The evidence that action shapes perception has become widely accepted, for example, in the domain of vision. However, the manner in which action-relevant factors might influence the neural dynamics of acute pain processing has remained underexplored, particularly the functional roles of anterior insula (AI) and midanterior cingulate cortex (mid-ACC), which are frequently implicated in acute pain. To address this, we examined a unique group of heterozygous carriers of the rare R221W mutation on the nerve growth factor (NGF) gene. R221W carriers show a congenitally reduced density of C-nociceptor afferent nerves in the periphery, but can nonetheless distinguish between painful and nonpainful stimulations. Despite this, carriers display a tendency to underreact to acute pain behaviorally, thus exposing a potential functional gap in the pain-action relationship and allowing closer investigation of how the brain integrates pain and action information. Heterozygous R221W carriers and matched controls performed a functional magnetic resonance imaging (fMRI) task designed to dissociate stimulus type (painful or innocuous) from current behavioral relevance (relevant or irrelevant), by instructing participants to either press or refrain from pressing a button during thermal stimulation. Carriers subjective pain thresholds did not differ from controls, but the carrier group showed decreased task accuracy. Hemodynamic activation in AI covaried with task performance, revealing a functional role in pain-action integration with increased responses for task-relevant painful stimulation ("signal," requiring button-press execution) over task-irrelevant stimulation ("noise," requiring button-press suppression). As predicted, mid-ACC activation was associated with action execution regardless of pain. Functional connectivity between AI and mid-ACC increased as a function of reported urge to withdraw from the stimulus, suggesting a joint role for these regions in motivated action during pain. The carrier group showed greater activation of primary sensorimotor cortices-but not the AI and mid-ACC regions-during pain and action, suggesting compensatory processing. These findings indicate a critical role for the AI-mid-ACC axis in supporting a flexible, adaptive action selection during pain, alongside the accompanying subjective experience of an urge to escape the pain.

In preterm children with very low birth weight (VLBW amp;lt;= 1500 g), reading problems are often observed. Reading comprehension is dependent on word decoding and language comprehension. We investigated neural activation-within brain regions important for reading-related to components of reading comprehension in young VLBW adolescents in direct comparison to normal birth weight (NBW) term-born peers, with the use of functional magnetic resonance imaging (fMRI). We hypothesized that the decoding mechanisms will be affected by VLBW, and expect to see increased neural activity for VLBW which may be modulated by task performance and cognitive ability. The study investigated 13 (11 included in fMRI) young adolescents (ages 12 to 14 years) born preterm with VLBW and in 13 NBW controls (ages 12-14 years) for performance on the Block Design and Vocabulary subtests of the Wechsler Intelligence Scale for Children; and for semantic, orthographic, and phonological processing during an fMRI paradigm. The VLBW group showed increased phonological activation in left inferior frontal gyrus, decreased orthographic activation in right supramarginal gyrus, and decreased semantic activation in left inferior frontal gyrus. Block Design was related to altered right-hemispheric activation, and VLBW showed lower WISC Block Design scores. Left angular gyrus showed activation increase specific for VLBW with high accuracy on the semantic test. Young VLBW adolescents showed no accuracy and reaction time performance differences on our fMRI language tasks, but they did exhibit altered neural activation during these tasks. This altered activation for VLBW was observed as increased activation during phonological decoding, and as mainly decreased activation during orthographic and semantic processing. Correlations of neural activation with accuracy on the semantic fMRI task and with decreased WISC Block Design performance were specific for the VLBW group. Together, results suggest compensatory mechanisms by recruiting additional brain regions upon altered neural development of decoding for VLBW.

This study investigates the relation between individual language ability and neural semantic processing abilities. Our aim was to explore whether high-level language ability would correlate to decreased activation in language-specific regions or rather increased activation in supporting language regions during processing of sentences. Moreover, we were interested if observed neural activation patterns are modulated by semantic incongruency similarly to previously observed changes upon syntactic congruency modulation. We investigated 27 healthy adults with a sentence reading task which tapped language comprehension and inference, and modulated sentence congruency employing functional magnetic resonance imaging (fMRI). We assessed the relation between neural activation, congruency modulation, and test performance on a high-level language ability assessment with multiple regression analysis. Our results showed increased activation in the left-hemispheric angular gyrus extending to the temporal lobe related to high language ability. This effect was independent of semantic congruency, and no significant relation between language ability and incongruency modulation was observed. Furthermore, there was a significant increase of activation in the inferior frontal gyrus (IFG) bilaterally when the sentences were incongruent, indicating that processing incongruent sentences was more demanding than processing congruent sentences and required increased activation in language regions. The correlation of high-level language ability with increased rather than decreased activation in the left angular gyrus, a region specific for language processing, is opposed to what the neural efficiency hypothesis would predict. We can conclude that no evidence is found for an interaction between semantic congruency related brain activation and highlevel language performance, even though the semantic incongruent condition shows to be more demanding and evoking more neural activation.

We aimed to study the effect of a potential default mode network (DMN) dysfunction on language performance in epilepsy. Language dysfunction in focal epilepsy has previously been connected to brain damage in language-associated cortical areas. In this work, we studied generalized epilepsy (GE) without focal brain damage to see if the language function was impaired. We used functional magnetic resonance imaging (fMRI) to investigate if the DMN was involved. Eleven persons with GE and 28 healthy controls were examined with fMRI during a sentence-reading task. We demonstrated impaired language function, reduced suppression of DMN, and, specifically, an inadequate suppression of activation in the left anterior temporal lobe and the posterior cingulate cortex, as well as an aberrant activation in the right hippocampal formation. Our results highlight the presence of language decline in people with epilepsy of not only focal but also generalized origin.

The right-hemispheric homologues to Broca’s and Wernicke’s area play an important, but currently poorly understood role in language ability. In the current study, we tested 27 healthy adults for their language ability. We acquired functional magnetic resonance imaging (fMRI) data when the participants performed a sentence reading and a word fluency task. The fMRI data were used to calculate a measure of brain laterality – the laterality index – in the inferior frontal gyrus, the superior and middle temporal gyrus, and the angular gyrus. These laterality measurements were correlated with performance scores on language tasks administered prior to fMRI. We expected to see that high performance was characterized by a more efficient, i.e. decreased, neural activation pattern in typical language areas. Furthermore, we expected to see activation in additional, right-hemispheric brain regions in high performing subjects as a sign of neural adaptability.

High performance in a test measuring subtle language deficits (BeSS test) was related to increased activation in the right middle temporal gyrus when the participants were reading sentences. Thus, semantic ability correlated negatively with laterality in the temporal lobe, but not in the frontal lobe. For increased verbal fluency ability, we did observe a decreased left-hemispheric dominance in the inferior frontal gyrus when the participants were generating words. Increased task demands in the word generation task were not related to brain activation, but in the sentence reading task, the bilateral inferior frontal gyrus did exhibit an increase in activation when the sentences increased in difficulty. This result was independent of individual language ability. Increased brain activation at increased difficulty of a language task is interpreted as a sign that the brain recruits additional resources upon higher demands. The negative correlation between language ability and laterality in the in right-hemispheric middle temporal gyrus indicates a higher degree of neural adaptability in the temporal lobes of high skilled individuals.

The main aim of this dissertation was to investigate the difference in neural language patternsrelated to language ability in healthy adults. The focus lies on unraveling the contributions of theright‐hemispheric homologues to Broca’s area in the inferior frontal gyrus (IFG) and Wernicke’s areain the posterior temporal and inferior parietal lobes. The functions of these regions are far from fullyunderstood at present. Two study populations consisting of healthy adults and a small group ofpeople with generalized epilepsy were investigated. Individual performance scores in tests oflanguage ability were correlated with brain activation obtained with functional magnetic resonanceimaging during semantic and word fluency tasks. Performance‐dependent differences were expectedin 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 lobeactivation, related to high semantic performance. The whole‐brain analysis results of PAPER IIrevealed numerous candidate regions for language ability modulation. PAPER II also confirmed thefinding of PAPER I, by showing several performance‐dependent regions in the right‐hemispheric IFGand 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 lefthemisphericIFG activation could be linked to high word fluency ability. In addition, task difficultywas modulated. Increased task complexity showed to correlate positively with bilateral IFGactivation.

Lastly, PAPER IV investigated anti‐correlated regions. These regions are commonly knownas the default mode network (DMN) and are normally suppressed during cognitive tasks. It wasfound 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 adaptabilityin the IFG and temporal lobe. Decreased left‐lateralization of the IFG and increased rightlateralizationof the posterior temporal lobe are proposed as characteristics of individuals with highlanguage ability.

Cognitive functions in people with epilepsy are affected by focality, number of generalized seizures, side effects of antiepileptic drugs (AEDs) or the underlying disease (Kwan, 2001). Newly diagnosed patients have cognitive deficits even before starting on AEDs. Performance declines already in the first year after diagnosis and the impairment continues in the following years (Taylor, 2010; Baker, 2011). In mesial temporal lobe epilepsy (TLE) the hippocampal damage seems to be progressive and accompanied by thinning of neocortex (Briellmann, 2002; Bernhardt, 2009). Widespread structural and functional abnormalities in left TLE can affect more distant networks (Bonilha, 2009); a damage pattern also seen in right TLE (Karunanayaka, 2011).