cortical activity with quite high precision. The second components of the x- and y-axis did not differ significantly in their latency. Thus, these two components may originate from an identical cortical response. The response seems to be the same as the N45m-P45m reported by Kakigi et al. because their latency and ECD direction are similar (Kakigi et al., 1995). It has been reported that the area 3b, which is located on the posterior bank of the central sulcus, was the source of N20 in SEPs (Allison et al., 1989a; Allison et al., 1989b) and of N20m in SEFs (Hari et al., 1984; Kakigi, 1994; Wood et al., 1985) after median nerve electrical stimulation. Our results suggest the existence and activity of the cortical area 3b, which is analogous to N20m in the SEFs observed after electrical stimulation of the median nerve. Consequently, this is the first report to suggest that the y1 component in the tibial nerve should be analogous to N20m in the median nerve using magnetoencephalography (Fig. 4). However, because the gyrus area for the lower extremities is much smaller than that for the upper extremities, our weak components were not observed in three individuals. In accord with median nerve SEPs/SEFs, the main portions of these evoked fields after tibial nerve stimulation were considered to originate from the areas 3b and 1 of the somatosensory cortices (Kakigi et al., 1995). Conversely, the initial transverse activation was reported to originate in the area 3b, facing the interhemispheric Copyright Ó 2014 by the American Clinical Neurophysiology Society
fissure, and the latter source, because of the systematic rotation of the field patterns, is assumed to reflect the activation of area 5 in the anterior wall of the marginal ramus of the cingulate sulcus (Hari et al., 1996). Hashimoto et al. detected a single peaked posterior tibial nerve P37m response that consists of two partially overlapping subcomponents, similar to those reported by Hari et al., and they concluded that those components were generated in area 3 and an area near the marginal sulcus (Hashimoto et al., 2001). The initial components in these two reports were directed transversely toward the ipsilateral hemisphere, and they are similar to the x1 component in our study. Therefore, our findings suggest that the y1 component exists with a shorter latency than the transverse x1 component. More recently, Terada et al. studied the generators of the initial components using subdural electrodes, and their results suggested that the initial response has at least three independent generators: a radial dipole on the primary motor area, a tangential dipole on the primary sensory area, and a dipole on the supplementary sensorimotor areas
FIG. 4. Scheme of cortical activation during the early somatosensory responses. A cross section of the right hemisphere viewed from the top. The top of the scheme represents the anterior direction. 239
Journal of Clinical Neurophysiology Volume 31, Number 3, June 2014
K. Nakanishi et al.
that was oriented perpendicularly to the mesial hemispheric surface (Terada et al., 2009). The latency and amplitude of the radial dipole are similar to our y1 component, except the ECD of our y1 component was estimated in the anterior wall of the central sulcus. These observations were not compatible with previous findings; however, it seems that similar components from the posterior to the anterior were actually detected before the transverse components in subjects 3, 5, or 8 in the study of Hari et al. (1996). The earliest response may have been difficult to detect because the amplitude of the response was small, the large x1 response was generated immediately after the y1 response, or these responses temporarily overlapped with each other. By focusing on the y-component in our study, we elucidated the existence of the posteroanterior component, which may originate from the area 3b (gyrus) in tibial nerve SEFs and is analogous to N20m of median nerve SEFs. Our results support the previous hypothesis that the component for the anterior direction is essentially equal to N20/N20m of median nerve SEPs/SEFs, and this activity for the tibial nerves varies in individuals. REFERENCES Allison T, McCarthy G, Wood CC, et al. Human cortical potentials evoked by stimulation of the median nerve. I. Cytoarchitectonic areas generating shortlatency activity. J Neurophysiol 1989a;62:694–710. Allison T, McCarthy G, Wood CC, et al. Human cortical potentials evoked by stimulation of the median nerve. II. Cytoarchitectonic areas generating longlatency activity. J Neurophysiol 1989b;62:711–722. Allison T, McCarthy G, Luby M, et al. Localization of functional regions of human mesial cortex by somatosensory evoked potential recording and by cortical stimulation. Electroencephalogr Clin Neurophysiol 1996;100:126–140. Baumgartner U, Vogel H, Ellrich J, et al. Brain electrical source analysis of primary cortical components of the tibial nerve somatosensory evoked potential using regional sources. Electroencephalogr Clin Neurophysiol 1998;108:588–599. Beric A, Prevec TS. The early negative potential evoked by stimulation of the tibial nerve in man. J Neurol Sci 1981;50:299–306. Desmedt JE, Bourguet M. Color imaging of parietal and frontal somatosensory potential fields evoked by stimulation of median or posterior tibial nerve in man. Electroencephalogr Clin Neurophysiol 1985;62:1–17. Hari R, Reinikainen K, Kaukoranta E, et al. Somatosensory evoked cerebral magnetic fields from SI and SII in man. Electroencephalogr Clin Neurophysiol 1984;57:254–263. Hari R, Nagamine T, Nishitani N, et al. Time-varying activation of different cytoarchitectonic areas of the human SI cortex after tibial nerve stimulation. Neuroimage 1996;4:111–118.
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