Recovery functions of early cortical median nerve SSEP components: normative data

ELSEVIER

Electroencephalography and clinical Neurophysiology 96 (1995) 475-478

Short communication

Recovery functions of early cortical median nerve SSEP components: normative data A. Romani *, R. Bergamaschi, M. Versino, R. Callieco, G. Calabrese, V. Cosi Fondazione, lstituto Neuroh)gico "C. Mondino, " Via Palestro 3, 27100 Pat,ia, Italy Accepted for publication: 26 June 1995

Abstract

The recovery functions o f parietal P14-N20, N20-P27 and frontal P22-N30 amplitudes were assessed in 17 healthy controls aged 2 0 - 5 0 years by means o f the paired stimulus technique. One unpaired and 4 paired stimuli with interstimulus intervals (ISis) o f 25, 50, 75 and 100 msec were cyclically presented in a single run. Responses to the unpaired stimulus were subtracted off-line from paired stimulus responses. The highest suppression was reached at shorter ISis for c o m p o n e n t s with shorter latencies. The mean suppression o f P22-N30 was influenced by the subject's age, being greater in younger subjects. Normative data are reported. Keywords: Somatosensory evoked potentials; Recovery function

1. Introduction

Few recent studies have addressed the recovery function of somatosensory evoked potentials (SSEPs), as obtained with the method of paired stimuli. Some authors have used this and other related methods to better identify and investigate the origin of specific EP components (Meyer-Hardting et al., 1983; Reisin et al., 1988; Delberghe et al., 1990; Cheron and Borenstein, 1991; Garcla-Larrea et al., 1992). The recovery function of a given EP component is obtained through the evaluation of the response amplitude ratio of test stimulus to conditioning stimulus for different interstimulus intervals (ISI). The response to test stimulus is generally "cleared" from superimposed conditioning stimulus components by the subtraction of the unpaired stimulus response from the paired stimulus response. However, the collection of averages separately recorded for the unpaired and different paired stimulations is inadequate, because of unavoidable changes in recording (i.e., impedance), in stimulus (i.e., strength, location) and in the subject's conditions (Nakamura et al., 1990; Emori et al., 1991). Therefore, most authors have alternated one unpaired with one paired stimulus in any one run and have repeated the procedure for each ISI. Nakamura et al. (1990) proposed a new method, which they tested in 3 subjects, and in which they continuously alternated 1 unpaired with 4 different paired stimuli, thus optimizing the stability of the recording conditions and reducing the number of unpaired stimuli needed. They adopted an on-line subtraction method which, however, is not directly transferable to market-available averagers. Moreover, Nakamura et al. (1990) and most other authors have adopted reference electrodes, which are not considered optimal for the evaluation of selected SSEP components. In the present study, we report normative data for the recovery functions of median nerve SSEP components. We programmed a market-

Corresponding author. Tel.: + 382-380275; Fax: + 382-380286.

available stimulation/recording equipment to cyclically alternate different ISis, and to collect averages referring to 5 different stimulation conditions in single runs.

2. Methods and subjects 2.1. Subjects Seventeen healthy subjects, 8 females and 9 males, with mean age of 33.5 years (range 20-50 years) were submitted to the procedure. Each decade was represented by at least 5 subjects (at least 2 subjects for each

sex). 2.2. Stimulation and recording procedure A Pathfinder plus system was used for stimulation, recording and off-line analysis. The subjects lay supine on a comtortable bed in an acoustically isolated room. Silver-silver chloride cup electrodes were placed at P3(4), C3(4), F3(4), Fpz and Al(2). Care was taken to keep impedance below 2 k ,(2. The right and left median nerves were stimulated at the wrist by 0.1 msec constant current square pulses with an intensity of 20% above motor threshold; the order of stimulation of the two nerves was randomized across subjects. The stimuli were given in the following order: 1 unpaired stimulus (S1) and 4 paired stimuli (S1-$2) with respective ISis of 25, 50, 75 and 100 msec. The interval between two SI stimuli was 1.1 sec, which ensured an interval of at least 1 sec between $2 and the following $l. For each of the 5 stimulus conditions, 4 channels were used (i.e., a total of 20 averaging memories, 512 points each): parietal, central and frontal electrodes contralateral to the stimulated side, and a midfrontal electrode, all of which were referenced to the contralateral earlobe. Two series of 200 artifact-free responses were averaged for each stimulus condition and each subject. The tracings were

0168-5597/95/$09.50 © 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0 0 1 3 - 4 6 9 4 ( 9 5 ) 0 0 1 4 5 - X

EEP 94765

A. Romani et al. / Electroencephalography and clinical Neurophysiology 96 (1995) 475-478

476

~"y
"

•

l ~. V

" '~"

•

,~,,g/*"J~cX,

•

P27 I

I

I

I I

I

I

I

I

I

I

.

I

I

I

I~

I

I

I

I

N30

I

I,

I

A. Romani et al. / Electroencephalography and clinical Neurophysiology 96 (1995) 475-478

P14-N20

N20-P27

A%

477

P22-N30

A%

t50

150

!50 i

I

106-. 96. --97 ........ 32 **,4"1 39

100

!

,"66 29

50

I

100

50

i /

O0

"

,."

-.65 ** 3i ..........s2 .......'s9 23 24

36

50

16 ...... 3 4

I I

0

0 25

50

75

100

0 25

ISI

50

75

100

ISI

25

50

75

100

ISI

Fig. 2. Values of percent amplitude (A%; single stimulus condition = 100%) of parietal P14-N20, N20-P27 and frontal P22-N30 components. Mean values and (2 S.D.) limits are displayed. The numbers reported indicate the mean and the S.D. values. The asterisks refer to the significance of the MANOVA contrasts ( * P < 0.01; * *P < 0.001).

checked for reproducibility, and in a few cases the sweep number was increased to 400. The input was amplified with a filter bandpass of 5-1500 Hz. The analysis time was 200 msec, including a 20 msec prestimulus. The responses obtained with unpaired stimuli were digitally subtracted from those obtained with paired stimuli. We interactively took the latencies and the peak-to-peak amplitudes (absolute amplitudes showed great intra- and inter-individual variability) of those peaks that were reliably detected in all subjects: P14, N20, P27 in the P3(4)-A2(1) tracing; P22, N30 in the F3(4)-A2(1) tracings. Precentral N18-P22 amplitude was often only about 0.1-0.2 /xV and could not be reliably assessed (see also Fig. 1). This parameter was therefore not considered.

2.3. Statistical analysis The SPSSPC ÷ package was used. The distribution of the parameters was checked for deviations from normality with the Koimogorow-Smirnow (K-S) test. Each parameter was submitted to repeated measures analysis of covariance (Greenhouse-Geisser correction) with the following within-subject factors: stimulus condition (5 levels) and stimulus side (2 levels), with sex as a between-subject factor and with age as a covariate (MANOVA). Contrasts with baseline amplitude as reference level were performed. The amplitudes of components obtained in the 4 S1-$2 conditions were expressed as a percentage of the amplitude of the component obtained in S1 condition (A%). After checking for normality (K-S), we expressed the limits of these percentages as mean + 2 S.D. To prevent abnormal A% values, at single ISis, giving rise, in a clinical context, to false-positive results, we also computed the following two indices of amplitude suppression for those components that showed significant suppression at more than one ISI: lowest amplitude (LA%) and mean amplitude (MA%). LA% represented the lowest percent amplitude across the 3 shortest paired stimulus conditions (suppression was never maximal at 100 msec ISI). MA% represented the mean value of the

same 3% amplitudes. The effects of sex and age on these indices (and on A% at 25 msec ISI for P14-N20 amplitude) were tested with analysis of covariance and with regression analysis. The alpha limit for significance was set at P = 0.05.

3. Results Reproducible tracings were obtained for all subjects. One example is reported in Fig. 1. The distribution of each parameter was not significantly different from normal. Analysis of covariance never showed significant interaction effects. Neither did the covariate (age) significantly influence latency and amplitude parameters. Sex showed significant effects on P14 and N20 latencies, which were shorter in females than in males ( P < 0.001). Of the within-subject factors, stimulus side exerted no significant effects, whereas the "stimulus condition" factor showed significant effects on all 3 amplitudes ( P < 0.001). The mean values for A% at the 4 ISis, along with their upper and lower limits (2 S.D.), are reported in Fig. 2. This figure also reports the significance levels of the contrasts, which considered the unpaired stimulus condition as reference level. LA% and MA% did not show sex-related differences. Age neither influenced P14-N20 A% at 25 msec ISI, nor N20-P27 LA% and MA% (mean and S.D. values for N20-P27 as follows: LA%: 37% + 22%; MA%: 59% + 18%). Both P22-N30 LA% and MA% were significantly ( P < 0.05) age-associated, with younger subjects showing greater amplitude reductions than did older ones (y = 21% + 0.8% X age and y = 44% + 0.8% X age respectively). Linear regressions and upper (2 S.E.) limits are reported in Fig. 3. Analysis of variance jointly performed on the A% values of the 3 components revealed a significant ISI X component interaction, showing that the time-course of amplitude suppression differed between the com-

Fig. 1. Example of right median SSEPs (two repetitions and their means) from P3-A2 (upper panel) and F3-A2 (lower panel) obtained with single stimulus (lower traces), and with paired stimuli (ISI = 25, 50, 75 and 100 msec from bottom to top, after subtraction of the response to a single stimulus). P14, N20, P27, P22 and N30 are evidenced by a marker. Calibration: 20 msec; 1.25 /~V.

A. Romani et al. / Electroencephalography and clinical Neurophysiology 96 (1995) 475-478

478 LA%

MA%

140

preceded, at least for some components, by a facilitation period that was reported at ISis of about 10-20 msec (Saito et al., 1992), and by an "early" suppression (ISI < 10 msec) of putative central origin (Saito ct al., 1992). With appropriate ISI values, our method may be used to assess these "early" effects too. P22-N30 recovery was selectively influenced by age, with younger subjects showing greater " m e a n " and "highest" suppression. This effect has not been considered by other authors and needs replication. Our results can be used as normative data to assess the recovery of median SSEP components in patients.

140 P22-N30

P22-N30 120

120

100

100

80

80

60

60

40

40

References 20

/

0

-

' 1 " 1 ' 1 / ! / ~ ' 1 " 1 '

I'

0

,

I

•

I

,

I

,

I

•

I

,

I

,

I

,

15 20 25 30 35 40 45 50 5S

15 20 25 30 35 40 45 50 55

YEARS

YEARS

Fig. 3. Relations of lowest amplitude (LA%) and mean amplitude (MA%) of P22-N30 to subject's age (in years). Predicted value and (2 S.E.) limits are reported.

ponents. This interaction effect remained in the 3 additional and similar analyses that we performed after removing one of the three components at a time.

4. Discussion

The method here proposed to obtain the recovery function of SSEP components solves the problems related to changes in the recording and in the subject's condition by cyclically alternating the unpaired and the different paired stimuli. The procedure is notably shorter than those in which one unpaired and only one paired stimuli are recorded in any one run, and in which the procedure is then repeated for each ISI. With our method, the time needed to obtain the recovery functions of median SSEPs is generally less than 1 h. In ambiguous cases the Fpz reference (and thus the P3(4)-Fpz derivation obtained by subtraction) may be helpful to identify parietal N20. The time-course of amplitude recovery differs between the components: highest suppression is reached at 25 msec ISI for P14-N20, at 50 msec ISI for N20-P27, and at 75 msec ISI for P22-N30. For the latter two components, the figure is U-shaped and is similar to that reported by other authors (Allison, 1962; Nakashima et al. 1992; Saito et al., 1992). We chose ISis which are commonly applied in clinical studies, particularly those on myoclonus-related conditions (Ugawa et al., 1991). The physiological meaning of the "late" amplitude attenuation, which is obtained with our ISis, is not completely known and is probably partially related to reafferent activity (Saito et al., 1992). This phase may be

Allison, T. Recovery functions of somatosensory evoked responses in man. Electroenceph. clin. Neurophysiol., 1962, 14: 331-343. Cheron, G. and Borenstein, S. Gating of the early components of the frontal and parietal somatosensory evoked potentials in different sensory-motor interference modalities. Etectroenceph. clin. Neurophysiol., 1991, 80: 522-530. Delberghe, X., Mavroudakis, D., Zegers de Beyl, D. and Brunko, E. The effect of stimulus frequency on post- and pre-central short-latency somatosensory evoked potentials (SEPs). Electroenceph. clin. Neurophysiol., 1990, 77: 86-92. Emori, T., Yamada, T., Seki, Y., Yasuhara, A., Ando, K., Honda, Y., Leis, A.A. and Vachatimanont, P. Recovery functions of fast frequency potentials in the initial negative wave of median SEP. Electroenceph, clin. Neurophysiol., 1991, 78: 116-123. Garcia-Larrea, L., Bastuji, H. and Maugui~re, F. Unmasking cortical SEP components by changes in stimulus rate: a topographic study. Electroenceph, clin. Neurophysiol., 1992, 84: 71-83. Meyer-Hardting, E., Wiederholt, W.C. and Budnick, B. Recovery function of short-latency components of the human somatosensory evoked potential. Arch. Neurol., 1983, 40: 290-293. Nakamura, M., Shibasaki, H., Nishida, S. and Neshide, R. A method for real-time processing to study recovery functions of evoked potentials. IEEE Trans. Biomed. Eng., 1990, 37: 738-740. Nakashima, K., Nitta, T. and Takahashi, K. Recovery functions of somatosensory evoked potentials in parkinsonian patients. J. Neurol. Sci., 1992, 108: 24-31. Reisin, R.C., Goodin, D.S., Aminoff, J. and Mantle, M.M. Recovery of peripheral and central responses to median nerve stimulation. Electroenceph, clin. Neurophysiol., 1988, 69: 595-588. Saito, T., Yamada, T., Hasegawa, A., Matsue, Y., Emori, T., Onishi, H. and Fuchigami, T. Recovery functions of common peroneal, posterior tibial and sural nerve somatosensory evoked potentials. Electroenceph. clin. Neurophysiol., 1992, 85: 337-344. Ugawa, Y., Genba, K., Shimpo, T. and Mannen, T. Somatosensory evoked potential recovery (SEP-R) in myoclonic patients. Electroenceph. clin. Neurophysiol., 1991, 80: 21-25.