nZsuzsa Londe c, Pter Klivenyi d, Zsigmond Tams Kincses d,f, Nikoletta Szab d,f, Lszl Vecsei d,g,Michael T. Ullman e

a Institute of Psychology, University of Szeged, Szeged, HbCentre for Research in Linguistics and Language ScienccAmerican Language Institute, University of Southern CadDepartment of Neurology, Albert Szent-Gyrgyi ClinicaeBrain and Language Lab, Department of Neuroscience,f International Clinical Research Center, St. Annes UnivegNeuroscience Research Group of the Hungarian Academ

pre-HD individuals exhibit apparently intact motor, cognitive,and linguistic functioning, the underlying pathology may alreadybe present (Stout et al., 2011). Thus, carefully designed and sensi-tive language measures might reveal already-present impairmentsin pre-HD individuals. Such tests could have potential diagnostic

provide a useful avenue for examining the dependence of languageon these structures. Because the present study focuses on Hungar-ian, an agglutinative language with complex morphology that hasnot been examined before in either HD or pre-HD, the resultsshould be useful for testing the cross-linguistic validity of previousresearch on HD that has investigated similar aspects of language inboth English (Longworth, Keenan, Barker, Marslen-Wilson, & Tyler,2005; Ullman et al., 1997) and French (Teichmann, Dupoux, Kouid-er, & Bachoud-Levi, 2006; Teichmann et al., 2005). Finally, although

Corresponding author. Address: Institute of Psychology, University of Szeged,Egyetem u. 2., 6722 Szeged, Hungary. Fax: +36 62 544 509.

Brain & Language 121 (2012) 248253

Contents lists available at

La

.eE-mail address: nemethd@edpsy.u-szeged.hu (D. Nemeth).Language productionRegular and irregular morphologyHungarian

already-present impairments. Indeed, in a Hungarian morphology production task, pre-HD patients madeboth over-sufxation and over-regularization errors. The ndings suggest the generality of over-activerule processing in both HD and pre-HD, across languages from different families with different morpho-logical systems, and for both verbal and noun inection. Because the neuropathology in pre-HD appearsto be largely restricted to the caudate nucleus and related structures, the ndings further implicate thesestructures in language, and in rule-processing in particular. Finally, the need for effective treatments inHD, which will likely depend in part on the ability to sensitively measure early changes in the disease,suggests the possibility that inectional morphology, and perhaps other language measures, may provideuseful diagnostic, tracking, and therapeutic tools for assessing and treating early degeneration in pre-HDand HD.

2012 Elsevier Inc. All rights reserved.

1. Introduction

This study examines particular aspects of language processingin individuals with genetically proven pre-symptomatic Hunting-tons disease (pre-HD) specically regular and irregular nounmorphology in an agglutinative language, Hungarian. Although

value for predicting the onset of the symptoms, possibly allowingfor appropriate timing of treatment. Moreover, since in the veryearly stages of HD, including in pre-HD, the neuropathology seemsto be relatively restricted to the caudate nucleus and related struc-tures (Harris et al., 1999; Henley et al., 2009; Kipps et al., 2005;Kloppel et al., 2008), the investigation of language in pre-HD maya r t i c l e i n f o

Article history:Accepted 2 April 2012Available online 24 April 2012

Keywords:Pre-symptomatic Huntingtons diseaseBasal gangliaCaudate nucleus0093-934X/$ - see front matter 2012 Elsevier Inc. Ahttp://dx.doi.org/10.1016/j.bandl.2012.04.001ungaryes, Newcastle University, Newcastle upon Tyne, United Kingdomlifornia, Los Angeles, USAl Center, University of Szeged, Szeged, HungaryGeorgetown University, Washington, DC, USArsity Hospital Brno, Brno, Czech Republicy of Sciences, Budapest, Hungary

a b s t r a c t

A limited number of studies have investigated language in Huntingtons disease (HD). These have gener-ally reported abnormalities in rule-governed (grammatical) aspects of language, in both syntax and mor-phology. Several studies of verbal inectional morphology in English and French have reported evidenceof over-active rule processing, such as over-sufxation errors (e.g., walkeded) and over-regularizations(e.g., digged). Here we extend the investigation to noun inection in Hungarian, a Finno-Ugric agglutina-tive language with complex morphology, and to genetically proven pre-symptomatic Huntingtons dis-ease (pre-HD). Although individuals with pre-HD have no clinical, motor or cognitive symptoms, theunderlying pathology may already have begun, and thus sensitive behavioral measures might revealDezso Nemeth a,, Cristina D. Dye b,e, Tams Sefcsik a, Karolina Janacsek a, Zsolt Turi a,Short Communication

Language decits in pre-symptomatic HuEvidence from Hungarian

Brain &

journal homepage: wwwll rights reserved.tingtons disease:

SciVerse ScienceDirect

nguage

lsevier .com/locate /b&l

of a trinucleotide (CytosineAdenineGuanine) repeat number in

clear. On the one hand, in one study HD subjects did not show

angword-nding difculties or other semantic decits in their sponta-neous speech (Podoll et al., 1988). However, another study reportedthat HD patients exhibited impaired performance at tasks involvingcertain aspects of lexical/semantics, in particular the BostonNaming Test and category uency (Chenery, Copland, & Murdoch,2002). Yet other studies have found impaired letter uency in HDthe Huntingtin gene. In healthy individuals, the CAG repeat num-ber ranges from 9 to 35, while in patients with HD the range is39121 (Kremer et al., 1994; Rubinsztein et al., 1996; The Hunting-tons Disease Collaborative Research Group, 1993). Individuals whodemonstrate no apparent motor, cognitive and linguistic impair-ments but have positive genetic test result for the expanded tripli-cate repeat are called pre-symptomatic HD, or pre-HD (Nopouloset al., 2010). There is a need for effective treatments in HD. Suchtreatments will likely depend in part on the ability to sensitivelymeasure early changes in the disease (e.g., to know when to beginadministering medications). Although neuroimaging techniquescan apparently pick up some neuropathology in pre-HD (Henleyet al., 2009; Kipps et al., 2005; Kloppel et al., 2008), it is not clearwhether such techniques are more sensitive than behavioral mea-sures. Moreover, evidence suggests that markers of disease pro-gression, particularly at pre-clinical stages of the disease, arelacking (Witjes-Ane et al., 2007). Given that previous evidence sug-gests that aspects of language, including morphology, may dependin part on the caudate nucleus (Beretta et al., 2003; Teichmannet al., 2006; Ullman & Pierpont, 2005; Ullman et al., 1997), mea-sures of morphological aspects of language might indeed be usefulfor revealing early stages of the disease, even in pre-HD.

3. Huntingtons disease and Language

Considerable evidence suggests that certain aspects of languageare abnormal in HD. In particular, syntax seems to be compromisedin the disorder. Studies of sentence processing in HD suggestimpairments of syntax that are tied to caudate abnormalities(Teichmann, Dupoux, Cesaro, & Bachoud-Levi, 2008; Teichmannet al., 2005). Similarly, studies of spontaneous speech in HD havefound apparent syntactic decits, characterized by the productionof sentences with simplied grammatical structure (Illes, 1989;Murray & Lenz, 2001; Podoll, Caspary, Lange, & Noth, 1988). In con-trast, the status of lexical/semantics in the disorder seems to be lessprevious studies of pre-HD have examined language-related taskssuch as verbal uency (Larsson, Almkvist, Luszcz, & Wahlin,2008; Lawrence et al., 1998) or articial grammar (De Diego-Balaguer et al., 2008), to our knowledge this is the rst study thatspecically examines morphology, or indeed any other particularcomponent of the language system, in pre-HD.

2. Huntingtons disease (HD)

HD is a rare autosomal dominantly inherited progressive neuro-degenerative disorder (Huntington Study Group, 1996). Abnormal-ities seems to be largely restricted to the caudate nucleus andrelated structures at early stages of the disease (Henley et al.,2009; Kipps et al., 2005; Kloppel et al., 2008). The degenerationleads to involuntary choreiform (hyperkinetic) movements, andeventually to personality changes and dementia (Reiner et al.,1988). The timing of symptom onset is variable, though it usuallyoccurs around ages 3545. The disease inevitably leads to deathwithin 1015 years. The mutation in HD involves the expansion

D. Nemeth et al. / Brain & L(Langbehn & Paulsen, 2007; Stout et al., 2011). Similarly, researchhas suggested that both letter and category uency appear to beimpaired in pre-HD individuals (Larsson et al., 2008).Thus, the picture from these studies appears to be somewhatmixed. Syntax appears to be impaired, while the status of lexical/semantics remains less clear. However, one of the problems draw-ing such conclusions is that it is difcult to separately probe gram-matical (rule-governed) aspects of language, such as syntax, andlexical/semantic aspects, while holding other factors constant(e.g., motivation, attention, phonological complexity, etc.).

To address this quite general problem, a large body of researchhas emerged that examines the distinction between regular andirregular inectional morphology, such as in English past tenses.Irregularly inected forms are at least partially idiosyncratic, inthat they cannot be fully predicted by their stems (e.g., sing-sang,bring-brought, ing-ung), and thus must depend on some sort ofstored (lexicalized) representation. In contrast, regulars are fullyrule-governed (stem + -ed afx), and thus do not need to be stored,but rather can depend instead on rule-based (grammatical) com-position. Since regulars and irregulars can be matched on manyfactors (e.g., frequency, phonological complexity), and can betested in the same task in the same contexts, one can examinethe distinction between irregular and regular morphology in orderto probe lexical and grammatical aspects of language while holdingother factors constant.

Whereas numerous studies have investigated regular and irreg-ular morphology in various languages in other disorders (Ullman,2004, 2008), only a handful of studies have examined this contrastin HD, and none in pre-HD. To our knowledge, these studies havethus far examined only verb-related morphology, specically onlyin English past tense (Longworth et al., 2005; Ullman et al., 1997)and French present and future tenses (Teichmann et al., 2005,2006). As we shall see, overall the preponderance of ndings seemsto suggest abnormal performance on rule-based processing but rel-ative normal performance on lexical-based processing, as com-pared to healthy control subjects.

Ullman et al. (1997) tested 17 native-English speaking HD pa-tients and eight neurologically intact control subjects. Participantswere asked to produce the past-tenses of English regular, irregularand novel (made-up) verbs. Error rates constituted the dependentvariable. As compared to the control subjects, HD patients pro-duced signicantly more over-regularization errors (e.g., digged)and regular and novel verbs with over-afxations, as reected inmultiple afxes or syllabic afxes (e.g., walkeded, walk-id). More-over, the number of both over-regularization and over-afxationerrors correlated with the patients level of hyperkinesia. In con-trast, over-regularizations did not correlate with the patients per-formance at lexical retrieval, as measured by the Boston NamingTest, suggesting that even though HD can lead to lexical retrievalproblems (see above), these did not explain the over-regularizationerrors. Ullman et al. (1997) concluded that overall, the evidencesuggests that the basal ganglia abnormalities in HD leading tohyperkinesias also lead to over-active rule use. Longworth et al.(2005) also investigated regular and irregular past-tense inectionin (mild and moderate) HD. Like Ullman et al. (1997), the patientsmade errors on both regular and irregular verbs, with the mostcommon error being over-regularizations. They also examinedpriming, and found normal priming facilitation for regulars (e.g.,walked primeswalk) as well as irregulars (e.g., taught primes teach),though only the mild HD patients were examined, since the mod-erate HD patients were unable to perform the task.

Teichmann and colleagues (2005) tested French verbal inec-tional morphology in a production task in 30 native-French speak-ing HD patients (both early and later stages) and healthy controlsubjects. Participants were presented with regular and irregularFrench verbs and novel verbs that were either regular or subreg-

uage 121 (2012) 248253 249ular (i.e., they were irregular in not following the default, mainrules). Compared to controls, morphology was relatively sparedin HD, expect for subregular novel verbs, on which HD patients

demonstrated impaired performance. Specically, rather than ap-ply the subregular (irregular) pattern, they often over-regularizedby applying the main rule, or produced double sufxations (theexcessive application of regular era sufx, such as garoust-er-era). Agreeing with Ullman et al. (1997), they interpreted thepattern as a consequence of over-active rule use in HD. Alongsomewhat similar lines, Teichmann et al. (2006) examined regularand irregular inectional morphology in HD with acceptabilityratings and lexical decision, and found abnormalities in ruleprocessing but not in lexical processing.

Thus, studies of inectional morphology in HD have largely re-ported problems with rule processing, in particular over-activerules. However, it is not clear whether such problems might be

larly to any noun form (including neologisms), provided that the

their stems. For example, to create the plural form lovak horses,the uninected stem l horse must undergo modication to lovprior to the attachment of the sufx Vk. Table 1 illustrates the reg-ulars and the irregulars in the four forms under investigation. Forfurther details on Hungarian morphology, see (Rounds, 2001).

5. The present study

The present study lls several empirical gaps. First, to ourknowledge, it is the rst study to examine inectional morphologyin pre-symptomatic HD. The presence of any impairments in pre-HD would implicate the caudate nucleus and related structuresin this language domain. Additionally, it might lead to useful diag-

lur

No/Vk/

ert- garden-PL garden-ACC garden-PL-ACCk-x-P

krgbarkma

bird-ak

250 D. Nemeth et al. / Brain & Language 121 (2012) 248253general phonological contexts required for their application aremet (Rounds, 2001). In contrast, Hungarian irregular nouns exhibitat least partially idiosyncratic morpho-phonological changes to

Table 1Examples of singular and plural forms of regular and irregular nouns (singular SG; p

Type SG? PL(stem +

Regular nouns No change kert? kgarden

Vowel lengthening rka? rfox fo

Irregular nouns Epenthetic kreg?bark

Shortening madr?bird

v-inserting l? lovfound even in pre-HD, in which the neuropathology is more re-stricted to the caudate nucleus and related structures, or in otherlanguages with more complex morphology such as Hungarian.

4. Hungarian noun morphology

In Hungarian, which is an agglutinative language with richinectional morphology, inected forms consist of a stem followedby one or more distinct inectional sufxes (Abondolo, 1988). Inthe present study, we focus on the singular and plural forms andnominative and accusative cases of nouns. The singular form in-volves zero morphology (no afxes), while the plural marker isthe sufx Vk (where -V marks a linking vowel whose phonologyagrees with the stem, following the rules of vowel harmony). Nom-inative case is associated with the subject (the agent role) and alsoinvolves zero morphology. Accusative case is associated with thedirect object (the patient/theme role) and involves the sufx -Vt.Thus, the singular nominative form of a noun involves the stemonly (e.g., kert; garden), the plural nominative form consists ofthe stem plus the plural sufx (e.g., kertek, kert + ek; garden + PL),the singular accusative form involves the stem plus the accusativesufx (e.g., kertet, kert + et; garden + ACC), and the plural accusa-tive form consists of the stem plus both the plural sufx and theaccusative sufx (e.g., kerteket, kert + ek + et; garden + PL + ACC).

Hungarian nouns have different stem classes that can begrouped into regular and irregular nouns on the basis of their mor-pho-phonological behavior. Although both regular and irregularnouns take the sufxes described above, the two types of nounsdiffer in their stems. In regular nouns, the stem either does notchange, or changes according to productive morpho-phonologicalrules such as vowel lengthening (Table 1). The morpho-phonolog-ical rules observed in regular nouns are productive, applying regu-horse ho

a The vowel e is a linking vowel. Depending on the word stem, sometimes the stem mk rk-t rk-k-atL fox-ACC fox-PL-ACC

-ek krg-et krg-ek-et-PL bark-ACC bark-PL-ACCdar-ak madar-at madar-ak-at-PL bird-ACC bird-PL-ACC

lov-at lov-ak-atjects in Hungary. All subjects completed a Hungarian noun mor-phology production task (see Section 8.2 in Methods). Theproduction of the three types of morphologically complex formswere elicited from pictures: the accusative singular form of thenoun, the nominative plural form, and the accusative plural form.Nominative singular forms of all nouns were also elicited, as a con-trol condition to ensure that subjects were familiar with eachword; all subjects achieved 100% accuracy on this condition. Thedependent variables of the morphologically complex forms wereaccuracy and error rates for various types of errors (for detailssee Section 8).

Statistical analyses were performed, rst of all, with MannWhitney tests to compare performance (accuracy and number oferrors of different error types) between the pre-HD and controlgroups, and second, with Wilcoxon tests to compare performance

al PL; accusative ACC).

minative SG Accusative PL Accusative) (stem + /Vt/) (stem + /Vk/ + /Vt/)

eka kert-et kert-ek-etnostic tests for identifying the onset of symptoms, as well as forfollowing the progression of the disorder. Second, by investigatingHungarian, the study extends the investigation of inectional mor-phology cross-linguistically to an agglutinative language that hasgreater morphological complexity than previously studied lan-guages in HD, and that comes from a different language family(Finno-Ugric rather than Indo-European). Finally, whereas previ-ous studies of inectional morphology in HD have been restrictedto verbal morphology, here we extend the investigation by exam-ining noun morphology, to test the generalizability of previouslyreported patterns. Although this was the rst study of pre-HD, aswell as the rst of Hungarian morphology in (pre-)HD, we broadlyexpected errors that might reect over-active rule use, such assome sort of over-afxation errors and over-regularizations.

6. Results

Seven genetically proven pre-HD participants and seven age-and education-matched healthy control subjects took part in thestudy (see Section 8.1 in Methods). The relatively small numberof pre-HD participants was due to the relative paucity of these sub-rse-PL horse-ACC horse-PL-ACC

ay need a linking vowel in order to facilitate the pronunciation of the sufxed noun.

on regular vs. irregular nouns within each subject group. The inter-action between the pre-HD and control groups and irregular andregular forms was analyzed by Bradleys collapsed and reducedtechnique (Sawilowsky, 1990). These non-parametric tests wereemployed because the dependent variables did not follow a normaldistribution.

As shown in Table 2, the pre-HD group had lower accuracy thanthe control group over both noun types (93.8% vs. 100%, p = 0.001),as well as at both regulars (p = 0.02) and irregulars (p = 0.001). Allpre-HD subjects made errors on irregulars, and four of the sevenmade errors on regulars. In contrast, the control group made no er-rors at all on either noun type; that is, they performed at ceiling. Inaddition, the pre-HD subjects were less accurate on irregular (89%)than regular (98%) nouns (Wilcoxon paired sample test: Z = 2.37,p = 0.02; see Fig. 1). Analyzing the interaction between groups(pre-HD vs. control) and regularity (regular vs. irregular), Bradleyscollapsed and reduced technique revealed that the difference be-tween the performance on regular vs. irregular forms was signi-cantly greater in the pre-HD group than in the controls(U(14) = 3.35, p < 0.001).

Further analyses were conducted separately for each of the fourerror types (substitution, under-sufxation over-sufxation, andover-regularization; see Table 2). For irregular forms, the error ratedifferences between the pre-HD and control groups did not reachsignicance either for substitution errors (p = 0.14) or under-suf-xation errors (p = 0.06). In contrast, the pre-HD subjects producedsignicantly more over-sufxation errors (p = 0.02) and especiallyover-regularization errors (p = 0.001) than the controls. For regularforms, on which the pre-HD patients made very few errors, therewere, not surprisingly, no signicant differences between the

only over-sufxation errors showed a signicant difference be-tween the two groups (p = 0.02).

7. Discussion

This is the rst study examining inectional morphology in pre-HD, or Hungarian morphology in either HD or pre-HD. In theabsence of any apparent motor, cognitive or other decits, thepre-HD patients showed impairments at producing inected formsfor both regular and irregular nouns. Their most common and reli-

in p

)

ean

9.01

1.10

1.10

3.30 0 0 U(14) = 10.50, Z = 2.24, p = 0.02*

5.49 0 0 U(14) = 0, Z = 3.36, p = 0.001**

8.30 42 100 U(14) = 38.50, Z = 2.26, p = 0.02*

0.34 0 0 U(14) = 21.0, Z = 1.0, p = 0.32

0.34 0 0 U(14) = 21.0, Z = 1.0, p = 0.32

1.02 0 0 U(14) = 14.00, Z = 1.88, p = 0.06

3.83 81 100 U(14) = 49, Z = 3.36, p = 0.001**

0.71 0 0 U(14) = 14.0, Z = 1.87, p = 0.06

0.71 0 0 U(14) = 14.0, Z = 1.870, p = 0.06

2.12 0 0 U(14) = 10.5, Z = 2.25, p = 0.02*

86

88

90

92

94

96

98

100

regular irregular

Production of morphologically complex nouns

Acc

ura

cy (%

)

pre-HDcontrol

Fig. 1. Accuracy (percentages) on regular and irregular morphologically complexnoun forms by subject group. The control group performed at ceiling both onregular and irregular nouns, whereas the pre-HD group was less accurate onirregulars than regulars. Error bars represent Standard Error of Mean.

D. Nemeth et al. / Brain & Language 121 (2012) 248253 251pre-HD and control groups on any of the error types, although evenin this condition the group difference in over-sufxation ratesshowed a trend (p = 0.06). Over both regular and irregular nouns,

Table 2Production of morphologically complex nouns (plural, accusative, plural + accusative)

Pre-HD group (N = 7

Mean (SD) M

Irregular (39) Accuracy 34.71 8(l: lvat, lovak, lovakat) (1.98)Error typesSubstitution 0.43(lovak for lvat) (0.79)Under-sufxation 0.43(lovak for lovakat) (0.54)Over-sufxation 1.29(lovakat for lovak) (1.60)Over-regularization 2.14(lt for lovat) (1.46)

Regular (42) Accuracy 41.29 9(kert: kertet, kertek, kerteket) (0.76)

Error typesSubstitution 0.14(kertek for kertet) (0.38)Under-sufxation 0.14(kertek for kerteket) (0.38)Over-sufxation 0.43(kerteket for kertek) (0.54)

Total (81) Accuracy 76.00 9(2.24)

Error typesSubstitution 0.57

(0.79)Under-sufxation 0.57

(0.79)Over-sufxation 1.71

(1.80)* p < 0.05.** p < 0.01.able errors were over-sufxation and over-regularization errors.Irregular nouns were produced less accurately than regular nouns.

The results seem to support the view that Huntingtons disease isassociated with over-active rule use (Ullman et al., 1997), and that

re-HD and control subjects.

Control group (N = 7) Group difference

(%) Mean Mean (%) (MannWhitney test)

39 100 U(14) = 49, Z = 3.35, p = 0.001**

0 0 U(14) = 17.5, Z = 1.47, p = 0.14

0 0 U(14) = 14.00, Z = 1.88, p = 0.06

(see above), in Hungarian it was instead reected by the attachmentof the accusative sufx to correctly pluralized forms (e.g.

anglovakat; horse + PL + ACC instead of lovak; horse + Pl, or lovat;horse + ACC). The reasons for this difference are not clear, thoughitmight be due to the fact that in Hungarian nounmorphologymorethan one afx is available (in this case, Vk, Vt), and moreover thesecan be combined to create a well-formed word. Further investiga-tions are needed to examine this issue.

The greater error rate observed on irregular than regular nounsis also unclear. However, it might be at least partly explained byadditional processing required for irregulars as compared to regu-lars: whereas for both types of nouns the sufx is applied, for irreg-ulars the stem is also transformed. Whether this transformationrelies on lexical retrieval (of a memorized irregular stem) and/orrule processing in Hungarian remains unclear. Thus, whereas thedata presented here strengthen previous ndings of over-activerule use in (pre-)HD, they remain agnostic about lexical decits.Therefore the present ndings do not specically demonstrate adissociation between grammatical and lexical processes (Ullman,2004; Ullman et al., 1997), though they are consistent with it. Incontrast, certain aspects of the data appear to be inconsistent withthe theoretical position that morphological errors on regulars aredue not to morphological rule impairments but to phonologicaldecits, which are claimed to result in the phonological simplica-tion of regulars in patients who have trouble with these forms (e.g.,resulting in the utterance of walk instead of walked) (Bird, LambonRalph, Seidenberg, McClelland, & Patterson, 2003). The presentstudy seems to be problematic for this view, at least for (pre-)HD, since the over-sufxation errors made by the patients weremore rather than less phonologically complex than the correctforms (e.g., kerteket for kertek).

Overall, the ndings go some way towards addressing theempirical gaps that the study set out to address. The results dem-onstrate that inectional morphology can indeed be impaired inpre-HD, moreover in similar ways as in HD. The observed patternof errors supports the view that pre-HD, as well as HD, is associ-ated with over-active rule use (Ullman et al., 1997). The fact thatthese results were observed in pre-HD further implicates the basalganglia in rule processing, and in particular the caudate nucleusand related structures. However, it remains unclear whether thebasal ganglia themselves or the frontal regions they are heavilyconnected to are implicated in over-active rule use in pre-HDand HD: it may be disinhibited frontal cortex rather than the basalganglia per se that are at least partly responsible for these errors(Ullman, 2006). The ndings also suggest the cross-linguistic gen-eralizability of the pattern of over-active rule use, from verbs tonouns, and even to Hungarian, an agglutinative language that isvery different from English and French, and comes from a differentlanguage family. Finally, the results of this study suggest the pos-sibility that inectional morphology, and perhaps other languagemeasures, may provide useful diagnostic tools for predicting theonset of symptoms in HD, possibly facilitating the appropriate tim-ing of treatment.

8. Methods

8.1. Subjectsthis pattern can be observed even in pre-HD. Both the over-sufxation and over-regularization errors are consistent withover-active afxation. Note that whereas in English, over-sufxation was characterized as multiple or syllabied afxation

252 D. Nemeth et al. / Brain & LFourteen adult participants took part in this study. All wereright-handed native speakers of Hungarian. The pre-HD group con-sisted of seven participants (two females) with a mean age of 31.86(SD = 11) and a mean education of 15.14 years (SD = 1.77). All pre-HD participants had a positive family history for HD and had ge-netic testing for the expanded triplet repeat in the huntingtingene at IT-15. Six of the subjects had more than 39 CAG repeats(range from 42 to 50) and one subject was borderline with 37CAG repeats. Based on standardized neurological examinations(including Unied Huntingtons Disease Rating Scales, HuntingtonStudy Group, 1996) administered independently by two neurolo-gists specializing in HD at the University of Szeged Hospital, itwas determined that the seven subjects were free of clinical neuro-logical and motor symptoms (UHDRS scores of zero for all pre-HDindividuals). No subject showed evidence of dementia on the Mini-Mental State Examination (Folstein, Folstein, & McHugh, 1975),with all subjects (range 2730) showing normal performance.The neurologically intact control group consisted of seven subjects(two females). This control group head a mean age of 32.29(SD = 11.1) and a mean education of 15.14 years (SD = 1.57). Allof them had negative family history for HD and other neurodegen-erative diseases. The study was conducted in accordance with theDeclaration of Helsinki. All procedures were carried out with theadequate understanding and written consent of the subjects andwith the approval of University of Szeged.

8.2. Task

All subjects participated in an experiment involving a nounmorphology production task. This is a picture-naming subtest ofa longer protocol developed previously for Hungarian language-impaired children by Plh, Palots, and Lorik (2002), and used pre-viously in several studies (e.g., Nemeth et al., 2008; Pleh, Lukacs, &Racsmany, 2003). The test items consisted of 42 regular nouns and39 irregular nouns. The noun stems ranged between 2 and 3 sylla-bles. Regular and irregular nouns were matched on word frequency(t(79) = 0.927, p = 0.357), word length in syllable (U(81) = 664.5,p = 0.115), and phonological complexity measured via the obstruc-tion of consonants (i.e., two or more adjacent consonants)(v2(1,N = 81) = 0.065, p = 0.798). The 81 test items were presentedin the same pseudorandomized order to all subjects. For each item,subjects saw four pictures, each of which was designed to elicit oneof four forms: the nominative singular form of the noun, the accu-sative singular form, the nominative plural form, and the accusa-tive plural form, presented one at a time in that order, viacomputer. For example, to elicit the nominative singular of sh,participants were presented with a picture showing a single sh;for the nominative plural, a picture depicting multiple sh; forthe accusative singular, a picture of a sherman catching a sh;and for the accusative plural, a picture of a sherman catchingmany sh. Participants were prompted with questions such asWhat are these? or What is the sherman catching?. Beforebeginning the task, participants were given instructions as wellas three practice items.

Responses were recorded and coded by the experimenters. A re-sponse was coded as correct if it exactly matched the target form;otherwise, it was considered an error. Errors for regular nounswere classied into the following types: substitution, under-sufx-ation, and over-sufxation. Substitution errors entailed the pro-duction of the accusative sufx instead of the plural sufx, orvice versa. For example, for the noun kert garden, the productionof kertet garden-Acc instead of kertek garden-Pl. Under-sufxa-tion errors entailed the production of either just the plural sufxor just the accusative sufx in contexts where both the accusativeand plural are required (e.g., kertek garden-Pl or kertet garden-Acc for kerteket garden-Pl-Acc). Over-sufxation errors entailed

uage 121 (2012) 248253the production of both the accusative and plural sufxes in con-texts where only the plural or only the accusative is required(e.g., kerteket garden-Pl-Acc for kertek garden-Pl or kertet gar-

den-Acc). Note that forms with more than one instance of thesame afx, such as kertekek or kertetet, would also have beencounted as over-sufxation errors, although no such forms were

203212.

Kloppel, S., Draganski, B., Golding, C. V., Chu, C., Nagy, Z., Cook, P. A., et al. (2008).White matter connections reect changes in voluntary-guided saccades in pre-symptomatic Huntingtons disease. Brain, 131, 196204.

D. Nemeth et al. / Brain & Language 121 (2012) 248253 253Huntington Study Group (1996). The unied Huntingtons disease rating scale:Reliability and consistency. Movement Disorders, 11(2), 136142.

Illes, J. (1989). Neurolinguistic features of spontaneous language productiondissociate three forms of neurogenerative disease: Alzheimers, Huntingtons,and Parkinsons. Brain and Language, 37, 628642.

Kipps, C. M., Duggins, A. J., Mahant, N., Gomes, L., Ashburner, J., & McCusker, E. A.(2005). Progression of structural neuropathology in preclinical Huntingtonsdisease: A tensor based morphometry study. Journal of Neurology, Neurosurgeryand Psychiatry, 76(5), 650655.produced. Errors for irregular nouns consisted of the same typesas for regular nouns except that they additionally included over-regularization errors, where an irregular noun such as l horsewas regularized, as in lt instead of lovat horse-Acc or lk insteadof lovak horse-Pl. Therefore, over-regularization errors are onlyfound on irregular nouns, when the plural afx is attached to theunchanged stem.

Statement of signicance

Our study examined language production in Hungarian patientswith pre-symptomatic Huntingtons disease (pre-HD). The im-paired performance found on the production of morphologicallycomplex nouns suggests that linguistic tests may be predictive bio-markers of the onset of clinical symptoms, thus helping early diag-nosis of subcortical dementia.

Acknowledgments

Support for this project was provided by Bolyai Scholarship andthe Hungarian National Research Fund (OTKA) K 82068 to DN, andNIH R01 MH58189 and NIH R01 HD049347 to MTU. Dr. ZsigmondTams Kincses was supported by the Bolyai Scholarship Pro-gramme of the Hungarian Academy of Sciences. Dr. Kincses andDr. Szab was supported by the project FNUSA-ICRC (no. CZ.1.05/1.1.00/02.0123) from the European Regional Development Fund.

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Language deficits in pre-symptomatic Huntingtons disease: Evidence from Hungarian1 Introduction2 Huntingtons disease (HD)3 Huntingtons disease and Language4 Hungarian noun morphology5 The present study6 Results7 Discussion8 Methods8.1 Subjects8.2 Task

Statement of significanceAcknowledgmentsReferences