Distribution of cerebral somatosensory evoked responses in normal man

ELECTROENCEPHALOGRAPHY AND CLINICAL NELIROPHYSIOLOGY

DISTRIBUTION EVOKED

697

OF CEREBRAL SOMATOSENSORY RESPONSES IN NORMAL MAN

WILLIAM R . G O F F , BLIRTON S. ROSNER AND TRLIETT ALLISON l

West Haven Veterans Administration Hospital and Yale University School of Medicine, New Haven, Conn. (U.S.A.) (.Received for publication: March 14, 1962)

Studies of distribution of evoked responses have helped to delimit cerebral cortical sensory projection areas in animals. Early work on somesthesis by Gerard et al. (1933, 1936), Marshall et al. (1937, 1941), and Adrian (1940, 1941) showed that a restricted cortical area (Somatic I) responded to tactile stimuli in anesthetized animals. Some of these studies also indicated the existence of the projection region subsequently labelled Somatic II. Later, Adrian (1943) and Woolsey and his co-workers (Woolsey 1958) demonstrated with the evoked potential technique the somatotopic organization of Somatic I and lI in various species. More recent observations on unanesthetized or chloralosed animals, however, show that peripheral somesthetic stimuli also evoke cortical activity in areas outside this dual projection system. Various reports localize these "secondary", "association", or "non-specific" responses in frontal, pre-central, posterior parietal, or temporal cortex. In unanesthetized animals, the small amplitude of peripherally evoked activity has required investigators to record directly from the brain surface of immobilized preparations or from chronically implanted electrodes. Evoked responses in man also are small and available techniques have permitted comparatively few studies on them. Responses to somesthetic stimulation recorded at the brain surface in neurosurgical patients have been described. Although these studies are invaluable, investigation of response distributions is confined to the operative field and is subordinate to surgical procedures. Studies using standard electroencephalo1 Present address: Brain Research Unit, Insurgenres Sur 3687, Mexico D.F., Mexico.

graphic methods have yielded some further data on distributions of somatic evoked responses in man. These methods select only those aspects of the response which have sufficient amplitude for detection above spontaneous activity. Studies using photographic superimposition of oscilloscope traces have succeeded in detecting smaller responses. No detailed analysis of distribution has been made. In 1951, Dawson reported a summation technique permitting extraction of small signals from a noisy background. This method separates evoked activity from ongoing spontaneous activity. Preliminary experiments on normal man in our laboratory using an automatic summation technique indicated that the response evoked by a slowly repeated electrocutaneous stimulus is complex, multiphasic, and lasts at least 300 msec. In light of these observations, it appeared that previous studies on man, for various reasons, had emphasized different parts of the evoked response. Moreover, the complexity of the response suggested that its components reflected activity mediated by multiple neural pathways. Evoked response data from animals indicated that these components might be differently distributed over the scalp. We therefore examined the waveform and distribution of evoked activity occurring ~'ithin 500 msec after peripheral stimulation. The results reported in this paper show that utilization of the greater signal detection power of a summation technique clarifies some relationships between previously reported aspects of human somatic evoked responses. The results also have contributed to a tentative parcellation of the response on the basis of differential distributions of its various components. This parcellation is necessary for further study of the Electroenceph.

clin. Neurophysiol., 1962, 14:697-713

698

W. R. GOFF, B. S. ROSNER AND T. ALLISON

functional significance and physiological mechanisms of somatic evoked potentials in man. PROCEDLIRE

All subjects were paid volunteer male graduate and medical students in apparently normal health. They were selected only for ability to relax in the recording situation in order to minimize electromyographic activity. Preliminary experiments on five subjects showed that the general form of the response was consistent among subjects and that different deflections did have different distributions. We then studied eleven additional subjects in more detail. In five of these we used up to fourteen electrode locations distributed over the head with emphasis on contralateral and ipsilateral parietal locations. On the basis of these results we designed our most extensive analysis and carried it out on the remaining six subjects. The analysis included the use of 21 cranial electrodes to delimit more precisely the projection areas of the various deflections and a study of distributions of responses to both median nerve and index finger stimulation. Whole nerve stimulation has the advantage of evoking larger responses in which components are more distinct. It has the possible disadvantage of simultaneously activating a large number of nerve fibers innervating a relatively large area. Thus, we checked whether whole nerve stimulation evokes a response whose waveform and distribution differ from those characterizing the response to the subjectively more localized, less intense finger stimulation. Stimuli were 100 ~sec, constant current, rectangular pulses delivered percutaneously through silver disk electrodes 9 m m in diameter. The disks contained bentonite and were taped over median nerve at the wrist or to the second and third phalanges of the index finger. The cathode was always proximal. We recorded responses to nerve and finger stimulation on the same arm in the same session. At the start of a session, we determined a median nerve stimulus intensity which produced a minimal thumb twitch and a sensation radiating into the hand field innervated by median nerve. This same intensity was then used for both nerve and finger stimulation. To minimize stimulus artifact, the stimu-

lator unit was isolated from ground and a grounded metal cuff was attached to the arm near the elbow. The inter-stimulus interval was always constant within a session but varied between sessions from 4.5-6.0 sec. One of us (Allison 1962) has shown that all comp~)nents of the evoked response occurring within 300 msec after stimulation are fuliy recovered in 4 sec.

Monopolar records were obtained with subdermal needle electrodes. The reference electrode was a silver disk, coated with electrode jelly and taped to the bridge of the nose. Tests carried out on the majority of our subjects showed that the bridge of the nose was inactive with respect to responses evoked by intense median nerve shocks and yel was sufficiently proximal to the scalp to minimize other electrical activity. For the importance of a truly indifferent, non-cranial reference point, see Discussion. The special purpose analog computer used to summate the evoked responses has been described in detail (Rosner et al. 1960). The entire system had a time constant of 0.2 sec and a frequency response flat to about 1 kc. Subjects were seated in a reclining chair inside a moderately illuminated, shielded room. The room was sound attenuating and ventilation blowers provided 75 db SPL of masking noise. The usual sounds emanating from outside the room could not be heard. The subject monitored his E E G on a small oscilloscope placed before him. He was instructed to a~sume a relaxed position, minimize "noise" on the oscilloscope, and to stay alert. An armrest supported the arm being stimulated and the subject gently closed his hand on a cross-bar. Maintaining this position minimized changes in orientation of the stimulating electrodes from transient movements of hand and arm. The location of recording sites appears in Fig. 1A. Their nomenclature follows: The vertex (V) was determined as the intersection of the midline and the coronal interaural circle. The locations 7 cm lateral to the vertex on this circle were termed contralateral post-Rolandic (cPR) and ipsilateral post-Rolandic (iPR) depending on the locus of peripheral stimulation. These two electrodes were about 2 cm posterior to the Electroenceph. clin. NeurophysicC, 1962, 14:697-713

SOMATIC EVOKED RESPONSE DISTRIBUTION

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120msecI I00r n s e ¢ I Fig. 1 A: schematic representation of a postero-dorsal view of head showing recording electrode locations (subject J.P.). For nomenclature and determination of electrode locations, see text. A rubber cap was fitted over the head, electrode placements were measured and marked and the cap photographed. The schematic was traced directly from an enlarged photograph. Heavy lines indicate approximate position of Rolandic sulci as determined by surface measurements. Subsequent figures show responses arrayed along contralateral (c6a-ml2p), ipsilateral (i6a-ml2p), midline (m8a-ml2p), and coronal (c4v-i4v) arcs. B: traced superimposition of six averaged responses and resulting visual average. Tracings made from X 5 magnification of photographed responses. Arrows indicate amplitude measurements on the components. For a discussion of these measurements, see Results. In this and all succeeding figures, upward deflection indicates positivity at recording electrode. Rolandic sulcus as located by surface measurements according to Kr6nlein (1898). They were at the approximate level of the sensory projection area of the hand (Penfield and Rasmussen 1950). All other contralateral and ipsilateral

699

recording sites were measured from the postRolandic locations. They were, contralaterally, 4 cm dorsal (c4d), 4 cm ventral (c4v), 4 and 6 cm anterior (c4a, c6a), 4 and 8 cm posterior (c4p, c8p) and 4 cm posterior and ventral (c4p-4v) to cPR. Ipsilateral locations were identically oriented with respect to iPR and called i4d, i4v, etc. On the midline, in addition to the vertex location (V), recording sites were 4 and 8 cm anterior (m4a, m8a) and 6 and 112 cm posterior (m6p, m l 2 p ) to V. Only seven recording locations were used in any one session. For control purposes, cPR was used every session; the remaining six locations were selected in random order with the restriction that each location occur in each of three separate sessions. A session consisted of recording two summated responses from each site for both nerve and finger stimulation on the same arm. Thus, six averages were obtained from each locus for each stimulus condition. In three subjects, median nerve was stimulated first; in the other three, index finger was first. This produced no discernible difference in the records of the two groups. Recording time was approximately 1 h and subjects were limited to one session per day. Generally, from 2-7 days intervened between sessions. For four of the six extensively studied subjects, responses were obtained at all 21 scalp loci for stimulation of both right and left median nerve at the wrist (designated R M N and LMN respectively) and both left and right index finger (designated R I F and L I F respectively). The summated responses of the remaining two subjects (I.G. and G.E.) were initially rather small and diminished further as the experiment continued over the course of 5 months. In addition, subject I.G. experienced a progressive inability to control myographic activity which obscured his evoked responses. For these reasons, we modified the experimental procedure on these two subjects in the following way. Complete data were collected at all recording loci on subject I.G. for LMN. For R M N in this subject, certain midline and contralateral electrode locations were examined less extensively for comparison purposes and these incomplete data are not included in our results. Complete data were recorded from subject G.E. for LMN and Electroenceph. clin. Neurophysiol., 1962, 14:697-713

700

W. R. GOFF, B. S. ROSNER AND T. ALLISON

RMN from scalp locations cPR, c4a, c4v, c4d, c4p, cSp, and m l 2 p (see Fig. 1A). Two summations were recorded from remaining locations. These data are included in our results. Index finger responses for these two subjects proved too small and indistinct for analysis. Each summated response for every subject was the sum of 40 single responses. Our corn-

mated responses for a given recording location for a given stimulus locus were superimposed on the same sheet of paper. A single curve summarizing the resulting group of traces was drawn through the estimated medians of the maxima and minima. Fig. I B illustrates this process. (For explanation of arrows indicating amplitude measurements in Fig. 1B, see Re-

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puter has two independent data channels; responses from two different recording sites were summated simultaneously. Summated responses were displayed oscilloscopically and photographed at sweep speeds of 10 and 50 msec/cm. To reduce the large amount of data thus collected to manageable form, photographs were magnified IX5 to improve resolution and traced on paper. For each sweep speed, sum-

suits.) Therefore, each curve shown in Fig. 2-7 is based on six summations or a total of 240 individual evoked responses. Our analysis, including amplitude and latency measurements, is based on these summary "averages". In Fig. 2-5 and 7, the earlier response components are shown at the faster sweep rate, while later ones are shown at the slower sweep rate. This composite was constructed by joining the Electroenceph. clin. Neurophysiol., 1962, 14:697 713

SOMATIC

EVOKED

"average" curves for each sweep rate at the point indicated by the dotted line. A time calibration for the two sweep rates is indicated on either side of this line. RESULTS

General form oJ the response Somatic evoked activity from the human

RESPONSE

o N T R A

70!

scriptive nature of our parcellation; we do not imply that the components are necessarily functional entities. Responses to both median nerve and index finger stimulation have similar waveforms within each subject. Median nerve shocks, however, evoke larger, more distinct potentials. The following description of the response and our par-

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scalp is a complex sequence of potentials lasting at least 300 msec. The general characteristics are quite consistent although waveform, latencies, and amplitudes of different components vary somewhat within and between subjects. Allison's (1962) classification into five components provides a convenient framework for describing responses at the various recording loci used in this study. We emphasize the de-

cellation of it is based, therefore, on median nerve results. The latencies of each component are medians and ranges based on all locations where the component was measurable in the six extensively studied subjects. Fig. 2 through 6 present nerve stimulation data for several individual subjects. We have numbered the components at parietal locations. The initial evoked activity at these locations is a triphasic, posiElectroenceph. clin. Neurophysiol., 1962, 14:697-713

702

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GOFF, B. S. ROSNER AND T. ALLISON

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Fig. 4 Distribution of averaged evoked responses. Subject J.P. Right median nerve stimulation.

tire, negative, positive complex which we designate as component 1. The first, small deflection has a peak latency of 16 ± 2 msec. It is immediately followed by a sharp negative spike peaking 3~, msec later. The third, positive phase, peaking at 25 ± 4 msec, is not consistently detectable in all subjects. Where apparent, it is superimposed on the rising phase of a succeeding, larger positivity. Components 2 and 3 designate positive deflections which are similar in duration and have peak latencies of 31 ± 6 and 48 ± 8 msec respectively. In most instances these two deflections are clearly separated (Fig. 2 and 3). The separation at some locations is actually a negativity extending below the baseline. This suggests an active neural process rather than inactivity intervening between the two positive processes. In some instances, components 2 and 3 merge into one prolonged positive wave

(Fig. 5). We designate the negativity peaking at 65 ± 14 msec and a positivity peaking at 85 ± 20 msec as component 4. This component shows the greatest intra- and inter-subject variability in waveform. On the contralateral arc (c6aml2p, see Fig. 1A), it usually appears as a large negative-positive potential. At some locations the positivity breaks up into two or more peaks. The latest potentials consistently time-locked to the peripheral shock consist of a very large negativity peaking at 135 ± 25 msec and a still larger positivity occurring at 220 ± 45 msec. The peak of the negativity occasionally encounters a small positive interruption. The peak of the positive phase breaks up into two processes at posterior electrode locations in the majority of subjects. We designate all of this activity as component 5. Electroenceph. clin. Neurophysiol., 1962, 14:697-713

703

SOMATIC EVOKED RESPONSE DISTRIBLITION

In the course of this and several other experiments, we have examined a total of 31 subjects. The general form of the total evoked response recorded from parietal scalp in all of these subjects differs in no significant way from the description above.

ments that could be made most consistently among recording locations and among subjects. (At present, we regard such measurements only as a descriptive convenience.) The arrows in Fig. 1B indicate where amplitude measurements were made. Component 1 was measured c4v

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Fig. 5 Distribution of averaged evoked responses. Subject T.T. Right median nerve stimulation. Subject was right handed.

Distribution of the response We will present data on distribution of components in the six subjects on whom 21 electrode locations were used. Distribution resuits from the five other subjects using fourteen electrode locations were entirely consistent with these findings. Our analysis concentrates on amplitude characteristics. In our experiments to date, we have found amplitudes more sensitive to experimental manipulations than latencies. The latter have proven useful primarily in identifying corresponding components in different subjects. We chose amplitude measure-

from the peak of the first positivity to the peak of the following negativity. Components 3, 4, and 5 were measured from the appropriate negative peak to the peak of the following positivity. Peak-to-peak measurement of 2 would be confused by the variable appearance of the last part of 1. Component 2, therefore, was measured from the point of zero potential to the peak of the positivity. Nerve stimulation Components 1 and 2 have similar distributions. They are projected mainly to the Electroenceph. clin. Neurophysiol., 1962, 14:697-713

704

W. R. GOFF, B. S. ROSNER AND T. ALLISON

posterior contralateral quadrant of the scalp extending from Rolandic locations (cPR, c4v, c4d) back to the occiput. Both components occasionally appear also at anterior contralateral locations. In five of six subjects, a small response resembling I and 2 was recorded from ipsilateral posterior parietal area (e.g., Fig. 3, locations i4p, i8p; Fig. 6, location i8p). For LEFT

NERVE

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Fig. Comparison of first three evoked response to left and lation. Subject B.S. Subject

6 components of averaged right median nerve stimu, was left-handed.

both RMN and LMN, components 1 and 2 are largest in contralateral posterior parietal areas. In the majority of subjects, the LMN maximum amplitude focus was slightly more anterior at c4p than the RMN focus which was in the c8p, c4p-4v region. In no subjects were the maximum amplitudes of either component recorded from the site presumably over postRolandic gyrus. The amplitudes of 1 and 2 seem generally smaller and the distribution seems somewhat more restricted for RMN as against LMN within individual subjects. In Fig. 3 and 4 illustrating complete distribution data for LMN and RMN for the same subject, compare responses for the two sides at cPR, c4d, c8p, m6p, and ml2p. Note, in the same Fig., how ipsilateral responses similar to 1 and 2 recorded at i4p and i8p for L M N are not :seen for RMN. Fig. 6

illustrates the more restricted RMN projection of 1 and 2 for another subject. In addition to the contralateral arc (c4a-ml 2p), Fig. 6 presents selected locations where differences in development of the response are apparent. Component 3 is more widespread anteriorly and medially than the preceding components. Its projection is predominantly contralateral. At contralateral and midline anterior locations (c6a, c4a, m8a, and m4a), where 1 and 2 do not appear, component 3 follows a slow negative potential. At present, we do not know the significance of this negativit 3 or its relationship to the negativity which separates 2 from 3 at more posterior locations. The maximum amplitude focus of 3 is rather variable. Four subjects showed consistent foci for both left and right side stimulation. One of them had an anterior contralateral focus; the maxima for the other three subjects were in the area of contralateral Rolandic sulcus. In a fifth subject (Fig. 5), where 2 and 3 merge at most locations, 3 seemed most distinct in the posterior midline region. Measurement difficulties, however, prevented definite localization of the maximum focus in this subject. Finally, we found one exception to the contralaterality of 3. Subiect B.S., for RMN only, showed a well defined 3 at all recording sites. Component 4 has a still more widespread distribution. Although variable in waveform, it occurs with minor exceptions at all locations. The variable waveform made meaningful amplitude measurements impractical in subject J.P. for LMN (see Fig. 3) and subject B.S. for RMN. Where measurements could be made, amplitude maxima were generally in the contralateral anterior section of the head. The incomplete data from subjects G.E. and I.G., however, showed a posterior midline focus. Component 5 was recorded from all electrode sites. The double positive peak occasionally occurs at extreme anterior locations. It becomes increasingly distinct towards posterior locations and is clearest in the posterior parietal-occipital region. A single positive peak appears at the vertex. Progressing coronally from the vertex, there is either a second peak or a marked broadening of the waveform. One subject showed the double positivity at all locations. In Electroenceph. c/in. Neurophysiol., 1962, 14:697-713

SOMATIC EVOKED RESPONSE DISTRIBLITION

three subjects, the RMN double peak projection was somewhat more anterior on the ipsilateral side than that of LMN. In three of the four subjects having well developed later responses, the amplitude of 5 was largest at or near the vertex. In the fourth subject (T.S.), the L M N maximum was at the vertex (see Fig. 2) and the R M N maximum was over contralateral post-Rolandic gyms. Subject I.G., for whom only L M N data are available, also showed a relatively more posterior projection with a maximum at locations c4p and m6p.

705

This subject showed a similar projection for 4. In addition to delimiting the projection areas for components, we investigated whether the amplitudes of a given component at different recording sites maintained the same relationships when compared: A. between subjects for the same stimulation locus; B. within the same subject between corresponding stimulus loci on the two arms. If the distributions are similar, they will be positively correlated. Positive correlations for the first type of comparison indicate inter-subject reproducibility of

TABLE I Distribution correlations A. Coefficients of concordance Components

Site of stimulation

1

RMN LMN RIF L|F

2

.40* .51"* ---

3

.41" .66** ---

4

5

.45* .29 .36 .38

m

.47*** .34** .66*** .67***

B. Spearman correlations - - left arm vs. right arm Components L M N vs. R M N . . . . . . . . . . . . . . . . . 1 2 3 (N--7) (N--7)

Subject

J.P.

.29

.69

T.S.

.64

.75*

B.S.

--.14

.62

T.T.

.62

.66

G.E.

.85*

.12

C. Spearman correlations--nerve

E l F vs. R I F 4 (N=21)

.56 (N=11) .47 ( ~ 17) .56** (N=21) --.47 ( N - - 11) .47 (N=13)

vs. index

5 (N

4 (N--21)

21)

5 (N

21)

--

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.30

.67**

.87***

.40

.40

.38

--

.72**

--.23

.72***

.63**

.36

.21

.45*

.64** .49*

finger Components

Subject

R I F vs. R M N 4

J.P. T.S. B.S. T.T.

.38 .70** -.40

L I F vs. L M N 5

4

.61"* .41 .71"* .62**

5

.72"*

-.34 .54* .82**

.60** .68** .73**

*p 4 . 0 5 ; * * p 4 . 0 1 ;*** p 4 . 0 0 1 . N - - n u m b e r of electrode locations for each subject. Electroenceph.

clin.

Neurophysiol.,

1962,

14:697-713

706

W.R.

GOFF, B. S. ROSNER AND T. ALLISON

relative response amplitude as a function of recording site. Results of the second type of comparison relate to the question of bilateral symmetry of somatic cortical representation. Since our amplitude measures may not meet the restrictive assumptions of the product-moment coefficient of correlation, we used rank-difference methods. Therefore the correlations indicate the degree to which the rank order of amplitudes among recording sites was invariant. We selected the Kendall coefficient of concordance (Siegel 1956) to test type A comparisons (Table I,A). Spearman correlations were used for type B (Table I,B). Components I and 2: The principal projection areas for 1 and 2 comprised seven electrode locations in the contralateral parietaloccipital region. Correlations for 1 and 2 are based on responses at these sites. Coefficients of concordance for both components were significantly positive for stimulation of each side (type A comparisons). Individual correlations for left vs. right side stimulation (type B) were positive but not consistently significant. Component 3: Between-subject differences in recording locations where 3 was measurable made the analysis of its amplitude distributions unsatisfactory. We could not use the coefficient of concordance which requires equal numbers of measurements per subject. For individual subjects, four of five possible comparisons between sides (type B) were positive, but only one was significant. Component 4: In certain subjects, the waveform of this component was quite variable. We could not be sure that we were measuring the same aspect of it at all locations. Correlations were therefore computed on the remaining, less variable subjects and must be qualified accordingly. The coefficient of concordance for RMN, computed for four subjects, was significantly positive. The concordance for LMN, computed for five subjects, was not significant. It appears that there was somewhat less intersubject variability in distributions for stimulation of right nerve than for left nerve. Comparisons between sides were possible in three subjects. Amplitude distributions were quite consistent in two of these subjects. Component 5: This diffusely projected corn-

ponent has the most homogeneous distribution of amplitudes both between subjects for the same stimulation locus and within the same subject for different sides of stimulation. The significantly positive concordances indicate the former; the significantly positive Spearman correlations indicate the latter. Index finger stimulation

Index finger responses were recorded under conditions identical to nerve stimulation. As explained under Procedure, only four subjects gave usable results for finger stimulation. Components 1, 2 and 3 for finger stimuli were markedly reduced or undetectable at many locations where the physically equal but subjectively stronger median nerve shocks evoked an ample response. Fig. 7 presents responses evoked by both left and right finger stimulation. Only the distribution along the contralateral arc is shown for two reasons: the appearance of 1, 2 and 3 for finger stimulation is limited essentially to this area, and the distribution of 4 and 5 practically duplicate nerve stimulation results and therefore are not presented further. Comparisons of LMN against L1F for subject T.S. (Fig. 2 and 7) and of RMN against R I F responses for T.T. (Fig. 5 and 7) illustrate the general finding that intersubject differences in the waveform of the first three components are fairly constant under nerve and finger stimulation. An exception occurred for subject J.P. in whom 2 and 3 were distinctly separate for LMN but merged into one prolonged positively for LIF. For RMN shocks in subjects J.P., B.S., and T.S., 1 and 2 were smaller and had more restricted distributions than their LMN counterparts. Fig. 7 shows a similar finding for finger stimulation in subject T.S. The differences are apparent at locations c8p and c4p-4v. For subject T.T., the R I F distribution of 1 and 2 also seems more restricted, but the coalescence of 2 with 3 complicates this assessment. Finally, as with nerve stimulatk, n, the maximum amplitude focus of 1 and 2 for finger stimulation was posterior to the recording electrode presumed to lie over post-Rolandic cortex. There is essentially no pre-central projection of 1, 2 and 3. The peak latency of l is about Electroenceph. clin. Neurophysiol., 1962, 14:697-713

707

SOMATIC EVOKED RESPONSE DISTRIBUTION

3 - 4 msec longer for finger than for nerve stimulation. This difference must reflect in part the 17-20 cm increase in the peripheral conduction pathway. The restricted number of electrode locations yielding measurable early components made correlation analysis of their distributions impractical. Where the first three components were rain-

beween subjects for the same side of stimulation and between sides for individual subjects. Individual comparisons between finger and nerve yield somewhat better agreement (Table I,C). In contrast to 4, the amplitude distributions of 5 have significant group concordances. Between sides and between finger and nerve for individual subjects, the majority

LEFT FINGER

RIGHT FINGER

SUBJECT; T S c4o

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Fig. 7 Distribution along contralateral arc (c4a-ml2p) of averaged evoked responses to left and right index finger stimulation for two subjects. Both subjects were right-handed.

ute or undetectable, 4 and 5 were still very large. Generally, their waveforms were similar to those of their median nerve counterparts. Table 1,A and B contains correlation analyses of amplitude distributions for these two components for finger stimulation. We also investigated the similarity in their distributions for stimulation of finger and nerve on the same arm. The Spearman correlations for these comparisons appear in Table I,C. Table I,A and B shows that 4 has no significant correlation

of correlations are also significantly positive. Finally, for both sides of stimulation, all four subjects showed a maximum amplitude of 5 at the vertex. For finger as for nerve stimulation, then, 5 has the most diffuse projection over the scalp and the most consistent distribution of amplitudes both between sides and between subjects. DISCUSSION

Monopolar recording of evoked responses Electroenceph. clin. Neurophysiol., 1962, 14:697-713

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W. R. GOFF, B. S. ROSNER AND T. ALLISON

from man through scalp leads has two important advantages over bipolar derivations. First, monopolar records are more directly comparable to the extensive, monopolarly obtained data on evoked responses in animals. Second, tests comparing monopolar records using the nasal indifferent electrode with various bipolar placements showed that the former yielded less variability in response waveform among subjects. Our subsequent finding of heterogeneous distributions of response components explained this result. Depending on electrode placement, bipolar derivation through scalp leads may alter the observed waveform and even fail to detect certain portions of the somatic evoked response thereby exaggerating intersubject variability. Monopolar rzcording has the disadvantage that passive spread may lead to overestimating the spatial distribution of responses. Bipolar recording, however, does not necessarily avoid such overestimation. The problem of passive spread of potentials through meninges, skull, and scalp is probably best attacked by recording simultaneously from these loci and from the cortex (Abraham and Ajmone Marsan 1958; Geisler 1960). Review of the literature on human somatic evoked responses in light of our distribution analysis indicates that some workers have recorded monopolarly, some bipolarly, and a few apparently obtained monopolar records of early components and bipolar records of later ones. Consequently, comparisons of results from different investigations are often hazardous. Form of the response

Previous studies using summation methods have tended to concentrate on earlier components of the evoked response. Our descript'on of the form, polarity, and latency of the earlier potentials (1, 2 and 3) generally agrees with these results. In the first application of automatic summation to somatosensory responses, Dawson (1954) recorded potentials comparable to 2 and 3 from post-Rolandic scalp leads in response to whole nerve stimuli. Calvet et al. (1956), Geisler (1960), and Shagass and Schwartz (1961a, b) have used various averag-

ing devices to detect cerebral potentials following whole nerve stimulation. These potentials seem identical to 1, 2 and 3. Prior to development of summation methods, Dawson (1947, 1950) and Larsson (1953, 1956, 1960) also detected early evoked somatosensory activity by photographic superimposition of successive oscilloscope traces. Their data agree with results from studies using summation techniques. Two groups have recorded early potentials from the exposed surface of the brain in neurosurgical patients. Jasper et al. (1960) describz the initial potentials evoked by stimulation of the ulnar nerve at the elbox¥ in seven fully conscious patients as a rapid di- or triphasic complex with peak latencies at about 20, 22 and 24 msec. This seems similar to component 1. They also show a larger amplitude, slow wave peaking from 35-50 msec. This wave resembles records from our subjects in which 2 and 3 coalesce into one prolonged deflection. The polarity of this deflection :~s not clear from the records of Jasper et a l Hirsch et al. (1961) u~ed automatic summation to record from patients undergoing cramotomy and ventriculography. These authors conclude that "a comparison of somesthetic evoked potential~ obtained on the scalp and on the cerebral cortex - - integration methods being used in both cases - - show a satisfactory similarity of responses" (p. 421, our translation). Considerable consistency thus exists between previous reports and present results on the waveform of the first 60-70 msec of the somatic evoked response recorded from the scalp. Furthermore, allowing for attenuation and possible smearing by passive spread, these scalp potentials seem to bc a reasonable representation of potentials recorded directly from the brain surface. Ther~ are, however, greater divergences between our results and previous reports on somatic evoked activity occurring after 60-70 msec. This later activity has not received systematic study with summation techniques. In reports noting such responses (Calvet et al. 1956; Shagass and Schwartz 1961b), their latencies overlap with the latencies of our 4 and 5. Shagass and Schwartz found greater inter-individual variaElectroenceph. clin. Neurophysiol., 1962, 14:697-713

SOMATIC

EVOKED

RESPONSE

bility in these later potentials than in earlier ones when stimulating ulnar nerve. For median nerve stimulation, we find considerable intersubject variability in the waveform of 4, but the waveform of 5 is very similar in all subjects. Shagass and Schwartz placed one lead at the approximate location of our post-Rolandic recording electrode and a second one 5 cm anterior in the same parasagittal plane. Our distribution results show that the anterior lead would be inactive for the early components and that the derivation at the post-Rolandic lead would be essentially monopolar. For the later components, however, the anterior lead would be quite active and the derivation would then be bipolar. As we indicated earlier, our preliminary tests suggested that evoked responses recorded differentially between two active leads may show greater inter-subject variability than when only one lead is active. The relatively large amplitude of evoked potentials after 60-70 msec permits their study by standard electroencephalographic techniques and photographic superimposition. Baneaud et al. (1953) used E E G procedures to record a monophasic, surface negative wave in response to various types of stimuli. Its latency for painful electric shock to the leg was 9 5 - 1 1 0 msec. Larsson (1953, 1956) recorded with photographic superimposition a diphasic negativepositive potential in response to shocks to the ulnar nerve at the elbow. The negative component had a latency of 50-90 msec and a similar duration. The latency of the positivity was 100-120 msec and its duration was 100150 msec. The records of Calvet et al. (1956) show two negative positive diphasic potentials with the positivities peaking at approximately 90 and 150 msec. The first corresponds in latency to 4; the latency of the second is somewhat earlier than 5. Calvet et al. refer to these two late responses as a cycle repeating one or two times with diminishing amplitude. We do not find that 5 diminishes relative to 4. It is usually larger than 4 and frequently the largest potential recorded. Roth et al. (1956) recorded long latency responses to tactile and other types of stimulation. They disagree with previous reports of the form of the response, stating that "though the most prominent deflec-

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tion is sometimes surface negative, careful examination has in our cases almost invariably revealed a small surface positive deflection preceding it" (p. 386). They also report that the voltage of the response influences its form. In the conscious subject, it most often appears as a low amplitude, monophasic wave. If the voltages are high, it is biphasic or triphasic. The onset latencies of the first positive wave reported for four subjects are 43, 55, 80 and 85 msec. Within the latency range reported in these studies, we routinely record two negative positive potentials. Their exact correspondence to previously reported potentials is not clear. On the basis of polarity and latency, the monophasic negativity of Bancaud et al. approximates the negative part of our 5. The negative-positive response reported by Larsson is either 4, 5, or a coalescence of the two. The first diphasic potential of Calvet et al. corresponds to our 4; the second is somawhat earlier than our 5. The earlier onset latencies of the mono-, bi-. or triphasic response reported by Roth et al. are in the range of our 3 and 4. The later latencies suggest the positivity of 4 followed by 5. Apparent discrepancies between previous investigations and this report undoubtedly reflect differences in recording techniques such as indifferent electrode placement and signal detection power of recording systems. Moreover, experimental conditions such as stimulus intensity or degree of alertness and conditioning history of the subject are reported to affect the waveform and amplitude of long latency evoked potentials. Distribution of the r e s p o n s e

Study of the distribution of the somatic evoked response over the scalp has been fragmentary. Available results on the earlier components, however, are consistent with ours. We found 1 and 2 confined to the contralateral posterior quadrant of the head from the postRolandic area back to the occiput. Maximum amplitudes were in the posterior parietal area rather than over the presumed location of somatosensory cortex. Infrequently, we detected 1 and 2 over precentral areas. Component 3 has a predominantly contralateral distribution and extends further anteriorly and medially Electroenceph. clin. Neurophysiol., 1962, 14:697-713

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W. R. GOFF, B. S. ROSNER AND T. ALLISON

than the preceding components. Dawson (1950) recorded from the scalp evoked responses to electrical stimulation of peripheral nerves which resemble our 1, 2, and 3. He found a response maximum over the surface marking of the Rolandic sulcus, but he noted that the antero-posterior potential gradients were asymmetrical around the maximum. Anterior to the Rolandic marking, the gradient declined steeply, while posteriorly it fell off slowly. Dawson suggested that a possible explanation was activity in areas outside the marking of the Rolandic sulcus. Our findings on the amplitude gradient of 1 and 2 support Dawson's report, and we find the focus of the activity posterior to the surface marking of the Rolandic sulcus. For 3, we did not observe a steep prefrontal drop-off. Dawson's use of a frontal reference electrode could account for the discrepancy regarding this component. Jasper e t al. (1960) recorded from the brain surface a "primary complex" with maximum voltage in those post-central gyms areas which yield sensations in contralateral hand and arm upon electrical stimulation. In one subject, however, responses to ulnar nerve stimulation were largest at locations posterior to the postcentral gyms. Some smaller, inconstant evoked responses appeared in several patients in precentral gyrus adjacent to the maximum response area of post-central gyms. The results of Hirsch e t al. (1961) extend those of Jasper e t al. Electrical stimulation of cutaneous nerves at the wrist gave a maximum response at the surface of the hand representation area of post-central gyms and frequent pre-central responses. In addition, responses consistently occurred several cm posterior to the central sulcus. These posterior parietal responses had the same latency as post-central responses; they were unique to somesthetic stimulation; and under local anesthesia, they consisted of a brief negative spike followed by one or more slower waves. Such findings on neurosurgical patients suggest that our records of short latency potentials from posterior parietal scalp reflect activity occurring on the underlying cortical surface and are not wholly attributable to the passive spread through the skull of potentials from remote locations. The significance of these po-

tentials is obscured, however, by the fact that electrical stimulation of the cortical surface in this area evokes no peripheral sensation at voltages considerably higher than those required to obtain such sensation when stimulating postcentral gyms (Hirsch e t al. 1961). This finding accords with that of Penfield and Rasmussen (1950) who found no sensory responses to cortical stimulation at a distance greater than 1 cm from the central fissure. Hirsch e t al. (1961) recorded from the superior bank of the Sylvian sulcus in one patient who had previously undergone temporal lobectomy. They found further evidence for a cortical area in man corresponding to somatosensory II in animals (Penfield and Jasper 1954). Ipsilateral as well as contralateral stimulation produced a diphasic response. Since this response did not appear at the cortical surface in the absence of temporal lobe ablation, it probably is undetectable at the scalp even with averaging techniques. Geisler (1960) concluded that with a response summation method he probably did not detect activity at the scalp arising from primary auditory cortex which also lies buried in the Sylvian fissure. In extensive studies on the effects of penetrating brain wounds on somatosensory perception, Semmes e t al. (1960) found that sensory deficits of the right hand occurred with significantly greater frequency after injury to the left pre-central, post-central, and posterior parietal subsector than after lesions elsewhere in the left hemisphere. They did not get comparable results for the left hand. On the basis of these and other compari;o~ls, they suggest that the left hand projects more diffusely to its contralateral hemisphere than does the right hand. Some of our electrophysiological evidence supports such a suggestion. We find that components 1 and 2 are localized to contralateral parietal cortex and in some subjects their projection for left side stimulation is somewhat more diffuse than for right side. The lack of significantly positive correlations for 1 and 2 between amplitude distributions for L M N v e r s u s RMN stimuli (Table I,B) yields further support by indicating asymmetry between the distributions of both components. Electroenceph. clin. Neurophysiol., 1962, 14:697-713

SOMATIC EVOKED RESPONSE DISTRIBUTION

Investigators who recorded long latency responses to somesthetic stimulation report that these potentials have widespread distributions, apparent bilateral synchrony, and maximum size around the vertex. Due to similarity of waveform, latency, and distribution, these potentials have been equated to the "on-effect" described by P. A. Davis (1939). H. Davis et al. (1939) regarded this response as the waking state counterpart of the initial slow component of the "K-complex" (Loomis et al. 1938). Bancaud et al. (1953) included both phenomena under the term "V-potential", since the maximum focus of both usually is at the vertex. Roth et al. (1956) state that apart from differences in voltage and relative predominance of components the change evoked by sensory stimuli in the EEG at different levels of conciousness is an identical phenomenon which they include under the term K-complex. The K-complex (V-potential, on-effect), then, is variously described as mono-, di-, or triphasic, or repetitive with diminishing amplitude. The two diphasic components which we record within the latency range of the K-complex have widespread distributions, but only that of 5 is reasonably symmetrical. Their latencies are relatively stable over the scalp although variations in waveform occur between recording locations for both components. Component 5 has its maximum amplitude at or near the vertex and is usually larger and more stable than 4. In some subjects at some locations, however, 4 is almost as prominent as 5. Functional significance oJ c o m p o n e n t s

Our analysis of the functional significance of earlier components of the human somatic evoked response has depended mainly on identification of their homologs in unanesthetized monkey (Cebus). We have made these identifications on the basis of similar results from the two species on distribution of responses, recovery cycles, and effects of barbiturates (Allison 1962; Allison et al, in press; Rosner et aI., in press a, b). Extrapolating from animal data in light of these homologies, we have suggested (Rosner et al., in press b) that 1 represents potentials in pre-synaptic thalamo-cortical fibers of the "primary" somatosensory projection

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pathway and 2 represents corresponding postsynaptic potentials. The fact that the final portion of 1 coalesces with 2 and the highly similar projection of 1 and 2 accord with this hypothesized relationship. Component 3 probably reflects extra-lemniscal activity similar to the variously called "association area", "ascending reticular formation", "secondary", or "irradiation" responses. Several authors have speculated on the functional significance and behavioral correlates of somatic evoked responses occurring later than 60-70 msec. Similar potentials in response to auditory and visual stimulation have been reported and many workers therefore contend that they are essentially modality non-specific and involve little or no sensory information. They are reported to be undetectable in a certain percentage of awake subjects and to appear best under conditions of sleep or light barbiturate anesthesia. Roth et al. (1956) regard these findings as support for the hypothesis that the potentials are associated with arousal mechanisms. Our data cannot deny or confirm any of these possibilities. We can only make the following points. First, using summation techniques, we have regularly recorded large complex potentials in the latency range of K-complex (V-potential, on-effect) in a total of 31 conscious, alert subjects. Second, we suggest the possibility that these events are not a single response but may consist of at least two diphasic potentials. Although these potentials have similarly diffuse projections, they have different recovery cycles (Allison 1962) and somewhat different properties in their amplitude distributions. Therefore, they may reflect activity in different though perhaps overlapping neural populations. Their diffuse bilateral projection suggests mediation by extra-/cmniscal pathways. SUMMARY

We have recorded averaged, electrocutaneously evoked potentials from 21 electrodes at the scalp in normal, alert humans. The total response time-locked to a shock to median nerve or index finger is complex, multiphasic, and lasts at least 300 msec. For descriptive purposes we have divided the response into five Electroenceph. clin. Neurophysiol., 1962, 14:697-713

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major components. The initial activity evoked by nerve stimulation consists of a small amplitude, positive-negative-positive sequence peaking at about 16, 20, and 25 msec respectively (component 1). There follows a larger positivity (component 2) peaking at approximately 31 msec. Components 1 and 2 are localized essentially on the posterior eontralateral quadrant of the scalp. Component 3 designates a positivity which peaks at about 48 msec. Its projection is also predominantly contralateral but is more widespread anteriorly and medially than 1 and 2. Component 4 is a diphasic sequence whose negativity peaks at about 65 msec and the positivity at about 85 msec. It is more diffusely distributed than preceding components; it is recorded with minor exceptions from all electrodes. Finally, another, large negative-positive potential (component 5) peaks at about 135 and 220 msec, occurs at all electrodes and has maximum peak-to-peak amplitude at or near the vertex. The highly similar projection of 1 and 2 to posterior contralateral cortex supports the hypothesis that they reflect "primary" somatosensory activity. Component 1 probably represents potentials in pre-synaptic thalamo-cortical fibers and 2 probably represents post-synaptic potentials. The relatively more diffuse distributions of the three subsequent potentials suggest extralemniscally mediated activity. On the basis of distribution and other evidence, we have proposed that 3 may be similar to evoked responses variously termed "association area", "irradiation", etc., in animals. Components 4 and 5 are probably related to responses previously termed "K-complex" or "V-potential". Prior investigations on man have emphasized various parts of the somatic evoked response. The relationships among the results of these investigations are somewhat clarified by comparison with the more complete response presented here. This work was supported in part by grant M-1530 from the National Institute of Mental Health, United States Public Health Service. REFERENCES

ABRAHAM, K. and AJMONE MARSAN, C. Patterns of cortical discharges and their relation to routine

scalp electroencephalography. Electroenceph. clin. Neurophysiol., 1958, 10: 447-461. ADRIAN, E. D. Double representation of the feet in the sensory cortex of the cat. J. Physiol. (LoAd.), 1940, 98: 16P-18P. ADRIAN. E. D. Afferent discharges to the cerebral cortex, from peripheral sense organs. J. Physiol. (LoAd.), 1941, 100: 159-191. ADRIAN, E. D. Afferent areas in the brain of Ungulates. Brain, 1943, 66: 89-103. ALLISON, T. Recovery functions of somatosensory evoked responses in man. Electroenceph. clin. Neurophysiol., 1962, 14: 331-343. ALLISON, T., GOFF, W. R., ABRAHAMIAN, H. A. and ROSNER, B. S. The effects of barbiturate anesthesia on h u m a n somatosensory ew~ked responses. In: R. HERNANDEZ-PE6N (Editor), The physiological basis of mental activity. In press. BANCAUD, J., BLOCH, V. et PAILLARD, J. Contribution EEG h l'dtude des potentiels 6voqu6s chez l'homme au niveau du vertex. Rev neurol., 1953, 89: 399418. CALVET, J., CATHALA, H. P., COYrAMIN, F., HIRSCH, J. et SCttERRER, J. Potentiels dvoqu6s corticaux chez l'homme. Rev. neurol., 1956, 95: 445-454. DAVIS, H., DAVIS, P. A., LOOMIS, A. L., HARVEY, E. N. and HOBART, G. Electrical reactions of the h u m a n brain to auditory stimulation during sleep, J. Neurophysiol., 1939, 2: 500-514. DAVIS, P. A. Effects of acoustic stimuli on the waking h u m a n brain. J. Neurophysiol. 1939, 2: 494-499. DAWSON, G. D. Cerebral responses to electrical stimulation of peripheral nerve in man. J. Neurol. Neurosurg. Psychiat., 1947, I0: 137-140. DAWSON, G. O. Cerebral responses to nerve stimulation in man. Brit. reed. B u l l , 1950, 6: 326-329. DAWSON, G. D. A summation technique for detecting small signals in a large irregular background. J. Physiol. (Lond.), 1951, 115: 2P-3P. DAWSON, G. D. A summation technique for the detection of small evoked potentials. Electroenceph. olin. Neurophysiol., 1954, 6: +~5-84. GEISLER, C. D. Average respomcs to clicks in man recorded by scalp electrodes. Res. Lab. Electron., Mass. lnst. Technol., 1960, Tc, h. Rep. 3 8 0 : 1 5 8 p. GERARD, R. W., MARSHALL, W. H. and SAUL, L. J. Cerebral action potentials. Proc. Soc. exp. Biol. (N.Y.), 1933, 30: 1123-1125. GERARD, R. W., MARSHALL, W. I-[. and SAUL, L. J. Electrical activity of the cat's brain. Arch. Neurol. Psychiat. (Chicago), 1936, 36: 675-735. HIRSCH, J. F., PERTUISET, B., C ILVET, J., BUISSONFEREY, J., FISCHGOLD, H. et SCHERRER, J. Etude des rdponses 61ectrocorticales obtenues chez l'homme par des stimulations somesthdsiques et visuelles. Electroenceph. olin. Neurophy~iol., 1961, 1 3 : 4 1 1 424. JASPER, H., LENDE, R. and RASMUSSEN, T. Evoked potentials from the exposed somato-sensory cortex in man. J. nerv. meat. Dis., 1960, 130: 526-537. KR6NLEIN, R. U. Zur cranio-cerebralen Topographie. Electroenceph. elin. Neurophysiol.,

1962, 1 4 : 6 9 7 - 7 1 3

SOMATIC EVOKED RESPONSE DISTRIBHT~ON

Bruns' Beitr. klin. Chir., 1898, 22: 364-370. LARSSON, L.-E. Electroencephalographic responses to peripheral nerve stimulation in man. Electroenceph, clin. Neurophysiol., 1953, 5: 377-384. LARSSON, L.-E. The relationship between the startle reaction and the non-specific LEG response to sudden stimuli with a discussion on the mechanism of arousal. Electroenceph. clin. Neurophysiol., 1956, 8 : 6 3 1 644. LARSSON, L.-E. Correlation between the psychological significance of stimuli and the magnitudes of the startle blink and evoked L E G petentials in man. Acta physiol, stand., 1960, 48: 276-294. LOOMIS, A. L., HARVEY, E. N. and HOBART, G. A. Distribution of disturbance-patterns in the h u m a n electroencephalogram, with special reference to sleep. J. Neurophysiol., 1938, 1: 413-430. MARSHALL, W. H., WOOLSEY, C. N. and BARD, P. Cortical representation of tactile sensibility as indicated by cortical potentials. Science, 1937, 85: 388-390. MARSHALL, W. H., WOOLSEY, C. N. and BARD, P. Observations on cortical somatic sensory mechanisms of cat and monkey. J. Neurophysiol., 1941, 4 : 1 24. PENFIELD, W. and JASPER, H. Epilepsy and the functional anatomy of the human brain. Little, Brown and Co., Boston, 1954, 896 p. PENEIELD, W. and RASMUSSEN, T. The cerebral corte~ of man. MacMillan, New York, 1950, 248 p. ROSNER, B. S.. ALLISON, T., SWANSON, E. and GOFE, W. R. A new instrument for the summation of

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evoked responses from the nervous system. Electroenceph, clin. Neurophysiol., 1960, I2: 745-747. ROSNER, B. S., GOFF, W. R. and ALLISON, T. Properties of cerebral somatic evoked responses in unanesthelized Cebus monkey. In R. HERN/,NDEZPE6N (Editor), The physiological basis of mental activity. In press, (a). ROSNER, B. S., GOFF, W. R. and ALLISON, T. Cerebral electrical responses to external stimuli. In G. H. GLASER (Editor), L E G and behavior. Basic Books, New York, in press, tb). ROTH, M., SHAW, J. and GREEN, J. The form. voltage distribution and physiological significance of the K-complex. Electroenceph. clin. Neurophysiol., 1956, 8: 385-402. SEMMES, J., WEINSTEIN, S., GHENT, L. and TEUBER, H.-L. Somatosensory changes after penetrating brain wounds in man. Harvard University Press, Cambridge, 1960, 80 p. SHAGASS, C. and SCHWARTZ, M. Reactivity cycle of somatosensory cortex in humans with and without psychiatric disorder. Science, 1961a, 134: 17571759. SHAGASS, C. and SCHWARTZ, M. Evoked cortical potentials and sensation in man. J. Neuropsychiat., 1961b, 2: 262-270. SIEGEL, S. Nonparametric statistics for the behavioral sciences. McGraw-Hill, New York, 1956, 312 p. WOOLSEY, C. N. Organization of somatic sensory and motor areas of the cerebral cortex. In H. F. HARLOW and C. N. WOOLSEY (Editors), Biological and biochemical bases of behavior. University of Wisconsin Press, Madison, 1958: 63-81.

Reference: GOFF, W. R., ROSNER, B. S. and ALLISON, T. Distribution of cerebral somatosensory evoked responses in normal man. Electroenceph. clin. Neurophysiol., 1962, I4:697-713.