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Topographical differences in the developmental profile of central motor conduction time
Clinical Neurophysiology 110 (1999) 1646±1649
Topographical differences in the developmental pro®le of central motor conduction time Atsuo Nezu*, Seiji Kimura, Saoko Takeshita Department of Pediatrics, Urafune Hospital of Yokohama City University School of Medicine, 3-46 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan Accepted 19 April 1999
Abstract Objectives: To study the topographical difference in the developmental pro®le of the central motor conduction time (CMCT) in upper extremity muscles, electromyographic (EMG) responses to transcranical magnetic stimulation (TMS) were examined in the ®rst dorsal interosseous, extensor carpi radialis (ECR), biceps (BCP), and deltoid (DT) muscles of 25 neurologically normal subjects aged from 2 to 26 years. Methods: The motor cortex and cervical spinal roots were magnetically stimulated, and CMCT was measured as the onset latency difference between these EMG responses. Results: CMCT in children was shorter in the more proximal muscle of each adjacent muscle pair, despite the tendency of a higher threshold intensity for TMS of the more proximal muscle. This topographical difference tended to be more distinct in younger children, whereas CMCT in adults did not show such a topographical difference. Consequently, the linear decrease in CMCT during maturation was less pronounced in the proximal muscles. Conclusions: We speculate that direct activation of corticospinal neurons to the more proximal muscles was preferentially produced by TMS in younger children, depending on the relationship between the spatial direction of axons, head circumference, and stimulating coil diameter. q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Transcranial magnetic stimulation; Central motor conduction time; Topography; Developmental change
1. Introduction Transcranial magnetic stimulation (TMS) of the motor cortex scarcely leads to discomfort and is useful for quantitative evaluation of development of the descending motor pathways and motor cortical excitability (Koh and Eyre, 1988; Eyre et al., 1991; MuÈller et al., 1991; Nezu et al., 1997a). TMS also exhibits promising potential not only for assessing motor disabilities associated with cerebral palsy but also for elucidating the characteristics of motor impairments in pediatric neurological diseases (MuÈller et al., 1992; Carr et al., 1993; Nezu et al., 1996; Nezu et al., 1997b; Nezu et al., 1998). The central motor conduction time (CMCT), i.e. the latency difference between electromyographical (EMG) responses to motor cortical and spinal root stimulation, is one of the most valuable parameters for the clinical application of TMS in children (Nezu et al., 1997a). CMCT consists of the intracortical delay during which
the corticospinal neurons are transsynaptically ®red, the conduction time during which the consequent multiple descending volleys come down through the motor tracts, the synaptic delay during which the spinal motoneurons are subsequently activated through temporal summation of the multiple descending volleys, and the time during which the nerve impulse runs through the spinal roots (Day et al., 1987). We previously reported that CMCT in the small hand muscle in children decreases linearly with age, and that the developmental prolongation of CMCT between 2 and 14 years of age mainly results from the more prominent intracortical delay due to immaturity of the motor cortex (Nezu et al., 1997a). The present study additionally demonstrates a topographical difference in this developmental pro®le of CMCT between upper extremity muscles.
2. Methods 2.1. Subjects
* Corresponding author. Tel.: 1 81-45-261-5656; fax: 1 81-45-2433886.
Twenty-®ve
1388-2457/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S13 88-2457(99)0011 8-2
neurologically
normal
subjects
were
CLINPH 98036
A. Nezu et al. / Clinical Neurophysiology 110 (1999) 1646±1649
Fig. 1. Age and height of the age groups, expressed as means and standard deviations.
assigned to 5 age groups (Fig. 1). Each of the groups consisted of 5 subjects aged between 2 and 3, 4 and 6, 7 and 9, 10 and 13 years, and 26 years, respectively. They all were right-handed. The parents of all the children and adult controls gave informed consent for participating in this study. 2.2. Transcranial magnetic stimulation EMG responses were recorded from surface electrodes placed over the right ®rst dorsal interosseous (FDI), extensor carpi radialis (ECR), biceps (BCP), and deltoid (DT) muscles, with a ®lter setting of 20±3000 Hz. Magnetic stimulation was delivered by a Magstim 200 magnetic stimulator (Magstim Co., UK) through a circular coil with a mean diameter of 90 mm (peak magnetic ®eld strength, 2.0 Tesla, here designated as 100% intensity). On TMS, the edge of the coil was placed tangentially over the respective optimal scalp position with the lowest threshold intensity, 1.0 cm apart along the coronal line connecting C3±Cz±T3 of the International 10-20 System. The current in the coil ¯owed anti-clockwise. The threshold intensity for TMS was de®ned as the lowest stimulator intensity needed to produce EMG responses of more than 100 mV amplitude in at least 3 of 5 trials. TMS was performed in this study with an intensity 10% above the threshold. To stimulate the spinal roots, the coil edge was placed over the respective optimal positions along the cervical spine. During stimulation, the subjects were instructed to relax the muscles tested. The CMCT was calculated by subtracting the onset latency obtained on cervical stimulation from that on TMS. 2.3. Statistical analysis Statistical comparison of CMCT between the proximal and distal muscles in each age group, and among the different age groups in the same target muscles was performed
1647
Fig. 2. Age-dependent change in the threshold intensity for transcranial magnetic stimulation of the ®rst dorsal interosseous muscle, expressed as means and standard deviations.
using analysis of variance (ANOVA). A probability of less than 0.05 was considered signi®cant.
3. Results The cortical representations for the 4 upper extremity muscles overlapped extensively in all subjects, and the distal muscles had larger representations. The optimal scalp position for activating FDI was approximately C3. The optimal scalp position for ECR was almost the same as that for FDI, while those for BCP and DT were medial to C3. The threshold intensity for FDI was approximately identical to that on ECR, and it was inversely correlated with age, as shown in Fig. 2. The threshold intensity for the proximal muscles tended to be higher than that for the distal muscles, although the difference was not signi®cant. In the child groups, CMCT was shorter in the more proximal muscle of each adjacent muscle pair (Table 1). This ®nding tended to be less apparent in the older group, and the adult group did not show such a topographical difference (Fig. 3). The difference in mean CMCT between the youngest and Table 1 Means ^ SD values of the central motor conduction time in 4 target muscles (ms) a Age (years)
FDI
ECR
BCP
2±3 4±6 7±9 10±13 26
13.0 ^ 0.7 c 11.6 ^ 1.9 c 11.0 ^ 0.8 c 7.8 ^ 1.0 8.3 ^ 0.8
11.4 ^ 0.7 b,c 10.9 ^ 1.8 c 9.9 ^ 1.4 7.0 ^ 2.2 8.8 ^ 0.6
9.6 9.2 7.1 6.1 8.6
a
^ 2.1 b,c ^ 1.8 c ^ 1.2 b ^ 0.3 b ^ 0.2
DT 8.8 7.5 6.0 5.3 8.0
^ 1.6 b,c ^ 2.1 b ^ 1.0 b ^ 0.6 b ^ 0.9
FDI, ®rst dorsal interosseous; ECR, extensor carpi radialis; BCP, biceps; DT, deltoid. c Shows signi®cant change compared to CMCT of the group of 10±13 years in each target muscle (P , 0:05, ANOVA). b Indicates signi®cant difference compared to CMCT of FDI in each age group.
1648
A. Nezu et al. / Clinical Neurophysiology 110 (1999) 1646±1649
Fig. 3. Topographical differences in the age-dependent change in the CMCT in the FDI, ECR, BCP, and DT muscles, expressed as means and standard deviations.
oldest child groups was 5.2 ms for FDI, but 3.5 ms for DT. Thus, the developmental change, the linear decrease in CMCT with age, was less signi®cant in the proximal muscles.
controlling the most delicate movements of the small hand muscles. Meanwhile, the tendency toward a higher threshold intensity in the proximal muscles is thought to be partially due to the fewer corticospinal neurons present. However, the corticospinal neurons innervating the leg muscles can be directly stimulated at the level of the axon hillock (Priori et al., 1993). In such direct activation, a higher stimulus intensity is generally required than in transsynaptic activation (Day et al., 1988). Direct activation of the corticospinal neurons to the proximal muscles could likewise be preferentially produced on TMS in younger children, since CMCT in the proximal muscles signi®cantly shortened despite the tendency toward a higher threshold intensity. This mechanism may depend on a particular relationship between the spatial direction of the axons, head circumference, and stimulating coil diameter. Although it is not known how the number of descending volleys required to ®re the spinal motoneurons differs between the distal and proximal muscles in children, it is crucial to understand the topographical difference in the developmental pro®le of CMCT, especially during assessment of the motor cortex in children. References
4. Discussion The overlapping cortical representations, which showed larger maps with lower threshold intensities in the distal muscles, were almost the same as those obtained in the previous studies using an 8-®gure coil (Brasil-Neto et al., 1992; Wassermann et al., 1992). This evidence is likely to re¯ect the greater number of corticospinal neurons to the distal muscles, and their more multiple descending volleys may reduce the time for achieving the temporal summation necessary for activation of the spinal motoneurons (Fuhr et al., 1991). According to this hypothesis, CMCT may be shorter in the distal muscles. Nevertheless, the present study showed that CMCT in adults was not substantially different between the distal and proximal muscles, and furthermore CMCT in children was shorter in the proximal muscles. Consequently, the maturational change in CMCT, i.e. the linear decrease inversely correlated with age, was shown more pronounced in the distal muscles. This topographical difference in childhood CMCT seemed to be mainly due to a difference in the intracortical response to TMS, rather than one in the conduction time in the descending motor tracts, since developmental myelination of the corticospinal tracts is complete morphologically by the age of 3 years (Yakovlev and Lecours, 1966). TMS, when used to activate the small hand muscles, generally depolarizes the corticospinal neurons transsynaptically, unless the coil is placed in a particular position (Amassian et al., 1989). The greatest change in CMCT in FDI presumably corresponded to development of intracortical integration for
Amassian VE, Cracco RQ, Maccabee PJ. Focal stimulation of human cerebral cortex with magnetic coil: a comparison with electrical stimulation. Electroenceph clin Neurophysiol 1989;74:401±416. Brasil-Neto JP, Mcshane LM, Fuhr P, Hallett M, Cohen LG. Topographic mapping of the human motor cortex with magnetic stimulation: factors affecting accuracy and reproducibility. Electroenceph clin Neurophysiol 1992;85:9±16. Carr LJ, Harrison LM, Evans AL, Stephens JA. Patterns of central motor reorganization in hemiplegic cerebral palsy. Brain 1993;116:1223± 1247. Day BL, Dressler D, Maertens de Noordhout A, Marsden CD, Nakashima K, Rothwell JC, Thompson PD. Electric and magnetic simulation of human motor cortex: surface EMG and single motor unit responses. J Physiol 1988;412:449±473. Day BL, Thompson PD, Dick JP, Nakashima K, Marsden CD. Different sites of action of electrical and magnetic stimulation of the human brain. Neurosci Lett 1987;75:101±106. Eyre JA, Miller S, Ramesh V. Constancy of central conduction delays during development in man: investigation of motor and somatosensory pathways. J Physiol 1991;434:441±452. Fuhr P, Cohen LG, Roth BJ, Hallett M. Latency of motor evoked potentials to focal transcranial stimulation varies as a function of scalp positions stimulated. Electroenceph clin Neurophysiol 1991;81:81±89. Koh THHG, Eyre JA. Maturation of corticospinal tracts assessed by electromagnetic stimulation of the motor cortex. Arch Dis Child 1988;63:1347±1352. MuÈller K, Homberg V, Lenard HG. Magnetic stimulation of motor cortex and nerve roots in children. Maturation of cortico-motoneuronal projections. Electroenceph clin Neurophysiol 1991;81:63±70. MuÈller K, Homberg V, Aulich A, Lenard HG. Magnetoelectrical stimulation of motor cortex in children with motor disturbances. Electroenceph clin Neurophysiol 1992;85:86±94. Nezu A, Kimura S, Kobayashi T, Sekiguchi H, Ikuta K, Matsuyama S, Oka A, Sakakihara Y. Transcranial magnetic stimulation in an adrenoleukodystrophy patient. Brain Dev 1996;18:327±329.
A. Nezu et al. / Clinical Neurophysiology 110 (1999) 1646±1649 Nezu A, Kimura S, Ohtsuki N, Tanaka M, Tada H. Alternating hemiplegia of childhood: report of a case having a long history. Brain Dev 1997;19:217±221. Nezu A, Kimura S, Uehara S, Kobayashi T, Tanaka M, Saito K. Magnetic stimulation of motor cortex in children: maturity of corticospinal pathway and problem of clinical application. Brain Dev 1997;19:176±180. Nezu A, Kimura S, Takeshita S, Tanaka M. Characteristic response to transcranial magnetic stimulation in Rett syndrome. Electroenceph clin Neurophysiol 1998;109:100±103. Priori A, Bertolasi L, Dressler D, Rothwell JC, Day BL, Thompson PD,
1649
Marsden CD. Transcranial electric and magnetic stimulation of the leg area of the motor cortex in humans. Electroenceph clin Neurophysiol 1993;89:131±137. Wassermann EM, Mcshane LM, Hallett M, Cohen LG. Noninvasive mapping of muscle representations in human motor cortex. Electroenceph clin Neurophysiol 1992;85:1±8. Yakovlev PI, Lecours R. The myelination cycles of regional maturation of the brain. In: Minkowski A, editor. Regional development of the brain in early life, Oxford: Blackwell, 1966. pp. 3±70.
Topographical differences in the developmental pro®le of central motor conduction time Atsuo Nezu*, Seiji Kimura, Saoko Takeshita Department of Pediatrics, Urafune Hospital of Yokohama City University School of Medicine, 3-46 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan Accepted 19 April 1999
Abstract Objectives: To study the topographical difference in the developmental pro®le of the central motor conduction time (CMCT) in upper extremity muscles, electromyographic (EMG) responses to transcranical magnetic stimulation (TMS) were examined in the ®rst dorsal interosseous, extensor carpi radialis (ECR), biceps (BCP), and deltoid (DT) muscles of 25 neurologically normal subjects aged from 2 to 26 years. Methods: The motor cortex and cervical spinal roots were magnetically stimulated, and CMCT was measured as the onset latency difference between these EMG responses. Results: CMCT in children was shorter in the more proximal muscle of each adjacent muscle pair, despite the tendency of a higher threshold intensity for TMS of the more proximal muscle. This topographical difference tended to be more distinct in younger children, whereas CMCT in adults did not show such a topographical difference. Consequently, the linear decrease in CMCT during maturation was less pronounced in the proximal muscles. Conclusions: We speculate that direct activation of corticospinal neurons to the more proximal muscles was preferentially produced by TMS in younger children, depending on the relationship between the spatial direction of axons, head circumference, and stimulating coil diameter. q 1999 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Transcranial magnetic stimulation; Central motor conduction time; Topography; Developmental change
1. Introduction Transcranial magnetic stimulation (TMS) of the motor cortex scarcely leads to discomfort and is useful for quantitative evaluation of development of the descending motor pathways and motor cortical excitability (Koh and Eyre, 1988; Eyre et al., 1991; MuÈller et al., 1991; Nezu et al., 1997a). TMS also exhibits promising potential not only for assessing motor disabilities associated with cerebral palsy but also for elucidating the characteristics of motor impairments in pediatric neurological diseases (MuÈller et al., 1992; Carr et al., 1993; Nezu et al., 1996; Nezu et al., 1997b; Nezu et al., 1998). The central motor conduction time (CMCT), i.e. the latency difference between electromyographical (EMG) responses to motor cortical and spinal root stimulation, is one of the most valuable parameters for the clinical application of TMS in children (Nezu et al., 1997a). CMCT consists of the intracortical delay during which
the corticospinal neurons are transsynaptically ®red, the conduction time during which the consequent multiple descending volleys come down through the motor tracts, the synaptic delay during which the spinal motoneurons are subsequently activated through temporal summation of the multiple descending volleys, and the time during which the nerve impulse runs through the spinal roots (Day et al., 1987). We previously reported that CMCT in the small hand muscle in children decreases linearly with age, and that the developmental prolongation of CMCT between 2 and 14 years of age mainly results from the more prominent intracortical delay due to immaturity of the motor cortex (Nezu et al., 1997a). The present study additionally demonstrates a topographical difference in this developmental pro®le of CMCT between upper extremity muscles.
2. Methods 2.1. Subjects
* Corresponding author. Tel.: 1 81-45-261-5656; fax: 1 81-45-2433886.
Twenty-®ve
1388-2457/99/$ - see front matter q 1999 Elsevier Science Ireland Ltd. All rights reserved. PII: S13 88-2457(99)0011 8-2
neurologically
normal
subjects
were
CLINPH 98036
A. Nezu et al. / Clinical Neurophysiology 110 (1999) 1646±1649
Fig. 1. Age and height of the age groups, expressed as means and standard deviations.
assigned to 5 age groups (Fig. 1). Each of the groups consisted of 5 subjects aged between 2 and 3, 4 and 6, 7 and 9, 10 and 13 years, and 26 years, respectively. They all were right-handed. The parents of all the children and adult controls gave informed consent for participating in this study. 2.2. Transcranial magnetic stimulation EMG responses were recorded from surface electrodes placed over the right ®rst dorsal interosseous (FDI), extensor carpi radialis (ECR), biceps (BCP), and deltoid (DT) muscles, with a ®lter setting of 20±3000 Hz. Magnetic stimulation was delivered by a Magstim 200 magnetic stimulator (Magstim Co., UK) through a circular coil with a mean diameter of 90 mm (peak magnetic ®eld strength, 2.0 Tesla, here designated as 100% intensity). On TMS, the edge of the coil was placed tangentially over the respective optimal scalp position with the lowest threshold intensity, 1.0 cm apart along the coronal line connecting C3±Cz±T3 of the International 10-20 System. The current in the coil ¯owed anti-clockwise. The threshold intensity for TMS was de®ned as the lowest stimulator intensity needed to produce EMG responses of more than 100 mV amplitude in at least 3 of 5 trials. TMS was performed in this study with an intensity 10% above the threshold. To stimulate the spinal roots, the coil edge was placed over the respective optimal positions along the cervical spine. During stimulation, the subjects were instructed to relax the muscles tested. The CMCT was calculated by subtracting the onset latency obtained on cervical stimulation from that on TMS. 2.3. Statistical analysis Statistical comparison of CMCT between the proximal and distal muscles in each age group, and among the different age groups in the same target muscles was performed
1647
Fig. 2. Age-dependent change in the threshold intensity for transcranial magnetic stimulation of the ®rst dorsal interosseous muscle, expressed as means and standard deviations.
using analysis of variance (ANOVA). A probability of less than 0.05 was considered signi®cant.
3. Results The cortical representations for the 4 upper extremity muscles overlapped extensively in all subjects, and the distal muscles had larger representations. The optimal scalp position for activating FDI was approximately C3. The optimal scalp position for ECR was almost the same as that for FDI, while those for BCP and DT were medial to C3. The threshold intensity for FDI was approximately identical to that on ECR, and it was inversely correlated with age, as shown in Fig. 2. The threshold intensity for the proximal muscles tended to be higher than that for the distal muscles, although the difference was not signi®cant. In the child groups, CMCT was shorter in the more proximal muscle of each adjacent muscle pair (Table 1). This ®nding tended to be less apparent in the older group, and the adult group did not show such a topographical difference (Fig. 3). The difference in mean CMCT between the youngest and Table 1 Means ^ SD values of the central motor conduction time in 4 target muscles (ms) a Age (years)
FDI
ECR
BCP
2±3 4±6 7±9 10±13 26
13.0 ^ 0.7 c 11.6 ^ 1.9 c 11.0 ^ 0.8 c 7.8 ^ 1.0 8.3 ^ 0.8
11.4 ^ 0.7 b,c 10.9 ^ 1.8 c 9.9 ^ 1.4 7.0 ^ 2.2 8.8 ^ 0.6
9.6 9.2 7.1 6.1 8.6
a
^ 2.1 b,c ^ 1.8 c ^ 1.2 b ^ 0.3 b ^ 0.2
DT 8.8 7.5 6.0 5.3 8.0
^ 1.6 b,c ^ 2.1 b ^ 1.0 b ^ 0.6 b ^ 0.9
FDI, ®rst dorsal interosseous; ECR, extensor carpi radialis; BCP, biceps; DT, deltoid. c Shows signi®cant change compared to CMCT of the group of 10±13 years in each target muscle (P , 0:05, ANOVA). b Indicates signi®cant difference compared to CMCT of FDI in each age group.
1648
A. Nezu et al. / Clinical Neurophysiology 110 (1999) 1646±1649
Fig. 3. Topographical differences in the age-dependent change in the CMCT in the FDI, ECR, BCP, and DT muscles, expressed as means and standard deviations.
oldest child groups was 5.2 ms for FDI, but 3.5 ms for DT. Thus, the developmental change, the linear decrease in CMCT with age, was less signi®cant in the proximal muscles.
controlling the most delicate movements of the small hand muscles. Meanwhile, the tendency toward a higher threshold intensity in the proximal muscles is thought to be partially due to the fewer corticospinal neurons present. However, the corticospinal neurons innervating the leg muscles can be directly stimulated at the level of the axon hillock (Priori et al., 1993). In such direct activation, a higher stimulus intensity is generally required than in transsynaptic activation (Day et al., 1988). Direct activation of the corticospinal neurons to the proximal muscles could likewise be preferentially produced on TMS in younger children, since CMCT in the proximal muscles signi®cantly shortened despite the tendency toward a higher threshold intensity. This mechanism may depend on a particular relationship between the spatial direction of the axons, head circumference, and stimulating coil diameter. Although it is not known how the number of descending volleys required to ®re the spinal motoneurons differs between the distal and proximal muscles in children, it is crucial to understand the topographical difference in the developmental pro®le of CMCT, especially during assessment of the motor cortex in children. References
4. Discussion The overlapping cortical representations, which showed larger maps with lower threshold intensities in the distal muscles, were almost the same as those obtained in the previous studies using an 8-®gure coil (Brasil-Neto et al., 1992; Wassermann et al., 1992). This evidence is likely to re¯ect the greater number of corticospinal neurons to the distal muscles, and their more multiple descending volleys may reduce the time for achieving the temporal summation necessary for activation of the spinal motoneurons (Fuhr et al., 1991). According to this hypothesis, CMCT may be shorter in the distal muscles. Nevertheless, the present study showed that CMCT in adults was not substantially different between the distal and proximal muscles, and furthermore CMCT in children was shorter in the proximal muscles. Consequently, the maturational change in CMCT, i.e. the linear decrease inversely correlated with age, was shown more pronounced in the distal muscles. This topographical difference in childhood CMCT seemed to be mainly due to a difference in the intracortical response to TMS, rather than one in the conduction time in the descending motor tracts, since developmental myelination of the corticospinal tracts is complete morphologically by the age of 3 years (Yakovlev and Lecours, 1966). TMS, when used to activate the small hand muscles, generally depolarizes the corticospinal neurons transsynaptically, unless the coil is placed in a particular position (Amassian et al., 1989). The greatest change in CMCT in FDI presumably corresponded to development of intracortical integration for
Amassian VE, Cracco RQ, Maccabee PJ. Focal stimulation of human cerebral cortex with magnetic coil: a comparison with electrical stimulation. Electroenceph clin Neurophysiol 1989;74:401±416. Brasil-Neto JP, Mcshane LM, Fuhr P, Hallett M, Cohen LG. Topographic mapping of the human motor cortex with magnetic stimulation: factors affecting accuracy and reproducibility. Electroenceph clin Neurophysiol 1992;85:9±16. Carr LJ, Harrison LM, Evans AL, Stephens JA. Patterns of central motor reorganization in hemiplegic cerebral palsy. Brain 1993;116:1223± 1247. Day BL, Dressler D, Maertens de Noordhout A, Marsden CD, Nakashima K, Rothwell JC, Thompson PD. Electric and magnetic simulation of human motor cortex: surface EMG and single motor unit responses. J Physiol 1988;412:449±473. Day BL, Thompson PD, Dick JP, Nakashima K, Marsden CD. Different sites of action of electrical and magnetic stimulation of the human brain. Neurosci Lett 1987;75:101±106. Eyre JA, Miller S, Ramesh V. Constancy of central conduction delays during development in man: investigation of motor and somatosensory pathways. J Physiol 1991;434:441±452. Fuhr P, Cohen LG, Roth BJ, Hallett M. Latency of motor evoked potentials to focal transcranial stimulation varies as a function of scalp positions stimulated. Electroenceph clin Neurophysiol 1991;81:81±89. Koh THHG, Eyre JA. Maturation of corticospinal tracts assessed by electromagnetic stimulation of the motor cortex. Arch Dis Child 1988;63:1347±1352. MuÈller K, Homberg V, Lenard HG. Magnetic stimulation of motor cortex and nerve roots in children. Maturation of cortico-motoneuronal projections. Electroenceph clin Neurophysiol 1991;81:63±70. MuÈller K, Homberg V, Aulich A, Lenard HG. Magnetoelectrical stimulation of motor cortex in children with motor disturbances. Electroenceph clin Neurophysiol 1992;85:86±94. Nezu A, Kimura S, Kobayashi T, Sekiguchi H, Ikuta K, Matsuyama S, Oka A, Sakakihara Y. Transcranial magnetic stimulation in an adrenoleukodystrophy patient. Brain Dev 1996;18:327±329.
A. Nezu et al. / Clinical Neurophysiology 110 (1999) 1646±1649 Nezu A, Kimura S, Ohtsuki N, Tanaka M, Tada H. Alternating hemiplegia of childhood: report of a case having a long history. Brain Dev 1997;19:217±221. Nezu A, Kimura S, Uehara S, Kobayashi T, Tanaka M, Saito K. Magnetic stimulation of motor cortex in children: maturity of corticospinal pathway and problem of clinical application. Brain Dev 1997;19:176±180. Nezu A, Kimura S, Takeshita S, Tanaka M. Characteristic response to transcranial magnetic stimulation in Rett syndrome. Electroenceph clin Neurophysiol 1998;109:100±103. Priori A, Bertolasi L, Dressler D, Rothwell JC, Day BL, Thompson PD,
1649
Marsden CD. Transcranial electric and magnetic stimulation of the leg area of the motor cortex in humans. Electroenceph clin Neurophysiol 1993;89:131±137. Wassermann EM, Mcshane LM, Hallett M, Cohen LG. Noninvasive mapping of muscle representations in human motor cortex. Electroenceph clin Neurophysiol 1992;85:1±8. Yakovlev PI, Lecours R. The myelination cycles of regional maturation of the brain. In: Minkowski A, editor. Regional development of the brain in early life, Oxford: Blackwell, 1966. pp. 3±70.