Daniel Güllmar

White matter abnormalities and brain activation in schizophrenia: A combined DTI and fMRI study

Diffusion tensor imaging (DTI) studies of schizophrenia have revealed white matter abnormalities in several areas of the brain. The functional impact on either psychopathology or cognition remains, however, poorly understood. Here we analysed both functional MRI (during a working memory task) and DTI data sets in 18 patients with schizophrenia and 18 controls. Firstly, DTI analyses revealed reductions of fractional anisotropy (FA) in the right medial temporal lobe adjacent to the right parahippocampal gyrus, likely to contain fibres of the inferior cingulum bundle, and in the right frontal lobe. Secondly, functional MRI revealed prefrontal, superior parietal and occipital relative hypoactivation in patients with the main effect of task. This was accounted for by reduced prefrontal activation during the encoding phase of the task, but not during maintenance or retrieval phases. Thirdly, we found a direct correlation in patients between the frontal FA reduction (but not medial temporal reductions) and fMRI activation in regions in the prefrontal and occipital cortex. Our study combining fMRI and DTI thus demonstrates altered structure-function relationships in schizophrenia. It highlights a potential relationship between anatomical changes in a frontal-temporal anatomical circuit and functional alterations in the prefrontal cortex.

Influence of anisotropic electrical conductivity in white matter tissue on the EEG/MEG forward and inverse solution. A high-resolution whole head simulation study.

To investigate the influence of anisotropic electrical conductivity in white matter on the forward and inverse solution in electroencephalography (EEG) and magnetoencephalography (MEG) numerical simulation studies were performed. A high-resolution (1 mm3 isotropic) finite element model of a human head was implemented to study the sensitivity of EEG and MEG source localization. In vivo information on the anisotropy was obtained from magnetic resonance diffusion tensor imaging and included into the model, whereas both a direct transformation and a direct transformation with volume normalization were used to obtain conductivity tensors. Additionally, fixed artificial anisotropy ratios were also used, while considering only the orientation information from DTI, to generate conductivity tensors. Analysis was performed using over 25,000 single dipolar sources covering the full neocortex. Major findings of the study include that EEG is more sensitive to anisotropic conductivities in white matter compared to MEG. Especially with the inverse analysis, we found that sources placed deep in sulci are located more laterally if anisotropic conductivity of white matter tissue is neglected. Overall, the single-source localization errors resulting from a neglect of anisotropy were found to be smaller compared to errors associated with other modeling errors, like misclassified tissue or the use of nonrealistic head models. In contrast to the small localization error we observed significant changes in magnitude and orientation. The latter is important since dipole orientation might be more important than absolute dipole localization in assigning, e.g., epileptic activity to the wall of the affected brain sulcal area. If high-resolution finite element models are used to perform source localization in EEG and MEG experiments and the quality of the measured data permits localization accuracy of 1 mm and below, the influence of anisotropic compartments has to be taken into account.

Influence of anisotropic conductivity on EEG source reconstruction: investigations in a rabbit model

The aim of our work was to quantify the influence of white matter anisotropic conductivity information on electroencephalography (EEG) source reconstruction. We performed this quantification in a rabbit head using both simulations and source localization based on invasive measurements. In vivo anisotropic (tensorial) conductivity information was obtained from magnetic resonance diffusion tensor imaging and included into a high-resolution finite-element model. When neglecting anisotropy in the simulations, we found a shift in source location of up to 1.3 mm with a mean value of 0.3 mm. The averaged orientational deviation was 10 degree and the mean magnitude error of the dipole was 29%. Source localization of the first cortical components after median and tibial nerve stimulation resulted in anatomically verified dipole positions with no significant anisotropy effect. Our results indicate that the expected average source localization error due to anisotropic white matter conductivity is within the principal accuracy limits of current inverse procedures. However, larger localization errors might occur in certain cases. In contrast, dipole orientation and dipole strength are influenced significantly by the anisotropy. We conclude that the inclusion of tissue anisotropy information improves source estimation procedures

High-Resolution MR Imaging of the Human Brainstem In vivo at 7 Tesla

The human brainstem, which comprises a multitude of axonal nerve fibers and nuclei, plays an important functional role in the human brain. Depicting its anatomy non-invasively with high spatial resolution may thus in turn help to better relate normal and pathological anatomical variations to medical conditions as well as neurological and peripheral functions. We explored the potential of high-resolution magnetic resonance imaging (MRI) at 7 T for depicting the intricate anatomy of the human brainstem in vivo by acquiring and generating images with multiple contrasts: T 2-weighted images, quantitative maps of longitudinal relaxation rate (R 1 maps) and effective transverse relaxation rate ([Formula: see text] maps), magnetic susceptibility maps, and direction-encoded track-density images. Images and quantitative maps were compared with histological stains and anatomical atlases to identify nerve nuclei and nerve fibers. Among the investigated contrasts, susceptibility maps displayed the largest number of brainstem structures. Contrary to R 1 maps and T 2-weighted images, which showed rather homogeneous contrast, [Formula: see text] maps, magnetic susceptibility maps, and track-density images clearly displayed a multitude of smaller and larger fiber bundles. Several brainstem nuclei were identifiable in sections covering the pons and medulla oblongata, including the spinal trigeminal nucleus and the reticulotegmental nucleus on magnetic susceptibility maps as well as the inferior olive on R 1, [Formula: see text], and susceptibility maps. The substantia nigra and red nuclei were visible in all contrasts. In conclusion, high-resolution, multi-contrast MR imaging at 7 T is a versatile tool to non-invasively assess the individual anatomy and tissue composition of the human brainstem.

3D printing of MRI compatible components: why every MRI research group should have a low-budget 3D printer.

PURPOSE To evaluate low budget 3D printing technology to create MRI compatible components. MATERIAL AND METHODS A 3D printer is used to create customized MRI compatible components, a loop-coil platform and a multipart mouse fixation. The mouse fixation is custom fit for a dedicated coil and facilitates head fixation with bite bar, anesthetic gas supply and biomonitoring sensors. The mouse fixation was tested in a clinical 3T scanner. RESULTS All parts were successfully printed and proved MR compatible. Both design and printing were accomplished within a few days and the final print results were functional with well defined details and accurate dimensions (Δ<0.4mm). MR images of the mouse head clearly showed reduced motion artifacts, ghosting and signal loss when using the fixation. CONCLUSIONS We have demonstrated that a low budget 3D printer can be used to quickly progress from a concept to a functional device at very low production cost. While 3D printing technology does impose some restrictions on model geometry, additive printing technology can create objects with complex internal structures that can otherwise not be created by using lathe technology. Thus, we consider a 3D printer a valuable asset for MRI research groups.

White matter structure and symptom dimensions in obsessive–compulsive disorder

There is evidence that the different symptom dimensions in obsessive-compulsive disorder (OCD) may be mediated by partially distinct neural systems. This DTI study investigated the relationship between symptom dimensions and white matter microstructure. Fractional anisotropy (FA), axial and radial diffusivity was analyzed in relation to the main OCD symptom dimensions. Symptom severity on the obsessing dimension was negatively correlated with FA in the corpus callosum and the cingulate bundle. Severity on the ordering dimension was negatively correlated with FA in, amongst others, the right inferior fronto-occipital fasciculus and the right optic radiation. All correlations were ascribable to alterations in radial diffusivity while there was no association between symptoms and axial diffusivity. Present results illustrate an association between alterations in visual processing tracts and ordering symptoms which are characterized by altered visual processing and increased attention towards irrelevant detail. They also indicate an association between obsessive thoughts and alterations in structures known to be relevant for cognitive control and inhibition. Hence, different symptom dimensions must be taken into account in order to disentangle the neurobiological underpinnings of OCD.

1H-MR spectroscopic detection of metabolic changes in pain processing brain regions in the presence of non-specific chronic low back pain.

Reliable detection of metabolic changes in the brain in vivo induced by chronic low back pain may provide improved understanding of neurophysiological mechanisms underlying the manifestation of chronic pain. In the present study, absolute concentrations of N-acetyl-aspartate (NAA), creatine (Cr), total choline (tCho), myo-inositol (mI), glutamate (Glu) and glutamine (Gln) were measured in three different pain processing cortical regions (anterior insula, anterior cingulate cortex, and thalamus) of ten patients with non-specific chronic low back pain by means of proton MR spectroscopy ((1)H-MRS) and compared to matched healthy controls. Significant decrease of Glu was observed in the anterior cingulate cortex of patients. Patients also revealed a trend of decreasing Gln concentrations in all investigated brain areas. Reductions of NAA were observed in the patient group in anterior insula and in anterior cingulated cortex, whereas mI was reduced in anterior cingulated cortex and in thalamus of patients. Reduced concentrations of Glu and Gln may indicate disordered glutamatergic neurotransmission due to prolonged pain perception, whereas decrease of NAA and mI may be ascribed to neuron and glial cell loss. No significant changes were found for Cr. The morphological evaluation of anatomic brain data revealed a significantly decreased WM volume of 17% (p<0.05) as well as a non significant trend for GM volume increase in the anterior insula of patients.

Determination of three‐dimensional muscle architectures: validation of the DTI‐based fiber tractography method by manual digitization

In the last decade, diffusion tensor imaging (DTI) has been used increasingly to investigate three‐dimensional (3D) muscle architectures. So far there is no study that has proved the validity of this method to determine fascicle lengths and pennation angles within a whole muscle. To verify the DTI method, fascicle lengths of m. soleus as well as their pennation angles have been measured using two different methods. First, the 3D muscle architecture was analyzed in vivo applying the DTI method with subsequent deterministic fiber tractography. In a second step, the muscle architecture of the same muscle was analyzed using a standard manual digitization system (MicroScribe MLX). Comparing both methods, we found differences for the median pennation angles (P < 0.001) but not for the median fascicle lengths (P = 0.216). Despite the statistical results, we conclude that the DTI method is appropriate to determine the global fiber orientation. The difference in median pennation angles determined with both methods is only about 1.2° (median pennation angle of MicroScribe: 9.7°; DTI: 8.5°) and probably has no practical relevance for muscle simulation studies. Determining fascicle lengths requires additional restriction and further development of the DTI method.

Neural activation and radial diffusivity in schizophrenia: combined fMRI and diffusion tensor imaging study

BACKGROUND Schizophrenia is associated with often widespread changes in white matter structure. Most studies have investigated changes in fractional anisotropy, whereas alterations in radial or axial diffusivity have barely been investigated until now. AIMS To investigate radial diffusivity as a potential marker of dysmyelination in direct relation to abnormalities in neural activation. METHOD Neural activation in association with decision-making under uncertainty was investigated in 19 people with schizophrenia and 20 healthy controls and linked to radial diffusivity as measured by diffusion tensor imaging. RESULTS Decision-making under uncertainty was associated with a significantly decreased activation in a frontostriatocingulate network in the schizophrenia group. Structurally, they exhibited increased radial diffusivity in temporal white matter that was negatively correlated with activation in parts of the frontostriatocingulate network. CONCLUSIONS Present data indicate that altered diffusivity within relevant white matter networks may be closely linked to abnormal neural activation in schizophrenia.

Disrupted white matter integrity of corticopontine-cerebellar circuitry in schizophrenia

Evidence for white matter abnormalities in patients with schizophrenia is increasing. Decreased fractional anisotropy (FA) in interhemispheric commissural fibers as well as long-ranging fronto-parietal association fibers belongs to the most frequent findings. The present study used tract-based spatial statistics to investigate white matter integrity in 35 patients with schizophrenia and 35 healthy volunteers. We found that patients exhibited significantly decreased FA relative to healthy subjects in the corpus callosum, the cerebral peduncle, the left inferior fronto-occipital fasciculus, the anterior thalamic radiation, the right posterior corona radiata, the middle cerebellar peduncle, and the right superior longitudinal fasciculus. Increased FA was detectable in the inferior sections of the corticopontine-cerebellar circuit. Present data indicate extended cortical-subcortical alterations of white matter integrity in schizophrenia using advanced data analysis strategies. They corroborate preceding findings of white matter structural deficits in mainly long-ranging association fibers and provide first evidence for neuroplastic changes in terms of an increased directionality in more inferior fiber tracts.