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The P18 component of the median nerve SEP recorded from a posterior to anterior neck montage
Clinical Neurophysiology 123 (2012) 2057–2063
Contents lists available at SciVerse ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
The P18 component of the median nerve SEP recorded from a posterior to anterior neck montage L.M.P. Giuliano, K.F. Nunes, G.M. Manzano ⇑ Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, SP, Brazil
a r t i c l e
i n f o
Article history: Accepted 21 March 2012 Available online 9 May 2012 Keywords: Somatosensory evoked potential Median nerve Primary afferent depolarisation Vibration Double-pulse stimulation Cord dorsum potential
h i g h l i g h t s The P18 component of the median nerve SEP can be recorded from a posterior to anterior neck montage. Vibration of the palm of the hand reduces the amplitude of all components except P18 and N18. Double-pulse stimulation attenuates the amplitude of the P18 component, as has been described for the positive component of the spinal cord dorsum potential.
a b s t r a c t Objective: To investigate the P18 component in the posterior to anterior neck montage after median nerve stimulation. Methods: Somatosensory evoked potentials, through electrical wrist stimulation, were collected. In 12 subjects, the presence of the P18 component was evaluated in the posterior to anterior neck montage. In 10 subjects, the effects of simultaneous vibration of the hand were evaluated. In five subjects, responses after double-pulse stimulation (ISI 20 ms) were evaluated. Results: The P18 component was identified in all subjects. Vibration reduced the amplitude of all components except the P18 and N18. Double-pulse stimulation reduced the amplitude of the P18 and the N18 components without significantly changing the amplitude of the other components. Conclusions: The posterior to anterior neck montage allows for recording the P18 component. The amplitude reduction of all components during vibration, except N18 and P18, is interpreted as reflecting inhibitory activities at the cuneiform nucleus and at the segmental dorsal horn of the spinal cord, respectively. The reduction in the P18 component after double-pulse stimulation is compatible with previous observations on the positive component of cord dorsum potentials. Significance: Studying this component may add to the knowledge of the function of the spinal cord in humans. Ó 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction The activity recorded after stimulation of the median nerve at the wrist from posterior and anterior neck electrodes with a distant reference shows a large negativity and a large positivity designated as lcN13 and acP13, respectively. These fields of potential are seen as different sides of the same generator, the postsynaptic activities at the spinal cord segmental level of the stimulated nerve (Desmedt and Cheron, 1981; Mauguière, 1983; Sonoo et al., 1990; Mauguière, 2000). The lcN13 component is seen as the skin surface counterpart of the negative field of the spinal cord dorsum potential (SCDP), as ⇑ Corresponding author. Address: Rua Dr. Tirso Martins, 264, Ap. 52, Vila Mariana, São Paulo, SP 04120-050, Brazil. Tel./fax: +55 11 55797181. E-mail address: [email protected] (G.M. Manzano).
recorded directly from the spinal cord in both animals (Gotch and Horsley, 1891; Gasser and Graham, 1933) and humans (Magadlery et al., 1951; Jeanmonod et al., 1989). The SCDP is also characterised by a large and long positive (LLP) field that ‘follows’ the negative field (Gotch and Horsley, 1891; Gasser and Graham, 1933; Magadlery et al., 1951; Jeanmonod et al., 1989). The LLP field of the SCDP also has a negative counterpart when recorded on the anterior face of the spinal cord (Austin and McCouch, 1955; Jeanmonod et al., 1989). Confirmation of these observations had been made through intrathecal and epidural recordings in humans (Shimoji et al., 1971; Shimoji, 2006; Ertekin, 1976; Beric et al., 1986; Cioni and Meglio, 1986; Hallström et al., 1989; Aida and Shimoji, 2006). The posterior LLP field is usually associated with a depolarisation of the primary afferents (primary afferent depolarisation (PAD)). The existence of a fair correlation of the duration of the
1388-2457/$36.00 Ó 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2012.03.010
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LLP field with intracellularly recorded PAD (Koketsu, 1956; Eccles and Krnjevic, 1959) and changes in the excitability of the primary afferent terminals (Wall, 1958), as well as studies on the duration of inhibition and field potentials at the spinal cord, have led to the proposal that these PADs could be responsible, and are therefore an expression of pre-synaptic inhibition (Eccles et al., 1961; Rudomin and Schmidt, 1999; Rudomin, 2009). It has been shown that double-pulse stimulation, with an interstimulus interval around 20 ms, causes a reduction in the LLP wave of the SCDP as well as in the similar positivity related to the dorsal column nuclei (Gasser and Graham, 1933; Magadlery et al., 1951; Therman, 1941; Andersen et al., 1964). Beric et al. (1986), Cioni and Meglio (1986) and Hallström et al. (1989), recording from the human epidural space, identified the positive field of the SCDP and named it the P18 component; both studies from 1986 showed that it has a negative counterpart at the anterior face of the spinal cord. Therefore, similar to the lcN13/acP13, the P18 component should be recorded at the skin surface, particularly using a posterior to anterior neck montage, albeit with low amplitude (Beric et al., 1986). Indeed, Emerson and Pedley (1986) described two stationary potentials that reversed phase between the posterior and anterior faces of the neck, designated CERV N13/P13 and CERV P17/N17, in a group of normal volunteers after stimulation of the median nerve at the wrist. Sonoo et al. (1992) also noted the occurrence of the P18 component at the posterior face of the neck; however, they found it infrequently and reasoned that the findings of Emerson and Pedley (1986) could be explained by the use of a high-pass filter at 30 Hz. In agreement with the observations of Sonoo et al. (1992), Aida and Shimoji (2006) found that with surface electrodes and using various references, they could not record this positivity in any of their studied subjects. Sonoo et al. (1992) proposed an association of the N18 component of the median nerve somatosensory evoked potential (SEP) and PAD at the cuneiform nucleus. Following this, Manzano et al. (1998a) showed some functional characteristics of the N18 component that were compatible with that proposition. In particular, following the confirmation that vibration interfered with input transmission at the cuneiform nucleus in humans (Ibañez et al., 1989), it was observed that simultaneous vibration of the palm of the hand and stimulation of the median nerve reduced the amplitude of all the short latency components, except the N18, a finding which was interpreted as related to that component with inhibitory activities at the cuneiform nucleus (Manzano et al., 1998b). In this study, our objectives were to investigate the presence of the P18 component in the posterior to anterior neck montage in a sample of normal subjects using a high-pass filter lower than 30 Hz. We intend to observe the effect of simultaneous vibration of the stimulated hand, since if indeed this component has a relationship with inhibitory activities at the spinal cord, it should behave similarly to the N18 component, as previously described (Manzano et al., 1998b). We also wanted to see if the effect of double-pulse stimulation was compatible with previous observations on the LLP field of the SCDP.
2. Methods We studied responses obtained from 16 normal volunteers (nine males) with an age range of 23–60 years (35.3 ± 12.2 years). All volunteers provided informed consent and the procedures were approved by a local ethics committee. Some of the volunteers participated in more than one experiment. Somatosensory evoked responses were recorded through surface electrodes (Ag/AgCl) fixed with conducting paste to the skin
Fig. 1. Somatosensory evoked responses recorded from one subject. Four replications are superimposed.
and secured in place, when necessary, with adhesive tape. The skin was cleaned and subjected to mild abrasion, providing an interelectrode impedance of 5 kX or less. Electrodes where placed over both parietal regions (P3 and P4 of the 10–20 international system) at the posterior face of the neck at the level of the second (C2) and sixth (C6) cervical vertebrae, at the anterior face of the neck at the supraglottal region (CA) and over the left (ClC) and right (ClI) clavicles. Montages were P3–P4, P4–C2, C6–CA and ClI–ClC. The ground electrode was applied similarly to the recording electrodes, over the forehead (Fpz of the 10–20 international system). The right median nerve was stimulated at the wrist, with the cathode proximal. Stimulus electrodes consisted of felt pads, 6 mm in diameter, previously soaked in a saline solution, connected with metal beds mounted on a resin base, with an intercentre distance of 2.5 cm. The stimulus consisted of a rectangular electrical pulse 0.2 ms in duration, delivered at a frequency of 4.9 s–1. The intensity of the stimulus was the sum of the sensory and motor thresholds. Responses were recorded on a Nihon–Khoden polygraph (model Sigma) on four simultaneous channels with 1024 points per channel over an analysis time of 100 ms; filters were set at 5 and 3000 Hz. To build the averaged curves between 500 and 2500, responses were recorded in each situation and all responses were replicated four times, except for the observations with doublepulse stimulation that were replicated twice. All responses were stored on floppy discs for subsequent analysis. Initially, for 12 volunteers, responses to right median nerve stimulation were collected and stored (first paradigm). In 10 of the subjects, the responses to right median nerve stimulation were collected again, associated with mechanical vibration of the palm of the right hand (second paradigm). Mechanical vibration was
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Table 1 Amplitude (mean ± SD), in lV, of the components of the median nerve SEP in the control and during vibration conditions.
N9 N13 P13 P14 P18 N18 N20 *
Fig. 2. Grand average of the responses recorded from 12 subjects. The area of the P18 component is hatched.
Control
Vibration
p*
6.8 ± 2.5 2.0 ± 0.3 2.2 ± 0.3 1.8 ± 0.3 0.8 ± 0.3 1.5 ± 0.3 1.2 ± 0.4
5.6 ± 3.1 1.7 ± 0.4 1.4 ± 0.4 1.2 ± 0.3 0.9 ± 0.1 2.3 ± 2.7 0.8 ± 0.4
0.01 0.03 0.01 0.01 0.11 0.96 0.01
The associated probability related to the Wilcoxon test.
accomplished through a physiotherapy apparatus that produced vibrations at approximately 120 Hz (with an amplitude of 2 mm) on a cylindrical structure attached at one end (6 cm in diameter and 3 cm in height). This vibrating cylinder was manually kept in contact with the palm of the examined hand by the examiner. In five subjects, on a different day, control SSEPs were acquired and then another set of responses was collected after stimulation on a double-pulse protocol with an inter-stimulus interval of 20 ms (third paradigm). In another three subjects, on a different day, SSEPs were acquired from positions C6, CA and midway among those positions, on the lateral sides of the neck, with a common reference on the ClC position (fourth paradigm). After checking the curves, all the replications obtained for each individual in each paradigm were averaged, and from these averaged curves, the following measurements were taken: the amplitude of the N20 component which was measured from the onset
Fig. 3. Four averaged responses superimposed from each of the 12 subjects studied showing the presence of the P18 component in all recordings.
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Fig. 4. Responses recorded from one subject before (thin lines) and during vibration (thick lines). On the left, four averaged superimposed responses are shown and on the right, the average of those superimposed responses is shown. Calibration 1 lV and 5 ms.
Table 2 Amplitude (mean ± SD), in lV, of the components of the median nerve SEP in the control and after double-pulse stimulation (ISI – 20 ms).
N9 N13 P13 P14 P18 N18 N20 *
Control
ISI-20 ms
p*
7.0 ± 2.4 1.3 ± 0.4 2.2 ± 0.7 2.0 ± 0.7 0.7 ± 0.3 1.3 ± 0.7 1.8 ± 1.5
6.7 ± 2.2 1.4 ± 0.4 2.3 ± 0.7 2.4 ± 0.6 0.1 ± 0.3 0.2 ± 0.6 0.6 ± 0.2
0.35 1.00 0.17 0.07 0.04 0.04 0.22
The associated probability related to the Wilcoxon test.
of the component to its peak from the P3–P4 montage, the amplitude of the P13/14 complex and the N18 component measured from the N11/P11 onset to the highest positivity and negativity, respectively, from the P4–C2 montage. From the posterior to anterior neck montage (C6–CA), the amplitude of the N13 and P18 components was measured as the highest negativity and the highest positivity following it, both measured from baseline. Occasionally, the P18 component was bilobed; when this occurred, the deeper peak was used for amplitude measurement. The amplitude of the N9 component was measured from the peak of the initial positivity to the main negative peak from the ClI–ClC montage. Latencies were measured for all analysed components.
2.1. Statistical analyses Fig. 5. Grand average of the responses of the 10 subjects studied, showing responses before (thin lines) and during vibration interference (thick lines). Responses were aligned at the peak of the N9 component.
To analyse the effect of vibration on the amplitude of each component, responses obtained before and during vibration were compared using the Wilcoxon matched-pairs signed-ranks test. The
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same test was used to compare the amplitude of the components in the control condition and after double-pulse stimulation. Differences were considered significant if p < 0.05. 3. Results
Fig. 6. Two replications and the mean after single (thin traces – displaced 20 ms to the right) and double pulse stimulation (thick traces) from one subject. Calibration 1 lV and 5 ms.
Following stimulation of the median nerve, the expected usual components were recorded in all subjects (Figs. 1 and 2). The latencies (mean ± SD) were 9.8 ± 0.7, 13.1 ± 0.8, 13.1 ± 0.7, 14.2 ± 0.7, 18.3 ± 0.8 and 19 ± 0.9 ms for the N9, N13, P13, P14, N18 and N20 components, respectively. A positive component with a mean latency of 18.4 ms following the N13 component in the C6–CA montage was also observed in the recordings of all subjects; therefore, we designated it as P18, as has been done previously (Fig. 3). To ascertain that this component was related to inhibitory activities at the spinal cord, we used a manipulation previously used to study the N18 component, the effect of vibration interference (Manzano et al., 1998a,b). The responses recorded during vibration showed a significant reduction in the amplitude (p < 0.05) for all components except for the N18 and P18 components (Table 1). This showed that the P18 component behaved as the N18 component and therefore could be similarly considered related to inhibitory activities. Responses from one subject and the grand average of the curves from all subjects are shown in Figs. 4 and 5. To verify the relation of the P18 and N18 components with the LLP recorded around the spinal cord and the dorsal column nuclei, we used a manipulation previously used to study the LLP fields. After double-pulse stimulation at 20-ms intervals, a significant reduction was observed in the N18 and P18 components in all studied subjects. The other analysed components did not change significantly (Table 2, Figs. 6 and 7). The N18 and the P18 components behaved similarly as the LLP from those two anatomical regions when submitted to the same challenging (Gasser and Graham, 1933; Magadlery et al., 1951; Therman, 1941; Andersen et al., 1964). Finally, to verify the antero-posterior distribution of the P18 component generators, we studied the fields around the neck in three volunteers and found the posterior positive and anterior negative fields related to the P18 component as was shown previously by Emerson and Pedley (1986). Fig. 8 shows the grand average of these field studies. 4. Discussion
Fig. 7. Grand average of the responses of the five subjects studied, showing the superimposed responses to single (thin lines – displaced 20 ms to the right) and double (thick lines) pulse stimulation. The area differences, showing reductions in the P18 and N18 components, are hatched. The stimulus artefact was removed for clarity.
We found that the use of the posterior to anterior neck montage allowed the recording of the P18 component in agreement with Emerson and Pedley (1986). Our findings show that the component recorded by those authors was not a distortion introduced by the high-pass filter, as suggested by Sonoo et al. (1992), since it could also be recorded with an open bandwidth in the present work. We believe that the difficulties in detecting this component, in previous attempts (Sonoo et al., 1992; Aida and Shimoji, 2006), were related to the use of a distant reference as used by the latter authors. It should be noted that the component has a relatively low amplitude and electrodes around the neck require good relaxation of the subject, since the muscles are quite close to the recording electrodes and can give large interfering signals at this region (Cracco and Bickford, 1968). A negative peak was infrequently observed on the positive profile of the P18 component, which may correspond to observations previously mentioned by others (Bernhard, 1953; Jeanmonod et al., 1989; Aida and Shimoji, 2006); however, a larger sample may be necessary to clarify the significance of such an observation. Recordings from the epidural space and directly from the surface of the
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Fig. 8. Grand average of the responses of three subjects. The grand averaged response is superimposed by the grand average of the curves and replications of the subjects. The figurine shows the approximate locations of the recording electrodes. Thin arrows show the N13 component and the thick arrows the P18 component on the posterior neck and their respective inverted counterpart on the anterior neck.
spinal cord, in both animals and humans (Bernhard, 1953; Jeanmonod et al., 1989; Aida and Shimoji, 2006), have also shown a similar negativity, although the occurrence of this negativity is not consistent (Bernhard, 1953; Lindblom and Ottosson, 1953; Aida and Shimoji, 2006). It has been suggested that its generation depends on a supraspinal structure (Lindblom and Ottosson, 1953; Aida and Shimoji, 2006). Beall et al. (1977) also showed negative peaks on the profile of the positive field of the SCDP in monkeys; however, they believed that they were related to the stimulation of fibres of different diameters. As we recorded this infrequently, we cannot add much to this discussion, except that it may represent the surface counterpart of the described negative peaks. The present investigation assumed that the posterior to anterior neck montage is ideally suited to record activities oriented perpendicular to the major axis of the neck in the mid-sagittal plane, which is the case for the potentials derived from the segmental activation of the spinal cord (Magadlery et al., 1951; Jeanmonod et al., 1989; Shimoji et al., 1971; Shimoji, 2006; Ertekin, 1976; Beric et al., 1986; Cioni and Meglio, 1986; Hallström et al., 1989; Aida and Shimoji, 2006). It was also assumed that the parietal (ipsilateral to the stimulated median nerve) to upper posterior neck electrode montage is close to ideal for recording activities around the dorsal column nuclei, according to the observations of Sonoo et al. (1992). It should be considered that the presumed independent generators of the cephalic N18 and the spinal P18 are active at almost the same time, and there is a possibility of some interference at the recording electrodes. These interferences are assumed to be small (if present), given the relation of the field potential orientations and the montages used. The association of non-cephalic reference montages, as suggested by Sonoo et al. (1992), may be deemed helpful, if not necessary, in the study of pathological cases were fields may be differently affected and eventually distorted. The study of cases with high cervical lesions affecting the posterior columns using posterior to anterior lower neck montage and parietal (ipsilateral to the stimulated median nerve) to upper posterior neck electrodes may allow a better characterisation of this eventual interference.
The vibration interference evidenced, as was previously shown (Ibañez et al., 1989; Manzano et al., 1998b), a reduction in all the normally recorded short latency components except the N18, confirming the absence of a reduction in the N18 component in a different group of individuals; this new finding adds further information in that the vibration did not reduce the amplitude of the P18 component as well. This suggests, first, that the P18 component is not directly, serially linked, in the pathway to the cortex; second, that it is not a far field related to the transit of the peripheral input; and third, that it is related to inhibitory activities at the spinal cord. The last argument follows the one put forward by Manzano et al. (1998b) for the N18 component in relation to the cuneiform nucleus, i.e. the reduction of the peripheral input indexed by the reduction of the Erb’s point potential suggests a relative increase of the unchanged potential. This seems to be occurring here with the P18 component in relation to the spinal cord. Using double-pulse stimulations, we tried to functionally link the P18 component with the positive field of the SCDP. Our reasoning was that the positive field of the SCDP was reduced after the second pulse (20 ms after the first pulse), and as that was found, it further strengthens the argument that both activities are related. As an added observation, a reduction in the amplitude of the N18 component was also found, concurring with the proposition of its association with inhibitory activities at the cuneiform nucleus. The study of the fields around the neck confirmed the previous observations of Emerson and Pedley (1986) showing the posterior positive and anterior negative orientations of the fields of the P18 component. In conclusion, the use of the C6–CA montage allowed for recording the P18 component in all studied volunteers; with vibration, the reduction of all components except the N18 and P18 can be interpreted as related to inhibitory activities at the cuneiform nucleus and at the segmental dorsal horn of the spinal cord, respectively; the P18 component showed a reduced amplitude when submitted to double-pulse stimulation, which suggests that it is the skin surface counterpart of the LLP component of the SCDP.
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Further study of the P18 component using non-invasive techniques may add to the knowledge of the function of the spinal cord in humans.
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Contents lists available at SciVerse ScienceDirect
Clinical Neurophysiology journal homepage: www.elsevier.com/locate/clinph
The P18 component of the median nerve SEP recorded from a posterior to anterior neck montage L.M.P. Giuliano, K.F. Nunes, G.M. Manzano ⇑ Department of Neurology and Neurosurgery, Federal University of São Paulo, São Paulo, SP, Brazil
a r t i c l e
i n f o
Article history: Accepted 21 March 2012 Available online 9 May 2012 Keywords: Somatosensory evoked potential Median nerve Primary afferent depolarisation Vibration Double-pulse stimulation Cord dorsum potential
h i g h l i g h t s The P18 component of the median nerve SEP can be recorded from a posterior to anterior neck montage. Vibration of the palm of the hand reduces the amplitude of all components except P18 and N18. Double-pulse stimulation attenuates the amplitude of the P18 component, as has been described for the positive component of the spinal cord dorsum potential.
a b s t r a c t Objective: To investigate the P18 component in the posterior to anterior neck montage after median nerve stimulation. Methods: Somatosensory evoked potentials, through electrical wrist stimulation, were collected. In 12 subjects, the presence of the P18 component was evaluated in the posterior to anterior neck montage. In 10 subjects, the effects of simultaneous vibration of the hand were evaluated. In five subjects, responses after double-pulse stimulation (ISI 20 ms) were evaluated. Results: The P18 component was identified in all subjects. Vibration reduced the amplitude of all components except the P18 and N18. Double-pulse stimulation reduced the amplitude of the P18 and the N18 components without significantly changing the amplitude of the other components. Conclusions: The posterior to anterior neck montage allows for recording the P18 component. The amplitude reduction of all components during vibration, except N18 and P18, is interpreted as reflecting inhibitory activities at the cuneiform nucleus and at the segmental dorsal horn of the spinal cord, respectively. The reduction in the P18 component after double-pulse stimulation is compatible with previous observations on the positive component of cord dorsum potentials. Significance: Studying this component may add to the knowledge of the function of the spinal cord in humans. Ó 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
1. Introduction The activity recorded after stimulation of the median nerve at the wrist from posterior and anterior neck electrodes with a distant reference shows a large negativity and a large positivity designated as lcN13 and acP13, respectively. These fields of potential are seen as different sides of the same generator, the postsynaptic activities at the spinal cord segmental level of the stimulated nerve (Desmedt and Cheron, 1981; Mauguière, 1983; Sonoo et al., 1990; Mauguière, 2000). The lcN13 component is seen as the skin surface counterpart of the negative field of the spinal cord dorsum potential (SCDP), as ⇑ Corresponding author. Address: Rua Dr. Tirso Martins, 264, Ap. 52, Vila Mariana, São Paulo, SP 04120-050, Brazil. Tel./fax: +55 11 55797181. E-mail address: [email protected] (G.M. Manzano).
recorded directly from the spinal cord in both animals (Gotch and Horsley, 1891; Gasser and Graham, 1933) and humans (Magadlery et al., 1951; Jeanmonod et al., 1989). The SCDP is also characterised by a large and long positive (LLP) field that ‘follows’ the negative field (Gotch and Horsley, 1891; Gasser and Graham, 1933; Magadlery et al., 1951; Jeanmonod et al., 1989). The LLP field of the SCDP also has a negative counterpart when recorded on the anterior face of the spinal cord (Austin and McCouch, 1955; Jeanmonod et al., 1989). Confirmation of these observations had been made through intrathecal and epidural recordings in humans (Shimoji et al., 1971; Shimoji, 2006; Ertekin, 1976; Beric et al., 1986; Cioni and Meglio, 1986; Hallström et al., 1989; Aida and Shimoji, 2006). The posterior LLP field is usually associated with a depolarisation of the primary afferents (primary afferent depolarisation (PAD)). The existence of a fair correlation of the duration of the
1388-2457/$36.00 Ó 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.clinph.2012.03.010
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LLP field with intracellularly recorded PAD (Koketsu, 1956; Eccles and Krnjevic, 1959) and changes in the excitability of the primary afferent terminals (Wall, 1958), as well as studies on the duration of inhibition and field potentials at the spinal cord, have led to the proposal that these PADs could be responsible, and are therefore an expression of pre-synaptic inhibition (Eccles et al., 1961; Rudomin and Schmidt, 1999; Rudomin, 2009). It has been shown that double-pulse stimulation, with an interstimulus interval around 20 ms, causes a reduction in the LLP wave of the SCDP as well as in the similar positivity related to the dorsal column nuclei (Gasser and Graham, 1933; Magadlery et al., 1951; Therman, 1941; Andersen et al., 1964). Beric et al. (1986), Cioni and Meglio (1986) and Hallström et al. (1989), recording from the human epidural space, identified the positive field of the SCDP and named it the P18 component; both studies from 1986 showed that it has a negative counterpart at the anterior face of the spinal cord. Therefore, similar to the lcN13/acP13, the P18 component should be recorded at the skin surface, particularly using a posterior to anterior neck montage, albeit with low amplitude (Beric et al., 1986). Indeed, Emerson and Pedley (1986) described two stationary potentials that reversed phase between the posterior and anterior faces of the neck, designated CERV N13/P13 and CERV P17/N17, in a group of normal volunteers after stimulation of the median nerve at the wrist. Sonoo et al. (1992) also noted the occurrence of the P18 component at the posterior face of the neck; however, they found it infrequently and reasoned that the findings of Emerson and Pedley (1986) could be explained by the use of a high-pass filter at 30 Hz. In agreement with the observations of Sonoo et al. (1992), Aida and Shimoji (2006) found that with surface electrodes and using various references, they could not record this positivity in any of their studied subjects. Sonoo et al. (1992) proposed an association of the N18 component of the median nerve somatosensory evoked potential (SEP) and PAD at the cuneiform nucleus. Following this, Manzano et al. (1998a) showed some functional characteristics of the N18 component that were compatible with that proposition. In particular, following the confirmation that vibration interfered with input transmission at the cuneiform nucleus in humans (Ibañez et al., 1989), it was observed that simultaneous vibration of the palm of the hand and stimulation of the median nerve reduced the amplitude of all the short latency components, except the N18, a finding which was interpreted as related to that component with inhibitory activities at the cuneiform nucleus (Manzano et al., 1998b). In this study, our objectives were to investigate the presence of the P18 component in the posterior to anterior neck montage in a sample of normal subjects using a high-pass filter lower than 30 Hz. We intend to observe the effect of simultaneous vibration of the stimulated hand, since if indeed this component has a relationship with inhibitory activities at the spinal cord, it should behave similarly to the N18 component, as previously described (Manzano et al., 1998b). We also wanted to see if the effect of double-pulse stimulation was compatible with previous observations on the LLP field of the SCDP.
2. Methods We studied responses obtained from 16 normal volunteers (nine males) with an age range of 23–60 years (35.3 ± 12.2 years). All volunteers provided informed consent and the procedures were approved by a local ethics committee. Some of the volunteers participated in more than one experiment. Somatosensory evoked responses were recorded through surface electrodes (Ag/AgCl) fixed with conducting paste to the skin
Fig. 1. Somatosensory evoked responses recorded from one subject. Four replications are superimposed.
and secured in place, when necessary, with adhesive tape. The skin was cleaned and subjected to mild abrasion, providing an interelectrode impedance of 5 kX or less. Electrodes where placed over both parietal regions (P3 and P4 of the 10–20 international system) at the posterior face of the neck at the level of the second (C2) and sixth (C6) cervical vertebrae, at the anterior face of the neck at the supraglottal region (CA) and over the left (ClC) and right (ClI) clavicles. Montages were P3–P4, P4–C2, C6–CA and ClI–ClC. The ground electrode was applied similarly to the recording electrodes, over the forehead (Fpz of the 10–20 international system). The right median nerve was stimulated at the wrist, with the cathode proximal. Stimulus electrodes consisted of felt pads, 6 mm in diameter, previously soaked in a saline solution, connected with metal beds mounted on a resin base, with an intercentre distance of 2.5 cm. The stimulus consisted of a rectangular electrical pulse 0.2 ms in duration, delivered at a frequency of 4.9 s–1. The intensity of the stimulus was the sum of the sensory and motor thresholds. Responses were recorded on a Nihon–Khoden polygraph (model Sigma) on four simultaneous channels with 1024 points per channel over an analysis time of 100 ms; filters were set at 5 and 3000 Hz. To build the averaged curves between 500 and 2500, responses were recorded in each situation and all responses were replicated four times, except for the observations with doublepulse stimulation that were replicated twice. All responses were stored on floppy discs for subsequent analysis. Initially, for 12 volunteers, responses to right median nerve stimulation were collected and stored (first paradigm). In 10 of the subjects, the responses to right median nerve stimulation were collected again, associated with mechanical vibration of the palm of the right hand (second paradigm). Mechanical vibration was
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Table 1 Amplitude (mean ± SD), in lV, of the components of the median nerve SEP in the control and during vibration conditions.
N9 N13 P13 P14 P18 N18 N20 *
Fig. 2. Grand average of the responses recorded from 12 subjects. The area of the P18 component is hatched.
Control
Vibration
p*
6.8 ± 2.5 2.0 ± 0.3 2.2 ± 0.3 1.8 ± 0.3 0.8 ± 0.3 1.5 ± 0.3 1.2 ± 0.4
5.6 ± 3.1 1.7 ± 0.4 1.4 ± 0.4 1.2 ± 0.3 0.9 ± 0.1 2.3 ± 2.7 0.8 ± 0.4
0.01 0.03 0.01 0.01 0.11 0.96 0.01
The associated probability related to the Wilcoxon test.
accomplished through a physiotherapy apparatus that produced vibrations at approximately 120 Hz (with an amplitude of 2 mm) on a cylindrical structure attached at one end (6 cm in diameter and 3 cm in height). This vibrating cylinder was manually kept in contact with the palm of the examined hand by the examiner. In five subjects, on a different day, control SSEPs were acquired and then another set of responses was collected after stimulation on a double-pulse protocol with an inter-stimulus interval of 20 ms (third paradigm). In another three subjects, on a different day, SSEPs were acquired from positions C6, CA and midway among those positions, on the lateral sides of the neck, with a common reference on the ClC position (fourth paradigm). After checking the curves, all the replications obtained for each individual in each paradigm were averaged, and from these averaged curves, the following measurements were taken: the amplitude of the N20 component which was measured from the onset
Fig. 3. Four averaged responses superimposed from each of the 12 subjects studied showing the presence of the P18 component in all recordings.
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Fig. 4. Responses recorded from one subject before (thin lines) and during vibration (thick lines). On the left, four averaged superimposed responses are shown and on the right, the average of those superimposed responses is shown. Calibration 1 lV and 5 ms.
Table 2 Amplitude (mean ± SD), in lV, of the components of the median nerve SEP in the control and after double-pulse stimulation (ISI – 20 ms).
N9 N13 P13 P14 P18 N18 N20 *
Control
ISI-20 ms
p*
7.0 ± 2.4 1.3 ± 0.4 2.2 ± 0.7 2.0 ± 0.7 0.7 ± 0.3 1.3 ± 0.7 1.8 ± 1.5
6.7 ± 2.2 1.4 ± 0.4 2.3 ± 0.7 2.4 ± 0.6 0.1 ± 0.3 0.2 ± 0.6 0.6 ± 0.2
0.35 1.00 0.17 0.07 0.04 0.04 0.22
The associated probability related to the Wilcoxon test.
of the component to its peak from the P3–P4 montage, the amplitude of the P13/14 complex and the N18 component measured from the N11/P11 onset to the highest positivity and negativity, respectively, from the P4–C2 montage. From the posterior to anterior neck montage (C6–CA), the amplitude of the N13 and P18 components was measured as the highest negativity and the highest positivity following it, both measured from baseline. Occasionally, the P18 component was bilobed; when this occurred, the deeper peak was used for amplitude measurement. The amplitude of the N9 component was measured from the peak of the initial positivity to the main negative peak from the ClI–ClC montage. Latencies were measured for all analysed components.
2.1. Statistical analyses Fig. 5. Grand average of the responses of the 10 subjects studied, showing responses before (thin lines) and during vibration interference (thick lines). Responses were aligned at the peak of the N9 component.
To analyse the effect of vibration on the amplitude of each component, responses obtained before and during vibration were compared using the Wilcoxon matched-pairs signed-ranks test. The
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same test was used to compare the amplitude of the components in the control condition and after double-pulse stimulation. Differences were considered significant if p < 0.05. 3. Results
Fig. 6. Two replications and the mean after single (thin traces – displaced 20 ms to the right) and double pulse stimulation (thick traces) from one subject. Calibration 1 lV and 5 ms.
Following stimulation of the median nerve, the expected usual components were recorded in all subjects (Figs. 1 and 2). The latencies (mean ± SD) were 9.8 ± 0.7, 13.1 ± 0.8, 13.1 ± 0.7, 14.2 ± 0.7, 18.3 ± 0.8 and 19 ± 0.9 ms for the N9, N13, P13, P14, N18 and N20 components, respectively. A positive component with a mean latency of 18.4 ms following the N13 component in the C6–CA montage was also observed in the recordings of all subjects; therefore, we designated it as P18, as has been done previously (Fig. 3). To ascertain that this component was related to inhibitory activities at the spinal cord, we used a manipulation previously used to study the N18 component, the effect of vibration interference (Manzano et al., 1998a,b). The responses recorded during vibration showed a significant reduction in the amplitude (p < 0.05) for all components except for the N18 and P18 components (Table 1). This showed that the P18 component behaved as the N18 component and therefore could be similarly considered related to inhibitory activities. Responses from one subject and the grand average of the curves from all subjects are shown in Figs. 4 and 5. To verify the relation of the P18 and N18 components with the LLP recorded around the spinal cord and the dorsal column nuclei, we used a manipulation previously used to study the LLP fields. After double-pulse stimulation at 20-ms intervals, a significant reduction was observed in the N18 and P18 components in all studied subjects. The other analysed components did not change significantly (Table 2, Figs. 6 and 7). The N18 and the P18 components behaved similarly as the LLP from those two anatomical regions when submitted to the same challenging (Gasser and Graham, 1933; Magadlery et al., 1951; Therman, 1941; Andersen et al., 1964). Finally, to verify the antero-posterior distribution of the P18 component generators, we studied the fields around the neck in three volunteers and found the posterior positive and anterior negative fields related to the P18 component as was shown previously by Emerson and Pedley (1986). Fig. 8 shows the grand average of these field studies. 4. Discussion
Fig. 7. Grand average of the responses of the five subjects studied, showing the superimposed responses to single (thin lines – displaced 20 ms to the right) and double (thick lines) pulse stimulation. The area differences, showing reductions in the P18 and N18 components, are hatched. The stimulus artefact was removed for clarity.
We found that the use of the posterior to anterior neck montage allowed the recording of the P18 component in agreement with Emerson and Pedley (1986). Our findings show that the component recorded by those authors was not a distortion introduced by the high-pass filter, as suggested by Sonoo et al. (1992), since it could also be recorded with an open bandwidth in the present work. We believe that the difficulties in detecting this component, in previous attempts (Sonoo et al., 1992; Aida and Shimoji, 2006), were related to the use of a distant reference as used by the latter authors. It should be noted that the component has a relatively low amplitude and electrodes around the neck require good relaxation of the subject, since the muscles are quite close to the recording electrodes and can give large interfering signals at this region (Cracco and Bickford, 1968). A negative peak was infrequently observed on the positive profile of the P18 component, which may correspond to observations previously mentioned by others (Bernhard, 1953; Jeanmonod et al., 1989; Aida and Shimoji, 2006); however, a larger sample may be necessary to clarify the significance of such an observation. Recordings from the epidural space and directly from the surface of the
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Fig. 8. Grand average of the responses of three subjects. The grand averaged response is superimposed by the grand average of the curves and replications of the subjects. The figurine shows the approximate locations of the recording electrodes. Thin arrows show the N13 component and the thick arrows the P18 component on the posterior neck and their respective inverted counterpart on the anterior neck.
spinal cord, in both animals and humans (Bernhard, 1953; Jeanmonod et al., 1989; Aida and Shimoji, 2006), have also shown a similar negativity, although the occurrence of this negativity is not consistent (Bernhard, 1953; Lindblom and Ottosson, 1953; Aida and Shimoji, 2006). It has been suggested that its generation depends on a supraspinal structure (Lindblom and Ottosson, 1953; Aida and Shimoji, 2006). Beall et al. (1977) also showed negative peaks on the profile of the positive field of the SCDP in monkeys; however, they believed that they were related to the stimulation of fibres of different diameters. As we recorded this infrequently, we cannot add much to this discussion, except that it may represent the surface counterpart of the described negative peaks. The present investigation assumed that the posterior to anterior neck montage is ideally suited to record activities oriented perpendicular to the major axis of the neck in the mid-sagittal plane, which is the case for the potentials derived from the segmental activation of the spinal cord (Magadlery et al., 1951; Jeanmonod et al., 1989; Shimoji et al., 1971; Shimoji, 2006; Ertekin, 1976; Beric et al., 1986; Cioni and Meglio, 1986; Hallström et al., 1989; Aida and Shimoji, 2006). It was also assumed that the parietal (ipsilateral to the stimulated median nerve) to upper posterior neck electrode montage is close to ideal for recording activities around the dorsal column nuclei, according to the observations of Sonoo et al. (1992). It should be considered that the presumed independent generators of the cephalic N18 and the spinal P18 are active at almost the same time, and there is a possibility of some interference at the recording electrodes. These interferences are assumed to be small (if present), given the relation of the field potential orientations and the montages used. The association of non-cephalic reference montages, as suggested by Sonoo et al. (1992), may be deemed helpful, if not necessary, in the study of pathological cases were fields may be differently affected and eventually distorted. The study of cases with high cervical lesions affecting the posterior columns using posterior to anterior lower neck montage and parietal (ipsilateral to the stimulated median nerve) to upper posterior neck electrodes may allow a better characterisation of this eventual interference.
The vibration interference evidenced, as was previously shown (Ibañez et al., 1989; Manzano et al., 1998b), a reduction in all the normally recorded short latency components except the N18, confirming the absence of a reduction in the N18 component in a different group of individuals; this new finding adds further information in that the vibration did not reduce the amplitude of the P18 component as well. This suggests, first, that the P18 component is not directly, serially linked, in the pathway to the cortex; second, that it is not a far field related to the transit of the peripheral input; and third, that it is related to inhibitory activities at the spinal cord. The last argument follows the one put forward by Manzano et al. (1998b) for the N18 component in relation to the cuneiform nucleus, i.e. the reduction of the peripheral input indexed by the reduction of the Erb’s point potential suggests a relative increase of the unchanged potential. This seems to be occurring here with the P18 component in relation to the spinal cord. Using double-pulse stimulations, we tried to functionally link the P18 component with the positive field of the SCDP. Our reasoning was that the positive field of the SCDP was reduced after the second pulse (20 ms after the first pulse), and as that was found, it further strengthens the argument that both activities are related. As an added observation, a reduction in the amplitude of the N18 component was also found, concurring with the proposition of its association with inhibitory activities at the cuneiform nucleus. The study of the fields around the neck confirmed the previous observations of Emerson and Pedley (1986) showing the posterior positive and anterior negative orientations of the fields of the P18 component. In conclusion, the use of the C6–CA montage allowed for recording the P18 component in all studied volunteers; with vibration, the reduction of all components except the N18 and P18 can be interpreted as related to inhibitory activities at the cuneiform nucleus and at the segmental dorsal horn of the spinal cord, respectively; the P18 component showed a reduced amplitude when submitted to double-pulse stimulation, which suggests that it is the skin surface counterpart of the LLP component of the SCDP.
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Further study of the P18 component using non-invasive techniques may add to the knowledge of the function of the spinal cord in humans.
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