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Kenneth Hugdahl

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19

YNIMG Journal 2018 Journal Article

Sex- and sex hormone-related variations in energy-metabolic frontal brain asymmetries: A magnetic resonance spectroscopy study

  • Helene Hjelmervik
  • Markus Hausmann
  • Alexander R. Craven
  • Marco Hirnstein
  • Kenneth Hugdahl
  • Karsten Specht

Creatine is a key regulator of brain energy homeostasis, and well-balanced creatine metabolism is central in healthy brain functioning. Still, the variability of brain creatine metabolism is largely unattended in magnetic resonance spectroscopy (MRS) research. In the human brain, marginal sex differences in creatine levels have been found in the prefrontal cortex. It is however not known to what degree these sex differences are stable or change with varying gonadal hormone levels. The current study therefore investigated creatine in the prefrontal cortex across the menstrual cycle. In addition, we explored cerebral asymmetries. Creatine, Choline (Cho), N-acetylaspartate (NAA), Myo inositol (mI), and glutamate + glutamine (Glx) were assessed three times in 15 women and 14 men using MRS. Women were tested in cycle phases of varying hormone levels (menstrual, follicular, and luteal phase). Prefrontal creatine was found to change across the menstrual cycle, in a hemisphere-specific manner. Women in the follicular phase showed increased left prefrontal creatine accompanied with reduced right prefrontal creatine, while this asymmetry was not present in the luteal phase. In men, the creatine levels remained stable across three testing sessions. In general, both men and women were found to have higher creatine levels in the left as compared to the right prefrontal cortex. Exploratory analyses of other metabolites showed similar asymmetries in NAA, Cho, and mI, while Cho also showed a menstrual cycle effect. This is the first time that sex hormone-related changes in creatine metabolism have been demonstrated in the human brain. These findings may have important methodological implications for MRS research, as it supports previous concerns against uncritical usage of creatine as a reference measure for other metabolites, assumed to be invariant across individuals and conditions

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YNIMG Journal 2017 Journal Article

Reading in dyslexia across literacy development: A longitudinal study of effective connectivity

  • Frøydis Morken
  • Turid Helland
  • Kenneth Hugdahl
  • Karsten Specht

Dyslexia is a literacy disorder affecting the efficient acquisition of reading and writing skills. The disorder is neurobiological in origin. Due to its developmental nature, longitudinal studies of dyslexia are of essence. They are, however, relatively scarce. The present study took a longitudinal approach to cortical connectivity of brain imaging data in reading tasks in children with dyslexia and children with typical reading development. The participants were followed with repeated measurements through Pre-literacy (6 years old), Emergent Literacy (8 years old) and Literacy (12 years old) stages, using Dynamic Causal Modelling (DCM) when analysing functional magnetic resonance imaging (fMRI) data. Even though there are a few longitudinal studies on effective connectivity in typical reading, to our knowledge, no studies have previously investigated these issues in relation to dyslexia. We set up a model of a brain reading network involving five cortical regions (inferior frontal gyrus, precentral gyrus, superior temporal gyrus, inferior parietal lobule, and occipito-temporal cortex). Using DCM, connectivity measures were calculated for each connection in the model. These measures were further analysed using factorial ANOVA. The results showed that the difference between groups centred on connections going to and from the inferior frontal gyrus (two connections) and the occipito-temporal cortex (three connections). For all five connections, the typical group showed stable or decreasing connectivity measures. The dyslexia group, on the other hand, showed a marked up-regulation (occipito-temporal connections) or down-regulation (inferior frontal gyrus connections) from 6 years to 8 years, followed by normalization from 8 years to 12 years. We interpret this as a delay in the dyslexia group in developing into the Pre-literacy and Emergent literacy stages. This delay could possibly be detrimental to literacy development. By age 12, there was no statistically significant difference in connectivity between the groups, but differences in literacy skills were still present, and were in fact larger than when measured at younger ages.

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YNICL Journal 2015 Journal Article

Assessing brain structural associations with working memory related brain patterns in schizophrenia and healthy controls using linked independent component analysis

  • Christine Lycke Brandt
  • Nhat Trung Doan
  • Siren Tønnesen
  • Ingrid Agartz
  • Kenneth Hugdahl
  • Ingrid Melle
  • Ole A. Andreassen
  • Lars T. Westlye

Schizophrenia (SZ) is a psychotic disorder with significant cognitive dysfunction. Abnormal brain activation during cognitive processing has been reported, both in task-positive and task-negative networks. Further, structural cortical and subcortical brain abnormalities have been documented, but little is known about how task-related brain activation is associated with brain anatomy in SZ compared to healthy controls (HC). Utilizing linked independent component analysis (LICA), a data-driven multimodal analysis approach, we investigated structure-function associations in a large sample of SZ (n = 96) and HC (n = 142). We tested for associations between task-positive (fronto-parietal) and task-negative (default-mode) brain networks derived from fMRI activation during an n-back working memory task, and brain structural measures of surface area, cortical thickness, and gray matter volume, and to what extent these associations differed in SZ compared to HC. A significant association (p < .05, corrected for multiple comparisons) was found between a component reflecting the task-positive fronto-parietal network and another component reflecting cortical thickness in fronto-temporal brain regions in SZ, indicating increased activation with increased thickness. Other structure-function associations across, between and within groups were generally moderate and significant at a nominal p-level only, with more numerous and stronger associations in SZ compared to HC. These results indicate a complex pattern of moderate associations between brain activation during cognitive processing and brain morphometry, and extend previous findings of fronto-temporal brain abnormalities in SZ by suggesting a coupling between cortical thickness of these brain regions and working memory-related brain activation.

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YNICL Journal 2014 Journal Article

Impact of glutamate levels on neuronal response and cognitive abilities in schizophrenia

  • Liv E. Falkenberg
  • René Westerhausen
  • Alexander R. Craven
  • Erik Johnsen
  • Rune A. Kroken
  • Else-Marie L⊘berg
  • Karsten Specht
  • Kenneth Hugdahl

Schizophrenia is characterized by impaired cognitive functioning, and brain regions involved in cognitive control processes show marked glutamatergic abnormalities. However, it is presently unclear whether aberrant neuronal response is directly related to the observed deficits at the metabolite level in schizophrenia. Here, 17 medicated schizophrenia patients and 17 matched healthy participants underwent functional magnetic resonance imaging (fMRI) when performing an auditory cognitive control task, as well as proton magnetic resonance spectroscopy ((1)H-MRS) in order to assess resting-state glutamate in the anterior cingulate cortex. The combined fMRI-(1)H-MRS analysis revealed that glutamate differentially predicted cortical blood-oxygen level-dependent (BOLD) response in patients and controls. While we found a positive correlation between glutamate and BOLD response bilaterally in the inferior parietal lobes in the patients, the corresponding correlation was negative in the healthy control participants. Further, glutamate levels predicted task performance in patients, such that lower glutamate levels were related to impaired cognitive control functioning. This was not seen for the healthy controls. These findings suggest that schizophrenia patients have a glutamate-related dysregulation of the brain network supporting cognitive control functioning. This could be targeted in future research on glutamatergic treatment of cognitive symptoms in schizophrenia.

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YNIMG Journal 2014 Journal Article

Mapping hemispheric symmetries, relative asymmetries, and absolute asymmetries underlying the auditory laterality effect

  • René Westerhausen
  • Kristiina Kompus
  • Kenneth Hugdahl

Functional hemispheric differences for speech and language processing have been traditionally studied by using verbal dichotic-listening paradigms. The commonly observed right-ear preference for the report of dichotically presented syllables is taken to reflect the left hemispheric dominance for speech processing. However, the results of recent functional imaging studies also show that both hemispheres – not only the left – are engaged by dichotic listening, suggesting a more complex relationship between behavioral laterality and functional hemispheric activation asymmetries. In order to more closely examine the hemispheric differences underlying dichotic-listening performance, we report an analysis of functional magnetic resonance imaging (fMRI) data of 104 right-handed subjects, for the first time combining an interhemispheric difference and conjunction analysis. This approach allowed for a distinction of homotopic brain regions which showed symmetrical (i. e. , brain region significantly activated in both hemispheres and no activation difference between the hemispheres), relative asymmetrical (i. e. , activated in both hemispheres but significantly stronger in one than the other hemisphere), and absolute asymmetrical activation patterns (i. e. , activated only in one hemisphere and this activation is significantly stronger than in the other hemisphere). Symmetrical activation was found in large clusters encompassing temporal, parietal, inferior frontal, and medial superior frontal regions. Relative and absolute left-ward asymmetries were found in the posterior superior temporal gyrus, located adjacent to symmetrically activated areas, and creating a lateral–medial gradient from symmetrical towards absolute asymmetrical activation within the peri-Sylvian region. Absolute leftward asymmetry was also found in the post-central and medial superior frontal gyri, while rightward asymmetries were found in middle temporal and middle frontal gyri. We conclude that dichotic listening engages a bihemispheric cortical network, showing a symmetrical and mostly leftward asymmetrical pattern. The here obtained functional (a)symmetry map might serve as a basis for future studies which – by studying the relevance of the here identified regions – clarify the relationship between behavioral laterality measures and hemispheric asymmetry.

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YNIMG Journal 2013 Journal Article

Structural white matter asymmetries in relation to functional asymmetries during speech perception and production

  • Sebastian Ocklenburg
  • Kenneth Hugdahl
  • René Westerhausen

Functional hemispheric asymmetries of speech production and perception are a key feature of the human language system, but their neurophysiological basis is still poorly understood. Using a combined fMRI and tract-based spatial statistics approach, we investigated the relation of microstructural asymmetries in language-relevant white matter pathways and functional activation asymmetries during silent verb generation and passive listening to spoken words. Tract-based spatial statistics revealed several leftward asymmetric clusters in the arcuate fasciculus and uncinate fasciculus that were differentially related to activation asymmetries in the two functional tasks. Frontal and temporal activation asymmetries during silent verb generation were positively related to the strength of specific microstructural white matter asymmetries in the arcuate fasciculus. In contrast, microstructural uncinate fasciculus asymmetries were related to temporal activation asymmetries during passive listening. These findings suggest that white matter asymmetries may indeed be one of the factors underlying functional hemispheric asymmetries. Moreover, they also show that specific localized white matter asymmetries might be of greater relevance for functional activation asymmetries than microstructural features of whole pathways.

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YNIMG Journal 2011 Journal Article

A critical re-examination of sexual dimorphism in the corpus callosum microstructure

  • René Westerhausen
  • Kristiina Kompus
  • Margaretha Dramsdahl
  • Liv E. Falkenberg
  • Renate Grüner
  • Helene Hjelmervik
  • Karsten Specht
  • Kerstin Plessen

Recent diffusion-tensor imaging (DTI) studies suggest sexual dimorphism in the micro-structural architecture of the corpus callosum. However, the corpus callosum is also found to be larger in males than in females, a fact that might introduce a systematic bias to the analysis of DTI parameters. Diffusion parameters obtained in the larger male corpus callosum could be less affected by partial-volume averaging with surrounding non-callosal tissue than respective parameters obtained in the smaller female corpus callosum, i. e. the sex of the subject and partial-volume effects would be confounded. The objective of the present DTI study was to re-examine microstructural sex differences in the corpus callosum, while controlling for corpus callosum size differences between sexes. We compared 41 female and 34 male participants using regional tract-based spatial statistics (TBSS) analysis. Clusters of significantly higher fractional anisotropy (FA) and lower diffusion strength in males compared to females were detected in the genu and truncus of the corpus callosum. However, only the sex difference located in the anterior genu subregions could be unequivocally interpreted. This was the only cluster where the diffusion parameters did not correlate with regional callosal size. The present results indicate a stronger inter-hemispheric connectivity between the frontal lobes in males than females, which might be related to sex differences in hemispheric asymmetry and brain size.

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YNIMG Journal 2011 Journal Article

Effective connectivity analysis demonstrates involvement of premotor cortex during speech perception

  • Berge Osnes
  • Kenneth Hugdahl
  • Karsten Specht

Several reports of premotor cortex involvement in speech perception have been put forward. Still, the functional role of premotor cortex is under debate. In order to investigate the functional role of premotor cortex, we presented parametrically varied speech stimuli in both a behavioral and functional magnetic resonance imaging (fMRI) study. White noise was transformed over seven distinct steps into a speech sound and presented to the participants in a randomized order. As control condition served the same transformation from white noise into a music instrument sound. The fMRI data were modelled with Dynamic Causal Modeling (DCM) where the effective connectivity between Heschl's gyrus, planum temporale, superior temporal sulcus and premotor cortex were tested. The fMRI results revealed a graded increase in activation in the left superior temporal sulcus. Premotor cortex activity was only present at an intermediate step when the speech sounds became identifiable but were still distorted but was not present when the speech sounds were clearly perceivable. A Bayesian model selection procedure favored a model that contained significant interconnections between Heschl's gyrus, planum temporal, and superior temporal sulcus when processing speech sounds. In addition, bidirectional connections between premotor cortex and superior temporal sulcus and from planum temporale to premotor cortex were significant. Processing non-speech sounds initiated no significant connections to premotor cortex. Since the highest level of motor activity was observed only when processing identifiable sounds with incomplete phonological information, it is concluded that premotor cortex is not generally necessary for speech perception but may facilitate interpreting a sound as speech when the acoustic input is sparse.

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YNIMG Journal 2009 Journal Article

Realignment parameter-informed artefact correction for simultaneous EEG–fMRI recordings

  • Matthias Moosmann
  • Vinzenz H. Schönfelder
  • Karsten Specht
  • René Scheeringa
  • Helge Nordby
  • Kenneth Hugdahl

In this work we introduce a new algorithm to correct the imaging artefacts in the EEG signal measured during fMRI acquisition. The correction techniques proposed so far cannot optimally represent transitions, i. e. when abrupt changes of the artefact properties due to head movements occur. The algorithm developed here takes the head movement parameters from the fMRI signal into account to calculate adequate EEG artefact templates and subsequently correct the distorted EEG data. The data reported in this work demonstrate that the realignment parameter-informed algorithm outperforms the commonly used moving average algorithm if head movements occur. The superiority is reflected by comparing the residual variance after artefact correction with either method. The residual variance is lower around head-movements that exceed head deflections of about 1 mm when applying the realignment parameter-informed algorithm. Additionally, the signal to noise ratio of a surrogate event-related potential (ERP) increased by 10–40% for head displacements larger than 1 mm. The algorithm developed here is particularly suited for studies where head movements of the subject cannot be prevented as in studies with patients, children, or during sleep. Furthermore, the enhanced signal to noise ratio of a single trial ERP indicates the power of the presented algorithm for single trial ERP-fMRI studies in which EEG signal quality is a critical factor.

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YNIMG Journal 2008 Journal Article

A new verbal reports fMRI dichotic listening paradigm for studies of hemispheric asymmetry

  • Maurits van den Noort
  • Karsten Specht
  • Lars M. Rimol
  • Lars Ersland
  • Kenneth Hugdahl

Dichotic listening (DL) is one of the most frequently used paradigms to study hemispheric asymmetry and has been employed in several neuroimaging studies. The classic behavioral DL paradigm requires the subject to give a verbal response on each trial, which may cause image artifacts due to head movements when applied to an imaging environment. In order to avoid such artifacts most studies have used modified versions of the classic DL paradigm, where no verbal response is required. The purpose of the present study was to test a new DL paradigm, specifically developed for the fMRI environment, which is based on collecting verbal responses and thus being as close as possible to the classic DL behavioral task. By employing a sparse-sampling EPI acquisition schema we attempted to limit the negative impact of overt speech on image quality. A 5-s ‘silent gap’ allowed for stimulus presentation and collection of a verbal response to occur between subsequent image acquisitions and served as a high-pass filter that was optimized to detect activations of interest. Hence, the contribution of response-related activations to the measured signal was reduced. Twelve healthy volunteers (six males and six females) participated in the study. In order to obtain a measure of reliability, all participants went through the classic DL paradigm three times. The results, based on the estimation of the intraclass correlation coefficient, functional probability maps as well as on laterality maps, showed consistent activation in the right and left superior temporal gyrus, left middle temporal gyrus, and right inferior temporal gyrus, thus replicating previous results with visual display and motor response DL paradigms. It is concluded that an fMRI DL paradigm based on overt verbal responses is feasible and could have general implications for future fMRI studies of speech perception and product in general.

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YNIMG Journal 2008 Journal Article

Separating the effects of alcohol and expectancy on brain activation: An fMRI working memory study

  • Hilde Gundersen
  • Karsten Specht
  • Renate Grüner
  • Lars Ersland
  • Kenneth Hugdahl

The aim of this study was to use BOLD fMRI to evaluate the effect of alcohol intoxication on neuronal activation, when controlling for expectancy. Behavioural studies have shown that both alcohol intoxication and expectancy affect cognition, mood and behaviour. However, previous neuroimaging studies have not separated the effects of alcohol intoxication from the possible confounding effects of expectancy. Forty-five healthy male participants participated in the study. A balanced placebo design with four groups was used together with a working memory paradigm. Half of the participants consumed a soft-drink before the MR scanning session (half of them were correctly informed about the content of their drink, and half were incorrectly informed that they consumed an alcoholic beverage), and the other half consumed an alcoholic beverage before the MR scanning session (half of them were correctly informed about the content of their drink, and half were incorrectly informed that they consumed a soft-drink). A blood alcohol concentration (BAC) of 0. 08% was used as the alcohol intoxication level. The most conspicuous result was that alcohol intoxication decreased neuronal activation especially in the dorsal anterior cingulate cortex (dACC) and in prefrontal areas, while expectancy increased neuronal activation in the same areas. This study shows that alcohol intoxication and expectancy have opposite effects on neuronal activation. The present results could have implications for pharmacological imaging studies.

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YNIMG Journal 2006 Journal Article

Controlling for individual differences in fMRI brain activation to tones, syllables, and words

  • Lars M. Rimol
  • Karsten Specht
  • Kenneth Hugdahl

Previous neuroimaging studies have consistently reported bilateral activation to speech stimuli in the superior temporal gyrus (STG) and have identified an anteroventral stream of speech processing along the superior temporal sulcus (STS). However, little attention has been devoted to the possible confound of individual differences in hemispheric dominance for speech. The present study was designed to test for speech-selective activation while controlling for inter-individual variance in auditory laterality, by using only subjects with at least 10% right ear advantage (REA) on the dichotic listening test. Eighteen right-handed, healthy male volunteers (median age 26) participated in the study. The stimuli were words, syllables, and sine wave tones (220–2600 Hz), presented in a block design. Comparing words > tones and syllables > tones yielded activation in the left posterior MTG and the lateral STG (upper bank of STS). In the right temporal lobe, the activation was located in the MTG/STS (lower bank). Comparing left and right temporal lobe cluster sizes from the words > tones and syllables > tones contrasts on single-subject level demonstrated a statistically significant left lateralization for speech sound processing in the STS/MTG area. The asymmetry analyses suggest that dichotic listening may be a suitable method for selecting a homogenous group of subjects with respect to left hemisphere language dominance.

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YNIMG Journal 2005 Journal Article

Processing of sub-syllabic speech units in the posterior temporal lobe: An fMRI study

  • Lars M. Rimol
  • Karsten Specht
  • Susanne Weis
  • Robert Savoy
  • Kenneth Hugdahl

The objective of this study was to investigate phonological processing in the brain by using sub-syllabic speech units with rapidly changing frequency spectra. We used isolated stop consonants extracted from natural speech consonant–vowel (CV) syllables, which were digitized and presented through headphones in a functional magnetic resonance imaging (fMRI) paradigm. The stop consonants were contrasted with CV syllables. In order to control for general auditory activation, we used duration- and intensity-matched noise as a third stimulus category. The subjects were seventeen right-handed, healthy male volunteers. BOLD activation responses were acquired on a 1. 5-T MR scanner. The auditory stimuli were presented through MR compatible headphones, using an fMRI paradigm with clustered volume acquisition and 12 s repetition time. The consonant vs. noise comparison resulted in unilateral left lateralized activation in the posterior part of the middle temporal gyrus and superior temporal sulcus (MTG/STS). The CV syllable vs. noise comparison resulted in bilateral activation in the same regions, with a leftward asymmetry. The reversed comparisons, i. e. , noise vs. speech stimuli, resulted in right hemisphere activation in the supramarginal and superior temporal gyrus, as well as right prefrontal activation. Since the consonant stimuli are unlikely to have activated a semantic–lexical processing system, it seems reasonable to assume that the MTG/STS activation represents phonetic/phonological processing. This may involve the processing of both spectral and temporal features considered important for phonetic encoding.

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YNIMG Journal 2004 Journal Article

Brain localization of attentional control in different age groups by combining functional and structural MRI

  • Tormod Thomsen
  • Karsten Specht
  • Åsa Hammar
  • Jarle Nyttingnes
  • Lars Ersland
  • Kenneth Hugdahl

The present study used functional and structural MRI to investigate differences in neuronal substrates underlying shifts of attention in young and old subjects, studied with dichotic listening. Two different consonant–vowel syllables were presented and the subjects were instructed to attend to and report from either the left or right ear stimulus. Typically, a right-ear advantage is observed when attending to the right-ear stimulus, and a left-ear advantage when attending to the left-ear stimulus. The behavioral results showed that the old group had difficulties with attentional modulation of the right-ear advantage in the attend left condition. This is interpreted as a failure of an important aspect of attentional control; the top-down biasing of attention for selection of task-relevant stimulus. The fMRI results showed that an area in the left middle frontal gyrus was more activated in the young group compared to the old group in the attend left condition. The structural MRI data showed reduced gray matter density of the same area in the old group. Based on these converging findings, we suggest that the left middle frontal gyrus plays an important role in top-down biasing of selecting task-relevant stimuli, and to inhibit processing of task-irrelevant stimuli. To our knowledge, this is one of the first studies addressing the question on how age-related changes in attentional processing is reflected in both functional and structural differences in the brain.

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YNIMG Journal 2004 Journal Article

Dichotic listening reveals functional specificity in prefrontal cortex: an fMRI study

  • Tormod Thomsen
  • Lars Morten Rimol
  • Lars Ersland
  • Kenneth Hugdahl

The present study used fMRI to investigate the relationship between stimulus presentation mode and attentional instruction in a free-report dichotic listening (DL) task with consonant–vowel (CV) syllables. Binaural and dichotic CV syllables were randomly presented to the subjects during four different instructional conditions: a passive listening instruction and three active instructions where subjects listened to both ears, right ear and left ear, respectively. The results showed that dichotic presentations activated areas in the superior temporal gyrus, middle and inferior frontal gyrus and the cingulate cortex to a larger extent than binaural presentations. Moreover, the results showed that increase of activation in these areas was differentially dependent on presentation mode and attentional instruction. Thus, it seems that speech perception, as studied with the DL procedure, involves a cortical network extending beyond primary speech perception areas in the brain, also including prefrontal cortex.

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v2026.09.13