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Cerebral magnetic fields to lingual stimulation
Electroencephalography and clinical Neurophysiology , 80 (1991) 459-468
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© 1991 Elsevier Scientific Publishers Ireland, Ltd. 0168-5597/91/$03.50
EVOPOT 90617
Cerebral magnetic fields to lingual stimulation * J. Karhu, R. Hari, S.-T. Lu, R. Paetau and J. Rif Low Temperature Laboratory, Helsinki University of Technology, SF-02150 Espoo (Finland) (Accepted for publication: 16 January 1991)
Summary We recorded cerebral magnetic fields to electric stimulation of the tongue in 7 healthy adults. The two main deflections of the response peaked around 55 msec (P55m) and 140 msec (N140m). During both of them the magnetic field pattern, determined with a 7- or 24-channel SQUID magnetometer, suggested a dipolar current source. The topography of P55m can be explained by a tangential dipole at the first somatosensory cortex (SI) in the posterior wall of the central sulcus. The equivalent source of N140m is, on average, about 1 cm lateral to the source of P55m. The reported method allows non-invasive determination of the cortical tongue representation area. Key words: Evoked responses; Magnetoencephalography; Somatosensory cortex; Tongue; Trigeminal nerve
Objective neurophysiological evaluation methods for the trigeminal system would be of much interest in sensory disturbances of the face and oral cavity, occurring in a number of clinical situations. The first trigeminal somatosensory evoked potentials (TSEPs) were reported to mechanical stimulation of the face (Larsson and Prevec 1970). Since then responses have been recorded mostly to electrical stimulation of lips and gums, both of which have relatively high sensory receptor density. The tongue shares this property; TSEPs have been recorded to tapping and electrical stimulation of the tongue (Ishiko et al. 1980; Altenmiiller et al. 1990). TSEP studies have been controversial due to variable stimulation and recording methods (cf., Table I): peak latencies from 1 to 150 msec have been recorded from the contralateral scalp of healthy adults. The most consistent responses to stimulation of lips, gums or tongue occur around 20 msec (St6hr and Petruch 1979; Barker et al. 1987; Altenmiiller et al. 1990), altfiough more variable peaks up to latencies of 120150 msec have been reported (Findler and Feinsod 1982; Drechsler and Neuhauser 1986). Attempts have also been made to use TSEPs diagnostically in a variety of trigeminal lesions, such as trigeminal neuralgia (St6hr et al. 1981), multiple sclerosis (Murray and Tan 1984), impairments following trauma or oral and max-
* A preliminary report of this study has been presented in abstract form (Karbu et al. 1990)
Correspondence to: J. Karhu, Low Temperature Laboratory, Helsinki University of Technology, SF-02150 Espoo (Finland). FAX: 358-0-4512969.
illofacial surgery (Barker et al. 1987), and lesions of the mandibular branches (Buettner et al. 1987). The first cortical TSEP has been suggested to appear as early as 10 msec (Leandri et al. 1987). Authors using surface stimulation have proposed responses at 14 msec (Drechsler and Neuhauser 1986) and around 20 msec (Barker et al. 1987; Altenmiiller et al. 1990) to be the first signs of cortical activity~ The exact generators of the later deflections, although thought to be cortical (Bennett et al. 1987), have remained unknown. In the present study we applied magnetoencephalography (MEG), a non-invasive method with good spatial resolution, to determine the sites of cortical activity after lingual nerve stimulation. Active areas in both the first (SI) and second (SII) somatosensory cortex have been located with MEG after stimulation of various peripheral nerves (Brenner et al. 1978; Hari et al. 1984, 1990; Okada et al. 1984; Wood et al. 1985; Kaukoranta et al. 1986a; Tiihonen et al. 1989).
Methods
Subjects and recordingprocedures Seven subjects (4 members of laboratory personnel and 3 paid volunteers; 5 males and 2 females; age range 19-41 years) were studied in a magnetically shielded room. The evoked magnetic field component B r normal to the head was measured from 28 to 63 locations over the right hemisphere with a low-noise (5-6 f T / ( ~ H ~ ) 7-channel first-order DC=SQUID gradiometer (Knuutila et al. 1987). The pickup coils of the device, separated by 36.5 mm, are installed in a
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TABLE I Examples of response latencies, stimulation sites, recording passbands and interstimulus intervals (ISis) used by different authors in recording trigeminal somatosensory evoked potentials. Surface electrodes were used for stimulation, unless otherwise stated. Peak latencies (msec)
Stimulation site
Passband (Hz)
ISI (sec)
Authors
13, 19, 26 8, 13, 18 24, 33, 46, 55, 101, 120 5, 9, 14, 34, 44, 100, 150 20, 29, 37
both lips lower lip
2 1 1 0.520 -
2000 3000 30 2000 1000
0.5 0.5
St6hr and Petruch (1979) Findler and Feinsod (1982)
3 0.5
Drechsler and N e u h a u s e r (1986) Barker et al. (1987)
10 - 1 0 0 0 0
0.3
Leandri et al. (1987)
16 - 1000
0.3
Altenmiiller et al. (1990)
1, 2, 3, 4, 5, 6, 7, 10 21
mental nerve upper lip gum infraorbital nerve (needle) tongue
hexagonal array on a spherical surface (radius 125 mm) covering an area with a diameter of 93 mm. Additional experiments were made with a 24-channel gradiometer recently constructed in our laboratory (Kajola et al. 1990). This device uses a planar flux transformer configuration: with two orthogonal loops at one location two off-diagonal field gradients, aBr/ax and aBr/ay, are obtained at 12 locations simultaneously, 30 mm apart (cf., Fig. 1). While the axial magnetometer detects the field extrema on both sides of the dipole, the planar gradiometer records the maximum total signal (~(3Br//Ox) 2 + (OBr//3y) 2 ) just above the dipolar source. Therefore, the coverage ( ~ = 12.5 cm) of this gradiometer often allowed the source area to be determined with one positioning of the instrument. The locations and orientations of the sensors with respect to the head were determined by analysing magnetic s~gnals resulting from the activation of a set of small coils fixed on known locations on the scalp (Knuutila et al. 1987). During the measurements the subject was lying with h i s / h e r head supported by a vacuum cast. •
Stimuli Constant-current pulses of 0.1 msec duration (Grass $88 stimulator, Grass SIU 4678 isolation unit and Grass CCU 1A constant current unit) were delivered to the anterior left side (in two subjects also to the right side) of the tongue through a self-made clip electrode, consisting of two Ag plates (diameter = 5 mm) and contacting the upper and lower sides of the tongue. The outside of the electrode was insulated to avoid synchronous stimulation of the oral mucosa. The tongue was held relaxed inside the slightly opened mouth to allow leads to come out between the upper and lower teeth• The stimulus current was adjusted to
produce a visible local contraction on the stimulated side of the tongue tip; this usually occurred at current strengths of 3 - 4 times the sensory threshold. The stimuli were not painful and did not cause any visible contraction of facial muscles or blinking. The interstimulus interval was 505 msec. Electrical control records were made to ensure that the magnetic records were not contaminated by muscle activity. Electromyographic activity was recorded with standard equipment (Dantec Neuromatic 2000 C) from a concentric needle electrode (Disa). Stimulation and averaging procedures were the same as for magnetic recording.
Signal analysis The recording passband was 0.05-500 Hz (3 dB points, high-pass roll-off 35 d B / d e c a d e and low-pass over 80 dB/decade). The signals were digitized at 2000 Hz and averaged on-line. The analysis period was 256 msec and response amplitudes were measured with respect to a 75 msec prestimulus baseline. The first two responses of each stimulus block were rejected from the analysis and about 350 responses were averaged at each location. Isocontour maps of B r of 7-channel records were constructed by projecting the measurement locations to a plane. If the pattern was dipolar by visual inspection, i.e., had two extrema of opposite polarities, the equivalent dipole was determined with a least-squares fit. The spherical conductor model was used with a radius corresponding to the local radius of curvature of the head in the measurement area. In this procedure the effects of source and volume currents on the measured field are taken properly into account (Sarvas 1987). To obtain isocontour maps for the gradient measurements, the minimum-norm current estimates
Fig. 1. Responses of one subject to alternating stimulation (ISI = 505 msec) of the left median nerve at the wrist and the left side of the tongue. The responses were recorded with the 24-channel gradiometer over the right hemisphere. Th e upper trace of each pair shows the field gradient in the vertical and the lower in the horizontal direction. Two records (N = 350) from both stimulation sites are superimposed. Passband is 0.05-190 Hz.
461
LINGUAL SEPs
MEDIAN NERVE N20m
-
P30m
E1oofT/cm
~ 11
~
12 ~ 456 1 8 910 1112
12
I m l
0
TONGUE
100 ms
1
Lr~
2
N1LOm
\ I m l
0
100 ms
P55m
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(MNE) corresponding to the measured data were first computed. Thereafter, B r generated by MNE was determined (H/im~il~iinen and Ilmoniemi 1990). This procedure accomplishes 3-dimensional interpolation suit-
able for the magnetic field. The gradiometer configurations and the deviations of the sensitivity axes of the gradiometers from the radial direction are taken into account. It is, however, emphasized that the field maps
MEDIAN NERVE N20m MEDIAN ~'" ~ /
AN NERVE 21 ms _OWER LIP
53 2 / UPPER LIP
/w
TONG~
_ I
/
:
I
I
10 nAm I
-F
I
x
I
0
lcm
TONGUE P55m Y
Fig. 2. Left: isocontour maps obtained from the same 24-channel recording as in Fig. 1 (the contours of B r have been calculated from the gradient measurements). Shadowed area indicates magnetic flu~, out of the head, white area flux into the head; the isocontour lines are separated by 20 fT. T h e locations and orientations of the equivalent dipoles are indicated by arrows in the maps. Right: the arrows in the upper right part of picture demonstrate the locations, orientations, and strengths (scale is given) of the equivalent dipoles for responses measured at the same location (goodness-of-fit values 90-97%). The coordinate system is demonstrated in the lower right corner: the x-axis passes the right eye corner and forms a 45 ° angle with the line connecting the ear canal and eye corner; the origiff is 70 nun posterior to the latter. The dotted line indicates the approximate course of the rolandic fissure.
LINGUAL SEPs
463
are only a visual aid and any subsequent dipole fitting for both types of record was done on the original data, using the measured locations and orientations of the sensors. Confidence limits for dipole locations were calculated using the standard errors of the averaged responses as the estimates of experimental noise (Kaukoranta et al. 1986b). These estimates contained both instrumental and brain noise.
Results
Fig. 1 shows responses of one subject, measured with the 24-channel gradiometer, when the contralateral median nerve at the wrist and the contralateral side of the tongue were stimulated alternately in the same session. The response to median nerve stimulation consists of two main deflections N20m and P30m (cf., Tiihonen et al. 1989). The two main deflections to tongue stimulation peak at 55 msec and 115 msec. The maximum amplitude, which in records with the planar gradiometer also suggests the source location, is seen in pair 4 for median nerve and in pairs 8 and 12 for tongue stimulation.
MEDIAN NERVE
Fig. 2 illustrates isocontour maps obtained from the 24-channel records for N20m (median nerve) and P55m (lingual nerve) responses. For comparison, equivalent sources following electrical stimulation are also shown for the contralateral upper and lower lips (at 53 and 51 msec, respectively), and for median nerve at the latency of 53 msec. The orientations of all dipoles are notably similar and the locations agree with the idea that the sources represent activity of the somatotopically organized SI, in the posterior wall of the rolandic fissure. Fig. 3 demonstrates ipsi- and contralateral responses to median nerve and lingual stimulation. For lingual stimulation, the ipsi- and contralateral responses are very similar, both in latency and in amplitude, whereas no clear response is seen for ipsilateral median nerve stimulation at the time of the main contralateral deflections. Responses to lingual stimulation were in all subjects qualitatively similar, with two main deflections, as shown in Fig. 4 for 7-channel records. The earlier deflection, P55m, peaked at 57 + 4 msec (mean _+ S.E.M. of 7 subjects; range 48-69 msec) and reversed in polarity between the upper and lower measurement locations along the central suleus. The later peak
TONGUE ' CONTRA
c3Br
f,
....
'IPSI
;gy
OBr
Ox I
0
•
100 ms
/
O0 f T / c m
0
I
100 ms
Fig. 3. Responses to contralateral (solid lines) and ipsilateral (dashed lines) stimulation of median nerve and tongue in channels with maximum amplitudes in Fig. 1. Other details as in Fig. 1.
464 I. K A R H U E T AL
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Fig. 5, Temporal evolution of magnetic field patterns in S1. Shadowed area indicates magnetic flux out of the head, white area flux into the head; the isocontour lines are separated by 10 f T , T h e locations and orientations of the equivalent dipoles are indicated by arrows. The approximate measurement area is shown in the insert• The maps are based on 63 measurement locations (7-channel recording).
(N140m) occurred at 1 4 2 + 7 msec (range 115-165 msec), with the polarity reversal between the posterior and anterior locations along the sylvian fissure. Responses at 20-24 msec were seen at some measurement locations, but because of their small size and possible contamination by muscular artefacts (cf., AItenmiiller et al. 1990) we did not analyse them in more detail• Fig. 4 also demonstrates that the high-pass filter setting at 10 Hz, commonly used in clinical SEP measurements, abolishes the main deflections. Fig. 5 shows the temporal evolution of the magnetic field pattern to lingual stimulation in subject 1. The patterns, based on 7-channel recording, are dipolar from 45 to 145 msec with two extremes of opposite
polarities. The orientations of the patterns differ from each other at 55 and at 115 msec, i.e., during P55m and N140m. In all our 7 subjects, the field patterns were dipolar during both P55m and N140m. The equivalent current dipoles explained 78-92% of the field variance and the residual field patterns showed no systematic features. The single-dipole model was thus considered to be adequate at these latencies. Fig. 6 shows source locations and the 95% confidence ellipsoids for P55m and N140m. They differ from each other in subjects 4, 5, 6 and 7 at the 95% confidence level. Further, in subjects 1 and 3 the source orientations were perpendicular to each other, although the source locations did not differ statistically
Fig. 4. Above: responses of all 7 subjects (S1-$7) at the superior (SUP) and inferior (INF) field extrema of P55m measured with the 7-channel gradiometer. The later (N140m) deflections are also easily seen in S1, $3 and $4 due to proximity of source locations (cf., Fig. 5). Passband is 0.05-190 Hz. Below: same responses after digital filtering from 10 to 190 Hz.
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J. KARHU ET AL.
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P55m v
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- 2 -1 Fig. 6. Source locations of P55m and N140m for all subjects (S1-$7). The dots show the locations and the arrows the orientations and strengths of the equivalent dipoles (scale is given). The 95% confidence limits for the x-y locations are indicated by ellipsoids (shaded for P55m). The mean (+ S.E.M.; 7 subjects) source locations and orientations are shown in the lower right corner. The coordinate system shown in the insert is equal to that in Fig. 2.
significantly. The mean angle of the dipole from the x-axis was 226 + 6 ° for P55m (mean + S.E.M.; range 201-246 °) and 99 + 14° for N140m (range 60-155°), resulting in an average orientation difference of 127 ° between the two dipoles ( P < 0.001, 2-tailed t test for pair differences). The mean source location for N140m was 7 mm lateral and 2 mm posterior to that for P55m (N.S.). The equivalent dipoles of both peaks were about 30 mm below the scalp. In two subjects both 24and 7-channel records were available, and the source locations did not differ from each other (cf., Fig. 2 for subject 1). Temporal muscle, partially overlying the investigated cortical areas, was monitored by electromyography in one subject during lingual stimulation. A concentric needle electrode was inserted into the upper, posterior corner of the muscle, at the location of the equivalent current source of P55m determined from the magnetic field patterns. Repeated contra- and ipsilateral stimulation of the tongue caused no detectable deflections in the averaged electromyogram.
D i s c u s s i o n
To our knowledge this is the first report of SEFs to trigeminal stimulation. In all our 7 subjects, the responses consisted of 2 main deflections, P55m and N140m, with different source locations and orientations. P55m reversed polarity between the u p p e r and lower recording locations along the central sulcus. In
line with earlier s E F studies, in which different body parts were stimulated, the field pattern suggests that P55m is generated by a tangential current source in the posterior wall of the central sulcus, at Brodmann area 3b (cf., Hari et al. 1984; Wood et al. 1985; Huttunen et al. 1987). This area is clearly lateral to the area activated by electrical stimulation of the median nerve and of other trigeminal branches, thus agreeing with the well-known somatotopic organization of SI (Penfield and Jasper 1954). The different location and orientation of the source of N140m would agree with activation of SII in the. upper bank of the sylvian fissure. The activity in SII around 100-140 msec has been earlier detected with M E G after both upper and lower limb stimulation (Hari et al. 1984, 1990; Kaukoranta et al. 1986a). The complex cortical folding and the proximity of face representation areas in SI and SII - - in line with the observed 1 cm mean separation between the sources - could explain the considerable interindividual variation in the relative locations of these two source areas. Electrical stimulation of cortical face areas causes - in addition to contralateral - - also bilateral and ipsilateral sensations (Penfield and Jasper 1954). Further evidence on bilateral cortical face representation has been obtained from the spatial distribution of somatosensory evoked potentials to mechanical tapping of the tongue (Ishiko et al. 1980), to electrical stimulation of the lips (Findler and Feinsod 1982) and mental nerve (Drechsler and Neuhauser 1986), and to air puff stimulation of the third trigeminal area
LINGUAL SEPs
(Hashimoto 1988). Bilateral face representation has also been well documented in monkey SI cortex (Kaas et al. 1981). In our study, rather symmetrical responses were obtained for stimulation of the ipsi- and contralateral sides of the tongue. We are convinced that this finding also supports bilateral cortical representation of the tongue and is not an artifact due to spread of the stimulus current to the other side of the tongue. The sensations and muscle twitches of the tongue were strictly unilateral. Since no responses were elicited by stimulus intensities below the sensory threshold, the possible spreading currents, which did not evoke any sensation, are not likely to evoke a response, either. The most prominent and reliable component of trigeminal and lingual SEPs occurs around 20 msec (St6hr and Petruch 1979; Barker et al. 1987; Bennett et al. 1987; Altenmiiller et al. 1990). Responses at this latency, possibly representing the primary cortical activity triggered by thalamo-cortical fibres, were seen in some of our records. Their small size may suggest mainly radial underlying sources, not easily detected in magnetic measurements. Long-latency trigeminal SEPs, suggested to originate in secondary cortical sensory areas and similar to SEFs observed in the present study, have been reported only infrequently (Findler and Feinsod 1982; Drechsler and Neuhauser 1986), evidently because most authors have filtered them out (cf., Table I for filter settings). TSEPs, especially the early deflections, are subject to contamination by myogenic reflex activity following stimulation, and it has even been postulated that all trigeminal responses after 10 msec are of myogenic origin (Leandri et al. 1987). Activation of jaw-opening and chewing muscles facilitates linguo-mandibular reflexes. Altenmiiller et al. (1990) found no reflex activity from masseter muscles or tragus around 15 msec and later with relaxed jaw position, whereas slight preactivation of the jaw-opening muscles caused reflex responses at 18-23 msec. These results are in agreement with our control measurements, in which no reflex activity could be detected from temporal muscle at the site of the equivalent current dipole after stimulation of the tongue. The observed somatotopic source organization to stimulation of different trigeminal branches (cf., Fig. 2) also strongly supports the cortical rather than myogenic origin of the recorded responses. According to the present results, lingual SEFs consist of two slow deflections, probably generated close to each other at the continuing representation area of the tongue at SI and SII. With MEG recording the tongue and face representation areas can now be localized non-invasively. In presurgical evaluation of epileptic patients, these areas might serve as additional functional landmarks, with respect to which the site of an epileptic focus can be determined. The stimulation method is simple and painless; we have been able to
467
study also children successfully. With proper electrode arrays and an adequate recording passband the corresponding long-latency SEPs could also be used in the clinical assesment of trigeminal lesions. This study was financially supported by the Academy of Finland, the Kfrber Foundation (Hamburg), and Sigrid Jus61ius Foundation. The impetus for this work was given by Priv.-Doz. Dr. U.W. Buettner and Dr. E. Altenmiiller (Tiibingen, F.R.G.), who informed us about their studies of the early SEPs following tongue stimulation. We are grateful for the possibility to Use the 24~-channel magnetometer constructed by our colleagues (Kajola e t al. 1990) for some of the recordings. We also thank Dr. M. H~im~il~iinenfor comments on the manuscript and Dr. J. Huttunen (Helsinki University Hospital) for assistance in the electromyographic measurements.
References Altenmiiller, E., Cornelius, C.P. and Buettner, U.W. Somatosensory evoked potentials following tongue stimulation in normal subjects and patients with lesions of the afferent trigeminal system. Electroenceph, clin. Neurophysiol., 1990, 76: 403-415. Barker, G.R., Bennett, A;J. and Wastell, D.G. Applications of trigeminal somatosensory potentials (TSEPs) in oral and maxillofacial surgery. Br. J. Oral Maxillofac. Surg., 1987, 26: 308-313. Bennett, A.J., Wastell, D.G., Barker, G.R., Blackburn, C.W. and Prood, J.P. Trigeminal somatosensory evoked potentials. A review of literature as applicable to oral dysaesthesias. Int. J. Oral Maxillofac. Surg., 1987, 16: 408-415. Brenner, D., Lipton, J., Kaufman, L. and Williamson, S.J. Somatically evoked fields of the human brain. Science, 1978, 189: 81-83. Buettner, U.W., Rieble, S., AltenmiJller, E. and Cornelius, C.P. Trigeminal evoked potentials in patients with lesions of the mandibular branches of the trigeminal nerve. In: C. Barber and T. Blum (Eds.), Evoked Potentials III. Butterworth, Boston, MA, 1987: 299-302. Drechsler, F. and Neuhauser, B. Somatosensory trigeminal e(,oked potentials in normal subjects and in patients with trigeminal neuralgia before and after thermocoagulation of the ganglion Gasseri. Electromyogr. Clin. Neurophysiol., 1986, 26: 315-326. Findler, G. and Feinsod, M. Sensory evoked response to electrical stimulation of the trigeminal nerve in humans. J. Neurosurg., 1982, 56: 545-549. H~imiil~iinen, M. and Ilmoniemi, R. Interpreting magnetic fields of the brain: minimum-norm estimates. IEEE Trans. Biomed. Eng., 1990, in press. Hari, R., Reinikainen, K., Kaukoranta, E., H~imiil~iinen, M., IImoniemi, R., Penninen, A., Salminen, J. and Teszner, D. Somatosensory evoked cerebral magnetic fields from SI and SII in man. Electroenceph. clin. Neurophysiol,, 1984, 57: 254-263. Hari, R., Hiimiiliiinen, H., Hiimiiliiinen, M., Kekoni, J., Sams, M. and Tiihonen, J. Separate finger representations at the human second somatosensory cortex. Neuroscience, 1990, 37: 245-249. Hashimoto, I. Trigeminal evoked potentials following brief air puff: enhanced signal-to-noise ratio. Ann. Neurol., 1988, 23: 332-338. Huttunen, J., Hari, R. and Leinonen, L. Cerebral magnetic responses to stimulation of ulnar and median nerves. Electroenceph. clin. Neurophysiol., 1987, 66: 391-400. Ishiko, N., Hanamori, T. and Murayama, N. Spatial distribution of somatosensory responses evoked by tapping the tongue and finger in man. Electroenceph. clin. Neurophysiol., 1980, 50: 1-10. Kaas, J.H., Sur, M., Nelson, R.J. and Merzenich, M.M. The postcentral somatosensory cortex: multiple representations of the body in primates. In: C.N. Woolsey (Ed.), Cortical Sensory Organization.
468 Vol. 1. Multiple Somatic Areas. Humana Press, Clifton, NJ, 1981: 29-45. Kajola, M., Ahlfors, S., Enholm, G.J., H~illstr6m, J., Hiim~il~iinen, M.S., Ilmoniemi, R.I., Kiviranta, M., Knuutila, J., Lounasmaa, O., Tesche, C. and Vilkman, V. A 24-channel magnetometer for brain research. In: S.J. Williamson et al. (Eds.), Advances in Biomagnetism. Plenum Press, New York, 1990: in press. Karhu, J., Hari, R., Lu, S.-T., Paetau, R. and Rif, J. Two cortical sources for evoked magnetic fields to electric stimulation of the tongue. Electroenceph. clin. Neurophysiol., 1990, 76: 76P-78P. Kaukoranta, E., Hari, R., H~im~il~iinen,M. and Huttunen, J. Cerebral magnetic fields evoked by peroneal nerve stimulation. Somatosens. Res., 1986a, 3: 309-321. Kaukoranta, E., H~im~il~iinen, M., Sarvas, J. and Hari, R. Mixed and sensory nerve stimulations activate different cytoarchitectonic areas in the human primary somatosensory cortex SI. Exp. Brain Res., 1986b, 63: 60-66. Knuutila, J., Ahlfors, S., Ahonen, A., H~illstr6m, J., Kajola, M., Lounasmaa, O.V., Tesche, C. and Vilkman, V. A large-area low-noise seven-channel DC SQUID magnetometer for brain research. Rev. Sci. Instr., 1987, 58: 2145-2156. Larsson, L.E. and Prevec, T.S. Somatosensory response to mechanical stimulation as recorded in the human EEG. Electroenceph. clin. Neurophysiol., 1970, 28: 162-172. Leandri, M., Parodi, C.I., Zattoni, J. and Favale, E. Subcortical and cortical responses following infraorbital nerve stimulation in man. Electroenceph. clin. Neurophysiol., 1987, 66: 253-262.
J. KARHU ET AL. Murray, N.M.F. and Tan, C.T. Trigeminal somatosensory evoked potentials compared with median SEPs and brainstem auditory evoked potentials in brainstem multiple sclerosis. Muscle Nerve, 1984, 7: 586. Okada, Y.C., Tanenbaum, R., Williamson, S.J. and Kaufman, L. Somatotopic organization of the human somatosensory cortex revealed by neuromagnetic measurements. Exp. Brain Res., 1984, 56: 197-205. Penfield, W. and Jasper, H. Epilepsy and the Functional Anatomy of the Human Brain. Little, Brown and Co., Boston, MA, 1954. Sarvas, J. Basic mathematical and electromagnetic concepts of the biomagnetic inverse problem. Phys. Med. Biol., 1987, 32: 11-22. St/Shr, M. and Petruch, F. Somatosensory evoked potentials following stimulation of the trigeminal nerve in man. J. Neurol., 1979, 220: 95-98. St6hr, M., Petruch, F. and Scheglmann, K. Somatosensory evoked potentials following trigeminal nerve stimulation in trigeminal neuralgia. Ann. Neurol., 1981, 9: 63-66. Tiihonen, J., Hari, R. and H~im~il~iinen, M. Early deflections of cerebral magnetic responses to median nerve stimulation. Electroenceph, clin. Neurophysiol., 1989, 74: 290-296. Wood, C.C., Cohen, D., Cuffin, B.N., Yarita, M. and Allison, T. Electric sources in the human somatosensory cortex: identification by combined magnetic and potentials field recordings. Science, 1985, 227: 1051-1053.
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© 1991 Elsevier Scientific Publishers Ireland, Ltd. 0168-5597/91/$03.50
EVOPOT 90617
Cerebral magnetic fields to lingual stimulation * J. Karhu, R. Hari, S.-T. Lu, R. Paetau and J. Rif Low Temperature Laboratory, Helsinki University of Technology, SF-02150 Espoo (Finland) (Accepted for publication: 16 January 1991)
Summary We recorded cerebral magnetic fields to electric stimulation of the tongue in 7 healthy adults. The two main deflections of the response peaked around 55 msec (P55m) and 140 msec (N140m). During both of them the magnetic field pattern, determined with a 7- or 24-channel SQUID magnetometer, suggested a dipolar current source. The topography of P55m can be explained by a tangential dipole at the first somatosensory cortex (SI) in the posterior wall of the central sulcus. The equivalent source of N140m is, on average, about 1 cm lateral to the source of P55m. The reported method allows non-invasive determination of the cortical tongue representation area. Key words: Evoked responses; Magnetoencephalography; Somatosensory cortex; Tongue; Trigeminal nerve
Objective neurophysiological evaluation methods for the trigeminal system would be of much interest in sensory disturbances of the face and oral cavity, occurring in a number of clinical situations. The first trigeminal somatosensory evoked potentials (TSEPs) were reported to mechanical stimulation of the face (Larsson and Prevec 1970). Since then responses have been recorded mostly to electrical stimulation of lips and gums, both of which have relatively high sensory receptor density. The tongue shares this property; TSEPs have been recorded to tapping and electrical stimulation of the tongue (Ishiko et al. 1980; Altenmiiller et al. 1990). TSEP studies have been controversial due to variable stimulation and recording methods (cf., Table I): peak latencies from 1 to 150 msec have been recorded from the contralateral scalp of healthy adults. The most consistent responses to stimulation of lips, gums or tongue occur around 20 msec (St6hr and Petruch 1979; Barker et al. 1987; Altenmiiller et al. 1990), altfiough more variable peaks up to latencies of 120150 msec have been reported (Findler and Feinsod 1982; Drechsler and Neuhauser 1986). Attempts have also been made to use TSEPs diagnostically in a variety of trigeminal lesions, such as trigeminal neuralgia (St6hr et al. 1981), multiple sclerosis (Murray and Tan 1984), impairments following trauma or oral and max-
* A preliminary report of this study has been presented in abstract form (Karbu et al. 1990)
Correspondence to: J. Karhu, Low Temperature Laboratory, Helsinki University of Technology, SF-02150 Espoo (Finland). FAX: 358-0-4512969.
illofacial surgery (Barker et al. 1987), and lesions of the mandibular branches (Buettner et al. 1987). The first cortical TSEP has been suggested to appear as early as 10 msec (Leandri et al. 1987). Authors using surface stimulation have proposed responses at 14 msec (Drechsler and Neuhauser 1986) and around 20 msec (Barker et al. 1987; Altenmiiller et al. 1990) to be the first signs of cortical activity~ The exact generators of the later deflections, although thought to be cortical (Bennett et al. 1987), have remained unknown. In the present study we applied magnetoencephalography (MEG), a non-invasive method with good spatial resolution, to determine the sites of cortical activity after lingual nerve stimulation. Active areas in both the first (SI) and second (SII) somatosensory cortex have been located with MEG after stimulation of various peripheral nerves (Brenner et al. 1978; Hari et al. 1984, 1990; Okada et al. 1984; Wood et al. 1985; Kaukoranta et al. 1986a; Tiihonen et al. 1989).
Methods
Subjects and recordingprocedures Seven subjects (4 members of laboratory personnel and 3 paid volunteers; 5 males and 2 females; age range 19-41 years) were studied in a magnetically shielded room. The evoked magnetic field component B r normal to the head was measured from 28 to 63 locations over the right hemisphere with a low-noise (5-6 f T / ( ~ H ~ ) 7-channel first-order DC=SQUID gradiometer (Knuutila et al. 1987). The pickup coils of the device, separated by 36.5 mm, are installed in a
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TABLE I Examples of response latencies, stimulation sites, recording passbands and interstimulus intervals (ISis) used by different authors in recording trigeminal somatosensory evoked potentials. Surface electrodes were used for stimulation, unless otherwise stated. Peak latencies (msec)
Stimulation site
Passband (Hz)
ISI (sec)
Authors
13, 19, 26 8, 13, 18 24, 33, 46, 55, 101, 120 5, 9, 14, 34, 44, 100, 150 20, 29, 37
both lips lower lip
2 1 1 0.520 -
2000 3000 30 2000 1000
0.5 0.5
St6hr and Petruch (1979) Findler and Feinsod (1982)
3 0.5
Drechsler and N e u h a u s e r (1986) Barker et al. (1987)
10 - 1 0 0 0 0
0.3
Leandri et al. (1987)
16 - 1000
0.3
Altenmiiller et al. (1990)
1, 2, 3, 4, 5, 6, 7, 10 21
mental nerve upper lip gum infraorbital nerve (needle) tongue
hexagonal array on a spherical surface (radius 125 mm) covering an area with a diameter of 93 mm. Additional experiments were made with a 24-channel gradiometer recently constructed in our laboratory (Kajola et al. 1990). This device uses a planar flux transformer configuration: with two orthogonal loops at one location two off-diagonal field gradients, aBr/ax and aBr/ay, are obtained at 12 locations simultaneously, 30 mm apart (cf., Fig. 1). While the axial magnetometer detects the field extrema on both sides of the dipole, the planar gradiometer records the maximum total signal (~(3Br//Ox) 2 + (OBr//3y) 2 ) just above the dipolar source. Therefore, the coverage ( ~ = 12.5 cm) of this gradiometer often allowed the source area to be determined with one positioning of the instrument. The locations and orientations of the sensors with respect to the head were determined by analysing magnetic s~gnals resulting from the activation of a set of small coils fixed on known locations on the scalp (Knuutila et al. 1987). During the measurements the subject was lying with h i s / h e r head supported by a vacuum cast. •
Stimuli Constant-current pulses of 0.1 msec duration (Grass $88 stimulator, Grass SIU 4678 isolation unit and Grass CCU 1A constant current unit) were delivered to the anterior left side (in two subjects also to the right side) of the tongue through a self-made clip electrode, consisting of two Ag plates (diameter = 5 mm) and contacting the upper and lower sides of the tongue. The outside of the electrode was insulated to avoid synchronous stimulation of the oral mucosa. The tongue was held relaxed inside the slightly opened mouth to allow leads to come out between the upper and lower teeth• The stimulus current was adjusted to
produce a visible local contraction on the stimulated side of the tongue tip; this usually occurred at current strengths of 3 - 4 times the sensory threshold. The stimuli were not painful and did not cause any visible contraction of facial muscles or blinking. The interstimulus interval was 505 msec. Electrical control records were made to ensure that the magnetic records were not contaminated by muscle activity. Electromyographic activity was recorded with standard equipment (Dantec Neuromatic 2000 C) from a concentric needle electrode (Disa). Stimulation and averaging procedures were the same as for magnetic recording.
Signal analysis The recording passband was 0.05-500 Hz (3 dB points, high-pass roll-off 35 d B / d e c a d e and low-pass over 80 dB/decade). The signals were digitized at 2000 Hz and averaged on-line. The analysis period was 256 msec and response amplitudes were measured with respect to a 75 msec prestimulus baseline. The first two responses of each stimulus block were rejected from the analysis and about 350 responses were averaged at each location. Isocontour maps of B r of 7-channel records were constructed by projecting the measurement locations to a plane. If the pattern was dipolar by visual inspection, i.e., had two extrema of opposite polarities, the equivalent dipole was determined with a least-squares fit. The spherical conductor model was used with a radius corresponding to the local radius of curvature of the head in the measurement area. In this procedure the effects of source and volume currents on the measured field are taken properly into account (Sarvas 1987). To obtain isocontour maps for the gradient measurements, the minimum-norm current estimates
Fig. 1. Responses of one subject to alternating stimulation (ISI = 505 msec) of the left median nerve at the wrist and the left side of the tongue. The responses were recorded with the 24-channel gradiometer over the right hemisphere. Th e upper trace of each pair shows the field gradient in the vertical and the lower in the horizontal direction. Two records (N = 350) from both stimulation sites are superimposed. Passband is 0.05-190 Hz.
461
LINGUAL SEPs
MEDIAN NERVE N20m
-
P30m
E1oofT/cm
~ 11
~
12 ~ 456 1 8 910 1112
12
I m l
0
TONGUE
100 ms
1
Lr~
2
N1LOm
\ I m l
0
100 ms
P55m
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(MNE) corresponding to the measured data were first computed. Thereafter, B r generated by MNE was determined (H/im~il~iinen and Ilmoniemi 1990). This procedure accomplishes 3-dimensional interpolation suit-
able for the magnetic field. The gradiometer configurations and the deviations of the sensitivity axes of the gradiometers from the radial direction are taken into account. It is, however, emphasized that the field maps
MEDIAN NERVE N20m MEDIAN ~'" ~ /
AN NERVE 21 ms _OWER LIP
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/w
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:
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10 nAm I
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TONGUE P55m Y
Fig. 2. Left: isocontour maps obtained from the same 24-channel recording as in Fig. 1 (the contours of B r have been calculated from the gradient measurements). Shadowed area indicates magnetic flu~, out of the head, white area flux into the head; the isocontour lines are separated by 20 fT. T h e locations and orientations of the equivalent dipoles are indicated by arrows in the maps. Right: the arrows in the upper right part of picture demonstrate the locations, orientations, and strengths (scale is given) of the equivalent dipoles for responses measured at the same location (goodness-of-fit values 90-97%). The coordinate system is demonstrated in the lower right corner: the x-axis passes the right eye corner and forms a 45 ° angle with the line connecting the ear canal and eye corner; the origiff is 70 nun posterior to the latter. The dotted line indicates the approximate course of the rolandic fissure.
LINGUAL SEPs
463
are only a visual aid and any subsequent dipole fitting for both types of record was done on the original data, using the measured locations and orientations of the sensors. Confidence limits for dipole locations were calculated using the standard errors of the averaged responses as the estimates of experimental noise (Kaukoranta et al. 1986b). These estimates contained both instrumental and brain noise.
Results
Fig. 1 shows responses of one subject, measured with the 24-channel gradiometer, when the contralateral median nerve at the wrist and the contralateral side of the tongue were stimulated alternately in the same session. The response to median nerve stimulation consists of two main deflections N20m and P30m (cf., Tiihonen et al. 1989). The two main deflections to tongue stimulation peak at 55 msec and 115 msec. The maximum amplitude, which in records with the planar gradiometer also suggests the source location, is seen in pair 4 for median nerve and in pairs 8 and 12 for tongue stimulation.
MEDIAN NERVE
Fig. 2 illustrates isocontour maps obtained from the 24-channel records for N20m (median nerve) and P55m (lingual nerve) responses. For comparison, equivalent sources following electrical stimulation are also shown for the contralateral upper and lower lips (at 53 and 51 msec, respectively), and for median nerve at the latency of 53 msec. The orientations of all dipoles are notably similar and the locations agree with the idea that the sources represent activity of the somatotopically organized SI, in the posterior wall of the rolandic fissure. Fig. 3 demonstrates ipsi- and contralateral responses to median nerve and lingual stimulation. For lingual stimulation, the ipsi- and contralateral responses are very similar, both in latency and in amplitude, whereas no clear response is seen for ipsilateral median nerve stimulation at the time of the main contralateral deflections. Responses to lingual stimulation were in all subjects qualitatively similar, with two main deflections, as shown in Fig. 4 for 7-channel records. The earlier deflection, P55m, peaked at 57 + 4 msec (mean _+ S.E.M. of 7 subjects; range 48-69 msec) and reversed in polarity between the upper and lower measurement locations along the central suleus. The later peak
TONGUE ' CONTRA
c3Br
f,
....
'IPSI
;gy
OBr
Ox I
0
•
100 ms
/
O0 f T / c m
0
I
100 ms
Fig. 3. Responses to contralateral (solid lines) and ipsilateral (dashed lines) stimulation of median nerve and tongue in channels with maximum amplitudes in Fig. 1. Other details as in Fig. 1.
464 I. K A R H U E T AL
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Fig. 5, Temporal evolution of magnetic field patterns in S1. Shadowed area indicates magnetic flux out of the head, white area flux into the head; the isocontour lines are separated by 10 f T , T h e locations and orientations of the equivalent dipoles are indicated by arrows. The approximate measurement area is shown in the insert• The maps are based on 63 measurement locations (7-channel recording).
(N140m) occurred at 1 4 2 + 7 msec (range 115-165 msec), with the polarity reversal between the posterior and anterior locations along the sylvian fissure. Responses at 20-24 msec were seen at some measurement locations, but because of their small size and possible contamination by muscular artefacts (cf., AItenmiiller et al. 1990) we did not analyse them in more detail• Fig. 4 also demonstrates that the high-pass filter setting at 10 Hz, commonly used in clinical SEP measurements, abolishes the main deflections. Fig. 5 shows the temporal evolution of the magnetic field pattern to lingual stimulation in subject 1. The patterns, based on 7-channel recording, are dipolar from 45 to 145 msec with two extremes of opposite
polarities. The orientations of the patterns differ from each other at 55 and at 115 msec, i.e., during P55m and N140m. In all our 7 subjects, the field patterns were dipolar during both P55m and N140m. The equivalent current dipoles explained 78-92% of the field variance and the residual field patterns showed no systematic features. The single-dipole model was thus considered to be adequate at these latencies. Fig. 6 shows source locations and the 95% confidence ellipsoids for P55m and N140m. They differ from each other in subjects 4, 5, 6 and 7 at the 95% confidence level. Further, in subjects 1 and 3 the source orientations were perpendicular to each other, although the source locations did not differ statistically
Fig. 4. Above: responses of all 7 subjects (S1-$7) at the superior (SUP) and inferior (INF) field extrema of P55m measured with the 7-channel gradiometer. The later (N140m) deflections are also easily seen in S1, $3 and $4 due to proximity of source locations (cf., Fig. 5). Passband is 0.05-190 Hz. Below: same responses after digital filtering from 10 to 190 Hz.
466
J. KARHU ET AL.
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- 2 -1 Fig. 6. Source locations of P55m and N140m for all subjects (S1-$7). The dots show the locations and the arrows the orientations and strengths of the equivalent dipoles (scale is given). The 95% confidence limits for the x-y locations are indicated by ellipsoids (shaded for P55m). The mean (+ S.E.M.; 7 subjects) source locations and orientations are shown in the lower right corner. The coordinate system shown in the insert is equal to that in Fig. 2.
significantly. The mean angle of the dipole from the x-axis was 226 + 6 ° for P55m (mean + S.E.M.; range 201-246 °) and 99 + 14° for N140m (range 60-155°), resulting in an average orientation difference of 127 ° between the two dipoles ( P < 0.001, 2-tailed t test for pair differences). The mean source location for N140m was 7 mm lateral and 2 mm posterior to that for P55m (N.S.). The equivalent dipoles of both peaks were about 30 mm below the scalp. In two subjects both 24and 7-channel records were available, and the source locations did not differ from each other (cf., Fig. 2 for subject 1). Temporal muscle, partially overlying the investigated cortical areas, was monitored by electromyography in one subject during lingual stimulation. A concentric needle electrode was inserted into the upper, posterior corner of the muscle, at the location of the equivalent current source of P55m determined from the magnetic field patterns. Repeated contra- and ipsilateral stimulation of the tongue caused no detectable deflections in the averaged electromyogram.
D i s c u s s i o n
To our knowledge this is the first report of SEFs to trigeminal stimulation. In all our 7 subjects, the responses consisted of 2 main deflections, P55m and N140m, with different source locations and orientations. P55m reversed polarity between the u p p e r and lower recording locations along the central sulcus. In
line with earlier s E F studies, in which different body parts were stimulated, the field pattern suggests that P55m is generated by a tangential current source in the posterior wall of the central sulcus, at Brodmann area 3b (cf., Hari et al. 1984; Wood et al. 1985; Huttunen et al. 1987). This area is clearly lateral to the area activated by electrical stimulation of the median nerve and of other trigeminal branches, thus agreeing with the well-known somatotopic organization of SI (Penfield and Jasper 1954). The different location and orientation of the source of N140m would agree with activation of SII in the. upper bank of the sylvian fissure. The activity in SII around 100-140 msec has been earlier detected with M E G after both upper and lower limb stimulation (Hari et al. 1984, 1990; Kaukoranta et al. 1986a). The complex cortical folding and the proximity of face representation areas in SI and SII - - in line with the observed 1 cm mean separation between the sources - could explain the considerable interindividual variation in the relative locations of these two source areas. Electrical stimulation of cortical face areas causes - in addition to contralateral - - also bilateral and ipsilateral sensations (Penfield and Jasper 1954). Further evidence on bilateral cortical face representation has been obtained from the spatial distribution of somatosensory evoked potentials to mechanical tapping of the tongue (Ishiko et al. 1980), to electrical stimulation of the lips (Findler and Feinsod 1982) and mental nerve (Drechsler and Neuhauser 1986), and to air puff stimulation of the third trigeminal area
LINGUAL SEPs
(Hashimoto 1988). Bilateral face representation has also been well documented in monkey SI cortex (Kaas et al. 1981). In our study, rather symmetrical responses were obtained for stimulation of the ipsi- and contralateral sides of the tongue. We are convinced that this finding also supports bilateral cortical representation of the tongue and is not an artifact due to spread of the stimulus current to the other side of the tongue. The sensations and muscle twitches of the tongue were strictly unilateral. Since no responses were elicited by stimulus intensities below the sensory threshold, the possible spreading currents, which did not evoke any sensation, are not likely to evoke a response, either. The most prominent and reliable component of trigeminal and lingual SEPs occurs around 20 msec (St6hr and Petruch 1979; Barker et al. 1987; Bennett et al. 1987; Altenmiiller et al. 1990). Responses at this latency, possibly representing the primary cortical activity triggered by thalamo-cortical fibres, were seen in some of our records. Their small size may suggest mainly radial underlying sources, not easily detected in magnetic measurements. Long-latency trigeminal SEPs, suggested to originate in secondary cortical sensory areas and similar to SEFs observed in the present study, have been reported only infrequently (Findler and Feinsod 1982; Drechsler and Neuhauser 1986), evidently because most authors have filtered them out (cf., Table I for filter settings). TSEPs, especially the early deflections, are subject to contamination by myogenic reflex activity following stimulation, and it has even been postulated that all trigeminal responses after 10 msec are of myogenic origin (Leandri et al. 1987). Activation of jaw-opening and chewing muscles facilitates linguo-mandibular reflexes. Altenmiiller et al. (1990) found no reflex activity from masseter muscles or tragus around 15 msec and later with relaxed jaw position, whereas slight preactivation of the jaw-opening muscles caused reflex responses at 18-23 msec. These results are in agreement with our control measurements, in which no reflex activity could be detected from temporal muscle at the site of the equivalent current dipole after stimulation of the tongue. The observed somatotopic source organization to stimulation of different trigeminal branches (cf., Fig. 2) also strongly supports the cortical rather than myogenic origin of the recorded responses. According to the present results, lingual SEFs consist of two slow deflections, probably generated close to each other at the continuing representation area of the tongue at SI and SII. With MEG recording the tongue and face representation areas can now be localized non-invasively. In presurgical evaluation of epileptic patients, these areas might serve as additional functional landmarks, with respect to which the site of an epileptic focus can be determined. The stimulation method is simple and painless; we have been able to
467
study also children successfully. With proper electrode arrays and an adequate recording passband the corresponding long-latency SEPs could also be used in the clinical assesment of trigeminal lesions. This study was financially supported by the Academy of Finland, the Kfrber Foundation (Hamburg), and Sigrid Jus61ius Foundation. The impetus for this work was given by Priv.-Doz. Dr. U.W. Buettner and Dr. E. Altenmiiller (Tiibingen, F.R.G.), who informed us about their studies of the early SEPs following tongue stimulation. We are grateful for the possibility to Use the 24~-channel magnetometer constructed by our colleagues (Kajola e t al. 1990) for some of the recordings. We also thank Dr. M. H~im~il~iinenfor comments on the manuscript and Dr. J. Huttunen (Helsinki University Hospital) for assistance in the electromyographic measurements.
References Altenmiiller, E., Cornelius, C.P. and Buettner, U.W. Somatosensory evoked potentials following tongue stimulation in normal subjects and patients with lesions of the afferent trigeminal system. Electroenceph, clin. Neurophysiol., 1990, 76: 403-415. Barker, G.R., Bennett, A;J. and Wastell, D.G. Applications of trigeminal somatosensory potentials (TSEPs) in oral and maxillofacial surgery. Br. J. Oral Maxillofac. Surg., 1987, 26: 308-313. Bennett, A.J., Wastell, D.G., Barker, G.R., Blackburn, C.W. and Prood, J.P. Trigeminal somatosensory evoked potentials. A review of literature as applicable to oral dysaesthesias. Int. J. Oral Maxillofac. Surg., 1987, 16: 408-415. Brenner, D., Lipton, J., Kaufman, L. and Williamson, S.J. Somatically evoked fields of the human brain. Science, 1978, 189: 81-83. Buettner, U.W., Rieble, S., AltenmiJller, E. and Cornelius, C.P. Trigeminal evoked potentials in patients with lesions of the mandibular branches of the trigeminal nerve. In: C. Barber and T. Blum (Eds.), Evoked Potentials III. Butterworth, Boston, MA, 1987: 299-302. Drechsler, F. and Neuhauser, B. Somatosensory trigeminal e(,oked potentials in normal subjects and in patients with trigeminal neuralgia before and after thermocoagulation of the ganglion Gasseri. Electromyogr. Clin. Neurophysiol., 1986, 26: 315-326. Findler, G. and Feinsod, M. Sensory evoked response to electrical stimulation of the trigeminal nerve in humans. J. Neurosurg., 1982, 56: 545-549. H~imiil~iinen, M. and Ilmoniemi, R. Interpreting magnetic fields of the brain: minimum-norm estimates. IEEE Trans. Biomed. Eng., 1990, in press. Hari, R., Reinikainen, K., Kaukoranta, E., H~imiil~iinen, M., IImoniemi, R., Penninen, A., Salminen, J. and Teszner, D. Somatosensory evoked cerebral magnetic fields from SI and SII in man. Electroenceph. clin. Neurophysiol,, 1984, 57: 254-263. Hari, R., Hiimiiliiinen, H., Hiimiiliiinen, M., Kekoni, J., Sams, M. and Tiihonen, J. Separate finger representations at the human second somatosensory cortex. Neuroscience, 1990, 37: 245-249. Hashimoto, I. Trigeminal evoked potentials following brief air puff: enhanced signal-to-noise ratio. Ann. Neurol., 1988, 23: 332-338. Huttunen, J., Hari, R. and Leinonen, L. Cerebral magnetic responses to stimulation of ulnar and median nerves. Electroenceph. clin. Neurophysiol., 1987, 66: 391-400. Ishiko, N., Hanamori, T. and Murayama, N. Spatial distribution of somatosensory responses evoked by tapping the tongue and finger in man. Electroenceph. clin. Neurophysiol., 1980, 50: 1-10. Kaas, J.H., Sur, M., Nelson, R.J. and Merzenich, M.M. The postcentral somatosensory cortex: multiple representations of the body in primates. In: C.N. Woolsey (Ed.), Cortical Sensory Organization.
468 Vol. 1. Multiple Somatic Areas. Humana Press, Clifton, NJ, 1981: 29-45. Kajola, M., Ahlfors, S., Enholm, G.J., H~illstr6m, J., Hiim~il~iinen, M.S., Ilmoniemi, R.I., Kiviranta, M., Knuutila, J., Lounasmaa, O., Tesche, C. and Vilkman, V. A 24-channel magnetometer for brain research. In: S.J. Williamson et al. (Eds.), Advances in Biomagnetism. Plenum Press, New York, 1990: in press. Karhu, J., Hari, R., Lu, S.-T., Paetau, R. and Rif, J. Two cortical sources for evoked magnetic fields to electric stimulation of the tongue. Electroenceph. clin. Neurophysiol., 1990, 76: 76P-78P. Kaukoranta, E., Hari, R., H~im~il~iinen,M. and Huttunen, J. Cerebral magnetic fields evoked by peroneal nerve stimulation. Somatosens. Res., 1986a, 3: 309-321. Kaukoranta, E., H~im~il~iinen, M., Sarvas, J. and Hari, R. Mixed and sensory nerve stimulations activate different cytoarchitectonic areas in the human primary somatosensory cortex SI. Exp. Brain Res., 1986b, 63: 60-66. Knuutila, J., Ahlfors, S., Ahonen, A., H~illstr6m, J., Kajola, M., Lounasmaa, O.V., Tesche, C. and Vilkman, V. A large-area low-noise seven-channel DC SQUID magnetometer for brain research. Rev. Sci. Instr., 1987, 58: 2145-2156. Larsson, L.E. and Prevec, T.S. Somatosensory response to mechanical stimulation as recorded in the human EEG. Electroenceph. clin. Neurophysiol., 1970, 28: 162-172. Leandri, M., Parodi, C.I., Zattoni, J. and Favale, E. Subcortical and cortical responses following infraorbital nerve stimulation in man. Electroenceph. clin. Neurophysiol., 1987, 66: 253-262.
J. KARHU ET AL. Murray, N.M.F. and Tan, C.T. Trigeminal somatosensory evoked potentials compared with median SEPs and brainstem auditory evoked potentials in brainstem multiple sclerosis. Muscle Nerve, 1984, 7: 586. Okada, Y.C., Tanenbaum, R., Williamson, S.J. and Kaufman, L. Somatotopic organization of the human somatosensory cortex revealed by neuromagnetic measurements. Exp. Brain Res., 1984, 56: 197-205. Penfield, W. and Jasper, H. Epilepsy and the Functional Anatomy of the Human Brain. Little, Brown and Co., Boston, MA, 1954. Sarvas, J. Basic mathematical and electromagnetic concepts of the biomagnetic inverse problem. Phys. Med. Biol., 1987, 32: 11-22. St/Shr, M. and Petruch, F. Somatosensory evoked potentials following stimulation of the trigeminal nerve in man. J. Neurol., 1979, 220: 95-98. St6hr, M., Petruch, F. and Scheglmann, K. Somatosensory evoked potentials following trigeminal nerve stimulation in trigeminal neuralgia. Ann. Neurol., 1981, 9: 63-66. Tiihonen, J., Hari, R. and H~im~il~iinen, M. Early deflections of cerebral magnetic responses to median nerve stimulation. Electroenceph, clin. Neurophysiol., 1989, 74: 290-296. Wood, C.C., Cohen, D., Cuffin, B.N., Yarita, M. and Allison, T. Electric sources in the human somatosensory cortex: identification by combined magnetic and potentials field recordings. Science, 1985, 227: 1051-1053.