Brain 1999 Hadders Algra 727 40

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Brain(1999), 122, 727740

Periventricular leucomalacia and preterm birth havedifferent detrimental effects on postural

adjustmentsMijna Hadders-Algra,1,2,3 Eva Brogren,1,2 Miriam Katz-Salamon1,2 and Hans Forssberg1,2

Departments of 1Woman and Child Health and Correspondence to: Dr Mijna Hadders-Algra, University2Neuroscience, Karolinska Institute, Stockholm, Sweden and Hospital Groningen, Developmental Neurology, CMC IV,3Department of Medical PhysiologyDevelopmental 3rd floor, Hanzeplein 1, 9713 GZ Groningen,

Neurology, University of Groningen, Groningen, The Netherlands

The Netherlands E-mail: [email protected]

SummaryPostural adjustments during sitting on a moveable

platform were assessed by means of multiple surfaceEMGs of neck, trunk and leg muscles and kinematics in

three groups of children, aged 1124

12years. The first group

consisted of 13 preterm children (born at a gestational

age of 2534 weeks), whose neonatal ultrasounds had

shown distinct lesions of the periventicular white matter

(PWM). The second group was the preterm control group,

consisting of 13 preterm children with normal neonatal

brain scans, matched to the PWM group with respect to

gestational age at birth, birth weight, sex and age of

postural assessment. The third group was formed by 13

healthy children born at term and matched to the PWM

group with respect to sex and age at examination. Inaddition to the postural assessment an age-specific

neurological examination was carried out. Three of the

Keywords: prematurity; periventricular leukomalacia; postural control; EMG; neurological development

Abbreviations: HAM hamstring muscles; NE neck extensor muscles; NF neck flexor muscles; PWM periventricular

white matter; RA rectus abdominis muscle; RF rectus femoris muscle; TE/LE thoracic and lumbar extensor muscles

IntroductionPreterm infants have a higher risk for the development ofmotor dysfunctions than babies born at term. The motor

dysfunctions range from the various forms of cerebral palsyto minor motor disabilities (Escobar et al., 1991; Ornsteinet al., 1991) which vary with age. During infancy, minordysfunctions especially are found in the regulation of muscletone (transient dystonia). The muscle tone dysregulationmainly affects the axial muscles and results in ahyperextended posture of neck and trunk (Drillien, 1972;Touwen and Hadders-Algra, 1983; De Groot et al., 1992).At school-age and during adolescence the most consistentlyreported minor dysfunctions are abnormalities in posturalcontrol and balance, co-ordination problems, and a poor

Oxford University Press 1999

children of the PWM group developed a cerebral palsy

syndrome, nine showed minor neurological dysfunctionand one child was neurologically normal. In the preterm

control group one child showed minor neurological

dysfunction, while the remaining 12 children of this group

and all children of the full-term group were neurologically

normal. The postural assessment revealed that preterm

birth was associated with two types of postural

dysfunction. One dysfunction was related to the presence

of a PWM lesion and consisted of a limited repertoire of

response variation. The other dysfunction was not related

to the presence of a PWM lesion, but to preterm birth

itself. It consisted of a change in the ability to modulate

the postural responses. Preterm children showed a higher

sensitivity to platform velocity than full-term children,and they lacked the capacity to modulate EMG amplitude

with respect to initial sitting position.

quality of gross and fine movements (Hadders-Algra et al.,1988; Largoet al., 1990, Soorani-Lunsinget al., 1993; Olse

n

et al., 1997). Pre- and perinatal brain lesions play a role inthe genesis of the major and minor motor dysfunctions, butthe relationship between the documented lesions and thefunctional outcome is not a simple one. Periventricularleukomalacia and haemorrhagic parenchymal lesions areassociated with a high risk for the development of cerebralpalsy, but not all infants with these types of brain lesion dodevelop a neurological handicap, nor can infants withoutsuch lesions be considered as free from risk for cerebralpalsy (De Vries et al., 1985; Fazzi et al., 1994; Rademakeret al., 1994). Likewise, an association has been found


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728 M. Hadders-Algraet al.

between the duration of periventricular echo densities and

the development of minor neurological dysfunction

(Jongmanset al., 1993), but children can also develop minor

motor dysfunction in the absence of abnormal ultrasound or

MRI scans of the brain (Roth et al., 1993; Weisglas-Kuperus

et al., 1994; Olse

n et al., 1997).

Deviant postural control can be considered as one of thekey dysfunctions in the major and minor motor abnormalities

of preterm children. Therefore, we decided to study the

relationship between brain lesion, neurological outcome and

postural control in children born before term age. Postural

control is a task of reputed complexity, as the nervous system

has to deal with a redundancy in degrees of freedom due to

the multitude of participating muscles and joints. Bernstein

(1935) suggested that the motor problem posed by the surplus

in degrees of freedom, can be solved by organizing motor

output with the help of synergies. These enable the nervous

system to reduce the number of afferent signals needed to

generate and guide an ongoing movement and to reduce thenumber of efferent activities involved in motor control. This

means that the brain does not need to specify each single

muscle contraction, but can have access to neuronal

representations of movements with prestructured motor

commands. The nervous system indeed organizes postural

control with the help of synergies/flexible synergies, which

can be fine-tuned to task-specific conditions (Horak and

Nashner, 1986; Keshner et al., 1988; Hirschfeld and

Forssberg, 1991; Allum et al., 1993; Macpherson, 1994).

Forssberg and Hirschfeld (1994), who studied postural

adjustments in sitting adults, formulated a functional model

on the organization of postural adjustmentsthe so-called

central pattern generator model. In general, central patterngenerator activity is used to describe the neural organization

of rhythmical movements like locomotion, respiration and

mastication. The central pattern generators refer to neural

networks co-ordinating the activity of many muscles. The

activity level in these networks is controlled by reticulospinal

neurons, whereas segmental afferent input results in

modulation of the output pattern (Grillner et al., 1995).

Essential to the central pattern generator model for postural

adjustments is its organization in two levels. The first level

is involved in the generation of the basic direction-specific

response pattern. Direction-specificity means that

perturbations inducing a forward sway of the body elicit a

response pattern in the muscles on the dorsal side of the

body, while perturbations inducing a backward body-sway

evoke responses in the ventral muscles. In sitting adults,

somatosensory information generated by pelvis rotation

triggers the activity of the direction-specific muscles. The

second level is involved in the fine-tuning of the basic

response pattern on the basis of multisensorial afferent input

from somatosensory, visual and vestibular systems. This

modulation can be achieved in various ways, for instance,

by changing the order in which the agonist muscles are

recruited (e.g. in a caudo-to-cranial sequence or in the reverse

order), by modifying the size of the muscle contraction (EMG

amplitude) or by altering the degree of antagonist activation.

In a recent series of ontogenetic studies we demonstrated

that three phases can be distinguished in the normal

development of postural adjustments during sitting (Hadders-

Algra et al., 1996a, 1998). The first phase is the primary

variability phase, which is characterized by a large variationin direction-specific postural response patterns. The variation

is especially noticeable in the combinations in which the

postural muscles are activated. During this phase, which

starts at pre-sitting age, postural adjustments cannot be

adapted to task specific conditions. At the end of the first

phase, around 910 months, the response pattern including

all direction-specific muscles (the complete pattern) is

selected, a process resulting in a decrease in response

variation. The second phase is the transient toddling phase,

which occurs between 910 months and 2123 years. It is

charaterized by an invariant use of the complete direction-

specific response patterns and a relatively high amount of

antagonist activation. These high-energy demanding postural

adjustments can be adapted to task specific conditions, such

as various sitting positions or different velocities of the

perturbation. During this phase the focus of adaptation lies

close to the support surface, i.e. it affects especially the

caudally located muscles. The third phase is the secondary

variability phase, during which the variation in the direction-

specific response patterns returns. The postural adjustments

are less energy demanding and consist of a variable activation

of agonistic and antagonistic postural muscles. Task specific

modulation is realized in a different way than during the

previous phase, as the focus of adaptation is now located in

the neck muscles. This phase starts at 21

23 years and

continues into adulthood, with further refinements in

adaptational abilities occurring with increasing age (cf. Berger

et al., 1985, 1995).

In the present study we assessed postural adjustments

during sitting on a moveable platform in three groups of

children, aged 112412 years: a group of preterms, whose

neonatal ultrasound scans of the brain showed distinct

periventricular white matter (PWM) pathology, a group of

preterms with normal ultrasound brain-scans and a group of

healthy children born at term. The following questions were

addressed. (i) Do PWM lesions result in (a) an absence of

the direction-specificity of postural adjustments or, in case

direction-specific postural adjustments are present, adominance of the response pattern, in which all direction-

specific muscles participate (the complete response pattern),

beyond the age of 2123 years, (b) an increased activation of

antagonist muscles as a simple solution to cope with postural

instability, (c) a delayed activation of the postural muscles,

and (d) a deficit in the ability to modulate the EMG amplitude

of the postural muscles? (ii) Do the abnormalities in postural

adjustments during platform perturbations correlate better

with findings at the neurological examination than with the

site or the size of the PWM lesions? (iii) Does preterm birth

itself affect the development of postural adjustments?


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Postural adjustments in preterm children 729

Table 1 Characteristics of preterm infants

With brain lesions Without brain lesionsPWM group PT control group

Age at assessment (years) 1.54.5 (median 3) 1.54.5 (median 3)Sex (M/F) 9/4 9/4

Gestational age at birth (weeks) 2534 (median 28) 2534 (median 28)Birthweight* (g) 7071463 (median 977) 7801135 (median 1135)Small-for-gestational age (n) 2 2Respiratory distress syndrome* (n) 8 4

*MannWhitney: no significant difference between the two groups.

Methods

SubjectsThree groups of 13 children, with ages varying from 1124

12

years, were assessed: two groups of preterm children and

one group of children born at term. The preterm children

were members of the Stockholm Neonatal Project, in which

series of infants with a birthweight 1500 g were admitted

to the neonatal unit of the Karolinska Hospital in Stockholm

during the period September 1988 to February 1993

(Lagercrantz et al., 1997). We selected from this series all

surviving children with distinct PWM lesions on the serial

neonatal ultrasound scans of the brain (Hesser et al., 1997).

This resulted in a study group of 13 children (PWM group),

whose ultrasounds either showed PWM lesions graded as

W3 (periventricular cyst formation, irrespective of the

appearance of the initial white matter echo densities) or W4

[large, intense echo densities extending into the deep layers

of the white matterincluding cases which in the Papile

classification system (Papile et al., 1978) would have been

categorized as grade IV haemorrhages]. Seven children of

the PWM group exhibited signs of haemorrhages in the

periventricular germinal matrix and in the ventricles (Table

2). For each PWM child we selected two control subjects:

(i) a preterm control from the Karolinska cohort with a

normal neonatal ultrasound scan of the brain, who was

matched to the PWM child with respect to gestational age at

birth, birthweight, sex and age at follow-up (pre-term control

group), and (ii) a healthy full-term child, matched to the

PWM child for sex and age at follow-up (full-term group).

Details on the characteristics of the preterm children are

listed in Table 1.

The children born at term were recruited amongst

acquaintances of the investigators. They had a birthweightwhich was appropriate for their gestational age and they

were free from developmental dysfunction. All parents gave

informed consent and the procedures were approved by the

medical ethical committee of the Karolinska Hospital. Prior

to each assessment on the platform, one of the investigators

(M.H.A.), who was blind with respect to the group

membership of the children, assessed neuromotor

development by means of Hempels examination technique

(Hempel, 1993). This examination technique is largely based

on a standardized, free field observation of spontaneous

motor behaviour and pays special attention to the presence

of minor neurological dysfunction. We also recorded the

body length and body weight of the children.

Experimental designThe protocol, recording and analyses techniques were similar

to those described in Hadders-Algra et al. (1996a). The

procedures were as follows.

ProtocolThe children sat on a moveable flat platform, which produced

a standard series of 32 random forward and backward

translations with an amplitude of 6 cm. It turned out that one

child was unable to sit independently. He was supported by

the experimenter. Shortly before the trial the support was

withdrawn, ensuring that the child was freely sitting during

the perturbation. Immediately after the trial, his support was

re-established. The support-withdrawal-support procedure

was also used in the study of non-sitting infants and turned

out to produce a body-sway in the direction opposite to the

platform translation (Hadders-Algraet al.,1996a). A standard

block of trials consisted of 16 slow perturbations (forward:

120 mm/s, 500 ms duration; backward: 180 mm/s, 333 ms

duration), followed by 16 fast ones (forward: 180 mm/s, 333

ms duration; backward: 220 mm/s, 272 ms duration), stimuli

that were well tolerated by young children. A higher platform

velocity was chosen for backward than for forward

translations because of the different response threshold for

the two situations (Forssberg and Hirschfeld, 1994). The

forward and backward trials were presented in a random

order, with a variable inter-trial interval of about 810 s.

EMG and kinematic recordingsSurface EMGs were recorded from the sternocleido-

mastoideus [neck flexor (NF)], rectus abdominis (RA), rectus

femoris (RF), neck, thoracic and lumbar extensor muscles

(NE, TE and LE) and hamstrings (HAM) on the left side of

the body. TE and LE were analysed together (TE/LE), as

they were usually activated in concert.

Additionally, we were able to record kinematics

simultaneously with the EMGs in five of the PWM children,

eight of the preterm control children and five of the full-term


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children. The kinematic data were recorded by an ELITE

system in a two camera configuration for 3 s, starting 1 s

prior to perturbation. Reflective markers were put on the left

side of the body (i) on the caput mandibulae, (ii) 1 cm in

front of the angulus mandibulae, (iii) on the anterior superior

iliac spine, and (iv) on the trochanter major. Additionally,

three markers were put on the lateral side of the platform.Off-line data processing consisted of the calculation of spatial

angles for the head (by a vector between markers 21), the

pelvis (markers 43) and the body sway (markers 41) in

relation to the horizontal axis. The ELITE data frequently

were incomplete, because the two camera systems often lost

track of a marker due to arm movements or slight rotations

of the head.

Data acquisition and analysisEMG analysis. The signals from the platform and the EMGs

were sampled at 800 Hz, digitized at 12-bit resolution and

stored on SC/ZOOM, a dedicated signal analysis computer

system (Department of Physiology, Ume University,

Sweden). The software program converted the signals to

root mean square with a 6 ms moving window averaging

technique. A graphics terminal was used to define

interactively EMG events for each trial separately. The

interactive assessment offered the possibility to differentiate

EMG bursts from regularly occurring electrocardiac activity,

which especially was present in RA. EMG base-line activity

was defined as the mean activity recorded 500 ms prior to

each perturbation. A perturbation related EMG burst was

considered to be present when, during the time the platform

moved, a burst occurred lasting at least 30 ms and exceeding

base line activity by 2 SD. Likewise EMG inhibition was

defined as a drop of activity below 1.5 SD of the baseline

level, which lasted for at least 30 ms.

The first step in the analysis consisted of the documentation

of muscle activation patterns by describing the presence of

bursts and inhibition in the recorded muscles. This resulted

for each child in each condition (forward-slow, forward-fast,

backward-slow, backward-fast) in rates of EMG events per

muscle and rates of muscle activation patterns. The response

rates were calculated for each child and each condition by

dividing the number of trials with a response by the total

number of trials. Response rates were calculated for the

direction-specific agonist muscles and for the antagonistmuscles. The activity of the direction-specific agonist muscles

was also expressed in patterns of muscle activation, i.e. in

the combinations in which agonists were activated in concert

(see Fig. 4). This resulted in a response rate of specific

patterns and in a pattern variation index (number of different

patterns divided by the number of trials).

The next step consisted of the analysis of EMG amplitudes

and latencies. Latencies were defined as the time-interval

between the onset of platform movement and the onset of

an EMG response. In order to be able to compensate for the

age-dependent changes in body-size, absolute latencies were

also transformed into relative latencies by dividing latencies

(in milliseconds) by body length (in metres). Amplitudes

were computed by calculating the mean amplitude during a

period of 100 ms and 400 ms, respectively, starting at the

onset of the first burst belonging to the postural response.

The baseline activity was subtracted from these raw mean

amplitude values. The amplitude during the 100 ms periodreflects the power of muscle activation during the early phase

of the response, whereas the amplitude during the 400 ms

period represents the overall activity, including the activity

based on long latency processes of presumed transcortical

origin (Marsdenet al.,1983; Palmer and Ashby, 1992). Mean

latencies and amplitudes were calculated for each child in

each condition separately. The effect of platform velocity on

EMG amplitude was expressed by means of an EMG velocity

ratio consisting of the ratio between mean EMG activity

during fast translations and that during slow translations.

The effect of brain lesions was evaluated with help of the

matched pairs design allowing for the use of the Wilcoxon

test. For the analysis of within-group differences (e.g. type

of brain lesion in preterm children, type of neurological

condition at follow-up) and the differences between all

preterm and full-term children the MannWhitney test was

used.

Kinematic analysis. Focus was on the angular values at

movement onset and the angular displacements (the difference

between peak value and onset value) of head, pelvis and

body sway. Pearsons correlation coefficient was used for the

calculation of correlations between initial sitting position and

angular displacement on the one hand and muscle activity

on the other hand. Before entering the angular values at

movement onset and the EMG amplitudes into the

correlations, the data were normalized. The initial angles

were normalized by subtracting the childs mean initial angle

from the actual trials value. The EMG amplitudes were

normalized with respect to the maximal amplitude (100%)

produced by the child in the relevant muscle and time-window.

Throughout the study differences and correlations where

P 0.05 were considered to be statistically significant. For

brevitys sake only the data during the fast translations will

be reported, unless there is a special need for the data

during the slow trials (e.g. in the evaluation of a platform

velocity effect).

Results

Neurological outcomeOnly one of the preterm children with a PWM lesion had no

neurological dysfunctions at follow-up. Nine children of the

PWM group showed minor neurological dysfunction and

three had developed a cerebral palsy, each of them a different

form: a spastic diplegia, a spastic hemiplegia and a spastic

tetraplegia with mental retardation and epilepsy. The children

with the diplegia and hemiplegia were able to walk without


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Fig. 1 Neurological outcome at pre-school age in preterm childrenwith and without PWM lesions and full-term children. Numberswithin brackets indicate the number of children in each group.US ultrasound findings; no data available; W3 periventricular cyst formation, without () and W3 with ()obvious loss of PWM; W4 large, intense echo densitiesextending into the deep layers of the white matter. CP cerebralpalsy; FT full-term; MND minor neurological dysfunction;N normal; PT preterm; MND hypotonia: mild diffusehypotonia and collapsed posture; MND block: see text; MNDawkward: movements (including speech movements) lack co-ordination and planning.

aids; the child with the tetraplegia was severely handicapped

and could not sit without help. The most frequent form of

minor neurological dysfunction was the so-called block

type of minor neurological dysfunction, which was

characterized by a stiff and block-like motility, an absence

of spontaneous rotations during standing and walking, and

mild problems in balance control. Muscle tone and tendon

reflexes were normal, but when testing the resistance against

passive movements, muscle tension rose rapidly when minor

increases in the velocity of the testing movements occurred.

In the preterm control group 12 children had a normal

neurological condition at pre-school age and one child showed

minor neurological dysfunction. All children born at term

were free from neurological dysfunction.

Neurological outcome was clearly related to the presence

and the severity of the brain lesions on the neonatal

ultrasounds (Fig. 1 and Table 2). Outcome was worse in case

of a W4 lesion or a W3 lesion with evident signs of tissue

loss in the PVM. No obvious relationship was present between

outcome and the presence and type of the asymmetry of

the lesions.

Direction-specific muscle activityForward and backward translations of the platform induced

a sway of the body in the opposite direction in all children.

All but one of the children were able to maintain balance

during the platform perturbations. They showed direction-

specific postural adjustments, consisting of a preference for

the activation of the ventral muscles during a backward sway

of the body and a primary activation of the dorsal postural

muscles during a sway of the body in the opposite direction

(Figs 2 and 3).

This basic level of postural control was absent in the child

with spastic tetraplegia, who was unable to sit without help

(Figs 2 and 3). He showed no responses during forward

translations. During backward translations he reacted with

an occasional weak activation of the direction specific dorsal

muscles, most frequently of the NE (36% of the trials),

which was followed by a late and clear response in the

ventral muscles.The activation rates of the individual direction-specific

agonist muscles during forward and backward translations

did not differ between the three groups. A difference was,

however, present in the rate of extensor inhibition during

forward translations. Such an extensor inhibition is in young

children part of the response pattern during forward

translations, but with increasing age extensor inhibition

gradually disappears (Fig. 2). Extensor inhibition occurred

in the present full-term children older than 212 years in 12%

of the trials (median value). When excluding the non-

responding tetraplegic child, the rate of extensor inhibition

was 90% in the group of children with PWM lesions over

212years, indicating a significant difference with the full-term

group (Wilcoxon, P 0.05). The rate of extensor inhibition

in the preterm control group fell in between that of the other

two groups (62%), thereby showing no statistically significant

difference with either.

Besides the response rates of the individual agonist

muscles, we also evaluated the way in which the agonists

were activated in concert. This resulted in a large variety of

response patterns (Fig. 4).

None of the patterns during forward or backward

translations occurred more often in a specific group of

children. This also held true for the patterns in which all

agonists participated (NF RA RF and NE TE/LE

HAM, respectively), patterns which are known to show

developmental changes (Hadders-Algra et al., 1998). Still a

remarkable difference was found between the PWM and

control groups in the response patterns during forward

translations. The difference was found in the variation of the

patterns within an individual child (Fig. 4). The response

variation during forward translations was significantly lower

in the PWM group than in both control groups, as was

reflected by a significant difference in the pattern variation

index (Fig. 5). The pattern variation index was related to the

presence of a PWM lesion, but not to its severity. Neither

did the pattern variation index show a relationship with the

neurological condition at follow-up. The pattern variationindex during backward translations did not differ between

the three groups.

Antagonist muscle activityDuring normal development antagonistic muscle activity is

transiently present between 9 months and 2123 years,

especially during forward translations (Hadders-Algra et al.,

1998). All full-term and the majority of preterm children

followed this developmental pattern of antagonist activity.

Two children were an exception to this general rule: the child


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Table 2 Ultrasound brain lesions and neurological outcome

Child Neonatal ultrasound scans of the brain* Follow-up

Haemorr. PWM Localization Asym. Tissue loss Age (years) Neurological condition

1 B3 W4 A M P R L 3.0 CP, spastic hemiplegia R

2 B3 W4 A M P R

L

3.5 CP, spastic diplegia3 B3 W4 A M P R L 3.5 MND, block-like motility

4 B3 W3 A M P R L 4.5 CP, spastic tetraplegia5 B3 W3 A M R L 2.0 MND, block-like motility6 B2 W3 A R L 3.0 MND, block-like motility7 B2 W3 A R L 4.5 Normal8 B0 W3 M R L 3.0 MND, block-like motility9 B0 W3 A R L 2.5 MND, awkward motility10 B0 W3 A M P R L 3.0 MND, mild hypotonia11 B0 W3 A M P R L 2.0 MND, block-like motility12 B0 W3 A M R L 4.5 MND, block-like motility13 B0 W3 M L R 1.5 MND, block-like motility

*Ultrasound classification according to Hesser et al., 1997 (see Methods). Haemorr. haemorrhages: germinal matrix (GMH) andintraventricular (IVH): B0 no haemorrhages, B2 GMH IVH without ventricular dilatation, B3 GMH IVH with ventriculardilatation; PWM periventricular white matter lesions; Localization: A anterior, M middle, P posterior; Asym. asymmetries:

L left, R right. borderline diplegia: no overtly handicapping condition, minimal hypertonia of legs, brisk tendon reflexes,Babinski R. CP cerebral palsy; MND minor neurological dysfunction.

with spastic diplegia (312 years) and the child with spastic

hemiplegia (3 years). These two children showed considerable

antagonist activity during forward translations, with NE, TE

and HAM showing a response in at least 50% of the trials

(in the hemiplegic child on both sides of the body). They

also showed unusual antagonist activity during backward

translations. In the diplegic child this antagonist activity was

restricted to the leg muscles (RF was activated in 30% of

the trials), whereas in the hemiplegic boy, the antagonist

activity occurred bilaterally from leg to neck (RF 100%, RA

5062%, NF 1244%). The pattern of antagonistic activity

was variable in all groups, with a pattern of co-activation

prevailing in the neck and leg muscles, and a pattern of

reciprocal activity dominating the trunk muscles.

Timing of agonist activityUp until 412 years of age, the relative latencies to agonist

activation during forward and backward translations decrease

significantly with increasing age. The latencies are not

affected by the velocity of the perturbation (Hadders-Algra

et al., 1998) (Fig. 6). All children of the full-term and preterm

control groups had age-adequate response latencies, whilethe relative latencies of the children in the PWM group, who

were older than 2 years, were considerably shorter than those

of the full-term group [during forward translations: NF, P

0.04; RA, P 0.09 (ns); RF, P 0.01; during backward

translations: NE, P 0.01; TE, P 0.07 (ns); HAM, P

0.14 (ns); Fig. 6]. The relative latencies were not related to

either the severity of the PWM-lesion or the neurological

condition at follow-up. The finding of reduced latencies in

children with significant brain lesions was supported by the

presence of a significant asymmetry in the latencies in the

child with spastic hemiplegia. The latencies on the affected

side of his body were significantly shorter than those on the

unaffected side [paired t test, differences during forward

translations: NF, P 0.01; RA, P 0.19 (ns); RF, P

0.01; during backward translations: NE, P 0.05; TE, P

0.38 (ns); HAM, P 0.01].

The sequence in which the agonistic muscles were recruited

during forward and backward translations showed

considerable variation in all groups. The order of muscle

recruitment was not clearly related to the presence or the

severity of a PWM lesion, preterm birth or the neurological

condition at follow-up.

Modulation of agonist EMG amplitudeFrom 9 months onwards children can modulate the EMG

amplitude of the agonistic ventral muscles during forward

translations with respect to platform velocity: a higher

platform velocity results in a moderate, but significant

increase of the EMG amplitudes (Hadders-Algraet al., 1996a,

1998). All children in the present study (except for the

child with the tetraplegia) showed this modulating capacity.

Remarkably, from the age of 212 years onwards, the velocity

effect turned out to be stronger in the preterm children thanin the full-term children. This difference in sensitivity to

platform velocity was reflected by significantly higher

velocity ratios of RA100and RF100(the mean amplitudes over

the first 100 ms of the response) in the preterm than in the

full-term children (Fig. 7). The higher velocity ratios were

found in both groups of preterm children, indicating that this

effect was not related to the presence of PWM lesions, but

to the preterm birth itself. Within the preterm children the

velocity ratios were not related to gestational age at birth,

birthweight or neurological condition.

In none of the children without cerebral palsy, nor in the


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Fig. 2 Response patterns during forward translations. Average activity during eight fast translations. Note the absence of extensorinhibition in the full-term (FT) child of 4 years, the brisk agonist activity and extensor inhibition in the preterm (PT) children (all fromthe PWM group), the antagonist activity in the diplegic and hemiplegic child and the absence of response activity in the tetraplegic child(single trial). MNDA minor neurological dysfunctionawkward; MNDB minor neurological dysfunctionblock; PLF platformdisplacement; NF neck flexors; NE neck extensors; RA musculus rectus abdominis; TE thoracic extensors; LE lumbarextensors; RF musculus rectus femoris; HAM hamstring muscles. Time calibration (horizontal bar): 100 ms; amplitude calibration(vertical bar): 0.4 mV.

child with spastic tetraplegia, was a velocity effect on EMG

amplitude present during backward translations, but the

children with spastic diplegia and spastic hemiplegia did

have such a velocity effect in the dorsal muscles. The boywith spastic diplegia showed significant velocity effects in

NE100 and TE400 (paired t test: P 0.02 and P 0.0001,

respectively) and the boy with hemiplegia demonstrated a

velocity effect bilaterally in TE400and HAM100(pairedttest:

P 0.01 and P 0.02, respectively) and on the unaffected

side in NE100(paired t test: P 0.001).

From 9 months onwards children are also able to modulate

EMG amplitude during forward translations with respect to

sitting position. The modulating effect is brought about by

initial pelvis position. Until about 3 years of age initial pelvis

position affects the amplitude of RF; in older children the

effect moves to NF (Hadders-Algra et al., 1996a, 1998). In

both groups of preterm children this modulating capacity

was totally absent (Fig. 8).

None of the full-term and preterm children showed duringthe present perturbation procedure, which consisted of two

series (a slow series and a fast series) of randomly distributed

forward and backward translations of a similar amplitude,

signs of central set or adaptation due to prior experience

(cf. Horaket al., 1989).

DiscussionThe present study revealed that the neural control of postural

adjustments in preterm children differs from that of age-

matched children born at term. Some of the postural


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Fig. 3 Response patterns during backward translations of the same children as represented in Fig. 2. Average activity during eight fasttranslations. Note the weak responses in the full-term (FT) child of 4 years, the moderate agonist activity in the minor neurologicaldysfunction children and the brisk agonist activity in the diplegic and hemiplegic child. The last recording is a single trial of thetetraplegic child (due to the variable and low agonist activation, the average recording did not show any response). In the present trial aresponse is present in NE and HAM, and after a longer interval there is significant activity in NR, RA and RF. For the abbreviations, seelegend of Fig. 2. Time calibration (horizontal bar): 100 ms; amplitude calibration (vertical bar): 0.4 mV.

dysfunctions were related to neonatal PWM lesions, others

to preterm birth itself. The presence of a PWM lesion was

not only associated with the development of neurological

dysfunctions, but also to deficient spatial and temporal

characteristics of the postural responses. Preterm birthaffected the ability to modulate the EMG responses. During

forward translations preterm children showed a higher

sensitivity to platform velocity than full-term children, but

they lacked the capacity to modulate EMG amplitude with

respect to initial sitting position.

Postural dysfunctions related to PWM lesionsSerious PWM lesions can result in a severely handicapping

condition, in which the subject cannot sit without help. One

of the children of the present PWM group developed such a

condition. His postural adjustments showed a profound

deficit: he did not show distinct direction-specific responses,

indicating that he lacked control at the basic level of postural

organization (cf. Forssberg and Hirschfeld, 1994). The

absence of direction-specificity cannot be attributed to theinability to sit without help, as non-sitting infants of 56

months do exhibit significant direction-specificity (Hirschfeld

and Forssberg, 1994; Hadders-Algra et al., 1996a). However,

the reverse is probably true: it is unlikely that children who

lack direction-specific postural responses develop the ability

to sit independently. Two explanations can be offered for the

absence of direction-specific responses: (i) the circuitries

producing the basic muscle patterns, i.e. the synergies, have

not developed, and (ii) the sensory pathways were not

sufficiently integrated to elicit activity in the synergies.

Variation is a primary property of normal neurological


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Fig. 4 Distribution of response patterns during fast forward translations in the full-term (FT) and the preterm (PT) PWM group. Eachhorizontal bar represents the distribution of response patterns for one subject. The PWM group is ranked according to the severity of theneurological condition at follow-up; the age-matched FT control subjects are displayed on the same horizontal level as the PWMsubjects. N neurologically normal; MND minor neurological dysfunction; MND-H MND with mild hypotonia; MND-B MND-block; MND-A MND with awkward motility; CP-HE cerebral palsy with spastic hemiplegia, A denoting the affected sideand U the unaffected side; CP-DI spastic diplegia; CP-TE spastic tetraplegia. The explanation of the colour-codes is given in B. Inthis panel hatching of a square indicates participation of a muscle in a particular pattern. The unusual diagram should be read as follows.Take for instance, the first (upper row) child of the PWM group, who was exposed to eight fast translations. She responded during onetrial with NF RA, (12.5% black hatching), during three trials with the combination of NF RA RF (37.5% dark green shading)and during four trials she responded with the combination of extensor inhibition and NF RA RF activation (50% red shading).

development, including the development of postural control

(Touwen, 1978; Forssberg, 1985; Edelman, 1989; Hadders-

Algra et al., 1998). A rich variation at an early age allows

the selection of the most appropriate response pattern, which,

as a result of following developmental processes, can be

adapted to task specific constraints (Hadders-Algra et al.,

1996a). Possibly, substantial variation in postural responses,offering the possibility of selection of the best response, is

a prerequisite for the development of the ability to modulate

postural activity. This suggestion is supported by the present

study: the children with a PWM lesion showed a reduced

variation in postural responses, and an inability to modulate

their postural adjustments with respect to the initial sitting

position. Others also noted that a lack of variation, reflected

by the presence of monotonous and stereotyped motor

behaviour, is an early marker of an abnormal neurological

development (Touwen, 1978; Hadders-Algra et al., 1997).

Moreover, a similar lack of variation has been reported

for postural adjustments of children with spastic diplegia

(Brogren et al., 1998).

Animal research demonstrated that early brain lesions

induce complex types of reorganization, the type depending

on the site and the size of the lesion and the subjects age at

the insult (Kolb and Whishaw, 1989). Undamaged parts of

the brain can take over functions of the lesioned parts, butthis may be at the expense of the quality of other functions

served by the hosting tissues (Huttenlocher and Raichelson,

1989; Kolb and Whishaw, 1989). The limited data available

on neural reorganization after early brain damage in humans

confirm the presence of complex patterns of reorganization,

such as the possibility of functional compensation by

undamaged parts of the brain (Brouwer and Ashby, 1991;

Carr et al., 1993). Our data corroborate the idea of complex

reorganization: in all but one of the children with a PWM

lesion the basic level of postural control had developed,

albeit with the help of seemingly simplified neural circuitries


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Fig. 5 Response pattern variation index during fast forwardtranslations in the three groups. The data are presented by ranges(vertical bars), interquartile ranges (shaded boxes) and medianvalues (horizontal bars). The asterisks indicate statistically

significant differences in pattern variation index between thegroups (Wilcoxon): *P 0.05, **P 0.01. FT full term,PT preterm, US-N normal ultrasound scans of the brain,PWM lesion of the periventricular white matter.

containing fewer interneuronal connections. Such simplified

circuitries would generate little variation in the output

patterns, and require relatively little processing time. This is

exactly what we found in the children with a PWM lesion:

less variation in the postural responses and shorter latencies

until response onset.

The shorter latencies (with a reduction in absolute values

of ~10 ms) seem to be at variance with the common finding

of longer latencies to various responses in children with brain

dysfunction. Two factors might explain the discrepancy. First,

differences in the type of the evaluated responses might play

role, e.g. visual or somatosensory evoked potentials or

cutaneomuscular reflexes (Evans et al., 1991; Cooke, 1992;

Taylor, 1992) versus postural adjustments in the present

study. Secondly, the age of the subject appears to be an

important factor. The majority of studies reporting longer

latencies to responses in children with brain dysfunction (e.g .

latencies to somatosensory or visual evoked potentials) have

been performed during the first year of life (Cooke, 1992;

Taylor, 1992). Also in the present study the younger children

tended to have increased latency values, whereas only afterthe age of 2 years were the shorter latencies found (Fig. 6).

This might imply that certain developmental processes in the

nervous system should have occurred (see Hadders-Algra

et al., 1998) before short-for-age latencies to motor responses

in children with brain-damage can be found. This, in turn,

could explain why others, who looked for longer latencies

in sensorimotor responses of children with brain dysfunction,

failed to find unequivocally longer latency values (Evans

et al., 1991; Mu

ller et al., 1992). The short-for-age latencies

could be due to altered polysynaptic spinal pathways induced

by the early damage of the brain (cf. Berger et al., 1985;

Harrison, 1988; Hadders-Algra, 1993; Myklebust and

Gottlieb, 1997).

The children of the PWM group showed more extensor

inhibition during forward translations than the control

children, slightly more than the preterm controls and

significantly more than the full-term controls. A prerequisite

for the manifestation of extensor inhibition in the EMGrecordings is a relatively high tonic background activity in

the dorsal extensor muscles (Hadders-Algra et al., 1996a).

This indicates that the preterm children, and especially those

with a PWM lesion, had a significantly higher tonic activity

in their neck and back muscles. It is conceivable that this

relatively high tonic activity in the extensor muscles is an

expression of the same pathophysiological condition which,

at earlier ages, produces the posture of hyperextension of

neck and trunk so characteristic of many preterm infants

(Drillien, 1972; Touwen and Hadders-Algra, 1983; De Groot

et al., 1992).

The majority of children with a PWM lesion did not differ

from the control children in the amount of antagonistic co-

activation. An excessive amount of antagonistic co-activation

was only found in the two children with a moderate form of

cerebral palsy, which is in agreement with findings of others

on postural control in children with spastic cerebral palsy

(e.g. Berger et al., 1984, 1985; Brogren et al., 1996, 1998;

Woollacott et al., 1998). The excessive co-activation can be

regarded as a primary dysfunction, based on altered intra-

and supra-spinal circuitries due to the early brain lesion

(Leonardet al., 1991a; Myklebust and Gottlieb, 1997), or as

a secondary phenomenon, as it could serve also as a functional

compensation for the postural instability inherent to cerebral

palsy (Woollacottet al., 1998). The finding of equal amounts

of co-activation on both sides of the body in the boy with

spastic hemiplegia might be an argument in favour of the

latter explanation.

The present study revealed that PWM lesions are related

to significant postural dysfunctions in the age period of 1 12

412 years. Whether or not the dysfunctions remain present at

older age needs to be determined. For the children with

cerebral palsy, it seems likely that the postural problems

persist, as EMG studies on the development of locomotor

behaviour in these children with cerebral palsy indicated that

the basic motor deficits do not change with increasing age

(Berger et al., 1984; Leonard et al., 1991b). Whether the

same holds true for the children with minor neurologicaldysfunction is less clear, as the expression of minor

neurological dysfunction changes substantially between

toddler age and adolescence (Hadders-Algra and Touwen,

1999).

Postural dysfunctions related to preterm birthPreterm birth was associated with an altered capacity to

modulate EMG amplitude during forward translations. First,

preterm children showed a higher sensitivity to platform

velocity than children born at term. This could point to a


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Fig. 6 Relative response latencies during fast forward and backward translations in the PWM group. The hatched areas denote the rangeof relative latency values found in a previous study on postural adjustments in healthy full-term pre-school age children (Hadders-Algraet al., 1998); the horizontal bars indicate the median values of this full-term-reference group. The asterisk indicate statistically significant

differences between the age-groups of the full-term children (KruskalWallis): *P 0.05, **P 0.01,***P 0.001. The black dotsrepresent the relative latency values of the individual children of the PWM group (n 1012, due to the interindividual variation inmuscle activation).

higher velocity sensitivity of muscles to stretch, analogous

to that of spastic children, which has been attributed to

changes in the intraspinal circuitry, such as low degree

of presynaptic inhibition of the muscle spindle afferents

(Crenna, 1998).

Secondly, preterm children lacked the ability to modulate

EMG amplitude with respect to initial sitting position.

Normally, this ability develops at 910 months (Hadders-

Algra et al., 1996a), indicating that from this age onwards,infants have access to complex postural control mechanisms

consisting of three basic components: (i) afferent information

on the orientation of body segments, including the information

from load receptors (cf. Bergeret al., 1995), and the position

of the centre of gravity; (ii) an internal postural reference

frame; and (iii) postural motor output (Massion, 1994).

Training experiments demonstrated that daily balance practice

accelerates the development of the modulating ability by 2

months (Hadders-Algra et al., 1996b), suggesting a role of

experience and learning. The inability of preterm children to

modulate the postural adjustments with respect to the sitting

position can be the result of dysfunction in any of the three

basic components. Considering the fact that preterm children

are at substantial risk for the development of learning

disorders (Hille et al., 1994), it can be hypothesized that

their inability to modulate postural responses to initial sitting

position is the result of a deficient capacity to learn from

prior experience. More specifically, this might point to a

dysfunction in the cerebellum or the basal ganglia, as these

systems play a particular role in the fine-tuning of motoroutput, including postural adjustments, to the environment

on the basis of prior experience (Bloedel, 1992; Graybiel,

1995; Kimura, 1995). The better candidate of these two

systems seems to be the basal ganglia, as a recent grip-and-

lift study of children with unilateral brain damage revealed

that, besides extensive cortical lesions, lesions of the basal

ganglia were associated with disturbances in the long-lasting

developmental process of the grip-lift synergy (Forssberg

et al., 1999). This is in line with Graybiels suggestion (1995)

that the basal ganglia might play a specific role in the

development of new motor patterns, i.e. in the formation of


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Fig. 7 Velocity ratios (VR) in ventral muscles during forwardtranslations in children 2 years. Velocity ratios (ratio of meanamplitude during fast perturbations and mean amplitude duringslow perturbations) of NF100, RA100and RF100 in children born atterm (n 10; open bars) and preterm children with and withoutPWM lesions (n 19; black bars). NF100, RA100 and RF100denote the mean amplitudes during the first 100 ms of thepostural response in the neck flexor (NF), musculus rectusabdominis (RA) and musculus rectus femoris (RF), respectively.The data are presented by ranges (vertical bars) and medianvalues (horizontal bars). The asterisks indicate statisticallysignificant differences between the full-term and preterm children(MannWhitney): *P 0.05, **P 0.01.

procedural memories. In this respect it is also interesting to

note that results from animal research indicated that the basal

ganglia seem to be particularly vulnerable to perinatal stress,

as early mild chronic hypoxia can result in long-term changes

in the striatal dopaminergic system (Gross et al., 1993).

Possibly, preterm birth, which is associated with a variety of

perinatal stresses, such as minor hypoxic insults, can induce

adverse changes in the basal ganglia which cannot be detected

on the neonatal ultrasound scans of the brain.

Concluding remarksThe present study revealed that preterm birth is associated

with two types of postural dysfunction. One is related to

distinct PWM lesions and consists of a limited repertoire of

response variation. The other dysfunction is not related to

lesions, which can be detected on neonatal ultrasounds of

the brain. It consists of a shift of postural control which is

guided by feedforward processes based on prior experience,to a form of postural control which is dominated by feedback

mechanisms.

AcknowledgementsWe thank Ingmarie Apel, Elien Oldekamp, Anneke Klip-Van

den Nieuwendijk and Roelof Hadders for technical assistance.

The study was supported by the Swedish Medical Research

Council (4X-5925), Norrbacka-Eugenia Stiftelsen, Sunner-

dahl Handikapp Fond, Josef och Linnea Carlssons Stiftelse,

Fo

rsta Majblommans Riksfo

rbund and Sven Jerring

Fig. 8 Correlations between (normalized) initial pelvis angle and(normalized) EMG amplitude in the RF muscle (RF100) duringslow forward translations in children 4.5 years. Available data:full-term (FT) group: 26 trials of four children; preterm (PT)control (US-N normal ultrasound): 24 trials of five children;PT-PWM without cerebral palsy: nine trials of two children.n.s. not significant.

Stiftelsen. M.H.A was supported by a grant from the Ter

Meulen Fund, Royal Netherlands Academy of Arts and

Sciences.


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Received August 28, 1998. Revised November 12, 1998.

Accepted November 18, 1998

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