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Variation and Variability: Key Words inHuman Motor DevelopmentMijna Hadders-Algra

This article reviews developmental processes in the human brain and basic principles

underlying typical and atypical motor development. The Neuronal Group Selection

Theory is used as theoretical frame of reference. Evidence is accumulating that

abundance in cerebral connectivity is the neural basis of human behavioral variability

(ie, the ability to select, from a large repertoire of behavioral solutions, the one most

appropriate for a specific situation). Indeed, typical human motor development is

characterized by variation and the development of adaptive variability. Atypical

motor development is characterized by a limited variation (a limited repertoire of

motor strategies) and a limited ability to vary motor behavior according to the

specifics of the situation (ie, limited variability). Limitations in variation are related

to structural anomalies in which disturbances of cortical connectivity may play a

prominent role, whereas limitations invariabilityare present in virtually all children

with atypical motor development. The possible applications of variation and variabil-

ity in diagnostics in children with or at risk for a developmental motor disorder are

discussed.

M. Hadders-Algra, MD, PhD, isProfessor of Developmental Neu-rology, Department of PediatricsDevelopmental Neurology, Uni-

versity Medical Center Groningen,University of Groningen, Hanz-eplein 1, 9713 GZ Groningen, theNetherlands. Address all corre-spondence to Dr Hadders-Algraat: [email protected].

[Hadders-Algra M. Variation andvariability: key words in humanmotor development. Phys Ther.2010;90:18231837.]

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Human behavior is character-ized by variation: each humanindividual has a large reper-

toire of motor, cognitive, and socialactions that can be arranged in

virtually endless combinations. Thisrepertoire allows for a flexible ad-justment to changing conditions,including the creation of newsolutions.

The wealth of distinctly human be-

havior is attributed to the neocortex,the part of the brain that expandedgreatly during evolution.1,2 For in-stance, in insectivores such as thehedgehog, the neocortex occupies10% to 20% of total brain volume,

whereas this proportion has risen toabout 80% in humans.3 The enlarge-ment of the neocortex has been

brought about mainly by expansionof the surface area and not so muchby an increase in cortical thickness.2

The expansion of cortical surface al-lowed for the emergence of new ar-eas (eg, language-related areas) andthe extension of the prefrontal cor-tex and association areas. Interest-ingly, the volume of the white mat-

termostly consisting of cortico-cortical connectionsincreased moreduring the evolutionary expansionof the cortex than the volume of graymatter.3,4

The development of the humanbrain is an intricate and long-lasting

process, which is mirrored by a mul-titude of developmental changes inbehavior. The latter include the

changes involved in the transfor-mation of nongoal-directed fetal

motility into the accurate and goal-directed movements of an adult per-son, such as those involved in writ-ing a letter or riding a bike. The aimof this article is to discuss putativemechanisms and principles underly-ing developmental changes in motor

behavior. Particular attention is paidto the notions of variation andvariability. The article starts with ashort overview of the ontogeny ofthe human brain. Sections on theo-retical considerations and typical

and atypical motor development fol-low. The emphasis is on the earlyphases of development and the Neu-

ronal Group Selection Theory(NGST) is used as a frame of refer-ence. The NGST was chosen becauseit highlights that variation and vari-ability are key elements of typicaldevelopment. Variation implies thepresence and expression of a broadrepertoire of behaviors for a specificmotor function. Variability denotes

the capacity to select from the rep-ertoire the motor strategy that fitsthe situation best. The article con-cludes with possible applications of

variation and variability in diagnos-tics in infants with or at risk for adevelopmental motor disorder.

Development of theHuman BrainThe development of the humanbrain, and in particular, that of theneocortical circuitries, lasts about 4decades.5 It starts during the earlyphases of gestation with the prolifer-ation of neurons. The majority of tel-encephalic neurons are produced inthe germinal layers near the ventri-

cles.2,6 Once neurons have been gen-erated, they move from their place oforigin to their final destination, thecortical plate.6,7 Before the corticalplate is formed, however, neuronshalt in the subplate. The subplate is a

temporary layer between the ven-tricular zones plus intermediate zone(the future white matter) and the

cortical plate.8 The subplate emergesin early fetal life, is thickest at around

29 weeks postmenstrual age (PMA),and disappears gradually until it isabsent at around 6 months post-term.9,10 The major proportion of itsafferent and efferent connectionsrun through the (future) periven-tricular white matter. The subplate

mediates fetal behavior.

Neurons start to differentiate duringmigration and during their stay inthe subplate. Neuronal differentia-tion includes the formation of den-

drites and axons, the production ofneurotransmitters and synapses, andthe elaboration of the intracellular

signaling machinery and complexneural membranes.11,12 The processof differentiation is particularly ac-tive in the few months prior to birthand the first postnatal months, but ittakes many years before the adultstate of differentiation is achieved.5

Besides neural cells, glial cells aregenerated. The peak of glial cell pro-

duction occurs in the second half ofgestation. Some of the glial cells takecare of axonal myelination. Myelina-tion takes place especially betweenthe second trimester of gestation andthe end of the first postnatal year.Thereafter, myelination continuestill the age of about 40 years, whenthe last intracortical connections

complete myelination.13

Brain development consists not onlyof creation of components, but alsoof an elimination of elements. Abouthalf of the created neurons die offby means of apoptosis. Apoptosis isbrought about by interaction be-tween endogenous programmed

processes and chemical and electri-cal signals induced by experience14;it occurs in particular during mid-gestation.5 Similarly, axons and syn-apses are eliminated, the latter espe-cially between the onset of puberty

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Variation and Variability in Human Motor Development

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and early adulthood. As a result, the

adult level of synaptic density in

the cortex is reached first in early

adulthood.5

For a long time, it had been debatedwhether brain development is

driven by endogenous processes or

by external input. Gradually, how-

ever, it became clear that genetic in-

struction (nature) and environ-

mental information (nurture) both

play an important role, albeit with

different weights during different

phases of development. In the early

phases, the role of the genome dom-

inates; later on, environment and ex-

perience become crucial. The impor-

tance of genetic instruction in earlydevelopment is reflected by animal

studies that indicated the primary

cortical areas, their connections,

their modular organization, and their

size are largely determined by differ-

ential gene expression in the neural

stem cells.1,15 Thus, the genetically

specified areas attract specific inputs

instead of inputs specifying the ar-

eas.2 This means that the functional

topography of the brain is primarily

driven by genetic instruction (ie, thefact that occipitally located neurons

virtually always become involved in

the processing of visual information

and frontally located networks in ac-

tivities such as planning and atten-

tion). A primary genetic determina-

tion, however, does not preclude

variation, as each individual has his

or her own sets of genes. Moreover,

the primary genetic determination is

only the starting point for epigenetic

cascades, allowing for abundant in-

teraction with the environment and

activity-dependent processes.1618

Note that the interaction is bidirec-

tional: experience affects gene ex-

pression, and genes affect how the

environment is experienced.18

Virtually all of the neurodevelop-

mental processes described above

are affected by experience, in-

cluding motor experience. Animal

studies have demonstrated that the

effect depends on the type of expe-

rience (eg, specific versus general-

ized motor experience), the age at

exposure, the individuals sex, and

the neural area.18,19

Experience mayaffect, for instance, apoptosis, axon

retraction, synapse elimination, and

synapse formation.1921 It may even

affect the somatotopic organization

of the primary motor cortex, as was

indicated by the recent human study

by Stoeckel et al.22 This imaging

study revealed that the motor foot

representation in individuals with

congenitally compromised hand

function and compensatory skillful

foot use had extended beyond the

classical foot area into the vicinity ofthe lateral hand area.

Theoretical ConsiderationsVarious Theoretical FrameworksDespite increasing knowledge of the

developmental processes in the hu-

man brain, our understanding of the

neural mechanisms underlying mo-

tor development is limited. As a re-

sult, multiple theories of motor de-

velopment have been produced, all

aiming to facilitate the understand-ing of typical and atypical motor de-

velopment. During the major part of

the previous century, motor devel-

opment basically was regarded as an

innate, maturational process,23,24 but

during the centurys last 2 decades, it

became increasingly clear that motor

development is largely affected by

experience.

Currently, 2 theoretical frameworks

are most popular: dynamic systems

theory2527 and NGST.28,29 The

frameworks share the opinion that

motor development is a nonlinear

process with phases of transition

that is affected by many factors. The

factors may vary from features of the

child to external influences such as

housing conditions, the presence of

stimulating caregivers, and the pres-

ence of toys. In other words,

both theories acknowledge the

importance of experience and the

relevance of context. The 2 theo-

ries differ, however, in their opin-

i on on the r ol e of genetically

determined neurodevelopmental

processes. Genetic factors playonly a limited role in dynamic sys-

tems theory, whereas genetic en-

dowment, epigenetic cascades, and

experience play equally prominent

roles in NGST.28,29 In the following

paragraphs, I will use the NGST

framework to discuss principles of

typical and atypical motor

development.

NGST and Typical MotorDevelopment

The NGST was developed by GeraldEdelman. He described motor devel-

opment as characterized by 2 phases

of variability: primary and second-

ary.28,29 The borders of variability are

determined by genetic instruc-

tions.1,15 During the phase of pri-

mary variability, motor behavior is

characterized by abundant variation.

The variation is brought about by

explorative activity of the nervous

system. The system explores all mo-

tor possibilities. The explorationgenerates a wealth of self-produced

afferent information, which, in turn,

is used for further shaping of the

nervous system. The exploration re-

flects the continuous, dynamic inter-

action between genes and experi-

ence, including experience with

changing body proportions. Initially,

however, the afferent information

is not used for adaptation of motor

behavior to environmental con-

straints. In other words, the phase of

primary variability is characterized

by variation in motor behavior and

the absence of the ability to adapt

the various movement possibilities

to the specifics of the situation (ie,

by the absence of variabilityin sensu

strictu, as defined in the introduc-

tion of the article).24

At a certain point in time, the ner-

vous system starts to use the afferent




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information produced by behaviorand experience for selection of themotor behavior that fits the situa-

tion best: the phase of secondary oradaptive variability starts. Hitherto,

the mechanisms underlying the shiftfrom primary variability to secondaryvariability are not understood. Theprocess of selection, which is char-acteristic of variability and thusthe phase of secondary variability,is based on active trial-and-error

experiences that are unique to theindividual.3032 Indeed, evidence isaccumulating that self-produced sen-sorimotor experience plays a pivotalrole in motor development.31,3335

To determine whether a movementis most adaptive, reference valuesare used that most likely are function

specific. The solution that is selectedis specific for the situation and theinfants stage of development. Forinstance, in sitting infants whosebalance is perturbed, informationlinked to the stability of the head inspace is used to select the posturaladjustment in which most of theso-called direction-specific postural

muscles are recruited (the en blocpattern).36 Selection of the en blocpattern depends on the degree ofbalance perturbationthe pattern isrecruited more often during largeperturbations than during smallperturbationsand the age of thechild.36,37 Children select the en blocpattern during marked perturbations

of balance especially often betweenthe ages of 9 months and 212 years.Thereafter, similar perturbations ofbalance are associated with child-specific postural adaptations in

which fewer direction-specific mus-cles are recruited.37

The process of learning to select the

most appropriate motor solutionin a specific situation is based onimplicit motor learning and does notinvolve conscious decision making.It occurs at various interdependentlevels of neural organization. Animal

data indicate that at the cellular level,selection is mediated by changes insynaptic strength, in which the to-

pology of the cells38 and the pres-ence or absence of coincident elec-

trical activity in presynaptic andpostsynaptic neurons play a role.39,40

In terms of the organization of motorcontrol, selection occurs at the levelof motor strategies and at the level oftemporal and quantitative tuning ofmotor output.36 Recent neurophysi-

ological data indicated that the basalganglia might play a major role inthe selection of motor strategies (ie,in motor sequence learning),32,41

whereas the cerebellum might bethe key structure involved in the se-

lection of situation-specific temporaland quantitative parameters of mo-tor output (ie, accurate motor adap-

tation).42,43 The idea that frontostria-tal circuitries play a role in theselection of motor strategies is sup-ported by a recent birth cohort studyby Murray et al.44 The study indi-cated that an earlier development ofthe ability to stand independently

which might be interpreted as anearlier ability to select an appropri-

ate strategy to keep balance in up-right stancewas associated withbetter executive functions in adult-hood. The association was specificfor executive functions, which aresubserved by frontostriatal circuit-ries; other cognitive functions suchas verbal and visual learning, whichare more closely related to temporal

cortex function, were not related toan earlier development of standing.

The transition from primary variabil-ity to secondary variability occurs atfunction-specific ages. For instance,in the development of sucking be-havior, the phase of secondary vari-ability starts prior to term age45; in

the development of postural adjust-ment, it emerges after the age of 3months46,47; and in the developmentof foot placement during walking, itstarts between 12 and 18 months.48

The age at which adaptive behavior

first can be observed depends on themethod of investigation. For in-stance, with the application of elec-

tromyographic recordings, the firstsigns of adaption in postural behav-

ior during sitting may be observedat the age of 4 months,46 but whensimple behavioral observation isused, signs of adaptive sitting behav-ior are first detected from 6 monthsonward.49 Around the age of 18months, all basic motor functions,

such as sucking, reaching, grasping,postural control, and locomotion,have reached the first stages of sec-ondary variability. Due to the in-genious interaction between self-produced motor activities with trial-

and-error learning and the long-lasting developmental processes inthe brain, such as dendritic refine-

ment, myelination, and extensivesynapse rearrangement,5 which fur-nish new neuromotor possibilities, ittakes until late adolescence beforethe secondary neural repertoire hasobtained its adult configuration. Inother words, the basic, variable mo-tor repertoire that is formed duringthe phase of primary variability con-

tinues to develop during the phaseof secondary variability and tochange throughout life.

The ongoing developmental changesin the nervous system, which arebased on a never-ending interactionbetween experience and genetic in-formation, allow for increasingly

precise and complex motor skills,which may be regarded as refine-ments of the basic, variable reper-toire. As a result, adult human beingsare equipped with a variable move-ment repertoire with an efficientmotor solution for each specificsituation.

NGST and Atypical MotorDevelopment

Atypical motor development mayoriginate from genetic aberrationsor adversities occurring duringearly development. Both etiological




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pathways may result in a structural

anomaly or lesion of the developing

brain or in a different setting of spe-

cific neurotransmitter systems, such

as the monoaminergic systems. Ac-

cumulating evidence indicates thatstressful situations in the prenatal

and perinatal periods may induce

lifetime changes in dopaminergic, se-

rotonergic, or noradrenergic circuit-

ries.50 The monoaminergic systems

are widespread systems involved in

the modulation of behavior.51 The 2

sequelaethe lesion of the brain and

the different setting of the monoam-

inergic systemswill be discussed

as different entities, but it should be

kept in mind that lesions of the im-

mature brain often are associatedwith changes in specific neurotrans-

mitter systems.52

The best example of atypical motor

development due to an early lesion

of the brain is the motor develop-

ment of children with cerebral palsy

(CP). Other examples are some chil-

dren with developmental coordina-

tion disorder and some children with

attention deficit hyperactivity disor-

der. It is important to note, however,that in general developmental coor-

dination disorder and attention defi-

cit hyperactivity disorder cannot be

attributed to a lesion of the brain.53

In the following paragraphs, CP is

used as a prototype to describe the

motor sequelae of a lesion occurring

in the fetal or infant brain.54

NGST and an Early Lesion ofthe Brain

According to NGST, an early lesion

of the brain has 2 major consequenc-

es.55 First, the repertoire of motor

strategies is reduced.5659 This re-

duced repertoire results in less vari-

able and more stereotyped motor

behavior (ie, in reduced variation

during both phases of variability).

The limited repertoire may result in

the absence of a specific motor strat-

egy, which would be available as the

best solution in a specific situation

for a child with typical development.

As a consequence of the absence

of the best solution, the child with

CP may have to choose a motor so-

lution that differs from that of the

child with typical development.60

This situation implies that the differ-

ent motor behavior of a child with

CP should not always be regarded as

deviant (ie, as something that de-

serves to be treated away), as it

may be the childs best and most

adaptive solution for the situation.61

Second, in the phase of secondary

variability, children with an early le-

sion of the brain have problems with

selection of the most appropriately

adapted strategy out of the reper-

toire. In other words, they have alimited capacity to vary motor behav-

ior in relation to the specifics of the

situation (ie, they have a limited

variability).

The deficient capacity to select has a

dual origin: it is related to deficits in

the processing of sensory informa-

tion that are virtually always present

in children with an early lesion of

the brain6267 and to the fact that the

best solution may not be availabledue to repertoire reduction. The dif-

ficulties in selection have 2 practical

consequences. First, impaired selec-

tion may give rise to the paradoxical

finding that results of motor tests of

children with CP often are more vari-

able than those of children with typ-

ical development.67,68 The variable

test results are brought about by pro-

longed periods of trial and error

needed to explore the reduced rep-

ertoire due to impaired selection.

This consequence means that a re-

duced repertoire may be associated

with more variable motor output.

Second, impaired selection induces

the need of ten- to hundredfold more

active motor experience than typi-

cally needed to find the best strate-

gy.69,70 Consequentially, children

with CP need considerably more

practice than their peers without CP

to learn a specific motor task.

Recall that exploratory drive is a fun-

damental feature of the typically de-

veloping nervous system. As a re-

sult, young infants spontaneously

generate a wealth of everyday motor

practice.35

The child with CP needsmuch more practice. In addition, the

brain lesion responsible for CP may

be associated with reduced explor-

atory drive.54 This reduced explor-

atory drive creates a challenging sit-

uation for the child with CP and his

or her environment. The need for

much practice requires strong moti-

vation, which is obtained most easily

when tasks to be learned have func-

tional significance or are enjoyable.

NGST and an Altered Setting ofMonoaminergic Systems

Adversities prior to term age, such as

low-risk preterm birth, intrauterine

growth retardation, or psychological

stress of the pregnant woman, may

give rise to a different setting of the

monoaminergic systems in the ab-

sence of a lesion of the brain. Most of

our knowledge about the effect of

stressful conditions during early life

on the developing brain is based on

animal data.50

The animal data indi-cate that stress during early life gives

rise to changes in serotonergic and

noradrenergic activity in the cerebral

cortex and alterations in dopaminer-

gic activity in the striatum and pre-

frontal cortex.71 These changes have

been associated with impaired devel-

opment of the maps of body repre-

sentation in the primary somato-

sensory cortex, inappropriately

developed ocular dominance col-

umns in the visual cortex, and mild

motor problems.7274 In terms of

NGST, this impaired development

may reflect a situation in which the

child has a typical movement reper-

toire but has difficulties in selecting

the best strategy in a specific situa-

tion due to the deficits in processing

of sensory information. In other

words, the child has an impaired

ability to vary motor behavioran

impaired variabilityin relation to




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task-specific requirements. As a re-sult, the child often exhibits more

variable behavior during motor tests

and needs more practiceand thusmore timeto learn new motor

skills. Indeed, such mechanisms ap-pear to play a role in the frequentlyencountered impaired motor devel-opment of preterm children withoutcerebral palsy.59,75,76

Early Phases of MotorDevelopmentTypical Motor DevelopmentNongoal-directed motility. Arecent, detailed ultrasound study onthe emergence of fetal motility re-

vealed that the earliest movementscan be observed at the age of 7

weeks 2 days PMA.77 The first move-ments are slow, small, sidewaysbending movements of head or

trunk. A few days later, these simplemovements develop into move-ments in which 1 or 2 arms or legsalso participate, but the movementscontinue to be slow, small, simple,and stereotyped. At the age of 9 to 10

weeks PMA, general movements(GMs) emerge (ie, movements in

which all parts of the body partici-pate). Initially, GMs show little vari-ation in movement direction, ampli-tude, and speed. After a few days,however, the majority of GMs showa substantial degree of variation inspeed, amplitude, participating bodyparts, and movement direction. In-terestingly, the emergence of GMs

with movement variation and com-

plexity at 9 to 10 weeks PMA coin-cides with the emergence of synap-

tic activity in the cortical subplate.78

This coincidence and the findingthat the evolution and transient na-ture of the subplate match that ofGM development inspired the hy-pothesis that variable and complexGMs result from activity of the sub-

plate modulating the basic activity ofGM networks in the spinal cord andbrain stem.79

Soon after the emergence of the firstmovements, other movements areadded to the fetal repertoire, such as

isolated arm and leg movements,startles, various movements of the

head (rotations, anteflexion, andretroflexion), stretches, periodicbreathing movements, and suckingand swallowing movements.80 Theage at which the various movementsdevelop shows considerable inter-individual variation, but at about 16

weeks PMA, all fetuses exhibit theentire fetal repertoire. The reper-toire continues to be presentthroughout gestation.

At birth, be it term or preterm, only

minor changes in the motor reper-toire occur. Breathing movementsbecome continuous instead of peri-

odic, the Moro reaction can be elic-ited for the first time, and the infant,

who is now hampered by the forcesof gravity, is no longer able to ante-flex the head in a supine position.81

General movements continue to bethe most frequently observed motorpattern.

Between 2 and 4 months postterm,infant behavior changes drastically.The infant is able to use smiles andpleasure vocalizations in social inter-action, the head can be stabilized onthe trunk, and a steady visual fixationand brisk visual orienting reactionshave been developed.81 Simulta-neously, GM activity is about to dis-

appear and to be replaced graduallyby goal-directed activity of arms andlegs. Interestingly, the final phase ofGMs, which occurs at 2 to 4 monthspostterm, is characterized by a spe-cific movement property: the fidg-ety nature of GMs. The fidgety char-acter denotes the presence of acontinuous stream of tiny, elegant

movements occurring irregularly allover the body.58 Functional neuroim-aging studies suggest that increasingactivity in the basal ganglia, thecerebellum, and the parietal, tempo-ral, and occipital cortices plays a

prominent role in the behavioraltransition at 2 to 4 months.82

Goal-directed motility. The de-velopment of goal-directed behavior

during infancy is characterized byintraindividual and interindividualvariation.55,57,83,84 The variation oc-curs, for instance, as variation in theemergence of a function, variation inthe performance of a function (Figs.1 and 2), variation in the duration of

specific developmental phases, andvariation in the disappearance of in-fantile reactions, such as the Mororeaction. The variation in develop-ment includes the co-occurrence ofdifferent developmental phases. For

instance, infants of a certain age canalternate belly crawling with crawl-ing on hands and knees.83,85 Infants

with typical development also mayexhibit a temporary regressionaninconsistencyin the develop-ment of a specific function.83As longas the regression is restricted to asingle function, it can be regarded asanother expression of developmen-tal variation. Large variation in theattainment of milestones in goal-

directed motor behavior (Fig. 3) im-plies that the assessment of mile-stones has less clinical value thanpreviously was thought.86 Slow de-

velopment of a single function usu-ally has no clinical significance, butthe finding of a general delay is clin-ically relevant.

Infancy is the period of transitionfrom primary variability to secondary

variability (ie, from motor behaviorthat cannot be adapted to task-specific conditions to adaptive mo-tor behavior). This transition occursat function-specific ages. A recentobservational study indicated thatthe transition in sitting behavior oc-

curs between 6 and 10 months, thatin abdominal progression occurs be-tween 8 and 15 months, that inreaching movements occurs be-tween 6 and 12 months, and that ingrasping occurs between 15 and 18




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months.49 These findings mean that

after the transition, people observing

the infants could notice a change in

their motor behavior.

A major accomplishment during in-

fancy is the development of pos-

tural control, resulting in the ability

to stand and walk without sup-

port.87 Postural control is aimed

primarily at the maintenance of a

vertical posture of head and trunk

against the forces of gravity be-

cause a vertical orientation of the

proximal parts of the body provides

an optimal condition for vision- and

goal-directed motility.88 In the con-

trol of posture, 2 functional levels

can be distinguished. The basic level

of control deals with the directional

specificity of the adjustments: when

the body sways forward, primarily

the dorsal muscles are recruited;

when the body sways backward, pri-

marily the ventral muscles are acti-

vated.89 A study by Hedberg et al90

indicated that 1-month-old infants

have direction-specific adjustments,

which suggests that the basic level of

postural control has an innate origin.

Young infants show a variable reper-

toire of direction-specific adjustments

from which, from the age of 4 months

onward, they learn to select by

means of active trial and error the ad-

justment that fits the situation best.46

Meanwhile, the infant learns to sit in-

dependently. With increasing age, the

means to adapt postural activity be-

come increasingly refined. A major de-

velopmental change is the emergence

of anticipatory postural activity be-

tween 12 to 14 months, an ability that

strongly promotes the development of

independent walking.87

Successful reaching is preceded by

various forms of prereaching activi-

ty.91 For instance, Von Hofsten92

demonstrated that newborn infants

move their hands closer to a nearby

object when they visually fixate on

it, than when they do not pay visual

attention to the object. Reaching

Figure 1.Variation in motor behavior in a supine position at 8 months postterm. The figure consists of frames selected from a videorecordingof about 3 minutes. Figure produced with permission of the parents.




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results in actual grasping of an object

from about 4 months onward.93 At

this age, reaching movements have

an irregular and fragmented trajec-

tory consisting of multiple movement

units. These characteristics under-

line the probing nature of early

reaches and the heavy reliance of the

first reaching movements on feed-

back control mechanisms.93 During

the following months, the reaching

movement becomes increasingly flu-

ent and straight, and the orientation

of the hand becomes increasingly

adapted to the object.94 After their

first birthday, infants increasingly

use the pincer grasp to pick up tiny

objects. This change in behavior

implies that corticomotoneuronal

pathways are being involved increas-

ingly in fine motor control.95

Figure 2.

Variation in motor behavior in a sitting position at 11 months postterm. The figure consists of frames selected from a videorecordingof about 3 minutes. Figure produced with permission of the parents.




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At birth, the infantlike the fetus

shows locomotor-like behavior in

the form of neonatal stepping move-

ments.96 These movements probably

are generated by spinal pattern gen-

erators analogous to the locomotionin the hind limbs of kittens after a

transection of the thoracic cord and

the locomotor-like activity in people

with a spinal cord injury.96 The in-

fant stepping movements are rather

primitive in character and differ from

the flexible plantigrade gait of adult-

hood.97 This non goal-directed neo-

natal stepping is characterized by a

lack of segment-specific movements,

implying that the legs tend to flex

and extend as a single unit; by the

absence of a heel-strike; by a variablemuscle activation with a high degree

of antagonistic coactivation; and by

short-latency bursts of electromyo-

graphic activity at the foot contact

due to segmental reflex activity.96,97

In the absence of specific training,

the stepping movements can no

longer be elicited after the age of 2 to

3 months.83

A period of locomotor silence fol-

lows, which is succeeded in thethird quarter of the first postnatal

year by goal-directed progression in

the form of crawling and supported

locomotion. When neonatal step-

ping is trained daily, the stepping

response can be elicited until it is

replaced by supported locomo-

tion.98 This progression is perhaps

not so surprising in light of the fact

that the locomotor pattern of sup-

ported locomotion is reminiscent

of that of neonatal steppingboth

lacking the determinants of planti-

grade gait.97 In addition, the mile-

stone transition into independent

walking is not associated with a ma-

jor change in specific locomotor ac-

tivity. This finding indicates that the

emergence of independent locomo-

tion is not primarily induced by

changes in the locomotor networks.

Presumably, the development of in-

dependent walking is largely depen-

dent on the development of postural

control,99 which, in turn, is depen-

dent in particular on developmental

changes in the subcortical-cortical

circuitries.96

Motor development beyond infancy

is characterized by a gradual increase

in agility, adaptability, and the ability

to make complex movement se-quences. It is the phase of secondary

variability, during which matura-

tional processes in continuous inter-

action with changing body propor-

tions and experience produce highly

adaptive secondary neuronal reper-

toires.24,28 The creation of secondary

repertoires is associated with exten-

sive synapse rearrangement, which

is the net result of synapse formation

and synapse elimination.5 It is facili-

tated by increasingly shorter process-

ing times, which can be attributed,

in part, to ongoing myelination.100

Atypical Motor DevelopmentDevelopmental changes in the

young brain have a large impact on

the expression of atypical motor be-

havior. It may happen that a lesion of

the developing brain results in neu-

romotor dysfunction in infancy but

is followed by a typical developmen-

tal outcome. The reverse may also

occur (ie, an apparently typical de-

velopment in the early phases of

infancy may be followed by the de-

velopment of CP).58

In infancy, atypical motor develop-

ment may be expressed by a delay

in the achievement of milestones

(which may be related to impairedselection), by mild or major devia-

tions in muscle tone (velocity-

dependent resistance to stretch), by

a persistence of infantile reactions

(eg, the Moro reaction), and by a

reduced variation in motor behavior.

The latter sign may be the most spe-

cific expression of an early lesion of

the brain,55,58,101 whereas the other

signs may be the result of a lesion of

the brain but also may be related to

other types of adversities during

early development, such as low-risk

preterm birth.102104 Reduced varia-

tion in motor behavior is well ex-

pressed in the quality of GMs: abnor-

mal GMs are characterized by limited

variation and limited complexity. In-

terestingly, definitely abnormal GMs

are related to white matter pathol-

ogy and not to abnormalities of the

brains gray matter.79,105 Further-

more, beyond the age of 4 months,

Figure 3.Schematic representation of the ages at which some motor skills emerge during infancy.The length of the bars reflect the interindividual variation. Adapted from Touwen.83




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when GMs have disappeared, atypi-

cal motor development is character-

ized by reduced variation (Figs. 4 and

5). Well-known stereotypies are fist-

ing of the hands, extension of the

legs, clawing of the toes, dominant

asymmetrical tonic neck reflex pos-

turing, hyperextension of the neck

and trunk, or stereotyped asymme-

tries.106 It has been postulated that

the degree to which movement vari-

ation is reduced may reflect the ex-

tent to which cortical connectivity is

impaired.79,107

Atypical motor development is asso-

ciated with postural dysfunction.

Children with a severe lesion of the

brain who develop severe bilateral

spastic CP or severe athetosis and

function at Gross Motor Function

Classification System level V108 pre-

sumably lack the basic level of pos-

tural control.109 In infants with less-

severe forms of CP, the basic level of

postural organization is more or less

intact. However, their postural de-

velopment is hamperedand, there-

fore, delayedby a limited reper-

toire of postural adjustments and a

deficient capacity to adapt posture

to the specifics of the situation.109

Diagnostic Application ofVariation and VariabilityGradually, European clinicians work-

ing in the field of developmental

neurology realized that variation and

variability may assist in the evalua-tion of motor development. How-

ever, before addressing the value of

these parameters, some general re-

flections on the significance of the

infant neuromotor assessment are

necessary. Evaluation of neuromotor

function in early life has 2 goals. First

and foremost, it aims at assessing

the infants current capacities and

limitations, as the assessment offers

Figure 4.Reduced variation in motor behavior in a supine position at 2 months postterm. The figure consists of frames selected from avideorecording of about 3 minutes. Figure produced with permission of the parents.




11/16

the basis for therapeutic guidance.

Second, an assessment at an early

age may assist in the prediction of

the infants developmental pros-

pects. However, as indicated in the

preceding paragraphs, the develop-

mental characteristics of the brain

preclude precise prediction. Predic-

tion of developmental outcome is

best when multiple sources of infor-

mation are used, such as the infants

history, the results of neuroimaging,

and neurophysiological assessments

in combination with a neurological,

developmental, and neuromotor as-

sessment.110 Prediction also is largely

facilitated when longitudinal series

of assessments are used.104,111

The various instruments available to

evaluate the infants neuromotor and

Figure 5.

Reduced variation in motor behavior in sitting at 10 months postterm. The figure consists of frames selected from a videorecordingof about 3 minutes. Figure produced with permission of the parents.




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developmental status have specific

aims, advantages, and disadvantages.

Most instruments provide informa-

tion on the childs function in terms

of age-adequate performance versus

underachievement or delay. Exam-ples are the Bayley Scales of Infant

Development112 and the Albert In-

fant Motor Scales.113 Neurological as-

sessments pair information on motor

performance with specific details on

sensorimotor function in terms of

muscle tone and reflexes.110 The

growing awareness that the quality

of motor behavior may assist in the

evaluation of the childs neuromotor

condition inspired the development

of 3 new assessment methods; the

Test of Infant Motor Performance(TIMP),114 the GM method,58,115 and

the Infant Motor Profile (IMP).116

The TIMP and the GM method are

applicable till the age of 4 months

postterm, whereas the IMP is de-

signed for infants aged 3 to 18

months postterm. In contrast to the

other 2 instruments, the TIMP does

not use variation or variability as ex-

plicit parameters of movement qual-

ity. The TIMP has good reliability,

and the limited data available suggestthat it is a valuable instrument in the

prediction of CP.110 The 2 methods

using the concepts of variation and

variability are discussed below. Vari-

ation (ie, the evaluation of the size of

the repertoire) is a parameter that

may be applied in the phase of pri-

mary and secondary variability. Vari-

ability (ie, the ability to make an

adaptive selection) is particularly rel-

evant from the emergence of second-

ary variability onward.

The examination of the quality of

GMs is a reliable assessment based

on the evaluation of movement vari-

ation.58,115 General movement as-

sessment does not include the eval-

uation of variability, as the nongoal-

directed GMs do not have a phase of

secondary variability.24 In the GM

method, 2 aspects of variation are

assessed: (1) GM complexity, which

denotes the spatial aspect of move-

ment variation, and (2) GM variation,

which represents the temporal vari-

ation of movements. Definitely ab-

normal GMs are characterized by a

severely reduced movement com-plexity and variation; in mildly

abnormal GMs, complexity and vari-

ation are present, but to an insuffi-

cient extent.58 The consistent pres-

ence of definitely abnormal GMs

during the first postnatal months is

associated with a very high risk for

the development of CP.58,115

The predictive value of single assess-

ments increases with age. Best pre-

diction is achieved with an assess-

ment in the final phase of GMs (ie, inthe phase of fidgety GMs at around

3 months postterm). In populations

of infants who are at risk for CP,

definitely abnormal GMs at 3 months

are associated with a risk of CP

that varies between 25% and

80%,79,115,117 whereas mildly abnor-

mal GMs are associated with an in-

creased risk of minor neurological

dysfunction and psychiatric morbid-

ity at school age.118,119 It should be

noted, however, that the predictivepower of mildly abnormal GMs at 3

months is so low that mildly abnor-

mal GMs as a single sign have no

clinical relevance. The recent finding

that the predictive value of GM qual-

ity is substantially higher in popula-

tions of infants who are at risk for CP

than in the general population120

supports the idea that the quality of

GMs reflects the integrity of cortical

connectivity (ie, the integrity of the

brains white matter), as large parts

of the brains white matter are situ-

ated in the periventricular area,

which is the site of predilection for

damage in the preterm period.121

The IMP is a novel instrument that

assesses infant motor behavior in 5

domains. Two domains are based on

the NGST: size of the repertoire

(variation) and ability to select (vari-

ability). The other 3 domains evalu-

ate more traditional aspects of motor

behavior: symmetry, fluency, and

performance.76,116 The reliability and

construct validity of the IMP are

good, and its predictive and evalua-

tive power is promising.76,116

Concluding RemarksAccumulating evidence indicates

that abundance in cerebral connec-

tivity is the neural basis of human

behavioral variability (ie, the ability

to select from a large repertoire of

behavioral solutions the one most

appropriate for a specific situation).

Indeed, typical human motor devel-

opment is characterized by variation

and the development of adaptive

variability, and atypical motor devel-opment is characterized by limita-

tions in variation and variability. Lim-

itations in variation are based on

structural anomalies, in which distur-

bances of cortical connectivity may

play a prominent role, whereas limi-

tations in variability are present in

virtually all children with atypical

motor development. In infants with

reduced variation, early intervention

may aim to enlarge the limited move-

ment repertoire, but animal data in-dicate that this aim is difficult to

achieve.52 This situation implies

thatdespite interventionreper-

toire reduction most likely will re-

main a feature of the motor behavior

of the child with an early lesion of

the brain. In such a situation, equip-

ment may offer a proper means to

facilitate functional activity and

participation.

The limited variability of childrenwith atypical motor development is

based on the limited ability to select

a strategy out of the movement rep-

ertoire due to deficiencies in the

processing of sensory information

brought about by self-produced ac-

tions. This fact suggests that children

with limited variability may profit

from ample, variable, self-produced,

trial-and-error activities.122,123




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