Scalp distribution of human auditory evoked potentials. II. Evidence for overlapping sources and involvement of auditory cortex

Electroencephalography and clinical Neurophysiology, 1982, 5 4 : 2 5 - 3 8 Elsevier Scientific Publishers Ireland, Ltd.

25

SCALP D I S T R I B U T I O N OF H U M A N AUDITORY EVOKED P O T E N T I A L S . II. EVIDENCE FOR O V E R L A P P I N G S O U R C E S AND I N V O L V E M E N T OF AUDITORY CORTEX t C H A R L E S C. W O O D ,.2 and J O N A T H A N R. W O L P A W **

* Neuropsychology Laboratory, Veterans Administration Medical Center, West Haven, Conn. 06516 and Departments of Neurology and Psychology', Yale University, New Haven, Conn. 06520, and ** Center for Laboratories and Research, New York State Department of Health, and Departments of Neurology and Anatomy, Albany Medical College, Albany, N.Y. 12201 (U.S.A.) (Accepted for publication: February 10, 1982)

The preceding paper (Wolpaw and Wood 1982) investigated the relative activity of alternative cephalic and non-cephalic reference sites for human auditory evoked potentials (AEPs). No detectable voltage gradients were observed at locations on or below the neck over the entire AEP sampling epoch. In contrast, large voltage gradients were observed at locations on the head, with sharpest gradients over the temporal scalp. We concluded that commonly used cephalic reference sites, including the nose, ear and mastoid process, lie in regions of the AEP field where sizable voltage gradients occur in most subjects, whereas non-cephalic reference sites such as the balanced sternovertebral (SV) reference of Stephenson and Gibbs (1951) do not. The latter appears to be the best available AEP reference because it is both relatively inactive with respect to AEPs and relatively insensitive to E K G artifact. In this paper, we examine in greater detail the spatial distributions of AEPs on the scalp and consider their implications for the sources of human AEPs. Previous experiments have analyzed AEP scalp distributions by plotting amplitude distributions at the peaks of major AEP deflections. This approach assumes that the scalp distribution over the entire duration of each deflection is accurately represented by the distribution at the peak. Such an Supported by the Veterans Administration and N I M H Grant MH-05286. We thank M. Reisenauer and J. Jasiorkowski for technical assistance, and T. Allison, T.M. Darcey, W.R. Goff, G. McCarthy, and J.D. Wicke for comments on the manuscript. To whom correspondence should be sent.

assumption is justified if the deflection is identical in morphology and latency across electrode locations, and varies only in amplitude. However, if there are changes in morphology or latency across electrode locations, then the scalp distribution at the peak does not adequately characterize the potential fields in question. In such cases, the conventional method of analysis can seriously misrepresent AEP scalp distributions and lead to inaccurate inferences concerning AEP sources. In this paper we do not assume that the scalp distributions at peaks of major AEP deflections accurately characterize the spatiotemporal distribution of scalp AEPs. Rather, we calculate scalp distributions at every time point throughout the sampling epoch in order to assess their stability over time and their relation to peaks of major deflections. A time period during which the scalp distribution is relatively stable in shape and changes only in magnitude indicates a stable source configuration. In contrast, a time period during which the scalp distribution changes in shape indicates corresponding changes in source configuration. Such changes could be due to changes in the pattern of synaptic activation of a given anatomical structure or to the overlapping but asynchronous activation of multiple sources. To summarize, if a given AEP deflection is accompanied by a stable scalp distribution, then our approach and the traditional peak-oriented approach will lead to similar inferences about AEP sources. However, if the scalp distribution changes in shape during a given AEP deflection, then our approach should provide a more accurate and comprehensive char-

0013°4649/82/0000-0000/$02.75 © 1982 Elsevier Scientific Publishers Ireland, Ltd.

26 acterization of the spatial and temporal properties of scalp AEPs and should lead to more accurate inferences concerning their sources. The major focus of previous AEP distribution studies has been the large, vertex maximal, negative-positive complex referred to as 'N1-P2,' 'N100-P200' (or other variants of the polaritylatency nomenclature), or the auditory 'vertex potential' (VP). As discussed by Wolpaw and Wood (1982) considerable disagreement exists concerning the scalp distribution of AEPs during the VP time period and their implications for AEP sources. Some investigators have concluded that the auditory VP is generated in or near primary auditory cortex on the superior temporal plane (Vaughan and Ritter 1970; Simson et al. 1977; Vaughan et al. 1980), whereas others have favored more widespread cortical sources, particularly frontal cortex (Kooi et al. 1971; Picton et al. 1974, 1978; Streletz et al. 1977). The problem of identifying sources for AEP activity in the VP time period is complicated further by reports suggesting additional simultaneous activity at temporal scalp locations (Kooi et al. 1971; Wolpaw and Penry 1975; Streletz et al. 1977; Picton et al. 1978; McCallum and Curry 1979). Such temporal scalp activity and its relation to the VP have not been addressed by previous scalp distribution studies. The results to be presented demonstrate that scalp AEPs are characterized by time periods during which the scalp distribution is relatively stable in shape and changes only in magnitude, and by time periods during which the scalp distribution changes markedly in shape. Some AEP deflections correspond to periods of relatively stable scalp distribution, whereas others, most notably the VP negativity (N1 or N100), do not. The discussion concentrates upon the implications of these results for the sources of scalp AEPs.

C.C. WOOD, J.R. WOLPAW intervals in blocks of 48, binaurally in 8 subjects and monaurally in 3. Each subject received 3 such blocks with short intervening breaks, for a total of 144 trials. For the 3 subjects receiving monaural stimulation, the data analyzed were the average of potentials for left and right ear stimulation. AEPs were recorded simultaneously from an array of 20 electrodes located over the right hemisphere, sampled at 1 msec per point, and averaged on-line by a PDP-12 computer. The EEG was monitored visually and the computer trigger circuit was interrupted manually during ocular, EMG and movement artifacts. Recordings over one hemisphere were used in order to maximize spatial resolution with the 20 available simultaneous recording channels. Thus, the present data do not address AEP distributions for ipsilateral and contralateral monaural stimulation. In addition to the standard midline and right hemisphere locations of the International 10-20 system, the following locations were used: Cz-C4, C4-T4, C4-P4, P4-T4, F4-T4, F8-T4, T4-T6, and tragus. The hyphen indicates locations halfway between those of the 10-20 system. AEPs from the ear and mastoid were ineluded from the array used by Wolpaw and Wood (1982) in order to provide comprehensive coverage of the temporal region, although they were not recorded simultaneously with the locations listed above. Potentials recorded from Cz in both arrays did not differ significantly; we therefore considered it justified to include the ear and mastoid sites in the distributions to be presented. All electrodes were referred to the balanced SV reference electrode of Stephenson and Gibbs (1951). The data to be presented will focus mainly on scalp distributions derived from grand average AEPs across the 11 subjects, in order to emphasize features common to all subjects. However, intersubject differences in scalp distributions were noted and will be discussed where appropriate (also see Wolpaw and Wood 1982).

Methods

Stimulation and recording conditions The same ll subjects and similar stimulating and recording procedures used by Wolpaw and Wood (1982) were employed. Click stimuli (0.5 msec. 50 dB SL) were presented at fixed 3.2 sec

Isovoltage topographic maps Isovoltage topographic maps were derived by a PDP-11 computer at every sample point (I msec resolution) for 250 msec following stimulus onset. The electrode sites were located on the lateral view of the head given by Jasper (1958), and the elec-

SCALP DISTRIBUTION OF HUMAN AEPs. II trode locations, the outline of the head, and the approximate locations of the sylvian and central fissures were translated into (X,Y) coordinates using a graphic digitizer. A network of triangles was constructed with the (X, Y) coordinates of the electrodes as vertices using the algorithm of Lawson (1972), and voltage values at locations between electrode locations were interpolated at the nodes of a 50 × 50 equal interval grid. Linear and non-linear bivariate interpolation algorithms (e.g., Akima 1978) were evaluated. The maps to be presented are based on linear interpolation since the non-linear algorithms can introduce undesirable distortions in the topographies (e.g., maxima and minima located between electrode locations), Isovoltage contours over the 3-dimensional (X, Y, voltage) surface were calculated using the algorithm of Snyder (1978) and plotted using a digital plotter.

Results

First we describe in traditional fashion the morphology of AEPs obtained at different scalp locations and present isovoltage topographies at the peaks of major deflections. Second, we present isovoltage topographies at high temporal resolution in order to: (a) identify time periods during which the scalp distribution is stable in shape and periods in which it changes significantly; and (b) to determine which major AEP deflections are accompanied by periods of stable distribution and which are not. A E P wave forms

Fig. 1 presents grand average AEP wave forms across subjects plotted as a function of electrode location on the same map (Jasper 1958) used for the topographies to be presented below. To facilitate comparison of wave forms across electrode locations in Fig. 1, the dotted vertical line through each wave form is plotted at the latency of the m a x i m u m negativity at Cz. The most striking feature of the data is that the morphology of AEPs at posterotemporal locations differs markedly from those at frontocentral locations. These differences in morphology are sum-

27

\

1

,

Fig. 1. AEP wave forms plotted as a function of electrode location on the same map of the lateral surface of the head used for the topographic maps. Electrode locations are indicated by dots and the dotted vertical line on each wave form indicates latency of the peak negativity at the vertex. Sampling epoch: 250 msec; positivity relative to a sternovertebral noncephalic reference is upward.

marized in the upper left panel of Fig. 2, which superimposes grand average frontocentral and posterotemporal wave forms at their locations of maximum amplitude (Fz and T4-T6, respectively). The wave form at Fz is similar to that previously reported (e.g., Picton et al. 1974; G o l f et al. 1977: Streletz et al. 1977). It consists of an initial positive-negative-positive complex followed by the large negative-positive complex of the auditory VP. For descriptive purposes these peaks will be labeled according to their frontocentral (F) location of maximum amplitude, their polarity, and their latency, as FP30, FP55, FN88 and FPI70. The temporal wave forms, in contrast, are characterized by a different set of peaks, again labeled according to their temporal (T) maximum, polarity and latency, as TN32, TN57, TP78, TN115 and TP190. The initial temporal peaks, TN32 and TN57, are nearly simultaneous with FP30 and FP55 and are opposite in polarity. Later temporal peaks (TP78, T N 115 and TP190) are not accompa-

28

C.C. W O O D , J.R. W O L P A W

C-RRND RVERRC-E

,.

/ V-I I

I

I

0

I

I

50

I

LGO t 5 0

I

,

Fz

,-

I

I

I

200

250

MSEC

T4-T8 \

",.Sl -I./

FZ

T&-T6

I~ t

p ~ •

50

tO0

T4-T8" ~ =

/L

v

T4-T8 / ~"-~F~ //7

LI:" t

t:'-\ t

0

.'."."/ t

17-111

50

tOO tSO 200 250 MSEC

0

50

tOO 150

MSEC

200

250

0

1.50 200 250

MSEC

Fig. 2. Comparison of frontocentral and posterotemporal wave forms at locations of maximal amplitude (Fz and T4-T6, respectively) in grand average AEPs (top left) and in individual subjects.

SCALP DISTRIBUTION OF HUMAN AEPs. II nied by peaks at frontocentral sites. Wave forms at other locations are either similar to those at Fz and T4-T6, or appear to have morphologies intermediate between these two extremes (see Fig. 1). Peaks earlier than 30 msec were not reliably resolved with the high-frequency cutoff, sampling rate and number of trials employed. The remaining panels in Fig. 2 present Fz and T4-T6 wave forms for each of the 11 subjects in order to illustrate the extent to which the grand average wave forms are representative of each subject's data. In the Fz wave forms, major peaks apparently corresponding to FN88 and FP170 in the grand averages are evident in all individuals, but there is considerable variability in latency, relative amplitude and morphological details across subjects. The FP30, FP55, TN32 and TN57 peaks are difficult to identify in individual subjects, although there is a consistent tendency for the frontocentral and temporal wave forms to be nearly 180 ° out of phase at these latencies. In the temporal wave forms, a peak apparently corresponding to TP78 is evident in most subjects, although in some subjects it is a relative positivity in a wave form that remains negative relative to baseline. Peaks roughly corresponding to TN115 and TP190 are evident in all subjects, again with some degree of variability in latency, relative amplitude and morphology. In summary, the grand average wave forms appear to be representative of the data of individual subjects, although considerable intersubject variability is present.

Isovoltage topographies at peaks of major deflections Fig. 3 A - F present isovoltage topographic maps at the major frontocentral and temporal peaks described above. Electrode locations are indicated by solid dots, except for the open square and open triangle which indicate the locations of the inset wave forms shown with each map (e.g., T4-T6 and Fz in Fig. 3A). The latency of each map is indicated on the wave forms by an asterisk. Solid and dotted isovohage contour lines indicate positive and negative voltage, respectively. Each of the 20 isovoltage contour lines in each map represents 5% of the difference between minimum and maximum voltage at that time point. Thus, contour lines

29 within a map represent equal voltage increments, but contour lines in different maps do not. Normalizing the contour intervals to the voltage range in this manner provides the same relative resolution in each map regardless of the total amplitude range at that time point. Fig. 3A and B present topographic maps for the two pairs of nearly simultaneous frontocentral and temporal peaks, henceforth referred to as F P 3 0 / T N 3 2 and F P 5 5 / T N 5 7 . The two distri~ butions are similar, with positive maxima frontocentrally and negative maxima posterotemporally. The zero potential line in both distributions falls between the sylvian and central fissures. The major difference between the two distributions is the location of the frontocentral peak; it is more lateral and tightly focused for F P 5 5 / T N 5 7 than for FP30/TN32. Fig. 3C and D present scalp distributions at the negative and positive frontocentral peaks, FN88 and FP170. The distribution of FN88 is negative over most of the head with a frontocentral maximum, but positive in the posterotemporal region. In contrast, the distribution of FP170 is positive at all locations sampled. In both cases the major axis of the potential field runs posterotemporally to frontocentrally. Fig. 3E and F present the scalp distributions at the positive and negative peaks of the posterotemporal wave form, TP78 and T N l l 5 . As noted above, the latencies of these temporal peaks do not correspond to those of the frontocentral peaks shown in Fig. 3C and D, and their scalp distributions differ as well. The shape of the distribution at TP78 is similar to that at FN88 shown in Fig. 3C, although there is more extensive positive voltage present in the temporal region at TP78. The distribution at TN115 consists of a negative peak over the centrolateral scalp maximum at C4-T4, which decreases in all directions from that point,

lsot~oltage topographies at high temporal resolution Fig. 4 presents isovoltage topographies at 2 msec intervals from 20 to 160 msec and at 10 msec intervals from 160 to 250 msec. Each of the maps in Fig. 4 is identical to those in Fig. 3, except that the outline of the head is omitted and each isovoltage contour line represents 5% of the voltage dif-

30

C.C. WOOD, J.R. WOLPAW f

A ~f,

: -/A

'

i

\

!

/

', j/

/

i, I

I

,,' /

It

',j

,

1 P ,Iy !

i

? /JV

i

M~EC

B

253

c (

2 U, 250

~3EC

250

HSEC

C

)

i;

D :::::::::::::::::::::::::::::: ,,,

{

,,~t

t

::" :A<:-" :"f ?-~ t" ~5~) ::: 2"::: :: " "" : I

~1,

'250

~5FC

/

,

....,

',,

] +

6

PISCC

250

g

~

250

NSEC

6

OSEC

250

\1

;750

G

'

/

~FC

4 f ~

F --~'~--:->.'S'::i~<~::::...i~\

,,'

::::::::::::::::::::::::::::: .., :::-

~

~ /.....

========================= J

--.~:::~

', '

' , uvj

~SEC

250 / (

S

"

G

~5:C

25C

7

~

',

+

6

::: 717--.

t~

~SEC

,,,,

',,,, :::,',,:.,,:,~',,,,',.,., : : ,~..~' ,.:,,.::,",,~,.>.','..-~<.:./..:.~-:<'r-,,"

\

"

',

,,

,, / 'd

)

"~S:<,'::,.%~:- /

,'

(,

250 /

\ )

M~CC

25~

$

Fig. 3. lsovoltage topographies at major frontocentral and temporal peaks. A: F P 3 0 / T N 3 2 . B: F P 5 5 / T N 5 7 . C: FN88. D: FPI70. E: TP78. F: TN115. See text for details.

ference between the maximum and minimum voltages across the entire sampling epoch. Thus, unlike Fig. 3 A - F , every isovoltage contour line in every map of Fig. 4 represents the same amount of voltage. Fig. 4 therefore illustrates changes in both the shape and magnitude of distributions over time. Latencies in Fig. 4 corresponding to FP30/TN32, F P 5 5 / T N 5 7 , TP78 and FN88 are so labeled. We have divided the 250 msec epoch into 8 time periods which are distinguished either by relatively stable versus rapidly changing scalp distributions or by distinct distribution patterns within periods of more gradual change. Each period

merges into preceding and following periods so that the exact dividing line between them is to some extent arbitrary. This subjective identification of periods of stability and change in scalp distributions is consistent with calculated measures of the difference between distributions at successive time points similar to those described by Lehmann and Skrandies (1980) (e.g., sum of absolute values of the differences in voltage between successive time points at each electrode location, square root of the sum of squared differences between voltages at successive time points, etc.). The 8 time periods and the distributional patterns

SCALP DISTRIBUTION

OF HUMAN

A E P s . It

31 :

•

-~ -.,, •

.

.

~2

20

*

•

•

,

26

24

•

•

•i

L. ~

',.

• 30

28

"

•

•

.

*

•

•

,

.

•

• , Fp3(~/T N32

•

•

42

q,

°

/=8

44

.,

:

.

" :.;" •

:

:

-

...:

.

•

•

"

"~,'~." •

•

"

•

38

"V""

•

•

,:

•

-¢

54

56

:

.

•

~5~t~n~

:-.

•" •

58

:

.~..

. • 62

611

•

~

•

64

•

66

:;,

-:.

"

•

6~

. -t.

70

. .':.

•

.

74

•

..3.

86

88

FN~

90

*

•

92

"

76

94 ,,

.,,¢ ~ -,_:,

•

"

"

"TPSS

~8

.

"5-'- " ~ ' t T " "

"i~f "~'''

•

.,,~.,..-... • -'~.,'.-.,." •

.,..,~...... ,, • v>'~_.~-,

•

t02

104

"

"

,~2

142

*

'•

• ',<',~',-.2-"

105

108

*'~

12o"'":.' ~''"

.®.

148

•

•~"

..,

~, ::"~'"

144

,,",ii(..~';:

,,..,",;'L~ , .,~. • ",'A, "~-,"

, ;,-~--.%.'.... 120

"

..

.

• :_'->

•

.

.,~~

.•

36

,

52

50

48

~

•

•

" ~

34

k.

•" ~

.

•

32

.

j"

,3~":"~''~''

•

.|--

. ; .

p

96 .

.'.2;--.

-'-

.-L

•

..;.?.-.

•

,','.~', •., ,'., ,,~,,~., , . . y

110

"

"

.

112

"-"

Ill

•

I15

*~*t~

•

•

13~' :'':'~

.

•

•

I18

•

•-'=

•

•

:N :N

•~••

160

98

"

•

•

*

200

*

"

240

35O

"

"

Fig. 4. I s o v o h a g e t o p o g r a p h i e s at 2 m s e c i n t e r v a l s f r o m 60 to 250 msec. See text for details.

that characterize them are: (1) 2 0 - 6 0 rnsec. The distribution during this period is relatively stable, consisting of positive maxima frontocentrally and negative minima posterotemporally, which are largest in amplitude at the latencies of the F P 3 0 / T N 3 2 and F P 5 5 / T N 5 7 peaks and are smaller before and after. Thus, this time period is one in which major AEP deflections are accompanied by a scalp distribution which is relatively stable in shape and changes primarily in magnitude. (2) 6 2 - 6 8 msec. This period is one of extremely rapid change in the scalp distribution. It corresponds to a sharp peak in the measures of difference between distributions at successive time points. During the interval from approximately 70 to 150 msec the scalp distribution changes more gradually. On the basis of shape and polarity, 4

distributional patterns were identified in this period. (3) 70-88 msec. This period consists of a frontocentral negativity and posterotemporal positivity corresponding closely to the distribution of the TP78 peak encompassed by this period (Fig. 3E). The major change over this period is an increase in the size of the frontocentral negativity and a decrease in area of the posterotemporal positivity. The small posterotemporal region of positive voltage evident in the map for FN88 (Fig. 3C) is not seen at 88 msec in Fig. 4 because of the different voltage ranges represented by each contour line in the two figures. (4) 9 0 - 1 0 0 rnsec. The distribution during this period is similar in shape to that in the preceding period, with a frontocentral maximum and posterotemporal minimum, except that voltage is negative at all locations sampled. Note that FN88,

32 the negative peak of the traditional N1-P2 complex, occurs at the transition between periods 3 and 4, and that the downward and upward slopes of FN88 have markedly different scalp distributions. (5) 102-120 msec. This period is characterized by a distribution having a lateral negativity which is initially maximum at frontocentral sites and then moves down the head, reaching a maximum near T4 at i ! 8 msec. The major negative peak in the temporal wave form, TN115, occurs in the middle of this period of lateral migration. (6) 122-152 msec. During this period the distribution shows a frontocentral positivity and a posterotemporal negativity. It is similar in shape to those in period 3 (70-88 msec) but is opposite in polarity. The temporal negativity gradually decreases in size and the zero potential line moves posterotemporally until the distribution is completely positive by 154 msec. This period corresponds in latency to the upward slope between the negativity (N1 or N100) and positivity (P2 or P200) of the traditional auditory VP. (7) 154-210 msec. The distribution during this period is relatively stable, consisting of positive voltage at all locations sampled, with a broad frontocentral maximum. The measures of difference between distributions at successive time points were at their minimum values during this period. The distribution is similar in shape to that of period 4 (90-100 msec) but is opposite in polarity. This period encompasses both FP170, the positive peak of the auditory VP and the posterotemporal peak TPI90. (8) 220-250 rnsec. In this p e r i o d the large frontocentral positivity of the preceding period diminishes in size, becoming negative near the end of the sampling epoch.

Discussion

Following brief consideration of interpretive issues in scalp distribution studies, we compare the present results to those of previous experiments and consider their implications for hypotheses regarding the sources of human AEPs.

c.c. WOOD, J.R. WOLPAW Interpretation and measurement of scalp distributions

The instantaneous potential field distribution over the scalp is determined by the instantaneous location and configuration of transmembrane current sources associated with active neural elements (for review, see Schlag 1973; Llinhs and Nicholson 1974; Vaughan 1974; Goff et al. 1978; Wood and Allison 1981). However, the converse is not true. The number, location and configuration of sources are not uniquely determined by the surface potential field. Therefore, hypothesized sources can be rejected if they conflict with empirical scalp distributions, but competing hypotheses that account equally well for empirical distributions must be evaluated using other data (e.g., intracranial recordings, lesion effects, animal studies, etc.). The concept of a dipole source has figured prominently in hypotheses about the sources of human AEPs (e.g., Vaughan and Ritter 1970; Kooi et al. 1971), as well as in discussions about the sources of EEG and evoked potential phenomena in general (e.g., Brazier 1949; Shaw and Roth 1955a, b; Schlag 1973; Vaughan 1974; Goff et al. 1978). A dipole source is a convenient fiction adopted because evoked potential distributions often approximate those generated by a theoretical dipole source and because a considerable body of theory exists for such sources (e.g., Plonsey 1969; Henderson et al. 1975; Sidman et al. 1978; Darcey et al. 1980; Wood 1982). Potential fields generated by different sources sum linearly at every point in a conductive medium (Helmholtz's principle of superposition), and the concept of an 'equivalent' or 'resultant' dipole is used to refer to the theoretical dipole source whose field best approximates the summated field from multiple sources. The location and orientation of such equivalent dipole sources can be good approximations of physiological sources if the active tissue is relatively restricted, but need not correspond to physiological sources in the case of extensive or multiple sources (see Sidman et al. (1978) and Wood (1982) for examples and discussion of both cases). Lehmann and Skrandies (1980) recently presented topographic analyses of visual evoked potentials from a perspective similar to that of the present paper. Although their approach and ours

SCALP DISTRIBUTION OF HUMAN AEPs. I1 are similar in many respects, the two approaches differ on two important points. First, Lehmann and Skrandies (1980) assume that 'a time point of maximal relief (or maximal power) of the evoked scalp field reflects the occurrence time of maximal activity of an evoked process in a given brain area' (p. 618). They compared a number of different measures of spatial power (e.g., the square root of the sum of squared differences in voltage between all pairs of electrodes) and in ,all cases peaks in spatial power were associated with periods of stable scalp distributions. In contrast, for our data measures of spatial power and distributional change similar to those used by Lehmann and Skrandies demonstrated that peaks in spatial power need not be accompanied by stable distributions. For example, the latency period between 70 and 120 msec (encompassing the FN88 peak) was associated with a major peak in spatial power, but was also accompanied by systematically changing scalp distributions. Thus, in our opinion, a peak in spatial power should not be regarded as a unitary 'component' reflecting a stable source configuration. Measures of distributional change appear to be more important in the context of source identification than measures of spatial power, since a changing distribution implies a changing source configuration even when associated with a peak in spatial power. Second, we disagree with the implication of Lehmann and Skrandies that the reference electrode employed is irrelevant in topographic studies. We agree with their emphasis on features of instantaneous scalp distributions that do not depend upon the reference employed. Such an approach emphasizes the physical fact that an instantaneous potential field can be determined only to within an additive constant (e.g., Plonsey 1963). However, since changes in distributions over time are not independent of the reference electrode employed, every attempt should be made to identify an indifferent reference electrode in the sense of minimal spatial and temporal gradients (Wolpaw and Wood 1982).

20-60 msec activity: FP30/TN32 and FP55/TN57 The two initial peaks F P 3 0 / T N 3 2 and F P 5 5 / T N 5 7 correspond in morphology and

33 latency to potentials previously termed 'middle latency components' (e.g., Picton et al. 1974; Streletz et al. 1977). These potentials are maximal in amplitude over frontocentral scalp, and previous investigators have suggested that they may be cortical in origin (Picton et al. 1974; Streletz et al. 1977). Our data are consistent with previous results in demonstrating a frontocentral maximum for the positive peaks FP30 and FP55 (Fig. 3A and B) and reveal two additional features of their scalp distributions: first, both FP30 and FP55 are accompanied by nearly simultaneous peaks at posterotemporal locations, TN32 and TN37. This apparent polarity inversion is evident in the grand average AEPs shown in Fig. 3A and B, but it is more difficult to observe in the data of individual subjects (Fig. 2). Vaughan and Ritter (1970) also noted polarity inversions in this latency range in some subjects. Second, there is a suggestion that the frontocentral maximum of F P 5 5 / T N 5 7 lies off the midline (Fig. 3B). Whether or not the same is true for F P 3 0 / T N 3 2 is difficult to determine from the present data. Bilateral recordings are required to verify this result for F P 5 5 / T N 5 7 and to examine the maximum of F P 3 0 / T N 3 2 in more detail. As noted above, the scalp distributions at the F P 3 0 / T N 3 2 and F P 5 5 / T N 5 7 peaks are representative of the distribution throughout the 20 60 msec period which encompasses these peaks. This distribution is consistent with the hypothesis that potentials throughout this period are generated by sources in the auditory cortices of both hemispheres. More specifically, the distribution is consistent with dipole layer sources in the posterior part of the superior temporal plane, including the temporoparietal junction, oriented tangentially to the surface of the temporal scalp. Although bilateral recordings were not obtained in the present experiment, we assume that a roughly comparable distribution would have been obtained over the left hemisphere. Additional data are necessary to test this assumption and to compare distributions over the left and right hemispheres and for ipsilateral and contralateral monaural stimulation. As recently shown by Galaburda and Sanides (1980), human primary auditory cortex as defined by cytoarchitectonic criteria extends into the most

34 posterior portions of the superior temporal plane and onto the parietal operculum. A similarly placed primary auditory cortex source might be responsible for the sharp forward tilt of the F P 3 0 / T N 3 2 and F P 5 5 / T N 5 7 fields shown in Fig. 3A and B. That F P 3 0 / T N 3 2 and P 5 5 / T N 5 7 do not arise in more anterior temporal cortex is suggested by 3 observations: (a) the maximum negativity in both distributions is located at extreme posterior temporal scalp locations; (b) the isovoltage contours in both distributions are more steeply sloped than the major plane of the anterior portion of the sylvian fissure; and (c) F P 3 0 / T N 3 2 has been reported to persist following resection of the anterior 6 cm of the temporal lobe but not after resection of the anterior 10 cm (Hammond et al. 1980), and to persist following bilateral temporal lobe damage that spared the temporoparietal junction (Parving et al. 1980). The origin of F P 5 5 / T N 5 7 in primary auditory cortex is also consistent with the auditory evoked magnetic field in that latency region (Farrell et al. 1980). Although the dipole-like configurations of the F P 3 0 / T N 3 2 and F P 5 5 / T N 5 7 fields and the nearly perfect synchrony of the frontocentral and posterotemporal peaks (Figs. 2, 3A and B) are consistent with a single dipole layer source in each hemisphere, we emphasize that other more complex generator configurations are also consistent with the obtained distributions. For example, positive and negative parts of the F P 3 0 / T N 3 2 and F P 5 5 / T N 5 7 fields might be generated by totally different sources. However, pending evidence to the contrary, we favor the simpler hypothesis that AEP activity between 20 and 60 msec is due to a relatively restricted dipole layer source in auditory cortex of each hemisphere. This activity probably does not reflect the initial postsynaptic response of auditory cortex (the so-called primary evoked response), since Goff et al. (1977) demonstrated that potentials apparently corresponding to FP30 and FP55 were abolished by surgical levels of barbiturate anesthesia. 60-250 msec activity: TP78, FN88, T N l l 5 , FP170, TP190 Previous experiments have reached one of two conclusions about the sources of AEPs in the

c.c. WOOD, J.R. WOLPAW 60-250 msec period. Some investigators, observing that the VP negativity and positivity were largest near the vertex and decreased uniformly in all directions, concluded that the VP originates in diffuse cortical or subcortical structures, particularly frontal cortex (e.g., Kooi et al. 1971; Picton et al. 1974, 1978; Streletz et al. 1977). Other investigators, observing temporal scalp potentials of opposite polarity or different morphology from potentials at the vertex, concluded that auditory cortical areas in the temporal lobe are responsible for all or part of scalp AEP activity during the VP time period (Vaughan and Ritter 1970; Peronnet et al. 1974, 1977; Wolpaw and Penry 1975; Simson et al. 1977; Vaughan et al. 1980). The scalp distributions obtained in the present experiment are consistent with the contribution of one or more regions of auditory cortex to scalp potentials in the 60-250 msec period. Furthermore, they demonstrate significant changes over time in the shape of AEP scalp distributions, and thus imply changes in source configuration. Although there is disagreement on many specific points, a number of kinds of data support the conclusion that AEP activity in the 60-250 msec period at least in part reflects sources in one or more regions of auditory cortex. These data include: (a) effects of temporal lobe lesions in humans on AEPs (Peronnet et al. 1974; Peronnet and Michel 1977; Knight et al. 1980); (b) ipsilateralcontralateral differences in temporal AEP latency and amplitude (Wolpaw and Penry 1975); (c) the location and form of auditory evoked magnetic fields in humans (Hari et al. 1980); (d) AEP recordings from the cortical surface in humans (Celesia 1976; Celesia and Puletti 1971); and (e) surface and intracranial AEP recordings in monkeys (Arezzo et al. 1975; Steinschneider et al. 1980). For a detailed review of these data and their implications, see Wood et al. (1982). In the remainder of this section, we outline two alternative hypotheses which account in part for the AEP scalp distributions reported here. The first is a modification of the hypothesis of Vaughan and Ritter (1970), and the second is the hypothesis of Wolpaw and Penry (1975). The two hypotheses are similar in 3 ways: (a) both propose multiple sources for AEPs in the 60-250 msec latency

SCALP DISTRIBUTION OF HUMAN AEPs. II period; (b) both propose significant involvement of auditory cortex; and (c) both leave significant portions of the AEP scalp distribution unexplained. The two hypotheses differ in the specific regions of auditory cortex hypothesized to contribute to scalp AEPs and in the specific parts of the spatiotemporal AEP field attributed to auditory cortical sources. Both hypotheses are supported to varying degrees by other evidence as noted below. Vaughan and Ritter (1970) proposed that a dipole layer source in primary auditory cortex on the superior temporal plane was responsible both for the negativity and positivity of the VP at frontocentral scalp locations, and for potentials of opposite polarity below the sylvian fissure (also see Simson et al. 1977; Vaughan et al. 1980). The present results and those of Wolpaw and Wood (1982) demonstrate that differences in polarity between frontocentral and posterotemporal locations are not due entirely to the use of a nose reference as Kooi et al. (1971) suggested. However, the data also demonstrate morphological differences between frontocentral and posterotemporal locations and changes in scalp distribution over time which indicate that the AEP scalp distribution is more complex than the data and interpretation of Vaughan and Ritter (1970) indicate. Scalp distributions of dipolar shape were obtained for some intervals during the VP region (e.g., 70-86 and 122-152 msec) and are consistent with dipole layer sources of the form hypothesized by Vaughan and Ritter (1970). However, modification of their hypothesis to include an additional source or sources, partially overlapping the first in time, is required to account for: (a) the evidence of changing source configurations over time; (b) the distributions of non-dipolar form at other latencies (88-100 and 154-210) during the VP period (Fig. 4); and (c) the observation that the temporal peak TP78 is not positive relative to baseline in all individuals (Fig. 2). Wolpaw and Penry (1975) also proposed two overlapping sources to account for activity in the 60-250 msec period. One source was secondary auditory cortex, located on the lateral surface of the temporal lobe, which was hypothesized to gen-

35 erate a positive-negative complex (the 'T-complex') distributed focally over the posterior temporal scalp. The existence of such a source is consistent with cortical surface AEP recordings in humans (Celesia and Puletti 1971; Celesia 1976)and with surface and intracranial recordings in monkeys (Arezzo et al. 1975). Unlike the modified Vaughan and Ritter hypothesis which attributes part of the AEP field at both temporal and frontocentral scalp locations to auditory cortical sources, the Wolpaw and Penry hypothesis attributes only the temporal positivity (70-86 msec) and the subsequent temporal negativity (122-152 msec) to auditory cortex. A second source, overlapping the first in time, was hypothesized to produce a widespread negativepositive complex comparable to the traditional auditory VP. Its activity would account for: (a) potentials at frontocentral locations throughout the 60-250 msec period; (b) for the exclusively negative and positive distributions in periods 4 (88-100 msec) and 7 (152-210 msec); and (c) for the observation that TP78 is not positive relative to baseline in all subjects. In summary, the present scalp distribution data and the results of lesion experiments, magnetic recordings and AEP recordings in monkeys strongly suggest that auditory cortical structures contribute significantly to scalp AEPs. However, available data do not distinguish the relative contribution of auditory cortex sources on the superior temporal plane and lateral temporal surface, which is the main difference between the alternative hypotheses outlined above. Furthermore, these two sources are not mutually exclusive. Evidence in the monkey indicates that both the superior temporal plane and the lateral surface generate long latency AEP activity (Arezzo et al. 1975), and both regions could contribute significantly to scalp AEPs in humans. Additional experiments are necessary to determine the relative contribution of different sources within auditory cortex and to identify cortical or subcortical sources outside auditory cortex. In particular, human lesion data are needed using a non-cephalic reference and detailed spatiotemporal mapping of scalp distributions.

36

Summary The scalp distributions of human auditory evoked potentials (AEPs) between 20 and 250 msec were investigated using non-cephalic reference recordings. AEPs to binaural click stimuli were recorded simultaneously from 20 scalp locations over the right hemisphere in 11 subjects. Computer-generated isovoltage topographic maps at high temporal resolution were used to assess the stability of AEP scalp distributions over time and relate them to major peaks in the AEP wave forms. For potentials between 20 and 60 msec, the results demonstrate a stable scalp distribution of dipolar form that is consistent with sources in primary auditory cortex on the superior temporal plane near the temporoparietal junction. For potentials between 60 and 250 msec, the results demonstrate changes in AEP morphology across electrode locations and changes in scalp distribution over time that lead to two major conclusions. First, AEPs in this latency period are generated by multiple sources which partially overlap in time. Second, one or more regions of auditory cortex contribute significantly to AEPs in this period. Additional data are needed to determine the relative contribution of auditory cortex sources on the superior temporal plane and the lateral temporal surface and to identify AEP sources outside the temporal lobe.

R6sume Distribution sur le scalp des A E P chez l'homme. II. Mise en bvidence des recouvrements des sources et de I'implication du cortex auditif

Les distributions sur le scalp des potentiels 6voqu6s auditifs (AEP) entre 20 et 250 msec ont 6t6 6tudi~es ~ l'aide d'enregistrements avec r~f6rence non-c6phalique. Les AEP en r6ponse ~t une stimulation par clics binauriculaires ont 6t6 enregistr6s simultan6ment au niveau de 20 localisations de scalp sur l'h6misph6re droit chez 11 sujets. Des cartes topographiques de gradients obtenues par calculateur h une haute r6solution temporelle ont

C.C. W O O D , J.R. W O L P A W

6t6 utilis6es pour mesurer la stabilit6 des distributions sur le scalp des AEP dans le temps et les relier aux pics principaux des ondes AEP. En ce qui concerne les potentiels entre 20 et 60 msec, les r6sultats montrent une distribution stable sur le scalp, de forme bipolaire, qui correspond h une source au niveau du cortex auditif primaire sur le plan temporal supbrieur pr6s de la jonction temporo-paribtale. En ce qui concerne les potentiels entre 20 et 250 msec, les r6sultats montrent des modifications de la morphologie du AEP entre les diverses localisations d'61ectrodes et des modifications de la distribution sur le scalp avec le temps qui entrainent deux conclusions principales: (1) dans cette p6riode de latence les AEP sont g6n6r6s par des sources multiples qui se chevauchent partiellement dans le temps; (2) une ou plusieurs r6gions du cortex auditif contribuent de faqon significative aux AEP dans cette p+riode. Des donn6es supplbmentaires sont n6cessaires pour d6terminer la contribution relative des sources du cortex auditif sur le plan temporal sup6rieur et sur la surface temporale lat6rale et pour identifier les sources des AEP en dehors du lobe temporal.

References Akima, H. A method for bivariate interpolation and smooth surface fitting for irregularly distributed data points. A C M Trans. math. Software, 1978, 4 : 1 4 8 159. Arezzo, J., Pickoff, A. and Vaughan, H.G. The sources and intracerebral distribution of auditory evoked potentials in the alert rhesus monkey. Brain Res., 1975, 90: 57-73. Brazier, M.A.B. The electrical fields at the surface of the head during sleep. Electroenceph. clin. Neurophysiol., 1949, 1: 195-204. Celesia, G.G. Organization of auditory cortical areas in man. Brain, 1976, 99: 403-414. Celesia, G.G. and Puletti, F. Auditory input to the h u m a n cortex during states of drowsiness and surgical anesthesia. Electroenceph. clin. Neurophysiol., 1971, 31 : 603-609. Cohen. M.M. Coronal topography of the middle latency auditory evoked potentials (MLAEP) in man. Electroenceph. clin. Neurophysiol., 1982, 53: 231-236. Darcey, T.M., Ary, J.P. and Fender, D.H. Methods for the localization of electrical sources in the h u m a n brain. In: H.H. Kornhuber and L. Deecke (Eds.), Motivation, Motor, and Sensory Processes of the Brain, Progr. in Brain Res.. Vol. 54. Elsevier/North-Holland. Amsterdam, 1980: 128134. Farrell, D.E.. Tripp, J.H., Norgren, R. and Teyler. T.J. A study

SCALP DISTRIBUTION OF HUMAN AEPs. II of the auditory evoked magnetic field of the human brain. Electroenceph. clin. Neurophysiol., 1980, 49: 31-37. Galaburda, A. and Sanides, F. Cytoarch~tectonic organization of the human auditory cortex. J. comp. Neurol., 1980, 190: 597-610. Golf, G.D., Matsumiya, Y., Allison, T. and Golf, W.R. The scalp topography of human somatosensory and auditory evoked potentials. Electroenceph. clin. Neurophysiol., 1977, 42: 57-76. Goff, W.R., Allison, T. and Vaughan, H.G. The functional neuroanatomy of event-related potentials. In: E. Callawayl P. Tueting and S.H. Koslow (Eds.), Event-related Brain Potentials in Man. Academic Press, New York, 1978: 1-79. Hammond, E.J., Bruni, J. and Wilder, B.J. Middle latency auditory evoked potentials in patients with temporal lobectomies. Soc. Neurosci. Abstr., 1980, 6: 563. Hari, R., Aittoniemi, K., Jarvinen, M.-L., Katila, T. and Varpula, T. Auditory evoked transient and sustained magnetic fields of the human brain. Exp. Brain Res., 1980, 40: 237-240. Henderson, C.J., Butler, S.R. and Glass, A. The localization of equivalent dipoles of EEG sources by the application of electrical field theory. Electroenceph. clin. Neurophysiol., 1975, 39: 117-130. Jasper, H.H. The 10-20 electrode system of the International Federation. Electroenceph. chn. Neurophysiol., 1958, 10: 371-375. Kooi, K.A., Tipton, A.C. and Marshall, R.E. Polarities and field configurations of the vertex components of the human auditory evoked response: a reinterpretation. Electroenceph. clin. Neurophysiol., 1971, 31: 166-169. Lawson, (?.L. Generation of a Triangular Grid with Application to Contour Plotting, Memo. 299. Jet Propulsion Lab., Calif. Inst. Technol., Pasadena, Calif., 1972. Lehmann, D. and Skrandies, W. Reference-free identification of components of checkerboard-evoked multichannel potential fields. Electroenceph. clin. Neurophysiol., 1980, 48: 609-621. Llin~, R. and Nicholson, C. Analysis of field potentials in the central nervous system. In: A. R~mond (Ed.), Handbook of Electroencephalography and Clinical Neurophysiology, Vol. 2B. Elsevier, Amsterdam, 1974: 61-83. McCallum, W.C. and Curry, S.H. Hemisphere differences in event related potentials and CNVs associated with monaural stimuli and lateralized motor responses. In: D. Lehmann and E. Callaway (Eds,), Human Evoked Potentials: Applications and Problems. Plenum, New York, 1979: 235--250. Parving, A., Salomon, G., Elberling, C., Larsen, B. and Lassen, N.A. Middle components of the auditory evoked response in bilateral temporal lobe lesions. Scand. Audiol., 1980, 9: 161-167. Peronnet, F. and Michel, F. The asymmetry of the auditory evoked potentials in normal man and in patients with brain lesions. In: J.E. Desmedt (Ed.), Prog. clin. Neurophysiol., Vol. 2. Basel, Karger, 1977: 130-141. Peronnet, F., Michel, F., Echallier, J.F. and Girod, J. Coronal topography of the human auditory evoked responses. Electroenceph, clin. Neurophysiol., 1974, 37: 225-230.

37 Picton, T.W., Hillyard, S.A., Krausz, H.I. and Galambos, R. Human auditory evoked potentials. I. Evaluation of components. Electroenceph. clin. Neurophysiol., 1974, 36: 179190. Picton, T., Woods, D., Stuss, D. and Campbell, K. Methodology and meaning of human evoked potential scalp distribution studies. In: D. Otto (Ed.), Multidisciplinary Perspectives in Event-related Brain Potential Research. U.S. Environmental Protection Agency EPA-600/9-77-043, Washington, D.C., 1978: 515-522. Plonsey, R. Current dipole images and reference potentials. IEEE Trans. biomed. Elect., 1963, BME-10: 3-8. Plonsey, R. Bioelectric Phenomena. McGraw-Hill, New York, 1969. Schlag, J. Generation of brain evoked potentials. In: R.F. Thompson and M.M. Patterson (Eds.), Bioelectric Recording Techniques. Part A: Cellular Processes and Brain Potentials. Academic Press, New York, 1973: 273-316. Shaw, J.C. and Roth, M. Potential distribution analysis. I. A new technique for the analysis of electrophysiological phenomena. Electroenceph. clin. Neurophysiol., 1955a, 7: 273284. Shaw, J.C. and Roth, M. Potential distribution analysis. II. A theoretical consideration of its significance in terms of electrical field theory. Electroenceph. clin. Neurophysiol., 1955b, 7: 285-292. Sidman, R.D., Giambalvo, V., Allison, T. and Bergey, P. A method for localization of sources of human cerebral potentials evoked by sensory stimuli. Sensory Processes, 1978, 2: 116-129. Simson, R., Vaughan, H.G. and Ritter, W. The scalp topography of potentials in auditory and visual discrimination tasks. Electroenceph. clin. Neurophysiol., 1977, 42: 528-535. Snyder, W.V. Contour plotting. ACM Trans. math. Software, 1978, 4: 290-294. Steinschneider, M., Arezzo, J. and Vaughan, H.G. Phase-locked cortical responses to a human speech sound and lowfrequency tones in the monkey. Brain Res., 1980, 198: 75-84. Stephenson, W.A. and Gibbs, F.A. A balanced non-cephalic reference electrode. Electroenceph. clin. Neurophysiol., 1951, 3: 237-240. Streletz, L.J., Katz, L., Hohenberger, M. and Cracco, R.Q. Scalp recorded auditory evoked potentials and sonomotor responses: an evaluation of components and recording techniques. Electroenceph. clin. Neurophysiol., 1977, 43: 192206. Vaughan, H.G. The analysis of scalp-recorded brain potentials. In: R.F. Thompson and M.M. Patterson (Eds.), Bioelectric Recording Techniques. B: Electroencephalography and Human Brain Potentials. Academic Press, New York, 1974: 158-207. Vaughan, H.G. and Ritter, W. The sources of auditory evoked responses recorded from the human scalp. Electroenceph. clin. Neurophysiol., 1970, 28: 360-367. Vaughan, H.G., Ritter, W. and Simson, R, Topographic analysis of auditory event-related potentials. In: H.H. Kornhuber and L. Deecke (Eds.), Motivation, Motor, and Sensory

38 Processes of the Brain, Progr. in Brain Res., Vol. 54. Elsevier/North-Holland, Amsterdam, 1980: 279-285. Wolpaw, J.R. and Penry, J.K. A temporal component of the auditory evoked response. Electroenceph. clin. Neurophysiol., 1975, 39: 609-620. Wolpaw, J.R. and Wood, C.C. Scalp distribution of human auditory evoked potentials. I. Evaluation of reference electrode sites. Electroenceph. clin. Neurophysiol., 1982, 54: 15-24.

C.C. WOOD, J.R. WOLPAW Wood, C.C. Application of dipole localization methods to source identification of human evoked potentials. Ann. N.Y. Acad. Sci., 1982, in press. Wood, C.C. and Allison, T. Interpretation of evoked potentials: a neurophysiological perspective. Canad. J. Psychol., 1981, 35: 39-61. Wood, C.C., McCarthy, G., Squires, N.K., Vaughan, H.G., Woods, D.L. and McCallum, W.C. Anatomical and physiological substrates of event-related potentials: two case studies. Ann. N.Y. Acad. Sci., 1982, in press.