Mind your Language, All Right?
Performance‐dependent neural patterns of language
Helene van Ettinger‐Veenstra
Center for Medical Image Science and Visualization
Division of Radiological Sciences
Department of Medical and Health Sciences
Linköping University, Sweden
Linköping
2013© Helene van Ettinger‐Veenstra, 2013 helene.veenstra@liu.se Published papers have been reprinted with permission of the copyright holders Cover design: Tjeerd Veenstra www.tjeerdveenstra.nl Printed in Sweden by LiU Tryck, Linköping, Sweden, 2013 ISSN 0345‐0082 ISBN 978‐91‐7519‐668‐8
voor mijn lieve Lucas Levi
They say the left side of the brain
Dominates the right
And the right side has to labor through
The long and speechless night
…
Maybe I think too much
‘Think Too Much (b)’ ‐ Paul SimonABSTRACT
The main aim of this dissertation was to investigate the difference in neural language patterns related to language ability in healthy adults. The focus lies on unraveling the contributions of the right‐hemispheric homologues to Broca’s area in the inferior frontal gyrus (IFG) and Wernicke’s area in the posterior temporal and inferior parietal lobes. The functions of these regions are far from fully understood at present. Two study populations consisting of healthy adults and a small group of people with generalized epilepsy were investigated. Individual performance scores in tests of language ability were correlated with brain activation obtained with functional magnetic resonance imaging during semantic and word fluency tasks. Performance‐dependent differences were expected in the left‐hemispheric Broca’s and Wernicke’s area and in their right‐hemispheric counterparts. PAPER I revealed a shift in laterality towards right‐hemispheric IFG and posterior temporal lobe activation, related to high semantic performance. The whole‐brain analysis results of PAPER II revealed numerous candidate regions for language ability modulation. PAPER II also confirmed the finding of PAPER I, by showing several performance‐dependent regions in the right‐hemispheric IFG and the posterior temporal lobe. In PAPER III, a new study population of healthy adults was tested. Again, the right posterior temporal lobe was related to high semantic performance. A decrease in left‐ hemispheric IFG activation could be linked to high word fluency ability. In addition, task difficulty was modulated. Increased task complexity showed to correlate positively with bilateral IFG activation. Lastly, PAPER IV investigated anti‐correlated regions. These regions are commonly known as the default mode network (DMN) and are normally suppressed during cognitive tasks. It was found that people with generalized epilepsy had an inadequate suppression of regions in the DMN, and showed poorer performance in a complex language test. The results point to neural adaptability in the IFG and temporal lobe. Decreased left‐lateralization of the IFG and increased right‐ lateralization of the posterior temporal lobe are proposed as characteristics of individuals with high language ability.
SAMMANFATTNING
Som vuxna människor är vi, även då vi är friska, väldigt olika, med olika förmågor. Så är det
också med språklig förmåga. Det varierar betydligt mellan olika personer hur bra
läsförståelse man har, eller hur lätt man har att hitta på ord. Denna avhandling bygger på att
dessa mätbara språkliga skillnader också kan synliggöras i hjärnan med hjälp av
hjärnscanning, så kallad funktionell magnetresonanstomografi. Hjärnaktivering vid
språkfunktion är ofta koncentrerad i den vänstra hjärnhalvan; i nedersta delen av
pannloben samt i bakre delen av tinningloben, men även den högra hjärnhalvan kan
aktiveras av flera olika språkfunktioner. Speciellt finns de funktioner som får en person att
förstå komplicerade språkkomponenter, till exempel bildspråk eller andra typer av
underliggande betydelser i språket, i den högra hjärnhalvan. I studierna som ligger till
grund för denna avhandling förväntades att hjärnaktiveringen i vanliga språkområden i den
vänstra hjärnhalvan skulle variera med språklig förmåga. Om personer som är bättre på
språk har en hjärna som fungerar mer effektivt, så skulle det visa sig som mindre aktivering
i vänstersidiga språkområden. Å andra sidan, om personer som presterar bra har bättre
kognitiv förmåga än sämre presterande, skulle det kunna synas som mer aktivering i de
understödjande språkområdena i höger hjärnhalva. Resultaten som framgår i denna
avhandling är framför allt att aktivering i höger tinninglob är involverad i bättre språklig
förmåga. Det finns också antydningar att nedre delen av den högra pannloben är mer
aktiverad när man är bra på språk. Resultaten visade sig dock att variera med språkuppgift;
det finns bevis för mer aktivering i höger pannlob i samband med bättre språkförståelse och
för mindre aktivering i vänster pannlob i samband med bättre förmåga att generera ord.
Dessutom är den nedre delen av pannloben mer aktiv vid svårare språkförståelseuppgifter.
Slutsatsen av dessa studier är att aktivering i den nedre pannloben är beroende av kognitiv
kapacitet, men att aktivering i den högersidiga bakre tinningloben är specifik för
språkförståelse. De studier som är inkluderade i avhandlingen visar att desto bättre man är
på språk, desto mindre använder man enbart den vänstra hjärnhalvan när man läser eller
genererar ord.
LIST OF PUBLICATIONS
This dissertation is based on the following original papers, which are referred to throughout the text by their Roman numerals:PAPER I Van Ettinger‐Veenstra HM, Ragnehed M, Hällgren M, Karlsson T, Landtblom A‐M, Lundberg P, and Engström M (2010). Right‐hemispheric brain activation correlates to language performance. NeuroImage 49(4): 3481–3488.
PAPER II Van Ettinger‐Veenstra HM, Ragnehed M, McAllister A, Lundberg P, and Engström M (2012). Right‐hemispheric cortical contributions to language ability in healthy adults. Brain and Language 120(3): 395–400.
PAPER III Gauffin H*, Van Ettinger‐Veenstra HM*, Landtblom A‐M, Ulrici D, McAllister A, Karlsson T, and Engström M. Impaired language function in generalized epilepsy: Inadequate suppression of the default mode network. Accepted in Epilepsy & Behavior, 2013.
PAPER IV Van Ettinger‐Veenstra HM, Karlsson T, McAllister A, Lundberg P, and Engström M. Laterality shifts in neural activation coupled to language ability. Submitted to PLoS ONE, 2013. * The first two authors contributed equally to this paper
Related Peer‐Reviewed Conference Abstracts
Veenstra HM, Ragnehed M, Hällgren M, Lundberg P, and Engström M. Brain lateralization assessed by fMRI and dichotic listening. Paper presented at the 15th Annual Meeting of the Organization for Human Brain Mapping, California, USA, 2009. Veenstra HM, Pettersson J, Nelli C, Ragnehed M, McAllister A, Lundberg P, and Engström M. Influence of performance‐related language ability on cortical activation. Paper presented at the 15th
Annual Meeting of the Organization for Human Brain Mapping, California, USA, 2009. Van Ettinger‐Veenstra H, Karlsson T, Ulrici D, Gauffin H, Landtblom AM, and Engström M. Language ability in healthy and epilepsy participants: an fMRI investigation. Paper presented at the 43rd European Brain and Behaviour Society Meeting, Seville, Spain, 2011. Van Ettinger‐Veenstra H, Gauffin H, McAllister A, Lundberg P, Ulrici D, Landtblom A‐M, and Engström M. Language deficits in Epilepsy, an fMRI study. Paper presented at the 18th Annual Meeting of the Organization for Human Brain Mapping, Beijing, China, 2012.
AT A GLANCE
PAPER (study) I (A) II (A) III (B) IV (B) METHODS 14 healthy adults. fMRI: Lateralization Index from sentence reading (SENCO) task was correlated with Read, BeSS, FAS & BNT performance scores. Also, Dichotic Listening laterality measurements were investigated. 18 healthy adults. Whole‐brain analyses from sentence reading (SENCO) and word fluency (WORGE); activation was correlated with Read, BeSS, FAS & BNT performance scores. 27 healthy adults. Lateralization Index from ROI analyses of sentence reading (SEN) and word fluency (WORD), correlated with performance scores on BeSS and FAS. Also, task difficulty related brain activation was investigated with multiple regression. 27 healthy & 11 Generalized Epilepsy participants. Investigated for deactivation in the default mode network during sentence reading (SEN). Also, language performance measurements of the epilepsy group.
RESULTS Activation in the right‐hemispheric ROIs was more pronounced for high performance. This correlated with the dichotic listening results. Especially high BeSS and Read scores correlated with increased right‐lateralization. Several clusters in right IFG and temporal lobe showed to correlate with BeSS and Read on the sentence reading fMRI task. No such results for word fluency. Activation in the temporal lobe was more right‐lateralized for high BeSS performance. Activation in left IFG was less left‐lateralized for high FAS performance. The difficult incongruent sentence reading condition was characterized by bilateral IFG activation People with Generalized Epilepsy showed worse performance in BeSS than healthy controls. They also showed diminished DMN deactivation, notable was the decreased left temporal lobe deactivation and increased hippocampal activation. CONCLUSIONS Both dichotic listening and fMRI results point to a right‐hemispheric activation as a characteristic for high language ability. Regions in inferior frontal gyrus (BA 47) and middle temporal gyrus (BA 21) are related to high semantic language ability. Activation in the inferior frontal gyrus is modulated by semantic difficulty, while right temporal lobe activation is specific for semantic ability. People with Generalized Epilepsy experience language difficulties. This could be explained by aberrant suppression of activation in the default mode network. A failure to suppress default mode network activation is disturbing for cognitive functioning.
ABBREVIATIONS
BA Brodmann Area BeSS “Bedömning av Subtila Språkstörningar” – Assessment of Subtle Language Deficits BNT Boston Naming Test BOLD Blood Oxygen Level Dependent DMN Default Mode Network fMRI functional Magnetic Resonance Imaging FWE Family‐Wise Error GE Generalized Epilepsy GLM General Linear Model IFG Inferior Frontal Gyrus LI Laterality Index MNI Montreal Neurological Institute MRI Magnetic Resonance Imaging P‐FIT Parieto‐Frontal Integration Theory ROI Region of Interest SEN sentence reading fMRI task used in PAPER III & PAPER IV SENCO sentence completion fMRI task used in PAPER I & PAPER II WORD word generation fMRI task used in PAPER III WORGE word generation fMRI task used in PAPER IICONTENTS
ABSTRACT
I
SAMMANFATTNING
III
LIST OF PUBLICATIONS
V
AT A GLANCE
VI
ABBREVIATIONS
IX
1 INTRODUCTION
1
1.1 L
ANGUAGEA
BILITY2
1.1.1
Language Abilities
2
1.1.2
Language Dysfunctions
3
1.2 N
EURALC
ORRELATES TOL
ANGUAGE4
1.2.1
Language Models
4
1.2.2
Semantics
8
1.2.3
Word Fluency
8
1.2.4
Right‐Hemispheric Influences
8
1.2.5
Laterality
9
1.2.6
Anti‐correlated Brain Activation
10
1.3 I
NTELLIGENCE MODELS FORL
ANGUAGEA
BILITY11
1.3.1
Relation Language Ability and Intelligence
11
1.3.2
Intelligence Models
11
1.4 A
IMS13
2 METHODS
15
2.1 N
EUROLINGUISTICM
EASURES15
2.1.1
Tests of Language Ability
15
2.1.2
Dichotic Listening
16
2.1.3
fMRI Language Paradigms
16
2.1.4
Study Population
17
2.1.5
Generalized Epilepsy
17
2.2 F
UNCTIONALMRI
18
2.2.1
Properties of Functional MRI
18
2.2.2
Region of Interest Analysis
19
2.2.3
Laterality Index Analysis
20
3 RESULTS
23
3.1 M
ULTIPLER
EGRESSIONA
NALYSES24
3.2 L
ATERALITYA
NALYSES27
3.3 T
ASKD
IFFICULTYM
ODULATION28
3.4 L
ANGUAGED
YSFUNCTIONS INE
PILEPSY29
4 DISCUSSION
31
4.1 N
EURALC
ORRELATES TOP
ERFORMANCE31
4.1.1
Multiple Regression Analyses
31
4.1.2
Laterality Analyses
33
4.1.3
Task Difficulty Modulation
34
4.1.4
Language Dysfunctions in Epilepsy
35
4.2 H
EALTHYA
DULTS36
4.3 I
NTERPRETATION OFA
CTIVATIONP
ATTERNS37
4.4 F
UTURED
IRECTIONS42
5 CONCLUSIONS
45
ACKNOWLEDGMENTS
46
REFERENCES
49
PAPER I
PAPER II
PAPER III
PAPER IV
Big black cloud
On a yellow plain
Sure enough it
Looks like rain
Packin' up all our
Faith and trust
Me and the wanderlust
‘Wanderlust’ ‐ Mark Knopfler
1
INTRODUCTION
Mapping of language disability patterns requires a thorough understanding of language ability patterns. The neural pathways for perceiving and generating language are slowly being unraveled, but the exact contributions of typical left‐hemispheric language areas (Broca’s and Wernicke’s area) are not yet completely clear. Neither is the role of language‐related regions in the – usually non‐ dominant – right hemisphere. The opinion about how right‐hemispheric regions influence language has changed. In the past, activation in the right hemisphere during language tasks was largely overlooked; but over time, researchers gained an understanding of the emotional content processing aspects. At present, additional roles of the right hemisphere in language are being explored, including language comprehension aspects. Evidence of these right‐hemispheric comprehensive aspects is presented in this dissertation within a framework of manifestations of language ability in the brain.
This dissertation presents four papers that investigated language ability, which was defined as language production and comprehension abilities. The first three papers describe how healthy adults were tested for brain activation evoked by neurolinguistic functional magnetic resonance imaging (fMRI) tasks. These fMRI tasks measured semantic processing and word fluency activations. The results were related to individual performance measurements in various tests of language ability, including reading, word fluency, picture naming and use of complex language. The fourth paper discusses how the brains of people with generalized epilepsy can express altered activation patterns in relation to lower language ability.
1.1
Language Ability
1.1.1
Language Abilities
The ability to produce language enables one to communicate one’s own thoughts and express oneself. Comprehension of language will enable one to perceive information that might be new or interesting. As in all skills; individual differences are present. The origins of these differences might be attributed to the amount of exposure to language, or to one’s own interests in reading or verbal expression. Whenever people manifest differences in behavior, neuroimagers will look for the neural correlates to these differences. Indeed, the rationale behind the performed experiments that led to this dissertation was to visualize language ability differences in healthy subjects. The current sub‐chapter will present previous research on language ability variation. In the following sub‐chapter, ‘Neural Correlates to Language’, a more detailed framework for language ability will be introduced.Language discussions often refer to the classical language areas of Broca’s area in the left inferior frontal gyrus (IFG) and Wernicke’s area in the left posterior temporal lobe. It is also known that other functional regions are involved in language processes; these will be explored in the next sub‐chapter. It seems that differences in language performance can be – at least partly – explained by differentiations in activation in Broca’s and Wernicke’s language areas, although their exact contribution is not yet clear. Studies investigating high performance in word fluency have shown an increase of left‐hemispheric IFG activation for high performance (Wood et al., 2001), but also no difference at all (Dräger et al., 2004). When semantic tasks are studied, increased activation of posterior temporal and parietal regions is shown for high performance (Booth et al., 2003; Meyler et al; 2007; Weber et al., 2006).
However, an opposing view emerges from an increasing number of works revealing a relationship between reading and sentence comprehension and decreased activation in left hemispheric language areas (Reichle et al., 2000; Prat et al., 2007; 2011, Prat & Just, 2011). The mechanism behind this activation reduction is thought to be a more efficient neural functioning. Efficacy in recruiting neural regions or pathways enables a person to re‐attribute cognitive resources guided by task demand. Thus, a person skilled in language may use his or her brain in a more optimal way for the presented task. Furthermore, there is evidence of a specific role of the right‐hemispheric homologues of Broca’s and Wernicke’s area in high language performance. Many of the results presented in the papers that are included in this dissertation point also to a right‐hemispheric contribution to high language ability. If people with a high language ability recruit additional language‐supporting areas, this may indicate that a high adaptability of neural resources is an explanatory mechanism for language ability differences. Research supporting the theories of neural adaptability and neural efficiency as
explicatory for high language ability will be presented in the sub‐chapter ‘Intelligence models for Language Ability’
1.1.2
Language Dysfunctions
The introduction started out by stating that knowledge of language ability will lead to an understanding of language disability. PAPER IV presents a group of people with epilepsy showing subtle language disabilities, and compares them with healthy subjects performing on a normal level. The reverse statement to the one above is also true; upon investigating language disabilities, a model for language abilities can be created. Much of our knowledge about the language system has been gained from lesion studies notably those on left‐hemispheric lesioned patients showing word production problems, as presented a little later in this section.
Language impairment can have a variety of underlying causes; impaired language functioning, cognitive ability, or sensory/motoric abilities, or lack of training or exposure to language. A disruption in any component of language production or comprehension in the language model1
evidently will result in a disruption of language ability. Since the studies included in this dissertation measure word generation and sentence reading, this section discusses reading impairment (dyslexia) and production problems.
Developmental dyslexia is characterized by various neurological differences throughout the brain, probably caused by anomalies during the development of language systems in the brain (Catts & Kamhi, 2005; Démonet et al., 2005). It has been suggested that this type of dyslexia is related to abnormal dominance patterns or abnormal development of dominance (Heim et al., 2010), but the causes are though probably multiple and more complex (Crystal 2010). Acquired dyslexia can occur after a lesion in one out of various brain regions (Price et al., 2003). Functional imaging studies on the neurological differences between people with dyslexia and normal performers show a diminished activation in temporal and parietal regions (Salmelin et al., 1996; Shaywitz et al., 1998), and an increase in inferior frontal activation (Shaywitz et al., 1998). Both the presence of expected activation and the absence of unexpected activation in the right hemisphere have been observed to act as distinguishers of people with dyslexia from people without reading impairment (Paulesu et al., 1996; Simos et al., 2000).
Word production problems are often not development‐related but result from lesions in the language‐dominant hemisphere. Problems with word fluency are seen in people with dementia and with left temporal lobe epilepsy (Ruff et al., 1997). Named after the location of brain damage, aphasia
can be classified as Broca’s aphasia, Wernicke’s aphasia or global aphasia – the latter being a combination of Broca’s and Wernicke’s aphasia. It is now known that in Broca’s aphasia, brain regions posterior to Broca’s area are often damaged; and that in Wernicke’s aphasia the location of damage can vary (Crystal 2010). Broca’s aphasia results in deficits in expressive abilities and is characterized by non‐fluent speech which is grammatically incorrect. Wernicke’s aphasia occurs when receptive systems are damaged and results in both comprehension problems and problems producing intelligible speech, even though it appears to be fluent. Furthermore, word retrieval problems are a common deficiency (Crystal 2010).
Studies on language disabilities can help us to find regions of interest for the investigation of language abilities. Lesion studies that have led to an understanding of language disabilities have shown that disruption of language functioning in the language‐dominant hemisphere has a much higher impact than a disruption in the non‐dominant hemisphere. Thus, the language functions in the non‐dominant hemisphere may not be compulsory for language production, but may support complex processing.
1.2
Neural Correlates to Language
1.2.1
Language Models
There are many possible theoretical models to describe the complex structure of language. Often, these models use similar distinctions between word forms, word structure, word meaning and understanding of text or speech. In other words, many models describe language as a process defining the range of linguistic information from small building blocks to complex meaningful communication. To understand language in the context of this dissertation, a useful model is the space station model as presented by Crystal (2010), and represented in Figure 1.
This model describes an interactive framework integrating the components of language that are investigated in the papers included in this dissertation. The different components are: phonetics (pronunciation attributes) and phonology (sounds that convey different meanings), morphology (word structure) and syntax (sentence structure), semantics (meaningful content) and pragmatics (discourse information). The connection between these components is not uni‐directional, but rather interconnected as represented in the space station model. This is consistent with the neural organization of language, where both top‐down and bottom‐up processes can be observed during language processes (Friederici 2012).
Figure 1. Representation of the Space Station Language Model. The linguistic levels presented in the
circles are interconnected, indicating free exchange of linguistic information between levels; thus all information is available at once for an external researcher. Figure adapted from Crystal (2010).
Measures of language ability preferably test for many linguistic components, including production and perception of language, and have a high enough difficulty level to measure variability in language skills. On the other hand, the total test duration should be kept to a minimum as to impose only minimally on the participants, especially on those with cognitive disabilities. The tests used in our studies, (see also Methods section for their description), show two approaches towards this goal. First; established tests such as the Boston Naming Test (Kaplan et al., 1983) or word fluency tests – testing word retrieval and word production skills – are used in many research studies that describe the neural mechanisms that lie behind. Moreover, these tests are easily translated to the magnetic resonance scanner environment without much adapting. However, both tasks are very focused; they do not test for the full spectrum of language ability. Other tests, such as comprehensive reading, investigate language perception and comprehension and could be translated to the scanner environment with some modification. A second approach is to gather multiple language ability tests in a battery, such as the Assessment of Subtle Language Deficits or BeSS test (Laakso et al., 2000). This relatively new complex language ability test is not yet established, but can detect subtle language dysfunctions without showing a ceiling effect (as the results of our papers will show). Moreover, this is a compact test, so that language ability can be assessed quickly without too much imposing on the
concentration skills of people with language dysfunctions (such as the people with generalized epilepsy from our PAPER IV). However, this test is less practical in a scanner environment.
Neurological models are often based on the classical Wernicke‐Geschwind model (Geschwind 1965), which describes the neurological dissociation between language production/speech attributed to Broca’s area, and language semantic comprehension (semantics) attributed to Wernicke’s area. Many later studies have shown that this description is insufficient, as it does not take into account other functional areas, nor does it describe accurately the precise boundaries of linguistic functional areas (Price 2000; 2012; Démonet et al., 2005; Smits et al., 2006).
An overview of the segregation in left‐hemispheric language areas is given in Figure 2. For instance, Broca’s area contains regions involved in semantics as well as in syntax processing (cf. Price 2012). Interestingly, although language studies often focus on the language‐dominant left hemisphere (Vigneau et al., 2006), the right hemisphere often shows a similar activation pattern (Démonet et al.,
2005). Nevertheless, aspects of neural correlates to the Wernicke‐Geschwind model are supported by recent lesion studies investigating aphasia (Yang et al., 2008) and by functional imaging studies (Price
2000; Bookheimer 2002). Therefore, Broca’s and Wernicke’s area are used as regions of interest in several of our analyses, in combination with other regions that were found in relation to semantic and word fluency tasks.
When using the labels of Broca’s and Wernicke’s areas, it is important to define their extent; the definition of Wernicke’s area in particular can vary from including only the posterior superior temporal gyrus to the inclusion of large parts of the parietal and temporal cortex. Throughout this dissertation, including all articles, the definition used is as follows: Broca’s area comprises the left IFG; specifically Brodmann areas (BA) 44 and 45. Wernicke’s area comprises the left posterior superior temporal gyrus (BA 22) and the posterior part of BA 21, as well as the posterior perisylvian2
region which consists of the left angular gyrus and the supramarginal gyrus (BA 39 & inferior BA 40). The right‐hemispheric counterparts of these areas are referred to as Broca’s and Wernicke’s area homologues. Language production and perception are by no means controlled solely by these regions3. The regions important for language will be discussed in the following sections which
introduce an overview of activation related to semantic and word fluency tasks. Since the topic of this dissertation is language ability, neural processes not directly related to language are not introduced here.
2 Perisylvian indicates the region around the Sylvian fissure. This fissure divides the frontal and parietal lobules from the temporal lobe. 3 An example is given by (Dronkers et al., 2007), who found that the patients of Paul Broca – whose brains evidenced the theory of speech production located in left IFG – had lesions that were spread over a wider region than just Broca’s area.
Figure 2. Finite overview (based on imaging studies by Cathy Price) of the segregation of functional
languagerelated areas in the left hemisphere. The colored areas each refer to different tasks, either differing in modality (auditory/visual) or in linguistic component. Figure reprinted with permission. See Price (2012) for details.
1.2.2
Semantics
Our studies have used semantic sentence reading fMRI tasks, either requiring completion of sentences or reading of congruent/incongruent sentences. Semantic tasks such as reading (Price
2000), and sentence and story comprehension (Sakai et al., 2001; Kaan & Swaab, 2002) typically activate Broca’s and Wernicke’s area in the left hemisphere (Price et al., 2003; overview in Binder et al., 2009). In the left IFG, BA 47 plays also a role in semantic processing (Dapretto & Bookheimer,
1999; Bookheimer 2002). Furthermore, the anterior temporal cortex and the fusiform gyrus are involved in semantic processing (Price et al., 2003; overview in Price 2012). Activation in the parietal perisylvian region has been shown to correlate with linguistic complexity in sentences (Carpenter et al., 1999) and semantic associating (Price 2000). Semantic processing often also activates right‐ hemispheric IFG and temporal lobe (Bookheimer 2002), which will be discussed in the section ‘Right‐ Hemispheric Influences’.
1.2.3
Word Fluency
Word generation (or: word fluency) tasks are frequently used to determine language lateralization by fMRI (Cuenod et al., 1995; Hertz‐Pannier et al., 1997). The generation of words evokes activation in the left middle and inferior frontal gyrus (Fu et al., 2002; Costafreda et al., 2006), with a particularly important role for the pars opercularis (Price 2000). Furthermore is activation observed in the inferior temporal cortex and in the adjacent fusiform area (Price 2000), and in the anterior cingulate cortex (Fu et al., 2002) The sub‐regions in the IFG have specific roles and the activation pattern is dependent on the nature of the fluency task (Heim et al., 2009).
1.2.4
Right‐Hemispheric Influences
Most language tasks evoke activation in bilateral frontal, temporal or parietal areas; the specific role of right‐hemispheric language areas is often interpreted as abstract linguistic functioning. Although lesion studies often indicate that the right‐hemisphere is not indispensable for language production, neuroimaging studies show that the right hemisphere plays an important and often distinct role, something we found evidence of in our studies as well. Vigneau and colleagues (2011) discuss in their meta‐analysis the right hemisphere in relation to language processing. They conclude that the right‐ hemispheric IFG seems to have no access to phonemic representations, unlike the left IFG. Activation in the right IFG is observed during processing of metaphors (Schmidt & Seger, 2009) and the perception of prosody (Buchanan et al., 2000). Furthermore, the right IFG is active when information is conflicting during complex language tasks; this is related to figurative language and increasingambiguity (Bookheimer 2002; Snijders et al., 2009). Bookheimer suggests that the role of the right IFG might be to help making decisions based on linguistic information.
The right hemisphere is also important for understanding and integrating spoken and written information (Bookheimer 2002). In particular, the understanding of context processing or pragmatics – which is necessary for interpreting for example ambiguous or emotionally loaded information – is attributed to the right temporal lobe (Vigneau et al., 2011). Examples of right temporal lobe activation are seen in studies investigating the interpretation of prosody (Vigneau et al., 2011), the integration of semantic information (Caplan & Dapretto, 2001), or the processing of metaphors (Bottini et al.,
1994; Mashal et al., 2005; Ahrens et al., 2007). The neural activation resulting from the processing of metaphors is possibly related to the metaphors being perceived as nonsensical or containing novel semantic information (Mashal et al., 2009). The right hemisphere is thus involved in pragmatic processing on a meta‐syntactic level (Mitchell & Crow, 2005).
1.2.5
Laterality
The dominance of a hemisphere in language processing can be quantified as the degree of lateralization. A non‐typical degree of lateralization has been attributed to both language abilities and disabilities (cf. the first section ‘Language Abilities’). Knecht and colleagues (2000) tested 188 healthy right‐handed adults for language lateralization in the brain with a word generation fMRI task. This task has been widely reported to be a powerful and effective paradigm for generating language production (Neils‐Strunjas 1998). Language lateralization study results have indicated that there is no difference in language lateralization ratios between males and females. Furthermore, a left‐ to right‐hemispheric dominance ratio of 13 to 1 was established (Knecht et al., 2000). Besides fMRI, dichotic listening is an alternative and feasible non‐invasive method to test for language lateralization (Hugdahl 2011). The dichotic listening method is based on the notion that bi‐aural auditory stimuli travel more easily to the contralateral rather than ipsilateral hemisphere, due to more extensive contralateral than ipsilateral pathways from the ear to the auditory cortex. Also, there is a blocking of ipsilateral pathways during conflicting input. After travelling to the contralateral cortex, the auditive signals are processed more automatically in the hemisphere that is dominant for language. Ergo, the language‐dominant hemisphere presumably resides contralateral to the ear that processes more stimuli during bi‐aural stimulation (Kimura, 2011).
Differences between methods to test for laterality are discussed by Abou‐Khalil (2007), who concluded that fMRI was one of the most realizable techniques4. The clear advantage of fMRI over
dichotic listening is that fMRI can localize activation. Nonetheless, dichotic listening is superior in practicality, both in terms of costs and of convenience. It is also important to realize that the laterality measurements obtained by fMRI are very much dependent on which language task is chosen. Both word fluency and sentence comprehension seem to be indicative of determining language lateralization (Niskanen et al., 2012).
Besides ear dominance, hand dominance is also seen to have a direct connection to the contralateral hemispheric. Right‐handedness is highly correlated with left‐hemispheric language dominance (in 94 – 96 % of right‐handers). In left‐handers, it is slightly more common to have right‐hemispheric dominance, yet 78 % of the left‐handed population is also left dominant for language (Szaflarski et al.,
2002).
Language lateralization is thought to correlate with differences in gray matter between hemispheres, and when the cortex is damaged, language lateralization for expressive language functions can change (Lee et al., 2008). Josse and colleagues (2009) investigated how gray matter differences could predict language lateralization, and showed that when gray matter is analyzed with a voxel‐by‐voxel method, structural asymmetry correlated well with language lateralization. However, these correlations were lost when global lateralization was compared with regional gray matter asymmetries. Nowadays, local lateralization is of interest and many researchers prefer to investigate the lateralization of separate regions (Seghier et al., 2011b). A strong lateralization of cognition has been linked to high cognitive performance (Güntürkün et al., 2000). Recently, an opposing view has emerged, namely that the optimal degree of lateralization for high cognitive performance was small. In other words; a higher degree of bilaterality might be more favorable for performance (Hirnstein et al., 2010).
1.2.6
Anti‐correlated Brain Activation
In PAPER IV we examine activation that is correlated negatively with language tasks; this can be labeled as deactivation. Deactivation is the decrease of signal in regions that are activated during rest but not during task condition, thus functions in these regions are thought to be suppressed. Some of these regions form a network that is consistently activated during rest and deactivated during tasks; this is called the Default Mode Network (DMN). DMN activation is associated with ‘free thinking’
4 cf. (Medina et al., 2007), who presents an overview of the reliability of fMRI‐obtained laterality
processes – often referred to as thinking about the day, shopping lists, and what’s for dinner – therefore the suppression of DMN activation enables a person to allocate more cognitive power to the task. Heterogeneity of the anti‐correlation during a semantic task in the different regions of the DMN is to be expected (Seghier & Price, 2012). A difference in suppression of the DMN between the task and control condition can also be expected, depending on how engaging the control condition is. Deactivation patterns might be just as necessary as activation patterns to explain brain functioning (Binder 2012).
1.3
Intelligence models for Language Ability
1.3.1
Relation Language Ability and Intelligence
There is an, although limited, correlation between language ability and intelligence (e.g. word fluency: Haier et al., 1992; Roca et al., 2010; semantics: Prat et al., 2007). Some intelligence models describe processes that can be applied to language ability as well, and help to understand the differences in language performance observed in previous and our current work. Intelligence is attributed to a parieto‐frontal network that includes several regions and connections that are shared with language processing functions. This network is described in the Parieto‐Frontal Integration Theory of intelligence (Jung & Haier, 2007). A second intelligence theory is the neural efficiency hypothesis of intelligence (Haier et al., 1992). This theory describes how well‐developed skills can be characterized by a more effective manner of processing in the brain. Thus; high‐skilled individuals will show a decreased brain activation compared with lower‐skilled persons. This reasoning can be applied to language skills as well, as will be put forward in the next section. Lastly, neural adaptability is discussed; this is a trait observed in high‐skilled individuals. These theories together may explain the functional activation patterns observed in high performers (e.g. Prat 2011; Langer et al., 2012).
1.3.2
Intelligence Models
The ParietoFrontal Integration Theory (PFIT) of intelligence is a summation of regions in a network found to show activation dependent on intelligence level (Jung & Haier, 2007). It has been known that neural correlates to high intelligence are located in the prefrontal cortex (Thompson et al., 2001), and that increased gray and white matter is observed in both frontal and parietal regions in correlationwith high intelligence (Neubauer & Fink, 2009). The P‐FIT of intelligence states that it takes a network of interactive regions to provide high abilities. The functions are divided within this network from caudally located rule generating processes, to rostral functions such like selecting, and testing of answers. The network includes the language processing areas in the posterior perisylvian region. The Neural efficiency hypothesis of intelligence states that networks for cognitive functions work in a more efficient manner in intelligent brains. Therefore, intelligent brains will show less activation in task‐specific networks during imaging studies. Haier and colleagues (1992) state that the mechanism behind neural efficiency might be deactivation of irrelevant brain areas, or a more specific use of task‐related areas. The neural efficiency hypothesis of intelligence appears to be limited to frontal regions, and conditional on task as well as task‐difficulty (Neubauer & Fink, 2009). Predominantly frontal activation patterns in high performers show efficient behavior during easy to moderately difficult tasks. Activation in the frontal region has previously been shown to decrease upon automation of processes (Ramsey et al., 2004). When demands get high, this is no longer true; high performers then recruit more brain regions to solve the task. The high intelligent individuals might have more adaptive strategies than low performers and can – depending on task demand – either use their brain efficiently or call in the help of supporting brain regions (Doppelmayr et al., 2005). Neural efficiency patterns have been observed in high capacity readers during sentence comprehension (Maxwell et al., 1974; Prat et al., 2007; Prat & Just, 2011).
The additional recruitment of supporting neural resources whenever a task is difficult may be described as Neural adaptability (Prat et al., 2007). It is hypothesized that individuals highly proficient in language show more neural adaptability compared with people with lower proficiency. This can be observed as activation in language‐related regions, either in main language regions or in additional supportive regions.
Evidently, the theories above outline a varied pattern of the relation between high performance and neural activation or deactivation. This pattern is dependent on task, task demands and functional region. In the Discussion the considerations concerning the interpretation of brain activation will be further explored.
1.4
Aims
Language ability in healthy adults was expected to be visualized as a modulation of activation in language‐related regions, with respect to the level of activation, but also the degree of lateralization between hemispheres.
PAPER I aimed to determine regional lateralization of semantic language functions in relation to performance in tests of language ability. It was expected to find laterality differences related to performance in the IFG and posterior temporal lobe, for both fMRI‐obtained laterality and for dichotic listening.
PAPER II aimed to find the neural correlates to language ability throughout the whole brain. The expectation was to find specific regions in the right IFG and posterior temporal lobe activated during from a semantic task that were related to high performance in tests of language ability. Furthermore, brain activation during word fluency was investigated and compared with semantic results, in order to find whether there were similarities in activation patterns related to high language ability.
PAPER III aimed to reproduce the findings of PAPER I and PAPER II in a new study population. Thus, activation during semantic and word fluency tasks that emerged in the right‐hemispheric homologues of Broca’s and Wernicke’s area were investigated for their correlation with high performance in tests of language ability. In addition, activation related to task demand was investigated. Brain activation patterns related to high performance were expected to show neural efficiency for low‐demand tasks in the IFG. Furthermore, high language ability was expected to be characterized by neural adaptability; i.e. increased right‐hemispheric contributions.
PAPER IV aimed to investigate language deficits in people with generalized epilepsy. This group was also expected to show an inadequate suppression of the default mode network that is normally highly anti‐correlated with the task.
Strength and courage overrides
The privileged and weary eyes
Of river poet search naiveté
Pick up here and chase the ride
The river empties to the tide
All of this is coming your way
‘Find the River’ – Bill Berry, Michael Stipe, Peter Buck, Michael Mills2
METHODS
2.1
Neurolinguistic Measures
2.1.1
Tests of Language Ability
In PAPER I and PAPER II, four tests to measure language ability were used: FAS and BNT measured word retrieval abilities, and BeSS and Read measured language comprehension abilities. In PAPER III and IV, only BeSS and FAS were used.FAS is a phonemic word generation test in which participants are cued with a letter (F, A, S), and have to generate as many words as possible, starting with the cue letter. Total score is the number of generated words for all three letters. BNT is the established Boston Naming Test. During the test, the participant is presented with 60 pictures that have to be named.
BeSS ( “Bedömning av Subtila Språkstörningar” or Assessment of Subtle Language Deficits) tests for the use of complex language by means of seven subtasks (Laakso et al., 2000). Those subtasks are:
REP repetition of long sentences (9‐16 words)
CON sentence construction (from three words, with given context, under time pressure) INF inferential reasoning (based on a read text) COM comprehension of complex embedded sentences GAR comprehension of garden‐path or ambiguous sentences MET comprehension of metaphors VOC vocabulary – word definition
Maximum score was 210 points. The Read test is selected from a Swedish exam for university students. Participants had to read three texts and answer four questions on each text. The total score was the number of correctly answered questions.
2.1.2
Dichotic Listening
Dichotic Listening scores were acquired in PAPER I with the use of a version of the Bergen Dichotic Listening Test (Hugdahl 1995), which is a consonant‐vowel test. Auditive stimuli created from the combination of a stop consonant and the vowel ‘a’ (e.g. ba – ga – pa) were presented bi‐aurally to the participants. Depending on the instructions, the participants had to report the stimuli; either heard in the left or the right ear; in both ears; or the most salient stimulus. The results were calculated as a right ear advantage; subtracting correct responses perceived by the left ear from those heard in the right ear, then dividing this figure by the number of total correct responses. A high right ear advantage meant that the subject was better at reproducing stimuli heard in the right ear, compared with the left ear. This was interpreted as a lateralization index for language; a high right ear advantage meant strong left‐hemispheric lateralization.2.1.3
fMRI Language Paradigms
The word generation task WORGE from PAPER II was as described in (Engström et al., 2010) but with moderation of the control condition. The participants were cued with a letter taken from the Swedish alphabet, excluding C, Q, W, X, Y, Z, Å, Ä, and Ö. They were instructed to generate words with the cued letter, as many as possible within the given time of 5 s. The cue letters were varied and presented in blocks containing three to five letters, pseudorandomly ordered. The baseline or control task consisted of presentation of an asterisk alternated with a row of asterisks.The word generation task WORD is described in PAPER III. Similarly to WORGE, a cue letter was presented, but this time the cue letters were divided into two difficulty categories; ‘easy’ (frequent starting letter in a Swedish word list) and ‘hard’ (infrequent starting letter). The letters were presented per category in a block of seven letters, alternating with control blocks. The control block differed from WORGE in the sense that only one asterisk was presented each trial.
The sentence completion task SENCO is described in PAPER I. This was a cloze task; the participant had to silently generate the missing last word of a sentence. The sentences were presented in blocks,
the presentation duration of a sentence was 3 s followed by display of an asterisk for 2 s. The control condition consisted of asterisks mimicking a short sentence.
The congruent/incongruent sentence reading task SEN is described in PAPER III. The participants were presented with blocks differing in difficulty level; either congruent (‘easy’ condition) or incongruent (‘hard’ condition) sentences, or control blocks containing a row of asterisks and arrows. The participants had to judge whether the situation described in the sentence took place inside or outside. During the control condition, the participants had to report in which direction the arrow was pointing.
2.1.4
Study Population
Study A investigated a healthy adult population of 18 participants: nine females and nine males aged21‐64 (mean age: 40). For PAPER 1, a subset of 14 participants (seven females, seven males) were investigated, aged 21‐55 (mean age: 36.9).
Study B investigated two groups. First, a healthy adult population of 27 participants: 14 females and
13 males aged 18‐35 (mean age: 25.5) was investigated. The analyses from PAPER III were performed on data from this group. For PAPER IV; the healthy control group was compared with a group of 11 people with generalized epilepsy: six females and five males, with an age range of 20‐35 years (mean age: 26.5). In both the healthy control group and in the group of people with generalized epilepsy there was a left‐handed individual.
All participants had Swedish as their first language and were screened by means of a questionnaire on the absence of neurological, cognitive or psychiatric disorders and magnetic resonance contra‐ indications.
2.1.5
Generalized Epilepsy
The different types of epilepsy can be classified according to etiology. This results in a distinction between generalized epilepsies with genetically inherited origin, and focal epilepsies (Berg et al.,
2010; Poduri & Lowenstein, 2011). People with generalized epilepsy (GE) show a widespread atypical cortical activity (Marini et al., 2003) and may experience language problems (Chaix et al., 2006; Caplan et al., 2009). GE is also related to an abnormal connectivity in the default mode network (McGill et al.,
2012).
