Parietal generators of low- and high-frequency MN (median nerve) SEPs: data from intracortical human recordings

Clinical Neurophysiology 115 (2004) 647–657 www.elsevier.com/locate/clinph

Parietal generators of low- and high-frequency MN (median nerve) SEPs: data from intracortical human recordings C. Barbaa,b,*, M. Valeriania,c, G. Colicchiod, P. Tonalia, D. Restucciaa b

a Department of Neurology, Catholic University, Rome, Italy Fondazione Santa Lucia, IRCCS, via Ardeatina 306, 00179 Rome, Italy c Division of Neurology, Bambino Gesu` Hospital, IRCCS, Rome, Italy d Department of Neurosurgery, Catholic University, Rome, Italy

Accepted 20 October 2003

Abstract Objective: To identify low and high-frequency median nerve (MN) somatosensory evoked potential (SEP) generators by means of chronically implanted electrodes in the parietal lobe (SI and neighbouring areas) of two epileptic patients. Methods: Wide-pass short-latency and long-latency SEPs to electrical MN stimulation were recorded in two epileptic patients by stereotactically chronically implanted electrodes in the parietal lobe (SI and neighbouring areas). To study high-frequency responses (HFOs) an off-line digital filtering of depth short-latency SEPs was performed (500 – 800 Hz, 24 dB roll-off). Spectral analysis was performed by fast Fourier transform. Results: In both patients we recorded a N20/P30 potential followed by a biphasic N50/P70 response. A little negative response in the 100 ms latency range was the last detectable wide-pass SEP in both patients. Two HFOs components (called iP1 and iP2) were detected by mere visual analysis and spectral analysis, and were supposed to be originated within the parietal cortex. Conclusions: This was the very first study that recorded wide bandpass and high frequency SEPs by electrodes, exploring both the lateral and the mesial part of the parietal lobe and particularly that of the post-central gyrus. q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. Keywords: Somatosensory evoked potentials; SI area; Intracortical potentials; High-frequency evoked responses; Epilepsy investigations; Epilepsy surgery

1. Introduction The human primary somatosensory area located on the postcentral gyrus, is subdivided into 4 territories: areas 3a, 3b, 2 and 1 (Brodmann, 1909; Zilles et al., 1995) that were believed to correspond to 4 distinct modality-related areas, as also described in non-human primates (Kaas et al., 1979). Furthermore, it has been suggested that these areas might represent hierarchical stages of cortical processing; in particular, 3a and 3b might correspond to primary areas, and 1 and 2 to secondary areas, both in primates (Kaas and Garraghty, 1991) and humans (Cottier Eskenasy and Clarke, 2000). The role of the SI area in generating both short and longlatency somatosensory evoked potentials (SEPs) to median nerve (MN) stimulation is still a matter of debate. * Corresponding author. Tel.: þ 39-6-515-011; fax: þ39-6-503-2097. E-mail address: [email protected] (C. Barba).

On the basis of scalp and depth recordings that show an inversion of early SEP components across the central sulcus, several researchers (Broughton, 1969; Goff et al., 1977; Allison et al., 1980, 1989a) hypothesized a post-central origin for all short-latency SEPs. On the contrary, after studying patients with focal lesions, Mauguie`re et al. (1983) suggested that the N30 potential recorded over the frontal scalp area may be generated rostral to the rolandic fissure, because this response was occasionally found to be selectively preserved in patients with parietal lesions and absence of early parietal responses. Other topographic studies suggested that the sources of the N30 response might be located in the SMA (Desmedt and Bourguet, 1985; Desmedt et al., 1987; Rossini et al., 1995). Conversely, Barba et al. (2001, 2003) recorded SEPs by chronically implanted electrodes in epileptic patients, and found that no SEP is generated in both pre-SMA and SMA-proper, during the first 50 ms that follow the stimulation of the MN.

1388-2457/$30.00 q 2003 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2003.10.024

648

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

By comparing long-latency scalp SEPs to those recorded from cortical surface, or directly within the brain, Allison et al. (1992) concluded that scalp potentials recorded within 100 ms after the stimulus probably originate in the primary somatosensory (SI) cortex. Srisa-an et al. (1996), by means of spatio-temporal source analysis of middle latency SEPs after median nerve, index and little fingers stimulation, hypothesized that the N60 response may be originated in area 1 of the primary somatosensory area. Conversely, the hypothesis of an N60 source located in the primary somatosensory cortex clashed with the finding of a dissociated loss of this response in some parietal lobe lesions that spared the SI area (Mauguie`re et al., 1983; Stohr et al., 1983), and with the analysis of scalp topography of middle latency potentials in healthy volunteers (Treede and Kunde, 1995). The comparison of scalp and depth SEP recordings in the same patients allowed Barba et al. (2002) to distinguish a temporal N70 response, possibly generated in the SII area, from the fronto-central N60 response, which seems to be originated in both SMA and SI areas. Besides the aforementioned low-frequency components of SEPs, recent studies recognized high-frequency bursts of wavelets (high-frequency oscillations, HFOs) that are more evident in the fronto-parietal region contralateral to the stimulated side (Curio, 2000). Although most HFOs is likely generated within or nearby the primary somatosensory area (Curio et al., 1994a,b), the 600 Hz burst shows a dramatic reduction in amplitude during sleep, while the primary N20 remains unaffected (Yamada, 1988; Hashimoto et al., 1996), suggesting that low-frequency and high-frequency SEPs are generated by different cell populations. Dipolar analysis studies have already demonstrated that several sources at subcortical and cortical levels can account for the generation of HFOs (Buchner et al., 1995; Restuccia et al., 2002a,b); the later part of scalp HFOs has been suggested to include two components, the former of which generated in the terminal part of thalamocortical relay cells and the latter within the somatosensory cortex (Haueisen et al., 2001). The aim of this study was to identify low- and highfrequency MN SEP generators by stereotactically implanted electrodes in the parietal lobe (SI and neighbouring areas) of two epileptic patients.

2. Materials and methods 2.1. Patients (Table 1) SEPs to electrical MN stimulation were recorded in two patients (one female, one male, 38 and 32 years old, respectively), who presented with drug-resistant epilepsy (in both cases, temporal lobe epilepsy), and were investigated by using stereotactically chronically implanted electrodes in the parietal lobe. In particular, while patient 1 was explored in the SI area, the second patient was implanted just posterior to the post-central gyrus. The choice of exploring this area resulted from the observation of scalp electroencephalographic (EEG) discharges or videotaped ictal symptoms, that suggested the possibility of a parietal spreading of the seizures. Besides the parietal area, other implanted areas were the temporal-mesial structures, the temporal neo-cortex and, in the first patient, also the furthermost anterior region of the frontal lobe. Moreover, on the basis of stereo-electroencephalographic (SEEG) recording in both patients, the epileptogenic zone was believed to spare the post-central area. Only patient 1 was operated (temporal lobectomy), obtaining satisfying results (class Ia of Engel, 1993), although the follow-up was performed earlier than 6 months after the intervention. The patients were fully informed of the MN stimulation paradigm and of the aim of SEP recording, which in our department is part of the routine functional mapping performed in all patients implanted with intracortical electrodes, prior to surgical intervention. 2.2. Implantation of stereo-electroencephalographic (SEEG) electrodes In both patients (Figs. 1 and 2), electrodes (Dixiw, Besanc¸on, France) were implanted orthogonally by using Talairach’s stereotactic frame; they could be left in place chronically up to 15 days. The post-central area was implanted with a single electrode per patient (10 and 15 contacts respectively, with a 2 mm length each, at intervals of 1.5 mm. Each contact could be localized on the basis of lateral and postero-anterior skull films, performed during stereotactic procedures and transferred into Talairach’s

Table 1 Case histories Patients

Sex

Age

DD

NE

Scalp interictal EEG

EF

Therapy

Pt 1 Pt 2

Female Male

38 32

32 21

Normal Normal

Left T-P spikes and slow waves BiT spikes and slow waves

Left T Right T

CBZ CBZ þ PB þ TPM

DD, disease duration in years; NE, neurological examination; CBZ, carbamazepine; TPM, topiramate; PB, Phenobarbital; T, temporal; P, parietal; and BiT, bitemporal.

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

649

Fig. 1. Coordinates of contacts where contralateral SEPs were recorded in the stereotactic system of Talairach and Tournoux. These contacts were restricted to the post-central area.

space by using angiographic and ventriculographic landmarks, as showed by Talairach et al. (1967). In this way, it was possible to calculate the distance between the contacts and the median sagittal plane, the anterior commissureposterior commissure (AC-PC) horizontal plane and the vertical anterior commissure (VAC) frontal plane. Thus, 3 coordinates were measured for each contact: x for the lateral medial axis, with x ¼ 0 as the coordinate of the sagittal inter-hemispheric plane; y for the rostro-caudal axis, with

y ¼ 0 as the coordinate of the VAC frontal plane, and z for the vertical axis, with z ¼ 0 as the coordinate of the horizontal plane (AC-PC). Finally, orthogonally implanted electrodes in the postcentral cortex enabled us to explore both lateral and mesial regions of the parietal lobe in our subjects. Since in patient 2 the electrodes were compatible to MRI, after implantation it was possible to check the localization of each electrode on individual MRI slices.

Fig. 2. Coordinates of contacts where contralateral SEPs were recorded in the stereotactic system of Talairach and Tournoux. These contacts were restricted to the area just posterior to the post-central gyrus.

650

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

Stereotactic coordinates of SI electrodes were the following: x: 7 (first contact), y: 23, z: 40 for patient 1; x: 12 (first contact), y: 2 33 and z: 32 for patient 2. 2.3. SEP recordings Depth SEP recordings (Micromed Italia, Conegliano Veneto, Italy) were performed 10 days after the electrode implantation. MN stimulations of 100 ms were delivered by skin electrodes at the wrist; the stimulus intensity was adjusted slightly above the motor threshold. In both patients, two different protocols were used:

1. analysis time of 50 ms with an interstimulus interval varying randomly between 640 and 780 ms, a sampling frequency of 5000 Hz and an analogue filter bandpass of 14 –1500; 2. analysis time of 512 ms with an interstimulus interval varying randomly between 4500 and 5500 ms, a sampling frequency of 1000 Hz and an analogue filter bandpass of 1– 250 Hz. Scalp SEPs were recorded simultaneously by means of disk electrodes (impedance below 5 KV), placed on the central area contralateral to MN stimulation according to the 10 –20 system. The reference electrode was at the earlobe ipsilateral to the stimulus, and the ground was a circular wrapped electrode at forearm ipsilateral to stimulation. In patient 1, SEPs were recorded after both ipsilateral and contralateral MN stimulation in the two recording conditions. Two runs of 100 and 600 responses each were averaged for long-latency and short-latency SEP recordings, respectively. In order to study high-frequency responses, an off-line digital filtering of depth and scalp short-latency SEPs was performed (500 –800 Hz, 24 dB roll-off). Spectral analysis was performed by fast Fourier transform. The frequency resolution was 16 Hz. 2.4. Stereotactic coordinates of the depth responses The depth coordinates (x) of the SEP sources were assessed by the depth of the contacts where polarity reversal occurred in referential recordings. When no polarity reversal was observed along the whole electrode track, the contact where the response reached its maximal amplitude was considered as the closest one to the source (see Frot and Mauguie`re, 1999 for a complete description of the procedure). Furthermore, an off-line bipolar analysis was performed to detect eventual phase reversals along the electrode trajectory.

3. Results 3.1. Short-latency scalp SEPs (0 – 50 ms latency range) In both patients, at central electrode contralateral to MN stimulation a P14 response (14.7 and 15.26 ms for patients 1 and 2, respectively) and a N20 potential (18.2 and 19.90 ms for patients 1 and 2, respectively) could be recognized. The N20 potential was followed by a positive potential at 25 and 25.2 ms for patients 1 and 2, respectively. 3.2. Long-latency SEPs (50 – 150 ms) In both patients, at central electrode we recorded a P45 potential (39.1 and 50 ms, respectively) followed by a N60 response (70.3 and 73.2 ms for patients 1 and 2) and a P100 potential (112 and 127 ms, for patients 1 and 2, respectively). 3.3. High-frequency SEPs In patient one it was not possible to clearly detect high frequency SEPs, since the traces were noisy due to technical problems. Conversely in patient 2 a 600 Hz burst was identified (Fig. 7). 3.4. Depth recordings 3.4.1. Short latency SEPs (0 – 50 ms latency range) In both patients (Figs. 3 and 4) SI electrode showed a P14 response (latencies: 15.50 and 15.75 ms for patients 1 and 2, respectively) followed by a biphasic response called N20/P30 potential (latencies: 19.17 and 28.20 ms for patient 1; 20.51 and 31.74 ms for patient 2). No phase reversal was found in referential recordings, and the N20/P30 response reached its maximal amplitude at x: 35 mm and x: 50.5 mm for patients 1 and 2, respectively. However, the N20/P30 inverted its polarity in bipolar recordings, as shown in Fig. 5 (depth of 35 – 38.5 mm from midline for patient 1 and depth of 47– 50.5 mm from midline for patient 2). In patient 1 a negativity at about 36 ms was recorded from the first contact to the one located at x: 24.5 mm, showing a clear phase reversal at a depth of 14 mm from midline. Ipsilateral recordings were performed in patient 1; no detectable response was obtained. 3.4.2. Long-latency SEPs (50 – 150 ms latency range) In both patients (Figs. 3 and 4) the N20 – P30 potential was followed by a negative potential at 56.64 and 50 ms of latency for patients 1 and 2, respectively. This response, named N50, was followed by a positive potential in the 70 ms latency range, the P70 potential. In referential recordings the N50/P70 response showed a clear phase reversal at x: 14 mm in patient 1, while in patient 2 it

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

651

Fig. 3. Short-latency SEPs (on the left) and long-latency SEPs (on the right), recorded by chronically implanted electrode in the SI area of patient 1. Distance from midline (x) is given in mm.

reached its maximal amplitude at the same stereotactic coordinates as the N20/P30 potential. In patient 1, a small negative response in the 100 ms latency range showed an increase in amplitude from the surface to the depth, inverting its polarity at x: 14 mm.

In patient 2 the same late response was detectable after the P70 potential, without any clear amplitude modification along the electrode track. No detectable response was obtained from patient 1, on whom ipsilateral recordings were performed.

Fig. 4. Short-latency SEPs (on the left) and long-latency SEPs (on the right), recorded by chronically implanted electrode in the parietal lobe posterior to SI area of patient 2. Distance from midline (x) is given in mm.

652

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

Fig. 5. Bipolar short-latency and high-frequency SEP recordings in patient 1 (top) and patient 2 (bottom). Dotted lines indicate phase reversal of both wideband and high-frequency SEPs. Contact 1 was the deepest one along electrode trajectory.

Fig. 6. On the left, high-frequency SEPs by chronically implanted electrode in the SI area of patient 1. The first row shows the scalp wide-pass SEPs at central lead. The two depth HFO components are underlined (see text). On the right, frequency analysis at 3 contacts. Contact 1 was the deepest one along electrode trajectory.

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

653

Fig. 7. On the left, high-frequency SEPs by chronically implanted electrode in the SI area of patient 2. The first row shows the scalp wide-pass and highfrequency SEPs at central lead. The two depth HFO components are underlined (see text). On the right, frequency analysis at 3 contacts.

3.4.3. High-frequency SEPs (Figs. 6 and 7) At the same depth coordinates as wide-pass shortlatency SEPs, it was possible to detect high-frequency bursts lasting between 14.8 and 26.1 ms after the stimulus in patient 1, and between 14.7 and 26.7 ms after the stimulus in patient 2. In both patients the mere visual analysis showed two subcomponents. In patient 1, the first component (latency range 17.5– 24.4 ms) was evident from x: 17.5 mm to the surface, and the second one (latency range 14.8 –26.1 ms) was detectable from x: 21 mm to the surface. In patient 2, the first component (latency range 14.7 –19.2 ms) was detectable along the whole electrode trajectory, and the second one (latency range 19.2– 26.7 ms) was recognizable from a depth of 29.5 mm to the surface. With regard to spectral analysis, by examining traces recorded at single contacts from surface to depth, in patient 1 we recognized a peak frequency of 576 Hz that reached its maximal amplitude at x: 35 mm, while another peak frequency at about 640 Hz was found at x: 17.5 mm. At deeper contacts, both frequencies progressively decreased. In patient 2, the first peak frequency of 672 Hz reached its maximum at x: 50.5 mm, and then reduced its amplitude from surface to depth, while another peak frequency at

about 608 Hz was found at x: 26 mm, decreasing at deeper contacts, as well. The two components, detected by mere visual analysis, were probably related to the two frequencies assessed by spectral analysis. We called the higher frequency iP1 (intracortical P1) and the lower frequency iP2 (intracortical P2). These two components did not show any phase reversal in referentials recordings. However, in bipolar recordings HFOs inverted their polarity at two differents x coordinates. In particular, in patient 1 the phase reversals were identifiable at x: 21– 24.5 and 35– 38.5, and in patient 2 the phase reversals were at x: 29.5– 33 and 50.5– 54 mm. The deeper component was earlier than the more superficial one in both patients (Fig. 5).

4. Discussion 4.1. Short-latency SEPs This was the very first study recording wide bandpass and high frequency SEPs by electrodes exploring both lateral and mesial part of parietal lobe, and particularly of the post-central gyrus. Allison et al. (1989a) recorded SEPs by means of a subdural grid from the surface of the hand

654

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

representation area of the sensorimotor cortex. They showed two potentials: the P20/N30 (positive was upwards) from the post-central locations, and the N20/P30 from the precentral area. The authors concluded that the P20/N30 and the N20/P30 were generated by a dipole tangentially oriented in the area 3b of the SI. In our two patients we could record a N20/P30 response by stereotactically implanted electrodes in the parietal lobe (SI and neighbouring areas). Furthermore, it was possible to assess that the N20/P30 response did not show any polarity reversal along the electrode track in referential recordings, clearly confirming the tangential orientation of its source (Valeriani et al., 1997, 2000; Restuccia et al., 1999). Conversely, an N20/P30 phase reversal was noticed in bipolar recordings at the same depth coordinates as the maximum showed in referential recordings, suggesting that the N20 –P30 generator was located in the explored region, i.e. the SI and neighbouring areas. The polarity reversal found in bipolar recordings allows to localize the maximum potential, thus the depth position of the source, although it does not give a clear orientation of the dipole in connection to that of the electrode track (Frot and Mauguie`re, 1999). The central sulcus is about 1.8 cm deep, and the 3b area occupies most of its posterior bank (Allison et al., 1991). Therefore, a dipolar generator located in the 3b area would lie within 1 cm from surface, as the source of the N20/P30 found in our patients. This response is likely analogous to the negative-positive potential recorded from the somatosensory cortex of monkeys (Allison et al., 1991; Arezzo et al., 1981), cats (Allison et al., 1966; Towe, 1966) and other mammals (Woolsey and Fairman, 1946), and it might represent the so-called primary response. Its positive part is due to the depolarization of the bodies of pyramidal cells, while the negative response seems to reflect the later depolarization of apical dendrites (Landau, 1967; Werner and Whitsel, 1968). As in our patients the depth and scalp SEPs could be recorded simultaneously, we showed that the scalp N20 was recorded at about the same latency as the depth N20 potential. On the contrary, since the N30 and the N24 could be hardly distinguished in fronto-central leads, it was not possible to determine a precise correspondence with the depth P30. Finally in our patient 1, a phase reversal was recorded at 36 ms of latency in referential recordings, thus suggesting a radial generator for this response (N36), located deeper than the N20/P30 potential source. Since the N36 potential was not recorded in patient 2, who was implanted just beyond the SI area, the N36 radially oriented dipole is likely to be located only in the SI area. 4.2. Long-latency SEPs In our patients, a N50/P70 potential was recorded at the same depth coordinates as the N20/P30, thus suggesting that it may be originated in the SI area and neighbouring areas.

Only a few authors analyzed the middle-latency SEPs recorded between 40 and 100 ms after MN stimulation. The fronto-central N60 response is believed to originate in the SI area (Srisa-an et al., 1996; Tarkka et al., 1996; Allison et al., 1992). In particular, while some authors (Srisa-an et al., 1996; Allison et al., 1992) explained the N60 activity by means of a radial dipole, Tarkka et al. (1996) showed a tangential orientation of the N60 source. Valeriani et al. (1997) modelled the N60 by means of a dipolar source radially oriented in the perirolandic region, while the P100 was explained by a tangential perirolandic dipole. In a recent SEP modelling study (Barba et al., 2002) two perirolandic dipoles (1 and 2), the first of which radially oriented, and the other one tangentially oriented, were active at the N60 latency, thus confirming these previous findings. We recorded a depth N50/P70 response by chronically implanted electrodes in the parietal cortex of both patients; however, in patient 1, this potential showed a clear phase reversal in intracortical referential recordings, suggesting that it may be generated by a radial dipole located in the SI area. Comparing the intracranial N50/P70 responses to scalp recordings at central leads, the depth N50 seemed to contribute to the scalp N60, while the depth P70 was recorded earlier than the scalp P100, probably because several generators located in different areas contribute to the P100 potential (Barba et al., 2002). Allison et al. (1989b, 1992) recorded SEPs from the cortical surface, and concluded that scalp potentials recorded within 100 ms after stimulus probably originate in the SI cortex. In particular they identified a N45/P80 response originated in area 3b, possibly corresponding to our N50/P70 potential. We could not analyze the cognitive modifications of late responses. In ‘neutral’ condition, in both patients the last reliable potential recorded in the SI area was a negative response in the 100 ms latency range. In patient 1, this N100 inverted its polarity at x: 14 mm, whereas this potential did not show any amplitude modification along the electrode track in patient 2, who received the implant just beyond the post-central gyrus, thus suggesting the presence of a radial source located in the SI area. In MEG and SEP source modelling studies (Mauguie`re et al., 1997; Barba et al., 2002; Valeriani et al., 2001) the SI activation occurred over 150 ms after the stimulus. Our data did not confirm this long activation, probably due to the low spatial sampling of SEEG recordings. 4.3. High frequency SEPs In both patients, a high-frequency SEP burst was detected just after the scalp P14 potential, as shown in Figs. 6 and 7; its onset coincided with the onset of the cortical N20 response. Spectral analysis of this burst showed two components in the 500– 800 latency range, called intracortical P1 (iP1) and P2 (iP2). It is conceivable that

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

both iP1 and iP2 have a cortical origin, since they were recorded just after the sub-cortical P14 response, and their amplitude decreased from the surface to depth. No HFO phase reversal was detected in referential recordings. Conversely, in bipolar recordings HFOs showed two phase reversals, suggesting that their sources are located along the electrode track in the parietal lobe, and particularly in the SI area of one patient. This finding was supported by the fact that in referential recordings the iP1 reached its maximum at the same depth coordinates as the N20 response, and in bipolar recordings the later HFO inversion polarity had one contact in common with the N20/P30 phase-reversing site. Several reports, both invasive and non-invasive, tried to clarify the high-frequency somatosensory evoked response generators. MEG studies (Curio et al., 1994a,b) suggested that the magnetic burst generators were located at, or near the area 3b, but they did not solve the question whether 600 Hz bursts are generated by the terminal part of the thalamocortical radiations, or by specialized cortical cells able to discharge with a bursting pattern, namely specialized types of pyramidal neurons (chattering cells, Gray and McCormick, 1996) and of GABAergic interneurons (fast spiking cells; Kawaguchi, 1993; Hashimoto et al., 1996). A previous stereotactic study in humans suggested that HFOs are generated by rapidly repeating spikes conducted subcortically in the thalamocortical radiation, as assessed by means of an electrode array in the vicinity of the ML and/or the VPL nucleus (Katayama and Tsubokawa, 1987). Baker et al. (2003) recorded epidural EEG and extracellular single-unit responses in awake monkeys, and supported the hypothesis of two different HFOs cellular generators, since only the middle part of the SEP burst aligned well with the SI singleunit response. Furthermore, Ikeda et al. (2002) compared MEG potentials obtained from the external surface of the piglet brain with simultaneous intracortical SEPs, before and after an injection of synaptic glutamatergic blockers, and demonstrated the existence of two different HFO preand post-synaptic components. To our knowledge, this is the very first study that recorded HFOs by implanted electrodes, exploring the whole depth of the human parietal cortex. This enabled us to demonstrate that two separate high-frequency SEP generators are located within this area, by means of both referential and bipolar recordings. However our technique did not allow us to define whether thalamocortical afferents rather than cellular generators contribute to these two responses. Recently Haueisen et al. (2001) found in the time interval of the first MEG cortical response 3 distinct frequency bands: the low-frequency band, the 200 Hz band and the 600 Hz band. The 600 Hz band consisted of two components (p1 and p2), and the division boundary between these two components coincided with the N20m peak latency. The p1 and p2 components were associated with the N20m and the P25m. Instead, in another SEP study, Mochizuki et al. (1999) associated the 600 Hz activity only with the P25 potential, as they are both enhanced in

655

myoclonus epilepsy. The dissociate behaviour of HFOs and conventional scalp SEPs during sleep demonstrated that the cell population responsible for generating bursts was different from the one that gives origin the conventional scalp SEPs (Hashimoto et al., 1996). This hypothesis was supported by Shimazu et al. (2000), who recorded scalp and depth MN SEPs in 6 monkeys, and found that the phasereversing point of HFOs was slightly deeper than the wideband components. In this study, the intracranial components named iP1 and iP2 were associated with the depth N20/P30 (see above); thus they are probably generated in the SI area and neighbouring areas. In our patients, the sources of intracortical P1 and P2 were located at different layers of the same cortical area, as assessed by their maximum. This finding solves the question raised by Haueisen et al. (2001) whether the scalp components p1 and p2 are originated in two areas of the SI, or in two different excitatory layers of the same area of the SI. Restuccia et al. (2002a,b) modelled high-frequency SEPs by two perirolandic dipolar sources, showing a tangential and a radial orientation, respectively. In our patients no phase reversal was found in referential recordings, while two different components inverted their polarity in bipolar recordings. This suggests that, as the N20 – P30 response, also the two intracranial HFOs components were generated by tangential sources in the SI and neighbouring areas. However, we cannot conclude about the presence of radial components, as the crown of the post-central gyrus (SI area) was not explored by means of depth probes.

References Allison T, Goff WR, Sterman MB. Cerebral somatosensory responses evoked during sleep in the cat. Electroenceph clin Neurophysiol 1966; 21(5):461–8. Allison T, Goff WR, Williamson PD, Van Gilder JC. On the neural origin of early components of the human somatosensory evoked potential. In: Desmedt JE, editor. Clinical uses of cerebral, brain-stem and spinal somatosensory evoked potentials. Progress in clinical neurophysiology, 7. Basel: Karger; 1980. p. 51–68. Allison T, McCarthy G, Wood CC, Darcey TM, Spencer DD, Williamson PD. Human cortical potentials evoked by stimulation of the median nerve. I. Cytoarchitectonic areas generating short-latency activity. J Neurophysiol 1989a;62:694 –710. Allison T, McCarthy G, Wood CC, Williamson PD, Spencer DD. Human cortical potentials evoked by stimulation of the median nerve. II. Cytoarchitectonic areas generating long-latency activity. J Neurophysiol 1989b;62:711–22. Allison T, McCarthy G, Wood CC, Jones SJ. Potentials evoked in human and monkey cerebral cortex by stimulation of the median nerve. A review of scalp and intracranial recordings. Brain 1991;114(Pt 6): 2465–503. Allison T, McCarthy G, Wood CC. The relationship between human longlatency somatosensory evoked potentials recorded from the cortical surface and from the scalp. Electroenceph clin Neurophysiol 1992;84: 301– 14.

656

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657

Arezzo JC, Vaughan Jr HG, Legatt AD. Topography and intracranial sources of somatosensory evoked potentials in the monkey. II. Cortical components. Electroenceph clin Neurophysiol 1981;51(1):1– 18. Baker NS, Curio G, Lemon NR. EEG oscillations at 600 Hz are macroscopic markers for cortical spike bursts. J Physiol 2003;5550.2: 529– 34. Barba C, Frot M, Gue`not M, Mauguie`re F. Stereotactic recordings of median nerve somatosensory evoked potentials in the human presupplementary motor area. Eur J Neurosci 2001;13(2):347–56. Barba C, Frot M, Valeriani M, Tonali P, Mauguie`re F. Distinct frontocentral N60 and supra-sylvian N70 middle-latency components of the median nerve SEPs as assessed by scalp topographic analysis, dipolar source modelling and depth recordings. Clin Neurophysiol 2002; 113(7):981–92. Barba C, Valeriani M, Restuccia D, Colicchio G, Faraca G, Tonali P, Mauguie`re F. The human SMA-proper (supplementary motor area) does not receive direct somatosensory inputs from the periphery. Data from stereotactic depth SEP (somatosensory evoked potential) recordings. Neurosci Lett 2003 Jul 3;344(3):161–4. Brodmann K. Vergleichende Localisationslehre der Grosshirnrinde in ihren Prinzipien Dargestellt auf Grund des Zellenbaue. Edited by Johann Ambrosius Barth, Leipzig, 1909. Broughton R. Discussion. In: Donchin E, Lindsley DB, editors. Average evoked potentials: methods, results, and evaluations. Washington: National Aeronautics and Space Administration; 1969. p. 79– 84. Buchner H, Waberski TD, Fuchs M, Wishmann HA, Beckmann R, Riena¨cker A. Origin of P16 median nerve SEP component identified by dipole source analysis. Subthalamic or within the thalamocortical radiations? Exp Brain Res 1995;104:511– 8. Cottier Eskenasy AC, Clarke S. Hierarchy within human SI: supporting data from cytchrome oxidase, acetylcholinesterase and NADPH diaphorase staining patterns. Somatos Motor Res 2000;17:123–32. Curio G. Linking 600-Hz ‘spikelike’ EEG/MEG wavelets (‘sigma-bursts’) to cellular substrates: concepts and caveats. J Clin Neurophysiol 2000; 17(4):377–96. Curio G, Mackert BM, Abraham-Fuchs K, Haerer W. High-frequency activity (600 Hz) evoked in human primary somatosensory cortex – a review of electric and magnetic recordings. In: Pantev C, Elbert T, Lu¨tkenho¨ner B, editors. Oscillatory event related brain dynamics. NATO ASI series A: life sciences, 271. New York: Plenum Press; 1994a. p. 205–18. Curio G, Mackert BM, Burghoff M, Koetitz R, Abraham-Fuchs K, Harer W. Localization of evoked neuromagnetic 600 Hz activity in the cerebral somatosensory system. Electroenceph clin Neurophysiol 1994b;91(6):483– 7. Desmedt JE, Bourguet M. Color imaging of parietal and frontal somatosensory potentials field evoked by stimulation of median or posterior tibial nerve in man. Electroenceph clin Neurophysiol 1985;62: 1–17. Desmedt JE, Nguyen TH, Bourguet M. Bit-mapped color imaging of human evoked potentials with reference to the N20, P22, P27 and N30 somatosensory responses. Electroenceph clin Neurophysiol 1987;68: 1–19. Engel Jr J. Update on Surgical treatment of the epilepsies. Summary of the Second International Palm Desert Conference on the surgical treatment of the epilepsies. Neurology 1993;43:1612 –7. Frot M, Mauguie`re F. Timing and spatial distribution of somatosensory responses recorded in the upper bank of the sylvian fissure (SII area) in humans. Cereb Cortex 1999;9:854–63. Goff GD, Matsumiya Y, Allison T, Goff WR. The scalp topography of human somatosensory and auditory evoked potentials. Electroenceph clin Neurophysiol 1977;42:57– 76. Gray CM, McCormick DA. Chattering cells: superficial pyramidal neurons contributing to the generation of synchronous oscillations in the visual cortex. Science 1996;274(5284):109–13. Hashimoto I, Mashiko T, Imada I. Somatic evoked high-frequency magnetic oscillations reflect activity of inhibitory interneurons in

the human somatosensory cortex. Electroenceph clin Neurophysiol 1996;100:189–203. Haueisen J, Schack B, Meier T, Curio G, Okada Y. Multiplicity in the highfrequency signals during the short-latency somatosensory evoked cortical activity in humans. Clin Neurophysiol 2001;112(7):1316–25. Ikeda H, Leyba L, Bartolo A, Wang Y, Okada Y. Synchronized spikes of thalamocortical axonal terminals and cortical neurons are detectable outside the pig brain with MEG. J Neurophysiol 2002;87:626–30. Kaas JH, Garraghty PE. Hierarchical, parallel and serial arrangements of sensory cortical areas: connections pattern and functional aspects. Curr Opin Neurobiol 1991;1:248–51. Kaas JH, Nelson RJ, Sur M, Lin CS, Merzenich MM. Multiple representation of the body within the primary somatosensory cortex of primates. Science 1979;204(521):523. Katayama Y, Tsubokawa T. Somatosensory evoked potentials from the thalamic sensory relay nucleus (VPL) in humans: correlations with short latency somatosensory evoked potentials recorded at the scalp. Electroenceph clin Neurophysiol 1987;68(3):187 –201. Kawaguchi Y. Physiological, morphological, and histochemical characterization of 3 classes of interneurons in rat neostriatum. J Neurosci 1993; 13(11):4908–23. Landau WM. Evoked potentials. In: Quartn GC, Melnechuk T, Schmitt FO, editors. The neurosciences. New York: Rockfeller Univ. Press; 1967. p. 469 –82. Mauguie`re F, Desmedt JE, Courjon J. Astereognosis and dissociated loss of frontal or parietal components of somatosensory evoked potentials in hemispheric lesions: detailed correlations with clinical signs and computerized tomographic scanning. Brain 1983;106:271 –311. Mauguie`re F, Merlet I, Forss N, Vanni S, Jousma¨ki P, Adeline R, Hari R. Activation of distributed somatosensory cortical network in the human brain, a dipole modelling study of magnetic fields evoked by median nerve stimulation, Part I: location and activation timing of SEF sources. Electroenceph clin Neurophysiol 1997;104:281–9. Mochizuki H, Ugawa Y, Machii K, Terao Y, Hanajima R, Furubayashi T, Uesugi H, Kanazawa I. Somatosensory evoked high-frequency oscillation in Parkinson’s disease and myoclonus epilepsy. Clin Neurophysiol 1999;110(1):185 –91. Restuccia D, Valeriani M, Barba C, Le Pera D, Tonali P, Mauguie`re F. Different contribution of joint and cutaneous inputs to early scalp somatosensory evoked potentials. Muscle Nerve 1999;22:910 –9. Restuccia D, Valeriani M, Grassi E, Gentili G, Mazza S, Tonali P, Mauguie`re F. Contribution of GABAergic cortical circuitry in shaping somatosensory evoked scalp responses: specific changes after single-dose administration of tiagabine. Clin Neurophysiol 2002a;113(5):656– 71. Restuccia D, Valeriani M, Grassi E, Mazza S, Tonali P. Dissociated changes of somatosensory evoked low-frequency scalp responses and 600 Hz bursts after single-dose administration of lorazepam. Brain Res 2002b;946(1):1 –11. Rossini PM, Bassetti MA, Pasqualetti P. Median nerve somatosensory evoked potentials. Apomorphine-induced transient potentiation of frontal components in Parkinson’s disease and in parkinsonism. Electroenceph clin Neurophysiol 1995;96(3):236 –47. Shimazu H, Kaji R, Tsujimoto T, Kohara N, Ikeda A, Kimura J, Shibasaki H. High-frequency SEP components generated in the somatosensory cortex of the monkey. NeuroReport 2000;11:2821 –6. Srisa-an P, Lei L, Tarkka IM. Middle latency somatosensory evoked potentials: non-invasive source analysis. J Clin Neurophysiol 1996; 13(2):156–63. Stohr PE, Dichgans J, Voigt K, Buettner UW. The significance of somatosensory evoked potentials for localization of unilateral lesions within the cerebral hemispheres. J Neurol Sci 1983;61:49–63. Talairach J, Szikla G, Tournoux P, Prossalentis A, Bordas-Ferrer M, Covello L. Atlas d’Anatomie Ste´re´otaxique du Te´lence´phale. Paris: Masson; 1967. Tarkka IM, Micheloyannis S, Stokic DS. Generators for human P300 elicited by somatosensory stimuli using multiple dipole source analysis. Neuroscience 1996;75(1):275–87.

C. Barba et al. / Clinical Neurophysiology 115 (2004) 647–657 Towe AL. On the nature of the primary evoked response. Exp Neurol 1966; 15(1):113–39. Treede RD, Kunde V. Middle-latency somatosensory evoked potentials after stimulation of the radial and median nerves: component structure and scalp topography. J Clin Neurophysiol 1995;12: 291–301. Valeriani M, Restuccia D, Di Lazzaro V, Le Pera D, Tonali P. The pathophysiology of giant SEPs in cortical myoclonus: a scalp topography and dipolar source modeling study. Electroenceph clin Neurophysiol 1997;104:122 –31. Valeriani M, Le Pera D, Niddam D, Arendt-Nielsen L, Chen ACN. Dipolar source modeling of painful and non-painful SEPs to median nerve stimulation. Muscle Nerve 2000;23:1164– 203.

657

Valeriani M, LePera D, Tonali P. Characterizing somatosensory evoked potential sources with dipole models: advantages and limitations. Muscle Nerve 2001;24(3):325–39. Woolsey CN, Fairman D. Contralateral, ipsilateral, and bilateral representation of cutaneous receptors in somatic areas I and II of the cerebral cortex of pig, sheep and other mammals. Surgery St. Louis 1946;19: 684– 702. Yamada T. The anatomic and physiologic bases of median nerve somatosensory evoked potentials. Neurol Clin 1988;6(4):705–33. Zilles K, Schlaug G, Matelli M, Luppino G, Schleicher A, Qu M, Dabringhaus A, Seitz R, Roland PE. Mapping of human and sensorimotor areas by integrating architectonic, transmitter receptor, MRI and PET data. J Anat 1995;187:515–37.