Neuroscience Letters, 117 (1990) 68 73 Elsevier Scientific Publishers Ireland Ltd.
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Corticobulbar projections to upper and lower facial motoneurons. A study by magnetic transcranial stimulation in man G. Cruccu, A. Berardelli, M. Inghilleri a n d M. M a n f r e d i Department of Neurosciences, University of Rome 'La Sapienza ', Rome (Italy) (Received 4 May 1990; Accepted 29 May 1990)
Key words: Magnetic brain stimulation; Single motor unit: Corticobulbar projection; Facial muscle: Man To investigate the human corticofacial projections, we recorded the compound motor potentials and single motor unit potentials evoked by magnetic transcranial stimulation, in the frontalis and lower facial muscles of healthy subjects. Potentials secondary to activation of the corticobulbar tract were contralateral in lower and bilateral in upper facial muscles. Even though the latency of responses was longer than would be expected for direct cortico-motoneuronal connections, these cannot be excluded either for lower or upper facial motoneurons.
The clinical features of the supranuclear facial palsy are traditionally explained with the assumption that the cortical innervation for the upper facial motoneurons is bilateral and for the lower facial motoneurons is contralateral. By stimulating the exposed motor cortex of man, Penfield and Rasmussen [11] induced a bilateral twitch of the eyelids and brows, but a contralateral twitch of the lips. Anatomic studies in humans have shown bilateral projections to facial motor nuclei: to the ventral facial subnuclei the projections were predominantly crossed, to the dorsal facial subnuclei symmetrical [8]. Interest in this subject has recently been renewed by electrophysiological and anatomical studies. Intracortical microstimulation studies in the monkey [6, 13] have demonstrated a representation of ipsilateral movements, intermingled with the contralateral representations in the anterior face motor cortex, although contralateral movements predominated [6]. Jenny and Saper [7] have traced anatomically in monkeys direct cortico-motoneuronal connections to the contralateral lower facial motoneurons, but not to the upper facial motoneurons. Corticobulbar projections onto cranial-nerve nuclei are also being studied in the intact man by means of electrical or magnetic transcranial brain stimulation (TCS) [2~,, 12]. However, probably beCorrespondence." G. Cruccu, Dipartimento Scienze Neurologiche, Viale Universitfi 30, 00185 Rome, Italy. 0304-3940/90/$ 03.50 ~': 1990 Elsevier Scientific Publishers Ireland Ltd.
69 cause of the different techniques used for stimulation and recording, the symmetry of corticofacial projections has not been clarified. In an attempt to clarify this subject, we studied the facial muscle responses to magnetic TCS in normal man. To ensure selectivity of the stimulus and recording, we used a small magnetic coil and bipolar concentric needles. Responses from the mentalis and orbicularis oris were compared with those from the frontalis muscle, because these muscles are among those respectively most and least affected in the supranuclear palsy, and are therefore expected to undergo the most and least asymmetrical cortical control. The experiments were carried out in 10 healthy subjects aged 22-54 years. A Novametrix MagStim 200 with a small coil (o.d. 6 cm) was used for TCS. The optimal position for activation of the corticobulbar tract was with the centre of the coil placed over the scalp 2 cm anterior and 4 cm lateral to the vertex. This position was not rigidly adhered to, since positioning of the coil, which was critical, differed slightly in each subject. Electromyographic signals were recorded by surface electrodes (filters 5-2000 Hz) from the lower and upper facial muscles bilaterally, in all subjects. The optimal position for surface recordings from the lower face was obtained with the active electrode placed 1-2 cm below and lateral to the corner of the mouth, and the reference electrode placed 2 cm medially. For the upper face, the active electrode was placed 2 cm above the eyebrow on a line with the pupil, and the other electrode 2 cm laterally. With these arrangements, the M waves evoked by electrical stimulation of the facial nerve at the stylomastoid foramen appeared as biphasic potentials starting with a large-amplitude upward deflection. Five subjects were also tested with bipolar concentric needle electrodes (filters 50-5000 Hz). Needle recordings showed that the signal picked up by the surface electrodes over the upper face was generated in the frontalis muscle; the signal from the lower face surface electrodes was generated in the mentalis and orbicularis oris, but other nearby facial muscles might have contributed. We measured the onset latency and peak-to-peak amplitude of the M waves and motor potentials evoked by TCS and secondary to activation of the corticobulbar tract (MEPs). Recordings were performed in both the relaxed muscle and the contracting muscle. To assess reproducibility of responses and minimize the interference by voluntary activity, 8 trials were repeated and averaged. Unless otherwise specified, results refer to surface recordings. In bipolar concentric needle recordings, 5 different motor unit potentials were studied in each muscle. The mean latency of M waves evoked by facial nerve stimulation in ipsilateral lower facial muscles was 3.2+0.6 ms (S.D.) and the amplitude was 8___3 mV. A smaller potential (20% of the amplitude of the ipsilateral potential), probably picked up by volume conduction from the nearby ipsilateral muscles, was also recorded from contralateral electrodes. In all subjects, TCS in optimal position (threshold 50-70% of stimulator output) evoked MEPs in contralateral muscles, but only when the muscles were active (Fig. 1). The minimum latency was 9.3+0.7 ms (range 8.4-11 ms), and maximum amplitude 1.8+ 1 mV (22% of M wave). As in M wave recordings, the ipsilateral surface
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Fig. 1. Compound motor potentials evoked by magnetic transcranial stimulation (TCS) in upper and lower facial muscles in a normal subject. Surface recordings from the right (1) and left (2) frontalis muscle (A), and from the right (1) and left (2) lower face muscle (B) during voluntary contraction. TCS (80% output) of left hemisphere. Average of 8 trials. Vertical calibration 250/iV. Motor evoked potentials are bilateral in the frontalis muscles and contralateral in the lower face muscles. The small deflection in B2 (ipsilateral lower face electrodes) is probably picked up by volume conduction.
electrodes often picked up a potential that was similar to the contralateral potential in latency and smaller in amplitude (21%). In single motor unit recordings, 5 motor unit potentials were identified as being evoked by contralateral TCS, none by ipsilateral TCS, even with shocks at maximum intensity (Fig. 2). We therefore concluded that the small ipsilateral potential seen with surface recordings mainly arose from contralateral muscles. TCS in the same position and at the same intensity as those used for contralateral lower facial responses, evoked bilateral MEPs in the frontalis muscles (Fig. 1). In 3 subjects, no response was obtained on either side, even with shocks at the maximum output of the stimulator; in the other 7, the responses were only obtained during voluntary contraction. The amplitude (0.3-0.9 mV) was similar in the contra- and ipsilateral muscles. The latency was 10.4+ 1.5 ms in the contralateral frontalis muscle, and 12.3 +0.9 ms in the ipsilateral. The latency difference between contra- and ipsilateral responses was statistically significant (P < 0.01, analysis of variance), wher-
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Fig. 2. Single motor unit potentials in upper and lower facial muscles after magnetic transcranial stimulation (TCS) in a normal subject. Bipolar concentric needle recordings from the right frontalis muscle (A) and from the right mentalis muscle (B) during voluntary contraction. TCS (100% output) of left (1) and right hemisphere (2). Four representative trials superimposed. The same single motor unit of the right frontalis muscle is repeatedly activated by both left and right TCS (Aj and A2). Occasional (voluntary) activity of a different motor unit can be seen at the end of the sweep. In BI, a single motor unit of the right mentalis muscle is repeatedly activated by contralateral TCS. B2 shows occasional (voluntary) activity of the same motor unit.
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eas the difference between upper and lower responses in contralateral facial muscles was not. In single motor unit recordings, 5 different motor unit potentials were identified as being evoked by both contralateral and ipsilateral TCS (Fig. 2). We therefore concluded that the frontalis muscle was activated by stimulation of either hemisphere. The magnetic coil possibly excites trigeminal afferents and thus evokes reflex responses (similar to the early blink reflex) in the facial muscles. In none of our subjects, however, did electrical stimulation of the supraorbital and infraorbital nerves evoke reflex responses within the range of latencies of MEPs in the frontalis or lower facial muscles, whether the muscles were active or relaxed. Other studies have established that the motor potentials evoked in facial muscles by TCS are secondary to activation of the corticobulbar tract. Positioning of the electrodes and the coil is critical, responses are often absent on the paretic side of hemiplegic patients, and are facilitated by voluntary contraction [2-4, 9, 12]. Indeed, we obtained no response at all in the relaxed facial muscle, neither did R6sler et al. [12]. In agreement with the conventional teaching on corticofacial projections, our single motor unit recordings demonstrate that the responses in the frontalis muscle are bilateral, whereas those in lower facial muscles are predominantly contralateral. Absence of frontalis muscle responses in some subjects is consistent with findings from intracortical stimulation in monkeys, showing a poor cortical representation of the frontalis movements [6]. Since the threshold for contra- and ipsilateral lower facial movement is similar in monkeys [6], it is unlikely that we missed ipsilateral responses in the lower face muscle because the stimulus intensity was not high enough. Furthermore, the same intensity yielded responses in the upper facial muscles of both sides yet in the lower facial muscle of the contralateral side alone. Although ipsilateral corticobulbar projections to the motor nucleus for the lower face probably do exist anatomically, they must be extremely weak in man. In the monkey, they represent about 20-25% [6, 7]. Using an 8-cm diameter coil and conventional needle-electrodes, Benecke and coworkers [2, 9] recorded from the orbicularis oculi muscle bilateral responses, that were distinguishable from the early blink reflex, and resembled our responses in the frontalis. Unlike ours, their recordings from the mentalis muscle showed ipsilateral responses in most subjects; these responses were low-threshold, but exhibited a smaller amplitude and longer latency than the contralateral responses [2]. The excitatory input from one hemisphere to the motor nuclei of the lower facial muscle was concluded to be bilateral, albeit more asymmetrical than the input for the tongue muscles [9]. The problem of the symmetry of the responses between sides was not debated in other studies [3, 4, 12]. Although a contralateral response was described by Cohen and Hallett, the electrical TCS used [3] directly excited the ipsilateral facial nerve, which might have hindered or interfered with possible ipsilateral MEPs. Using magnetic TCS with large coils, Cruccu et al. [4] were unable to ensure excitation of one hemisphere alone, and R6sler et al. [12] had to keep the stimulus intensity low to prevent bilateral excitation of the facial nerves. In this study, in surface recordings, the latency of contralateral MEPs in lower (9.3
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ms) and upper (10.2 ms) facial muscles was similar to or shorter than that obtained with electrical TCS [3] or magnetic TCS with larger coils [3, 4, 12]. Yet these values are relatively long if compared to the latency of MEPs evoked by magnetic TCS in the sternomastoid (7 ms) [unpublished data] or the trigeminal muscles (6 ms) [4], i.e. in territories with a grossly similar conduction distance. The conduction time from the lower motoneuron to the facial muscle, calculated from the latency of the M wave evoked by electrical direct intracranial stimulation or magnetic transcranial stimulation of the facial root [2, 10, 12], is approximately ~ 5 ms. The central latency (from cortex to facial root) is therefore long - about 5 ms - and we cannot prove a direct monosynaptic connection either for the lower or for the upper facial motoneurons. The corticofacial connections, however, are not necessarily multisvnaptic. The central conduction time is probably longer than expected: in monkeys, the histogram of antidromic conduction times of the corticobulbar neurons (from brainstem to the cortex) peaks at 1.8-2 ms [14], a latency longer than that of corticospinal neurons (from C2 to cortex), peaking at 1.2-1.6 ms [13]. It is also possible that the facial motoneurons are high-threshold and need a high level of temporal summation by multiple descending volleys before being fired [2]. Finally, the longer latency of ipsilateral responses in the frontalis muscle 2 ms longer than that of contralateral responses - still requires explanation. One reason could be a higher number of synaptic stations along the pathway to the motoneurons. A transcallosal activation of the contralateral cortex is instead virtually excluded by the long conduction time along callosal connections, at least 9 ms in man [l], and the observation that transection of the corpus callosum in cats does not affect ipsilateral facial responses to intracortical stimulation [5]. l Amassian, V.E. and Cracco, R.Q., Human cerebral cortical responses to contralateral transcranial stimulation, Neurosurgery, 20 (1987) 148 155. 2 Benecke, R., Meyer, B.U., Sch6nle, P. and Conrad, B., Transcranial magnetic stimulation of the human brain: responses in muscles supplied by cranial nerves, Exp. Brain Res., 71 (1988) 623~,32. 3 Cohen, L.G. and Hallen, M., Noninvasive mapping of human motor cortex, Neurology, 38 (1988) 904 909. 4 Cruccu. G., Berardelli, A., lnghilleri, M. and Manfredi, M., Functional organization of the trigeminal motor system in man. A neurophysiological study, Brain, 112 (1989) 1333 1350. 5 Guandalini, P., Franchi, S. and Spidalieri, G., Low threshold unilateral and bilateral facial movements evoked by motor cortex stimulation in cats, Brain Res., 508 (1990) 273-282. 6 Huang, C.S., Sirisko, M.A, Hiraba, H., Murray, G.M. and Sessle, B.J., Organization of the primate I:ace motor cortex as revealed by intracortical microstimulation and electrophysiological identification of afferent inputs and corticobulbar projections, J. Neurophysiol., 59 (1988) 796-818. 7 Jenny, A.B. and Saper, C.B., Organization of the facial nucleus and corticofacial projection in the monkey. A reconsideration of the upper motor neuron facial palsy, Neurology, 37 (1987) 930 939. 8 Kuypers, H.G.J.M., Corticobutbar connections to the pons and the lower brainstem in man, Brain, 81 (1958) 364 388. 9 Meyer, B.-U., Britton, T.C. and Benecke, R., Magnetic stimulation of the corticonuclear system and of proximal cranial nerves in humans. In A. Berardelli et al. (Eds.), Motor Disturbances I I, Academic Press, London, 1990, pp. 235 248. 10 Meller, A.R., Jannena, P.J., Hemifacial spasm: results of electrophysiologic recording during microvascular decompression operations, Neurology, 35 (1985) 969 974. I I Penfield, W. and Rasmussen, T.. The Cerebral Cortex of Man, Macmillan, New York, 1950, pp. 11 65.
73 12 R6sler, K.M., Hess, C.W. and Schmid, U.D., Investigation of facial motor pathways by electrical and magnetic stimulation: sites and mechanisms of excitation, J. Neurol. Neurosurg. Psychiatry, 52 (1989) 1149-1156.
13 Sessle, B.J. and Wiesendanger, M., Structural and functional definition of the motor cortex in the monkey (Macacafaseicularis), J. Physiol., 323 (1982) 245-265. 14 Sirisko, M.A. and Sessle, B.J., Corticobulbar projections and orofacial and muscle afferent inputs of neurons in primate sensorimotor cerebral cortex, Exp. Neurol., 82 (1983) 716-720.