Exp Brain Res (1991) 86:216-218
Experimental BrainResearch 9 Springer-Verlag1991
Research Note
Transcranial magnetic brain stimulation: lack of oculomotor response K. Wessel and D. K6mpf Department of Neurology, Medical University, Ratzeburger Allee 160, W-2400 Lfibeek, Federal Republic of Germany Received December 6, 1990 / Accepted April 10, 1990
Summary. We have investigated whether eye movements can be evoked by transcranial magnetic brain stimulation (TMS) from frontal, precentral, posterior- and inferiorparietal, occipital and temporal positions o f the stimulating coil. Our findings were negative, even for structures concerned with voluntary eye movements, such as the frontal eye field (FEF) and the inferior parietal lobe (IPL). The lack o f o c u l o m o t o r responses after stimulation of the cortex shall be discussed in the following context: (1) Low-threshhold intracortical stimulation experiments suggest that in functional terms, the F E F is confined to small areas which are extend to the floor of sulci. TMS does not reach these structures to a sufficient extent. Furthermore efferent connections of the cortex to the paramedian pontine reticular formation (PPRF) seem to be polysynaptic. (2) The function o f the cortex in rapid eye movement is to analyze and process conditions with differing functional requirements, rather than to directly generate saccades. TMS does not elicit oculomotor responses, demonstrating again that the role played by the cortex in eye movement is not analogous to the role of the somatic m o t o r cortex in controlling skeletal movements.
Key words: Transcranial magnetic s t i m u l a t i o n - Voluntary eye movements - Frontal eye field - Inferior parietal lobe - H u m a n
Introduction Recent experiments indicate that presaccadic neurons in the F E F play a causal role in the generation o f visually evoked voluntary saccades (Bruce and Goldberg 1985). Earlier studies suggested that in the m o n k e y eye movements can also be elicited by electrical stimulation o f the posterior-parietal, occipital and temporal cortex (Fig. 1) Offprint requests to: K. Wessel (address see above)
(Wagman 1964). In humans, the technique of TMS has recently become available (Barker et al. 1985; Benecke et al. 1988). The aim of this study is to investigate whether TMS of different structures can evoke oculomotor responses and to relate these findings to clinical and experimental data on the significance of cortex in the initiation of eye movements.
Methods The authors performed TMS upon each other as test subjects. Additionally three patients (aged 21-56 years) with complete unilateral paresis of the 7th cranial nerve were examined. We used a commercially available magnetic stimulator (Magstim 200), the peak magnetic field of which was about 1.5 Tesla after 150 gs in the centre of the stimulating coil. The induced electric current within the conducting tissue of the brain reaches approximately 0.25 A at maximal output of the device. The positioning of the magnetic coil for eliciting oculomotor responses was varied from frontal to precentral, posterior- and inferior-parietal, occipital and temporal positions of both hemispheres. Magnetic stimuli were discharged at increasing intensities up to the maximal output. TMS was performed both at rest and when the eyes were directed towards different parts of the visual field. The test subjects and the patients were observed clinically for signs of eye movements during TMS. In addition, we performed conventional electronystagmographic recordings from which data were digitalized and on-line computations were carried out with the help of a personal computer. Measurements were taken over a total of one second with a sampling interval of 5 ms. Electronystagmographic registrations during TMS were performed at rest, with the eyes directed to different parts of the visual field, during reflexive saccades to a sudden unpredictable target and during smooth pursuit eye movements while tracking a sinusoidally moving target (Fig. 2).
Results Clinical observation and electronystagmographic registration failed to reveal any oculomotor response after TMS with frontal, precentral, posterior- and inferiorparietal, occipital and temporal positions o f the stimula-
217
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.-.e ~ /e ~ ~e [ ~ 0
Control. HO~IZ. Control. Oblique Down
Conlrol. Oblique Up No Response
i
a
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Fig. 1. Eye movements elicited upon electrical stimulation of the
,
i
,
i
i
I
I
20 mS
b
IO0 500
ms
cerebral cortex of alert monkeys in three studies using different parameters, a Points with conjugate contralateral eye movements with high current levels. The line originating at each point indicates the direction of the eye movement (Wagman 1964). b Map of
moving target in square wave patterns with amplitudes of 20 degrees unpredictable in frequency and direction, b Represents de-
saccadic eye movements evoked by stimulation with currents between 1 and 3 mA. arc.s. = arcuate sulcus, pri.s. = principal sulcus (Robinson and Fuchs 1969). c Frontal lobe with the surface extent of the low-threshold (50 pA) frontal eye field region cross-hatched. AS=arcuate sulcus, PS=principal sulcus, CS=central sulcus (Bruce et al. 1985)
tail of a) (rectangular window -~). ~=stimulation artefact, - - = normally performed saccadic eye movement, simulated during stimulation artefact, e Example of a smooth pursuit eye movement. The target is moving sinusoidally with a frequency of 0.1 Hz and maximal amplitudes of 30 degrees. --, = stimulation artefact
tion coil over b o t h hemispheres. In addition T M S did not modulate reflexive saccades to a sudden unpredictable target (Fig. 2a, b) nor smooth pursuit eye movements while tracking a sinusoidally moving target (Fig. 2c). F r o m frontal, precentral and temporal stimulation points, eye lid artefacts occurred either by stimulating the face-associated m o t o r cortex or by direct stimulation of the peripheral facial nerve. In patients with complete paresis of the facial nerve blink reflexes were missing on the affected site, as shown by electromyographic recordings f r o m the M. orbicularis oculi. Yet under all conditions we were unable to elicit any oculomotor responses by TMS.
brain likewise fails to elicit oculomotor responses (Merton and M o r t o n 1980, Merton 1989, personal communication). This seems to conflict with the finding that in humans and monkeys eye movements can be elicited by direct electrical stimulation of widespread cortical areas (Fig. 1) (Penfield and Jasper 1954, W a g m a n 1964, Robinson and Fuchs 1969, Bruce et al. 1985). In monkeys the extent o f the cortical regions that yield saccades varies with the strength of the electric current applied. By systematically varying the parameters of stimulation with fairly large currents up to 3 mA, and using stimulation trains, Robinson and Fuchs (1969) described a m a p of elicited eye movements from the F E F confined to a small cortex area enclosed by the arcuate sulcus (Fig. l b). Using recording microelectrodes and thresholds of 50 gA, the m a p of elicited eye movements became even smaller and confined the F E F to the immediate vicinity of the arcuate sulcus at its posterior band (Fig. lc). The surface view was inadequate, however, as m o s t low threshold sites lay buried in the anterior bank of the arcuate, extending to the floor of this sulcus (Bruce et al.
Discussion
Our findings indicate that in awake humans eye movements cannot be evoked by T M S of the cortex, even of the F E F or the posterior- and inferior-parietal lobe (IPL). Transcranial electric stimulation o f the h u m a n
Fig. 2. Example of a reflexive saccade to the right side. Horizontally
218 1985). Stimulation of retrorolandic cortical areas yielded corresponding findings. In monkeys the effective site of stimulation for saccades in the posterior parietal association cortex, which in h u m a n s seem to correlate with the IPL, was mainly localized in a small region on the posterior b a n k of the intraparietal sulcus (Shibutani et al. 1984; Keating and Gooley 1988). Thus it can be suggested that in humans, T M S fails to stimulate enough specific o c u l o m o t o r neurons in the very small F E F (Fig. lc) and the I P L for eliciting an o c u l o m o t o r response. This m a y be a consequence of: (1) low stimulation strength, (2) p o o r centralization of the stimulus, (3) the type of stimulation used in T M S which is composed o f multiple Iwaves, rather than the pulse trains used in electrical stimulation experiments in m o n k e y s (4) impossibility for facilitating the o c u l o m o t o r system in the same way as seen for skeletal muscles and (5) stimulation of an inhibitory pathway, connecting the F E F , substantia nigra, colliculus superior and the P P R F (Kennard 1986). Furthermore cortical efferences to the P P R F seem to be polysynaptic (Leichnetz et al. 1984; Schnyder et al. 1985). A lesion o f the P P R F eliminates all saccades in particular directions (Henn et al. 1984); cortical lesions, however, induce different disturbances of rapid eye m o v e m e n t s dependent on the behavioral pattern of the respective saccade. After parietal lesions, visually guided reflexive saccades are particularly impaired (Tsutsui et al. 1980). In frontal lesions, volitional saccades are reduced (Guitton et al. 1988; Bruce and Bordon 1986). Unilateral lesions of frontal and parietal areas disturb all volitional and reflexive saccades whereas spontaneous saccades remain unimpaired (Tusa et al. 1986). The role o f cortex in eye movements is therefore to contribute aspects of sophisticated processing to the basic apparatus for rapid eye movements. Thus, the function of the cortex for saccades is to analyze and process conditions with differing functional requirements, rather than to generate saccades directly. This m a y explain why T M S of the cortex seems to be unable to elicit o c u l o m o t o r response. The m o t o r c o m m a n d in the o c u l o m o t o r system cannot be generated only in the cortex, for this purpose, the P P R F is necessary, which is not stimulated by TMS.
References Barker AT, Jalinous R, Freeston IL (1985) Noninvasive magnetic stimulation of the human motor cortex. Lancet I: 1t06-1107 Benecke R, Meyer BU, Sch6nle P, Conrad B (1988) Transcranial magnetic stimulation of the human brain: responses in muscles supplied by cranial nerves. Exp Brain Res 71:623-632 Bruce CJ, Goldberg ME (1985) Primate frontal eye fields. I. Single neurons discharging before saccades. J. Neurophysiol 53 : 603-635 Bruce CJ, Borden JA (1986) The primate frontal eye fields are necessary for predictive saccadic tracking. Soc Neurosci 12:1086 Guitton D, Buchtel HA, Douglas RM (1985) Frontal lobe loss in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades. Exp Brain Res 58:455-472 Henn V, Lang W, Hepp K, Reisine H (1984) Experimental gaze palsies in monkeys and their relation to human pathology. Brain 107: 619-636 Keating EG, Gooley SG (1988) Disconnection of parietal and occipital access to the saccadic oculomotor system. Exp Brain Res 70:385-398 Kennard C (1986) Higher control mechanisms of saccadic eye movements. Trans Ophthalmol Soc UK 105:705-708 Leichnetz GR, Smith D J, Spencer RF (1984) Cortical projections to the paramedian tegmental and basilar pons in the monkey. J Comp Neurol 228:388-408 Merton PA, Morton HB (1980) Electrical stimulation of human motor and visual cortex through the scalp. J Physiol 305:9-10 Penfield W, Jasper H (1954) Epilepsy and the functional anatomy of the human brain. Little Brown, Boston Robinson DA, Fuchs AF (1969) Eye movements evoked by stimulation of frontal eye fields. J Neurophysiol 32:637-648 Schnyder H, Reisine H, Hepp K, Henn V (1985) Frontal eye field projection to the paramedian pontine reticular formation traced with wheat germ agglutinin in the monkey. Brain Res 329:151-160 Shibutani H, Sakata H, Hyv/irinen J (1984) Saccade and blinking evoked by microstimulation of the posterior parietal association cortex of the monkey. Exp Brain Res 55: 1-8 Tsutsui J, Takeda J, Ichihashi S, Kimura H, Shirabe T (1980) Ocular motor apraxia and lesions of the visual association area. Neuroophthalmology 1: 149-154 Tusa R J, Zee DS, Herdmann SJ (1986) Effect of unilateral cerebral cortical lesions on ocular motor behavior in monkeys: saccades and quick phases. J. Neurophysiol 56:1590-1625 Wagman JH (1964) Eye movements induced by electric stimulation of cerebrum in monkeys and their relationship to bodily movements. In: Bender MB (ed) The oculomotor system. Harper and Row, New York Evanston London, pp 18-39
Experimental BrainResearch 9 Springer-Verlag1991
Research Note
Transcranial magnetic brain stimulation: lack of oculomotor response K. Wessel and D. K6mpf Department of Neurology, Medical University, Ratzeburger Allee 160, W-2400 Lfibeek, Federal Republic of Germany Received December 6, 1990 / Accepted April 10, 1990
Summary. We have investigated whether eye movements can be evoked by transcranial magnetic brain stimulation (TMS) from frontal, precentral, posterior- and inferiorparietal, occipital and temporal positions o f the stimulating coil. Our findings were negative, even for structures concerned with voluntary eye movements, such as the frontal eye field (FEF) and the inferior parietal lobe (IPL). The lack o f o c u l o m o t o r responses after stimulation of the cortex shall be discussed in the following context: (1) Low-threshhold intracortical stimulation experiments suggest that in functional terms, the F E F is confined to small areas which are extend to the floor of sulci. TMS does not reach these structures to a sufficient extent. Furthermore efferent connections of the cortex to the paramedian pontine reticular formation (PPRF) seem to be polysynaptic. (2) The function o f the cortex in rapid eye movement is to analyze and process conditions with differing functional requirements, rather than to directly generate saccades. TMS does not elicit oculomotor responses, demonstrating again that the role played by the cortex in eye movement is not analogous to the role of the somatic m o t o r cortex in controlling skeletal movements.
Key words: Transcranial magnetic s t i m u l a t i o n - Voluntary eye movements - Frontal eye field - Inferior parietal lobe - H u m a n
Introduction Recent experiments indicate that presaccadic neurons in the F E F play a causal role in the generation o f visually evoked voluntary saccades (Bruce and Goldberg 1985). Earlier studies suggested that in the m o n k e y eye movements can also be elicited by electrical stimulation o f the posterior-parietal, occipital and temporal cortex (Fig. 1) Offprint requests to: K. Wessel (address see above)
(Wagman 1964). In humans, the technique of TMS has recently become available (Barker et al. 1985; Benecke et al. 1988). The aim of this study is to investigate whether TMS of different structures can evoke oculomotor responses and to relate these findings to clinical and experimental data on the significance of cortex in the initiation of eye movements.
Methods The authors performed TMS upon each other as test subjects. Additionally three patients (aged 21-56 years) with complete unilateral paresis of the 7th cranial nerve were examined. We used a commercially available magnetic stimulator (Magstim 200), the peak magnetic field of which was about 1.5 Tesla after 150 gs in the centre of the stimulating coil. The induced electric current within the conducting tissue of the brain reaches approximately 0.25 A at maximal output of the device. The positioning of the magnetic coil for eliciting oculomotor responses was varied from frontal to precentral, posterior- and inferior-parietal, occipital and temporal positions of both hemispheres. Magnetic stimuli were discharged at increasing intensities up to the maximal output. TMS was performed both at rest and when the eyes were directed towards different parts of the visual field. The test subjects and the patients were observed clinically for signs of eye movements during TMS. In addition, we performed conventional electronystagmographic recordings from which data were digitalized and on-line computations were carried out with the help of a personal computer. Measurements were taken over a total of one second with a sampling interval of 5 ms. Electronystagmographic registrations during TMS were performed at rest, with the eyes directed to different parts of the visual field, during reflexive saccades to a sudden unpredictable target and during smooth pursuit eye movements while tracking a sinusoidally moving target (Fig. 2).
Results Clinical observation and electronystagmographic registration failed to reveal any oculomotor response after TMS with frontal, precentral, posterior- and inferiorparietal, occipital and temporal positions o f the stimula-
217
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~
9 9
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s
oS ~P
I
9 ,* * tt
,, 9 9
5"
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I
ms
8.
"-~
9
.-.e ~ /e ~ ~e [ ~ 0
Control. HO~IZ. Control. Oblique Down
Conlrol. Oblique Up No Response
i
a
C
Fig. 1. Eye movements elicited upon electrical stimulation of the
,
i
,
i
i
I
I
20 mS
b
IO0 500
ms
cerebral cortex of alert monkeys in three studies using different parameters, a Points with conjugate contralateral eye movements with high current levels. The line originating at each point indicates the direction of the eye movement (Wagman 1964). b Map of
moving target in square wave patterns with amplitudes of 20 degrees unpredictable in frequency and direction, b Represents de-
saccadic eye movements evoked by stimulation with currents between 1 and 3 mA. arc.s. = arcuate sulcus, pri.s. = principal sulcus (Robinson and Fuchs 1969). c Frontal lobe with the surface extent of the low-threshold (50 pA) frontal eye field region cross-hatched. AS=arcuate sulcus, PS=principal sulcus, CS=central sulcus (Bruce et al. 1985)
tail of a) (rectangular window -~). ~=stimulation artefact, - - = normally performed saccadic eye movement, simulated during stimulation artefact, e Example of a smooth pursuit eye movement. The target is moving sinusoidally with a frequency of 0.1 Hz and maximal amplitudes of 30 degrees. --, = stimulation artefact
tion coil over b o t h hemispheres. In addition T M S did not modulate reflexive saccades to a sudden unpredictable target (Fig. 2a, b) nor smooth pursuit eye movements while tracking a sinusoidally moving target (Fig. 2c). F r o m frontal, precentral and temporal stimulation points, eye lid artefacts occurred either by stimulating the face-associated m o t o r cortex or by direct stimulation of the peripheral facial nerve. In patients with complete paresis of the facial nerve blink reflexes were missing on the affected site, as shown by electromyographic recordings f r o m the M. orbicularis oculi. Yet under all conditions we were unable to elicit any oculomotor responses by TMS.
brain likewise fails to elicit oculomotor responses (Merton and M o r t o n 1980, Merton 1989, personal communication). This seems to conflict with the finding that in humans and monkeys eye movements can be elicited by direct electrical stimulation of widespread cortical areas (Fig. 1) (Penfield and Jasper 1954, W a g m a n 1964, Robinson and Fuchs 1969, Bruce et al. 1985). In monkeys the extent o f the cortical regions that yield saccades varies with the strength of the electric current applied. By systematically varying the parameters of stimulation with fairly large currents up to 3 mA, and using stimulation trains, Robinson and Fuchs (1969) described a m a p of elicited eye movements from the F E F confined to a small cortex area enclosed by the arcuate sulcus (Fig. l b). Using recording microelectrodes and thresholds of 50 gA, the m a p of elicited eye movements became even smaller and confined the F E F to the immediate vicinity of the arcuate sulcus at its posterior band (Fig. lc). The surface view was inadequate, however, as m o s t low threshold sites lay buried in the anterior bank of the arcuate, extending to the floor of this sulcus (Bruce et al.
Discussion
Our findings indicate that in awake humans eye movements cannot be evoked by T M S of the cortex, even of the F E F or the posterior- and inferior-parietal lobe (IPL). Transcranial electric stimulation o f the h u m a n
Fig. 2. Example of a reflexive saccade to the right side. Horizontally
218 1985). Stimulation of retrorolandic cortical areas yielded corresponding findings. In monkeys the effective site of stimulation for saccades in the posterior parietal association cortex, which in h u m a n s seem to correlate with the IPL, was mainly localized in a small region on the posterior b a n k of the intraparietal sulcus (Shibutani et al. 1984; Keating and Gooley 1988). Thus it can be suggested that in humans, T M S fails to stimulate enough specific o c u l o m o t o r neurons in the very small F E F (Fig. lc) and the I P L for eliciting an o c u l o m o t o r response. This m a y be a consequence of: (1) low stimulation strength, (2) p o o r centralization of the stimulus, (3) the type of stimulation used in T M S which is composed o f multiple Iwaves, rather than the pulse trains used in electrical stimulation experiments in m o n k e y s (4) impossibility for facilitating the o c u l o m o t o r system in the same way as seen for skeletal muscles and (5) stimulation of an inhibitory pathway, connecting the F E F , substantia nigra, colliculus superior and the P P R F (Kennard 1986). Furthermore cortical efferences to the P P R F seem to be polysynaptic (Leichnetz et al. 1984; Schnyder et al. 1985). A lesion o f the P P R F eliminates all saccades in particular directions (Henn et al. 1984); cortical lesions, however, induce different disturbances of rapid eye m o v e m e n t s dependent on the behavioral pattern of the respective saccade. After parietal lesions, visually guided reflexive saccades are particularly impaired (Tsutsui et al. 1980). In frontal lesions, volitional saccades are reduced (Guitton et al. 1988; Bruce and Bordon 1986). Unilateral lesions of frontal and parietal areas disturb all volitional and reflexive saccades whereas spontaneous saccades remain unimpaired (Tusa et al. 1986). The role o f cortex in eye movements is therefore to contribute aspects of sophisticated processing to the basic apparatus for rapid eye movements. Thus, the function of the cortex for saccades is to analyze and process conditions with differing functional requirements, rather than to generate saccades directly. This m a y explain why T M S of the cortex seems to be unable to elicit o c u l o m o t o r response. The m o t o r c o m m a n d in the o c u l o m o t o r system cannot be generated only in the cortex, for this purpose, the P P R F is necessary, which is not stimulated by TMS.
References Barker AT, Jalinous R, Freeston IL (1985) Noninvasive magnetic stimulation of the human motor cortex. Lancet I: 1t06-1107 Benecke R, Meyer BU, Sch6nle P, Conrad B (1988) Transcranial magnetic stimulation of the human brain: responses in muscles supplied by cranial nerves. Exp Brain Res 71:623-632 Bruce CJ, Goldberg ME (1985) Primate frontal eye fields. I. Single neurons discharging before saccades. J. Neurophysiol 53 : 603-635 Bruce CJ, Borden JA (1986) The primate frontal eye fields are necessary for predictive saccadic tracking. Soc Neurosci 12:1086 Guitton D, Buchtel HA, Douglas RM (1985) Frontal lobe loss in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades. Exp Brain Res 58:455-472 Henn V, Lang W, Hepp K, Reisine H (1984) Experimental gaze palsies in monkeys and their relation to human pathology. Brain 107: 619-636 Keating EG, Gooley SG (1988) Disconnection of parietal and occipital access to the saccadic oculomotor system. Exp Brain Res 70:385-398 Kennard C (1986) Higher control mechanisms of saccadic eye movements. Trans Ophthalmol Soc UK 105:705-708 Leichnetz GR, Smith D J, Spencer RF (1984) Cortical projections to the paramedian tegmental and basilar pons in the monkey. J Comp Neurol 228:388-408 Merton PA, Morton HB (1980) Electrical stimulation of human motor and visual cortex through the scalp. J Physiol 305:9-10 Penfield W, Jasper H (1954) Epilepsy and the functional anatomy of the human brain. Little Brown, Boston Robinson DA, Fuchs AF (1969) Eye movements evoked by stimulation of frontal eye fields. J Neurophysiol 32:637-648 Schnyder H, Reisine H, Hepp K, Henn V (1985) Frontal eye field projection to the paramedian pontine reticular formation traced with wheat germ agglutinin in the monkey. Brain Res 329:151-160 Shibutani H, Sakata H, Hyv/irinen J (1984) Saccade and blinking evoked by microstimulation of the posterior parietal association cortex of the monkey. Exp Brain Res 55: 1-8 Tsutsui J, Takeda J, Ichihashi S, Kimura H, Shirabe T (1980) Ocular motor apraxia and lesions of the visual association area. Neuroophthalmology 1: 149-154 Tusa R J, Zee DS, Herdmann SJ (1986) Effect of unilateral cerebral cortical lesions on ocular motor behavior in monkeys: saccades and quick phases. J. Neurophysiol 56:1590-1625 Wagman JH (1964) Eye movements induced by electric stimulation of cerebrum in monkeys and their relationship to bodily movements. In: Bender MB (ed) The oculomotor system. Harper and Row, New York Evanston London, pp 18-39
