Neural development in children: A neurophysiological study

Elec troencephalography and Clinical N europh y siology , 1981, 52:249--256

249

Elsevier/North-Holland Scientific Publishers, Ltd.

N E U R A L DEVELOPMENT IN C H I L D R E N : A N E U R O P H Y S I O L O G I C A L STUDY PARVEEN BAWA Department o f Kinesiology, Simon Fraser University, Burnaby, B.C. V5A IS6 (Canada)

(Accepted for publication: May 13, 1981)

Most of the information on the developm e n t of the human nervous system comes from neuroanatomical, behavioural and electroencephalographic studies (Jacobson 1978; Faulkner and Tanner 1979). N e u r o a n a t o m y focusses on cell proliferation, cell size, neural density, myelination and dendritic and synaptic growth (Yakovlev and Lecours 1967; Lecours 1975; Purpura 1975). However, it does not explain when the circuits become fully functional once they are anatomically laid out. Behavioural studies are unquantitative since it is hard to separate the interaction of various c o m p o n e n t s of the nervous system. Electroencephalographic patterns show a gradual change with age and hence may be used to follow the central development in children (Bergstrom 1969; Eeg-Olofsson 1970; Petersen and Eeg-Olofsson 1970; Petersen et al. 1975). These patterns are localisable to certain parts of the brain b u t n o t a particular fibre system. Little information is available on neural development of m o t o r control. Neurophysiological studies on infants have shown that the spinal stretch reflex and flexion and crossed extension reflexes are present in newborns (Schulte et al. 1968, 1969; Scott 1979). One does n o t know whether these reflex arcs are functioning optimally at that age or whether they become more effective gradually with age. Stepping movements are present at birth b u t are then inhibited for a b o u t the first year of development. Looking at the central structures involved in m o t o r control, precentral gyrus takes an adult-like appearance after the

age of 6 years (Rabinowicz 1979). This sparse information reflects the need to design simple, non-invasive experiments that can be conducted on children. Lately, in addition to the shorter latency spinal reflex (termed M1), the presence of longer-latency reflexes (termed M2, M3) has been shown in adult m o n k e y s and human subjects (Bawa and Tatton 1979). It has been suggested that the longer-latency reflex pathways involve supraspinal structures and/or reflect more elaborate spinal reflexes. Similar experiments conducted on children to determine the development of these later components may provide insight into a sequential development of the human m o t o r system with a non-invasive technique. In addition to studying the 'hard-wired' reflex pathways, the next step is to look at the variation with age of simple reaction times to kinaesthetic inputs. These reaction times involve a minimal a m o u n t of central processing. This may be an example of a further stage of development of the m o t o r system. Results from the present work show that longer-latency reflex c o m p o n e n t s are present at all ages studied. However, they attain adultlike responses between the ages of 6 and 8 years after birth. Furthermore, reaction times take longer to approach adult-like figures.

Methods

The child was brought to the laboratory with the parents' consent. A child who was

0013-4649/81/0000---0000/$02.50 © 1981 Elsevier/North-Holland Scientific Publishers, Ltd.

250 n o t willing or was afraid of doing the experim e n t was n o t forced. Eighty-four experiments were done on 54 normal children between the ages o f 2 and 13 years (32 girls, 22 boys). The data from 15 experiments were rejected because either: (1) the short latency spinal reflex was n o t present and hence the excitability of the m o t o n e u r o n e pool could not be judged, or (2) the electrical and m o v e m e n t artifacts made the interpretation difficult, or (3) the responses were n o t very clear for quantification.

Apparatus The subject held the handle attached parallel to the shaft of a precision t o r q u e motor {Aeroflex Laboratories, TQ-82W) through a horizontal bar. The t o r q u e m o t o r (TM) was driven by a servo amplifier with step-load pulses {provided by an $88 Grass stimulator). The step-loads could be superimposed on a constant background bias {termed preload). The handle was fixed at a distance (between 3 and 6 cm f r om the TM shaft) such t h a t the r o tatio n o f the wrist was coaxial with the shaft o f the TM. The r o t a t i o n of the shaft and hence the angular r ot at i on of the wrist was measured with the help of a pot ent i om eter (Bourns Inc.) coupled to the shaft o f the TM. Calibration for loads was carried out at a distance of 10 cm from the shaft; all loads q u o t ed below will be for this distance for simplicity. At this distance the step-load range was 0.2--1.0 kg and the duration of the steploads was varied between 100 and 400 msec.

Recording The subject sat c o m f o r t a b l y with his/her forearm resting horizontally on a platform. The handle h e l d by the subject was adjusted so t h a t the wrist was coaxial with the shaft of the t or q u e m o t o r . To record EMG, two silver disc electrodes were pasted over the wrist flexor muscles along with the ground electrode on the u p p e r arm. The o u t p u t signals were amplified by Grass P15 preamplifiers (bandpass 30 Hz--3 kHz) and stored on one channel o f a Hewlett-Packard 4 channel FM tape recorder. Angular wrist position (the

P. BAWA p o t e n t i o m e t e r o u t p u t ) , torque pulses and 50 msec prepulses were recorded on the remaining 3 channels. T he subject was asked to hold the handle at a particular position (about 20 ° wrist flexion shown by the p o t e n t i o m e t e r o u t p u t as a line on an oscilloscope) till his/her hand was displaced by the handle. This was repeated 15 times for one load. If the subject was willing, further loads were tried (up to 4 loads) to test the i n p u t - o u t p u t behaviour of the reflex loops. Reaction times were also tested for those children who could follow more elaborate instructions. The subject was asked to perform either a {i) passive task: not to interfere with the imposed displacement, or (ii) compensate task: return the handle as quickly as possible in a direction opposite to that o f the imposed displacement.

Analysis Data were analysed on a PDP 11/'34 comput er with a 4-channel averaging program at a sampling rate of 2000/sec. The EMG record was rectified and filtered. All records of position, t orque pulse and EMG were passed through conditioning amplifiers before feeding into the com put er. In order to get an estimate of the background muscular activity, a 50 msec prepulse was used to trigger each sweep. Separate average response histograms (ARHs) were constructed for each load (15 sweeps/load). In order to quantify the magnitude of the reflex peaks, the following c o m p u t a t i o n s were made: Axi = area under the peak x for load i, x = SL or LL, i = 1, 2, 3, 4. Bi -- area between t he 50 msec prepulse and t o r q u e pulse at time zero. This gives an estimate of the background EMG for the i th load. Axi/msec = Axi/duration of peak x. Bi/msec = Bi/50 msec. (Axi)p = Axi/msec Bi/msec, area per msec under the peak x above the background.

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Children below the ages of 8 or 9 years had difficulty understanding the task and, hence, had to be helped during the experiments. Major difficulty seemed to be in holding the handle steady at the same position while waiting for the stimulus. For very y o u n g children, even when they were helped to return the handle to the initial position, the handle drifted as the experimenter let go. For such children it was difficult to maintain and assess the background EMG. Typical average response histogram for a

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Fig. 2. A sample of EMG responses from wrist flexors of 6 children from 3 to 12 years is shown above. The top trace represents typical time course of wrist extension. With an increase in the chronological age, the width of the longer latency reflex c o m p o n e n t decreases. Responses from 7-year--l-month-old and 7-year--5-month-old subjects emphasize the inter-subject variability. In addition to the reflex responses, the last subject performed a 'compensate' task. The arrow marks onset of reaction time in this subject. Time zero marks onset of the torque pulse for all subjects.

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4-year- and 11-month-old (4 y r - - l l too) child is shown in Fig. l a along with the response of an adult in Fig. lb. The top trace in each shows the time course of wrist rotation while the lower trace represents rectified and filtered surface EMG. The responses are clearly separated into two components; a shorter latency component (SL) starts between 20 and 30 msec (arrow 1), and a longer latency c o m p o n e n t (LL) starts between 40 and 60 msec (arrow 2). The latency for the onset of each of the components varied with the size of the subject. Comparison of the two responses shows that the duration of the LL c o m p o n e n t is much longer in the 5-year-old child than in an adult. The duration of LL response was not affected by the duration of the step toad (between 100 and 400 msec). A sample of the responses for various ages is shown in Fig. 2. The age for each subject is shown on the right of every trace. All children below 6 years of age were found to have a longer duration LL component. Between 6 and 8 years some children showed adult-like responses. Panel 3 for 7 yr--1 mo girl shows adult-like responses, while panel 4 for 7 yr--5 mo girl still shows undeveloped LL components. After 9 years, all responses were adultlike. The next question examined was whether the change in LL component duration is abrupt or, instead, whether there is a gradual decrease in duration from early years until the appearance of the adult-like response. For this, a horizontal line was drawn through the background EMG activity and the point of onset of the SL component. The distance between the minima of the SL and LL components (arrow 2 in Fig. 1) and where the horizontal line crossed the falling phase of the LL c o m p o n e n t (arrow 3) was plotted against the age of the child (Fig. 3). Means and standard deviations were computed for 1 year intervals. Observations from adult subjects are shown on the right of the graph. The graph shows that initially between the ages of 2 and 6 years there is a slow decrease in the LL width,

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followed by a fast decrease between 6 and 8 years. After 8 years of age most of the children exhibited adult-like responses.

Input-output properties Both the single m o t o r unit data in the monkeys and surface EMG work in humans show that the magnitude of the reflex response is proportional to the magnitude of the input load (Tatton and Bawa 1977, 1979). One may ask whether this is also true of a developing neural pathway. Conversely, it may be that the o u t p u t is n o t strictly related to the input. Uncoordinated movements in younger children may partially be attributed to such unpredictable behaviour of the neural system. Fig. 4 shows data from a child (6 years and 6 months old) before LL development and his 8-yr--4-mo-old sister whose responses are adult-like. Original EMG traces are shown for 4 different loads for each child (Fig. 4A1 and B~). Corresponding normalised areas are plotted in Fig. 4A2 for 4A1 and 4B2 for 4B1 (see Methods). One can s e e t h a t the peaks are more distinct at higher loads for both subjects. The input-output curves show

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times, the subject was asked to perform the 'compensate task'. The reaction time was measured by the onset of the EMG compon e n t after the LL c o m p o n e n t was over (arrow in the last panel of Fig. 2). In adults, the onset of reaction times is between 75 and 125 msec. No child before 10 years of age attained those short values. The fastest ones were around 200 msec with a gradual reduction between the ages of 8 and 10 years. Although most of the younger children had difficulty in understanding the task, some as y o u n g as 3 years of age could differentiate well between the compensate and the passive tasks. Even in these children, the fastest reaction times were around 200 msec. Further studies are being conducted on this aspect.

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that for both children, the higher the load, the higher the reflex response. Although it was difficult to maintain the same background EMG for all loads, still the m o n o t o n i c nature of input-output curves was true for all children tested. However, very few younger children were tested for 4 loads. Most o f them gave up after 2 or 3 loads. Reaction times

In order to measure kinaesthetic reaction

A gradual neural development of reflex pathways in humans has been demonstrated above. In adults the longer-latency reflex c o m p o n e n t receives input from the two separate reflex pathways represented by M2 and M3 peaks (Bawa and Tatton 1979). The greater duration of the LL c o m p o n e n t is n o t dependent on the duration of the step-load which was varied between 100 and 400 msec. One may suggest the presence of another c o m p o n e n t which becomes inhibited with development. This possibility seems less likely since the decrease in duration of the LL comp o n e n t is gradual rather than abrupt. The next possibility is that both the M2 and M3 responses are spread out in time. One cannot strictly assume lower conduction velocities in children since the onset times of both the SL and L L components are much shorter in children, as would be expected from normal condition velocities and shorter conduction distances. Yet the possibility exists t h a t n o t all axons are conducting at their optimal velocities; their diameters and myelination are still developing. The contribution of the peripheral axons can be ruled out since they attain their optimal conduction

254 velocities earlier. Thomas and Lambert (1960) demonstrated a sharp increase in ulnar and peroneal m o t o r axon conduction velocities during the first 12 m o n t h s followed by a slow increase up t o 5 years. By the age of 5 years, conduction velocities reach adult-like values. On the sensory side the peripheral neurones attain adult-like conduction velocities in the first 18 months after birth (Desmedt et al. 1973). Therefore the development is central. Neuroanatomical data show that myelination of different areas of the CNS is completed at different stages of life and proceeds late into adulthood {Yakovlev and Lecours 1967; Rabinowicz 1979). In addition to the conduction velocities, the spread m a y also be due to weaker synaptic connections in younger children as a result of poorer synaptic transmission, fewer synapses or the absence of a facilitatory input. The later development of inhibitory function in the CNS may also account for the elongated M2-M3 EMG responses (Traverthen 1979). Given the appropriate onset latency of the LL component, one may then assume optimally developed synapses and conduction velocities and say that the lack of inhibition allows longer activity in the central pathways and/or the motoneurones. Similar elongation of tendon jerks in preterm infants has been reported by Schulte et al. {1969) and has been attributed to the lack of inhibition in the spinal cord. The individual variation in age observed for the LL reflex development is also seen in the anatomical studies (Rabinowicz 1979). If one were to take precentral gyrus as one o f the structures in the efferent limb of the LL reflex arc {Phillips 1969; Marsden et al. 1976) then the development of the LL c o m p o n e n t between the ages o f 6 and 8 years matches the anatomical development of the cortex (Rabinowicz 1979). Recent studies by Laszlo and Bairtow {1980) on kinaesthetic sensitivity of children report that children learn to differentiate between position and m o v e m e n t at 7 years of age. Desmedt et al. (1976) have reported that the development of somatosen-

P. BAWA sory evoked potentials (SEPs) continues up to the first 8 years and have attributed it to an increase in the conduction velocity of the central pathways. However, the development of SEPs and LL reflex component during the first 8 years does not necessarily imply the development of the same neural pathway. The former shows an abrupt change during the first year and then a gradual change up to 8 years. The LL component, on the other hand, shows a sudden change-between 6 and 8 years of age. The large scatter observed in the above data has physiological and experimental contributions in addition to the measurement error. These include the conduction distances, variability in afferent conduction velocities, effectiveness of central processing, dynamics of the applied load and state of central excitability of the subject. The visco-elastic properties of the tissue being perturbed must vary among children and must also be considerably different from that of adults. Higher loads which inherently include higher velocity and acceleration information to the afferents result in more clearly defined response peaks than do lower loads. This is attributed to the more synchronous firing of the afferents and other elements of the reflex arc. In adults, the onset of the LL c o m p o n e n t has a range of 15 20 msec depending on the size of the subject. Children whose CNS matures early but are still small, show narrower SL and LL components as compared to taller adults. The LL c o m p o n e n t has a higher gain and hence a greater duration during the 'compensate' task than in the 'passive' task (Bawa and Tatton 1979). Since it was difficult for most children to follow a given instruction, they generally reacted in a very slow-compensating manner. Therefore, the gain could not be categorized as 'passive' or 'compensating'. This also contributed to the scatter of data. Is the long duration of the longer-latency reflex just simply a reflection of the response of an undeveloped nervous system, or is it functionally useful? In other words, is the

REFLEX DEVELOPMENT gain of the reflex loop higher in the children than in the adults to make up for the slower load compensating voluntary reactions? It has been suggested by Bawa and Tatton (1979) that the LL component recruits faster motor units. Therefore, if the faster motor units are not developed to generate maximal tension, then the higher central gain of the reflex arc would make up fc.r the lower tension development by the muscle fibres. Thus a longer duration LL component would compensate for slower reaction times and less developed motor units. In adult human subjects and monkeys, both the single motor unit and surface EMG data show that the magnitude of the shorter and longer reflex responses varies directly with the magnitude of the input load (Tatton and Bawa 1977). This is also true in children as demonstrated in the present work. Simple reaction times involve more voluntary processing for the motor output than do the reflex responses. Hence, one may expect the simpler reflex processing to develop earlier than the optimal processing for voluntary reactions, as has been seen in this study. However, it is not suggested that spinal reflex -* longer-latency reflex -* simple kinaesthetic reaction time is the strict sequential development of the motor system. There could be other circuits maturing at the same time, e.g., walking, running, speech, writing and hand-eye coordination. But it seems that the more 'automatic' or 'hard-wired' circuits develop earlier than the more 'open' circuits where more elaborate processing may be required.

Summary In adult human subjects torque motor imposed angular displacements of the upper limb joints result in two major reflex EMG components as identified by their latency. The shorter latency (SL) component is probably the spinal stretch reflex and the longer latency (LL) reflex component may involve

255 supraspinal structures. Tendon jerk, arising via the spinal reflex pathway, is present in children at birth. In this study the presence and the development of the LL component in wrist flexors was investigated in children between the ages of 2 and 13 years. Kinaesthetic reaction times were tested simultaneously. In young children, the duration of the LL component was much longer than that in adults. The duration decreased slowly from 2 to 6 years, following which a relatively abrupt decrease between the ages of 6 and 8 years took place. After 8 years of age responses looked more adult-like. Kinaesthetic reaction times attained adult-like values after 10 years of age. Various possibilities underlying these observations are discussed.

Rdsumd Ddveloppement nerveux chez l'enfant: dtude neurophysiologique Chez des sujets adultes auxquels des ddplacements angulaires des articulations des membres supdrieurs ont dtd impos~s par un couple moteur, on observe deux composantes principales des rdflexes EMG identifides par leur latence. La composante de courte latence correspond probablement au rdflexe d'~tirement spinal et la composante plus tardive du rdflexe tardif pourrait mettre en jeu des structures supraspinales. Le rdflexe tendineux, qui se produit via la voie du rdflexe spinal, existe chez l'enfant d~s la naissance. Dans cette dtude, la presence et le ddveloppement de la composante tardive au niveau des muscles fldchisseurs du poignet ont dt~ examinds chez des enfants de 2 ~ 13 ans. Les temps de r~actions kinesthdtiques ont dtd testds simultandment. Chez les jeunes enfants, la dur~e de la composante tardive est beaucoup plus longue que chez les adultes. Cette durde diminue lentement de 2 ~ 6 ans, apr~s quoi, une diminution relativement abrupte survient entre 6 et 8 ans. Apr~s l'~ge de 8 ans, les rdponses ressem-

256

blent ~ celles enregistrdes chez l'adulte. Les temps de rdactions kinesthdtiques rejoignent ceux de l'~ge adulte aprds l'~ge de 10 ans. Diverses possibilitds sous-jacentes ~ ces observations sont discutdes. This work was supported by the B.C. Health Care Research Foundation. I am grateful to Dr. R.G. Lee for the use of his computer and to Dr. R.B. Stein for the torque motor. Technical assistance by Mr, David White is appreciated.

References Bawa, P. and Tatton, W.G. Motor unit responses in muscles stretched by imposed displacements of the monkey wrist. Exp. Brain Res., 1979, 37: 417-437.

Bergstrom, R.M. Electrical parameters of the brain during ontogeny. In: R.J. Robinson (Ed.), Brain and Early Behaviour: Development in the Fetus and Infant. Academic Press, New York, 1 9 6 9 : 1 5 - 41. Desmedt, J.E., Noel, P., Debecker, J. and Nameche, J. Maturation of afferent conduction velocity as studied by sensory nerve potentials and by cerebral evoked potentials. In: J.E. Desmedt (Ed.), New Developments in Electromyography and Clinical Neurophysiology, Vol. 2. Karger, Basel, 1973 : 52--63. Desmedt, J.E., Brunko, E. and Debecker, J. Maturation of the somatosensory evoked potentials in normal infants and children, with special reference to the early N 1 component. Electroenceph. clin. Neurophysiol., 1976, 40 : 43--58. Eeg-Olofsson, O. The development of the electroencephalogram in normal children and adolescents from the age of 1 to 21 years. Acta paediat. scand., 1970, 208 (Suppl.): 1--46. Faulkner, F. and Tanner, J.M. (Eds.) Human Growth: Neurobiology and Nutrition. Plenum Press, New York, 1979. Jacobson, M, Developmental Neurobiology. Plenum Press, New York, 1978. Laszlo, J.I. and Bairtow, P.J. The measurement o f kinaesthetic sensitivity of children and adults. Develop. Med. Child Neurol., 1980, 22: 454--464. Lecours, A.R. Myelogenetic correlates of the development of speech and language. In: E,H. Lenneberg

and E. Lenneberg (Eds.),Foundations of Language Development: a MultidiseiplinaryApproach. UniversityPublishers,N e w York, 1975: 75--94. Marsden, C.D., Merton, P.A. and Morton, H.B. Stretch reflex and servo action in a variety of human muscles. J. Physiol. (Lond.), 1976, 259: 531--560.

P. BAWA Petersen, I. and Eeg-Olofsson, O. The development of the electroencephalogram in normal children from the age of 1 through 15 years. Neurop~diatrie, 1970, 2--3: 247--304. Petersen, I., Sellden, U. and Eeg-Olofsson, O. The evolution of the EEG in normal children and adolescents from 1 to 21 years. In: A. R~mond (Ed.), Handbook of Electroencephalography and Clinical Neurophysiotogy, Vol. 6B. Elsevier, Amsterdam, 1975: 31---68. Phillips, C.G. Motor apparatus of the baboon's hand. Proc. roy. Soc. B, 1969, i 7 3 : 1 4 1 174. Purpura, D.P. Normal and aberrant neuronal development in the cerebral cortex of human fetus and young infant. In: N.A. Buchwald and M.A.B. Brazier (Eds.), Brain Mechanisms in Mental Retardation. Academic Press, New York, 1 9 7 5 : 1 4 1 169. Rabinowicz, T. The differentiate maturation of the human cerebral cortex. In: F. Faulkner and J.M Tanner (Eds.), Human Growth: Neurobiology and Nutrition. Plenum Press, New York, 1979: 97-144 Schulte, F.J., Michaelis. R., Linke, [. and Nolte, R. Motor nerve conduction velocity in term, preterm and small-for-dates and newborn infants, Pediatrics, 1968, 42: 17--26. Schulte, F.J., Linke, I.. Michaelis, R. and Nolte, R. Excitation, inhibition and impulse conduction in spinal motoneurones of preterm and small-fordates newborn infants. In: R.J. Robinson (Ed.), Brain and Early Behaviour. Academic Press, London, 1969: 87--114. Scott, J.P. Critical periods in organisational processes. In: F. Faulkner and J.M. Tanner (Eds.), Human Growth: Neurobiology and Nutrition. Plenum Press, New York, 1979: 223--241. Tatton, W.G. and Bawa, P., Input-output relationships for 'long-loop' reflexes: alterations by preexisting loads and volitional set. Canad. Physiol., 1977, 8: 67. Tatton, W.G. and Bawa, P. Input-output properties of motor unit responses in muscles stretched by imposed displacements of the monkey wrist. Exp. Brain Res., 1979, 37: 439--457. Thomas, J.E. and Lambert, E.H. Ulnar nerve conduction velocity and H-reflex in infants and children. J. appl. Physiol., 1960, 15: 1--9. Traverthen, C. Neuroembryology and the development of perception. In: F. Faulkner and J.M. Tanner (Eds.), Human Growth: Neurobiology and Nutrition. Plenum Press, New York, 1979 : 3--96. Yakovlev, P.I. and Lecours, A.R. The myelogenetic cycles of regional maturation of the brain. In: A. Minkowski (Ed.), Regional Development of the Brain in Early Life. Blackwell, Oxford, 1967' 3--70.