cross-cultural assessment of neuropsychological performance and electrical brain function measures:...

20
Intern. J. Neuroscience, 117:549–568, 2007 Copyright C 2007 Informa Healthcare ISSN: 0020-7454 / 1543-5245 online DOI: 10.1080/00207450600773665 CROSS-CULTURAL ASSESSMENT OF NEUROPSYCHOLOGICAL PERFORMANCE AND ELECTRICAL BRAIN FUNCTION MEASURES: ADDITIONAL VALIDATION OF AN INTERNATIONAL BRAIN DATABASE ROBERT H. PAUL Department of Psychology Behavioral Neuroscience University of Missouri, St. Louis St. Louis, Missouri, USA JOHN GUNSTAD Department of Psychology Kent State University Kent, Ohio, USA NICHOLAS COOPER The Brain Resource International Database Brain Resource Company Ultimo, NSW, Australia LEANNE M. WILLIAMS Department of Psychological Medicine University of Sydney, Australia and The Brain Dynamics Centre Western Clinical School Westmead Millennium Institute Hospital Received 8 March 2006. Address correspondence to Dr. Robert Paul, Department of Psychology, Behavioral Neuro- science University of Missouri, St. Louis, One University Blvd, Stadler 412, St. Louis, MO 63121, USA. E-mail: [email protected] 549 Int J Neurosci Downloaded from informahealthcare.com by Queen's University on 08/24/14 For personal use only.

Upload: evian

Post on 04-Feb-2017

215 views

Category:

Documents


0 download

TRANSCRIPT

Intern. J. Neuroscience, 117:549–568, 2007Copyright C© 2007 Informa HealthcareISSN: 0020-7454 / 1543-5245 onlineDOI: 10.1080/00207450600773665

CROSS-CULTURAL ASSESSMENT OFNEUROPSYCHOLOGICAL PERFORMANCE ANDELECTRICAL BRAIN FUNCTION MEASURES:ADDITIONAL VALIDATION OF ANINTERNATIONAL BRAIN DATABASE

ROBERT H. PAUL

Department of PsychologyBehavioral NeuroscienceUniversity of Missouri, St. LouisSt. Louis, Missouri, USA

JOHN GUNSTAD

Department of PsychologyKent State UniversityKent, Ohio, USA

NICHOLAS COOPER

The Brain Resource International DatabaseBrain Resource CompanyUltimo, NSW, Australia

LEANNE M. WILLIAMS

Department of Psychological Medicine University ofSydney, Australiaand The Brain Dynamics CentreWestern Clinical SchoolWestmead Millennium Institute Hospital

Received 8 March 2006.Address correspondence to Dr. Robert Paul, Department of Psychology, Behavioral Neuro-

science University of Missouri, St. Louis, One University Blvd, Stadler 412, St. Louis, MO 63121,USA. E-mail: [email protected]

549

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

550 R. H. PAUL ET AL.

University of SydneySydney, Australia

C. RICHARD CLARK

School of PsychologyFlinders UniversityAdelaide, Australia

RONALD A. COHEN

Department of PsychiatryCenters for Behavioral MedicineBrown Medical SchoolProvidence, Rhode Island, USA

JEFFREY J. LAWRENCE

Department of PsychiatryTransdisciplinary Research GroupBrown Medical SchoolProvidence, Rhode Island, USA

EVIAN GORDON

Department of Psychological Medicine Universityof Sydney, Australiaand The Brain Resource International Databaseand Brain Resource CompanyThe Brain Dynamics CentreWestern Clinical SchoolWestmead HospitalUniversity of SydneySydney, Australia

Previous studies haverevealed significant differences in performance on non-language dependent cognitive tests across international settings among youngerindividuals, with less pronounced differences evident among older individuals (>54years of age). The present study examined a broad range of cognitive performance aswell as electrophysiological indices of brain function in a multisite and internationalcontext. A total of 200 individuals in the United States, 233 individuals in Europe,and 829 individuals in Australia were administered a standardized computerizedneuropsychological battery, and complementary electroencephalogram (EEG)recordings were completed. Results revealed no significant differences in cognitive

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 551

function or electrophysiology across the three continents. Similarly, although therewas a main effect for age, the interaction between age and continent was notsignificant in any of the omnibus analyses. These findings indicate a high degree ofsimilarity in neurocognitive and electrophysiological function among individualsresiding in developed Western cultures, consistent with a traitlike status and thehigh heritability of the EEG.

Keywords cognition, cross-cultural assessment, EEG, multicultural, neuropsy-chology

INTRODUCTION

The international application of neuropsychological tests represents an impor-tant area of current and future focus. In some cultures, few neuropsychologicalmeasures have been developed for either research purposes or patient care, andthere may be pressure to directly modify and translate tests developed in othercultures. In cultures where many tests have been developed and are availablefor general use (e.g., in Europe and North America), the generalizability ofneuropsychological findings, normative data sets, and interpretative schemesacross countries and cultural settings is not a straightforward process.

In both scenarios, it remains unclear whether findings and relationshipsregarding neuropsychological function and underlying brain function holdacross international settings. As an example, it is reasonable to believe thatamong some cultures the concept of “timed” performance (e.g., on a test ofpsychomotor speed) or sustained performance (e.g., on a sustained attentiontest) has different value or interpretation relative to Western cultures (Angeret al., 1993; Byrd et al., 2004; Chung et al., 2003).

In addition, studies have demonstrated that in some cultures spatialrelations and other nonverbal skills are not prominent elements of educationaland cultural practice, and therefore, do not represent universal aspects ofcognitive ability (Ardila & Moreno, 2001; Boivin et al., 1995; Salmonet al., 1995; Salmon et al., 1989). As noted by Rosselli and Ardila (2003),inclusion of spatial-based tests in international testing environments likelyintroduces remarkable variability, and it could be added that de-emphasizinglanguage-based tests may significantly reduce the sensitivity and clinicalvalue of neuropsychological testing. Further, development of local normativedatabases for reference to clinical populations would not solve the cross-culturaldifferences, as the very concept under study has a different interpretation.

Few studies have examined whether patterns of neuropsychologicalperformances remain consistent across multiple international settings. Thisalmost certainly reflects, in part, the pragmatic difficulties associated with

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

552 R. H. PAUL ET AL.

these efforts. Anger et al. (1993) examined neuropsychological performancesamong 16–65-year-old healthy individuals on a cognitive battery developed toassess neurological effects of toxic exposure. In this study, participants from10 countries were administered measures of attention, information processingspeed, and visual retention. Results from this study revealed that performanceson simple reaction time and visual retention were similar across countries,whereas performances on measures of simple attention and informationprocessing speed differed significantly by continent.

Somewhat different results were reported by Levav et al. (1998). Inthis study, neuropsychological function was examined among persons from5 different countries ranging in age from 8 to 90. The participant populationwas heterogeneous, including individuals from the United States (urban andsuburban separately), Canada, Israel, Ireland, and Ecuador. Results fromthis study revealed very high consistency across countries on measures ofreaction time, and sustained attention, and subtle differences in performanceacross countries on tests of focused attention, problem solving, cognitiveflexibility, and response inhibition. Interestingly, the impact of culture onneuropsychological performances was largely absent among individuals overthe age of 54, although the explanation for this finding remains unclear. Whenconsidered from a clinical perspective, the authors noted that few differencesidentified across countries had clinical relevance based on the magnitude of theabsolute differences relative to the standard deviations. Overall the resultssuggest that most cognitive skills (especially reaction time and sustainedattention) are robust to cultural differences.

Although the Levav et al. (1998) study is highly informative, the authorsnoted a few methodological issues that warrant further study. Specifically,the study sample included relatives of persons with epilepsy and the childrenfrom Ecuador were infected with intestinal parasitic pathogens and they hadnot been treated for the infections at the time of the cognitive assessment. Asnoted by the authors, these factors raise questions regarding the generalizabilityof the findings. It is also important to note that tests involving language(except the Stroop) were avoided. As noted earlier, language measures areimportant aspects of cross-cultural studies, and there is extensive evidencedemonstrating the value of language-based neuropsychological tests indetecting memory impairment associated with dementia (for review see Bondi& Monsch, 1998), and differentiating different types of dementia (Tierney et al.,2001).

The current authors have recently demonstrated evidence of preliminaryvalidity of a computerized cognitive assessment system (Paul et al., 2005).

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 553

This study observed good correlations between the computerized measuresand traditional measures of cognitive function. It also demonstrated strongeffects for advanced age, with older individuals performing significantlymore poorly than younger individuals on most cognitive tests. The purposeof the present study was to examine neuropsychological function amongmedically and psychiatrically healthy individuals from three regions (NorthAmerica, Europe, and Australia) using the computerized battery of tests andelectrophysiological function. Individuals between the ages of 18 and 90were included and performances were examined for relationships to sex andeducation. Importantly, the computerized cognitive battery included tests thatmeasured similar constructs examined by Levav et al. (1998) including reactiontime, attention, cognitive flexibility as well as language-based tests (verbalmemory and verbal response fluency).

To the authors’ knowledge brain function assessed using the electroen-cephalogram (EEG) has not been compared between cultures and/or countries.Because the EEG has very high reliability (both intra- and inter-subject;e.g., Gasser et al., 1985; Pollock et al., 1991), and is unlikely to beinfluenced by cultural factors that might impact on cognitive testing (suchas language-based differences), it would be expected to be very consistentacross sites. From another line of research, the only indication of minorvariations across countries are findings from a clinical EEG study of epilepsy,which reported small variations in the abnormal EEG characteristics usedto classify epileptic syndromes across developed and developing countries(Shah et al., 1992). Because these differences were in the context of generallysimilar EEG profiles, Shah et al. suggested that they might reflect smallgenetic differences, which would be consistent with the high heritability ofthe EEG (van Beijsterveldt et al., 2002). Studies of healthy subjects show thatactivity in the EEG alpha frequency band (8–13 Hz) is a particularly closecorrelate of cognitive performance. This study expected that, as for cognitiveperformance, normal alpha activity would show the same characteristics acrosssites.

Electrophysiological (EEG) indices of brain function were also examinedto determine whether any regional differences in cognitive function covariedwith direct measures of electrical brain activity. It was predicted that cognitiveperformances and EEG indices would be similar across these sites andrelationships between age, education, and sex would hold across the threeregions. Evidence of similar performances and EEG findings across the threecontinents would provide further evidence of validity for the computerizedsystem and the application of the Brain Resource International Database.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

554 R. H. PAUL ET AL.

METHODS

Participants

A total of 1,288 healthy individuals ranging in age from 18–82 were includedin the present study. See Table 1 for a list of the participants included from eachcontinent and the related demographic data. The Australian cohort consisted ofa larger sample compared to the U.S. and European sites. All individuals wererecruited as part of the Brain Resource International Database (BRID; Gordon,2003). Participants were required to be free of any psychological or physicalcondition that could negatively influence cognitive performance. As such,individuals with a history of mental illness, physical brain injury, neurologicaldisorder, genetic disorder, or other medical condition (hypertension, diabetes,cardiac disease, thyroid disease), were excluded. Similarly, individuals with ahistory of drug or alcohol addiction were excluded. Major psychopathologywas screen using the SPHERE (Hickie et al., 2001), which was constructedfor use in large scale studies, and is valid and reliable structured questionnaire.In addition to these exclusion criteria, individuals with a family history ofschizophrenia, bipolar disorder, or attention deficit disorder were excluded.

All participants completed a Web-based questionnaire to obtain demo-graphic data including age, gender, years of education, and current mood.Mood was examined with the short form of the Depression Anxiety StressScale (DASS; Lovibond & Lovibond, 1995). All participants voluntarily signeda written informed consent form to participate in the database, according tolocal Institutional Review Boards.

Table 1. General demographics for the overall sample

Sample size Age Education

Main site 18–53 54 & over 18–53 54 & over 18–53 54 & over

United StatesRhode Island 65 48 32.6 (10.2) 65.3 (7.5) 15.2 (1.8) 14.5 (2.2)New York 77 10 30.7 (8.7) 62.2 (6.7) 15.4 (2.2) 13.7 (3.3)

EuropeHolland 95 43 30.0 (5.9) 65.0 (7.9) 13.5 (3.1) 14.4 (2.1)London 84 11 33.9 (9.1) 59.3 (4.6) 14.1 (2.9) 13.7 (3.3)

AustraliaAdelaide 280 128 32.9 (11.1) 64.1 (6.5) 14.4 (2.3) 12.2 (2.6)Sydney 357 64 30.5 (10.3) 63.6 (7.9) 15.0 (2.2) 13.9 (2.9)

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 555

To facilitate comparison to the extant literature (Levav et al., 1998),the samples from each site were subdivided. Specifically, the participantswere subdivided into 18 to 53 year olds, and 54 to 82 year olds. The basicdemographic data for each of these cohorts are presented in Table 1.

Procedure

All participants completed a computerized battery of cognitive measures. Thecomputerized battery is both reliable (Williams et al., 2005) and valid (Paulet al., 2005). The same tests were administered to all individuals. The testingenvironments at each of the testing sites were identical in terms of computerhardware/software, instructions (using both text and audio files), and generalprocedures. Two separate sites were involved in collecting data in each region(U.S., Australia, and Europe). The computerized battery was administeredin a sound-attenuated testing room, with participants seated in front of atouch-screen (NEC MultiSync LCD 1530V). The touch-screen was poweredby a personal computer located in a separate room. No keyboard or mouse wasrequired for the computerized tests, and therefore the apparatus did not resemblea traditional computer. Moreover, computer literacy in terms of keyboard andmouse skills was not required. The cognitive tests were administered usingstandardized task instructions presented via headphones and visual screendisplay. All responses to the tests were recorded via the touch-screen or recordedas wav. files. Each test was explained thoroughly in English (for the U.S.,Australian, and Great Britain sites) or Dutch (Netherlands). Further, to increasefamiliarity, country-specific accents were used for the three English versions.

Each cognitive test was preceded by a practice trial and participants wererequired to successfully complete the practice trial prior to the test trial for eachmeasure. In the event that an individual failed a practice trial, the computerizedbattery immediately moved on to the next test in the battery. The order of testadministration was fixed as part of the standardization protocols.

Computerized Cognitive Tests

The computerized cognitive battery tapped five domains of cognitive functionincluding sensori-motor, language, memory, executive planning, and attention.Automated software programs were employed to score most responses to thetests, however, hand-scoring was conducted on the wav. files (the language testsand the verbal memory test). Trained research assistants conducted the handscoring of the wav. files. The individual tests and the dependent measures foreach test are described in what follows.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

556 R. H. PAUL ET AL.

Sensori-Motor Domain.

Simple motor tapping task: Participants were required to tap a circle on thetouch-screen with their index finger as fast as possible for 30 s. The dependentvariable was total number of taps with the dominant hand.

Choice reaction time task: On this test participants were presented with fourcircles at the top of the touch screen. They were required to rest the palm of theirdominant hand at the base of the touch screen. The participants were informedthat one of the four circles would illuminate, and they were required to touchthe illuminated circle with their index finger as fast as possible. Twenty trialswere administered in random order with a random delay between trials of 2–4s. The dependent variable was the mean reaction time across trials.

Attention Domain.

Span of visual memory: This test is a computerized adaptation of the SpatialSpan test from the Wechsler Memory Scale (III; Wechsler, 1999). Participantswere presented with squares arranged in a random pattern and the squareswere highlighted in a sequential order. Participants were required to repeat theorder in which the squares were highlighted by touching the squares with theirforefinger. Both forward and reverse trials were conducted. The total correctwas the dependent variable.

Digit span: Participants were presented with a series of digits on thetouch-screen separated by a one-second interval. The participant was thenimmediately asked to enter the digits on a numeric keypad on the touch-screen.In the first part of the test, participants were required to recall the digits inforward order (Digits forwards); in the second part, they were required to recallthem in reverse order (Digits backwards). In each part, the number of digitsin each sequence was gradually increased with two sequences at each level.The dependent measure for each part was the maximum number of digits theparticipant recalled without error.

Continuous performance task: On this test, a series of letters (B, C, D, orG) were presented to the participant on the computer screen (for 200 ms),separated by an interval of 2.5 s. When the same letter appeared twice in arow, the participant was asked to depress a response box on the computerscreen. There were 125 stimuli presented in total, 85 being non-target letters

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 557

and 20 being target letters (i.e., repetitions of the previous letter). The dependentvariables was the number of false positive errors.

Switching of attention task: This test is a computerized adaptation of theTrail Making test (Reitan, 1958). It consists of two parts. In the first part, theparticipant was presented with a pattern of 25 numbers in circles and asked totouch them in ascending numerical sequence (i.e., 1 2 3 . . .). Following eachcorrect connection, a line is drawn automatically to connect it to the precedingnumber in the sequence. This allowed the participant to visualize the pathtouched. The dependent variable was time to completion. The second part ofthe test is described later.

Executive Function Domain.

Switching of attention task; part 2: In the second part of this task, theparticipant was presented with a pattern of 13 numbers (1–13) and 12 letters(A–L) on the screen and was required to touch numbers and letters alternativelyin ascending sequence (i.e., 1 A 2 B 3 C. . .). The dependent variable was timeto completion.

Verbal interference: This task taps the ability to inhibit automatic andirrelevant responses and has similarities to the Stroop task (Golden, 1978).The participant was presented with colored words presented serially one at atime. Each word was drawn from the following set of lower case words: red,yellow, green, and blue. The color of each word is drawn from the followingset of colors: red, yellow, green, and blue. A response pad was provided onthe touch-screen and it consisted of four possible words displayed in black andin fixed format. The test has two parts. In part 1, the participant is required toidentify the name of each word as quickly as possible after it is presented onthe screen. In part 2, the participant is required to name the color of each wordas quickly as possible. Each part lasts for 1 min. Responses are made on thescreen by touching the appropriate word on the response pad. The dependentvariable was the difference in the number of words correctly identified betweentrial 2 and trial 1 (i.e., interference).

Maze task: This task was a computerized adaptation of the Austin Maze(Walsh, 1985). The participant was presented with a grid (8 × 8 matrix) ofcircles on the computer screen. The object of the task was to identify thehidden path through the grid, from the beginning point at the bottom of the grid

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

558 R. H. PAUL ET AL.

to the end point at the top. The participant was able to navigate around the gridby pressing arrow keys (up, down, left, right). A total of 24 consecutive correctmoves were required to complete the maze. The participant was presented withone tone (and a red cross at the bottom of the screen) if they made an incorrectmove, and a different tone (and a green tick at the bottom of the screen) if theymade a correct move. Only one maze was presented across trials, and the testended when the participant completed the maze twice without error or after 10min had elapsed. The dependent variable was the total number of errors.

Language Domain.

Letter fluency: Participants were required to generate by speech words thatbegan with the letters F, A, and S. Sixty were allowed for each letter and propernouns were not allowed. Responses were recorded via the microphone andhand-scored. Intrusive or perseverative responses were not included in the totalnumber correct. The total number of correct words generated across the threetrials was the dependent measure.

Animal fluency: Participants were required to name animals as quickly aspossible for 60 s. Intrusions and perseverative responses were not allowed.Total correct served as the dependent variable.

Memory Domain.

Verbal list-learning: The participants were read a list of 12 words, which theywere asked to memorize. The list contained 12 concrete words from the Englishlanguage. Words were closely matched on concreteness, number of letters, andfrequency. The list was presented orally 4 times (and received by the participantusing headphones). On each of the 4 trials, the participant was required to recallas many words as possible by speaking directly into the attached microphone.The participant was then presented with a list of distracter words and asked torecall them after presentation. Immediately following this, the participant wasthen asked to recall the 12 words from the original list (short-delay recall trial).A long delayed recall trial was completed approximately 20 min later aftera number of intervening tasks. A recognition trial was then completed afterthe delayed trial. The dependent variables were the number of words correctlyrecalled across the four learning trials and the delayed recall trial.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 559

Psychophysiology Acquisition and Analysis. Participants were seated ina sound and light attenuated room, set at an ambient temperature of 24◦C.Each individual’s hearing threshold was assessed prior to data acquisition, andall auditory stimuli were presented at 75 db above each individual’s hearingthreshold. Data were acquired from a 32-channel Nuamps cap (Neuroscan).The channels included: Fp1, Fp2, F7, F3, Fz, F4, F8, FC3, FCz, FC4, T3, C3,Cz, C4, T4, CP3, CPz, CP4, T5, P3, Pz, P4, T6, O1, Oz and O2 electrodesites, 4 EOG channels, orbicularis oculus and masseter (Quikcap; NuAmps;10–20 electrode international system). Data were recorded relative to the virtualground, but referenced offline to linked mastoids. Horizontal eye movementswere recorded with electrodes placed 1.5 cm lateral to the outer canthus of eacheye. Vertical eye movements were recorded with electrodes placed 3 mm abovethe middle of the left eyebrow and 1.5 cm below the middle of the left bottomeye-lid. Skin resistance was <5 kOhms. A continuous acquisition system wasemployed and data were EOG corrected offline.

As part of the overall Brain Resource International Database, data acquiredin the current study were recorded during a resting eyes-open paradigm,a resting eyes-closed paradigm, and during an auditory oddball paradigm.Paradigm order was fixed within subjects, such that the eyes-open paradigmand eyes-closed paradigm were done first for 4 min, followed by a 2-minauditory habituation period, followed by a 6-min auditory oddball trial. For thepurpose of the present study, data were included from the resting eyes-opencondition, and the peak alpha frequencies (8–13 Hz) at midline sites (Fz, Cz,Pz) were the dependent variables. It was expected that no significant differenceswould be found between regions on midline sites.

Data Analysis

Raw scores more than 4 standard deviations from the group mean were removed(<5% of the data), and raw scores on two tests (Maze errors, and switchingof attention mixed) were log-transformed due to skewed distributions. Thelog-transformed scores were included in the primary data analyses. Cognitiveand electrophysiological function were examined in overall 2 × 2 MANCOVAwith age (18–53 and 54–82) and continent (Australia, U.S., Europe) servingas the independent variables and performances on the cognitive tests and theelectrophysiological measures as the dependent variables; education and genderwere entered as covariates. Separate MANCOVAs were conducted for thecognitive variables and the electrophysiological variables.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

560 R. H. PAUL ET AL.

RESULTS

Main Effects of Continent on Neuropsychological Performanceand EEG Indices

The overall model examining the effect of continent on neuropsychologicalperformance was not statistically significant (F = .960, p > .05). Similarly,the overall model examining the effect of continent on EEG indices was notstatistically significant (F = .184, p > .05).

Interactions between Age and Continent on NeuropsychologicalPerformance and EEG Indices

The overall model examining the interaction of Age and Continent was notstatistically for either Neuropsychological performances (F = .804, p > .05)or EEG indices (F = 1.65, p > .05).

Exploratory Analyses of Neuropsychological Performance among18–53 Year Olds

Although the ombmibus tests were not statistically significant, exploratoryunivariate analyses were conducted to allow for comparison to previous studies.It is important to note, however, that caution is warranted in interpretingthese univariate analyses given the lack of statistical significance from theoverall MANCOVA. Results of these analyses revealed a number of significantdifferences in performance on the cognitive battery. Specifically, the regionsdiffered on animal fluency (F(2, 741) = 4.8, p < .05), switching of attentiondigits (F(2, 862) = 7.9, p < .05), verbal memory total recall (F(2, 415) = 34.4,p < .01), span of visual memory (F(2, 863) = 4.9, p < .05), choice reactiontime (F(2, 837) = 12.6), and maze errors (F(2, 733) = 3.2, p < .05).

Post-hoc Tukey’s tests revealed that U.S. participants performed signif-icantly lower than the Australians on animal fluency (p < .05), Australianparticipants performed significantly lower than U.S. participants on switchingof attention digits (p < .05), and European participants performed significantlylower than both Australian and U.S. participants on total verbal recall (p < .05).Further, European participants performed lower than Australian participants onthe span of visual memory test (p < .05). U.S. participants were significantlyslower than European participants on choice reaction time (p < .05). Further,European participants committed more errors on the maze test than Australianparticipants (ps < .05), and Australian participants committed fewer falsepositive errors on the sustained attention task compared to European and U.S.participants.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 561

Table 2. Exploratory analyses of cognitive performances for individuals 18–53

Cognitive measure Australia U.S. Europe F

Motor tapping (total) 170.0 (27.1) 166.3 (21.4) 164.9 (27.1) 2.4Choice reaction time 694.0 (114.7) 757.9 (157.4) 697.5 (127.7) 12.6∗Span of visual memory 8.12 (2.01) 7.8 (1.92) 7.57 (2.05) 4.9∗Digit span total 7.77 (2.39) 7.7 (2.36) 7.4 (2.31) 1.2Sustained attention .81 (1.12) .82 (1.33) .68 (1.45) .76Switching of attention digits 9.8 (2.5) 9.9 (2.5) 9.9 (2.3) 7.9∗Switching of attention mixed 42.5 (10.4) 44.0 (11.3) 43.1 (10.5) 1.1Verbal interference 18.7 (2.91) 18.2 (2.80) 18.0 (2.51) .23Maze errors 3.3 (.481) 3.45 (.497) 3.49 (.554) 3.2∗Letter fluency 15.5 (3.54) 16.0 (3.99) 15.6 (3.94) .90Animal fluency 24.8 (5.57) 23.1 (5.53) 24.5 (6.04) 4.8∗Verbal memory learning trials 33.6 (5.04) 32.9 (5.19) 27.3 (9.87) 34.4∗Verbal long recall 7.9 (2.28) 7.6 (1.96) 8.4 (2.37) 2.7

Given the large sample sizes included in the analyses, it is important toconsider the clinical magnitude of the noted differences. A review of Table 2highlights the degree of similarity of scores across regions despite the significantdifferences. From a clinical perspective, most of the significant differencesidentified in the posthoc analyses were not meaningful (i.e., did not exceed2 standard deviations from the mean of comparison groups). For example,performances on the span of visual attention test all fell within one response ofone another; a value far less than the pooled standard deviation. Similarly, onthe switching of attention digits test, participants from the three continents werenearly identical. After considering the overall magnitude of these comparisons,none of the differences across regions were clinically meaningful.

Exploratory Analyses of EEG Indices—18–53 Year Olds

The exploratory univariate contrasts comparing groups on EEG indices revealedno significant differences (see Table 3).

Table 3. Exploratory analyses of EEG variables for individuals 18–53

EEG Measure Australia U.S. Europe F

Eyes open Alpha power Pz 4.2 (.93) 4.1 (.90) 4.0 (.97) 0.83Eyes open Alpha power Cz 3.9 (.72) 3.9 (.70) 3.8 (.77) 1.2Eyes open Alpha power Fz 3.8 (.67) 3.8 (.60) 3.8 (.83) 0.0

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

562 R. H. PAUL ET AL.

Table 4. Exploratory analyses of cognitive performances for individuals 54 and over

Cognitive measure Australia U.S. Europe F

Motor tapping—total taps 156.4 (28.4) 156.2 (25.5) 151.0 (26.9) .59Choice reaction time 834.1 (176.4) 783.1 (155.1) 766.8 (168.8) 3.5Span of visual memory 6.3 (2.0) 5.7 (1.9) 6.0 (2.4) 2.0Digit span total 6.8 (2.3) 6.7 (2.1) 5.9 (1.8) 2.7Sustained attention 1.1 (1.6) .86 (1.3) .89 (1.0) 1.0Switching of attention digits 10.2 (.26) 10.2 (.27) 10.1 (.26) .49Switching of attention mixed 55.7 (7.2) 54.6 (9.2) 55.7 (7.8) .67Verbal interference 15.2 (2.5) 15.6 (2.6) 14.8 (3.15) 1.7Maze errors 3.8 (.54) 4.1 (.66) 3.8 (.56) 3.2∗Letter fluency 15.5 (4.4) 14.1 (4.1) 14.1 (3.4) 2.1Animal fluency 19.7 (4.9) 19.1 (4.7) 21.6 (5.1) 1.0Verbal memory learning trials 29.8 (4.8) 27.0 (5.8) 27.3 (7.5) 2.9Verbal long recall 6.4 (2.1) 5.0 (2.2) 6.9 (1.9) 5.4∗

∗p < .05.

Exploratory Analyses of NeuropsychologicalPerformance—54–82 Year Olds

An ANOVA was conducted to examine cognitive performances across thethree regions. The overall ANOVA revealed a few significant differencesin performance on the cognitive battery (See Table 4). Specifically, regionsdiffered on verbal delayed recall (F(2, 115) = 5.4, p < .05), choice reactiontime (F(2, 257) = 3.5), and maze errors (F(2, 228) = 3.2, p < .05). Post-hocTukey’s comparisons revealed that U.S. participants performed lower thanAustralian and European participants on the verbal memory delayed recalltest (p < .05). Australian participants were significantly slower than allother participants on choice reaction time, and U.S. participants committedsignificantly more errors than all other participants on the maze task. Consistentwith the procedure described earlier for the younger subjects, the absolutedifferences in performances were examined for clinical significance, and noneof the comparisons were considered clinically meaningful.

Exploratory Analyses of EEG Indices—54–82 Year Olds

Similar to the results for the younger cohort, the exploratory contrastscomparing groups on the EEG indices revealed no significant differences onany of the electrophysiological sites (Table 5).

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 563

Table 5. Exploratory analyses of EEG variables for individuals 54 and over

EEG measure Australia U.S. Europe F

Eyes open Alpha power Pz 3.6 (.85) 3.8 (.85) 3.9 (.97) 1.7Eyes open Alpha power Cz 3.6 (.72) 3.7 (.73) 3.8 (.86) 1.3Eyes open Alpha power Fz 3.6 (.85) 3.7 (.73) 3.7 (.78) 1.0

DISCUSSION

To the authors’ knowledge this report represents the most extensive analysisof multinational neuropsychological performance and electrophysiologicalindices across the adult lifespan. Using a computerized battery of teststhe authors examined cognitive function across three Western cultures andidentified a number of subtle differences. However, the results were largelyinfluenced by the large sample size included in the study and relatedly, the highpower to detect small differences. Of the cognitive performances comparedacross sites, there was no pattern of superior or inferior performance byregion, and none of the differences were determined to be clinically relevant.Importantly, significant differences in performance were not identified acrossregions according to the age of the participants. In this study, performancesacross sites were generally similar for both younger and older individuals.

Levav et al. (1998) examined multinational neuropsychological perfor-mances among individuals residing in the United States, Israel, Ireland, Canada,and Ecuador. Children, adolescents, middle age adults, and older adults wereincluded in the study, although the age groupings were broad (e.g., 13–53year olds) and as such were likely influenced by significant developmentaleffects. Cognitive tests were administered that avoided significant languagecomponents (e.g., verbal memory) and there was a strong emphasis onattention, information processing speed and executive function. For the youngerindividuals (ages 18–53), the authors reported significant main effects forcountry of origin, particularly on tests of executive function and morecomplex information processing speed; differences were not observed forsimple attention and reaction time. Importantly, these group differences wereretained after removing data from Ecuador from the analyses (due to lowscores). Another important finding from the study is that most differences incognitive function across regions were limited to the older group (54 yearsand older). Overall, the authors concluded that the magnitude of differencesin cognitive performances across most sites was unlikely to be of clinicalsignificance.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

564 R. H. PAUL ET AL.

The results are generally in agreement with those reported by Levav et al.(1998). Although the omnibus test results were not significant, the exploratoryunivariate contrasts revealed subtle differences in cognitive performance acrosssites among younger individuals. Further, most of the identified differenceswere evident on the more demanding tests. By contrast, performance onmeasures of simple attention (e.g., Digit Span) did not differ across the sites.Significant differences across regions were identified on a test of simple visualattention (Span of Visual Memory), although the magnitude of this differencewas relatively small. Although it is possible that some individuals within thegroups evidenced significantly poorer performances on individual tests (e.g.,Choice Reaction Time and Verbal Memory), the overall group scores wereremarkably similar. Another consistent finding with the results of the Levavet al. study is that fewer significant differences were observed across regionsamong the older sample.

The similarity between the present findings and those reported byLevav et al. (1998) are noteworthy considering the degree of methodologicaldifferences between the studies. The present study only examined Westerncultures, whereas Levav et al. also examined participants in Ecuador,although this group was removed from many analyses due to low scoresand the small sample size. This study also focused only on adults to avoidconfounding neurodevelopmental effects, which are well characterized intothe late adolescence (Nagy et al., 2004; Paus, 2005; Span et al., 2004).Finally, the present study group comprised very healthy individuals, who hadbeen screened for both medical and psychiatric conditions among potentialparticipants and their first-degree relatives. In light of these methodologicaladditions, it is reassuring that the results between studies are highly consistent.As such, the authors agree with the conclusion offered by Levav et al. (1998)that cross-cultural assessment in a multinational setting should be consideredclinically practical, at least in developed regions.

A major contribution of the present study is the observation thatlanguage-based tests can provide meaningful information in multinationalstudies, including settings that necessitate translation of test instructions. Thecomputerized cognitive battery included in the present study involved four teststhat included a strong language component (Letter Fluency, Animal Fluency,Verbal Memory, Spot The Word), and additional tests with less involvedlanguage involvement (Switching of Attention Mixed, Verbal Interference). Theimportance of these language-based tests for clinical and research applicationshas been well described, as these particular tests are important measures forthe diagnosis of mild cognitive impairment, the prodromal stage of dementia,

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 565

and probable Alzheimer’s disease (Albert et al., 2001). These particular testsalso facilitate the differentiation of AD from other forms of dementia (Tierneyet al., 2001).

The language requirements for the computerized test battery were alladapted for use in Holland, and required complete translation in Dutch.The observation that performances did not differ between participants inHolland and London in the current study provides strong support for theuse of language-based tests in multinational settings. The importance of thisfinding should not be underemphasized, as a large literature has emergeddemonstrating that efforts to develop “culture free” nonlanguage cognitive testshave largely failed (for review see Rosselli & Ardila, 2003). With the exceptionof remote regions and similar special circumstances, language demands areimportant markers of cognitive integrity, and are therefore critical aspects ofcomprehensive cognitive assessment.

Additional studies are needed to examine this particular issue using thecomputerized neuropsychological tests in non-western and less developedcountries. This will be particularly true regarding populations that have lessfamiliarity with computerized testing systems. The methods employed inthe current study were developed with the intent of minimizing confoundsassociated with computer familiarity. For example, the computerized systemdoes not require the use of a mouse or keyboard and each test is precededby an example and a practice test to ensure familiarity with the demands ofeach test. Nevertheless, additional studies are needed in order to determine theconsistency of applications in cross-cultural populations.

The general absence of meaningful differences across continents is furthersupported by the results of the electrophysiological analyses. There were nosignificant differences between continents on any of the electrophysiologicalindices. The authors are not aware of many previous efforts to incorporateelectrophysiological methodology in multinational studies of brain functionsimilar to approach employed in the current investigation. Results from thepresent study suggest that highly consistent data can be obtained across sites,however, it is important to recognize the potential pragmatic considerationswith these efforts. The methodology incorporated in the BRID was highlystandardized and all EEG data were analyzed at one central facility. Ensuringdata fidelity in future multisite international studies will require a similar degreeof standardization.

In conclusion the results extend previous work demonstrating the utility ofmultinational cognitive assessment. This study included a broader range of tests,including language-based tests, and the cognitive measures were administered

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

566 R. H. PAUL ET AL.

on an automated computer system. A primary benefit of the latter is thestandardization of test administration and scoring, which serves to decreaseerror variance. In agreement with previous work, this study suggests thatmultinational cognitive and psychophysiological assessment is feasible, andfew clinically meaningful differences exist on these indices of brain functionamong individuals in Western cultures. Collectively, the results provide furtherevidence of validity for the BRID computerized system. It is important tonote that the cohorts were all derived from industrialized nations and thereforeapplication of these methods to resource-poor cultures will be an importantnext step. These future studies will be important as the methodology hasthe potential to significantly contribute to patient assessment and clinicalcare.

REFERENCES

Albert, M. S., Moss, M. B., Tanzi, R., & Jones, K. (2001). Preclinical prediction of ADusing neuropsychological tests. Journal of the International NeuropsychologicalSociety, 7, 631–639.

Anger, W. K., Cassitto, M. G., Liang, Y. X., Amador, R., Hooisma, J., Chrislip, D. W.,Mergler, D., Keifer, M., Hortnagl, J., Fournier, L., Dudek, B., & Zsogon, E. (1993).Comparison of performance from three continents on the WHO-RecommendedNeurobehavioral Core Test Battery. Environmental Research, 62(1), 125–147.

Ardila, A., & Moreno, S. (2001). Neuropsychological test performance in AruacoIndians: An exploratory study. Journal of the International NeuropsychologicalSociety, 7(4), 510–515.

Baddeley, A., Emslie, H., & Nimmo-Smith, I. (1993). The Spot-the-Word test: A robustestimate of verbal intelligence based on lexical decision. British Journal of ClinicalPsychology, 32, 55–65.

Boivin, M. J., Giordani, B., & Bornefeld, B. (1995). Use of the tactual performancetest for cognitive ability testing with African children. Neuropsychology, 9, 409–417.

Bondi, M. W., & Monsch, A. U. (1998). The role of memory assessment in preclinicalAlzheimer’s disease. In A. I. Troster (Ed.), Memory in neurodegenerative disease:Biological, cognitive and clinical perspectives. (pp. 278–289). Cambridge:Cambridge University Press.

Byrd, D. A., Touradji, P., Tang, M. X., & Manly, J. J. (2004). Cancellation testperformance in African American, Hispanic, and White elderly. Journal of theInternational Neuropsychological Society, 10(3), 401–411.

Chung, J. H., Sakong, J., Kang, P. S., Kim, C. Y., Lee, K. S., Jeon, M. J., Sung, N. J.,Ahn, S. H., & Won, K. C. (2003). Cross-cultural comparison of neurobehavioralperformance in Asian workers. Neurotoxicology, 24, 533–540.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

INTERNATIONAL NEUROPSYCHOLOGICAL ASSESSMENT 567

Gasser, T., Bacher, P., & Steinberg, H. (1985). Test-retest reliability of spectralparameters of the EEG. Electroencephalography and Clinical Neurophysiology,60, 312–319.

Golden, C. (1978). Stroop Color and Word Test, Chicago: Stoelting Company.Gordon, E. (2003). Integrative neuroscience. Neuropsychopharmacology, 28, 52–58.La Rue, A., Romero, L. J., Ortiz, I. E., Liang, H. C., & Lindeman, R. D. (1999).

Neuropsychological performance of Hispanic and non-Hispanic older adults: Anepidemiologic survey. The Clinical Neuropsychologist, 13(4), 474–486.

Levav, M., Mirsky, A. F., French, L. M., & Bartko, J. J. (1998). Multinationalneuropsychological testing: Performance of children and adults. Journal of Clinicaland Experimental Neuropsychology, 20(5), 658–672.

Lovibond, P., & Lovibond, S. (1995). The structure of negative emotional states:comparison of the Depression Anxiety Stress Scales (DASS) with the BeckDepression and Anxiety Inventories. Behavior Research and Therapy, 33(3),335–343.

Nagy, Z., Westerberg, H., & Klingberg, T. (2004). Maturation of white matter isassociated with the development of cognitive functions during childhood. Journalof Cognitive Neuroscience, 16(7), 1227–1233.

Paul, R. H., Lawrence, J., Williams, L. M., Richard, C. C., Cooper, N., & Gordon,E. (2005). Preliminary validity of “integneuro”: a new computerized batteryof neurocognitive tests. International Journal of Neuroscience, 115(11), 1549–1567.

Paus, T. (2005). Mapping brain maturation and cognitive development duringadolescence. Trends in Cognitive Sciences, 9(2), 60–68.

Pollock, V. E., Schneider, L. S., & Lyness, S. A. (1991). Reliability of topographicquantitative EEG amplitude in healthy late-middle-aged and elderly subjects.Electroencephalography and Clinical Neurophysiology, 79, 20–26.

Reitan, R. (1958). Validity of the Trail Making Test as an indicator of organic braindamage. Perceptual and Motor Skills, 8, 271–276.

Rosselli, M., & Ardila, A. (2003). The impact of culture and education on non-verbalneuropsychological measurements: A critical review. Brain and Cognition, 52(3),326–333.

Salmon, D. P., Jin, H., Zhang, M., Grant, I., & Yu, E. (1995). Neuropsychologicalassessment of Chinese elderly in the Shanghai Dementia Survey. The ClinicalNeuropsychologist, 9, 159–168.

Salmon, D. P., Riekkinen, P. J., Katzman, R., Zhang, M. Y., Jin, H., & Yu, E. (1989).Cross-cultural studies of dementia. A comparison of mini-mental state examinationperformance in Finland and China. Archives of Neurology, 46(7), 769–772.

Shah, K. N., Rajadhyaksha, S. B., Shah, V. S., Shah, N. S., & Desai, V. G. (1992).Experience with the International League Against Epilepsy classifications ofepileptic seizures and epilepsies and epileptic syndrome in epileptic children in adeveloping country. Epilepsia, 33(6), 1072–1077.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.

568 R. H. PAUL ET AL.

Span, M. M., Ridderinkh, K. R., & van derMolen, M. W. (2004). Age-related changesin the efficiency of cognitive processing across the life span. Acta Psychologica(Amst), 117(2), 155–183.

Tierney, M. C., Black, S. E., Szalai, J. P., Snow, W. G., Fisher, R. H., Nadon, G.,& Chui, H. C. (2001). Recognition memory and verbal fluency differentiateprobable Alzheimer disease from subcortical ischemic vascular dementia. Archivesof Neurology, 58, 1654–1659.

van Beijsterveldt, C. E., & van Baal, G. C. (2002). Twin and family studies of the humanelectroencephalogram: A review and a meta-analysis. Biological Psychology, 61,111–138.

Wechsler, D. (1999). Wechsler Adult Intelligence Scale-Three. San Antonio: ThePsychological Corporation.

Williams, L. M., Simms, E., Clark, C. R., Paul, R. H., Rowe, D., & Gordon, E. (2005).The test-retest reliability of a standardized neurocognitive and neurophysiologicaltest battery: “Neuromarker.”. International Journal of Neuroscience, 115(12),1605–1630.

Wittchen, H. U., Robins, L. N., Cottler, L. B., Sartorius, N., Burke, J. D., &Regier, D. (1991). Cross-cultural feasibility, reliability and sources of varianceof the Composite International Diagnostic Interview (CIDI). The MulticentreWHO/ADAMHA FieldTrials. British Journal of Psychiatry, 159, 645–653.

Int J

Neu

rosc

i Dow

nloa

ded

from

info

rmah

ealth

care

.com

by

Que

en's

Uni

vers

ity o

n 08

/24/

14Fo

r pe

rson

al u

se o

nly.