hydrocephalus: a test of the dual pathway model

NEURAL PLASTICITY VOLUME 11, NO. 1-2, 2004

The Nature of Hyperactivity in Children and Adolescents withHydrocephalus: A Test of the Dual Pathway Model

Jim Stevenson and Ineke Pit-ten Cate

School ofPsychology, University ofSouthampton,Highfield, Southampton, England S017 1BJ

SUMMARY

To determine the strength and nature of theassociation between hydrocephalus and hyper-activity and to test the dual pathway model

(DPM) of AD/HD, we compared a group of 51children and adolescents with hydrocephaluswith 57 normally developing controls from thegeneral population on a battery of neuro-

psychological assessments. The mean hyper-activity scores were significantly greater in the

group with hydrocephalus (effect size 0.94).This association was not just part of a generalelevated rate of behavior problems and was notaffected by sex or age. Variation in the clinical

features of hydrocephalus was not related tothe severity of hyperactivity. Path analysis wasused to examine the relation between IQ, delayaversion, and executive function. In accordancewith the DPM, the effect of hydrocephalus onhyperactivity was completely mediated via

delay aversion and executive functions.

KEY WORDS

hyperactivity, delay aversion, executive functionhydrocephalus, dual pathway model

Reprint requests to: Prof. Jim Stevenson, School ofPsychology, University of Southampton, Highfield, SouthamptonSO17 1BJ; e-mail: [email protected]

INTRODUCTION

Hydrocephalus is a neurological condition thatoccurs when there is an abnormal accumulation ofcerebrospinal fluid within the ventricles and/or thesubarachnoid space of the brain. Hydrocephaluscauses raised intracranial pressure and can distortthe surrounding brain tissue. The condition canresult from an overproduction of cerebrospinalfluid, an obstruction of the cerebrospinal fluidflow, or a failure of the structures of the brain toreabsorb the fluid. Hydrocephalus can be presentat birth (congenital hydrocephalus) or acquiredafter birth from a variety of causes. Hydrocephaluscan be caused by spina bifida but is also associatedwith other conditions such as meningitis andpremature birth. The effects of hydrocephalus onchild functioning vary considerably and depend onthe areas of the brain most affected. These effectscan include impaired fine motor skills, executivefunctioning, learning, attention, and behavior(Tew, 1991).

There is evidence that children with hydro-cephalus are at increased risk of range of behavioralproblems. Some studies suggest that only whenhydrocephalus is associated with mental retardationis an increase found in such behaviors as hyper-activity (Femell et al., 1991a) and autistic-likebehavior (Femell et al., 1991b). A more recentstudy, however, has suggested that a wide range ofchildren with hydrocephalus are at risk of elevatedbehavior problem scores (Fletcher et al., 1995). This

(C) 2004 Freund & Pettman, U.K. 13

14 J. STEVENSON AND I. PIT-TEN CATE

study also demonstrated that the behavior problems(particularly those related to attention) were morecommon in more severely affected hydrocephalicchildren amongst a sample of very low birthweight infants (<1750g) (Fletcher et al., 1997).

These studies therefore indicate that a particularfeature of the behavioral profile in children withhydrocephalus is the presence of hyperactivity. Thisis a behavioral style characterized by inattention,impulsivity, and overactivity (Taylor, 1999).Children with a pervasive and enduring extremehigh level of hyperactivity are designated asshowing attention deficityper-activity disorders(AD/HD) (Swanson et al., 1998). It has beenpostulated that AD/HD can develop as a conditioneither as a consequence of executive dysfunctionarising from disturbances in the fronto-dorsalstriatal circuit or of delay aversion arising fromaltered reward processes stemming from alterationsin the fronto-ventral striatal circuits (Sonuga-Barke,2002; Sonuga-Barke, 2004 this issue).

The presence of high levels of hyperactivity inchildren with hydrocephalus provides an opporttmityto test the generalizability of the dual pathwaymodel (DPM) of AD/HD. The aim of this paper isto establish whether dysfunctions in delay aversionand in executive function present separate but co-acting influences on the development of hyper-activity in children with hydrocephalus. If so, theresults would be a demonstration that the DPMcan account for the behavior of children withhyperactivity arising as a secondary consequenceof brain damage, as well as for children in thegeneral population for whom genetic factors areseen to play the primary etiological role (Kuntsi &Stevenson, 2000).

EXPERIMENTAL

Participants

The samples were obtained in two parallelstudies. For the Child Study (6-12 years), the

following numbers of children completed thestudy: 20 children with spina bifida only, 31children with hydrocephalus only, 16 children withspina bifida and hydrocephalus combined, 30normally developing children, and 31 childrenborn prematurely (defined here as less than 32weeks gestation). For the Adolescent Study (13-18years) the following numbers of childrencompleted the study: 9 adolescents with spinabifida only, 20 adolescents with hydrocephalusonly, 20 adolescents with spina bifida andhydrocephalus combined, and 27 normallydeveloping adolescents.

The following inclusion criteria were appliedfor participants in the Child and AdolescentStudies:1. English must be the child’s first language2. They must not have marked vision or hearing

impairments3. They must have a developmental age of

approximately 6 years or above.4. There should be no co-morbidity with brain

tumors5. Co-morbidity with meningitis or cerebral palsy

should be allowed only if criteria 2 and 3 aremet.

An invitation letter was sent to families attendingclinics in the South of England requesting theirparticipation in the study. The letter explained thata follow-up phone call would be made to themduring the next week to arrange a convenient timeif they were willing to take part. Families ofchildren in the general population sample wereobtained through contact with local schools.Information was sent out in school newsletters andinterested families contacted us to arrange anappointment.

Measures

Executive function. The CANTAB is acomputerized battery of tests of separate aspects ofcognitive functioning related to executive

HYPERACTIVITY AND HYDROCEPHALUS 15

function. The psychometric properties of theCANTAB are well established and it is becomingwidely adopted with children (Luciana, 2003).

In this study, 9 of the 11 subtests were used:Motor Screening (MOT), Stockings of Cambridge(SOC), Spatial Working Memory (SWM), ReactionTime (RTI), Paired Associates Learning (PAL),Pattern Recognition Memory (PRM), SpatialRecognition Memory (SRM), Big/Little Circle

(BLC), and Intra/Extra-dimensional Shift (lED).A discriminant function analysis was used to

obtain a weighted aggregate of the scores on thesubtests of the CANTAB that best predicted highscores (6 or more) on the SDQ Hyperactivity scale:Attention-Intra/Extra dimensional shift, Reactiontime; Visual memory-Pattern recognition memory,Spatial recognition memory, Paired associatelearning; Working memory and planning-Stockings ofCambridge, Spatial working memory.

Delay Aversion Task. This task uses a computerto present a game in which the child has to destroyenemy spacecraft by the child clicking on themouse. The aim was to score as many points aspossible and to motivate the child, the tester tellsthe child that (s)he will receive a small prize (apen) at the end. For each of the 20 trials, the childhas to choose between a small immediate reward(which gives a score of one point) and a delayedreward (score of three points). The test-re-testreliability of the measure has been found to begood (Kuntsi et al., 2001). For the present analysis,the tester’s ratings of the child’s behavior whilstwaiting for the delayed reward (on a three-pointscale) were used as an index of aversion to delay.

1Q. The following four sub-tests of the WISC-Ill R (Wechsler, 1992) were used to obtain a pro-rated full-scale IQ: comprehension, information,block design, and picture completion.

Hyperactivity. Hyperactivity was measuredbased on the parent’s report. The parents completed

the Strengths and Difficulties Questionnaire(Goodman, 1997). This questionnaire is a well-validated measure that includes a hyperactivity sub-scale that provides a score for the degree of hyper-activity shown by the child.

RESULTS

What is the degree of hyperactivity associatedwith hydrocephalus?

The mean score for participants with hydro-cephalus and normally developing controls on thefour sub-scales ofthe SDQ are presented in Table 1.

TABLE 1

a) Mean SDQ score for participants with hydro-ephalus and for normally developing controls

Dependentvariable

ConductproblemsEmotionalsymptomsPeerproblemsHyperactivity

HydrocephalusN=51

Mean SD

2.45 2.07

3.57

2.79

2.59

4.98 3.11

ControlsN=58

Mean SD

1.60

1.54

1.30

2.65

1.71

1.82

1.61

2.47

b) Summary ofMANOVA

Dependentvariable

ConductproblemsEmotionalsymptoms

Peerproblems

Hyperactivity

No. covariatesMean F psquare

19.65 5.51 <.02

114.67 21.09 <.001

138.75 30.61 <.001

146.29 18.82 <.001

With covariatesMean F Psquare

5.77 2.99 ns

13.92 3.19 ns

24.87 8.45 <.004

29.40 6.35 <.01


There were significant differences between thegroups for each of the subscales. To test whetherthere were specific behavioral problems, werepeated the ANOVA with the other three sub-scales as covariates. With this analysis, the effectsof hydrocephalus on conduct and emotionalproblems were no longer significant. Nevertheless,both hyperactivity and peer problems remained asshowing a significant excess of problems in theparticipants with hydrocephalus.

Is the degree of hyperactivity the same for hydro-cephalus alone and for hydrocephalus with spinabifida?

The above result compared participants withhydrocephalus alone with normally developingcontrols. Table 2 shows that in participants withhydrocephalus associated with spina bifida, thehyperactivity scores are significantly greater thanthose in normally developing controls. In addition,participants who were born prematurely also havesignificantly elevated levels of hyperactivity.Although the effect of hydrocephalus on hyper-activity is similar for hydrocephalus alone andhydrocephalus plus spina bifida, the subsequentanalyses were restricted to the hydrocephalus aloneparticipants to test for effects using a moreetiologically homogeneous group.

Does this association remain when the effects ofpremature birth are taken into account?

Because hydrocephalus can be associated with

premature birth, this finding raises the possibilitythat it is not hydrocephalus but premature birththat carries the risk of later hyperactivity.Accordingly, an analysis of the effects of pre-maturity and of hydrocephalus on the meanhyperactivity scores for children under the age of12 years (prematurely born adolescents were notincluded in the study) is presented in Table 3. Thechildren with hydrocephalus are divided into those

TABLE 2Comparison ofthe effects ofcondition on mean

SDQ hyperactivity scores

Condition

Spina bifida (S)Hydr0cephalu.s (H)Spina bifida +Hdro,,qepha!usS+H)Premature (P)

N29

51 4.98

36 4.31 2.18

31 4.03 2.98

Mean3.66

Controls (C) 57 2.65 2.47

MeanFactor df Square F p

Condition 4 39.204 5.25 <.001

Error 199 7.473

SD

2.87

3.11

Planned contrasts- compared to Controls

Condition

Spina bifida (S)Hydrocephalus (H)Spina bifida +Hydrocephalus (S+H)Premature (P)

Effect Tsize

0.41 1.61

0.94 4.42

0.67 2.85

0.56 2.27

(Condition mean- Control mean )/Control SD

P

<.001

<.005

TABLE 3

Comparison ofthe effects ofhydrocephalus andprematurity on mean SDQ hyperactivity scores

Group N MeanPremature

10 4.90HydrocephalusTerm HydrocePhalus 20 5.20

Premature 31 4.03

Term Controls 30 3.00

SD

3.41

3.37

2.98

2.74

MeanFactor df SquareHydrocephalus (h) 43.65

Prematurity (P) 2.49

Hx P 8.23

Error 87 9.25

F

4.72

0.27

0.89

P

<.033

ns

ns


with and without a premature birth and comparedin a 2x2 ANOVA with prematurely born childrenand normally developing controls. It can be seenthat only the hydrocephalus factor is significant.

Does this relate to other origins of hydrocephalus?

Hydrocephalus has a number of possiblecauses. The participants with hydrocephalus weredivided into four groups according to the origin oftheir condition: intracranial hemorrhage (n 21),meningitis (n 7), other (n 11), not known (n11). There were no significant differences betweenthese four groups in the mean SDQ hyperactivityscores (F(3,46) 0.18, ns).

Does this relate to the clinical features ofhydrocephalus?

A number of features of the presentation ofhydrocephalus might be related to the degree ofhyperactivity shown. These include the presenceof a shunt, undergoing a third ventriculostomy,occurrence of fits, association with cerebral palsyand visual difficulties, including squints andnystagmus. For each of these clinical features, theparticipants were divided into those with thefeature and those without. A series of independentsample t-tests were conducted with the SDQhyperactivity score as the dependent variable. Inno case was the mean significantly different forthose with or those without these clinical features.

Is there any evidence of moderators such as sex orage?

Two 2x2 ANOVAs were conducted toestablish whether sex and age respectively interactwith the presence of hydrocephalus to influencelevels of hyperactivity. For both sex [Sex (F(1,104)

0.06, p .802), Hydrocephalus (F(1,104) 17.39,p<.001), Sex x Hydrocephalus (F(1,104) 0.02,p .883)] and age [Age (F(1,104) 1.77, p .187),

TABLE 4

Correlation between cognitive measures and SDQhyperactivity in hydrocephalus and control

children

IQ EFDS

IQ 1.oo

EFDS -.45** 1.00

Delayaversion

-.07

SDQH

.08

Delayaversion

1.00

SDQH

1.00

EFDS EF diseriminant score; SDQH SDQ hyperactivityhydrocephalus (N 28), controls (N 28)

* p<.05, ** p<01

Hydrocephalus (F(1,104) 17.41, p<.001), Age xHydrocephalus (F(1,104) 0.01, p .976)], therewere neither significant main effects nor inter-actions between hydrocephalus and these factors.

Psychological correlates of hyperactivity in thehydrocephalus and in control samples

The above analyses have shown thathydrocephalus is associated with elevated levels ofhyperactivity, regardless of other associated clinicalcharacteristics of the child. The DPM suggests thatboth cognitive (executive function abilities) andmotivation (delay aversion) will be related to thedegree of hyperactivity. Table 4 presents thecorrelations between these plus IQ and the SDQhyperactivity score for the combined hydro-cephalus and control samples. It can be seen thathyperactivity is significantly correlated with eachof these three measures. Executive functioning andIQ are significantly correlated but neithercorrelates significantly with delay aversion. Thispattern of correlations provides initial support forthe notion that cognitive and motivational


Hydrocephalus

ControlHyperactivity

Final model" zz(5,N-60) 5.21, ns; CFI 1.00; RMSEA -0.03 (CI.9o 0.00 to 0.18)

Fig. 1: The dual pathway model fitted to the relationships between hydrocephalus and hyperactivity

characteristics are independent predictors ofhyperactivity. This possibility is investigated moresystematically in the following path analysis.

A path model of the influence of cognitive factorson hyperactivi,ty

The dual pathway model (DPM) predicts thatthe delay aversion and executive function measuresare independent predictors of hyperactivity.Accordingly, a path model was developed thatallows hydrocephalus to have both direct effects onhyperactivity and two separate indirect effects,mediated via delay aversion and executive function.

The correlations reported above indicated thatthe executive function influence on hyperactivitymight in part be a function of a more generalcognitive effect on behavior. The IQ measure wastherefore introduced as a possible mediator of theeffect of hydrocephalus on executive function. It isalso possible that IQ mediates some of the effectsof hydrocephalus on delay aversion. The DPMexplicitly excludes the possible impact ofexecutive function on delay aversion and viceversa. This path model was fitted to the variance/

covariances between the variables and the finalmodel retaining all the significant paths and noother is presented in Fig. 1.


As predicted by the DPM, hyperactivity is theproduct of two independent pathways. The effectof hydrocephalus on hyperactivity is equallydivided between two pathways. One indirect routemediated via delay aversion (.35 x -.29 -.10) anda second mediated via IQ and executive function(.43 x-.56 x .46 =-.11). Importantly, the modeldoes not require paths linking the motivational andcognitive routes to achieve a good fit to the data.

DISCUSSION

The DPM was developed to explain thefindings in studies of children with AD/HD

showing a series of consistent and well replicateddeficits in both motivational aspects of taskengagement (delay aversion) and in executivefunction and state regulation. We have shownpreviously that these two components influencinghyperactivity might reflect different etiologicalfactors. State regulation (shown for example byhigh variance in reaction times) carries geneticinfluences on ADHD. Delay aversion, on the otherhand, can carry some of the environmentalinfluences on ADHD (Kuntsi & Stevenson, 2001).

The studies from which the DPM wasdeveloped are based on the general population oron referred samples without establishedneurological deficits. The present paper aimed toextend the testing of the DPM to hyperactivity thatarises from frank neurological damage arisingfrom hydrocephalus. The findings show that in thisgroup of children and adolescents, hyperactivity isa relatively specific behavioral deficit that is notmoderated by gender or age. The origins ofhydrocephalus and the clinical characteristics ofthe participants were not related to the degree ofhyperactivity shown. Children and adolescentswith hydrocephalus are, as a group, at risk ofelevated hyperactivity.

The pattern of cognitive and motivationaldeficits associated with hyperactivity in thissample was similar to those in the referred andgeneral population samples mentioned above.Individual differences in executive function and indelay aversion were significantly related to thelevel of hyperactivity shown. These two factorsaccounted for the elevated rate of hyperactivity inchildren and adolescents with hydrocephalus, i.e.once the differences between normally developingcontrols and children/adolescents with hydro-cephalus were taken into account, there was nolonger a direct effect of hydrocephalus onhyperactivity. Within the neurologicallycompromised sample, the risk of hyperactivity wasaccounted for by two independent routes---one viamotivational factors reflecting delay aversion andthe second via executive dysfunction.

The findings therefore represent support forthe DPM and for its general applicability todiverse groups at risk for elevated levels ofhyperactivity. There are, however, a number oflimitations with the data presented in this paper.The first is that the number of children andadolescents meeting the criteria for ADHD weretoo few to use this measure as the dependentvariable in the analyses. Nevertheless, there isgood evidence that ADHD can be veryappropriately characterized as the extreme of acontinuum of degrees of hyperactivity (Gjone etal., 1996; Levy et al., 1997).

The second limitation was that although therewere a number of indicators of executivedysfunction, we used only a single measure ofdelay aversion. It would be important to replicatethese findings with a wider range ofdelay aversionindicators.

Third, although we have shown that the DPMcan account for the elevated levels of hyperactivityin children and adolescents with hydrocephalus,the generalizability of the DPM needs to beexamined in other groups having a high risk of


ADHD or with elevated levels of hyperactivity.One such group comprises children raised ininstitutional settings whose behavioral profilesarise from adverse early experiences. There isevidence from children born in the U.K. (Hodges& Tizard, 1989) and Romania (Kreppner et al.,2001) that institutional rearing carries an increasedrisk of hyperactivity. It would be of considerableinterest to establish whether the DPM can alsoaccount for elevated rates of hyperactivity inchildren with these early averse experiences.

These limitations do not detract from theconclusion that for children and adolescents withhydrocephalus, their levels of hyperactivity arisefrom the same two pathways that are responsiblefor hyperactive behavior in the general population.It appears that DPM is a powerful but parsimoniousaccount of the processes within the child that leadto hyperactive patterns ofbehavior.

ACKNOWLEDGMENTS

We would like to express out thanks to thefamilies and to the children and adolescents thattook part in this research for their willingparticipation. We had excellent cooperation fromteachers in local schools, both in identifyingcontrol subjects and in providing information ontheir behavioral and educational development. Theauthors would like to acknowledge thecontribution to the study made by Jane Wilkinson,Gemma Buckle, and Aine Fulcher in testing andinterviewing and by Teresa Rivers in givingadministrative support. We are grateful to cliniciansat Southampton General, Princess Anne, and JohnRadcliffe Hospitals for assistance with identifyingsuitable families for the study. Dr. Colin Kennedyprovided valuable guidance on the neurologicalaspects of the study. The study was funded byresearch grants from the Association for SpinaBifida and Hydrocephalus.

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hydrocephalus: a test of the dual pathway model

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