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Dissociation between contingent negative variation and Bereitschaftspotential in a patient with cerebellar efferent lesion
Electroencephalography and clinical Neurophysiology , 90 (1994) 359-364 © 1994 Elsevier Science Ireland Ltd. 0013-4694/94/$07.00
359
EEG 93043
Dissociation between contingent negative variation and Bereitschaftspotential in a patient w i t h cerebellar efferent lesion Akio Ikeda a,,, Hiroshi Shibasaki a, Takashi Nagamine a, Kiyohito Terada a, Ryuji Kaji b, Hidenao Fukuyama b and Jun Kimura b Departments o f o Brain Pathophysiology and b Neurology, Kyoto University School o f Medicine, Shogoin, Sakyo-ku, Kyoto 606 (Japan) (Accepted for publication: 21 October 1993)
Summary Contingent negative variation (CNV) and Bereitschaftspotential (BP) were recorded from the scalp in a patient with a discrete infarct in the mesial tegmentum of the midbrain involving the decussation of the superior cerebellar peduncle. Bereitschaftspotential in association with hand movements was completely absent while CNV was normally present at the frontocentral midline. This indicates that CNV is, as opposed to BP, generated without cerebro-cerebellar interactivation, suggesting different generating mechanisms. Key words: Contingent negative variation; Bereitschaftspotential; Cerebellar efferent lesion
Since W a l t e r et al. initially d e s c r i b e d c o n t i n g e n t n e g a t i v e v a r i a t i o n ( C N V ) in 1964, similarities a n d diff e r e n c e s in C N V a n d B e r e i t s c h a f t s p o t e n t i a l (BP) ( K o r n h u b e r a n d D e e c k e 1965) have b e e n d i s c u s s e d ( R o h r b a u g h et al. 1976, 1980; G r i i n e w a l d et al. 1979; T e c c e a n d C a t t a n a c h 1993). R e c e n t l y cortical g e n e r a tors o f BP in h u m a n s have b e e n c l a r i f i e d by invasive r e c o r d i n g in e p i l e p s y p a t i e n t s , d e m o n s t r a t i n g t h a t b o t h primary and supplementary motor areas equally play a significant role in g e n e r a t i n g B P ( N e s h i g e et al. 1988; S a k a m o t o et al. 1991; I k e d a a n d S h i b a s a k i 1992; I k e d a et al. 1992, 1993). H o w e v e r , t h o s e o f C N V a r e still u n c l e a r , which m a k e s clinical utility o f C N V in n e u r o l ogy u n c e r t a i n . W e will r e p o r t on a p a t i e n t with m i d b r a i n infarct in w h o m C N V a n d BP s h o w e d a signific a n t d i f f e r e n c e , b e i n g indicative o f t h e d i f f e r e n t g e n e r ating mechanisms.
p r e d o m i n a n t on the left side. D i s t u r b a n c e of right eye a d d u c t i o n , left eye n y s t a g m u s on a b d u c t i o n (right internuclear ophthalmoplegia) and normal convergence w e r e also seen, b e i n g c o n s i s t e n t with t h e right m e d i a l l o n g i t u d i n a l fasciculus ( M L F ) s y n d r o m e . N o m o t o r w e a k n e s s o r sensory d i s t u r b a n c e was s e e n except for a mildly d e c r e a s e d v i b r a t i o n sense in the right leg. A
Materials and m e t h o d s
Pat ien t T h e p a t i e n t was a 5 7 - y e a r - o l d right h a n d e d w o m a n p r e s e n t i n g with a c u t e o n s e t o f d i p l o p i a . N e u r o l o g i c a l e x a m i n a t i o n on t h e t h i r d d a y a f t e r o n s e t d e m o n s t r a t e d right a b d u c e n s nerve palsy a n d b i l a t e r a l limb ataxia
* Corresponding author. Tel.: 81-75-751-3603; Fax: 81-75-751-3202. SSDI 0013-4694(93)E0275-B
Fig. 1. An axial T2-weighted MRI at the caudal midbrain level (TR 3000 msec and TE 80 msec). A high intensity signal abnormality was seen in the mesial tegmentum with some extension to the right side, at which anatomically the decussation of the superior cerebellar peduncle is located.
360
cranial M R I on T2-weighted images demonstrated a high intensity abnormal area in the mesial tegmentum at the caudal midbrain level with more extension to the right side (Fig. 1). Otherwise no significant abnormal lesions were seen in the cerebral hemispheres or cerebellum. Cerebrospinal fluid examination revealed no abnormality. The patient had been well with no history of neurological deficits. It was, therefore, concluded that the patient suffered from an infarction in the midbrain, and it was most likely that her limb ataxia was due to the lesion involving the decussation of the superior cerebellar peduncle as demonstrated by MRI. Methods Both BP and CNV were recorded from this patient in common recording conditions. Seventeen scalp electrodes (Fpz, F7, F3, Fz, F4, FS, FCz, T3, C3, Cz, C4, T4, TS, P3, Pz, P4 and T6) (American E E G Society 1990), referenced to linked earlobes, were used for E E G recording. The electro-oculogram ( E O G ) was also recorded from an electrode placed 1.5 cm lateral to the right outer canthus, referenced to the right earlobe. Bandpass filters applied for both E E G and E O G were 0.05-100 Hz (NEC San-el, B I P T O P 6R12) and the filtered signals were further processed by a compact signal processing machine (NEC San-el, DPI100). For BP recording the conventional method was used (Shibasaki et al. 1980). Brisk voluntary unilateral extensions of the middle finger at the metacarpophalangeal joint were repeated at a self-paced rate of every 4 - 5 sec. The surface electromyogram ( E M G ) was recorded from the extensor muscle of the middle finger with a bandpass filter of 20-100 Hz and rectified. The electroencephalogram ( E E G ) segments from 2 sec before to 1 sec after the trigger movement were digitized and stored at a sampling rate of 300 Hz. Noticed trials with apparently significant artifacts were rejected to store during recording by a special on-line rejection program. The stored E E G segments (70-100 trials) were averaged time-locked to the precise onset of the rectified E M G which was determined through off-line inspection of each trial using a program originally developed by Barrett et al. (1985). During this procedure, trials contaminated with artifacts were excluded. The baseline was determined as the average of the initial 400 msec epoch of the analysis window for each channel. Bereitschaftspotential was recorded for each hand alternately in 6 separate sessions altogether on 1 day, and it was repeated 2 weeks later in order to confirm the initially obtained findings. For CNV recording, a pair of tone bursts was used as warning and target signals. Two seconds after the warning signal (SI: 1000 Hz, 20 msec in duration), either a 2000 Hz (S2h) or a 1500 Hz (S2m) tone burst of 20 msec in duration was delivered as a target signal
A. I K E D A E l AL.
in a random order but at almost equal frequency on average. The patient was instructed to extend the middie finger as soon as she heard S2m (go signal), but not to move her finger upon hearing S2h (no-go signal). The patient was also instructed to keep her eyes closed, to avoid any eye movement, and not to count during recording sessions. The E M G of the middle finger extensor muscle was recorded in the same way as for BP recording. A warning signal was set to be delivered at a variable interval between 3.5 and 7.5 sec after each target signal. Noticed trials with apparently significant artifacts and erroneous responses of the subjects were rejected to store during recording by a special on-line rejection program. The E E G segments from 1 sec before S1 to 1.5 scc after S2h or S2m were then digitized and stored at a sampling rate of 200 Hz. After having excluded segments associated with erroneous movements or artifacts using a visual inspection program specifically devised for this purpose, the stored EEG segments {36--40 trials) were averaged timelocked to S I for each task condition separately (S1-S2h and S1-S2m). The baseline was determined by averaging the 500 msec epoch just before the time of S I presentation for each channel to measure the amplitude of CNV at a certain time. Contingent negative variation was recorded for each hand alternately in 4 separatc sessions altogether 5 days after the first BP recording session.
Results
In association with the self-paced right middle finger extension, no pre-movement potentials were recognized (Fig. 2). No clear post-motion potentials were recognized either. The findings with the left middle finger extension were almost the same as those with the right finger movements. These findings were again obtained 2 weeks later. In the SI-S2m condition (go paradigm) employing the right hand task in the CNV paradigm, a slow negative potential started about 1000 msec after the S1 presentation at the frontocentral midline (Fig. 3). It gradually became larger before the S2m presentation with amplitudes of - 2.9 p.V at Fz, - 2.3 p.V at Cz, and - 0 . 6 p.V at Pz at - 100 msec to S2m. This is consistent with a late CNV component (Tecce and Cattanach 1993). This potential was not clearly seen at the parietal area. In the CNV paradigm with no motor response (SIS2h: no-go paradigm) (Fig. 4), the wave forms prior to the S2h presentation were almost identical to those with motor response (S1-S2m) shown in Fig. 3 ( - 3 . 1 #V at F'z, -- 2.6 ~V at Cz, and - 1.3/_~V at Pz at - 100 msec to S2h). The negative slow potentials following the S2h presentation remained longer as compared
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with those following the S2m presentation, especially at the frontal area. With the left hand task, the CNV in both S1-S2m and S1-S2h paradigms showed almost similar findings to those in association with the right hand task ( - 2 . 3 izV at Fz, - 1.7/xV at Cz, - 1.1/~V at Pz at - 100 msec to S2h, and - 2 . 3 / z V at Fz, - 1 . 6 / ~ V at Cz, - 1 . 3 / z V at Pz at - 1 0 0 msec to S2m).
Discussion It is currently understood that, prior to and during voluntary movements, the cerebellum plays a significantly important role in aiding the movement control by sending feedforward as well as feedback information to the primary and supplementary motor cortices through cerebro-ponto-dentato-thalamic connections (Allen and Tsukahara 1974; Sasaki 1979; Wiesendanger 1986). This cerebellar activity was demonstrated by experimental animal studies by Sasaki et al. (1979). When one cerebellar hemisphere was resected to interrupt the cerebellar efferent pathway to the motor cortex, BP normally seen at the contralateral motor cortex to the resected cerebellum had disappeared com-
pletely. The same p h e n o m e n o n was also observed in humans (Shibasaki et al. 1978, 1986). Namely, in patients with either unilateral or bilateral cerebellar lesion involving the efferent pathways and the dentate nucleus, scalp-recorded BP was also absent in association with hand movements contralateral to the lesion. Furthermore, it was also described by Shibasaki et al. (1986) that in this situation even post-movement potentials were absent. A recent study has confirmed these observations in patients with spino-cerebellar degenerative disorders (Machado-Joseph disease, dentatorubro-pallido-luysian atrophy and dyssynergia cerebellaris myoclonia) mainly involving the cerebellar dentate nucleus (Washimi et al. 1992). This cerebro-cerebellar interactivation was demonstrated by motor activation studies with positron emission tomography (PET) (Seitz and Roland 1992). In the present patient in whom the lesion involving the decussation of the superior cerebellar peduncle was clearly demonstrated by MRI, not only BP but also post-movement potentials were absent. This is consistent with the previous findings as described above. This finding, i.e., no potentials at all throughout the recording segment ( - 2 to + 1 sec to movement onset), was obtained on 2 different days. Therefore, it is unlikely that it erroneously reflects some technical problems.
A . IKEDA ET AL.
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The reason why the post-motion potential is also lost in spite of the apparently normal execution of finger movements remains to be discovered. In contrast to BP, however, the late CNV component (Tecce and Cattanach 1993) was present in this patient. The wave form of CNV is consistent with the normal one described in the literature at least enough to differentiate early and late CNV components (J~irvilehto and Fruhstorfer 1970; Tecce and Cattanach 1993). Previously it was argued that the late CNV component might actually represent just BP (Rohrbaugh et al. 1976, 1980). Currently it is accepted that late CNV is not entirely identical to BP, because the CNV paradigm with no motor task in response to the second signal can still elicit a negative potential prior to the second signal (Ruchkin et al. 1986; Tecce and Cattanach 1993). However, as long as the CNV paradigm involves a motor task in response to the second signal (Rohrbaugh et al. 1976, 1980) as in the original description by Walter et al. (1964), the question whether the late CNV component is either identical to BP or contains BP as its constituent remains unanswered.
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The present result suggests that the generating mechanism of the late CNV component is different from that of BP. It fits previous animal experiments (Gemba et al. 1987, 1990; Sasaki and G e m b a 1991). In their studies cortical field potentials of monkeys were recorded in a CNV paradigm. Potentials corresponding to CNV were seen at the prefrontal, premotor, primary motor, supplementary motor and primary sensory cortices. They further documented that cerebellar hemispherectomy in these monkeys then eliminated only the potential arising from the primary motor cortex corresponding to BP, whereas the potentials arising from the other frontal areas, at least part of which correspond to the late CNV component, remained ( G e m b a et al. 1987, 1990; Sasaki and G e m b a 199t). The present study does not completely exclude the possibility that BP is one of the components of the late CNV. However, the present result that the scalp-recorded late CNV component is well recognized and that the BP is completely absent in this patient leads us to the conclusion that BP itself is neither the late CNV itself nor one of the main components. The late CNV component is most likely to be generated without neu-
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sec. Fig. 3. Contingent negative variation (CNV) in the SI-S2m condition (go paradigm) in a choice-reacnon time paradigm. Upon hearing S2m (1500 Hz) 2 sec after S1 (1000 Hz), the patient had to extend the right middle finger as soon as possible. The EEGs were recorded from the same electrodes as for Fig. 2. Following the initial transient negativity between + 300 and + 600 msec to Sl, another slow negative potential began to appear + 1000 msec to St at the frontocentral area. It gradually increased in amplitude until S2m. Average of 36 trials.
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ronal input from the cerebellum while BP strongly depends on the input from the cerebellum. The late CNV component shows the maximum amplitude at the frontal area in the present study as seen in Figs. 3 and 4, being consistent with the previous report (J~irvilehto and Fruhstorfer 1970), while BP is usually seen with the maximum at the central area more on the contralateral side (Shibasaki et al. 1980). Griinewald et al. (1979) also studied the topographic difference between BP and the late CNV in a simplereaction time paradigm. They concluded that BP was much more laterally located contralateral to the movement side than the late CNV component. A further study with invasive recording in epilepsy patients would help to delineate cortical generators of CNV, as was recently done in invasive recording of BP. This study was partly supported by Grant-in-Aid for Scientific Research 05857073 for A.I. and Grant-in-Aid for New Program 05NP0101 for H.S. from the Japan Ministry of Education, Science and Culture.
References Allen, G.I. and Tsukahara, N. Cerebrocerebellar system. Physiol. Rev., 1974, 54: 957-1006.
Barrett, G., Shibasaki, H. and Neshige, R. A computer-assisted method for averaging movement-related cortical potentials with respect to E M G onset. Electroenceph. clin. Neurophysiol., 1985, 60: 276-281. Gemba, H., Tsujimoto, T. and Sasaki, K. Contingent negative variation (CNV) and readiness potential in the frontal lobe of monkeys. J. Physiol. Soc. Jap., 1987, 49: 326. Gemba, H., Sasaki, K. and Tsujimoto, T. Cortical field potentials associated with hand movements triggered by warning and imperative stimuli in the monkey. Neurosci. Lett., 1990, 113: 275-280. Griinewald, G., Griinewald-Zuberbier, E., Netz, J., H/Smberg, V. and Sander, G. Relationship between the late component of the negative contingent variation and the Bereitschaftspotential. Electroenceph. clin. Neurophysiol., 1979, 46: 538-545. Ikeda, A. and Shibasaki, H. Invasive recording of movement-related cortical potentials in humans. J. Clin. Neurophysiol., 1992, 9: 509-520. Ikeda, A., Liiders, H.O., Burgess, R.C. and Shibasaki, H. Movement-related potentials recorded from supplementary motor area and primary motor area: role of supplementary motor area in voluntary movements. Brain, 1992, 115: 1017-1043. lkeda, A., Liiders, H.O., Burgess, R.C. and Shibasaki, H. Movement-related potentials associated with single and repetitive movement recorded from h u m a n supplementary motor area. Electroenceph. clin. Neurophysiol., 1993, 89: 269-277. J~irvilehto, T. and Fruhstorfer, H. Differentiation between slow cortical potentials associated with motor and mental acts in man. Exp. Brain Res., 1970, 11: 309-317. Kornhuber, H.H. and Deecke, L. Hirnpotential~inderungen bei WillkiJrbewegungen und passiven Bewegungen den Menschen:
364 Bereitschaftspotential und reafferente Potentiale. Pflfigers Arch., 1965, 284: 1-17. Neshige, R., Liiders, H. and Shibasaki, H. Recording of movementrelated potentials from scalp and cortex in man. Brain, 1988, 11t: 719-736. Rohrbaugh, J.W., Syndulko, K. and Lindsley, D.B. Brain wave components of the contingent negative variation in human. Science, 1976, 191: 1055-1057. Rohrbaugh, J.W., Syndulko, K., Sanquist, T.F. and Lindsley, D.B. Synthesis of the contingent negative variation brain potentials from noncontingent stimulus and motor elements. Science, 1980, 208:1165-1168. Ruchkin, D.S., Sutton, S., Mahaffey, D. and Glaser, J. Terminal CNV in the absence of motor response. Electroenceph. clin. Neurophysiol., 1986, 63: 445-463. Sakamoto, A., Liiders, H. and Burgess, R. lntracranial recording of movement-related potentials to voluntary saccades. J. Clin. Neurophysiol., 1991, 8: 223-233. Sasaki, K. Cerebro-eerebellar interconnection in cats and monkeys. In: J. Massion and K. Sasaki (Eds.), Cerebro-Cerebellar Interaction. Elsevier, Amsterdam, 1979: 105-124. Sasaki, K. and Gemba, H. How do the different cortical motor areas contribute to motor learning and compensation following brain dysfunction. In: D.R. Humphrey and H.-J. Freund (Eds.), Motor Control: Concepts and Issues. Wiley, Chichester, 1991: 445-461. Sasaki, K., Gemba, H., Hashimoto, S. and Mizuno, N. Influences of cerebellar hemispherectomy on slow potentials in the motor cortex preceding self-paced hand movement in the monkeys. Neurosci. Lett., 1979, 15: 23-28.
A. IKEDA ET AL. Seitz. R.J. and Roland, ILK. l,earning of sequential finger movcments in man: a combined kinematic and positron emisskm tomography (PET). Eur..I. Neurosci., 1992, 4: 154-165. Shibasaki, H., Shima, F. and Kuroiwa, Y. Clinical studies of the movement-related cortical potential (MP) and the relationship between the dentato-rubro-thalamic pathways and readiness potential (RP). J. Neurol.. 1978, 219: 15-25. Shibasaki, H., Barrett, G., Halliday, E. and Haltiday, A.M. Components of the movement-related cortical potentials and their scalp topography. Electroenceph. clin. Neurophysiol., 1980, 49:213 226. Shibasaki, H., Barrett, G., Neshige, R., Hirata, 1. and Tomoda, H. Volitional movement is not preceded by cortical slow negativity in cerebellar dentate lesion in man. Brain Res.. 1986, 368: 361-365. Tecce, J.J. and Cattanach, L Contingent negative variation. In: E. Niedermeyer and F. l,opes da Silva (Eds,), Electroencephalography. Basic Principles, Clinical Applications and Related Field. Williams and Wilkins, Baltimore. MD, 1993: 887-910. Walter, W.G., Cooper. R., Aldridge, V.J., McCallum, W.C. and Winter, A.L. Contingent negative variation: an electrical sign of sensorimotor association and expectancy in the human. Nature. 1964, 203: 380-384. Washimi, Y.. Kaneoka, Y., Sakurai, N., Koike, Y. and Takahashi, A. Movement-related cortical potentials in patients with cerebellar dentate degeneration. Clin. Neurol., 1992, 32:567-571 (English abstr.). Wiesendanger, M. Recent developments in studies of the supplementary motor area of primates. Rev. Physiol. Biochem. Pharmacol., 1986, 1(13: 1-59.
359
EEG 93043
Dissociation between contingent negative variation and Bereitschaftspotential in a patient w i t h cerebellar efferent lesion Akio Ikeda a,,, Hiroshi Shibasaki a, Takashi Nagamine a, Kiyohito Terada a, Ryuji Kaji b, Hidenao Fukuyama b and Jun Kimura b Departments o f o Brain Pathophysiology and b Neurology, Kyoto University School o f Medicine, Shogoin, Sakyo-ku, Kyoto 606 (Japan) (Accepted for publication: 21 October 1993)
Summary Contingent negative variation (CNV) and Bereitschaftspotential (BP) were recorded from the scalp in a patient with a discrete infarct in the mesial tegmentum of the midbrain involving the decussation of the superior cerebellar peduncle. Bereitschaftspotential in association with hand movements was completely absent while CNV was normally present at the frontocentral midline. This indicates that CNV is, as opposed to BP, generated without cerebro-cerebellar interactivation, suggesting different generating mechanisms. Key words: Contingent negative variation; Bereitschaftspotential; Cerebellar efferent lesion
Since W a l t e r et al. initially d e s c r i b e d c o n t i n g e n t n e g a t i v e v a r i a t i o n ( C N V ) in 1964, similarities a n d diff e r e n c e s in C N V a n d B e r e i t s c h a f t s p o t e n t i a l (BP) ( K o r n h u b e r a n d D e e c k e 1965) have b e e n d i s c u s s e d ( R o h r b a u g h et al. 1976, 1980; G r i i n e w a l d et al. 1979; T e c c e a n d C a t t a n a c h 1993). R e c e n t l y cortical g e n e r a tors o f BP in h u m a n s have b e e n c l a r i f i e d by invasive r e c o r d i n g in e p i l e p s y p a t i e n t s , d e m o n s t r a t i n g t h a t b o t h primary and supplementary motor areas equally play a significant role in g e n e r a t i n g B P ( N e s h i g e et al. 1988; S a k a m o t o et al. 1991; I k e d a a n d S h i b a s a k i 1992; I k e d a et al. 1992, 1993). H o w e v e r , t h o s e o f C N V a r e still u n c l e a r , which m a k e s clinical utility o f C N V in n e u r o l ogy u n c e r t a i n . W e will r e p o r t on a p a t i e n t with m i d b r a i n infarct in w h o m C N V a n d BP s h o w e d a signific a n t d i f f e r e n c e , b e i n g indicative o f t h e d i f f e r e n t g e n e r ating mechanisms.
p r e d o m i n a n t on the left side. D i s t u r b a n c e of right eye a d d u c t i o n , left eye n y s t a g m u s on a b d u c t i o n (right internuclear ophthalmoplegia) and normal convergence w e r e also seen, b e i n g c o n s i s t e n t with t h e right m e d i a l l o n g i t u d i n a l fasciculus ( M L F ) s y n d r o m e . N o m o t o r w e a k n e s s o r sensory d i s t u r b a n c e was s e e n except for a mildly d e c r e a s e d v i b r a t i o n sense in the right leg. A
Materials and m e t h o d s
Pat ien t T h e p a t i e n t was a 5 7 - y e a r - o l d right h a n d e d w o m a n p r e s e n t i n g with a c u t e o n s e t o f d i p l o p i a . N e u r o l o g i c a l e x a m i n a t i o n on t h e t h i r d d a y a f t e r o n s e t d e m o n s t r a t e d right a b d u c e n s nerve palsy a n d b i l a t e r a l limb ataxia
* Corresponding author. Tel.: 81-75-751-3603; Fax: 81-75-751-3202. SSDI 0013-4694(93)E0275-B
Fig. 1. An axial T2-weighted MRI at the caudal midbrain level (TR 3000 msec and TE 80 msec). A high intensity signal abnormality was seen in the mesial tegmentum with some extension to the right side, at which anatomically the decussation of the superior cerebellar peduncle is located.
360
cranial M R I on T2-weighted images demonstrated a high intensity abnormal area in the mesial tegmentum at the caudal midbrain level with more extension to the right side (Fig. 1). Otherwise no significant abnormal lesions were seen in the cerebral hemispheres or cerebellum. Cerebrospinal fluid examination revealed no abnormality. The patient had been well with no history of neurological deficits. It was, therefore, concluded that the patient suffered from an infarction in the midbrain, and it was most likely that her limb ataxia was due to the lesion involving the decussation of the superior cerebellar peduncle as demonstrated by MRI. Methods Both BP and CNV were recorded from this patient in common recording conditions. Seventeen scalp electrodes (Fpz, F7, F3, Fz, F4, FS, FCz, T3, C3, Cz, C4, T4, TS, P3, Pz, P4 and T6) (American E E G Society 1990), referenced to linked earlobes, were used for E E G recording. The electro-oculogram ( E O G ) was also recorded from an electrode placed 1.5 cm lateral to the right outer canthus, referenced to the right earlobe. Bandpass filters applied for both E E G and E O G were 0.05-100 Hz (NEC San-el, B I P T O P 6R12) and the filtered signals were further processed by a compact signal processing machine (NEC San-el, DPI100). For BP recording the conventional method was used (Shibasaki et al. 1980). Brisk voluntary unilateral extensions of the middle finger at the metacarpophalangeal joint were repeated at a self-paced rate of every 4 - 5 sec. The surface electromyogram ( E M G ) was recorded from the extensor muscle of the middle finger with a bandpass filter of 20-100 Hz and rectified. The electroencephalogram ( E E G ) segments from 2 sec before to 1 sec after the trigger movement were digitized and stored at a sampling rate of 300 Hz. Noticed trials with apparently significant artifacts were rejected to store during recording by a special on-line rejection program. The stored E E G segments (70-100 trials) were averaged time-locked to the precise onset of the rectified E M G which was determined through off-line inspection of each trial using a program originally developed by Barrett et al. (1985). During this procedure, trials contaminated with artifacts were excluded. The baseline was determined as the average of the initial 400 msec epoch of the analysis window for each channel. Bereitschaftspotential was recorded for each hand alternately in 6 separate sessions altogether on 1 day, and it was repeated 2 weeks later in order to confirm the initially obtained findings. For CNV recording, a pair of tone bursts was used as warning and target signals. Two seconds after the warning signal (SI: 1000 Hz, 20 msec in duration), either a 2000 Hz (S2h) or a 1500 Hz (S2m) tone burst of 20 msec in duration was delivered as a target signal
A. I K E D A E l AL.
in a random order but at almost equal frequency on average. The patient was instructed to extend the middie finger as soon as she heard S2m (go signal), but not to move her finger upon hearing S2h (no-go signal). The patient was also instructed to keep her eyes closed, to avoid any eye movement, and not to count during recording sessions. The E M G of the middle finger extensor muscle was recorded in the same way as for BP recording. A warning signal was set to be delivered at a variable interval between 3.5 and 7.5 sec after each target signal. Noticed trials with apparently significant artifacts and erroneous responses of the subjects were rejected to store during recording by a special on-line rejection program. The E E G segments from 1 sec before S1 to 1.5 scc after S2h or S2m were then digitized and stored at a sampling rate of 200 Hz. After having excluded segments associated with erroneous movements or artifacts using a visual inspection program specifically devised for this purpose, the stored EEG segments {36--40 trials) were averaged timelocked to S I for each task condition separately (S1-S2h and S1-S2m). The baseline was determined by averaging the 500 msec epoch just before the time of S I presentation for each channel to measure the amplitude of CNV at a certain time. Contingent negative variation was recorded for each hand alternately in 4 separatc sessions altogether 5 days after the first BP recording session.
Results
In association with the self-paced right middle finger extension, no pre-movement potentials were recognized (Fig. 2). No clear post-motion potentials were recognized either. The findings with the left middle finger extension were almost the same as those with the right finger movements. These findings were again obtained 2 weeks later. In the SI-S2m condition (go paradigm) employing the right hand task in the CNV paradigm, a slow negative potential started about 1000 msec after the S1 presentation at the frontocentral midline (Fig. 3). It gradually became larger before the S2m presentation with amplitudes of - 2.9 p.V at Fz, - 2.3 p.V at Cz, and - 0 . 6 p.V at Pz at - 100 msec to S2m. This is consistent with a late CNV component (Tecce and Cattanach 1993). This potential was not clearly seen at the parietal area. In the CNV paradigm with no motor response (SIS2h: no-go paradigm) (Fig. 4), the wave forms prior to the S2h presentation were almost identical to those with motor response (S1-S2m) shown in Fig. 3 ( - 3 . 1 #V at F'z, -- 2.6 ~V at Cz, and - 1.3/_~V at Pz at - 100 msec to S2h). The negative slow potentials following the S2h presentation remained longer as compared
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with those following the S2m presentation, especially at the frontal area. With the left hand task, the CNV in both S1-S2m and S1-S2h paradigms showed almost similar findings to those in association with the right hand task ( - 2 . 3 izV at Fz, - 1.7/xV at Cz, - 1.1/~V at Pz at - 100 msec to S2h, and - 2 . 3 / z V at Fz, - 1 . 6 / ~ V at Cz, - 1 . 3 / z V at Pz at - 1 0 0 msec to S2m).
Discussion It is currently understood that, prior to and during voluntary movements, the cerebellum plays a significantly important role in aiding the movement control by sending feedforward as well as feedback information to the primary and supplementary motor cortices through cerebro-ponto-dentato-thalamic connections (Allen and Tsukahara 1974; Sasaki 1979; Wiesendanger 1986). This cerebellar activity was demonstrated by experimental animal studies by Sasaki et al. (1979). When one cerebellar hemisphere was resected to interrupt the cerebellar efferent pathway to the motor cortex, BP normally seen at the contralateral motor cortex to the resected cerebellum had disappeared com-
pletely. The same p h e n o m e n o n was also observed in humans (Shibasaki et al. 1978, 1986). Namely, in patients with either unilateral or bilateral cerebellar lesion involving the efferent pathways and the dentate nucleus, scalp-recorded BP was also absent in association with hand movements contralateral to the lesion. Furthermore, it was also described by Shibasaki et al. (1986) that in this situation even post-movement potentials were absent. A recent study has confirmed these observations in patients with spino-cerebellar degenerative disorders (Machado-Joseph disease, dentatorubro-pallido-luysian atrophy and dyssynergia cerebellaris myoclonia) mainly involving the cerebellar dentate nucleus (Washimi et al. 1992). This cerebro-cerebellar interactivation was demonstrated by motor activation studies with positron emission tomography (PET) (Seitz and Roland 1992). In the present patient in whom the lesion involving the decussation of the superior cerebellar peduncle was clearly demonstrated by MRI, not only BP but also post-movement potentials were absent. This is consistent with the previous findings as described above. This finding, i.e., no potentials at all throughout the recording segment ( - 2 to + 1 sec to movement onset), was obtained on 2 different days. Therefore, it is unlikely that it erroneously reflects some technical problems.
A . IKEDA ET AL.
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The reason why the post-motion potential is also lost in spite of the apparently normal execution of finger movements remains to be discovered. In contrast to BP, however, the late CNV component (Tecce and Cattanach 1993) was present in this patient. The wave form of CNV is consistent with the normal one described in the literature at least enough to differentiate early and late CNV components (J~irvilehto and Fruhstorfer 1970; Tecce and Cattanach 1993). Previously it was argued that the late CNV component might actually represent just BP (Rohrbaugh et al. 1976, 1980). Currently it is accepted that late CNV is not entirely identical to BP, because the CNV paradigm with no motor task in response to the second signal can still elicit a negative potential prior to the second signal (Ruchkin et al. 1986; Tecce and Cattanach 1993). However, as long as the CNV paradigm involves a motor task in response to the second signal (Rohrbaugh et al. 1976, 1980) as in the original description by Walter et al. (1964), the question whether the late CNV component is either identical to BP or contains BP as its constituent remains unanswered.
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The present result suggests that the generating mechanism of the late CNV component is different from that of BP. It fits previous animal experiments (Gemba et al. 1987, 1990; Sasaki and G e m b a 1991). In their studies cortical field potentials of monkeys were recorded in a CNV paradigm. Potentials corresponding to CNV were seen at the prefrontal, premotor, primary motor, supplementary motor and primary sensory cortices. They further documented that cerebellar hemispherectomy in these monkeys then eliminated only the potential arising from the primary motor cortex corresponding to BP, whereas the potentials arising from the other frontal areas, at least part of which correspond to the late CNV component, remained ( G e m b a et al. 1987, 1990; Sasaki and G e m b a 199t). The present study does not completely exclude the possibility that BP is one of the components of the late CNV. However, the present result that the scalp-recorded late CNV component is well recognized and that the BP is completely absent in this patient leads us to the conclusion that BP itself is neither the late CNV itself nor one of the main components. The late CNV component is most likely to be generated without neu-
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ronal input from the cerebellum while BP strongly depends on the input from the cerebellum. The late CNV component shows the maximum amplitude at the frontal area in the present study as seen in Figs. 3 and 4, being consistent with the previous report (J~irvilehto and Fruhstorfer 1970), while BP is usually seen with the maximum at the central area more on the contralateral side (Shibasaki et al. 1980). Griinewald et al. (1979) also studied the topographic difference between BP and the late CNV in a simplereaction time paradigm. They concluded that BP was much more laterally located contralateral to the movement side than the late CNV component. A further study with invasive recording in epilepsy patients would help to delineate cortical generators of CNV, as was recently done in invasive recording of BP. This study was partly supported by Grant-in-Aid for Scientific Research 05857073 for A.I. and Grant-in-Aid for New Program 05NP0101 for H.S. from the Japan Ministry of Education, Science and Culture.
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Barrett, G., Shibasaki, H. and Neshige, R. A computer-assisted method for averaging movement-related cortical potentials with respect to E M G onset. Electroenceph. clin. Neurophysiol., 1985, 60: 276-281. Gemba, H., Tsujimoto, T. and Sasaki, K. Contingent negative variation (CNV) and readiness potential in the frontal lobe of monkeys. J. Physiol. Soc. Jap., 1987, 49: 326. Gemba, H., Sasaki, K. and Tsujimoto, T. Cortical field potentials associated with hand movements triggered by warning and imperative stimuli in the monkey. Neurosci. Lett., 1990, 113: 275-280. Griinewald, G., Griinewald-Zuberbier, E., Netz, J., H/Smberg, V. and Sander, G. Relationship between the late component of the negative contingent variation and the Bereitschaftspotential. Electroenceph. clin. Neurophysiol., 1979, 46: 538-545. Ikeda, A. and Shibasaki, H. Invasive recording of movement-related cortical potentials in humans. J. Clin. Neurophysiol., 1992, 9: 509-520. Ikeda, A., Liiders, H.O., Burgess, R.C. and Shibasaki, H. Movement-related potentials recorded from supplementary motor area and primary motor area: role of supplementary motor area in voluntary movements. Brain, 1992, 115: 1017-1043. lkeda, A., Liiders, H.O., Burgess, R.C. and Shibasaki, H. Movement-related potentials associated with single and repetitive movement recorded from h u m a n supplementary motor area. Electroenceph. clin. Neurophysiol., 1993, 89: 269-277. J~irvilehto, T. and Fruhstorfer, H. Differentiation between slow cortical potentials associated with motor and mental acts in man. Exp. Brain Res., 1970, 11: 309-317. Kornhuber, H.H. and Deecke, L. Hirnpotential~inderungen bei WillkiJrbewegungen und passiven Bewegungen den Menschen:
364 Bereitschaftspotential und reafferente Potentiale. Pflfigers Arch., 1965, 284: 1-17. Neshige, R., Liiders, H. and Shibasaki, H. Recording of movementrelated potentials from scalp and cortex in man. Brain, 1988, 11t: 719-736. Rohrbaugh, J.W., Syndulko, K. and Lindsley, D.B. Brain wave components of the contingent negative variation in human. Science, 1976, 191: 1055-1057. Rohrbaugh, J.W., Syndulko, K., Sanquist, T.F. and Lindsley, D.B. Synthesis of the contingent negative variation brain potentials from noncontingent stimulus and motor elements. Science, 1980, 208:1165-1168. Ruchkin, D.S., Sutton, S., Mahaffey, D. and Glaser, J. Terminal CNV in the absence of motor response. Electroenceph. clin. Neurophysiol., 1986, 63: 445-463. Sakamoto, A., Liiders, H. and Burgess, R. lntracranial recording of movement-related potentials to voluntary saccades. J. Clin. Neurophysiol., 1991, 8: 223-233. Sasaki, K. Cerebro-eerebellar interconnection in cats and monkeys. In: J. Massion and K. Sasaki (Eds.), Cerebro-Cerebellar Interaction. Elsevier, Amsterdam, 1979: 105-124. Sasaki, K. and Gemba, H. How do the different cortical motor areas contribute to motor learning and compensation following brain dysfunction. In: D.R. Humphrey and H.-J. Freund (Eds.), Motor Control: Concepts and Issues. Wiley, Chichester, 1991: 445-461. Sasaki, K., Gemba, H., Hashimoto, S. and Mizuno, N. Influences of cerebellar hemispherectomy on slow potentials in the motor cortex preceding self-paced hand movement in the monkeys. Neurosci. Lett., 1979, 15: 23-28.
A. IKEDA ET AL. Seitz. R.J. and Roland, ILK. l,earning of sequential finger movcments in man: a combined kinematic and positron emisskm tomography (PET). Eur..I. Neurosci., 1992, 4: 154-165. Shibasaki, H., Shima, F. and Kuroiwa, Y. Clinical studies of the movement-related cortical potential (MP) and the relationship between the dentato-rubro-thalamic pathways and readiness potential (RP). J. Neurol.. 1978, 219: 15-25. Shibasaki, H., Barrett, G., Halliday, E. and Haltiday, A.M. Components of the movement-related cortical potentials and their scalp topography. Electroenceph. clin. Neurophysiol., 1980, 49:213 226. Shibasaki, H., Barrett, G., Neshige, R., Hirata, 1. and Tomoda, H. Volitional movement is not preceded by cortical slow negativity in cerebellar dentate lesion in man. Brain Res.. 1986, 368: 361-365. Tecce, J.J. and Cattanach, L Contingent negative variation. In: E. Niedermeyer and F. l,opes da Silva (Eds,), Electroencephalography. Basic Principles, Clinical Applications and Related Field. Williams and Wilkins, Baltimore. MD, 1993: 887-910. Walter, W.G., Cooper. R., Aldridge, V.J., McCallum, W.C. and Winter, A.L. Contingent negative variation: an electrical sign of sensorimotor association and expectancy in the human. Nature. 1964, 203: 380-384. Washimi, Y.. Kaneoka, Y., Sakurai, N., Koike, Y. and Takahashi, A. Movement-related cortical potentials in patients with cerebellar dentate degeneration. Clin. Neurol., 1992, 32:567-571 (English abstr.). Wiesendanger, M. Recent developments in studies of the supplementary motor area of primates. Rev. Physiol. Biochem. Pharmacol., 1986, 1(13: 1-59.