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Role of human SII cortices in sensorimotor integration
Clinical Neurophysiology 113 (2002) 1573–1578 www.elsevier.com/locate/clinph
Role of human SII cortices in sensorimotor integration Ken Inoue a,*, Takamasa Yamashita b, Toshihide Harada a, Shigenobu Nakamura a a
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan b Institute of Health Science, Hiroshima University School of Medicine, Japan Accepted 15 May 2002
Abstract Objectives: To elucidate the functional properties of neurons in the human primary (SI) and ipsilateral and contralateral secondary (iSII or cSII) cortices in response to stimuli during finger movement. Methods: We measured somatosensory evoked fields (SEFs) produced by electric stimuli delivered to the median nerve at 0.2 Hz in 6 healthy subjects. Results: The amplitudes of evoked fields from both iSII and cSII were gradually attenuated with time. Consecutive blocks of trials were obtained to assess the habituation of each evoked field. Complex finger movements with attention (gating session) increased the amplitude of evoked fields from the iSII cortices but reduced the amplitudes of evoked fields from the cSII cortices ðP , 0:01Þ. In contrast, the amplitude of P30m from the SI did not show habituation effects but decreased significantly in the gating session ðP , 0:01Þ. Conclusions: The enhanced iSII as well as suppressed cSII cortices during complex finger movements with attention are not only considered to be result of gating effect but also attention. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: SII cortices; Sensorimotor integration; Somatosensory evoked fields; Attention
1. Introduction Somatosensory information is important for motor control. Sensory input is integrated with motor commands at several levels of the motor system: spinal, subcortical and cortical. Recently, a number of studies have provided electrophysiological evidence of sensorimotor integration at the cortical level. For example, transcranial magnetic stimulation (TMS) studies have shown modulation of motor evoked potential (MEP) size when conditioned by sensory afferents (Bertolasi et al., 1998) or when tested in various motor tasks (Lemon et al., 1995). Studies on somatosensory evoked potentials or fields (SEP or SEF) have also revealed a change in activities of the primary somatosensory (SI) cortices (Cohen and Starr, 1987; Rossini et al., 1989; Kristeva-Feige et al., 1996; Rossi et al., 2002). However, most of these investigations focused on the relationship of SI cortices to SEP or SEF, and few studies have electrophysiologically demonstrated a sensorimotor integration of SII cortices (Huttunen et al., 1996; Forss and Jousmaki, 1998; Kakigi et al., 1997). Magnetoencephalography (MEG), which has high sensitivity and temporal resolution, has made it possible to non* Corresponding author. Present address: 1-2-3 Kasumi Minami-ku, Hiroshima 734-8551, Japan. Tel.: 181-82-257-5201; fax: 181-82-5050490. E-mail address: [email protected] (K. Inoue).
invasively determine the strength of neuronal activity in SII cortices in the human brain (Mima et al., 1997). Using MEG, we demonstrated the habituation process of activities of SII cortices in control and gating sessions. We also found that these activities are facilitated in the ipsilateral SII cortices (iSII) by electrical stimulation and inhibit activities of the contralateral cortices (cSII) during the performance of manipulative finger movements that require intensive attention to complete co-contraction of hand muscles for the best-level performance.
2. Subjects and methods 2.1. Subjects The subjects were 6 right-handed neurologically intact adults (5 males and one female; mean age (^SD), 30.8 (^6.9) years; range, 22–45 years). Informed consent for participation in the study was obtained from all subjects. Each of the subjects sat in a magnetically shielded room while SEFs were recorded. 2.2. SEF studies Electrical stimuli of 0.2 ms in duration were delivered to the left median nerve at the wrist (cathode proximal). The
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stimulus intensity was approximately 3 times greater than the sensory threshold but was painless and elicited a mild twitch of the thumb at regular intervals with a repetition rate of 0.2 Hz. The conditions during the stimulation were rest (control session) and opposing the left thumb with the tip of each digit sequentially, as d2, d2, d3, d4, d4, d4 and d5, repetitively (gating session). The subjects were instructed to pay careful attention to the stimulated moving fingers during the gating session and to relax and watch a film of their own choice during the control session. Magnetic recordings in a frequency range of 0.05–200 Hz were taken from the whole-head SQUID gradiometer system (Vector view TM, Neuromag) comprising 204 first-order magnetic gradiometers. The sampling rate was 800 Hz. Epoch length was 350 ms, including a 50 ms prestimulus baseline. Six consecutive blocks of MEG data, each block containing 30 stimuli, were averaged off-line for each condition. DC offset was based on the 50 ms prestimulus baseline. Among the 204 gradiometer channels, we selected each channel showing the largest influx in amplitude for evoked fields of N20m and P30m from the SI cortices and from the iSII and cSII cortices. We assigned evoked fields from the iSII or cSII cortices as P50m/N100m since electrically negative and positive peaks appeared
around 50 and 100 ms after the electrical stimulation, respectively. The peak amplitudes and latencies of N20m, P30m and P50m/N100m were measured using the same channel. The peak deflections of N20m, P30m and P100m were measured for latency. The amplitude was measured from the baseline to maximum upward influx for N20m, from the maximum upward influx of N20m to maximum downward influx for P30m, and from the maximum upward influx to maximum downward influx for P50m/N100m. 2.3. Statistical analysis One-way analysis of variance (ANOVA) was used for testing the statistical difference in amplitude, and Pearson’s correlation test was used for correlation analysis. P values less than 0.01 were considered significant. 3. Results Fig. 1 shows representative 204-channel SEF waveforms during control and gating sessions. The earliest response, N20m, peaked over the contralateral anterior parietal cortex at 22.2 ms (Fig. 1(a)). N20m was followed by a stronger response, P30m, with opposite polarity at 34.2 ms (Fig.
Fig. 1. Representative 204-channel SEF responses to left median nerve stimulation in subject H.O. Enlarged responses: (a) contralateral SI, (b) cSII cortices, and (c) iSII cortices. The head is viewed from above with the nose pointing upwards. Two sets of responses in the control (continuous line) and gating (dashed line) sessions are superimposed. Note the increase in responses from iSII cortices and suppression from cSII cortices.
K. Inoue et al. / Clinical Neurophysiology 113 (2002) 1573–1578
1(a)). Later deflections were observed at 52.2/88.5 ms (Fig. 1(b)) over the contralateral and at 56.5/84.2 ms (Fig. 1(c)) over the ipsilateral temporoparietal cortices. Maximum response waveforms from the SII region were seen bilaterally a few centimeters above the ear (Fig. 1). The biphasic responses were observed in all subjects and were used for quantitative comparison using the same gradiometer between the control and gating sessions. 3.1. Comparison of SI and SII cortices in control and gating sessions A total of 180 averages of SEF demonstrated significant decreases in the amplitudes of N20m and P30m from the SI cortices and in the amplitude of P50m/N100m from the cSII cortices during the gating session compared with control values, while P50m/N100m from the iSII cortices was enhanced during the gating session (Table 1, P ¼ 0:0074 for cSII and P ¼ 0:0001 for iSII). Peak latency of P30m was significantly delayed in gating session compared with control values (Table 1, P , 0:01), while no significant difference was detected between peak latencies of P50m/ N100m in the control and gating sessions. 3.2. Habituation The amplitudes of P50m/N100m from the iSII and cSII cortices changed time-dependently according to consecutive averaged waveforms of each block (Fig. 2, Fig. 3(b)). The higher amplitude of P50m/N100m from iSII cortices
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and the lower amplitude from cSII cortices during gating session compared to the control remained, although the amplitude progressively decreased over time in both conductions of P50m/N100m. The amplitude of N20m and P30m did not show much change (Fig. 3(a)), contrasting that of P50m/N100m from the iSII and cSII which showed a progressive decline of amplitude from the initial (first block) to the final (6th block) sections. The amplitudes of N20m and P30m were significantly correlated with the responses of cSII, but not of iSII, in amplitude ðP , 0:001Þ (Table 2).
4. Discussion This study demonstrated that P50m/N100m from both SII cortices by median nerve stimulation gradually decreased as the number of blocks increased. This result is in accordance with findings regarding the characteristics of cSII and iSII cortices (Wegner et al., 2000). The higher sensitivity of long-latency responses to repetitive stimulations may reflect a long-term habituation of these long-latency responses. While sensory adaptation is accepted as a peripheral phenomenon in somatosensory nerve fibers, the word ‘habituation’ has been used for somatosensory evoked responses (Tomberg et al., 1989). Tomberg et al. studied a shorterlatency potential, parietal P30/N45, and demonstrated that the amplitude attenuation produced by short-interval stimulation (450 ms) was less than that produced by long-interval stimulation (4000 ms). In our study, compared with shorter-
Table 1 Mean amplitudes and latencies of Si and Sii responses to stimuli (6 subjects) a (a) Primary somatosensory (SI) cortices Peak N20m latency Control
Gating
1st block 2nd block 3rd block 4th block 5th block 6th block
22.9 22.7 22.4 22.5 22.9 22.4 22.3 22.1 22.5 22.2 22.5 22.3 P ¼ 0.4755 (b) Secondary somatosensory (SII) cortices Peak cSII latency*
1st block 2nd block 3rd block 4th block 5th block 6th block
Peak N20m Control 104.7 113.7 83.2 78.1 107.5 127.3 P ¼ 0.0021
Gating 83.0 76.4 69.8 69.2 78.0 65.4
Peak cSII
Peak P30m latency
Peak P30m
Control
Gating
Control
Gating
35.4 35.1 34.4 33.5 34.2 32.6 P ¼ 0.0038
39.1 36.4 36.7 36.9 35.9 37.0
284.7 294.2 262.2 274.0 276.9 279.7 P , 0.0001
154.6 149.7 154.2 176.9 137.8 155.0
Peak iSII latency*
Peak iSII
Control
Gating
Control
Gating
Control
Gating
Control
Gating
107.9 108.7 106.5 106.1 103.3 110.4 P ¼ 0.3830
111.4 109.8 106.7 106.9 104.8 110.1
232.0 233.3 226.5 239.0 218.2 185.8 P ¼ 0.0037
207.0 207.1 174.4 176.6 179.6 178.0
80.3 77.4 82.2 83.7 87.7 81.5 P ¼ 0.0004
95.8 91.6 96.3 92.6 94.6 95.6
164.2 139.9 130.6 104.1 116.5 95.6 P , 0.0001
202.4 176.6 160.7 150.8 141.5 140.4
a The measurements were made from the channel showing the maximum signal. P-values that are statistically significant ðP , 0:01Þ are underlined. *P , 0:0001, either in control or gating sessions peak iSii latency appeared significantly earlier than peak cSii latency. i*P , 0:0001 for control sessions and P ¼ 0:1873 for gating sessions. The amplitude of response from cSii was larger in control sessions, but no significant difference was found between amplitudes in the cSii and iSii in gating sessions.
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Fig. 2. P50m/N100m evoked responses from the iSII and cSII cortices to stimuli during control and gating sessions in consecutive trials. The figures on the left and right indicate control and gating sessions, respectively. Upper and lower figures indicate the waveforms from cSII and iSII, respectively. Six blocks are superimposed in each figure. Note that the responses decrease with time. The responses from iSII are enhanced and those from cSII are decreased in the gating session compared with those in the control session.
latency responses such that of P30m, which showed no habituation with long-interval stimuli (5 s), the responses of SII cortices showed a significant habituation and needed a longer recovery period (Fig. 3(a, b)). Together with the appearance of waveforms in the similar latencies, habituation of the SII responses resembles that of the 100 ms auditory evoked fields (Lu et al., 1992). By adding a motor integration task that requires intensive attention to the moving fingers, our data showed inhibition of activities from cSII cortices but facilitation of activities from iSII cortices. Gating effects are thought to reduce sensory responses at the SI in monkeys (Chapman, 1994) and humans (Rushton et al., 1981; Kakigi et al., 1995; Huttunen and Homberg, 1991). The reduced amplitudes of N20m and P30m in our study were in accord with the results of the above studies. However, the peak latency of P30m was significantly delayed in our study. In SEP studies, these latencies have been reported to be unchanged (Rossini et al., 1999). It is likely that the radial components of waveforms, which are not detected by MEG could stay at their peak with the same latency during gating session. Therefore, the delayed peak latency of P30m is shown without having a radial component response in MEG recordings during gating session (Hoshiyama and Kakigi, 2001). As for the gating effect on SII cortices, increased SII responses in amplitude were noted during the muscle contraction or finger movement on the side of stimulation
in human (Huttunen et al., 1996; Forss and Jousmaki, 1998). However, these increments might not be solely explained by the gating effect. The effect of attention in these changes must also be taken into account. It has been shown that intensive attention causes an increase in the amplitude of both cSII and iSII responses (Mima et al., 1998; Lam et al., 2001). There have been no experiments on the relationship between attention and finger movement. Although Huttunen et al. reported that the dipole strength of both iSII and cSII responses are increased by finger movement on the right side during stimulation on the same side, they also demonstrated that this strength is reduced by left-side finger movement during stimulation on the opposite side (Huttunen et al., 1996). The suppression of responses from SII cortices might be due to negligence on the side of stimulation. However, in our study suppression of responses from cSII were observed even during complex finger movements that require intensive attention. This leads to the possibility that gating suppresses the activation of SII. Therefore, the dissociation between reduced cSII and enhanced iSII activities might be due to the greater gating effect than the attention effect on cSII, although the former is smaller than the latter on iSII. Thus, the attention needed for a complete best-level performance such as that in complex finger movements activates iSII cortices more than cSII cortices. It was shown in a recent study that activities of SI cortices induced by stimuli were enhanced during similar movement
K. Inoue et al. / Clinical Neurophysiology 113 (2002) 1573–1578
on the side opposite to that of the electrical stimulation for SEF recording (Rossini et al., 1999). Studies on recovery from hemispherectomy in young children have shown that iSII plays a greater role than does iSII in movements of the hemiplegic hand (Holloway et al., 2000). Furthermore, there was no significant difference between
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the amplitudes from the SII cortices during the control and gating sessions throughout recordings by a consecutive number of blocks, suggesting that complex finger movement does not affect any habituation process. SEF modulation from the SI was not correlated with that from the iSII either in the control or in the gating session
Fig. 3. Relationship between the grand averaged amplitude and time-course trial blocks ðn ¼ 6Þ in the control or gating sessions. iSII, P50m/N100m from the iSII cortex. cSII, P50m/N100m from the cSII cortex. (a) N20m and P30m, (b) P50m/N100m from iSII and cSII. Note that N20m, P30m and P50m/N100m from cSII showed suppression in the gating session, while P50m/N100m from iSII was enhanced.
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Table 2 Correlation study a Control
N20m vs. cSII N20m vs. iSII P30m vs. cSII P30m vs. cSII P30m vs. iSII
Gating
P-value
Correlation
P-value
Correlation
,0.0001 0.0016 0.9348 0.0945 0.0196
0.678 0.500 0.014 0.089 0.296
,0.0001 0.0016 0.3353 0.6431 0.816
0.707 0.500 20.166 0.080 0.021
a
Amplitudes of N20m, P30m, N50m/P100m from cSII) and those from iSII in each block are compared in the control and gating sessions. Underlined P-values are statistically significant ðP , 0:01Þ.
(Table 2), suggesting that SII responsiveness is largely independent on SI. Since both SI and SII cortices receive direct projections from the ventral posterior thalamic nucleus (see Jones, 1985), it has usually been thought that SI and SII are involved in parallel processing of tactile somatosensory information derived from this thalamic source (Mountcastle, 1986; Rowe, 1990). Therefore, the increase in P50m/ N100m amplitude from the iSII is due to additional modulatory afferentation, probably from other areas such as the thalamus, but not by the increase in input to the SI. 5. Conclusions Our recording of P50m/N100m from the iSII and cSII cortices demonstrated that these responses have a character of habituation. Those potentials are facilitated in the iSII and inhibited in the cSII cortices by a complex motor integration. Thus, in the case of a complex motor integration with intensive attention, the iSII cortices are thought to have a greater excitatory effect on the ipsilateral sensorimotor cortices, while the complex sensorimotor integration process does not affect habituation. Acknowledgements We are grateful to Dr Yasuyo Mimori for his comments regarding our study. References Bertolasi L, Priori A, Tinazzi M, Bertasi V, Rothwell JC. Inhibitory action of forearm flexor muscle afferents on corticospinal outputs to antagonist muscles in humans. J Physiol 1998;511:947–956. Chapman CE. Active versus passive touch: factors influencing the transmission of somatosensory signals to primary somatosensory cortex. Can J Physiol Pharmacol 1994;72:558–570. Cohen L, Starr A. Localization, timing and specificity of gating of somatosensory evoked potentials during active movement in man. Brain 1987;110:451–467. Forss N, Jousmaki V. Sensorimotor integration in human primary and secondary somatosensory cortices. Brain Res 1998;781:259–267. Holloway V, Gadian DG, Vergha-Khadem F, Porter DA, Boyd SG,
Connelly A. The organization of sensorimotor function in children after hemispherectomy. A functional MRI and somatosensory evoked potential study. Brain 2000;123:2432–2444. Hoshiyama M, Kakigi R. Correspondence between short-latency somatosensory evoked brain potentials and cortical magnetic fields following median nerve stimulation. Brain Res 2001;908:140–148. Huttunen J, Homberg V. Modification of cortical somatosensory evoked potentials during tactile exploration and simple active and passive movements. Electroenceph clin Neurophysiol 1991;81:216–223. Huttunen J, Wikstroem H, Korvenoja A, Seppaelaeinen A-M, Aronen H, Ilmoniemi J. Significance of the second somatosensory cortex in sensorimotor integration: enhancement of sensory responses during finger movements. NeuroReport 1996;7:1009–1012. Jones EG. The thalamus, New York, NY: Plenum Press, 1985. Kakigi R, Koyama S, Hoshiyama M, Watanabe S, Shimojo M, Kitamura Y. Gating of somatosensory evoked responses during active finger movements magnetoencephalographic studies. J Neurol Sci 1995;128:195– 204. Kakigi R, Shimojo M, Hoshiyama M, Koyama S, Watanabe S, Naka D, Suzuki H, Nakamura A. Effects of movement and movement imagery on somatosensory evoked magnetic fields following posterior tibial nerve stimulation. Brain Res Cogn Brain Res 1997;5:241–253. Kristeva-Feige R, Rossi S, Pizzella V, Lopez L, Erne SN, Edrich J, Rossini PM. A neuromagnetic study of movement-related somatosensory gating in the human brain. Exp Brain Res 1996;107:504–514. Lam K, Kakigi R, Mukai T, Yamasaki H. Attention and visual interference stimulation affect somatosensory processing: a magnetoencephalographic study. Neuroscience 2001;104:689–703. Lemon RN, Johansson RS, Westling G. Corticospinal control during reach, grasp, and precision lift in man. J Neurosci 1995;15:6145–6156. Lu ZL, Williamson SJ, Kaufman L. Behavioral lifetime of human auditory sensory memory predicted by physiological measures. Science 1992;258:1668–1670. Mima T, Ikeda A, Nagamine T, Yazawa S, Kunieda T, Mikuni N, Taki W, Kimura J, Shibasaki H. Human second somatosensory area: subdural and magnetoencephalographic recording of somatosensory evoked responses. J Neurol Neurosurg Psychiatry 1997;63:501–505. Mima T, Nagamine T, Nakamura K, Shibasaki H. Attention modulates both primary and second somatosensory cortical activities in humans: a magnetoencephalographic study. J Neurophysiol 1998;109:168–177. Mountcastle VB. The neural mechanism of cognitive function can now be studied directly. Trends Neurosci 1986;9:505–508. Rossi S, Tecchio F, Pasqualetti P, Ulivelli M, Pizzella V, Romani GL, Passero S, Battistini N, Rossini PM. Somatosensory processing during movement observation in humans. Clin Neurophysiol 2002;113:16– 24. Rossini PM, Narici L, Romani GL, Peresson M, Torrioli G, Traversa R. Simultaneous motor output and sensory input: cortical interference site resolved in humans via neuromagnetic measurements. Neurosci Lett 1989;96:300–305. Rossini PM, Babiloni C, Babiloni F, Ambrosini A, Onorati P, Carducci F, Urbano A. ‘Gating’ of human short-latency somatosensory evoked cortical responses during execution of movement. A high resolution electroencephalography study. Brain Res 1999;843:161–170. Rowe MJ. Organization of the cerebral cortex in monotremes and marsupials. Jones EG, Peters A, editors. Cerebral cortex. Comparative structure and evolution of cerebral cortex, vol. 8B, part II. New York, NY: Plenum Press, 1990. pp. 263–334. Rushton DN, Rothwell JC, Craggs MD. Gating of somatosensory evoked potentials during different kinds of movement in man. Brain 1981;104:465–491. Tomberg C, Desmedt JE, Ozaki I, Nguyen TH, Chalklin V. Mapping somatosensory evoked potentials to finger stimulation at intervals of 450 to 4000 msec and the issue of habituation when assessing early cognitive components. Electroenceph clin Neurophysiol 1989;74:347–358. Wegner K, Forss N, Salenius S. Characteristics of the human contra-versus ipsilateral SII cortex. Clin Neurophysiol 2000;111:894–900.
Role of human SII cortices in sensorimotor integration Ken Inoue a,*, Takamasa Yamashita b, Toshihide Harada a, Shigenobu Nakamura a a
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan b Institute of Health Science, Hiroshima University School of Medicine, Japan Accepted 15 May 2002
Abstract Objectives: To elucidate the functional properties of neurons in the human primary (SI) and ipsilateral and contralateral secondary (iSII or cSII) cortices in response to stimuli during finger movement. Methods: We measured somatosensory evoked fields (SEFs) produced by electric stimuli delivered to the median nerve at 0.2 Hz in 6 healthy subjects. Results: The amplitudes of evoked fields from both iSII and cSII were gradually attenuated with time. Consecutive blocks of trials were obtained to assess the habituation of each evoked field. Complex finger movements with attention (gating session) increased the amplitude of evoked fields from the iSII cortices but reduced the amplitudes of evoked fields from the cSII cortices ðP , 0:01Þ. In contrast, the amplitude of P30m from the SI did not show habituation effects but decreased significantly in the gating session ðP , 0:01Þ. Conclusions: The enhanced iSII as well as suppressed cSII cortices during complex finger movements with attention are not only considered to be result of gating effect but also attention. q 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: SII cortices; Sensorimotor integration; Somatosensory evoked fields; Attention
1. Introduction Somatosensory information is important for motor control. Sensory input is integrated with motor commands at several levels of the motor system: spinal, subcortical and cortical. Recently, a number of studies have provided electrophysiological evidence of sensorimotor integration at the cortical level. For example, transcranial magnetic stimulation (TMS) studies have shown modulation of motor evoked potential (MEP) size when conditioned by sensory afferents (Bertolasi et al., 1998) or when tested in various motor tasks (Lemon et al., 1995). Studies on somatosensory evoked potentials or fields (SEP or SEF) have also revealed a change in activities of the primary somatosensory (SI) cortices (Cohen and Starr, 1987; Rossini et al., 1989; Kristeva-Feige et al., 1996; Rossi et al., 2002). However, most of these investigations focused on the relationship of SI cortices to SEP or SEF, and few studies have electrophysiologically demonstrated a sensorimotor integration of SII cortices (Huttunen et al., 1996; Forss and Jousmaki, 1998; Kakigi et al., 1997). Magnetoencephalography (MEG), which has high sensitivity and temporal resolution, has made it possible to non* Corresponding author. Present address: 1-2-3 Kasumi Minami-ku, Hiroshima 734-8551, Japan. Tel.: 181-82-257-5201; fax: 181-82-5050490. E-mail address: [email protected] (K. Inoue).
invasively determine the strength of neuronal activity in SII cortices in the human brain (Mima et al., 1997). Using MEG, we demonstrated the habituation process of activities of SII cortices in control and gating sessions. We also found that these activities are facilitated in the ipsilateral SII cortices (iSII) by electrical stimulation and inhibit activities of the contralateral cortices (cSII) during the performance of manipulative finger movements that require intensive attention to complete co-contraction of hand muscles for the best-level performance.
2. Subjects and methods 2.1. Subjects The subjects were 6 right-handed neurologically intact adults (5 males and one female; mean age (^SD), 30.8 (^6.9) years; range, 22–45 years). Informed consent for participation in the study was obtained from all subjects. Each of the subjects sat in a magnetically shielded room while SEFs were recorded. 2.2. SEF studies Electrical stimuli of 0.2 ms in duration were delivered to the left median nerve at the wrist (cathode proximal). The
1388-2457/02/$ - see front matter q 2002 Elsevier Science Ireland Ltd. All rights reserved. PII: S 1388-245 7(02)00162-1
CLINPH 2001190
1574
K. Inoue et al. / Clinical Neurophysiology 113 (2002) 1573–1578
stimulus intensity was approximately 3 times greater than the sensory threshold but was painless and elicited a mild twitch of the thumb at regular intervals with a repetition rate of 0.2 Hz. The conditions during the stimulation were rest (control session) and opposing the left thumb with the tip of each digit sequentially, as d2, d2, d3, d4, d4, d4 and d5, repetitively (gating session). The subjects were instructed to pay careful attention to the stimulated moving fingers during the gating session and to relax and watch a film of their own choice during the control session. Magnetic recordings in a frequency range of 0.05–200 Hz were taken from the whole-head SQUID gradiometer system (Vector view TM, Neuromag) comprising 204 first-order magnetic gradiometers. The sampling rate was 800 Hz. Epoch length was 350 ms, including a 50 ms prestimulus baseline. Six consecutive blocks of MEG data, each block containing 30 stimuli, were averaged off-line for each condition. DC offset was based on the 50 ms prestimulus baseline. Among the 204 gradiometer channels, we selected each channel showing the largest influx in amplitude for evoked fields of N20m and P30m from the SI cortices and from the iSII and cSII cortices. We assigned evoked fields from the iSII or cSII cortices as P50m/N100m since electrically negative and positive peaks appeared
around 50 and 100 ms after the electrical stimulation, respectively. The peak amplitudes and latencies of N20m, P30m and P50m/N100m were measured using the same channel. The peak deflections of N20m, P30m and P100m were measured for latency. The amplitude was measured from the baseline to maximum upward influx for N20m, from the maximum upward influx of N20m to maximum downward influx for P30m, and from the maximum upward influx to maximum downward influx for P50m/N100m. 2.3. Statistical analysis One-way analysis of variance (ANOVA) was used for testing the statistical difference in amplitude, and Pearson’s correlation test was used for correlation analysis. P values less than 0.01 were considered significant. 3. Results Fig. 1 shows representative 204-channel SEF waveforms during control and gating sessions. The earliest response, N20m, peaked over the contralateral anterior parietal cortex at 22.2 ms (Fig. 1(a)). N20m was followed by a stronger response, P30m, with opposite polarity at 34.2 ms (Fig.
Fig. 1. Representative 204-channel SEF responses to left median nerve stimulation in subject H.O. Enlarged responses: (a) contralateral SI, (b) cSII cortices, and (c) iSII cortices. The head is viewed from above with the nose pointing upwards. Two sets of responses in the control (continuous line) and gating (dashed line) sessions are superimposed. Note the increase in responses from iSII cortices and suppression from cSII cortices.
K. Inoue et al. / Clinical Neurophysiology 113 (2002) 1573–1578
1(a)). Later deflections were observed at 52.2/88.5 ms (Fig. 1(b)) over the contralateral and at 56.5/84.2 ms (Fig. 1(c)) over the ipsilateral temporoparietal cortices. Maximum response waveforms from the SII region were seen bilaterally a few centimeters above the ear (Fig. 1). The biphasic responses were observed in all subjects and were used for quantitative comparison using the same gradiometer between the control and gating sessions. 3.1. Comparison of SI and SII cortices in control and gating sessions A total of 180 averages of SEF demonstrated significant decreases in the amplitudes of N20m and P30m from the SI cortices and in the amplitude of P50m/N100m from the cSII cortices during the gating session compared with control values, while P50m/N100m from the iSII cortices was enhanced during the gating session (Table 1, P ¼ 0:0074 for cSII and P ¼ 0:0001 for iSII). Peak latency of P30m was significantly delayed in gating session compared with control values (Table 1, P , 0:01), while no significant difference was detected between peak latencies of P50m/ N100m in the control and gating sessions. 3.2. Habituation The amplitudes of P50m/N100m from the iSII and cSII cortices changed time-dependently according to consecutive averaged waveforms of each block (Fig. 2, Fig. 3(b)). The higher amplitude of P50m/N100m from iSII cortices
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and the lower amplitude from cSII cortices during gating session compared to the control remained, although the amplitude progressively decreased over time in both conductions of P50m/N100m. The amplitude of N20m and P30m did not show much change (Fig. 3(a)), contrasting that of P50m/N100m from the iSII and cSII which showed a progressive decline of amplitude from the initial (first block) to the final (6th block) sections. The amplitudes of N20m and P30m were significantly correlated with the responses of cSII, but not of iSII, in amplitude ðP , 0:001Þ (Table 2).
4. Discussion This study demonstrated that P50m/N100m from both SII cortices by median nerve stimulation gradually decreased as the number of blocks increased. This result is in accordance with findings regarding the characteristics of cSII and iSII cortices (Wegner et al., 2000). The higher sensitivity of long-latency responses to repetitive stimulations may reflect a long-term habituation of these long-latency responses. While sensory adaptation is accepted as a peripheral phenomenon in somatosensory nerve fibers, the word ‘habituation’ has been used for somatosensory evoked responses (Tomberg et al., 1989). Tomberg et al. studied a shorterlatency potential, parietal P30/N45, and demonstrated that the amplitude attenuation produced by short-interval stimulation (450 ms) was less than that produced by long-interval stimulation (4000 ms). In our study, compared with shorter-
Table 1 Mean amplitudes and latencies of Si and Sii responses to stimuli (6 subjects) a (a) Primary somatosensory (SI) cortices Peak N20m latency Control
Gating
1st block 2nd block 3rd block 4th block 5th block 6th block
22.9 22.7 22.4 22.5 22.9 22.4 22.3 22.1 22.5 22.2 22.5 22.3 P ¼ 0.4755 (b) Secondary somatosensory (SII) cortices Peak cSII latency*
1st block 2nd block 3rd block 4th block 5th block 6th block
Peak N20m Control 104.7 113.7 83.2 78.1 107.5 127.3 P ¼ 0.0021
Gating 83.0 76.4 69.8 69.2 78.0 65.4
Peak cSII
Peak P30m latency
Peak P30m
Control
Gating
Control
Gating
35.4 35.1 34.4 33.5 34.2 32.6 P ¼ 0.0038
39.1 36.4 36.7 36.9 35.9 37.0
284.7 294.2 262.2 274.0 276.9 279.7 P , 0.0001
154.6 149.7 154.2 176.9 137.8 155.0
Peak iSII latency*
Peak iSII
Control
Gating
Control
Gating
Control
Gating
Control
Gating
107.9 108.7 106.5 106.1 103.3 110.4 P ¼ 0.3830
111.4 109.8 106.7 106.9 104.8 110.1
232.0 233.3 226.5 239.0 218.2 185.8 P ¼ 0.0037
207.0 207.1 174.4 176.6 179.6 178.0
80.3 77.4 82.2 83.7 87.7 81.5 P ¼ 0.0004
95.8 91.6 96.3 92.6 94.6 95.6
164.2 139.9 130.6 104.1 116.5 95.6 P , 0.0001
202.4 176.6 160.7 150.8 141.5 140.4
a The measurements were made from the channel showing the maximum signal. P-values that are statistically significant ðP , 0:01Þ are underlined. *P , 0:0001, either in control or gating sessions peak iSii latency appeared significantly earlier than peak cSii latency. i*P , 0:0001 for control sessions and P ¼ 0:1873 for gating sessions. The amplitude of response from cSii was larger in control sessions, but no significant difference was found between amplitudes in the cSii and iSii in gating sessions.
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Fig. 2. P50m/N100m evoked responses from the iSII and cSII cortices to stimuli during control and gating sessions in consecutive trials. The figures on the left and right indicate control and gating sessions, respectively. Upper and lower figures indicate the waveforms from cSII and iSII, respectively. Six blocks are superimposed in each figure. Note that the responses decrease with time. The responses from iSII are enhanced and those from cSII are decreased in the gating session compared with those in the control session.
latency responses such that of P30m, which showed no habituation with long-interval stimuli (5 s), the responses of SII cortices showed a significant habituation and needed a longer recovery period (Fig. 3(a, b)). Together with the appearance of waveforms in the similar latencies, habituation of the SII responses resembles that of the 100 ms auditory evoked fields (Lu et al., 1992). By adding a motor integration task that requires intensive attention to the moving fingers, our data showed inhibition of activities from cSII cortices but facilitation of activities from iSII cortices. Gating effects are thought to reduce sensory responses at the SI in monkeys (Chapman, 1994) and humans (Rushton et al., 1981; Kakigi et al., 1995; Huttunen and Homberg, 1991). The reduced amplitudes of N20m and P30m in our study were in accord with the results of the above studies. However, the peak latency of P30m was significantly delayed in our study. In SEP studies, these latencies have been reported to be unchanged (Rossini et al., 1999). It is likely that the radial components of waveforms, which are not detected by MEG could stay at their peak with the same latency during gating session. Therefore, the delayed peak latency of P30m is shown without having a radial component response in MEG recordings during gating session (Hoshiyama and Kakigi, 2001). As for the gating effect on SII cortices, increased SII responses in amplitude were noted during the muscle contraction or finger movement on the side of stimulation
in human (Huttunen et al., 1996; Forss and Jousmaki, 1998). However, these increments might not be solely explained by the gating effect. The effect of attention in these changes must also be taken into account. It has been shown that intensive attention causes an increase in the amplitude of both cSII and iSII responses (Mima et al., 1998; Lam et al., 2001). There have been no experiments on the relationship between attention and finger movement. Although Huttunen et al. reported that the dipole strength of both iSII and cSII responses are increased by finger movement on the right side during stimulation on the same side, they also demonstrated that this strength is reduced by left-side finger movement during stimulation on the opposite side (Huttunen et al., 1996). The suppression of responses from SII cortices might be due to negligence on the side of stimulation. However, in our study suppression of responses from cSII were observed even during complex finger movements that require intensive attention. This leads to the possibility that gating suppresses the activation of SII. Therefore, the dissociation between reduced cSII and enhanced iSII activities might be due to the greater gating effect than the attention effect on cSII, although the former is smaller than the latter on iSII. Thus, the attention needed for a complete best-level performance such as that in complex finger movements activates iSII cortices more than cSII cortices. It was shown in a recent study that activities of SI cortices induced by stimuli were enhanced during similar movement
K. Inoue et al. / Clinical Neurophysiology 113 (2002) 1573–1578
on the side opposite to that of the electrical stimulation for SEF recording (Rossini et al., 1999). Studies on recovery from hemispherectomy in young children have shown that iSII plays a greater role than does iSII in movements of the hemiplegic hand (Holloway et al., 2000). Furthermore, there was no significant difference between
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the amplitudes from the SII cortices during the control and gating sessions throughout recordings by a consecutive number of blocks, suggesting that complex finger movement does not affect any habituation process. SEF modulation from the SI was not correlated with that from the iSII either in the control or in the gating session
Fig. 3. Relationship between the grand averaged amplitude and time-course trial blocks ðn ¼ 6Þ in the control or gating sessions. iSII, P50m/N100m from the iSII cortex. cSII, P50m/N100m from the cSII cortex. (a) N20m and P30m, (b) P50m/N100m from iSII and cSII. Note that N20m, P30m and P50m/N100m from cSII showed suppression in the gating session, while P50m/N100m from iSII was enhanced.
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Table 2 Correlation study a Control
N20m vs. cSII N20m vs. iSII P30m vs. cSII P30m vs. cSII P30m vs. iSII
Gating
P-value
Correlation
P-value
Correlation
,0.0001 0.0016 0.9348 0.0945 0.0196
0.678 0.500 0.014 0.089 0.296
,0.0001 0.0016 0.3353 0.6431 0.816
0.707 0.500 20.166 0.080 0.021
a
Amplitudes of N20m, P30m, N50m/P100m from cSII) and those from iSII in each block are compared in the control and gating sessions. Underlined P-values are statistically significant ðP , 0:01Þ.
(Table 2), suggesting that SII responsiveness is largely independent on SI. Since both SI and SII cortices receive direct projections from the ventral posterior thalamic nucleus (see Jones, 1985), it has usually been thought that SI and SII are involved in parallel processing of tactile somatosensory information derived from this thalamic source (Mountcastle, 1986; Rowe, 1990). Therefore, the increase in P50m/ N100m amplitude from the iSII is due to additional modulatory afferentation, probably from other areas such as the thalamus, but not by the increase in input to the SI. 5. Conclusions Our recording of P50m/N100m from the iSII and cSII cortices demonstrated that these responses have a character of habituation. Those potentials are facilitated in the iSII and inhibited in the cSII cortices by a complex motor integration. Thus, in the case of a complex motor integration with intensive attention, the iSII cortices are thought to have a greater excitatory effect on the ipsilateral sensorimotor cortices, while the complex sensorimotor integration process does not affect habituation. Acknowledgements We are grateful to Dr Yasuyo Mimori for his comments regarding our study. References Bertolasi L, Priori A, Tinazzi M, Bertasi V, Rothwell JC. Inhibitory action of forearm flexor muscle afferents on corticospinal outputs to antagonist muscles in humans. J Physiol 1998;511:947–956. Chapman CE. Active versus passive touch: factors influencing the transmission of somatosensory signals to primary somatosensory cortex. Can J Physiol Pharmacol 1994;72:558–570. Cohen L, Starr A. Localization, timing and specificity of gating of somatosensory evoked potentials during active movement in man. Brain 1987;110:451–467. Forss N, Jousmaki V. Sensorimotor integration in human primary and secondary somatosensory cortices. Brain Res 1998;781:259–267. Holloway V, Gadian DG, Vergha-Khadem F, Porter DA, Boyd SG,
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