René C W Mandl

Universitair Medisch Centrum Utrecht, Utrecht, Provincie Utrecht, Netherlands

Are you René C W Mandl?

Claim your profile

Publications (20)116.71 Total impact

  • Article: Structural and Functional Aspects Relating to Cost and Benefit of Rich Club Organization in the Human Cerebral Cortex.
    [show abstract] [hide abstract]
    ABSTRACT: Recent findings have demonstrated that a small set of highly connected brain regions may play a central role in enabling efficient communication between cortical regions, together forming a densely interconnected "rich club." However, the density and spatial layout of the rich club also suggest that it constitutes a costly feature of brain architecture. Here, combining anatomical T1, diffusion tensor imaging, magnetic transfer imaging, and functional MRI, several aspects of structural and functional connectivity of the brain's rich club were examined. Our findings suggest that rich club regions and rich club connections exhibit high levels of wiring volume, high levels of white matter organization, high levels of metabolic energy usage, long maturational trajectories, more variable regional time series, and more inter-regional functional couplings. Taken together, these structural and functional measures extend the notion that rich club organization represents a high-cost feature of brain architecture that puts a significant strain on brain resources. The high cost of the rich club may, however, be offset by significant functional benefits that the rich club confers to the brain network as a whole.
    Cerebral Cortex 04/2013; · 6.54 Impact Factor
  • Article: Glutamate changes in healthy young adulthood.
    [show abstract] [hide abstract]
    ABSTRACT: Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system and has been associated with several cognitive functions that are known to change with age. In rodents and humans age-related glutamate changes have been found in several brain areas. In this cross-sectional study the presence and extent of age-associated glutamate changes in the medial frontal cortex of healthy young adults were measured. Proton magnetic resonance spectroscopy ((1)H-MRS) and brain imaging were performed at 7T in a 2×2×2cm(3) voxel in 33 participants between 18 and 31 years old. Glutamate concentrations and grey and white matter volume could be successfully determined at an ultra-high magnetic field strength. Glutamate concentrations were lower in older individuals (0.33mM/year). This decline is in line with grey matter thinning in the medial frontal cortex, but could not be explained by cortical thinning alone. Therefore, the decrease in glutamate in young adulthood may be due to physiological changes rather than anatomical changes.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 12/2012; · 3.68 Impact Factor
  • Article: Tract-based diffusion tensor imaging in patients with schizophrenia and their non-psychotic siblings.
    [show abstract] [hide abstract]
    ABSTRACT: Structural brain abnormalities have consistently been found in patients with schizophrenia. Diffusion tensor imaging (DTI) has been shown to be a useful method to measure white matter (WM) integrity in this illness, but findings in the earlier disease stages are inconclusive. Moreover, the relationship between WM microstructure and the familial risk for developing schizophrenia remains unresolved. From 126 patients with schizophrenia, 123 of their non-psychotic siblings and 109 healthy control subjects, DTI images were acquired on a 1.5 T MRI scanner. Mean fractional anisotropy (FA) was compared along averaged WM tracts, computed for the genu, splenium, left and right uncinate fasciculus, cingulum, inferior fronto-occipital fasciculus, fornix, arcuate fasciculus, and inferior longitudinal fasciculus. Fractional anisotropy (FA) was assessed for its unique environmental and familial (possibly heritable) aspects associated with schizophrenia, using structural equation modeling for these white matter tracts. The results of this study show that young adult (mean age 26.7 years) patients with schizophrenia did not differ in mean FA from healthy controls along WM fibers; siblings of patients showed higher mean FA in the left and right arcuate fasciculus as compared to patients and controls. With increasing age, an excessive decline in mean FA was found in patients as compared to siblings and healthy controls in the genu, left uncinate fasciculus, left inferior fronto-occipital fasciculus, and left inferior longitudinal fasciculus. Moreover, symptom severity was negatively correlated to mean FA in the arcuate fasciculus bilaterally in patients with schizophrenia. In young adult patients with schizophrenia integrity of individual tract-based (corticocortical) fibers can (still) be within normal limits. However, changes in the arcuate fasciculus may be relevant to (the risk to develop) psychosis, while a general and widespread loss of fiber integrity may be related to illness progression.
    European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 07/2012; · 3.68 Impact Factor
  • Article: Altered white matter connectivity in never-medicated patients with schizophrenia.
    [show abstract] [hide abstract]
    ABSTRACT: Numerous diffusion tensor imaging (DTI) studies have implicated white matter brain tissue abnormalities in schizophrenia. However, the vast majority of these studies included patient populations that use antipsychotic medication. Previous research showed that medication intake can affect brain morphology and the question therefore arises to what extent the reported white matter aberrations can be attributed to the disease rather than to the use of medication. In this study we included 16 medication-naïve patients with schizophrenia and compared them to 23 healthy controls to exclude antipsychotic medication use as a confounding factor. For each subject DTI scans and magnetization transfer imaging (MTI) scans were acquired. A new tract-based analysis was used that combines fractional anisoptropy (FA), mean diffusivity (MD) and magnetization transfer ratio (MTR) to examine group differences in 12 major white matter fiber bundles. Significant group differences in combined FA, MD, MTR values were found for the right uncinate fasciculus and the left arcuate fasciculus. Additional analysis revealed that the largest part of both tracts showed an increase in MTR in combination with an increase in MD for patients with schizophrenia. We interpret these group-related differences as disease-related axonal or glial aberrations that cannot be attributed to antipsychotic medication use. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.
    Human Brain Mapping 03/2012; · 5.88 Impact Factor
  • Source
    Article: White matter development in early puberty: a longitudinal volumetric and diffusion tensor imaging twin study.
    [show abstract] [hide abstract]
    ABSTRACT: White matter microstructure and volume show synchronous developmental patterns in children. White matter volume increases considerably during development. Fractional anisotropy, a measure for white matter microstructural directionality, also increases with age. Development of white matter volume and development of white matter microstructure seem to go hand in hand. The extent to which the same or different genetic and/or environmental factors drive these two aspects of white matter maturation is currently unknown. We mapped changes in white matter volume, surface area and diffusion parameters in mono- and dizygotic twins who were scanned at age 9 (203 individuals) and again at age 12 (126 individuals). Over the three-year interval, white matter volume (+6.0%) and surface area (+1.7%) increased, fiber bundles expanded (most pronounced in the left arcuate fasciculus and splenium), and fractional anisotropy increased (+3.0%). Genes influenced white matter volume (heritability ~85%), surface area (~85%), and fractional anisotropy (locally 7% to 50%) at both ages. Finally, volumetric white matter growth was negatively correlated with fractional anisotropy increase (r = -0.62) and this relationship was driven by environmental factors. In children who showed the most pronounced white matter growth, fractional anisotropy increased the least and vice-versa. Thus, white matter development in childhood may reflect a process of both expansion and fiber optimization.
    PLoS ONE 01/2012; 7(4):e32316. · 4.09 Impact Factor
  • Article: Aberrations in the arcuate fasciculus are associated with auditory verbal hallucinations in psychotic and in non‐psychotic individuals
    [show abstract] [hide abstract]
    ABSTRACT: The pathophysiology of auditory verbal hallucinations (AVH) is still unclear. Cognitive as well as electrophysiological studies indicate that a defect in sensory feedback (corollary discharge) may contribute to the experience of AVH. This could result from disruption of the arcuate fasciculus, the major tract connecting frontal and temporo-parietal language areas. Previous diffusion tensor imaging studies indeed demonstrated abnormalities of this tract in schizophrenia patients with AVH. It is, however, difficult to disentangle specific associations with AVH in this patient group as many other factors, such as other positive and negative symptoms, medication or halted education could likewise have affected tract integrity. We therefore investigated AVH in relative isolation and studied a group of non-psychotic individuals with AVH as well as patients with AVH and non-hallucinating matched controls. We compared tract integrity of the arcuate fasiculus and of three other control tracts, between 35 non-psychotic individuals with AVH, 35 schizophrenia patients with AVH, and 36 controls using diffusion tensor imaging and magnetization transfer imaging. Both groups with AVH showed an increase in magnetization transfer ratio (MTR) in the arcuate fasciculus, but not in the other control tracts. In addition, a general decrease in fractional anisotropy (FA) for almost all bundles was observed in the patient group, but not in the non-psychotic individuals with AVH. As increased MTR in the arcuate fasciculus was present in both hallucinating groups, a specific association with AVH seems plausible. Decreases in FA, on the other hand, seem to be related to other disease processes of schizophrenia. Hum Brain Mapp, 2011. © 2011 Wiley Periodicals, Inc.
    Human Brain Mapping 11/2011; · 5.88 Impact Factor
  • Article: Decreased frontostriatal microstructural organization in attention deficit/hyperactivity disorder.
    [show abstract] [hide abstract]
    ABSTRACT: Frontostriatal brain areas have been implicated in the neurobiology of attention deficit/hyperactivity disorder (ADHD), but little work has directly addressed the white matter connections between these regions. The present study investigates the microstructural organization and myelination of frontostriatal white matter in children with ADHD and controls. Diffusion tensor imaging and magnetization transfer imaging scans were acquired in 30 children with ADHD and 34 controls. A study specific volume of interest (VOI) of frontostriatal white matter was created using a tractography based statistical group map. Fractional anisotropy (FA, indexing microstructural organization) and magnetization transfer ratio (MTR, indexing macromolecular content, myelin in particular) were computed for the frontostriatal VOI and for total cerebral white matter. Exploratory analyses were conducted investigating the effect of stimulant use on these measures. Frontostriatal FA but not MTR was decreased in ADHD compared with controls. There were no differences in FA or MTR for total cerebral white matter. Frontostriatal FA correlated negatively with teacher-rated attention problems in controls but not children with ADHD. The duration of stimulant use did not affect the main results. Changes in frontostriatal connectivity in ADHD appear to be related to changes in microstructural organization rather than myelination per se. A correlation with attention problems for controls suggests that frontostriatal organization is relevant to ADHD-related behaviors.
    Human Brain Mapping 08/2011; 33(8):1941-51. · 5.88 Impact Factor
  • Article: Tract-based magnetic resonance spectroscopy of the cingulum bundles at 7 T.
    [show abstract] [hide abstract]
    ABSTRACT: The cingulum bundle is a white matter fiber bundle in the human brain that is believed to be implicated in various neurological and psychiatric diseases. Subtle disease-related differences in metabolite concentrations in the cingulum tracts that may underlie these diseases may be detected using MR spectroscopic information. However, to date, limited signal to noise and lack of spatial resolution have prevented a reliable and reproducible measurement of metabolites in the cingulum bundle in vivo. Here we propose a new method that combines MR spectroscopic imaging at 7 T with fiber tracking to select only those MR spectroscopy voxels that are actually part of the cingulum bundles. The spectra of the selected spectroscopy voxels are processed per voxel and then combined yielding one spectrum at high spectral resolution for each cingulum bundle. In this way sensitivity is increased, as large parts of the cingulum are included while partial volume effects with both gray matter and white matter from other tracts is kept to a minimum. Three healthy volunteers were scanned to assess the feasibility of the method. For all three healthy volunteers spectra for the left and right cingulum tracts were computed, partial volume fractions calculated and metabolite fractions were quantified yielding similar results suggesting that tract-based MR spectroscopy allows us to study metabolic concentrations of individual white matter fiber bundles with high sensitivity and high specificity.
    Human Brain Mapping 06/2011; 33(7):1503-11. · 5.88 Impact Factor
  • Article: Sex steroids and connectivity in the human brain: a review of neuroimaging studies.
    [show abstract] [hide abstract]
    ABSTRACT: Our brain operates by the way of interconnected networks. Connections between brain regions have been extensively studied at a functional and structural level, and impaired connectivity has been postulated as an important pathophysiological mechanism underlying several neuropsychiatric disorders. Yet the neurobiological mechanisms contributing to the development of functional and structural brain connections remain to be poorly understood. Interestingly, animal research has convincingly shown that sex steroid hormones (estrogens, progesterone and testosterone) are critically involved in myelination, forming the basis of white matter connectivity in the central nervous system. To get insights, we reviewed studies into the relation between sex steroid hormones, white matter and functional connectivity in the human brain, measured with neuroimaging. Results suggest that sex hormones organize structural connections, and activate the brain areas they connect. These processes could underlie a better integration of structural and functional communication between brain regions with age. Specifically, ovarian hormones (estradiol and progesterone) may enhance both cortico-cortical and subcortico-cortical functional connectivity, whereas androgens (testosterone) may decrease subcortico-cortical functional connectivity but increase functional connectivity between subcortical brain areas. Therefore, when examining healthy brain development and aging or when investigating possible biological mechanisms of 'brain connectivity' diseases, the contribution of sex steroids should not be ignored.
    Psychoneuroendocrinology 06/2011; 36(8):1101-13. · 5.81 Impact Factor
  • Article: Aberrant frontal and temporal complex network structure in schizophrenia: a graph theoretical analysis.
    [show abstract] [hide abstract]
    ABSTRACT: Brain regions are not independent. They are interconnected by white matter tracts, together forming one integrative complex network. The topology of this network is crucial for efficient information integration between brain regions. Here, we demonstrate that schizophrenia involves an aberrant topology of the structural infrastructure of the brain network. Using graph theoretical analysis, complex structural brain networks of 40 schizophrenia patients and 40 human healthy controls were examined. Diffusion tensor imaging was used to reconstruct the white matter connections of the brain network, with the strength of the connections defined as the level of myelination of the tracts as measured through means of magnetization transfer ratio magnetic resonance imaging. Patients displayed a preserved overall small-world network organization, but focusing on specific brain regions and their capacity to communicate with other regions of the brain revealed significantly longer node-specific path lengths (higher L) of frontal and temporal regions, especially of bilateral inferior/superior frontal cortex and temporal pole regions. These findings suggest that schizophrenia impacts global network connectivity of frontal and temporal brain regions. Furthermore, frontal hubs of patients showed a significant reduction of betweenness centrality, suggesting a less central hub role of these regions in the overall network structure. Together, our findings suggest that schizophrenia patients have a less strongly globally integrated structural brain network with a reduced central role for key frontal hubs, resulting in a limited structural capacity to integrate information across brain regions.
    Journal of Neuroscience 11/2010; 30(47):15915-26. · 7.11 Impact Factor
  • Source
    Article: Heritability of DTI and MTR in nine-year-old children.
    [show abstract] [hide abstract]
    ABSTRACT: Overall brain size is strikingly heritable throughout life. The influence of genes on variation in focal gray and white matter density is less pronounced and may vary with age. This paper describes the relative influences of genes and environment on variation in white matter microstructure, measured along fiber tracts with diffusion tensor imaging and magnetization transfer imaging, in a sample of 185 nine-year old children from monozygotic and dizygotic twin pairs. Fractional anisotropy, a measure of microstructural directionality, was not significantly influenced by genetic factors. In contrast, studying longitudinal and radial diffusivity separately, we found significant genetic effects for both radial and longitudinal diffusivity in the genu and splenium of the corpus callosum and the right superior longitudinal fasciculus. Moreover, genetic factors influencing the magnetization transfer ratio (MTR), putatively representing myelination, were most pronounced in the splenium of the corpus callosum and the superior longitudinal fasciculi, located posterior in the brain. The differences in the extent to which genetic and environmental factors influence the various diffusion parameters and MTR, suggest that different physiological mechanisms (either genetic or environmental) underlie these traits at nine years of age.
    NeuroImage 03/2010; 53(3):1085-92. · 5.89 Impact Factor
  • Source
    Article: Functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain.
    [show abstract] [hide abstract]
    ABSTRACT: During rest, multiple cortical brain regions are functionally linked forming resting-state networks. This high level of functional connectivity within resting-state networks suggests the existence of direct neuroanatomical connections between these functionally linked brain regions to facilitate the ongoing interregional neuronal communication. White matter tracts are the structural highways of our brain, enabling information to travel quickly from one brain region to another region. In this study, we examined both the functional and structural connections of the human brain in a group of 26 healthy subjects, combining 3 Tesla resting-state functional magnetic resonance imaging time-series with diffusion tensor imaging scans. Nine consistently found functionally linked resting-state networks were retrieved from the resting-state data. The diffusion tensor imaging scans were used to reconstruct the white matter pathways between the functionally linked brain areas of these resting-state networks. Our results show that well-known anatomical white matter tracts interconnect at least eight of the nine commonly found resting-state networks, including the default mode network, the core network, primary motor and visual network, and two lateralized parietal-frontal networks. Our results suggest that the functionally linked resting-state networks reflect the underlying structural connectivity architecture of the human brain.
    Human Brain Mapping 03/2009; 30(10):3127-41. · 5.88 Impact Factor
  • Article: Tract-based analysis of magnetization transfer ratio and diffusion tensor imaging of the frontal and frontotemporal connections in schizophrenia.
    [show abstract] [hide abstract]
    ABSTRACT: In the pathophysiology of schizophrenia, aberrant connectivity between brain regions may be a central feature. Diffusion tensor imaging (DTI) studies have shown altered fractional anisotropy (FA) in white brain matter in schizophrenia. Focal reductions in myelin have been suggested in patients using magnetization transfer ratio (MTR) imaging but to what extent schizophrenia may be related to changes in MTR measured along entire fiber bundles is still unknown. DTI and MTR images were acquired with a 1.5-T scanner in 40 schizophrenia patients and compared with those of 40 healthy participants. The mean FA and mean MTR were measured along the genu of the corpus callosum and the left and right uncinate fasciculus. A higher mean MTR of 1% was found in the right uncinate fasciculus in patients compared with healthy participants. A significant negative correlation between age and mean FA in the left uncinate fasciculus was found in schizophrenia patients but not in healthy participants. Decreased FA in the left uncinate fasciculus may be more prominent in patients with longer illness duration. The increased mean MTR in the right uncinate fasciculus could reflect a compensatory role for myelin in these fibers or possibly represent aberrant frontotemporal connectivity.
    Schizophrenia Bulletin 12/2008; 36(4):778-87. · 8.80 Impact Factor
  • Source
    Article: Functional diffusion tensor imaging: measuring task-related fractional anisotropy changes in the human brain along white matter tracts.
    [show abstract] [hide abstract]
    ABSTRACT: Functional neural networks in the human brain can be studied from correlations between activated gray matter regions measured with fMRI. However, while providing important information on gray matter activation, no information is gathered on the co-activity along white matter tracts in neural networks. We report on a functional diffusion tensor imaging (fDTI) method that measures task-related changes in fractional anisotropy (FA) along white matter tracts. We hypothesize that these fractional anisotropy changes relate to morphological changes of glial cells induced by axonal activity although the exact physiological underpinnings of the measured FA changes remain to be elucidated. As expected, these changes are very small as compared to the physiological noise and a reliable detection of the signal change would require a large number of measurements. However, a substantial increase in signal-to-noise ratio was achieved by pooling the signal over the complete fiber tract. Adopting such a tract-based statistics enabled us to measure the signal within a practically feasible time period. Activation in the sensory thalamocortical tract and optic radiation in eight healthy human subjects was found during tactile and visual stimulation, respectively. The results of our experiments indicate that these FA changes may serve as a functional contrast mechanism for white matter. This noninvasive fDTI method may provide a new approach to study functional neural networks in the human brain.
    PLoS ONE 02/2008; 3(11):e3631. · 4.09 Impact Factor
  • Article: Focal gray matter changes in schizophrenia across the course of the illness: a 5-year follow-up study.
    [show abstract] [hide abstract]
    ABSTRACT: Recent volumetric magnetic resonance imaging (MRI) studies have suggested brain volume changes in schizophrenia to be progressive in nature. Whether this is a global process or some brain areas are more affected than others is not known. In a 5-year longitudinal study, MRI whole brain scans were obtained from 96 patients with schizophrenia and 113 matched healthy comparison subjects. Changes over time in focal gray and white matter were measured with voxel-based morphometry throughout the brain. Over the 5-year interval, excessive decreases in gray matter density were found in patients in the left superior frontal area (Brodmann areas 9/10), left superior temporal gyrus (Brodmann area 42), right caudate nucleus, and right thalamus as compared to healthy individuals. Excessive gray matter density decrease in the superior frontal gray matter was related to increased number of hospitalizations, whereas a higher cumulative dose of clozapine and olanzapine during the scan interval was related to lesser decreases in this area. In conclusion, gray matter density loss occurs across the course of the illness in schizophrenia, predominantly in left frontal and temporal cortices. Moreover, the progression in left frontal density loss appears to be related to an increased number of psychotic episodes, with atypical antipsychotic medication attenuating these changes.
    Neuropsychopharmacology 11/2007; 32(10):2057-66. · 7.99 Impact Factor
  • Source
    Article: Genetic contributions to human brain morphology and intelligence.
    [show abstract] [hide abstract]
    ABSTRACT: Variation in gray matter (GM) and white matter (WM) volume of the adult human brain is primarily genetically determined. Moreover, total brain volume is positively correlated with general intelligence, and both share a common genetic origin. However, although genetic effects on morphology of specific GM areas in the brain have been studied, the heritability of focal WM is unknown. Similarly, it is unresolved whether there is a common genetic origin of focal GM and WM structures with intelligence. We explored the genetic influence on focal GM and WM densities in magnetic resonance brain images of 54 monozygotic and 58 dizygotic twin pairs and 34 of their siblings. For genetic analyses, we used structural equation modeling and voxel-based morphometry. To explore the common genetic origin of focal GM and WM areas with intelligence, we obtained cross-trait/cross-twin correlations in which the focal GM and WM densities of each twin are correlated with the psychometric intelligence quotient of his/her cotwin. Genes influenced individual differences in left and right superior occipitofrontal fascicle (heritability up to 0.79 and 0.77), corpus callosum (0.82, 0.80), optic radiation (0.69, 0.79), corticospinal tract (0.78, 0.79), medial frontal cortex (0.78, 0.83), superior frontal cortex (0.76, 0.80), superior temporal cortex (0.80, 0.77), left occipital cortex (0.85), left postcentral cortex (0.83), left posterior cingulate cortex (0.83), right parahippocampal cortex (0.69), and amygdala (0.80, 0.55). Intelligence shared a common genetic origin with superior occipitofrontal, callosal, and left optical radiation WM and frontal, occipital, and parahippocampal GM (phenotypic correlations up to 0.35). These findings point to a neural network that shares a common genetic origin with human intelligence.
    Journal of Neuroscience 11/2006; 26(40):10235-42. · 7.11 Impact Factor
  • Article: Gray and white matter density changes in monozygotic and same-sex dizygotic twins discordant for schizophrenia using voxel-based morphometry.
    [show abstract] [hide abstract]
    ABSTRACT: Global gray matter brain tissue volume decreases in schizophrenia have been associated to disease-related (possibly nongenetic) factors. Global white matter brain tissue volume decreases were related to genetic risk factors for the disease. However, which focal gray and white matter brain regions best reflect the genetic and environmental risk factors in the brains of patients with schizophrenia remains unresolved. 1.5-T MRI brain scans of 11 monozygotic and 11 same-sex dizygotic twin-pairs discordant for schizophrenia were compared to 11 monozygotic and 11 same-sex dizygotic healthy control twin-pairs using voxel-based morphometry. Linear regression analysis was done in each voxel for the average and difference in gray and white matter density separately, in each twin-pair, with group (discordant, healthy) and zygosity (monozygotic, dizygotic) as between subject variables, and age, sex and handedness as covariates. The t-maps (critical threshold value mid R:tmid R: > 6.0, P < 0.05) revealed a focal decrease in gray matter density accompanied by a focal increase in white matter density in the left medial orbitofrontal gyrus and a focal decrease in white matter density in the left sensory motor gyrus in twin-pairs discordant for schizophrenia as compared to healthy twin-pairs. Focal changes in left medial (orbito)frontal and left sensory motor gyri may reflect the increased genetic risk to develop schizophrenia. Focal changes in the left anterior hemisphere may therefore be particularly relevant as endophenotype in genetic studies of schizophrenia.
    NeuroImage 07/2006; 31(2):482-8. · 5.89 Impact Factor
  • Article: The influence of amphetamine on language activation: an fMRI study.
    [show abstract] [hide abstract]
    ABSTRACT: Amphetamine administration has been found to affect the degree of cerebral dominance for motor control in animals. In humans, cerebral dopamine neurotransmission is also correlated to motor dominance. Since language dominance is related to motor dominance, amphetamine might also affect cerebral dominance for language. To test this hypothesis, language activation was measured twice with functional magnetic resonance imaging in ten healthy right-handed men in a double-blind crossover design 2 h after amphetamine or placebo administration. Language-related activation increased significantly in task-related areas, but the individual lateralization index was not affected in the amphetamine condition as compared to placebo. This finding suggests that short-termed alterations in the dopaminergic neurotransmission do not affect language dominance.
    Psychopharmacologia 02/2006; 183(4):387-93. · 4.08 Impact Factor
  • Article: Language activation in monozygotic twins discordant for schizophrenia.
    [show abstract] [hide abstract]
    ABSTRACT: In previous functional magnetic resonance imaging (fMRI) studies, participants with schizophrenia showed decreased language lateralisation, resulting from increased activation of the right hemisphere compared with controls. To determine whether decreased lateralisation and increased right cerebral language activation constitute genetic predispositions for schizophrenia. Language activation was measured using fMRI in 12 right-handed monozygotic twin pairs discordant for schizophrenia and 12 healthy right-handed monozygotic twin pairs who were twin pairs who were matched for gender, age and education. Language lateralisation was decreased in discordant twin pairs compared with the healthy twin pairs. The groups did not differ in activation of the language-related areas of the left hemisphere, but language-related activation in the right hemisphere was activation in the significantly higher in the discordant twin pairs than in the healthy pairs. Within the discordant twin pairs, language lateralisation was not significantly different between patients with schizophrenia and their co-twins. Decreased language lateralisation may constitute a genetic predisposition for schizophrenia.
    The British Journal of Psychiatry 03/2004; 184:128-35. · 6.62 Impact Factor
  • Article: Focal white matter density changes in schizophrenia: reduced inter-hemispheric connectivity.
    [show abstract] [hide abstract]
    ABSTRACT: Gray matter changes have been demonstrated in several regions in schizophrenia. Particularly, the frontal and temporal cortices and amygdala-hippocampal region have been found decreased in volume and density in magnetic resonance imaging (MRI) studies. These abnormalities may reflect an aberrant neuronal network in schizophrenia, suggesting that white matter fibers connecting these regions may also be affected. However, it is unclear if particular white matter areas are (progressively) affected in schizophrenia and if these are related to the gray matter changes. Focal white matter changes in schizophrenia were studied in whole brain magnetic resonance images acquired from 159 patients with schizophrenia or schizophreniform disorder and 158 healthy comparison subjects using voxel-based morphometry. White matter density changes in the patients with schizophrenia were correlated to gray matter density changes and to illness severity. In the patients with schizophrenia, significant decreases in white matter density were found in the genu and truncus of the corpus callosum in the left and right hemisphere, in the right anterior internal capsule and in the right anterior commissure. No interactions between diagnosis and age were found. Increased illness severity was correlated with low density of the corpus callosum and anterior commissure. Decreased corpus callosum density correlated with decreased density of thalamus, lateral inferior frontal and insular gray matter in patients and controls and with decreased density of medial orbitofrontal and superior temporal gyri in patients. Decreased internal capsule and anterior commissure density correlated with increased caudate, and globus pallidus density in patients and controls. These findings suggest aberrant inter-hemispheric connectivity of anterior cortical and sub-cortical brain regions in schizophrenia, reflecting decreased hemispheric specialisation in schizophrenia.
    NeuroImage 02/2004; 21(1):27-35. · 5.89 Impact Factor