primary progressive aphasia a study of picture naming

Primary Progressive Aphasia: A study of picture naming, interference

and lexical access

Laura ten Dijke

University of Amsterdam

MA Thesis General Linguistics

2019

MA THESIS: PRIMARY PROGRESSIVE APHASIA 2

Table of Contents

Table of Contents ...................................................................................................................................................... 2

1. Introduction …. ..................................................................................................................................................... 3

2. Primary Progressive Aphasia ........................................................................................................................... 5

2.1 The semantic variant ........................................................................................................................................ 6

2.2 The nonfluent variant ....................................................................................................................................... 7

2.3 The logopenic variant ....................................................................................................................................... 7

3. The present study ................................................................................................................................................. 9

3.1 Naming abilities and executive functions in PPA ........................................................................................ 9

3.2 The use of the PWI paradigm ......................................................................................................................... 9

3.3 Predictions ........................................................................................................................................................ 11

4. Methods and materials....................................................................................................................................... 12

4.1 Participants ....................................................................................................................................................... 12

4.2 PWI task ........................................................................................................................................................... 12

4.2.1 Stimuli .......................................................................................................................................................... 12

4.2.2 Procedure ...................................................................................................................................................... 13

4.2.3 Response time analysis ................................................................................................................................... 14

4.2.4 Error analysis ............................................................................................................................................... 14

4.3 Additional cognitive and language tests ...................................................................................................... 14

4.3.2 Procedure ...................................................................................................................................................... 15

5. Results ..................................................................................................................................................................... 16

5.1 Response times ................................................................................................................................................ 16

5.2 Naming accuracy ............................................................................................................................................. 17

5.3 Additional cognitive tests and language tests ............................................................................................. 19

6. Discussion .............................................................................................................................................................. 21

6.1 Limitations ....................................................................................................................................................... 22

6.1 Future perspectives ......................................................................................................................................... 23

7. Conclusion ............................................................................................................................................................ 24

References ................................................................................................................................................................. 25

Acknowledgments................................................................................................................................................... 29


1. Introduction

The speech production in day to day life is thought to be an effortless and automatic mechanism. The

actuality, however, reflects a much more complex picture. It involves a multitude of processes including

conceptualization, semantic, syntactic, phonological processing and articulation (see Harley, 2014b for a

more detailed discussion). Schiller and Verdonschot (2015) highlight lexical access as its crucial component.

Lexical access refers to ‘‘the process of retrieving a word from the mental lexicon and encoding it for

speech’’ (Wilson et al., 2017, p. 90). While the underlying workings and models of lexical access are still

debated (e.g. Garrett, 1975; Dell, 1986; Levelt, 2001), most of these models assume that the process of

retrieving words is a competitive one (e.g. Starreveld and La Heij, 1996). This indicates that there is a

competition between candidates for lexical selection (Schiller & Verdonshot, 2015). A testing paradigm that

has been used to empirically to examine this claim is the (visual) picture-word interference (PWI) paradigm,

which is a modification of the Stroop task (e.g. Glaser & Düngelhoff, 1984). The paradigm elicits

interference effects and relies on executive (interference) control processes needed for successful word

selection (Pai, Roelofs & Schriefers 2012). Piai, Roelofs and Schriefers (2012) claim that these mechanisms

‘‘allow the participants to respond to the target picture, rather than to the distractor word’’ (p. 615). This

implies that selective attention toward the target is needed. Selective inhibition plays an additional role.

Shao, Meyer and Roelofs (2013) define selective inhibition as the ability to ‘‘suppress specific competing

responses’’ (p. 1200). This is relevant when a distractor needs to be ignored in order to name the target1.

The experimental design of PWI and its implications will be further discussed in chapter three.

The present study examines naming abilities2 of individuals with Primary Progressive Aphasia (IwPPA)

with the use of a picture-word interference task (with related and neutral distractors), in which response

time and accuracy are measured as experimental output parameters. In addition, the cognitive and linguistic

performance is taken into consideration. The present investigation aims to explore the breakdown in

naming in relation to the interference control processes mentioned above. Moreover, this thesis explores

the factors that play a role in the difficulties and errors that arise. Word finding difficulties or anomia3 in

naming are especially present among individuals with aphasia, a language disorder due to brain damage.

This is also the case with Primary Progressive Aphasia (PPA), a disorder characterized by the progressive

deterioration of language functions with relatively spared cognitive domains (Mesulam, 1982, 2003;

Grossman & Ash, 2004). PPA has been categorized in three main variants of a semantic, nonfluent and

logopenic kind (Gorno-Tempini et al., 2011).

1 Diamond (2013) states that interference control consists of selective attention and cognitive inhibition). Moreover, Thomas, Rao & Devi (2016) reported that the processes of attention and inhibition are related, showing a significant association between the two. They will therefore not be analysed separately, and instead I will use the term interference control. 2 In this thesis, naming is understood as the process comprised of three stages including the identification of the object, access to its semantic representation so that it can be recognized and the activation of its phonological representation so that its lexicalized and used for speech (Spezzano & Radanovic, 2010). 3 Harley (2014) defines anomia as ‘‘an impairment of retrieving the names of objects and pictures of objects’’ (p. 438).


Thus far only few studies have included PWI to investigate aphasia and PPA (e.g. Hashimoto &

Thompson, 2010; Thompson et al., 2012; Vandenberghe et al., 2005 Thompson et al., 2012). There is much

room to apply PWI in order to obtain new insights into different variants of PPA. This study may provide

a stepping-stone for future more in-depth research with aim to come to a better understanding of lexical

access in PPA and of the stratification of PPA patients into subgroups.

In the following sections I elaborate on PPA and the characteristics of the recognized subtypes. In

addition, I discuss the various theories concerning the nature of naming deficits and how they are exhibited

by the variants. Along with the aims, the experimental study is introduced. These results are presented and

subsequently discussed. I emphasize the need for including more participants of different subtypes and

interference stimuli to obtain more conclusive results. I reflect on how my results compare with those

obtained in previous studies and conclude with a future perspective. I stress the importance of using a

broader approach by performing additional measures, testing executive functions as well as other modalities

like neuroimaging in future studies.


2. Primary Progressive Aphasia

Primary Progressive Aphasia (PPA) is a relatively rare neurodegenerative disorder characterized by a

progressive deterioration of specific language functions. Marked by an insidious onset, there is a gradual

degeneration of neural networks governing production, comprehension, word finding, and object naming,

in particular. Considering that a decline in cognitive processing domains4 is relatively spared in the early

stages of the disease, the language impairment should be viewed as an isolated problem. Moreover, whereas

cognitive processing decline and behavioural changes5 increase during the (later) progression of the illness,

the language deficit remains the most prominent feature (Mesulam, 1982, 2001; Grossman & Ash, 2004;

Gorno-Tempini et al., 2011). PPA is typically related to brain atrophy of the frontal and temporal regions

of the left hemisphere and absence of strokes, head traumas, or other specific causes that might account

for the language deficits (Mesulam, 2003; Grossman & Ash, 2004).

It should be noted that while these criteria are straightforward, the diagnosis of PPA is not (see Marshall

et al., 2018 for more in-depth discussion). Like in many cases of aphasia, the linguistic impairment may

have effects on the outcome since the diagnostic materials often rely on ‘‘linguistically mediated

instructions’’ (Grossman & Ash, 2004, p. 4). Any results of performed neuropsychological testing in PPA

should therefore be carefully interpreted (Amici et al., 2006). Moreover, this caution is often necessary to

avoid possible misdiagnosis in view of other progressive disorders displaying certain language impairment

symptoms as well, such as corticobasal degeneration or progressive supranuclear palsy (Battista et al., 2017).

Aside from this root diagnosis of PPA, a consensus has been established in further classifying the

disorder into a semantic (svPPA), a nonfluent (nfvPPA) and a logopenic variant (lvPPA). Following the

proposed clinical guidelines by Gorno-Tempini et al. (2011), the categorization of these subtypes is mainly

based on clinical diagnosis, the underlying pathology6 and brain atrophy that is assessed through

neuroimaging. In trying to classify the variants based on clinical diagnosis, a series of main language domains

should be considered. Gorno-Tempini et al. (2011) propose the evaluation of ‘‘speech production features,

repetition, single-word and syntax, comprehension, confrontation naming, semantic knowledge and

reading/spelling’’ to be able to correctly identify the language symptoms of a subtype (p. 1008). Notable is

that various language batteries (e.g. Boston Naming test, CAT-NL, location learning test) can be used as

long as they address these areas.

In addition to the speech and language abilities, specific pathology presents itself indicative of the type

of PPA, namely its variants are often linked to degeneration of the frontotemporal lobar (FLTD) or

pathologies within the large spectrum of Alzheimer’s disease (Gorno-Tempini et al., 2011; Marshall et al.,

2018). However, numerous studies have pointed out that these are rather heterogeneous (e.g. Gorno-

4 As stated by Mesulam (2003, 2013) this entails faculties like episodic memory, executive functions, visuospatial skills, reasoning and comportment. 5 For example, individuals with svPPA can experience changes including absent or misplaced sympathy, social disinhibition, exaggerated reactions to pain among others (see Marshall et al, 2018 for in-depth reading). 6 This refers to the disease correlations and underlying mechanisms with which the disease, i.e. the PPA variant, is associated.


Tempini et al., 2011; Marshall et al., 2018; Battista et al., 2017), and that observations related to them only

reflect ‘‘groupwide probabilities’’. This suggest only relative relation between the specific subtypes and

pathology (Gorno-Tempini et al., 2011, p. 1007).

While the study by Gorno-Tempini et al. (2011) provides a compelling case for PPA categorization,

there are cases where deficit patterns do not align with the proposed criteria and represent an atypical or

mixed subtype. In a study reported by Harris et al. (2013), for example, some patients could not be classified,

exposing problems with the categorization criteria. Similar reports emerge in an investigation by

Vandenberghe (2016). In a meta-analysis study, 15-30% of the tested individuals could not be assigned to

any of the three variants. He clarified that this is due to a lack of specific features that are necessary for a

categorization, or because an individual has features of multiple subtypes, suggesting a mixed variant.

Possible ways to improve this matter include the modification on imaging as well as more in-depth

neuropathological testing. In the same manner, Battista et al. (2017) recommend the use of suitable

neuropsychological and linguistically fine-grained tests with methods more suitable in order to evaluate a

patient’s linguistic abilities. Moreover, PPA research advocate for the implementation of specific ad-hoc

clinical tests for PPA to improve current categorization (Battista et al. 2017; Bisenius, Neumann &

Schroeter, 2016).

While this certainly calls for deeper investigation, it exceeds the scope of the present thesis. This paper

only takes the main three variants into consideration, whose characteristics are further specified in the

sections below.

2.2 The semantic variant

The semantic variant is categorized by a progressive loss of semantic knowledge (Gorno-Tempini et al.,

2011; Kertesz & Harciarck, 2014). According to Gorno-Tempini et al. (2011), individuals diagnosed with

svPPA typically experience word finding difficulties and single word comprehension deficits. Even though

word finding difficulties are common across all subtypes, the anomia in svPPA is severe. Faced with a loss

of meaning of words, verbal communication becomes gradually empty and verbose (Marshall et al., 2018).

Patients employ simplifications, circumlocutions, and increasingly use close-cased words (Mesulam, 2001;

Wilson et al., 2010). Single word comprehension is gravely impaired as well, where comprehension of less

familiar and low-frequency items is lost first. Patients are likely to use generalizations, omissions,

circumlocutions or substitutions for atypical items (Vandenberghe, 2016). Additionally, semantic

paraphasias are consistent as well, especially in object naming (Kertesz & Harciarck, 2014). Other features

present in the subtype are the manifestations of surface dyslexia, an impairment in the ability to read

irregular words, and dysgraphia, a similar disorder concerning writing. Irregular words are regularized in

their pronunciation and spelling. This is due to the fact that patients rely of phonology rather than meaning

(Gorno-Tempini et al., 2011; Kertesz & Harciarck, 2014; Harley, 2014). Patients retain relative speech

production (grammar and motor speech), as well as repetition (Gorno-Tempini et al., 2011; Kertesz &

Harciarck, 2014). In terms of neuroimaging, the subtype is associated with cerebral atrophy in the anterior


temporal lobes (Kertesz & Harciarck, 2014; Leyton & Hodges, 2014). Additionally, the semantic variant is

linked to ubiquitin-positive, TDP43-positive pathology (Gorno-Tempini et al., 2011).

2.2 The nonfluent variant

In contrast to the semantic variant that is characterized by fluent speech, the nonfluent subtype is defined

by a strenuous, effortful language production and evident signs of agrammatism (Gorno-Tempini et al.,

2011; Leyton & Hodges, 2014). Patients demonstrate telegraphic speech by omitting grammatical elements

like verbs, function words and inflectional morphemes (Hillis, Tussiash & Caramazza, 2002; Gorno-

Tempini et al., 2011). Sentence comprehension is another affected component, where patients are unable

to understand sentences due to their grammatical complexity. Phrases containing negation, passives and

object relative clauses are examples of this (Leyton & Hodges, 2014; Peelle et al., 2007). In addition to

deficits in syntax, nfvPPA is categorized by an impaired motor planning or apraxia of speech. Individuals

exhibit motor problems resulting in slurring, as well as phonological errors including deletions or

transpositions of sounds. Moreover, prosody is affected with individuals displaying abnormalities in

loudness, pitch and intonational stress (Vandenberge, 2016; Gorno-Tempini et al., 2011; Marshall et al.,

2018). Per contra, single word comprehension and object knowledge is relatively preserved. Oher than the

existent word finding difficulties, no profound semantic deficits are present (Gorno-Tempini et al., 2011;

Kertesz & Harciarck, 2014). The majority of patients with nfvPPA show atrophy in the interior frontal

gyrus and the insula cortex of the dominant hemisphere (Marshall et al., 2018). Neuropathologically there

are greater individual differences, although frontotemporal lobar degeneration with tau-positive inclusions

pathology is often expressed (Gorno-Tempini et al., 2011).

2.3 The logopenic variant

The logopenic variant is dominated by word retrieval and sentence repetition deficits (Gorno-Tempini et

al., 2011). Similar to nfvPPA, the fluency of speech is compromised. In lvPPA, speech output is slowed,

consisting of word-finding pauses and hesitations (Gorno-Tempini et al., 2011; Vandenberghe, 2016).

Considering these retrieval difficulties, patients show no obvious syntax deficits and have relative intact

semantics and single word comprehension (Kertesz & Harciarck, 2014; Marshall et al., 2018). Impairments

in confrontation naming7 are less severe than in the semantic variant. Sentence comprehension is distorted

however. A manifestation that is caused by the length rather than grammatical complexity of the phrase

(Leyton & Hodges., 2014). With patients displaying short term phonological memory deficit, the repetition

of longer phrases is also impaired (Vandenberghe, 2016). Individuals with lvPPA often present

phonological paraphasias, including syllable mis-selections, either in spontaneous speech or in naming

7 Rayner (2017) defines this as ‘‘a type of task used in assessment when problems with anomia or word retrieval are of concern. Confrontation naming involves the selection of a specific label corresponding to a viewed picture of an object or action’’ (p. 1).


(Gorno-Tempini et al., 2011; Marshall et al., 2018). Reading aloud is affected is a similar manner as well

(Marshall et al., 2018). In regards to neuroanatomy, most cases of the logopenic variant reveal atrophy

involving the temporo-parietal junction zone, as well as regions including the left parietal and temporal

cortices, (Leyton & Hodges, 2014). The variant is moreover linked to an underlying pathology of

Alzheimer’s Disease (Gorno-Temipini et al. 2011).


3. The present study

As previously mentioned in the introduction, the present study examines the naming ability of IwPPA and

the role of executive interference control processes including attention and selective inhibition. Whereas

the importance of executive control in naming abilities was shown in stroke patients (e.g. Piai & Knight,

2018), very little is known in this respect regarding PPA. In this section, I will present the various papers

covering the naming deficits that are exhibited in PPA. Furthermore, I will discuss the use of the PWI as

an experimental design in investigating these notions and how the task taps into the involved control

processes. The main aims of this thesis are to (1) investigate the performance of picture naming of IwPPA

and control participants using a PWI task (through response times and error analysis), (2) investigate the

response times and errors between the three PPA variants, and (3) to measure how the performance on

the PWI task compares to other cognitive and language tests. At the end of this section I offer my

predictions on the results that I will obtain.

3.1 Naming abilities and executive functions in PPA

A common denominator in IwPPA is the difficulty in word finding/retrieval and naming (Race et al., 2013;

Vandenberghe et al., 2005; Kirschner, 2014). As noted in chapter two, individuals with svPPA demonstrate

this as a consequence of deterioration of conceptual knowledge. Van Scherpenberg et al. (2019) affirm that

‘‘semantic features constituting semantic representations of objects are progressively lost in people with

svPPA and are therefore consistently unavailable during naming’’ (p. 13). Though Wilson et al. (2017) have

shown that some patients also reflect difficulties in the post semantic stage of word retrieval8. With respect

to the other non-semantic variants, Henry et al. (2013) suggest that in lvPPA lexical retrieval is impaired at

a post-semantic or phonological stage. In this case the access to phonological representations is distorted.

Though pointed out in an earlier study, in nfvPPA and lvPPA the deficit extends into the prior levels of

lexical semantics as well (Rogalski et al., 2008).

Another point to raise in the (possible) effect of impaired executive functions on PPA. In the diagnosis

of PPA it is made explicit and assumed that cognitive abilities i.e. executive functions, should not be

deteriorated in the beginning stages of the disease. However, Macoir et al. (2017) indicate that a decline in

these functions is present in all three variants of PPA with a magnitude that exceeds what is expected from

the natural aging process and PPA diagnosis criteria.

3.1 The use of the PWI paradigm

The PWI paradigm is an on-line naming task where participants are presented with a set of pictures, each

8 This would mean that the semantic stage is intact but subsequent stages reflect difficulties. These difficulties could recur in the stage of phonological encoding, for example.


accompanied by a written (or spoken9) distractor. They are usually instructed to name the picture whilst

ignoring the distractor. The relation to the distractor to the picture can be modified in several ways. The

distractor can be presented as semantically related or unrelated to the picture, promoting a semantic

interference effect. Lexical interference can also be measured when distractors are presented as unrelated

or neutral. Phonological facilitation is another possibility when distractors are phonologically related or

unrelated to the picture. Additionally, presentation time of the distractor can be altered as well. They can

be presented before (-300 ms), simultaneously (0 ms) or after the picture (+500 ms), also known as the

stimulus onset asynchrony (SOA) (Collina, Tabossi & De Simone, 2013; Shao & Meyer, 2017). Critical

determinants that are measured during this task, is the accuracy and the time it takes from the presentation

of the picture to its naming (the naming latency). As presented by Harley (2014a), how the participants are

instructed may influence the response. Telling the participants to react quickly makes them respond faster

but at expense of making more errors. Conversely, stimulating the participants to be accurate makes them

respond slower. Therefore, both error rates and response times are measured in PWI studies. The errors

found in these tasks may say something about the naming abilities of participants. Impairment can be shown

by a heightened pattern of hesitations or no responses, as well as phonological and semantic paraphasias

(Hashimoto & Thompson, 2010).

The use of the PWI paradigm is an appropriate experimental method for investigating naming abilities

of aphasic individuals. A study by Hashimoto and Thompson (2010) corroborates this claim. They analysed

the use of the PWI in aphasia by studying the course of semantic and phonological activation needed for

naming in aphasic individuals (n=11) and control participants (n=20). In their PWI task they utilized

semantic, phonological and unrelated distractors presented at SOAs ranging from -300 ms, 0 ms and +300

ms. Results showed that significant semantic interference as well as phonological facilitation was present at

0 ms. In the case of semantic interference, the individuals with aphasia were significantly slower than the

control group at SOAs of -300 and 0 ms, with the largest effect measured at 0 ms. The subsequent error

analysis showed that more are errors present in the semantic related than in the neutral condition. The

error of ‘no responses’ was the most frequent for the aphasic group. They indicate that the observed effects

were caused by breakdowns in the phonological processing stage.

The claim that PWI can be useful for exanimating lexical selection and interference control is provided

by studies reported by Piai, Riès and Wick (2016) and Piai and Knight (2018). The possibility that

interference control has an influence on the naming difficulties in PPA as measured by PWI. For example,

an investigation reported by Vandenberghe et al., (2005) analysed word finding difficulty and word selection

in the semantic (n=6) and the nonfluent variant (n=5) of PPA. A primed picture naming paradigm was

applied with the use of a semantically related, unrelated and a neutral nonword condition. Results

demonstrated more errors and slower word retrieval for IwPPA when the prime was semantically related.

9 A spoken distractor usually refers to an auditory PWI paradigm. The paradigm that is taken into consideration in this thesis is the visual PWI.


Moreover, they proposed that during lexical retrieval, the characteristics10 of PPA interfere with the ability

to select and to discriminate semantically related words. Moreover, a noteworthy study by Thompson et al.,

(2012) used a PWI task to study the time course of object naming between individuals with nfvPPA (n=8)

and lvPPA (n=13) in comparison to controls (n=17). They utilized related and unrelated stimuli in order

to test overall semantic interference. Results showed slower reaction times for all groups in the related

condition in comparison to the unrelated condition over SOAs of -500, -100 and 0ms. However, only the

PPA groups presented effects at a SOA of -1000 ms, implying a greater magnitude of semantic interference.

They suggested that this magnitude is due to heightened activation of semantic networks as well as higher

vulnerability to the interference from distractors. They further deduced that this is caused by semantic

mapping deficits marked by difficulty in rapidly dissociating the distractor from the target. The study

highlights that besides phonological encoding deficits, defective semantic processing is accounted for also

in the naming deficits in these subtypes. Important to note is that the presence of these deficits due to poor

cognitive functions is ruled out. Patients performed well on the cognitive tests and results showed no

significant correlations.

3.3 Predictions

In accordance to the previous studies on PPA using PWI (Vandenberghe et al., 2005; Thompson et al.,

2012), I expect to find that the IwPPA exhibit slower response times and more frequent naming errors in

comparison to the control participants. I predict that more difficulty will arise in the related compared to

the neutral condition. With respect to the error analysis, based on the general difficulty in word-finding, I

expect hesitations to be present in all PPA variants (Kirschner, 2014). In addition, I expect that the semantic

variant demonstrates more semantic paraphasias and the logopenic variant displays a heightened frequency

of phonological paraphasias. Moreover, as certain variants only have few to only one patient, and the high

diversity within each subtype, I expect that no sufficient statistical power will be reached to categorize the

different PPA variants.

10 These were not specified in the paper.


4. Methods and materials

4.1 Participants

Twelve individuals with PPA (6 svPPA, 5 lvPPA and 1 nfvPPA) and thirteen healthy controls, matched on

age (p = 0.60), sex (p = 1) and education (p = 0.495), participated in the study11. They were recruited from

various hospitals in the Netherlands through geriatricians, neurologist and/or neurophysiologists. Patients

were clinically diagnosed with PPA. The diagnosis, based on a multi-disciplinary evaluation, was established

according to official clinical criteria (Gorno-Tempini, 2011). Patients did not have any neurological diseases

other that PPA and, like the control participants, did not present any physical or sensory deficits that could

interfere with their performance in the study. The controls were acquired through the personal contacts of

my supervisors at the Radboud University Nijmegen. All participants were native speakers of Dutch. The

study has been approved by the ethical committee and written consent was obtained from all the

participants. Only controls received monetary compensation. Specific demographic data on the participants

is illustrated in Table 1 below.

Table 1. Demographic information of patients and controls

Participant

Age at testing (in years)

Sex Education level (Verhage, 1964)

PPA classification

Years of symptoms

P1 73 M 4 lvPPA 2.5

P2 64 M 4 lvPPA 1.0

P3 55 M 6 lvPPA 2.0

P4 75 M 4 svPPA 2.5

P5 68 F 6 svPPA NA

P6 63 F 6 svPPA 4.0

P7 74 F 6 svPPA NA

P8 70 F 5 svPPA 2.0

P9 71 M 4 lvPPA 2.0

P10 80 M 6 lvPPA NA

P11 67 M 4 nfvPPA NA

P12 66 F 4 svPPA 5.0

PPA mean 68.8 ± 6.3 7M/5F

Control mean 68 ± 3.2 8M/5F

4.2 PWI task

4.2.1 Stimuli

Stimuli included twelve colour pictures of living objects that the participants were asked to name. These

items were selected from two different semantic categories (either an animal or a fruit) with six objects per

11All participants are part of the Language and Progressive Aphasia (LAPA) study (N. Janssen, personal communication, September 10th, 2018.


category. The pictures were considered for inclusion because of their easy and frequent use in daily life.

This was done in order to minimize the response times caused by word finding problems, since the focus

was on the degree of inhibition rather than the naming speed (N. Janssen, personal communication, 7

January, 2019). However, I cannot discard the possibility that frequency or word length effected the

outcomes of the results. Two different distractor types were used for each picture measuring an overall

interference effect12 (Starreveld & La Heij, 2017). The distractor was either a word from the same semantic

category, the related condition, or a row of X’s (XXX), the neutral condition. All the distractor words

belonged to the response set, meaning that for the image of an apple there was also a distractor word

“apple”. The task was divided into six blocks, with each block containing twenty items, 120 items in total.

In the test session the participants saw the experimental item each with a neutral and related distractor (five

times per condition). Every trial was randomized per participant.

4.2.2 Procedure

The PWI task was conducted in a sound-proof cubicle where participants were seated in front of a 24-inch

BenQ (XL2420Z) monitor and a Stage Line DM-5000LM microphone. Before the start of the experiment,

participants were shown a sheet of paper containing the images that would appear in the task. After

reviewing each one and highlighting the target names, which were provided below each image, participants

underwent a practice session. The familiarization phase comprised of twelve practice items in total.

Instructions appeared on screen and were offered orally as well. Participants were asked to name the images

presented in the centre of a white screen while ignoring a distractor that was superimposed on every image

(SOA= 0 ms). Each participant was encouraged to be as fast and accurate as possible. As mentioned

previously, the task was divided into six blocks. After each block, the participant had the option to take a

small break if needed. To begin each block, the phrase ''ATTENTION! The experiment is beginning'' was

presented on the screen for 1500 ms. After this, the experimental item with a distractor appeared for 4000

ms in the middle of the screen. A white screen was shown for 1000 ms before the start of the next trial.

It should be noted that the control group was tested by me and that the IwPPA were tested by one of

my internship supervisors. The tests were conducted in a similar environment. A comparable monitor,

microphone and similar settings for the audio recording were used. All patients underwent an MRI13 scan

first, and after a small break proceeded to partake in the PWI task and other neuropsychological tests. The

MRI task was administered first, followed by the PWI task and neuropsychological research. Likewise, the

control participants underwent an MRI scan. In 3 control cases the MRI and the PWI task were performed

on the same day (as was done for PPA patients), the scan was carried out first followed after a short break

by the PWI task. In the other 10 control cases the MRI was done on a different day as the PWI task.

12 Note that the interference effect is neither of semantic or lexical nature. This is discussed in further detail in the Discussion. 13 This MRI included a fMRI task.


4.2.3 Response time analysis

The naming response times (RT) were all manually determined using Praat (Boersma & Weenink, 2018). A

spectrogram generated by Praat was used to mark the first sound of each word made by the participant.

Only the beginning sound, and not the duration or end, was taken into consideration. This was done prior

to error coding and separating trials by condition. Responses containing errors or speech dysfluency were

coded as incorrect and their corresponding trials were excluded from the RT analysis14 (Piai, Riès & Swick,

2016; Piai & Knight, 2017; Thompson et al., 2012). The following responses were coded as errors: (1) an

existing word—but not the target—was named. (2) the distractor word was named. (3) response contained

hesitations (e.g. these entailed responses that began with stutters and filled pauses). (4) phonological

paraphasias. (5) a semantically related response (e.g. instead of responding with dog, responding with

Labrador). (6) RT is unreliable (e.g. the previous trial could be heard, participant was talking to the examiner

or coughed). (7) response contained a phrase or a determiner in addition to the target (e.g. participants

would start with ‘that is a [mouse]’). (8) no response is given. Trials containing slight variations, such as

consistent mispronunciation of a word, the use of the diminutive, modification after the target (e.g., cow

… calf), and a late response in the next trial, provided no distractor word was named, were coded as correct.

In accordance to Piai and Knight (2017), the RTs were log-transformed first to reduce skewedness.

Next, they were analysed with a linear mixed-effects model in R (R Core Team, 2019). There were fixed

effects for group (control vs. IwPPA) and condition (neutral vs. related), as well as their interaction.

Random intercepts were included for both participants and item. Condition was added as a random slope

for participant and group for item.

4.2.4 Error analysis

The coding of errors was identical to the one applied in the RT analysis. In this case, all correct responses

were excluded, with the addition of responses coded with (6) RT is unreliable and (7) response contained a

phrase or a determiner in addition to the target. The responses coded as 6 and 7 were excluded from the

RT analysis due to their influence on the response time but did not contain any errors.

The errors were analysed with a mixed-effects logistic regression in R (R Core Team, 2019). Similar to

the formula utilized for the RT analysis, there were fixed effects for group (control vs. IwPPA) and

condition (neutral vs. related), as well as their interaction. Random intercepts were included for both

participants and item. Only condition was added as a random slope for participant, on account of more

complex models failing to converge.

4.3 Additional cognitive and language tests

Additional tests were administered in order to examine the cognitive and language abilities of the

participants and to check how these correlate (and act as predictors) to their performance of the PWI task.

14 This was done in order to assure that the participant had understood and correctly processed the picture.


The tests included: (1) The Sydney Language Battery (Sydbat-NL, Savage et al., 2013, Dutch version

modified by Eikelboom et al., 2017), designed to help clinicians differentiate the PPA subtypes. It consists

of a naming, repetition, comprehension and semantic association task. (2) the Montreal Cognitive

Assessment (MoCa), designed to be a screening tool for mild cognitive impairments. There is an assessment

made on domains including ‘‘memory, language, executive functions, visuospatial skills, calculation,

abstraction, attention, concentration, and orientation’’ (Julayanont et al., 2013, p. 111). (3) the Digit Span

(of Wechsler Adult Intelligence Scale-IV), consisting of a forward, backward and sequencing15 component

is aimed at measuring auditory recall, short term memory and working memory (Coalson et al., 2010). (4)

the Trail Making Test (TMT), consisting of part A and B, is used to assess domains of speed, visual scanning

and executive function (attention and switching) (Llinàs-Reglà et al., 2017).

4.3.1 Procedure

With respect to the healthy controls, the administration of the additional tests occurred after the PWI task

in the same audio booth. The investigator was seated in front of the participants and proceeded to

administer the tests in a continuing manner. This was done following the specific instructions provided by

the test. No specific order of tests was adhered, only if a certain test required sections to follow a specific

order16. Due to the nature of PPA, the patients were burdened as little as possible. This meant that relevant

test results from the hospital were used as much as possible. If certain tests were not available or if the

neuropsychological research from the hospital had been conducted more than a half year ago, the tests were

taken again on the same testing day as the PWI task17.

15 Although the Digit Span consist of these three subtests, the results obtained reflect the total score. It would have been more insightful if each section was analysed. 16 For the SYDBAT-NL the order of the test administration is important. The subtest ‘Naming’ must always be administered first. The subtest ‘Repetition’ may then be administered 2nd, 3rd, or as last. However, the subtest 'Comprehension' must always be administered before the subtest 'Semantic association’. 17 This was done prior to my involvement in the study.


Control

PPA

5. Results

The PWI task results are first reported. Figure 1 and Table 2 show individual-average as well as group-

average response times and naming accuracy. Notably, the response times for the IwPPA are longer in

comparison to the control participants, with relatively more variation present as well. It is evident that that

that data points of the control participants are grouped tightly together, but that the data points of IwPPA

demonstrate a high degree of heterogeneity, as seen in Figure 1. As expected, the naming accuracy of the

healthy controls is much higher (nearing ceiling level) than the IwPPA. Again, there is extensive variation

present.

Figure 1. Individual averages of response times and naming accuracy for the two groups across conditions in PWI task

Table 2. Group averages of response times in ms and naming accuracy (and their standard deviation).

Condition RT in ms Naming accuracy

Control

Related 896 (116) 97.4 (2.4)

Neutral 759 (94) 99.6 (0.7)

PPA Related 1367 (457) 81.5 (18.2)

Neutral 1141 (384) 92.1 (7.4)

5.1 Response times

With regard to the response times seen in Table 3, the IwPPA were significantly slower in the naming of

pictures in comparison to the control participants by an average estimated difference of 153 ms (p=<0.001).

A significant overall interference effect was observed as well. Response times were higher in the related

condition in comparison to the neutral condition by an average estimated difference of 77 ms (p=<0.001).

Conversely, no inference can be drawn as to whether the IwPPA are slower than the healthy controls over

0

500

1000

1500

2000

2500

3000

Related Neutral

Res

po

nse

Tim

es (

ms)

0.0

20.0

40.0

60.0

80.0

100.0

120.0

Related Neutral

Nam

ing

accu

racy

(%

)


the two conditions. There was no significant effect found between these two notions (p=0.227). The same

holds true for this comparison between the different PPA subtypes and controls. Only a main effect of

group and condition were thus found.

Table 3. Inferential statistics for response times (top) and naming accuracy (below).

Response times

b SE t (df) p

Controls vs. PPA 0.153 0.036 4.217 (25) <0.001

Related vs. neutral 0.077 0.006 12.066 (24) <0.001

Related vs. neutral : controls

Related vs. neutral : PPA

Related vs. neutral : controls vs. PPA 0.016 0.013 1.240 (23) 0.227

Related vs. neutral : controls vs. svPPA 0.017 0.018 0.977 (18) 0.341

Related vs. neutral : controls vs. lvPPA 0.014 0.012 1.206 (18) 0.243

Related vs. neutral : controls vs. nfvPPA 0.023 0.025 0.909 (28) 0.371

Error rate

B SE z p

Controls vs. PPA 3.089 0.724 4.265 <0.001

Related vs. neutral 1.867 0.671 2.782 0.005

Related vs. neutral : controls

Related vs. neutral : PPA

Related vs. neutral : controls vs. PPA -0.892 0.688 -1.296 0.195

Related vs. neutral : controls vs. svPPA -1.117 0.751 -1.487 0.137

Related vs. neutral : controls vs. lvPPA -0.592 0.722 -0.820 0.412

Related vs. neutral : controls vs. nfvPPA -1.496 0.915 -1.635 0.102

5.2 Naming accuracy

The error rate results in Table 3 show that the control participants, in contrast to the IwPPA, score

significantly better on the task by an estimated log difference of 3.1 (p=<0.001). According to this, the

calculated odds ratio is 22.0, meaning that the control participants scored 22.0 times better than the IwPPA.

A significant interference effect was again observed. Participants were significantly less accurate in the

related condition than the neutral condition by an estimated log difference of 1.9 (p=0.005). The calculated

odds ratio is 6.5, meaning that in the related condition 6.5 times more errors were produced than in the

neutral condition. Once more, no significant effect in the interaction between group and condition was

found (p=0.195), nor between the control participants and PPA subtypes. Only a main effect of group and

condition were present.

The error distribution is shown in Figure 2. Based on the graphs of the two groups, a substantial

difference in the frequency of errors is noticeable. The IwPPA produce more errors both in the related

(n=133) and the neutral condition (n=58). The difference is observed in the number of distractors named,

hesitations and no responses given. Considering the small number of PPA participants, a more detailed

account of the produced errors per variant and participant can be provided. In Figure 3 the error


PPA

Control

distributions of the logopenic variant are shown. It can be observed that most errors stem from P3 (n=41)

and P10 (n=46) in their own variant and the PPA group in total. It is noteworthy that phonological

paraphasias are not on the forefront of most made errors. The semantic variant, shown in Figure 4, displays

a more varying image. Apart from a higher concentration of no responses from P4, no clear outliers are

present. Figure 6 presents the errors made by P11, the only participant in the nonfluent variant, with

hesitations as the most frequent made error.

Figure 2. Error distribution for the two groups across the related and the neutral condition

Figure 3. Error distribution for the logopenic variant, shown by participant. nt=not target, dis=distractor, hes=hesitation, phon=phonological paraphasia, sem=semantically related response, nr=no response

0

5

10

15

20

25

30

35

40

45

50

Fre

quen

cy o

f er

rors

Related Neutral

0

5

10

15

20

25

30

35

40

45

50

Related Neutral

0

4

8

12

16

20

nt

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

P1 P2 P3 P9 P10

lvPPA

Related Neutral


Figure 4. Error distribution for the semantic variant, shown by participant.

Figure 5. Error distribution for the semantic variant, shown by participant.

5.3 Additional cognitive and language tests

Table 4 presents the group-averaged scores and p-values (Mann-Whitney U test) on the various cognitive

and linguistic tests. The results show a significant difference between the two groups on almost all tests.

Only the repetition and comprehension components of the SydBat-NL rendered non-significant results.

Though it should be clarified that there were missing test values from the IwPPA on some parts of the

tests, which has an influence of the overall significance.

Figure 6 reveals the correlations between the cognitive tests (MoCa, Digit-span, TMT A and TMT B)

and the RT and error rate. The plot shows various coloured circles with the Pearson’s correlation coefficient

presented in the middle. For the sake of this analysis only the first two rows are of interest. It can be seen

that error rate is negatively correlated with the TMT B, MoCa, Naming and Repetition of the SydBat-NL,

and the Digit Span. RT is negatively correlated with all tests, but especially with the MoCa. This implies

that the RT and the numbers of errors increases when the score on the test decreases.

0

4

8

12n

t

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

nt

dis

hes

ph

on

sem nr

P4 P5 P6 P7 P8 P12

svPPA

Related Neutral

0

4

8

nt dis hes phon sem nr

P11

nfvPPA

Related Neutral


Figure 6. Correlations between the error rates, response times, and the additional tests

Table 4. Group averages scores on the cog. And linguistic tests (and their standard deviation).

Cog. and linguistic tests

Scores Controls

Scores PPA p

MoCa 27 (2.3) 22 (3.2) <0.001

TMT A 51 (5.9) 39 (13.3) 0.008

TMT B 51 (7.5) 41 10.9) 0.042

Digit Span 11 (2.2) 6 (3.6) 0.003

SB-NL Nam 27 (1.4) 18 (4.6) <0.001

SB-NL Rep 29 (0.5) 28 (2.2) 0.093

SB-NL Com 29 (0.9) 28 (1.6) 0.125

SB-NL Asso 28 (2.5) 24 (4.8) 0.003


6. Discussion

The objectives of the thesis where to investigate the performance in picture naming of IwPPA and controls

participants using a PWI task and to investigate the three PPA variants more closely. In my study the IwPPA

performed significantly slower and showed less accuracy in naming compared to the controls. In addition,

a significant interference effect was observed. The related condition proved to be more problematic than

the neutral condition in both the RTs and accuracy analysis. The results related to group difference are in

agreement with the findings obtained from the studies of Vandenberghe et al. (2005) and Thompson et al.

(2012). The significant interference effect in my study and the aforementioned studies, however, cannot be

fully compared. Whereas my study employed a combined interference effect of semanticity and lexicality,

the other studies investigated the role of semantic interference. The combined effect was so designed to

maximize the chance of finding a difference in effect between the IwPPA and healthy controls (N. Janssen,

personal communication, 24 June 2019). In terms of interpretation it cannot be said whether the effect is

lexical or semantic. The breakdown in naming and support to the claims on naming deficits as shown in

chapter three, is therefore challenging to uncover. No time course was measured by virtue of various SOAs

(see chapter three). This makes it complicated to uncover at which stage (e. g. semantic representation, post

semantic stage or phonological representations) difficulty occurs.

The additional Sydbat-NL test showed significant differences in the naming and semantic association

subtests between IwPPA and controls whereas comprehension and repetition did not. Relative intact

comprehension, but slower RTs, could imply deficits in lexical access. IwPPA can understand the word,

implying relative intact semantic knowledge, but not access it for naming. But again, it is difficult to

determine at what stage this may occur. The vital analysis of the three variants and their characteristic

features are also missing because of a low number of data points. The comparison between them did not

converge in the statistical measures taken in R due to low participant number. My results do not support

the results obtained by others (e.g. van Scherpenberg et al., 2019; Wilson et al., 2017; Henry et al., 2013)

regarding claims of naming deficits.

Still, the notion of interference control of attention and inhibition was measured through the distractor

in the PWI. Though in the same manner, to discover the precise role in the slower RTs of IwPPA is

complicated. The limitation of only measuring at 0 ms makes it difficult to infer if a heightened activation

and difficulty in lexical selection is present. This was described by Thompson et al., 2012 where activity was

present at a SOA of -1000 ms. In any case, the fact that faulty executive functions (Macoir et al., 2017) may

have an influence on lexical selection should be further investigated. There were significant differences on

the cognitive tests between the IwPPA and controls. Moreover, these tests proved to be predictors in the

performance of the PWI task.

A clear distinction of the two groups can be made with respect to the error distribution shown in Figure

2. As predicted, there were high rates of hesitation errors in PPA patients. While not predicted, frequent

distractor errors and no response errors were obtained in IwPPA. In the subsequent figures, variance among

the patients can be observed. Participants P3 and P10 (lvPPA) and P4 (svPPA) contributed most. Due to


the small number of participants per PPA type, it cannot be directly said that these individuals can be treated

as outliers. Moreover, this may also simply be indicative of the heterogeneity of PPA and also the

heterogeneity between the subtypes. The diagnosis and stratification of subtypes based on the errors

produced by the PWI was not possible. Characteristic errors of the variants such as semantic paraphasias

in svPPA and phonological paraphasias in lvPPA did not appear frequently. In part this can be explained

by that the specific test was not sensitive enough to elicit those type of errors.

6.1 Limitations

There are a number of limitations to this study. The most vital, mentioned throughout the paper, is the

small number of participants present in the investigation. This is especially holds true for the nonfluent

PPA variant, where there was only one individual tested. As mentioned before, this undermines the

statistical power of my study, which increases the chance of type І error. Moreover, the lack of SOAs and

other interference effects (semantic or lexical) in this investigation limit its scope. It would have been

interesting to explore the process of various stimuli onsets (see Thompson et al., 2012) in addition to the

SOA of 0 ms used in this study. Likewise, addition of stimuli testing semantic interference or phonological

facilitation would allow for a more detailed account of lexical access breakdown.

The assumption that the cognitive tests utilized here truly measure the executive functions necessary

for lexical selection is not guaranteed. The low scores obtained could also reflect the language impairment

in IwPPA, which was already discussed by Grossman & Ash (2004, see introduction).

The RT analysis is another possible drawback of this study. The manual calculation of the RT data

leaves room for human error and inconsistencies. Though I tried to be as consistent as possible, it would

have been beneficial if there were specific indicators for word sound onset or to have a second coder check

for inter-rater reliability. The error distribution analysis was conducted by using descriptive graphs,

speculating about patterns found rather than performing statistical analysis to analyse the differences.

Further analysis was not possible due to a limited number of datapoints.

Furthermore, as previously reported, the testing of the IwPPA was performed by my supervisor,

whereas I tested the controls, which could lead to interobserver variability. Also, some control participants

underwent different testing schedules of MRI and PWI task. This may also lead to different results, e.g. if

participants make more errors if they have been subjected just before with MRI testing. To minimize the

error rate the PWI task was mainly recorded through computerized operating.

Lastly, the fact that a control participant had to be re-tested due to an error in the recording is also far

from desirable. Though it is important to note that the time between test and re-testing consisted of a

period of 46 days. Nevertheless, the PWI effect assumes the same underlying processes as the Stroop effect,

which adheres to extremely robust findings (Maanen, van Rijn & Borst, 2009; Starreveld & La Heij, 2017).


6.2 Future perspective

The PWI method has proven useful in distinguishing between IwPPA and control participants, but the

classification of patients into the three PPA variants on the basis of PWI was not possible. This is because

PPA is a very heterogeneous disease and progression path from initial diagnosis during aging is likely to be

different for each patient. The time between onset of the disease and initial disease diagnosis varies for each

patient. Moreover, loss of executive function will be confounding factor. PWI testing needs to be integrated

with other tests, including imaging and cognitive tests, explicitly testing executive functions like selective

attention and inhibition. This will allow for early PPA diagnosis, make accurate predictions on how the

disease will progress and allow for the development of new therapeutic modalities as the intervention can

be better assessed. Altogether, this will result in better care and optimal treatment for each individual PPA

patient.


7. Conclusion

This thesis investigated the naming abilities of IwPPA with the use of a PWI task. The study tried to explore

the breakdown in naming in relation to interference control processes evoked through nature of the task.

While the results showed that IwPPA are significantly slower and less accurate than healthy control

participants, profound conclusions on the breakdown of naming cannot be made. This applies to the role

of interference control as well, which needs to be investigated more deeply. The differences in the PPA

variants could not be established, due to the low number of participants per each subtype. Nevertheless,

the present study should be seen as a pilot study as many pitfalls in the experimental design became

apparent. Important is also that the PWI and linguistic tasks should be integrated with other tests on

cognitive functions and neuroimaging to allow for better diagnosis and results that can be used to guide for

better treatment of IwPPA.


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ACKNOWLEDGEMENTS

The process of finishing the thesis and finally completing my master program has been quite the challenge.

Still, above all, it has been a great learning experience for which I owe many people my sincerest gratitude.

First, I wish to thank my thesis supervisor dr. Nada Vasic. I am very grateful for the feedback and

insights you provided.

I would also like to thank my supervisors at the Donders Institute, dr. Vitória Piai and Nikki Janssen

for giving me the opportunity to learn and be a part of valuable research. Thank you so much for guiding

me throughout the internship period and making the experience immensely worthwhile.

Special thanks to the all of those who were willing to participate and bared with my initial testing

sessions. Although I did not have direct contact with the patients in my study, I extend this gratitude and

appreciation.

Likewise, I would like thank the patients and personnel of the speech therapy department at the

Radboud UMC, who were so helpful and allowed me to observe and obtain great understanding into the

workings of speech or language impairment assessment.

Finally, I express my deepest gratefulness to my family and friends who have supported me throughout

my university years, and this thesis especially. Thank you for your constant encouragement18.

18 Parts that should remain confidential were removed from this master thesis.

primary progressive aphasia a study of picture naming

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